阿霉素和阿克拉霉素A对HeLa细胞DNA的嵌合作用

本文用琼脂糖电泳观察国产阿霉素和阿克拉霉素A对HeLa细胞DNA的嵌合作用.DNA经琼脂糖电泳及溴乙锭染色后,紫外荧光摄影,以药物与双链DNA发生嵌合作用时DNA的溴乙锭染色性丧失为嵌合指标.实验发现阿霉素在低浓度时(25μg/ml)即可与HeLa细胞DNA发生嵌合作用,而阿克拉霉素A仅在高浓度(400～800μg/ml)才发生此作用.本实验实现了这两个蒽环类抗生素对DNA嵌合能力的差异.     

羟考酮对左旋氧氟沙星在人体内药物动力学的影响

目的研究羟考酮对左旋氧氟沙星(LVFX)在人体内药物动力学的影响。方法8名健康志愿者,单用LVFX或合用羟考酮,用HPLC法测定血药浓度。结果单用LVFX500mg后的药物动力学参数分别为tmax(1.562±1.050)h,cmax(6.6419±0.15860)μg/ml,AUC(47.65±11.29)h*μg/ml,T1/2(β)(7.034±0.941)h;合用羟考酮时,LVFX的药物动力学参数分别为tmax(1.125±0.641)h,cmax(7.652±2.594)μg/ml,AUC(48.74±10.58)h*μg/ml,T1/2(β)(6.275±0.588)h。两者除T1/2ka和cmax外,无显著性差异。结论羟考酮对LVFX在人体内药物动力学参数无影响。     

克拉维酸钾/羟氨苄青霉素(1∶4)分散片生物等效性的研究

目的　18名男性健康受试者采用随机交叉给药方法 ,单剂量口服试验制剂阿莫西林 克拉维酸钾分散片 (4∶1)和参比制剂阿莫西林 克拉维酸钾片 ,阿莫西林 5 0 0mg,克拉维酸钾 12 5mg,进行人体生物利用度和药代动力学比较。 方法 　用HPLC二极管阵列检测器同时测定阿莫西林和克拉维酸钾血药浓度。 结果 　试验制剂和参比制剂中阿莫西林的Tmax 分别为 1 2 5± 0 38h和 1 2 5± 0 38h ,Cmax 分别为 14 49± 1 42 μg/ml 和14 46± 1 40 μg/ml,AUC0 -Tn 分别为 5 2 87± 5 32 μg·h/ml和 5 2 79± 5 38μg·h/ml,AUC0 -inf分别为 5 5 36±5 2 3μg·h/ml和 5 5 41± 5 43μg·h/ml;试验制剂中羟氨苄青霉素的相对生物利用度 (F) :F (AUC(0 -Tn) )为10 0 2 0 % ,F(AUC(0 -inf) )为 99 97%。试验制剂和参比制剂中克拉维酸钾的Tmax分别为 0 92± 0 2 4h和 0 94±0 2 8h ,Cmax 分别为 2 2 7± 0 34 μg/ml和 2 2 6± 0 32 μg/ml,AUC0 -Tn 分别为 4 74± 0 85 μg·h/ml和 4 71±0 77μg·h/ml,AUC0 -inf分别为 4 92± 0 86 μg·h/ml和 4 89± 0 77μg·h/ml,试验制剂中克拉维酸钾的相对生物利用度 (F) :F(AUC(0 -Tn) )为 10 0 46 %、F(AUC(0 -inf) )为 10 0 5 7%。 结论 　两种制剂的     

三尖杉酯碱和高三尖杉酯碱与白血病细胞DNA的结合实验

本文用琼脂糖电泳观察国产三尖杉酯碱(H)及高三尖杉酯碱(H.H)与白血病细胞DNA的作用模式。实验发现H及H.H在高浓度(800μg/ml),37℃作用16h,可与DNA发生嵌合效应,48h这种现象更为明显,同时该过程也伴有一定程度的DNA断链效应。阿霉素在低浓度(50μg/ml)作用30min即可显示嵌合效应。本实验表明H.H对白血病细胞DNA的嵌合能力较H有所增强,但两者所见嵌合效应与阿霉素比较相距甚远。     

姜黄素对IGF-1调控的宫颈癌淋巴转移的影响

目的:研究姜黄素对IGF-1调控的宫颈癌淋巴转移的影响。方法:运用实时荧光定量PCR检测IGF-1不同浓度、作用时间以及姜黄素作用下宫颈癌siha细胞中VEGF-C mRNA的表达。结果:①宫颈癌siha细胞VEGF-C mRNA的表达随IGF-1浓度的递增而变化,10ng/ml时达峰值。0.5ng/ml1、ng/ml、5ng/ml、10 ng/ml、50 ng/ml组VEGF-C mRNA表达量依次为对照组的1.34、1.67、3.14、5.28和3.02倍。5ng/ml(6.73±0.25)1、0 ng/ml(5.98±0.18)、50 ng/ml(6.79±0.12)组较对照组差异具有统计学意义(P<0.05)。②宫颈癌siha细胞VEGF-C mRNA表达随IGF-1不同作用时点而变化,6h达峰值。2h组、4h组、6h组和8h组的表达量分别为对照组的1.30、2.51、5.33和2.83倍。4h(6.80±0.12)、6h(5.66±0.24)和8h组(6.03±0.10)较对照组差异具有统计学意义(P<0.05)。③IGF-1I、GF-1+Cur(10μm/ml)和IGF-1+Cur(20μm/ml)组VEGF-C mRNA的表达量依次为对照组的5.51、1.42和0.67倍。IGF-1组(7.20±0.85)I、GF-1+Cur(20μm/ml)(10.23±1.28)的表达量较对照组差异具有统计学意义。IGF-1+Cur(10μm/ml)(9.15±0.47)和IGF-1+Cur(20μm/ml)(10.23±1.28)组的表达量与IGF-1组差异具有统计学意义。IGF-1+Cur(20μm/ml)(10.23±1.28)的表达量与对照组差异亦具有统计学意义。结论:姜黄素能有效降低VEGF-C的表达,显著抑制IGF-1调控的宫颈癌淋巴转移。     

复方磺胺甲恶唑分散片在正常人体内的药代动力学及相对生物利用度

本文采用HPLC法同时测定血浆中复方磺胺甲噁唑吐分散片中SMZ和TMP的浓度,采用HypersilODS柱,流动相为乙腈:醋酸钠(pH6.4 0.lmol/L)=22:78(V/V),检测波长230nm,流速为1.00ml/min.10名志愿受试者自身交叉口服Go-SMZ片和Co-SMZ分散片800mg,结果显示SMZ和TMP的Cmax分别为46.69±7.66μg/ml,44.61±6.37μg/ml和1.82±0.49μg/ml,1.63±0.43μg/ml;Tmax为3.41±1.59h,3.4±0.84h和1.48±0.83h,1.50±0.81h;AUC为761±l29.37μg.h/ml,761.79±145.6μg.h/ml和26.91±3.89μg.h/ml,26.96±4.7lμg.h/ml.分散片中SMZ和TMP相对于参比制剂的相对生物利用度分别为101.28±14.35%,101.26±15.76%.     

雾霾对慢性阻塞性肺疾病患者呼出气冷凝液中炎症指标水平的影响

目的 分析雾霾对慢性阻塞性肺疾病(COPD)患者呼出气冷凝液中炎性指标水平的影响.方法 选择经本院诊断为稳定期的COPD患者62例为研究对象,根据患者所住区域分为城区组(n=30例)、郊区组(n=32例),并收集患者呼出气冷凝液(EBC),检测EBC中白细胞介素(IL)-4、IL-6、肿瘤坏死因子(TNF)-α、8-异前列腺素(8-iso-PG)及白三烯B4(LTB4)水平.结果 城区组PM2.5、PM10、SO2、NO2分别为(128.56±65.32)μg/m3、(101.38±63.17) μg/m3、(76.85±44.32)μg/m3、(293.12±171.38) μg/m3,显著高于郊区组[(92.72±40.41)μg/m3、(72.53±45.32)μg/m3、(56.20±33.57)μg/m3、(202.46± 115.63) μg/m3],差异有统计学意义(均P＜0.05);城区组IL-4、IL-6、TNF-α、8-iso-PG及LTB4水平分别为(6.27±1.78)pg/ml、(5.81±1.60) pg/ml、(15.43±2.82) pg/ml、(14.15±2.83)pg/ml、(48.35±9.42) pg/ml,郊区组分别为(5.37±1.72) pg/ml、(5.03±1.35) pg/ml、(14.06±2.43)pg/ml、(12.32±1.57)pg/ml、(40.32±6.47) pg/ml,城区组各指标均显著高于郊区组(均P＜0.05).结论 COPD患者体内存在一定的炎性反应,当机体受到雾霾刺激后可加重炎性反应,危害机体健康,临床应对雾霾提高警惕,可通过收集患者呼出气冷凝液对病情进行监测.     

高效液相色谱法测定美西律血清浓度和正常人药代动力学研究

本文报道了HPLC法测定抗心律失常药美西律血药浓度,方法灵敏、快速,并以此法研究8名正常成人单剂量口服美西律药代动力学。本测定方法以安定为内标物,流动相为甲醇和磷酸盐绥冲溶液(pH5.25),固定相为ODS(10μm),紫外检测器波长210nm。美西律和内标物的保留时间分别为5.49min和6.78rnin。在0.2～5μg/ml浓度范围与两者峰面积之比呈线性关系,y=0.7184x-0.064,r=0..9998。在三个浓度水平测得结果天内和天间变异系数均小于5％,回收率为94.3—99.6％。8名健康志愿者一次口服美西律片(100mg×3),其药——时曲线以一室开放模型拟台,并以此求算药代动力学参数,结果如下:K_a=1.328±0.634h~(-1);t_(112)=7.07±2.42h;V_d=6.23±2.22L/kg;Cl=0.509±0.157L/kg/h;T_(max)=2.79±0.71h;C_(max)=0.927±0.371μg/ml;AUC=11.723±4.870μg·h/ml。男、女间无显著性差异(p>0.1)。     

7例妇女应用布比卡因硬膜外阻滞后的药物动力学和药效学

采用HPLC法对7例妇女应用布比卡因硬膜外阻滞后的药物动力学(药动学)和药效学进行研究,数据用PKBP-N_1药动学程序包经IBM-PC计算机处理,结果符合血管外开放二室模型。T_p=19±8min;C_p=1.6±0.7μg/ml;T_((1/2)β)=166±59min;AUC=273±124μg/(min·ml);V_d=2.0±0.7L/kg。测得该药的作用完善时间和麻醉持续时间分别为21±3min和104±30min。手术期间未见明显不良反应。应用测得之药动学参数估算作用完善时和局麻持续时间的血药浓度.     

克拉霉素对铜绿假单胞菌生物被膜的影响

目的研究克拉霉素对铜绿假单胞生物被膜生物特性的影响.方法采用平板法建立生物被膜模型,银染法快速鉴定;结晶紫染色法测定生物被膜中细菌的粘附性;浓度梯度渗透法测定生物被膜的渗透性;采用卡唑/乙醇法测定克拉霉素对藻酸盐的合成抑制作用.结果采用平板法7天可建立稳定的生物被膜,1/4MIC克拉霉素与8×MIC加替沙星联合应用后光密度值由0.126±0.011显著的降低至0.114±0.012,4μg/ml组、8μg/ml组、16μg/ml组加替沙星的渗透浓度(μg/ml)可由1.210±0.091、2.911±0.112、5.911±0.213显著的增加至1.730±0.132、3.911±0.111、7.902±0.354;80μg/ml、40μg/ml、20μg/ml、10μg/ml克拉霉素组中藻酸盐的含量(μg/108CFU)由10.07±0.55显著的降低至2.34±0.21、4.91±0.16、7.22±0.36、8.82±0.50.结论克拉霉素可降低铜绿假单胞菌生物被膜中细菌的粘附性,增强加替沙星在生物被膜中的渗透能力,抑制铜绿假单胞菌藻酸盐的合成.     

平阳霉素局部注射治疗瘢痕疙瘩的实验研究

目的:应用平阳霉素局部注射治疗瘢痕疙瘩,进一步探讨平阳霉素治疗瘢痕疙瘩的作用机制。方法:收治瘢痕疙瘩患者126例,随机分为治疗组(A组:n=74)和对照组(B组:n=52)。治疗组取平阳霉素8mg,用2%利多卡因5ml稀释,自瘢痕边缘进针,针尖达瘢痕中部,自进针部位呈扇面均匀注射,使瘢痕呈现苍白色或桔皮样外观为度;对照组用醋酸泼尼松龙注射液125mg溶于2%盐酸利多卡因注射剂5ml,皮损基底部封闭治疗,注射方法和疗程同治疗组。各组连续治疗半年取材,进行组织学及组织化学观察平阳霉素局部注射治疗后瘢痕组织中Ⅲ型胶原纤维含量的变化,利用HPIAS-2000图像分析系统测定Ⅲ型胶原纤维在以上各组中的平均阳性面积率,并进行统计学分析。结果:A组中的Ⅲ型胶原纤维密集分布,B组中的Ⅲ型胶原纤维分布稀疏。图像分析结果显示,A组与B组之间Ⅲ型胶原纤维阳性面积率的差异有显著性意义(P<0.01)。结论:平阳霉素能使瘢痕组织中成纤维细胞的DNA断裂,破坏胶原纤维形成,促进胶原溶解。     

Interaction of doxorubicin with nuclei isolated from rat liver and kidney

The interaction of doxorubicin with nuclei isolated from rat liver and kidney was studied by fluorospectrometry . The nuclei had at least two different types of binding sites for the drug. Both Mg2+ and Ca2+ competitively inhibited the binding of doxorubicin to the nuclei, which showed a remarkable temperature dependency. No significant difference was observed between the numbers of binding sites (n = 6.70 X 10(-2) mol/mol of DNA for liver; 6.41 X 10(-2) mol/mol of DNA for kidney) or the affinity constants (Ka = 4.85 X 10(5) M-1 for liver; 5.41 X 10(5) M-1 for kidney) under quasi-physiological conditions. These results obtained from in vitro binding experiments support previous suggestions that the differences in the in vivo distribution of doxorubicin among tissues are not due to differences in the nuclear binding of the drug. The amount of nuclei per gram of tissue is the primary determinant of the characteristic tissue distribution of doxorubicin.     

肾病患者连续腹膜透析头孢唑林的药物动力学及给药方案

本文报告5例肾病患者连续腹膜透析应用头孢唑林的药物动力学及给药方案。1g/2L头孢唑林灌入腹腔,留置4h后,流出液内药浓度为187±53μg/ml,吸收量为57±13％;同时测得血清内药峰浓度为76±8μg/ml。停药后20h,用不含头孢唑林的透析液交换3次后,血清内药浓度为50±9μg/ml,经腹膜累积排出率为体内药量的16±3％。建议给药方案为头孢唑林0.5-1.0g/d,分2次分别加于第二、四次交换的透析液中较为合适。     

Oxidative stress studies of six TiO₂ and two CeO₂ nanomaterials: immuno-spin trapping results with DNA

Six TiO? and two CeO? nanomaterials with dry sizes ranging from 6-410 nm were tested for their ability to cause DNA centered free radicals in vitro in the concentration range of 10-3,000 ug/ml. All eight of the nanomaterials significantly increased the adduction of the spin trap agent 5,5-dimethyl-1-pyroline N-oxide (DMPO) to DNA as measured by the experimental technique of immuno-spin trapping. The eight nanomaterials differed considerably in their potency, slope, and active concentration. The largest increase in DNA nitrone adducts was caused by a TiO? nanomaterial (25 nm, anatase) from Alfa Aesar. Some nanomaterials that increased the amount of DNA nitrone adducts at the lowest exposure concentrations (100 ug/ml) were Degussa TiO? (31 nm), Alfa Aesar TiO? (25 nm, anatase) and Nanoamor CeO? (8 nm, cerianite). At exposure concentrations of 10 or 30 ug/ml, no nanomaterials showed significant in vitro formation of DNA nitrone adducts.     

平阳霉素和DNA的相互作用

平阳霉素是一种抗肿瘤抗生素，它可以和ＤＮＡ发生嵌合效应并伴有ＤＮＡ的断链。实验表明，在Ｆｅ（ＩＩ）存在下，平阳霉素对质粒ＤＮＡ和几ＤＮＡ均产生非特异性断链作用，还原剂二硫苏糖醇（ＤＴＴ）对这种断链起促进作用，螯合剂ＥＤＴＡ则起抑制作用。平阳霉素与小牛胸腺ＤＮＡ作用后，在２６０ｎｍ处吸收峰随平阳霉素浓度的增加而加强，而ＣＤ谱负带振幅明显变小，表明ＤＮＡ分子构象发生了明显变化。     

Development of pulmonary tolerance in mice exposed to zinc oxide fumes.

As a result of repeated exposures to inhaled toxicants such as zinc oxide (ZnO), numerous individuals acquire tolerance to the exposures and display reduced symptoms. To ascertain whether tolerance is developed in an animal model, NIH-Swiss mice were exposed to 1.0 mg/m(3) ZnO for 1, 3, or 5 days (1X, 3X, or 5X), and polymorphonuclear leukocyte (PMN) and protein levels in bronchoalveolar lavage (BAL) were measured. Mice acquired tolerance to neutrophil infiltration into the lungs, as total PMNs returned near baseline in 5X-exposed animals as compared to that of the 1X exposure group (1X = 2.7 +/- 0.4 x 10(4), 5X = 0.2 +/- 0.1 x 10(4), mean +/- SE, p < 0.05). Development of tolerance to changes in lavageable protein, however, was not observed (1X = 313 +/- 29 microg/ml, 5X = 684 +/- 71 microg/ml, p < 0.05). Tolerance to PMN influx did not persist following re-exposure to ZnO after 5 days of rest. In contrast to ZnO exposure, following single and repeated exposure to aerosolized endotoxin there was development of tolerance to protein in BAL (1X = 174 +/- 71 microg/ml, 5X = 166 +/- 14 microg/ml, p > 0.05), but not to PMN influx (1X = 5.5 +/- 1.7 x 10(4), 13.9 +/- 1.7 x 10(4), p < 0.05). Induction of lung metallothionein (MT) was also observed in mice exposed once or repeatedly exposed to ZnO, suggesting that MT may play a role in its molecular mechanism.     

癫痫患者苯妥英钠血药浓度与眼球震颤的关系

观察32例(男20,女12,年龄32±6a)癫痫患者眼球震颤出现及消失与苯妥英钠血浓度的关系,发现(1)出现眼球震颤的血药浓度为37±6μg/mL,提示药物过量;(2)眼球震颤出现在眼球偏斜角度的大小与苯妥英钠血浓度有关,浓度越高,角度越小,在≤45°组为48±3μg/mL,在>45°组则为35±5μg/mL;(3)眼球震颤消失时的血药浓度在20μg/mL左右。     

Oxidative stress studies of six TiO2 and two CeO2 nanomaterials: Immuno-spin trapping results with DNA

Abstract

Six TiO₂ and two CeO₂ nanomaterials with dry sizes ranging from 6–410 nm were tested for their ability to cause DNA centered free radicals in vitro in the concentration range of 10–3,000 ug/ml. All eight of the nanomaterials significantly increased the adduction of the spin trap agent 5,5-dimethyl-1-pyroline N-oxide (DMPO) to DNA as measured by the experimental technique of immuno-spin trapping. The eight nanomaterials differed considerably in their potency, slope, and active concentration. The largest increase in DNA nitrone adducts was caused by a TiO₂ nanomaterial (25 nm, anatase) from Alfa Aesar. Some nanomaterials that increased the amount of DNA nitrone adducts at the lowest exposure concentrations (100 ug/ml) were Degussa TiO₂ (31 nm), Alfa Aesar TiO₂ (25 nm, anatase) and Nanoamor CeO₂ (8 nm, cerianite). At exposure concentrations of 10 or 30 ug/ml, no nanomaterials showed significant in vitro formation of DNA nitrone adducts.     

Multiple mechanisms of adriamycin resistance in the human leukemia cell line CCRF-CEM

CEM cells exhibiting a 25-fold (C25X) or 80-fold (C80X) increase in resistance to adriamycin were isolated and characterized. C25X cells were cross-resistant to daunomycin and etoposide (VP-16) but not to vincristine or colchicine. These cells were not defective in the cellular accumulation of drug and did not contain detectable levels of P-glycoprotein. Continued exposure of C25X cells to adriamycin resulted in increased levels of resistance and additional phenotypic changes. These cells (C80X) now contained high levels of P-glycoprotein and were cross-resistant to a variety of agents including vincristine and colchicine. A fluorometric assay for DNA unwinding was used to measure levels of drug-induced DNA breaks in sensitive and C25X resistant cells. Studies carried out with VP-16, 4'9-acridinyl-aminomethanesulfon-m-anisidide (m-AMSA), adriamycin, or daunomycin showed that the level of drug-induced DNA strand breakage in resistant cells was considerably less than that occurring in drug-treated sensitive cells. These studies, therefore, show that treatment of CEM cells with adriamycin resulted in a nuclear alteration that contributed to drug resistance. They also demonstrate that prolonged treatment of cells with adriamycin resulted in membrane alterations that affect cellular drug accumulation. Adriamycin resistance in CEM cells can thus occur as a result of at least two distinct mechanisms.