1,2,4-三氯苯对小鼠血液和脑抗氧化系统的影响

1,2,4-三氯苯（1,2,4-TCB）在自然环境和工业生产中广泛存在,国内外许多学从20世纪80年代以后对1,2,4-TCB的毒性作了大量研究.本观察1,2,4-TCB急性染毒小鼠血和脑中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、巯基（SH）及脂质过氧化物（LPO）含量变化对小鼠抗氧化系统的影响及其毒作用机制.结果报告如下.     

1,2,4-三氯苯对谷胱甘肽过氧化物酶活力的影响

1,2,4-三氯苯(1,2,4-TCB)是三氯苯的3种同分异构体之一,是工业合成的中间产品产物,具有广泛的工业用途.主要经消化道吸收进入体内,也可经口吸入和经皮吸收.国内外研究资料表明,1,2,4-TCB可引起中枢神经抑制和肝肾损害[1],高剂量时小鼠骨髓微核增多[2].由于1,2,4-TCB在体内主要通过一系列酶促反应而形成相对稳定的氧化中间产物,而GSH-Px作为体内重要的抗氧化酶,在1,2,4-TCB的代谢中起重要作用.为进一步探讨其毒作用机理进行本实验研究.     

三氯苯诱发小鼠淋巴细胞DNA损伤的实验研究

采用单细胞凝胶电泳(SCGE)技术检测1,2,4-三氯苯(1,2,4-TCB)在不同剂量下对小鼠淋巴细胞DNA的损伤作用,并探讨其遗传毒性作用。结果显示除了低剂量染毒组外,各组与对照组比较差异有显著性。说明1,2,4-TCB可致小鼠淋巴细胞DNA损伤。     

1,2,4-三氯苯的阈限值

1,2,4-三氯苯(简称1,2,4-TCB)是工业合成的中间产物,为一无色液体,难溶于水,有苦辣的芳烃化合物的味道,嗅阈约为3ppm。大鼠、兔、猴慢性吸入中毒实验(1,2,4-TCB纯度为99.07%):吸入浓度分别为0、25、50、100ppm,7小时/日/周,共26周。每组雄性大鼠30只、雄兔16只、雄猴9只。中毒组的监测平均浓度分别为25.3,49.2和92.8ppm。[观察指标] 肺功能检查,包括肺静态的应变性,CO扩散能力、通气分布、肺体积和呼吸阻力等,每组选3只猴经训练后用于实验中测定动作行为(operant behavior)。生化指标包括血清谷草转氨酶(SGOT)、     

1,2,4-三氯苯对小鼠心脏、肝脏和肾脏抗氧化系统的影响

目的探讨1,2,4-三氯苯(1,2,4-TCB)对小鼠心脏、肝脏和肾脏抗氧化系统的影响。方法经皮下注射染毒,分为1 382.2、2 764.4、4 146.6 mg/kg低、中、高3个剂量,测定心、肝、肾脏中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总巯基(T-SH)、非蛋白巯基(NP-SH)、蛋白巯基(P-SH)及脂质过氧化物(LPO)的含量。结果心脏检测示低剂量组NP-SH含量显著高于对照组;肝脏检测示中、高剂量组LPO含量显著增高,GSH-Px活力和NP-SH含量显著低于对照组,高剂量组SOD活力增高,与对照组相比差异有显著性;肾脏检测示3个剂量组GSH-Px活力有所降低,与对照组相比差异有显著性,低剂量组NP-SH含量显著低于对照组。结论1,2,4-TCB可使小鼠心、肝和肾脏脂质过氧化作用增强,并相应地引起抗氧化酶活力和抗氧化物质含量的变化。     

三氯苯的毒理学研究

三氯苯(TriChloroBenrene,简称TCB)广泛应用于化工、杀虫剂、制药等行业。TCB有三种同分异构体,即1,2,4—TCB、1,2,3—TCB及1,3,5—TCB。在工业应用中以1,2,4—TCB为多见。它在常温下为无色透明的液体,易挥发,熔点为17℃,沸点为210℃,比重(d_4~(16))为1.4613,     

1,2,4三氯苯对小鼠抗氧化能力的影响

目的：通过测定1,2,4－三氯苯（1,2,4－TCB）染毒小鼠全血及组织中超氧化物歧化酶（Superoxide Dismutase,SOD)及谷胱甘肽过氧化物酶（Glutahione Peroxidase,GSH-Px）活力的变化,探讨三氯苯对 氧化能力的影响。采用经后肢皮下注射染毒法,于小鼠染毒24小时后采集血样,摘取肝、肾、心和脑并制成匀浆,分别测定全血及组织中SOD和GSH-Px活力的变化。结果：在肝脏高剂量组和脑高、中、低剂量组SOD活力显著升高,在全血高、中、低剂量组、肝脏的高和中剂量组,肾脏的高、中、低剂量组GSH-Px活力均显著降低,脑的高剂量组GSH-Px活力显著升高。结论,1,2,4－TCB能导致肝脏和脑中SOD活力及脑中GSH-Px活力代偿性升高,血液,肝脏和肾脏GSH-Px活力显著下降。     

洋葱油主要化学成分的分析

从洋葱中提取洋葱油並分析鉴定了洋葱油中的15种成分,其中主要成分为含硫的有机化合物。例如:2,5-二甲基噻吩,二丙基二硫化物,二甲基三硫化物,二丙基三硫化物和3,5-二乙基1,2,4-三噻烷等。     

工作场所空气中3-硝基-1,2,4-三唑-5-酮的高效液相色谱测定方法

目的:建立工作场所空气中3-硝基-1,2,4-三唑-5-酮的高效液相色谱测定方法。方法:采用ODSC18柱(200 mm×4.6 mm×5μm);流动相∶水∶冰乙酸∶三乙胺=800∶2∶1;流速:1.0 ml/min;检测波长:220 nm。结果:检出限为0.30μg/mL(进样10μl洗脱液),最低检出浓度为0.004 mg/m3(以采集150 L空气样品计)。回归方程为y=26.51x-4.06,相关系数为r=0.9999,高、中、低三个浓度的样品,相对标准偏差为1.0%～1.1%,洗脱效率为98.3%～99.7%,方法的回收率为96.9%～102.2%,样品在室温至少可保存14 d,在该条件下与3-硝基-1,2,4-三唑-5-酮可能共存的三硝基甲苯、黑索今、奥克托今等不干扰测定。结论:该方法具有样品处理简便、测定周期短、灵敏度高、重现性好的优点,适用于工作场所空气中3-硝基-1,2,4-三唑-5-酮的检测。     

氯代苯类化合物对斑马鱼胚胎的单一急性毒性

[目的]为进一步开展水生生物毒理实验研究剂量和毒理学终点选择提供科学依据,并初步揭示氯代苯类化合物致毒机制。[方法]以氯代苯类化合物为测试毒物（包括一氯苯、邻二氯苯、间二氯苯、对二氯苯和1,2,4-三氯苯）,以斑马鱼胚胎为测试对象,进行单一急性毒性测试。实验选用24孔细胞培养板作为胚胎染毒实验容器。从胚胎染毒开始间隔4h显微观察,记录氯代苯类化合物对斑马鱼胚胎单一急性毒性效应（包括致死效应和亚致死效应）,描述相应毒理学终点的变化情况,直至72h结束。[结果]通过实验测出氯代苯类化合物各毒理学终点的EGo值,例如4h胚胎发育终止EC50值（mg／L）：1,2,4．三氯苯为24．72,对二氯苯为76．47,间二氯苯为77.35,邻二氯苯为86.31,一氯苯为89．43等;大量数据显示其毒性大小依次为：1,2,4．三氯苯〉对二氯苯〉间二氯苯〉邻二氯苯〉一氯苯。[结论]氯代苯类化合物对斑马鱼胚胎毒性大小与化合物相对分子质量大小、取代基数量多少以及取代位置有关,相对分子质量越大、取代基数量越多其毒性越大。     

Synthesis, cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immunocompetent cells

Novel derivatives of 4,5-substituted-1,2,4-triazole-thiones and 2,5-substituted-1,3,4-thiadiazoles were synthesized and evaluated for their cytotoxicity. The biological study indicated that compounds 4-ethyl-5-(4,5,6,7-tetrahydro-1-benzothien-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 13, N-ethyl-5-(4,5,6,7-tetrahydro-1-benzothien-2-yl)-1,3,4-thiadiazol-2-amine 16, 4-amino-5-(4,5,6,7-tetrahydro-1-benzothien-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 20 and 4-amino-5-(5-phenylthien-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 21 possessed high cytotoxicity in vitro against thymocytes. The corresponding IC(50) values were 0.46 microM, 5.2 x 10(-6)microM, 0.012 microM and 1.0 x 10(-6)microM. Most toxic against lymphocytes was compound 21, IC(50) - 0.012 microM. The tested compounds showed a general stimulation effect on B-cells' response.     

Acute and chronic toxicity of some chlorinated benzenes,chlorinated ethanes,and tetrachloroethylene toDaphnia magna

Chronic effect and no effect concentrations (28 day) and acute toxicity (48 hr, LC50 and EC50) values were determined forDaphnia magna with some chlorinated benzenes, chlorinated ethanes, and tetrachloroethylene. Acute and chronic toxicity generally increased with the degree of chlorine substitution with these chemicals. The 48 hr LC50 values for hexachloroethane, pentachloroethane, 1,1,2,2-tetrachloroethane, 1,1,2-trichloroethane, 1,2-dichloroethane, 1,2,4-trichlorobenzene, 1,3-dichlorobenzene, and tetrachloroethylene were 2.9, 7.3, 62, 190, 270, 2.1, 7.4, and 18 mg/L, respectively. The lowest observable effect concentrations (LOEC) based on either reproductive impairment or growth for 1,1,2,2-tetrachloroethane, 1,1,2-trichloroethane, 1,2-dichloroethane, 1,2,4-trichlorobenzene, 1,3-dichlorobenzene, and tetrachloroethylene were 14, 26, 20, 0.69, 1.5, and 1.1 mg/L, respectively. Length of animals at the end of chronic exposure was at least as sensitive a measure of toxic effect as reproduction with every chemical tested except 1,2-dichloroethane. The acute-chronic ratio ranged from 3 to 16 with these chemicals.     

镉的肾脏毒理学

镉（Cd)是一种有毒的重金属,人体长期暴露于镉可造成肾脏的慢性中毒性损伤。本文综述了近年来关于镉所致慢性肾损伤的研究进展,重点介绍镉导致慢性肾损伤的作用机理。     

Cellular toxicity in Chinese hamster ovary cell cultures. II: A statistical appraisal of sensitivity with the rabbit alveolar macrophage,Syrian hamster embryo,BALB 3T3 mouse,and human neonatal fibroblast cell systems

Chinese hamster ovary, rabbit alveolar macrophage, Syrian hamster embryo, BALB 3T3 mouse, and human neonatal fibroblast cells were employed in a statistical evaluation of the relative sensitivity of the cells to toxic substances. The cells were exposed to 1,2,4-trichlorobenzene, 2,4-dimethylphenol, Aroclor 1248, cadmium chloride, lead sulfate, nickel nitrate, lead oxide-coated fly ash, and a fine particulate from coal combustion. A filter-disk technique was used to measure the inhibition of protein and DNA synthesis. A quantitative ranking of cell-system sensitivity was determined from comparisons of statistically significant differences (P ? 0.01) in protein and DNA synthesis expressed as a percentage of control. An overall ranking of sensitivity showed that rabbit alveolar macrophages, Syrian hamster embryo cells, and Chinese hamster ovary cells were more sensitive than another of the five cell systems in 75, 68, and 62% of the experiments, respectively. The corresponding values for BALB 3T3 mouse and human neonatal fibroblast cells were 38 and 28%, respectively, under our experimental conditions. Detailed data on the control cell cultures are also presented.     

Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae

The toxicity of SSRIs to algae/phytoplankton was investigated using the US EPA ECOSAR, acute single-species growth inhibition assays, species sensitivity distributions (SSDs), and an outdoor microcosm mixture experiment. Worst-case ECOSAR estimates of SSRI toxicity to algae ranged from 0.73 to 13.08 mg/L. Sertraline was the most toxic SSRI tested in single-species growth inhibition assays followed by fluoxetine and fluvoxamine with worst-case 96-h IC10s of 4.6, 31.3, and 1662 microg/L, respectively. HC5s of 2.4, 3.6, and 1100 microg/L were estimated, respectively, for sertraline, fluoxetine, and fluvoxamine toxicity to algae-using SSDs. Microcosm phytoplankton structural endpoints were more sensitive than functional endpoints in the short term. However, in the long term, structural endpoints were resilient and functional endpoints remained impacted even after a period of recovery. The worst-case EC10 determined from the outdoor microcosm mixture toxicity to phytoplankton communities was 15.2 nM. Although SSRIs are toxic to algae, hazard quotients using worst-case PECs represent a margin of safety of 20 to phytoplankton. Although SSRIs do not appear to pose a hazard to primary production, this assessment is not protective of higher aquatic organisms and further research into the chronic toxicity to low levels of SSRIs to higher-level aquatic species is recommended.     

1,2,4-Triazole D-ribose derivatives: design, synthesis and antitumoral evaluation

Herein we report the design, synthesis and characterization of novel 1,2,4-triazole d-ribose derivatives, as well as their synthetic precursors. The antitumoral activity against T cell lymphoma cell line of these products was studied. Structures containing a 1,2,4-triazolic ring linked by sulfur to the carbohydrate moiety showed a moderate antiproliferative activity. The presence of the second heterocyclic ring did not show significant changes in their biological activity. Meanwhile, structures with 3-thiobenzyl-5-substituted-1,2,4-triazole ring linked by nitrogen leads to compounds with a biphasic behavior, stimulating cell proliferation at low concentrations and inhibiting it at higher ones. An increment in the polarity was associated with a decrease in the activity of the evaluated compounds. A preliminary antitumoral screening pointed the 1,2,4-triazolic structures linked to protected sugars as promising leaders for further studies.     

ApoE genotype,past adult lead exposure,and neurobehavioral function

Our objective in this study was to determine if the known relation between tibia bone lead levels and neurobehavioral test scores are influenced by the apolipoprotein E (ApoE) genotype. We collected data on 20 neurobehavioral tests in 529 former organolead workers who had an average of 16 years since last occupational exposure to lead. We used linear regression to model the relations between each of 20 neurobehavioral test scores and tibia lead, a binary variable for ApoE genotype (i.e., at least one Epsilon4 allele vs. none), and an interaction term between tibia lead and the binary term for ApoE genotype. At the time of testing, former lead workers were an average of 57.6 years of age; 82% were younger than 65 years. In regression analysis, we observed one statistically significant and one borderline significant coefficient for ApoE genotype alone. Coefficients for the ApoE and tibia lead interaction term were negative in 19 of the 20 regression models. This indicates that the slope for the relation between tibia lead and each neurobehavioral test was more negative for individuals with at least one Epsilon4 allele than for those who did not have an Epsilon4 allele. Four of 19 negative coefficients for the interaction term were statistically significant (digit symbol, Purdue pegboard assembly, Purdue pegboard-dominant hand, complex reaction time); another three of the remaining 16 coefficients (symbol digit, trail-making A, Stroop) were borderline significant (i.e., p < 0.10). This study suggests that individuals may vary in susceptibility to the long-term effects of lead on the central nervous system (CNS). In particular, the persistent CNS effect of lead may be more toxic in individuals who have at least one ApoE-Epsilon4 allele.     

安徽省食物中毒病因变迁与防治对策评析

目的　探讨我省食物中毒病因变迁规律 ,为今后食物中毒防治工作提供参考。方法　按照不同时期对全省食物中毒发生情况、中毒场所、中毒原因食品、致病因素等进行归类统计、对比分析。结果　全省食物中毒发生起数、中毒人数和死亡人数逐年下降 ,年均发病率大幅度下降 ,食物中毒发生规模逐渐减小。在各个时期 ,家庭食物中毒的构成均占首位 ,且在死亡人数中占 70 %以上。动物性食物中毒所占比重下降 ,植物性食物中毒比例上升 ;微生物性食物中毒、有毒动植物食物中毒比例下降 ,农药及化学物食物中毒比例上升 ;在死亡人数中 ,由有毒动植物中毒引起的所占比例在下降 ,由植物性食物中毒引起的所占比例逐步上升。结论　应重视和加强植物性食品、农药及化学物食物中毒防治工作 ,重点要做好农村及家庭食物中毒防治措施的研究和落实     

Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities

4-Phenyl-5-pyridin-4-yl-4H-1,2,4-triazole-3-thiol (3) was obtained in basic media via the formation of 2-isonicotinoyl-N-phenylhydrazinecarbothioamide (2), and converted to some alkylated derivatives (4a,b) and Mannich base derivatives (5a-c). 2-[(4-Phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]acetohydrazide (7) that was obtained by using compound 3 as precursor in two steps was converted to thiosemicarbazide derivative (8), Schiff base derivatives (9) and 5-{[(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-1,3,4-oxadiazole-2-thiol (10). Moreover, 5-{[(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-3-{[(2-morpholin-4-ylethyl)amino]methyl}-1,3,4-oxadiazole-2(3H)-thione (11) was synthesized via reaction of compound 10 with 2-(4-morpholino)ethylamine. The treatment of compound 8 with NaOH gave 4-(4-methylphenyl)-5-{[(4-phenyl-5-pyridine-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-4H-1,2,4-triazole-3-thiol (12), while the acidic treatment of compound 8 afforded 5-{[(4-phenyl-5-pyridin-4-yl-4H-1,2,4-triazol-3-yl)thio]methyl}-2(4-methylphenyl)-amino-1,3,4-thiadiazole (14). N-Methyl derivative of compound 14 and a Mannich base derivative of compound 12 were synthesized from the reactions of these precursors with methyl iodide and methyl piperazine, respectively. All newly synthesized compounds were screened for their antimicrobial activities. The antimicrobial activity study revealed that all the compounds screened showed good or moderate activity except compounds 3, 5c, 7, 9c, 9e, 9g, 9h, 11, and 13.     

调强放射治疗联合周剂量紫杉醇治疗食管癌的近期疗效研究

目的观察调强放疗联合周剂量紫杉醇治疗食管癌的近期疗效及毒性反应。方法103例食管癌患者随机分为放疗组（单放组，n=43），调强放疗＋紫杉醇组（放化组，n=60）。单放组采用调强放疗，95％PIV：66Gy／30—33次，每周5次；放化组调强放疗同时紫杉醇60mg第1、8、15、22、29、36天静滴。结果1、2年生存率，单放组为55．8％、32．5％，放化组为86．6％、68．3％，差异有统计学意义（P〈0．05）。放化组毒副反应稍高于单放组，差异无统计学意义（P〉0．05）。结论调强放疗联合周剂量紫杉醇治疗食管癌近期疗效较好，虽毒性反应增加但能耐受。