α-Adrenoceptor-mediated inhibitory effect of the sympathetic nervous system on the isoprenaline-induced increase in plasma renin concentration

Summary The importance of the sympatho-adrenal system for the isoprenaline-induced increase in plasma renin concentration was investigated in conscious rats. Ganglionic blockade by trimethidinium (10 mg kg^–1) increased the dose-dependent elevation of plasma renin concentration induced by isoprenaline (0.03–0.48 g kg^–1 min^–1). Also treatment of the rats with guanethidine (6 mg kg^–1) or reserpine (2.5 mg kg^–1, given 16 and 7 h prior to the experiments) further increased the effect of isoprenaline (0.5 g kg^–1 min^–1) on plasma renin concentration. Unilateral renal denervation combined with contralateral nephrectomy doubled the effect of the -sympathomimetic amine on renin release. The -adrenoceptor antagonist phenoxybenzamine (3 mg kg^–1) also enhanced the effect of isoprenaline on this parameter.It is concluded that apart from a stimulation of renin release via -adrenoceptors the sympathetic nervous system may inhibit renin release via stimulation of -adrenoceptors.Supported by DFG Me 541/1Partial preliminary communication: Meyer et al. (1976)     

Binding of 16α-gitoxin and its 16-acetate to human serum albumin

Summary The binding of semi-synthetic (16-gitoxin and its 16-acetate) and naturally occurring cardioactive glycosides (digitoxin, ouabain) to human serum albumin was studied using equilibrium dialysis, ultracentrifugation and gel filtration. 16-gitoxin was 75% bound and its 16-acetate 95%. The percentage binding of digitoxin and ouabain was in good agreement with values reported in literature.     

Bioavailability assessment: Methods to estimate total area (AUC 0-∞) and total amount excreted (A e ∞ ) and importance of blood and urine sampling scheme with application to digoxin

Five methods are compared to estimate the total area under the digoxin plasma or serum concentrationtime curve (AUC0-) after a single dose of drug. To obtain accurate estimates of AUC0-, data required are concentrations at a sufficient number of sampling times to define adequately the concentration-time curve prior to the log-linear phase, and at least three, but preferably four or more equally spaced points in the terminal loglinear phase. One method (designated Method I) requires a digital computer; another (Method III) is the classical method (these two methods do not require equally spaced points in the loglinear phase). Method IIA is the accelerated convergence method of Amidon et al.; Methods IIB and IIC are modifications of this method, but incorporate usual and orthogonal least squares, respectively, which make them more accurate with real (noisy) data. Methods I and IICgave very comparable estimates of AUC0-. Results indicate that digoxin administered orally in aqueous solution was completely (100%) absorbed when bioavailability estimates were based on oral and intravenous AUC0- estimates and the actual doses, whereas formerly only about 80% absorption was reported, based on areas, under plasma concentration curves which were truncated at 96 hr. It is shown that the sampling scheme of blood can produce biased apparent bioavailability estimates when areas under truncated curves are employed, but an appropriate sampling scheme and application of method IIyield accurate bioavailability estimates. This is important particularly in those bioavailability studies where one is attempting to determine the appropriate label dose for a new fastrelease digoxin preparation relative to the label dose and bioavailability of currently marketed tablets. It is shown that the magnitudes and variability of apparent elimination rate constants and halflives of digoxin, estimated from urinary excretion data by the ^– method, depend on which value of A _e is used. The formerly reported greater interindividual variability of AUC data compared to At data for digoxin is explained in that the AUCs, but not the A_e,'s, involve the renal clearance, which exhibits considerable inter- and intraindividual variation.     

乌鲁木齐地区维汉哮喘儿童ADAM33基因多态性与IgE、维生素D的相关性研究

目的 探讨乌鲁木齐地区维汉支气管哮喘儿童ADAM33基因多态性、IgE及VitD水平及其相关性研究,期望从基因水平为指导喘患儿的防治提供理论依据.方法 选取同期3 ～15岁于乌鲁木齐地区生活的维汉哮喘息儿197例(其中汉族111例,维族86例),同时设立对照组120例(汉族64例,维族56例),首先采用PCR对ADAM 33基因S2位点SNP分型,用ELISA法检测IgE、VitD水平,进一步根据民族进行组内分层,进行S2位点SNP、IgE、VitD水平分析并进行相关性分析.结果 ①ADAM33 s2位点基因型频率分布在病例组和对照组间差异有统计学意义(x2 =24.949,P＜0.001),同时等位基因频率间差异也有统计学意义(x2 =25.640,P=0.000).②S2位点3种基因型频率分布在维、汉哮喘儿童中分布均存在统计学意义(x2=7.992,P=0.018;x2 =20.140,P＜0.001).③实验组IgE水平高于对照组、VitD水平低于对照组,差异有统计学意义(x2 =13.250,P＜0.001;x2=4.793,P＜0.001).④实验组组内维族哮喘儿童IgE水平高于、VitD水平低于汉族哮喘儿童,差异有统计学意义(x2=2.434,P=0.016;x2 =2.956,P=0.004);对照组组内维汉儿童IgE、VitD比较无统计学差异(x2=1.072,P=0.286;x2 =0.619,P=0.537).⑤ADAM 33基因s2位点与IgE、VitD均无明显相关(r=0.129,P=0.021;r=-0.181,P=0.001).结论 ①ADAM33基因S2位点突变与乌鲁木齐地区维汉哮喘儿童发病均相关,可能是维汉哮喘儿童共同易感基因.②维族哮喘儿童IgE水平高于、VitD水平低于汉族哮喘儿童.③ADAM33基因S2位点不影响IgE及VitD水平.     

Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C virus-positive patients of North India

Purpose: Humans are the only known natural hosts of hepatitis C virus (HCV). This study was undertaken to examine the frequencies of human leucocyte antigens (HLAs) Class I and Class II genotype profiles in anti-HCV-infected patients of Northern India. Materials and Methods: From a period of January 2013 to August 2014, 148 anti-HCV-positive patients of North India referred to the Department of Molecular Biology and Transplant Immunology, Indraprastha Apollo Hospitals, New Delhi, for performing HLA typing were included in the study. Results: A*02, A*31 allele frequency decreased significantly in anti-HCV-positive patients. Frequencies for HLA-B loci did not reach any statistical significance. Among the Class II alleles, HLA-DRB1*03 and HLA-DRB1*10 were significantly higher in the patient population, and HLA-DRB1*15 was significantly decreased in the patient population as compared to the controls. Conclusion: HLA-A*33 was significantly increased as compared to control population and showed geographic variation in HCV-infected individuals of India.     

DADS上调miR-200b抑制视网膜母细胞瘤细胞的生长与侵袭

目的 探索miR-200b和二烯丙基二硫(DADS)相关的抑瘤机制,为揭示DADS抑制视网膜母细胞瘤生长及侵袭的内在分子机制提供理论依据.方法 采用qRT-PCR分别检测不同浓度的DADS对Y79细胞miR-200b表达的影响,DADS分别设置六种浓度:0 μmol/L、25 μmol/L、50 μmol/L、100 μmol/L、200 μmol/L和400 μmol/L.MTT和Transwell侵袭实验分别检测DADS和miR-200b对Y79细胞生长及侵袭能力的影响,将实验设置成五个组,即miRNA阴性对照组(瞬时转染scramble 40μmol/L);miR-200b组(瞬时转染miR-200b-mimics 40μmol/L);DADS阴性对照组(DMSO 10μmol/L,即mock组);DADS组(DADS 200μmol/L)和DADS+miR-200b组(瞬时共转染miR-200b-mimics 40μmol/L)和DADS (200μmol/L).结果 DADS可上调Y79细胞中miR-200b的表达,且其呈剂量依赖性(P<0.05);在MTT实验中,miR-200b组的OD值(0.549±0.057)较miRNA阴性对照组(0.737±0.135)明显降低;DADS组的OD值(0.508±0.064)较DADS阴性对照组(0.722±0.145)明显降低;而DADS+miR-200b组的OD值(0.362±0.081)较miRNA阴性对照组和DADS阴性对照组降低最为显著(P<0.05),即DADS可以通过上调miR-200b抑制Y79细胞的增殖能力.在Transwell侵袭实验中,外源性的高表达miR-200b组(105±13)较miRNA阴性对照组(162±12)能够显著抑制Y79细胞的穿膜细胞数,DADS组(102±13)较DADS阴性对照组(154±8)能够显著降低Y79的穿膜细胞数,且DADS+miR-200b组(77±8),细胞穿膜细胞数较miRNA阴性对照组和DADS阴性对照组减少最显著(P<0.05),即DADS通过上调miR-200b抑制Y79细胞侵袭.结论 DADS通过上调miR-200b的表达抑制视网膜母细胞瘤细胞的生长及侵袭.     

子宫内膜异位症中miR-143、miR-145和miR-126的差异表达

目的探索子宫内膜异位症（EMs）中miR-143、miR-145和miR-126的差异表达,以及不同月经周期的影响。方法利用realtimeRT-PCR技术,比较miR-143、miR-145和miR-126在EMs患者在位内膜（EU,2例）、异位内膜（EC,14例）、配对EU+EC（14例）,与非EMs患者内膜（EN,28例）中的表达差异;并分析EN和EC组不同月经周期对miR-143、miR-145和miR-126表达的影响。结果不同月经周期的影响分析,发现仅EN标本中miR-143增生期表达量高于分泌期,差异有统计学意义（P＜0.05）。与EN相比,miR-143和miR-145在EU中均表达上调（P＜0.05）,miR-143、miR-145和miR-126在EC中均表达上调（P＜0.01）。配对EU-EC中,miR-143、miR-145和miR-126在EC中均表达上调（P＜0.01）。结论miR-143、miR-145和miR-126在EMs中表达高于非EMs,在EC中表达高于EU。     

人白细胞介素-33在胶质瘤中高表达并能促进胶质瘤细胞U251的侵袭作用

目的:探讨人白细胞介素(interleukin,IL)-33在胶质瘤中的表达及在胶质瘤细胞U251侵袭中的作用?方法:采用免疫组化法检测了16例正常脑组织及86例不同级别胶质瘤标本IL-33蛋白的表达情况;应用Transwell小室检测IL-33对U251侵袭的影响;应用Western blot检测IL-33对胶质瘤细胞NF-κB及其磷酸化状态的影响?结果:免疫组化结果显示,IL-33在胶质瘤组织中表达高于正常脑组织(54.65% vs. 6.25%,P < 0.001)?IL-33在低级别胶质瘤(WHO Ⅰ?Ⅱ级)和高级别胶质瘤(WHO Ⅲ?Ⅳ级)组织中的阳性表达率分别为17.4%和68.3%(P < 0.001)?体外胶质瘤细胞的功能试验中,IL-33能促进U251细胞的侵袭(P < 0.05),并伴随NF-κB蛋白表达上调(P < 0.05)?结论:IL-33在胶质瘤中高表达,IL-33可能通过促进胶质瘤细胞NF-κB磷酸化,从而促进胶质瘤细胞的侵袭能力,对IL-33作用机制的进一步研究将为胶质瘤的临床治疗提供新思路?     

下调CD133表达对肝癌细胞恶性生物学行为的影响

目的:探讨下调CDl33基因的表达对肝癌细胞生物学行为的影响。方法:将合成的CDl33小干扰核糖核酸分子(si RNA)转染至肝癌SMMC7721细胞并检测转染效率;分别以无转染与转染随机si RNA序列的SMMC7721细胞为空白对照和阴性对照,观察CDl33 si RNA转染后CDl33基因沉默效果,以及SMMC7721细胞主要生物学行为的变化。结果:转染24 h后,转染效率可达到(80.8±9.1)%;与空白对照组比较,CDl33 si RNA转染后的SMMC7721细胞CD133 m RNA及蛋白表达量分别降至空白对照组的10%与35%、细胞增殖活性明显降低、细胞凋亡率明显增加(41.3%vs.25.3%)并出现明显的S期阻滞,集落形成能力明显降低(均P0.05)。阴性对照组与空白对照组各指标无统计学差异(均P0.05)。结论:CDl33在肝癌细胞中可能起了癌基因作用,下调其表达能抑制肝癌的恶性生物学行为。     

飞利浦彩色超声iE33掉电故障排查整体思路解析

目的：根据飞利浦彩色超声iE33日常使用当中出现的掉电故障,探讨此类故障行之有效的诊断维修思路。方法：根据掉电故障类型分为连续型以及间歇型分析,结合测量以及隔离等有效手段,按部就班确定故障。结果：设计的故障排查整体思路,可顺利快捷地将故障圈定,能够明显提高故障处理效率。结论：该诊断思路可针对飞利浦iE33常见的掉电故障,通过测量及隔离等手段,为更有效率地处理掉电故障提供了可靠的排查整体思路。