人白细胞髓过氧化物酶代谢活化致癌物4－氨基联苯

本文研究人白细胞髓过氧化物酶（ＭＰＯ）体外代谢芳胺类致癌物４－氨基联苯（４－ＡＢＰ〕在Ｈ２Ｏ２存在下，ＭＰＯ代谢活化４－ＡＢＰ生成二种可与ＤＮＡ共价结合的代谢产物。高效液相色谱和质谱分析表明。在没有ＤＮＡ存在时４－ＡＢＰ的主要代谢产物是偶氮二联苯。抗坏血酸和谷胱甘肽显著抑制活化的４－ＡＢＰ与ＤＮＡ结合。而且可将活化产物还原成４－ＡＢＰ．这些结果结合质谱资料提示活性中间产物可能是４－ＡＢＰ自由基。３２Ｐ－后标记实验证实ＤＮＡ加合物形成，用此种方法检测出８个４－ＡＢＰ－ＤＮＡ加合物。并表明ＭＰＯ介导产生的４－ＡＢＰ－ＤＮＡ加合物与细胞色素Ｐ４５０代谢产物Ｎ－羟基－４－ＡＢＰ和ＤＮＡ反应产生的加合物性质不同．这些结果提示。ＭＰＯ代谢活化途径可能在４－ＡＢＰ诱发肝外组织肿瘤过程中起一定的作用．     

人白细胞髓过氧化物酶代谢活化致癌物4－氨基联苯

本文研究人白细胞髓过氧化物酶（ＭＰＯ）体外代谢芳胺类致癌物４－氨基联苯（４－ＡＢＰ〕在Ｈ２Ｏ２存在下，ＭＰＯ代谢活化４－ＡＢＰ生成二种可与ＤＮＡ共价结合的代谢产物。高效液相色谱和质谱分析表明。在没有ＤＮＡ存在时４－ＡＢＰ的主要代谢产物是偶氮二联苯。抗坏血酸和谷胱甘肽显著抑制活化的４－ＡＢＰ与ＤＮＡ结合。而且可将活化产物还原成４－ＡＢＰ．这些结果结合质谱资料提示活性中间产物可能是４－ＡＢＰ自由基。３２Ｐ－后标记实验证实ＤＮＡ加合物形成，用此种方法检测出８个４－ＡＢＰ－ＤＮＡ加合物。并表明ＭＰＯ介导产生的４－ＡＢＰ－ＤＮＡ加合物与细胞色素Ｐ４５０代谢产物Ｎ－羟基－４－ＡＢＰ和ＤＮＡ反应产生的加合物性质不同．这些结果提示。ＭＰＯ代谢活化途径可能在４－ＡＢＰ诱发肝外组织肿瘤过程中起一定的作用．     

TNT及代谢产物对大鼠肝细胞核的还原活化

ＴＮＴ及代谢产物对大鼠肝细胞核的还原活化李中，王玉玲，杨建会ＴＮＴ经体内生物转化后可形成多种代谢产物。在接触ＴＮＴ工人尿中检出的代谢产物有：２－氨基－４，６－二硝基甲苯（２－Ａ），４－氨基－２，６－二硝基甲苯（４－Ａ）。２，４－二氨基－６－硝基甲苯（...     

CTLA—4基因工程药物研究进展

ＣＴＬＡ－４（ｃｙｔｏｔｏｘｉｃ Ｔ ｌｙｍｐｈｏｃｙｔｅ－ａｓｓｏｃｉａｔｅｄ ａｎｔｉｇｅｎ－４，ＣＤ１５２）是在毒性Ｔ淋巴细胞ＤＮＡ文库中发现的第４个特有基因表达产物，因其与ＣＤ２８是同源基因并且两者能竞争性结合Ｂ７家族分子，故在免疫信号传导中发挥重要作用。研究其在自身免疫性疾病、抗移植排斥及肿瘤免疫中的作用机制，对开发基因工程药物及相关化学合成药物具有深远的现实意义。     

10－羟基－2－癸烯酸对小鼠T淋巴细胞及其亚型和白介素2产生的影响

观察了１０－羟基－２－癸烯酸（１０－ＨＤＡ）对小鼠Ｔ淋巴细胞及其亚型和白介素２产生的影响．结果表明，１０－ＨＤＡ１，５，２５ｍｇ·ｋｇ－１·ｄ－１ｉｐ，５ｄ可拮抗环磷酰胺１００ｍｇ·ｋｇ－１对小鼠迟发型超敏反应（ＤＴＨ）的抑制作用．体外给药，１０－ＨＤＡ可促进刀豆球蛋白Ａ诱导的Ｔ淋巴细胞增殖反应；促进小鼠脾细胞产生白介素２．采用单克隆抗体间接免疫荧光法证明１０－ＨＤＡ可增加小鼠胸腺Ｌ３Ｔ＋４细胞数，而对Ｌｙｔ－２＋细胞无明显影响．结果提示１０－ＨＤＡ可调节Ｔ淋巴细胞参与的免疫反应．     

限量饮食对化学致癌物—DNA加合物生成的影响

用黄曲霉毒素Ｂ１（ＡＦＢ１）、苯并（ａ）芘（ＢａＰ）和２－乙基氨基芴（２－ＡＡＦ）作为致癌物代表，研究限量饮食（Ｄｉｅｔａｒｙｒｅｓｔｒｉｃｔｉｏｎ，ＤＲ）对雄性Ｆ３４４大鼠和Ｂ６Ｃ３Ｆ１小鼠代谢活化致癌物的影响。以几种致癌物主要的ＤＮＡ加合物作为代谢活化的生物指标。结果显示：限量饮食降低大鼠和小鼠的体重，降低ＡＦＢ１－ＤＮＡ加合物（ＡＤＡ）的生成，增加ＡＦＢ１－谷胱甘肽结合物（ＡＦＢ１－ＳＧ）的生成，增加ＢａＰ－ＤＮＡ加合物（Ｂｐ－Ｎ２－ｄＧ）的生成，但对２－ＡＡＦ－ＤＮＡ加合物（ＡＦ－Ｃ８－ｄＧ）的作用有双重性，染毒后２４，４８小时ＡＦ－Ｃ８－ｄＧ在两组动物肝中无差别，而７２小时后则明显降低ＡＦ－Ｃ８－ｄＧ的生成。结果说明：对于不同的致癌物，ＤＲ有选择性改变代谢酶活性的作用，这种作用可以改变致癌物的活化进而影响致癌过程的起始阶段     

三硝基甲苯及其代谢产物对离体人红细胞溶血作用的观察

三硝基甲苯及其代谢产物对离体人红细胞溶血作用的观察李中，王玉玲，杨建会三硝基甲苯（ＴＮＴ）能引起作业工人出现溶血性贫血［１］。已知ＴＮＴ进入机体后形成一系列代谢物［３］，即：２－氨基－４，６－二硝基甲苯（２－Ａ）、４－氨基－２，６－二硝基甲苯（４－Ａ...     

Detection of DNA damage in peripheral lymphocytes by 7 compounds using comet assay

目的：检测过氧化氢（Ｈ２Ｏ２）、甲磺酸乙酯（ＥＭＳ）、丝裂霉素Ｃ（ＭＭＣ）、二甲基亚硝胺（ＤＭＮＡ）、苯并（ａ）芘（ＢａＰ）、２氨基芴（２ＡＦ）和环磷酰胺（ＣＰ）诱发小鼠、大鼠及人外周血淋巴细胞ＤＮＡ单链断裂．方法：体外单细胞微量凝胶碱性电泳试验（慧星试验）．结果：除ＥＭＳ０９７ｍｍｏｌ·Ｌ－１在小鼠淋巴细胞，ＭＭＣ３０μｍｏｌ·Ｌ－１在小鼠、人淋巴细胞中呈阴性外，其余均为阳性．最低可检测浓度分别为Ｈ２Ｏ２１μｍｏｌ·Ｌ－１，ＥＭＳ０４８ｍｍｏｌ·Ｌ－１，ＢａＰ５０μｍｏｌ·Ｌ－１，ＣＰ２０ｍｍｏｌ·Ｌ－１，ＭＭＣ１０μｍｏｌ·Ｌ－１，ＤＭＮＡ２７３ｍｍｏｌ·Ｌ－１，２ＡＦ６２５μｍｏｌ·Ｌ－１．ＣＰ、ＢａＰ、２ＡＦ需经Ｓ９Ｍｉｘ代谢活化才显示毒性．结论：彗星试验检测出ＭＭＣ诱导大鼠，ＥＭＳ诱导大鼠和人，以及Ｈ２Ｏ２、ＤＭＮＡ、ＢａＰ、ＣＰ和２ＡＦ诱导小鼠、大鼠和人外周血淋巴细胞ＤＮＡ单链断裂损伤．     

通过自动与被动免疫防御日本蜱传脑炎病毒

作者在人和小鼠中评估了欧洲的蜱传脑炎病毒（ＴＢＥＶ）疫苗诱导抗日本ＴＢＥＶ Ｏｓ－ｈｉｍａ ５－１０株免疫应答的情况,还在小鼠模型中检测了暴露前后注射多克隆兔抗－ＴＢＥＶ血清的保护效力。 ＦＳＭＥ－ＩＭＭＵＮ疫苗系由 ＴＢＥＶ西方亚型株Ｎｅｕｄｏｅｒｆｌ灭活纯化制成。对１０名健康志愿者间隔４周肌注疫苗２次,其中４人１年后免疫第３次,于免疫当天及每次免疫４周后采血。对１０只６周龄ＩＣＲ小鼠在０、７天皮下注射０．２ｍｌ４倍稀释的疫苗,对照小鼠则注射ＰＢＳ,第２针后１周采血。为了解是否存在交叉保护作用,用…     

盐藻β—胡萝卜素的免疫药理研究：II对T淋巴细胞增殖及T淋巴细胞亚…

采用植物血凝素（ＰＨＡ）诱导Ｔ淋巴细胞转化率和单克隆抗体间接免疫荧光技术，分析了盐藻β－胡萝卜素（β－Ｃ）对Ｔ淋巴细胞的增殖及Ｔ淋巴细胞亚群的作用，结果表明，β－Ｃ对ＰＨＡ诱导的Ｔ淋巴细胞增殖有明显促进作用，对环磷酰胺（ＣＴＸ）抑制的Ｔ淋巴细胞转化率能明显升高；β－Ｃ能明显提高正常小鼠和免疫能力低下小鼠Ｌ３Ｔ４细胞的百分率，使Ｌ３Ｔ４／Ｌｙｔ－２的比值升高，大剂量可对抗ＣＴＸ的作用，降低Ｌｙｔ－２     

北豆根总碱对环磷酰胺模型小鼠的免疫调节作用

从非特异性免疫功能及特异性免疫功能方面研究了北豆根总碱对环磷酰胺所致的免疫功能低下模型小鼠的免疫调节作用．实验结果表明,北豆根总碱２５ｍｇ／ｋｇ、５０ｍｇ／ｋｇ腹腔注射能显著增强模型小鼠单核巨噬细胞吞噬功能、迟发型超敏反应及增加其外周血淋巴细胞ＡＮＡＥ阳性百分率;北豆根总碱２５ｍｇ／ｋｇ腹腔注射能显著提高模型鼠血清溶血素生成能力．初步机理研究表明,北豆根总碱５０ｍｇ／ｋｇ腹腔注射能显著拮抗环磷酰胺对小鼠胸腺ＤＮＡ含量的抑制作用,提示北豆根总碱可能通过促进ＤＮＡ合成而达到增强免疫功能的作用．     

肝素经静脉及肺两种途径给药的血药浓度比较

目的：为比较肝素经静脉和肺两种途径给药的血药浓度变化特点。方法：给慢性阻塞性肺病（ＣＯＰＤ）患者经静脉及射流雾化定时予肝素１００ｍｇ·ｄ－１，共７ｄ。首次给药后定时查肝素血药浓度。结果：发现肝素确可经肺途径入血，首次雾化后１．５ｈ血药浓度达高峰，以后迅速降低，第７天再度升高，停药３ｄ血中仍有低浓度肝素存在。静脉给药者血药浓度高峰亦出现于首次给药后１．５ｈ，但峰值明显高于经肺给药者（Ｐ＜０．０１），以后渐降低，２４ｈ已大部排泄。第７天血中虽可检出微量肝素，但明显低于经肺给药者（Ｐ＜０．０１）。结论：肝素静脉给药血中药物浓度高，维持时间短。而经肺给药可长时间、低水平的维持血中肝素浓度，停药７２ｈ血中仍可检出微量肝素     

二苯乙烯(芪)的一些药理作用

芪(二苯乙烯)通常用于化学工业,对其药理活性的研究很少。通过动物实验我们发现芪能明显保护CCl₄引起的小鼠肝损害,表现在使高的SGPT及SGOT降低、BSP潴留减少、肝组织病变减轻等。芪明显促进肝糖元生成,此作用强度与可的松相近,但芪没有可的松那样的抗炎作用。在去肾上腺小鼠,芪仍能明显促进肝糖元生成,故此作用似乎不通过体内的垂体-肾上腺系统。芪对小鼠戊巴比妥睡眠时间影响不明显。根据实验资料分析,芪对CCl₄肝损害的保护机制大概不是通过酶诱导,也不象某些抗氧化剂那样直接对抗CCl₄的作用,但有可能与其促进肝糖元生成有某种关系。芪有微弱的雌激素作用(约为己烯雌酚的数万分之一)。芪的毒性很低,小鼠一次腹腔注射LD₅₀为6.5 g/kg,灌胃LD₅₀大于8 g/kg,但油溶液毒性较大(灌胃LD₅₀为0.92g/kg)。长期大量给予芪,对雄小鼠的生长及睾丸发育有抑制作用,给狗服芪50 mg/kg/天连续一个月以上未见明显异常反应。     

合成鱼腥草素对小鼠免疫功能的影响

对于脾切除致免疫功能低下小鼠,合成鱼腥草素（ＨＯＵ）６０ｍｇ／ｋｇ,１２０ｍｇ／ｋｇ灌胃给药均能增强其腹腔巨噬细胞的吞噬功能（Ｐ＜０００１）;迟发型超敏反应强度（Ｐ＜０００１）;明显提高血清溶血素水平（Ｐ＜００５;Ｐ＜０００１）;外周血淋巴细胞ＡＮＡＥ阳性百分率（Ｐ＜０００１）;ＨＯＵ６０ｍｇ／ｋｇ还能明显提高脾切小鼠腹股沟淋巴结中淋巴细胞个数（Ｐ＜００１）,表明ＨＯＵ对脾切除致免疫功能低下小鼠的特异性、非特异性免疫功能均有明显增强作用．     

Effects of the immune system on cyclosporine absorption

1. The pharmacokinetics and toxicodynamics of single and multiple doses of cyclosporine were studied in the immunized rat model and compared with non-immunized rats. 2. The pharmacokinetics of cyclosporine i.v. (5 mg/kg per day) were similar in immunized and non-immunized rats after single or multiple doses. 3. The absolute bioavailabilities of single and multiple doses of cyclosporine (10 mg/kg per day) given orally were significantly decreased in immunized rats compared with non-immunized rats. 4. Oral administration of cyclosporine (10 mg/kg per day) did not alter renal function of non-immunized rats compared with untreated controls. However, inulin clearance decreased greater than four-fold in immunized rats given cyclosporine for 7 days. 5. In summary, the pharmacokinetics and toxicodynamics of cyclosporine given orally to rats are affected by the immune system.     

Subchronic toxicity of trinitrotoluene in Fischer 344 rats rats

This study was conducted to evaluate the toxicity of trinitrotoluene (TNT) in Fischer 344 rats when administered in the diet for 13 weeks. Groups of 10 rats per sex received TNT at doses of 1, 5, 25, 125 or 300 mg/kg/day. Thirty rats per sex served as untreated controls. Toxicologic endpoints included clinical signs, body weight, food consumption, hematology, clinical biochemistry, organ weights and gross/histopathology. Toxic effects following 125 mg/kg/day or greater included decreased food intake and body weight gain, elevated serum cholesterol levels, and anemia (reduced hemoglobin, hematocrit and RBC counts). Splenomegaly, hepatomegaly/hepatocytomegaly and testicular atrophy with degeneration of the seminiferous tubular epithelium were also seen at 125 and 300 mg/kg/day. Hemosiderin-laden macrophages, congestion of the splenic red pulp, methemoglobin production indicative of the oxidizing activity of TNT and/or its metabolites, and the lack of bone marrow toxicity suggested hemolysis as the mechanism of anemia.     

Lack of Antiinflammatory Activity of Metronidazole

Abstract: Metronidazole was given to rats with experimentally induced inflammation to evaluate whether the drug has any antiinflammatory effect. Inflammation was caused by injection of Freund's complete adjuvant into a paw. The oedema of the paw measured on the 4th day was not influenced after metronidazole 20 mg/kg/day or 160 mg/kg/day, whereas phenylbutazone 80 mg/kg/day significantly decreased the volume of the paw. The concentration of orosomucoid did not differ in the group of rats given metronidazole 20 mg/kg/day as compared to the control group. However, the orosomucoid concentration was lower in the group given metronidazole 160 mg/kg/day, as was the case in the phenylbutazone group. In groups of rats with polyarthritis studied on the 14th and 21st day there was no difference of arthritic index, volume of paw or orosomucoid concentration in neither low nor high dose metronidazole as compared to the control groups. The phenylbutazone groups, however, showed a lower arthritic index, lower volume of paw and lower orosomucoid concentration.     

不同剂量盐酸右美托咪定对骨科手术患者术后恢复及血清CRP的影响

目的:探讨不同剂量盐酸右美托咪定(DEX)对骨科手术患者术后恢复及血清CRP的影响。方法:选取2018年1月—2019年9月在我院骨科接受骨科手术治疗的患者68例作为研究对象,按照麻醉维持DEX剂量的不同分为高剂量组(n=23)、低剂量组(n=23)以及生理盐水组(n=22)。三组麻醉诱导方法一致,高剂量组给予DEX0.8(kg·h)持续静脉泵入,低剂量组给予DEX0.4(kg·h)持续静脉泵入,生理盐水组给予同等剂量0.9%氯化钠持续静脉泵入。比较三组认知功能、苏醒时间、拔管时间、血清CRP水平以及并发症发生率。结果:术后1 d以及术后3 d,低剂量组MMES评分均高于高剂量组和生理盐水组,差异有统计学意义(P<0.05)。术后1 d以及术后3 d低剂量组血清CRP低于高剂量组和生理盐水组,差异有统计学意义(P<0.05)。高剂量组并发症发生率为60.9%(14/23),高于低剂量组和生理盐水组,差异有统计意义(P<0.05)。结论:对骨科手术患者采用0.4μg/(kg·h)盐酸右美托咪定持续静脉泵入有利于提高患者术后认知功能,缩短苏醒时间和拔管时间,降低血清CRP水平和并发症的发生,促进患者康复。     

Determination of the effect of calcineurin inhibitors on the rat's immune system after KLH immunisation

The calcineurin inhibitors cyclosporin A (CsA), tacrolimus (FK506) and pimecrolimus (ASM981) are on the market for the oral treatment of psoriasis and atopic dermatitis and topical treatment of atopic dermatitis, respectively. The effect of these treatments on the immune response was investigated in this study after immunisation of rats with keyhole limpet hemocyanin (KLH). Male rats (10 per group) were orally administered pimecrolimus at 10 or 30 mg/kg/day), tacrolimus at 3 mg/kg/day or CsA at 20 mg/kg/day for 4 weeks. Control animals similarly received the vehicle only. The last five animals per group were immunised and challenged with KLH on days 16 and 24, respectively. Eight days after the last injection, the immune function was investigated by detecting KLH-specific antibodies in the serum and by examination of cell infiltration at the site of the KLH-challenge. In addition, a correlation between functional and structural changes was established by quantification of lymphocyte sub-populations in the blood or residing in lymphatic tissue. In KLH-immunised rats, CsA caused complete suppression of the KLH-specific IgM and IgG production, whereas only IgG production was affected by pimecrolimus at 30 mg/kg/day and more so by tacrolimus at 3 mg/kg/day. Immunophenotyping of lymphocyte sub-populations in spleen and lymph node indicated a decrease in T lymphocytes with pimecrolimus at 30 mg/kg/day, tacrolimus and CsA, whereas these changes were marginal for pimecrolimus at 10 mg/kg/day. Immunophenotyping of peripheral white blood cells (WBC) revealed a decrease in the absolute number of T lymphocytes with all three test items. In comparison with non-immunised animals, a slight increase in absolute numbers of T lymphocytes was observed in KLH-immunised animals treated with pimecrolimus at 10 or 30 mg/kg/day. In conclusion, the ability of the immune system to respond to KLH was not affected by pimecrolimus at 10 mg/kg/day whereas a decrease in immune function was noted in the other groups as follows: pimecrolimus (30 mg/kg/day) < tacrolimus (3 mg/kg/day) < CsA (20 mg/kg/day).     

TNT对大鼠LD_(50)及肝脏特异病变观察

本实验取Wistar大鼠雄、雌各60只,用悬浮于2.5％淀粉液内的TNT研碎,以1ml/100g灌胃,一次染毒后观察10天,死亡鼠随即取肝。至第11天中毒未死及对照组鼠全部处理并取肝作光镜和超微结构观察。结果表明TNT对雌鼠LD_(50)为1663.8mg/kg发现,雄鼠为1837.8mg/kg。肝脏除发现变性、坏死及线粒体破坏外,低剂量中毒鼠约50％出现胆小管淤胆和肝细胞核畸变。从而提示TNT可能与变态反应以至致癌作用有关。