血浆内源性洋地黄样物质在围体外循环期的动态变化

目的探讨围体外循环(CPB)期患者血浆内源性洋地黄样物质(EDLS)浓度的变化及对心功能的影响。方法29例心功能分级(纽约心脏学会分级)为~级的先天性或后天性成年心脏病患者纳入研究。分别于CPB前、停机、术后2 h、6 h、1 d和3 d取静脉血,放免法测定血浆EDLS浓度。结果级心功患者术前血浆内EDLS浓度〔(403±27)pg/mL〕显著高于级〔(221±98)pg/mL,P<0.01〕和级患者〔(296±71)pg/mL,P<0.01〕。CPB能够引起EDLS的浓度升高,至术后2 h〔(683±371)pg/mL〕和6 h〔(577±274)pg/mL〕达峰值,显著高于术前〔(324±79)pg/mL,P<0.01〕,术后24 h恢复至术前水平。然而,无论在手术后2 h或6 h,高浓度EDLS(>1000 pg/mL)患者血压和正性肌力药物的使用与中等浓度(401~999 pg/mL)和低浓度EDLS(<400 pg/mL)患者差异无统计学意义,但术后高浓度EDLS组级心功患者比例(术后2 h:50%;术后6 h:63%)显著高于低浓度组(术后2 h:0%;术后6 h:8%)和中等浓度组(术后2 h:11%;术后6 h:30%)。相关性分析显示,手术后2 h和6 h血浆EDLS浓度与升主动脉阻断时间无关(r分别为0.0748和0.0393)。结论心力衰竭和CPB手术均能够引起EDLS的释放。手术后2~6 h血浆EDLS的浓度迅速升高。高浓度的EDLS与心脏缺血损伤的严重程度无关,但可能增强心功能。     

人血白蛋白热原去除工艺的实验

在热原不合格的白蛋白制品中，加入血浆蛋白Ｃｏｈｎ分部ＩＶ－１、ＩＶ－４组份进行热变性沉淀去除热原。经处理后，热原检测（兔法）表明，４批平均降温０．４７℃回收率为７２．５％，白蛋白５７％５０ｈ的热稳定性试验合格。其它常规检测项目均符合生物制品规程要求。     

Activation of A1 adenosine receptors decreases the release of serotonin in the rabbit hippocampus,but not in the caudate nucleus

Summary The effects of A1 adenosine receptor ligands on the evoked release of serotonin (5-HT) were studied in slices of the hippocampus and the caudate nucleus of the rabbit, preincubated with ³H-5-HT. In hippocampal tissue electrical stimulation elicited a release which was inhibited by the adenosine receptor agonist N⁶-cyclohexyladenosine (CHA) and enhanced by the selective A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The concentration-response curve of CHA was shifted to the right by DPCPX. The shift corresponded to a pA₂ value of 9.4 for DPCPX. CHA, R-N⁶-phenylisopropyladenosine (R-PIA) and DPCPX were ineffective in caudate nucleus tissue. When instead of electrical pulses high K⁺ was used to induce 5-HT release in the presence of the Na⁺ channel blocker tetrodotoxin (TTX), which was present in order to exclude effects mediated by interneurones, CHA was equally effective in the hippocampus but again failed to modify 5-HT release in the caudate nucleus. The disinhibition by DPCPX of the evoked 5-HT release was used to calculate the extracellular concentration of endogenous adenosine at the A₁ receptor. The calculation greatly depended on the dissociation constant of adenosine at the A1 receptor.It is concluded that A1 adenosine receptors, activated by the endogenous agonist at a concentration of about 0.7 mol/l, are located on serotonergic nerve endings in the hippocampus, but not in the caudate nucleus. The estimated extracellular concentration of endogenous adenosine is in reasonable agreement with actually measured concentrations reported in the literature. Send offprint requests to T. J. Feuerstein at the above address     

茴香注射液热原检查方法学研究

目的:验证红茴香注射液热原检查的适用性。方法:参考《中国药典》2010年版一部附录中药注射剂安全性检查法应用指导原则,对红茴香注射液进行热原检查的方法学验证。结果:红茴香注射液原液在剂量为1 mL.kg-1有一定的毒性反应,不适宜进行热原试验;10倍稀释液对热原检查无干扰。结论:可用热原检查法检查红茴香注射液中可能存在的热原,浓度为其10倍稀释液,剂量为1 mL.kg-1。     

血清胱抑素C测定在糖尿病肾病早期肾损伤中的检测价值

目的：检测血清半胱氨酸蛋白酶抑制剂C（胱抑素C,Cys—C）浓度,评价其对糖尿病肾病患者的早期诊断价值。方法：应用乳胶颗粒增强散射免疫比浊法（PENIA）测定88例糖尿病患者和30名健康体检者的血清Cys—C浓度,并同时测定血清肌酐（SCr）、β2-微球蛋白（β2-MG）、糖化血红蛋白A1c）HbA1c）、尿微量白蛋白（UMA）和尿肌酐（UCr）,计算出内生肌酐清除率（CCr）。比较Cys-C与其他指标的相关性。结果：微量白蛋白尿组和临床白蛋白尿组的Cys—C、SCr、CCr、β2-MG、UMA均较正常白蛋白尿组和健康对照组有显著性差异;Pearson相关分析显示：糖尿病患者血Cys—C与SCr、β2-MG、UMA呈正相关,与CCr呈负相关。结论：Cys-C在评价糖尿病患者的肾功能状况时与SCr的相关性好且灵敏度高于Ccr、UMA和β2-MG等肾小球滤过率标志物。故Cys—C对糖尿病肾病早期诊断价值较其他指标更高。     

Vinyl Chloride—A Classical Industrial Toxicant of New Interest

The carcinogenicity of vinyl chloride in humans was recognized in 1974 based on observations of hepatic angiosarcomas in highly exposed workers. A multiplicity of endpoints has been demonstrated. The primary target organ, the liver, displays differential susceptibilities of hepatocytes and sinusoidal cells, which are modified by factors of age and dose. There is consistency in organotropism between experimental animals and humans. Vinyl chloride is a pluripotent carcinogen, predominantly directed toward hepatic endothelial (sinusoidal) cells, and second toward the parenchymal cells of the liver. The similarity of results between experimental animals and humans is a solid basis of an amalgamation of experimental and epidemiological risk estimates. Vinyl chloride requires metabolic activation for carcinogenicity and mutagenicity, and toxicokinetics are a key to interpret the dose response. Practically the entire initial metabolism of vinyl chloride is oxidative. At higher exposure concentrations this is nonlinear, and metabolic saturation of metabolism in rats is reached at about 250 ppm. This is consistent with the plateau of hepatic angiosarcoma incidence in rat bioassays. Physiologically based pharmacokinetic/toxicokinetic (PBPK) models have been developed and successfully applied within the frame of human cancer risk assessments. The major DNA adduct induced by vinyl chloride (～ 98% of total adducts in rats), 7-(2-oxoethyl)guanine, is almost devoid of promutagenic activity. The clearly promutagenic “etheno” adducts N²,3-ethenoguanine and 3,N⁴-ethenocytosine each represent ～ 1% of the vinyl chloride DNA adducts in rats, and 1,N⁶-ethenoadenine is found at even lower concentrations. Etheno adducts appear to have a long persistence and are repaired by glycosylases. Vinyl chloride represents a human carcinogen for which a series of mechanistic events connects exposure with the carcinogenic outcome. These include (1) metabolic activation (to form chloroethylene oxide), (2) DNA binding of the reactive metabolite (to exocyclic etheno adducts), (3) promutagenicity of these adducts, and (4) effects of such mutations on protooncogenes/tumor suppressor genes at the gene and gene product levels. In rat hepatocytes, a further event is a biomarker response. Cancer prestages (enzyme-altered foci), as quantitative biomarkers, provide a tool to study dose response even within low dose ranges where a carcinogenic risk cannot be seen in cancer bioassays directly. Such biomarker responses support a linear nonthreshold extrapolation for low-dose assessment of carcinogenic risks due to vinyl chloride. Published risk estimates based on different sets of data (animal experiments, epidemiological studies) appear basically consistent, and on this basis an angiosarcoma risk of ～ 3 × 10^?4 has been deduced by extrapolation, for exposure to 1 ppm vinyl chloride over an entire human working lifetime. An important point that should be considered in regulatory standard settings is the presence of a physiological background of those etheno DNA adducts, which are also produced by vinyl chloride. Likely reasons for this background are oxidative stress and lipid peroxidation. In essence, fundamentals of the hepatocarcinogenicity of vinyl chloride appear now well established, providing a solid scientific basis for regulatory activities.     

内源性类洋地黄样物质的放免测定及与高血压的关系

本文应用地高辛放射免疫测定法对46例正常人及36例高血压患者进行了血清内源性类洋地黄样物质(EDLC)测定。结果表明高血压患者血清EDLC含量为0.50±0.39nmol/L(X±S)明显高于正常对照组(P<0.01)。同时设备在压患者EDLC水平与心纳素(ANO)含量呈正相关而与醛固酮(ALD)含量呈负相关。     

兔法与鲎试剂法检测大输液热原控制标准探讨

采用家兔法和鲎试剂法抽检临床４８２批大输液的热原，并对４０批（８０００瓶）大输液的临床热原反应作追踪调查。结果表明大输液产品质量是临床热原反应的主要原因。经比较认为鲎试剂法检测热原的准确度和灵敏度较家兔法为高。提出家兔法检测热原的新控制标准为三只兔升温总和＜１℃。     

新的人内源性逆转录病毒NP9基因的分子克隆与病毒蛋白表达

目的:研究新近发现的人内源性逆转录病毒NP9基因与自身免疫性疾病的相关性及其可能的作用机制,构建该基因的蛋白表达系统. 方法:提取自身免疫性疾病患者外周血单个核细胞(PBMCs)的总RNA,利用RT-PCR 技术,扩增NP9基因,然后将该片段进行T-A克隆并测序鉴定,纯化回收后亚克隆于原核表达载体pQE30中,然后提取质粒,酶切鉴定;最后经IPTG诱导,原核表达重组子在M15宿主菌进行表达,并进行SDS-PAGE与Western 印迹分析与鉴定.结果:应用RT-PCR 技术,从系统性红斑狼疮患者外周血单个核细胞的总RNA中扩增到一条大小约为250 bp的片段,经T-A克隆与测序鉴定,证实此片段为NP9基因,具有一个完整的开放阅读框架;将pQE 30-NP9重组子转化入宿主菌,用IPTG诱导菌体表达NP9重组蛋白,经SDS-PAGE电泳和Western印迹技术鉴定证实:在相对分子量约9kD处见明显的病毒特异性的高表达条带.结论:已成功克隆了新的人内源性逆转录病毒NP9基因,并经IPTG诱导,在M15宿主菌中表达了相应的病毒蛋白,为进一步研究该逆转录病毒与自身免疫性疾病的相关性奠定基础.