血清镁离子的丙酮酸激酶法测定

目的：建立经济、准确、特异的酶法测定血清镁离子新技术。方法：根据Ｍｇ＾２＋为丙酮酸激酶（ＰＫ）的活动剂的原理，偶联乳酸脱氢酶（ＬＤＨ）反应测定Ｍｇ＾２＋，并进行方法学研究。结果：该法与定值血清的相对误差为１．０５％～２．５０％，批纳ＣＶ〈２．０２％，日间ＣＶ〈３．１２％，线性范围０．２～２．０ｍｍｏｌ／Ｌ，回收率９８．０％～１０２．８％。钾、氨、钙、锰、铜、锌、铁离子以及胆红素、甘油三酯和血红蛋白     

丙酮酸激酶的离子激活

丙酮酸激酶(pyruvate kinase,PK,EC2.7.1.40)又称三磷酸腺苷、丙酮酸2-O-磷酸转移酶,是调节糖酵解的3个限速酶之一。PK在有锰离子和镁离子存在情况下催化磷酸烯醇式丙酮酸生成丙酮酸,这一原理被用来测定血清钾离子浓度。为了证实PK活性与血清阳离子之间的关系,特别是确定与此酶活性有关的无机离子,我们进行了PK的离子激活研究,测定钾、钠、钙、锂、锰、氨和镁7种离子对PK活性的影响。由于PK的反应产物丙酮酸并不能直接指示PK活性,因而需偶联LDH系统,通过测定NADH的衰减程度来间接指示PK活性。     

石斛合剂对HepG2细胞葡萄糖激酶与丙酮酸脱氢酶活性的影响

目的探讨石斛合剂促进葡萄糖代谢的酶学机制。方法①以5%、10%、15%石斛合剂的含药血清培养HepG2细胞24h,测定葡萄糖激酶、丙酮酸脱氢酶活性;②以高浓度胰岛素培养HepG2细胞24h,继10%含药血清干预24h,测定葡萄糖激酶、丙酮酸脱氢酶的活性。结果石斛合剂的含药血清能提高HepG2细胞葡萄糖激酶、丙酮酸脱氢酶的活性（P〈0.05）;高浓度胰岛素能降低葡萄糖激酶、丙酮酸脱氢酶活性（P〈0.05）,石斛合剂的治疗能增加葡萄糖激酶、丙酮酸脱氢酶的活性（P〈0.05）。结论高浓度胰岛素能诱发胰岛素抵抗,石斛合剂能提高葡萄糖代谢关键酶活性,缓解胰岛素抵抗。     

血清微量元素和幽门螺杆菌与胃癌关系的研究

目的研究胃癌患者体内血清微量元素和幽门螺杆菌的变化关系。方法对胃癌、慢性胃炎患者和正常人(对照组)进行血清6种微量元素和幽门螺杆菌感染的测定。结果胃癌组镁(Mg)、钙(Ca)、铜(Cu)、锌(Zn)明显低于对照组,分别为Mg(0.71±0.15)mmol/L与(0.97±0.26)mmol/L,Ca(1.68±0.28)mmol/L与(2.03±0.31)mmol/L,Cu(12.27±5.91)mmol/L与(16.57±3.55)mmol/L,Zn(16.18±4.77)mmol/L与(21.78±7.37)mmol/L;胃癌患者Hp的感染率为71.4%,对照组的Hp感染率为27.3%,两组差异有显著意义(χ2=6.201,P=0.013)。结论血清微量元素变化和幽门螺杆菌感染可能与胃癌的发生有关。     

GC法检测脑脊液中乳酸的含量

用气相色谱法探讨脑瘤、脑外伤患者和正常人脑脊液中乳酸的浓度。采用 3mm× 1m不锈钢柱 ,填充涂渍为 15%聚乙二醇丁二酸酯。结果表明 :脑瘤患者 ( 2 .5± 0 .7mmol/ L)和脑外伤患者 ( 9.2± 1.7mmol/ L)脑脊液中乳酸含量与正常值 ( 1.7± 0 .9mmol/ L )比较均相差非常显著 ( P <0 .0 1)     

血清脂肪酶乳浊度速率分析法

我们应用乳浊度速率分析法测定血清脂肪酶,线性相关V=0.9933,Y_(LPS)=2119_A-8.6,平均回收率为101.3％,精密度试验批内CV为6.1％,批间CV为8.0％。TBlL80umol/L,TG2.16mmol/L,GLV10.5mmol/L对结果无干扰。用本法测定42名正常健康成人,其参考值为12.4-184V/L(±1.96S)。本方法准确,可靠,并具有简单快速的特点,可做为临床化学分析的常规检测。     

连续监测法测定血清中胆碱酯酶

采用连续监测法测定血清中的胆碱酯酶,其线性相关 r=0.9981,Y_(CHE)=1.08X—7.6,精密度实验批内 CV=3.05%,批间 CV=3.66%,平均回收率为103.0%。11.0mmol/LGLV,42umol/LTBIL 和0.5g/Hb 对测定结果干扰,用本法测定40例正常成人血清(男/女23/17)其=589ou/L 参考值范围(±1.96S)为3864—8096μ/L,本法简单快速,结果准确可靠,适合于日常临床生化检验工作中应用。     

胆固醇含量鉴别良恶性腹水的意义

目的 :探讨胆固醇含量在鉴别良恶性腹水的临床意义。方法 :对50例良性腹水和51例恶性腹水的患者同时用胆固醇氧化酶比色法测定血清、腹水胆固醇含量。结果 :50例良性腹水组腹水胆固醇为 (0 69±0 19)mmol/L,血清胆固醇 (4 1±0 65)mmol/L ;51例恶性腹水组腹水胆固醇为 (2 1±0 79)mmol/L ,血清胆固醇 (4 2±0 67)mmol/L ;二组血清胆固醇差异无显著意义(t=1,P>0 05) ,腹水胆固醇差异有显著意义 (t=9.3,P<0 001)。结论 :腹水胆固醇含量的测定有助于良恶性腹水的鉴别诊断     

检测血清尿素水平评估慢性肝炎病情

目的检测慢性肝病患者血清尿素(Urea)水平的变化,探讨其在评估慢性肝炎病情中的意义。方法采用连续监测法测定186例(分5组)慢性肝病患者及40例正常人血清Urea水平,同时测定肝功能指标,进行比较分析。结果正常对照组血清Urea水平为5.01±0.68mmol/L,慢性肝炎轻度患者为4.90±0.76mmol/L、中度患者为4.14±0.81mmol/L、重度患者为4.09±0.69mmol/L。慢性肝炎中度及重度患者血清Urea水平明显低于正常对照组(t=4.635、3.819,P<0.01)和慢性肝炎轻度患者(t=2.818、2.093,P<0.01、P<0.05)。肝硬化代偿组患者Urea(4.88±1.24mmol/L)与正常对照组比较无显著性变化(t=0.559,P>0.05),但肝硬化失代偿组患者Urea水平(6.08±2.67mmol/L)明显高于正常对照组(t=2.446,P<0.05)。结论慢性肝炎患者血清Urea水平降低,且随着病情的加重呈进行性下降,血清Urea测定可作为慢性肝炎肝脏受损的一项指标,同时对慢性肝炎病情的估计有一定价值。     

小剂量甘露醇合用加镁极化液治疗重型脑梗塞34例

目的观察小剂量甘露醇合用加镁极化液对脑梗塞的疗效.方法选取确诊的重型脑梗塞34例,予20%甘露醇注射液125ml,静脉滴注,每6～12h一次,连用10天,同时合用加镁极化液,监测血清镁水平,并与仅用20%甘露醇注射液250ml的对照组比较.结果治疗组治疗前后血清镁水平由0.78±0.12mmol/L升至1.13±0.21mmol/L,差异显著(P＜0.01),对照组则无显著差异(P＞0.05);两组显效率分别为79.4%和55.9%,总有效率分别为94.1%和73.5%,差异显著(P＜0.01).结论小剂量甘露醇合用加镁极化液对重型脑梗塞疗效肯定,值得推广.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

2010调脂治疗领域进展

2010年在调脂治疗领域针对他汀治疗心血管病的防治又进行了许多探索。本文通过综述他汀类药物的国际大规模临床试验结果,重新评价了他汀类药物在冠心病一级预防和冠心病二级预防中的地位,阐明了强化他汀治疗的意义;对他汀的心肾保护作用和安全性新证据进行了说明。