佝偻病婴幼儿血微量元素测定及临床研究

为探讨婴幼儿佝偻病和血微量元素锌、铁、铜、钙、镁、铅、镉水平的关系,以2003-2004年在保健门诊就诊的佝偻病婴幼儿120例为研究组,随机选择同一时期进行常规保健的健康婴幼儿100例为对照组,用原子吸收分光光度法对两组小儿进行了血锌、铁、铜、钙、镁、铅、镉含量测定。结果表明,佝偻病组血锌(52.42±12.80)μmol/L,与对照组相比差异非常明显(P<0.001);血铁(7.21±2.5)μmol/L,血铅(65±18.23)μg/L,与对照组相比差异明显(P<0.05)。可见佝偻病婴幼儿多伴有锌、铁缺乏和血铅偏高,治疗的同时要注意补锌补铁,并要防治铅过量。     

胎儿脐带血铅水平与钙、锌、铁的关系研究

目的研究胎儿脐带血中的铅与钙、锌、铁的含量以及两两之间的相关性。方法采用原子吸收光谱法对398例脐带血铅和钙、锌、铁的含量进行测定,并对它们进行相关性分析。结果 398例脐带血铅和钙、锌、铁的质量浓度分别为铅(37.96±17.78)μg/L、钙(1.51±0.29)mmol/L、锌(30.01±11.14)μmol/L、铁(8.63±1.39)mmol/L。线性回归分析显示:铅与钙(r=-0.563,P0.01)、铅与锌(r=-0.424,P0.01)有相关性,铅与铁无显著相关(r=0.018,P0.05)。结论随着胎儿体内血铅水平的上升,二价元素钙、锌含量有下降趋势,即中毒元素铅会干扰胎儿体内的必需二价元素的代谢。     

中药与铅(2)

宫道华选用枸杞子、益智仁、煅牡蛎、牛磺酸组成智子颗粒剂,对162名血铅浓度高于0.966μmol/L(2oμg/dL)的7～12岁的儿童进行调查观察,6c名给药组与60名对照组分别服用智子颗粒剂与杞菊地黄丸各一个月,结果给药组血铅浓度降低0.633μmol/L(13.1μg/dL),而对照组仅降低0.149μmol/L(3.1μg/dL),给药组血红蛋白和     

钆对斑马鱼胚胎发育的影响

斑马鱼胚胎毒性技术是国际标准化组织(ISO)认可的标准毒性测定方法之一,具有成本低、易操作、灵敏度高、可记录多项毒性指标等特点.本工作通过观察斑马鱼受精卵染毒后胚胎发育过程,评价了水环境中稀土元素钆的毒理学效应.实验暴露浓度为0,0.001,0.005,0.01,0.1,0.3,0.5和1.0 mmo1·L-1,观察指标包括72 h孵化率、96h幼鱼死亡率、体长及半数致死浓度(LC50)等.实验结果表明钆离子浓度低于0.005 mmol·L-1时各项观察指标均无显著影响,而随着暴露浓度的升高,钆的毒性效应逐渐增强,对斑马鱼胚胎发育产生明显抑制作用.     

高效液相色谱-电感耦合等离子体质谱联用测定DNA分子中4种脱氧核苷酸

建立了用反相离子对色谱和电感耦合等离子体质谱的联用技术同时测定DNA分子中4种脱氧核苷酸的含量。液相流动相最佳条件是:pH4.8,甲醇2.5%,10mmol/LNH4Ac。为了避免直接测定31P时14N16O1H ,15N16O 等复合离子的干扰造成信噪较差的问题,利用碰撞/反应池技术(CCT)加入O2和31P生成31P16O复合离子后测定该复合离子的信号可提高测定磷的信噪比。使用该联用技术测定4种脱氧核苷酸的检出限分别为0.211μmol/L(dCMP)、0.204μmol/L(dTMP)、0.173μmol/L(dGMP)和0.225μmol/L(dAMP),并且测定经过核酸酶酶解的质粒DNA后生成的4种脱氧核苷酸的含量分别是:152.9±2.4μmol/L(dCMP)、228.2±4.0μmol/L(dTMP)、125.3±3.0μmol/L(dGMP)和222.9±3.3μmol/L(dAMP)。     

聚多巴胺修饰电极对痕量铅的测定研究

通过多巴胺(DA)的自聚反应在玻碳电极(GCE)表面修饰一层聚多巴胺(PDA)膜,对DA的自聚条件和方波溶出伏安法测试条件进行优化。优化的实验条件为:以2 mg/m L DA的Tris-HCl(0.01 mol/L,p H8.5)溶液为自聚溶液,自聚反应时间为2.5 h,铅的测试底液为0.1 mol/L HCl溶液,修饰电极在铅测试溶液中于-1.0 V富集300 s时,溶出峰的峰形好,且峰电流大。峰电流与铅浓度分别在0.1~1.0μg/L和1.0~10.0μg/L范围内呈良好的线性关系,检出限为0.016 5μg/L。实验结果表明,该聚多巴胺修饰电极制备简单、灵敏度高、成本低,可用于加碘盐、纯净水和自来水中痕量铅的测定。     

铅暴露对学龄前儿童淋巴细胞免疫表型的影响

探讨了低水平铅暴露对学龄前儿童淋巴细胞免疫表型的影响。用石墨炉原子吸收光谱法对 2 1 7名学龄前儿童进行血铅浓度筛查 ,并在此基础上用流式细胞仪检测不同血铅水平对学龄前儿童淋巴细胞免疫表型CD+ 3 、CD+ 3 CD+ 4 、CD+ 3 CD+ 8、CD- 3 CD+ 19、CD- 3 CD+ 56的影响。结果表明 ,高铅组 (血铅≥ 0 4 83μmol/L的学龄前儿童CD+ 3 CD+ 4 、CD+ 3 CD+ 4 /CD- 3 CD+ 8水平与低铅组 (血铅 <0 4 83μmol/L)比较显著下降 (P <0 0 1 ) ;而CD+ 3 CD+ 8细胞显著升高 (P <0 0 5 ) ;CD+ 3 、CD- 3 CD+ 19、CD- 3 CD+ 56细胞无显著差异 (P <0 0 5 )。低水平铅暴露对学龄前儿童淋巴细胞免疫表型具有不利影响     

微量元素对胎儿发育影响的临床研究

为了解小于胎龄儿的血锌、铜、铅的变化 ,对 3 8例小于胎龄儿 (其中 1 2例有先天缺陷 )进行了血锌、铜、铅三种微量元素检测 ,并与 3 1例健康足月适于胎龄儿比较。结果表明 ,3 8例小于胎龄儿血锌、铜、铅结果分别为 49 4± 1 9 88μmol/L、 1 0 7± 3 3 μmol/L、 1 5± 0 83 μmol/L ;与正常对照组 (分别为 62 3 9± 1 5 2 9μmol/L、 1 1 0 2± 1 73 μmol/L、 0 82± 0 3 9μmol/L)比较 ,血锌明显低于正常组 ,t=-2 88,P <0 0 1 ;血铅明显高于对照组 ,t =4 6,P <0 0 1 ,有显著性差异。两组血铜无明显差异。小于胎龄儿血锌降低 ,血铅增高 ,而且其先天性缺陷者占3 5 .5 8% ,证明胎儿的低锌高铅状态对其生长发育有重要影响。     

子宫内低铅暴露对婴儿早期神经行为影响的研究

为探讨低铅暴露对婴儿智能发育的影响,随机选择足月顺产新生儿110例,0.48 μmol/L＞脐血铅水平≥0.24 μmol/L,作为观察组;同一时期配对足月顺产新生儿110例,脐血铅水平＜0.24 μmol/L,作为对照组;采用新生儿20项新生儿神经行为、Gesell婴幼儿发育检查量表,在出生24～36 h和3月龄时进行测试.结果表明,观察组神经行为总得分显著性低于对照组;头竖立得分显著低于对照组,头竖立时间较对照组缩短;3月龄观察组适应性、语言能力和个人社会交往显著低于对照组. 提示血铅水平低于0.48 μmol/L时,仍可对婴儿神经行为发育产生不良影响.     

电感耦合等离子体质谱法分析大鼠血、毛发及脏器中铅浓度及同位素比值

建立了电感耦合等离子体质谱(ICP-MS)同时测定铅浓度及同位素比值的方法,并应用于染毒大鼠血、毛发及组织脏器测定,以考察大鼠体内铅浓度及同位素比值分布情况及染毒剂量对其的影响.标准物质牛全血铅浓度测定结果为(278±4) μg/L,在证书标准值(283±18)μg/L范围内;测定10 μg/L Pb标准溶液的RSD<...     

An assessment of contemporary atomic spectroscopic techniques for the determination of lead in blood and urine matrices

The preparation and validation of a number of clinical reference materials for the determination of lead in blood and urine is described. Four candidate blood lead reference materials (Lots, 047–050), and four candidate urine lead reference materials (Lots, 034, 035, 037 and 038), containing physiologically-bound lead at clinically relevant concentrations, were circulated to up to 21 selected laboratories specializing in this analysis. Results from two interlaboratory studies were used to establish certified values and uncertainty estimates for these reference materials. These data also provided an assessment of current laboratory techniques for the measurement of lead in blood and urine. For the blood lead measurements, four laboratories used electrothermal atomization AAS, three used anodic stripping voltammetry and one used both ETAAS and ICP-MS. For the urine lead measurements, 11 laboratories used ETAAS (most with Zeeman background correction) and 10 used ICP-MS. Certified blood lead concentrations, ±S.D., ranged from 5.9±0.4 μg/dl (0.28±0.02 μmol/l) to 76.0±2.2 μg/dl (3.67±0.11 μmol/l) and urine lead concentrations ranged from 98±5 μg/l (0.47±0.02 μmol/l) to 641±36 μg/l (3.09±0.17 μmol/l). The highest concentration blood lead material was subjected to multiple analyses using ETAAS over an extended time period. The data indicate that more stringent internal quality control practices are necessary to improve long-term precision. While the certification of blood lead materials was accomplished in a manner consistent with established practices, the urine lead materials proved more troublesome, particularly at concentrations above 600 μg/l (2.90 μmol/l).     

Does bisphenol A bioaccumulate on zebrafish? Determination of tissue bisphenol A level

Bisphenol A (BPA) is a high-production-volume industrial chemical mainly used in the production of polycarbonates and epoxy resins utilized in the manufacture of containers, bottles, toys, and medical devices. It has systemic effects as an endocrine disruptor even at low doses. To analyze its quantity in biological materials, sensitive and reproducible methods have to be used. Different doses and duration (90 and 900 μg/L, 24 and 120 h, and 21 days) of BPA exposure to whole body zebrafish were analyzed after specific homogenization of tissue, and then a modified method HPLC was used. The mobile phase was acetonitrile and water using a gradient method of reversed-phase C18 column, and excitation = 227 nm/emission = 313 nm. The calibration curve for BPA using HPLC-fluorescence detection method was between a concentration range of 1 and 1000 ng/mL and linear, and r² = 0.999. The mean and standard error of mean values were 4.29 ± 1.05, 2.50 ± 0.92, and 2.53 ± 0.68 for control; 10.43 ± 2.61, 11.46 ± 3.24, and 8.55 ± 3.11 for BPA-90 μg/L; and 17.78 ± 4.39, 21.55 ± 4.37, and 25.32 ± 3.25 for BPA-900 μg/L (24 h, 120 h, and 21 days, respectively). Although some statistical significance among dose/time was observed between two different dose-treated groups, statistical significance was not found in dose/time results within the group. However, the positive result of BPA in the control group can be explained by low-dose, chronic exposure or prevalence of endocrine-disrupting chemicals.     

Electrochemical determination of lead using bismuth modified glassy carbon electrode

Electrochemical application of bismuth film modified glassy carbon electrode was studied with the objective of lead detection. Bismuth film on glassy carbon substrate was formed in a plating solution of 2 mmol/L Bi(NO₃)₃, in 1 mol/L HCl at ?1.1 V (vs. Ag/AgCl) for 300 s. Lead was detected by differential pulse anodic voltammetry in acetate buffer of pH 5.0 in the concentration range of 7.5 nmol/L to 12.5 μmol/L. Factors influencing the anodic stripping performance, including deposition time, solution pH, Bi(III) concentration, potential, pulse amplitude, pulse width, have been optimized. Three linear calibration plots in the range 7.5 nmol/L to 0.1 μmol/L, 0.25 to 1 μmol/L, 2.5 to 12.5 μmol/L with regression coefficients of 0.991, 0.986 and 0.978 respectively were obtained. The theoretical detection limit equivalent to three times standard deviation for 7.5 nmol/L lead (n = 5) was calculated to be 5.25 nmol/L utilizing a 5 min deposition time and sensitivity 83.97 A L/mol. The sensitivity and detection limit of the method was compared with reported voltammetric methods for detection of lead and the result obtained was found to be promising for determination of lead.     

铅染毒对大鼠体内钙、锌、铁元素的影响研究

Wistar大鼠每天腹腔注射醋酸铅649mg/kg,在第4周醋酸铅剂量降至329．5mg/kg,8周停止染毒。结果表明,随着铅染毒,大鼠出现高尿铅、高尿锌、高尿钙;脑、肝、肾中铁、锌、钙却都有不同程度提高,肝脏中锌、钙、铁、肾脏中锌、钙增加极明显;在8周停止染毒后,脑铅含量大幅度降低（P＜0．01）,肝脏铅却梢有上升（P＞0．05）,肾铅急剧增加,从47．9320μmol／L升至633．85μmol／L,大约上升13倍（P＜0．01）。     

O2-2,4-二硝基苯基偶氮二醇盐类化合物的设计、合成及抗肿瘤活性

以O2-2,4-二硝基苯基偶氮二醇盐(PABA/NO)为先导化合物,选择适当的仲胺作为偶氮二醇盐中相应的胺片段,并用碳氮键取代苯环5位的碳氧酯键,设计合成了化合物2a,2b和4a~4j,以期获得活性更强且稳定性好的抗肿瘤药物.目标化合物经1H NMR,13C NMR及HRMS进行了结构确证.生物活性测试结果表明,目标化合物可不同程度地抑制结肠癌HCT-116细胞的增殖,其中化合物4h的活性最强(IC50=7.945±0.421 μmol/L),优于PABA/NO(IC50=12.134±0.675 μmol/L).NO释放实验结果表明,此类化合物的NO释放量与细胞毒性呈正相关.化合物4h在HCT-116细胞中释放NO的量最多,约是正常细胞的2倍.此外,化合物4h在大鼠血浆中的体外稳定性显著优于PABA/NO,值得进一步研究.     

具有四氢苯并[4,5]咪唑并[1,2-a]吡嗪骨架凝血酶抑制剂的设计合成及生物活性研究

以具有四氢苯并[4,5]咪唑并[1,2-a]吡嗪新骨架的凝血酶抑制剂1为先导化合物,设计合成了14个氨基甲酸酯衍生物(2a~6a,2b~6b和7~10).同时,在化合物1结构的基础上,引入具有抗血栓活性的川芎醇(HTMP),设计合成了新型结构的化合物11.目标化合物的结构均经1H NMR,13C NMR和HRMS确证.生物活性测试结果显示,所有目标化合物对凝血酶诱导的血小板聚集均有一定的抑制活性,其中化合物4b的抑制活性[IC50=(0.11±0.08)μmol/L]强于对照药达比加群酯[IC50=(0.60±0.05)μmol/L].在体内抗血栓活性测试中,化合物4b能以剂量依赖的方式减少大鼠静脉血栓的形成.化合物11对凝血酶诱导的血小板聚集的抑制活性较弱,但其抑制大鼠静脉血栓形成的作用与达比加群酯相当,这可能是由于化合物11在体内水解为川芎醇和化合物1,两者协同产生抗血栓作用所致.     

Fast simultaneous determination of trimethoprim and sulfamethoxazole by capillary zone electrophoresis with capacitively coupled contactless conductivity detection

The association of trimethoprim and sulfamethoxazole is a very effective with antibiotic properties, and commonly used in the treatment of a variety of infections. Due to the importance in diseases treatment of humans and also of animals, the development of methods for their quantification in commercial formulations is highly desirable. In the present study, a rapid method for simultaneous determination of these compounds using CE with capacitively coupled contactless conductivity detection was developed. A favorable working region for both analytes was from 12.5 to 200 μmol/L (linear responses with R > 0.999 for N = 5). Other parameters calculated were sensitivity (1.28 ± 0.10/1.45 ± 0.11) min/(μmol L), RSD (4.5%/2.0%), and LOD (1.1/3.3) μmol/L for trimethoprim and sulfamethoxazole, respectively. Under this condition, the total run time was only 2.6 min. The proposed method was applied to the determination of trimethoprim and sulfamethoxazole in commercial samples and the results were compared to those obtained by using a HPLC pharmacopoeia method. This new method is advantageous for quality‐control analyses of trimethoprim and sulfamethoxazole in pharmaceuticals samples, because it is rapid and precise. Moreover, it is less laborious and demands minimum amounts of reagents in comparison to the recommended method.     

Evaluation of antioxidants in Dong quai (Angelica sinensis) and its dietary supplements

The antioxidant activity (AA), total phenolic content (TPC) and total flavonoids content (TFC) in Dong quai (DQ, Angelica sinensis) raw materials and dietary supplements (DS) containing this plant were determined using the CUPRAC, FRAP and fluorescence methods. The antioxidant activity for DQ aqueous extracts revealed by CUPRAC was (1330.45 ± 1.30) μmol Trolox equivalent (TE) per 100 g of dry mass (DM), whereas the antioxidant activity as determined by FRAP was (1813.9 ± 2.0) μmol of TE per 100 g of DM. Lower values were noted for the fluorescence method than for CUPRAC and FRAP (ranging from (35.96 ± 0.3) to (304.6 ± 1.4) μmol of TE per 100 g of DM). The highest TPC values were determined for an aqueous extract of DQ ((3330.3 ± 2.3) μmol of TE per 100 g of DM), while TFC for ethanolic extracts of DQ was ((146.50 ± 0.5) mg of quercetin equivalent (QE) per 100 g of DM). Cinnamic acid, isomers of benzoic acid and derivatives of quercetin were analysed by HPLC-PDA. The ferulic acid concentration in an ethanolic extract of DQ was (21.83 ± 0.07) mg per 100 g of DM. Of the flavonols detected, rutin exhibited the highest concentration in ethanolic extract of DQ ((3.32 ± 0.13) mg of QE per 100 g of DM). Other phytochemicals (alkaloids, saponins, flavonoids, anthraquinones, tannins, steroids, etc.) were identified by phytoscreening colour reaction. The results were analysed by principal component analysis (PCA), cluster analysis and one-way ANOVA tests.     

CTP synthetase activity assay by liquid chromatography tandem mass spectrometry in the multiple reaction monitoring mode

Cytidine 5′‐triphosphate synthetase (CTPS) is known to be a central enzyme in the de novo synthesis of CTP. We have recently demonstrated that a deficiency in CTPS1 is associated with an impaired capacity of activated lymphocytes to proliferate leading to a combined immunodeficiency disease. In order to better document its role in immunomodulation, we developed a method for measuring CTPS activity in human lymphocytes. Using liquid chromatography‐mass spectrometry, we quantified CTPS activity by measuring CTP in cell lysates. A stable isotope analog of CTP served as internal standard. We characterized the kinetic parameters V_max and K_m of CTPS and verified that an inhibition of the enzyme activity was induced after 3‐deazauridine (3DAU) treatment, a known inhibitor of CTPS. We then determined CTPS activity in healthy volunteers, in a family whose child displayed a homozygous mutation in CTPS1 gene and in patients who had developed or not a chronic lung allograft dysfunction (CLAD) after lung transplantation. Linearity of the CTP determination was observed up to 451 μmol/L, with accuracy in the 15% tolerance range. Michaelis‐Menten kinetics for lysates of resting cells were K_m=280±310 μmol/L for UTP, V_max=83±20 pmol/min and, for lysates of activated PBMCs, K_m=230±280 μmol/L for UTP, V_max=379±90 pmol/min. Treatment by 3DAU and homozygous mutation in CTPS1 gene abolished the induction of CTPS activity associated with cell stimulation, and CTPS activity was significantly reduced in the patients who developed CLAD. We conclude that this test is suitable to reveal the involvement of CTPS alteration in immunodeficiency.     

Influence of heavy metals, especially lead, on lipid metabolism, serum alpha-tocopherol level, total antioxidant status, and erythrocyte redox status of copper smelter workers

An assessment of influence of the occupational exposure to heavy metals, especially lead, on serum lipids (including lipid peroxides), total antioxidant status, erythrocyte redox status, and serum alpha-tocopherol level was performed in a group of 141 healthy male copper smelter workers. The following parameters were measured: blood lead and cadmium levels, serum manganese, copper, zinc, calcium and magnesium levels, free erythrocyte protoporphyrins (FEP), total cholesterol, HDL₂-, HDL₃-cholesterol, triglycerides and lipid peroxides in serum, erythrocyte superoxide dismutase (SOD_E), catalase (Cat_E) and glutathion peroxidase (PxGSH_E) activities, erythrocyte reduced glutathione level (GSH_E), serum alpha-tocopherol level, and serum total antioxidant status (TAS). Mean Pb_B was within the norm range (328.2 ± 141.7 μg/L), but mean Mn_S concentration slightly exceeded 10 μg/L (11.04 ± 3.79 μg/L). Mean cholesterol and triglycerides concentrations were near the highest borderline values. We found a significantly negative correlation between lead levels and HDL₃-cholesterol (r = 0.253, P < 0.05). Erythocyte catalase activity and TAS were lowered. TAS showed significant negative correlation with Pb_B. A group of workers with Pb_B≥ 400 μg/L had significantly lower Cat_E, lower TAS, and lower HDL₃-cholesterol, compared to the workers with Pb < 400 μg/L. We have also found positive correlation between alpha-tocopherol and total cholesterol (r = 0.267, P < 0.05) and between alpha-tocopherol and LDL-cholesterol (r = 0.207, P < 0.05).