复方鱼腥草口服液质控项目的研究

目的：建立复方鱼腥草口服液质量控制项目。方法：用聚酰胺薄层色谱法对口服液中的主要成分之一绿原酸进行定性鉴别。用ＲＰ－ＨＰＬＣ法对黄芩苷进行含量测定。采用ＯＤＳ柱,流动相为甲醇－０．２％磷酸水溶液（５２：４８）。结果：线性范围０．１６２４～１．６２４ｕｇ。平均回收率为１０１．６％,ＲＳＤ＝１．２％。结论：上述方法简便、重复性好。可用于本品的质量控制。     

Genome-wide association with select biomarker traits in the Framingham Heart Study

Background

Systemic biomarkers provide insights into disease pathogenesis, diagnosis, and risk stratification. Many systemic biomarker concentrations are heritable phenotypes. Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations.

Methods

We examined the association of Affymetrix 100K GeneChip single nucleotide polymorphisms (SNPs) to 22 systemic biomarker concentrations in 4 biological domains: inflammation/oxidative stress; natriuretic peptides; liver function; and vitamins. Related members of the Framingham Offspring cohort (n = 1012; mean age 59 ± 10 years, 51% women) had both phenotype and genotype data (minimum-maximum per phenotype n = 507–1008). We used Generalized Estimating Equations (GEE), Family Based Association Tests (FBAT) and variance components linkage to relate SNPs to multivariable-adjusted biomarker residuals. Autosomal SNPs (n = 70,987) meeting the following criteria were studied: minor allele frequency ≥ 10%, call rate ≥ 80% and Hardy-Weinberg equilibrium p ≥ 0.001.

Results

With GEE, 58 SNPs had p < 10^-6: the top SNPs were rs2494250 (p = 1.00*10^-14) and rs4128725 (p = 3.68*10^-12) for monocyte chemoattractant protein-1 (MCP1), and rs2794520 (p = 2.83*10^-8) and rs2808629 (p = 3.19*10^-8) for C-reactive protein (CRP) averaged from 3 examinations (over about 20 years). With FBAT, 11 SNPs had p < 10^-6: the top SNPs were the same for MCP1 (rs4128725, p = 3.28*10^-8, and rs2494250, p = 3.55*10^-8), and also included B-type natriuretic peptide (rs437021, p = 1.01*10^-6) and Vitamin K percent undercarboxylated osteocalcin (rs2052028, p = 1.07*10^-6). The peak LOD (logarithm of the odds) scores were for MCP1 (4.38, chromosome 1) and CRP (3.28, chromosome 1; previously described) concentrations; of note the 1.5 support interval included the MCP1 and CRP SNPs reported above (GEE model). Previous candidate SNP associations with circulating CRP concentrations were replicated at p < 0.05; the SNPs rs2794520 and rs2808629 are in linkage disequilibrium with previously reported SNPs. GEE, FBAT and linkage results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.

Conclusion

The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.

     

睡眠剥夺对力竭运动大鼠胸腺谷胱甘肽、丙二醛、超氧化物歧化酶的影响

目的:观察不同睡眠剥夺时间后力竭运动对大鼠胸腺谷胱甘肽、丙二醛含量和超氧化物歧化酶活性的变化,探讨睡眠剥夺对大鼠抗氧化能力的影响。方法:实验于2006-04/05在湖南师范大学体育学院运动生物化学实验室完成。实验分组:选择10周龄健康雄性SD大鼠30只,按随机数字表法分为5组,每组6只:睡眠非运动组,睡眠 力竭运动组和睡眠剥夺24,48,72h 力竭运动组。实验方法:①采用轻柔刺激法制备大鼠睡眠剥夺模型。②睡眠非运动组和睡眠 力竭运动组不进行睡眠剥夺。③睡眠 力竭运动组和睡眠剥夺各组大鼠运动方案:跑台坡度为10°,速度为19.3m/min(相当于76%VO2max),所有大鼠运动至力竭(运动末期,大鼠先后滞留跑道后1/3处达3次以上,各种刺激驱赶均无效,停跑后体征表现为呼吸急促,神情倦怠,腹卧位,对刺激反应迟钝,捕捉时,逃避反应较运动前减弱)。实验评估:①大鼠一般状态。②力竭时间。③大鼠力竭后麻醉处死,测定胸腺谷胱甘肽、丙二醛含量和超氧化物歧化酶活性。结果:纳入大鼠30只,均进入结果分析。①大鼠一般状态:睡眠 力竭运动组大鼠表现为形态正常,活泼好动,皮毛光亮,眼睛有神;睡眠剥夺48,h 力竭运动组大鼠均出现神态倦怠,眼神黯淡,四肢亦有不同程度的红肿;睡眠剥夺24h 力竭运动组大72鼠介于以上两者之间。②睡眠 力竭运动组和睡眠剥夺24,7248,h组大鼠的力竭时间分别为(232.36±37.67),(269.19±38.61),(162.42±35.70),(141.07±28.56)。③谷胱甘肽含量、超氧化物歧化酶活性:睡眠 力竭运动组谷胱甘肽含量和超氧min化物歧化酶活性均低于睡眠非运动组[分别为(25.54±0.79),(27.09±1.31)mg/g;(±0.21),(±0.10)mkat/g],差异有显4.594.88著性意义(P<0.05);睡眠剥夺24h 力竭运动组谷胱甘肽含量和超氧化物歧化酶活性均高于睡眠非运动组[分别为(28.60±0.96),(27.09±1.31)mg/g;(±0.10),(±0.10)5.234.88mkat/g],差异有显著性意义(P<0.05),睡眠剥夺48,h 力竭运动组P72均低于睡眠非运动组[分别为(23.74±1.19),(22.43±0.52),(27.09±1.31)mg/g;(±0.14),(±0.18),(±0.10)mkat/g],4.523.354.88差异均有非常显著性意义(P<0.01);睡眠剥夺各组与睡眠 力竭运动组间谷胱甘肽含量和超氧化物歧化酶活性差异均有非常P显著性意义(P<0.01);睡眠剥夺各组间比较差异有显著性意义(P<0.05)。④丙二醛浓度:睡眠 力竭运动组丙二醛浓度高于P睡眠非运动组[分别为(±0.27),(±0.24)μmol/L],差异有非常显著性意义(P<0.01);睡眠剥夺各组与睡眠非运动组之间6.565.35P差异均有非常显著性意义(P<0.01);睡眠剥夺24,48,72h 力竭运动组丙二醛含量均高于睡眠 力竭运动组[分别为(±0.12),(±P7.398.850.72),(10.89±0.82),(±0.27)μmol/L],差异有显著性意义(P<0.05;P<0.01);睡眠剥夺各组间比较,睡眠剥夺48h与睡眠剥夺24h差6.56异无显著性意义(P>0.05),睡眠剥夺72h与睡眠剥夺24h、睡眠剥夺72h与睡眠剥夺48h间比较差异有非常显著性意义(P<0.01)。结论:①睡眠剥夺24h可引起大鼠胸腺氧化应激,使氧自由基能力有所增强。②睡眠剥夺48,72h力竭运动后氧自由基能力降低。     

The effectiveness of the confidential unit exclusion option

BACKGROUND: The confidential unit exclusion (CUE) option is intended to reduce human immunodeficiency virus (HIV) transmission by excluding donors newly infected with HIV who have not yet developed HIV antibody (window-period donors); however, its efficacy in excluding window- period donors has not been evaluated. STUDY DESIGN AND METHODS: The use of the CUE option was studied among the donors of 3.7 million units at 18 American Red Cross blood services regions during 1991 and 1992 and among 322 previously HIV-1-seronegative donors who subsequently donated a seropositive unit between 1987 and 1990 at 40 United States blood centers. These seroconverting donors had previously been shown to be highly likely to donate during their window period. RESULTS: On the basis of data from these two populations, it was estimated that only 3 to 5 percent of units donated by window-period donors were not transfused because of the CUE option, that 0.4 percent of all donations were from donors who confidentially excluded their blood from transfusion, and that donors who confidentially excluded their blood were 21 times more likely to be HIV antibody-positive than donors who did not use the CUE option. It is estimated that, if all US blood centers used the CUE option, a total of 2 to 17 otherwise acceptable units donated by window-period donors would not be transfused annually. CONCLUSION: Although donors who confidentially exclude their blood from transfusion are 21 times more likely to have HIV antibody, the rarity of window-period donors and the infrequency of confidential exclusion by window-period donors cause the CUE option to have minimal impact on transfusion safety.     

POLYCYTHAEMIA RUBRA VERA PRESENTING WITH DEPRESSION: RECOGNISING THE SYNDROME ABULIA

SUMMARY A patient with polycythaemia rubra vera is described, presenting primarily with symptoms attributed to depression. While in the ward she developed a stroke, confirmed on CT scan of the head. Venesection alone produced marked improvement in her neurological and psychiatric symptoms. The clinical picture corresponds most accurately to the neurological syndrome of abulia, which is an important differential diagnosis of depression with psychomotor retardation. The pathophysiology of impaired cerebral blood flow causing neuropsychiatrie symptoms in polycythaemia is discussed.     

Mapping of monoclonal antibodies to human factor IX

We used recombinant DNA techniques to map a panel of six monoclonal antibodies (MoAbs) to regions of the human factor IX molecule. A-2 maps to 17 amino acids at the amino terminus of the heavy chain of IXa; 2D5, an inhibitor of clotting, is defined to 36 amino acids of the first EGF- like domain of human factor IX. A-4, A-5, C10D, and FXC008 all map to a region of the heavy chain containing amino acids 180 through 310, suggesting an immunodominant site. FXC008 has been reported to interfere with binding of factor IXa to factor VIII:Ca.     

Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem-cell disorder in which the glycolipid-anchored membrane proteins, including the cell-surface complement inhibitors, CD55 and CD59, are partially or completely deleted from the plasma membranes of mature blood cells. To gain insight into the pathogenesis of thrombosis that is frequently observed in this disorder, the procoagulant responses of PNH platelets exposed to the human terminal complement proteins C5b-9 were investigated. C5b-9 complexes were assembled on gel-filtered platelets by incubation with purified C5b6, C7, C9, and limiting amounts of C8. Platelet microparticle formation and exposure of plasma membrane- binding sites for coagulation factor Va were then analyzed by flow cytometry. PNH platelets exhibiting undetectable levels of surface CD59 antigen showed an approximately 10-fold increase in sensitivity to C5b- 9-stimulated expression of membrane-binding sites for factor Va when compared with platelets from normal controls. Expression of catalytic surface for the prothrombinase complex (VaXa) paralleled the exposure of factor Va-binding sites; the rate of prothrombin conversion by C5b-9- treated PNH platelets exceeded that of C5b-9-treated normal controls by approximately 10-fold at the maximal input of C8 tested (500 ng/mL). These data indicate that PNH platelets deficient in plasma membrane CD59 antigen are exquisitely sensitive to C5b-9-induced expression of prothrombinase activity, and suggest that the tendency toward thrombosis in these patients may be due, at least in part, to the deletion of this complement inhibitor from the platelet plasma membrane.