丙丁酚可干预小鼠动脉粥样硬化病变并调节B类I型清道夫受体的表达

目的研究丙丁酚对高脂高胆固醇饲养的载脂蛋白E基因敲除小鼠和C57BL6/J小鼠血脂及动脉粥样硬化病变的影响,以及肝脏B类I型清道夫受体和PPARγ表达的变化。方法分别随机将20只载脂蛋白E-/-小鼠和20只C57BL6/J小鼠分为载脂蛋白E-/-高脂组和载脂蛋白E-/-高脂 0.5%丙丁酚组。动物喂     

丙丁酚对动脉粥样硬化小鼠抗氧化作用的比较

目的观察丙丁酚对高脂高胆固醇饲养的C57BL/6J小鼠和载脂蛋白E基因缺陷(载脂蛋白E-/-)小鼠抗氧化作用的影响,比较丙丁酚对两种小鼠的作用差异。方法以高脂高胆固醇饲料饲喂小鼠,制作高脂血症模型。采用酶比色法及相关检测试剂盒分别测定小鼠血脂水平及与氧化应激相关的指标;采用双抗夹心ELISA法测定氧化型低密度脂蛋白的水平;采用改良的Eckerson方法测定对氧磷酶1的活性,采用逆转录聚合酶链式反应检测对氧磷酶1mRNA的表达。结果与两种小鼠各自的基础饲料组比较,高脂高胆固醇组血脂水平均有升高;与各自的高脂高胆固醇组比较,丙丁酚处理后,C57BL/6J小鼠血清的甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平分别降低了41.0%、43.6%、44.8%和41.3%(P<0.05),载脂蛋白E-/-小鼠血清的甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平,分别降低了36.2%、28.2%、31.3%、33.9%(P<0.05)。小鼠主动脉内膜的动脉粥样硬化病变与各自高脂高胆固醇组比较,C57BL/6J小鼠经丙丁酚处理后病变面积减少了61.1%,载脂蛋白E-/-小鼠经丙丁酚处理后病变面积减少了27.2%(P<0.05)。与各自基础饲料组比较,高脂血症小鼠丙二醛及氧化型低密度脂蛋白的水平增高,而总抗氧化能力和超氧化物歧化酶水平降低(P<0.05);与各自的高脂高胆固醇组比较,丙丁酚处理组小鼠的总抗氧化能力和超氧化物歧化酶水平上升,丙二醛及氧化型低密度脂蛋白的水平则降低(P<0.05)。两组小鼠高脂高胆固醇组血清对氧磷酶1的活性较基础饲料组均下降,经高脂饮食加丙丁酚处理后对氧磷酶1活性比单纯高脂饮食组有所增加;肝脏对氧磷酶1mRNA的表达在高脂高胆固醇组下调,而丙丁酚处理组则上调(P<0.05)。结论丙丁酚可以减轻高脂血症小鼠动脉粥样硬化病变,减轻高脂高胆固醇饮食诱导的氧化应激,而载脂蛋白E基因缺陷则一定程度减弱丙丁酚的上述作用。     

丙丁酚可干预小鼠动脉粥样硬化病变并调节B类I型清道夫受体的表达

目的研究丙丁酚对高脂高胆固醇饲养的载脂蛋白E基因敲除小鼠和C57BL6／J小鼠血脂及动脉粥样硬化病变的影响，以及肝脏B类Ⅰ型清道夫受体和PPARγ表达的变化。方法分别随机将20只载脂蛋白E^-/^-小鼠和20只C57BL6／J小鼠分为载脂蛋白E^-／^-高脂组和载脂蛋白E^-/^-高脂＋0．5％丙丁酚组。     

AMD3100促进载脂蛋白E~(-/-)小鼠动脉粥样硬化斑块形成

目的探讨AMD3100对载脂蛋白E-/-小鼠主动脉动脉粥样硬化斑块形成的影响及其可能机制。方法12只8周龄雄性载脂蛋白E-/-小鼠随机分为AMD3100组(2.5mg/kg,隔天注射)和对照组(PBS 0.1mL,隔天注射),高脂高胆固醇饲料喂养12周后,获取组织标本和骨髓细胞,石蜡切片HE染色检测小鼠主动脉根部动脉粥样硬化病变;通过计数典型内皮祖细胞克隆形成单位和观察次级集落单位的大小与细胞密度检测内皮祖细胞的克隆形成能力;逆转录聚合酶链反应和Western blotting检测内皮祖细胞CXCR4 mRNA和蛋白的表达。结果AMD3100组小鼠主动脉窦横切面粥样斑块面积与管腔面积之比与对照组比较增加了38.8%(37.2%±3.6%比26.8%±2.5%,P<0.05);AMD3100组小鼠骨髓源内皮祖细胞的克隆形成能力显著低于对照组(初级内皮祖细胞集落单位个数为9.67±2.16比21.83±2.64,次级内皮祖细胞集落单位个数为1.67±0.31比4.11±0.65,P<0.01);AMD3100组CXCR4 mRNA和蛋白的表达均显著低于对照组(P<0.01)。结论AMD3100促进载脂蛋白E-/-小鼠动脉粥样硬化斑块形成,可能与抑制骨髓源内皮祖细胞的克隆形成并下调CXCR4表达相关。     

老龄载脂蛋白E基因敲除小鼠血脂及病理组织学观察

目的:观察用普食喂养而非以往研究中的高脂饮食喂养的载脂蛋白E基因敲除小鼠(Apo E-/-)的血脂及病理组织学变化特点。方法:各选取20只8周龄雄性小鼠和同龄同性C57BL/6J小鼠为对照,普食喂养6~8个月,测定血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)的含量。常规制备主动脉的病理切片,进行HE染色,观察病理学变化。结果:Apo E-/-小鼠血清中TC、TG、LDL含量明显高于对照组(P0.05),且Apo E-/-小鼠主动脉根部病理切片明显脂质斑块形成。结论:普食喂养8月龄Apo E-/-小鼠是研究动脉粥样硬化(AS)的理想动物模型,为AS性心血管疾病研究者提供了参考资料。     

载脂蛋白E基因敲除小鼠动脉粥样硬化病变进展过程中循环单核细胞亚群和斑块内增殖巨噬细胞的动态变化

目的观察载脂蛋白E基因敲除(Apo E-/-)小鼠动脉粥样硬化病变进展过程中循环单核细胞亚群(Ly6G-CD11b+Ly Chi和Ly6G-CD11b+Ly6Clo)比例和斑块内局部增殖巨噬细胞密度的动态变化。方法 40只Apo E-/-小鼠随机分为正常饮食组和高脂饮食组,分别于饮食干预后第2周末、第4周末、第6周末和第8周末处死部分动物,油红O染色检测主动脉根部动脉粥样硬化斑块面积,免疫荧光染色和共聚焦显微镜成像检测斑块内的巨噬细胞和增殖巨噬细胞(F4/80和Ki67双阳性细胞),流式细胞术分析循环单核细胞亚群比例。结果随着高脂饮食时间的增加主动脉动脉粥样硬化病变逐渐加重;动脉斑块中总巨噬细胞和增殖巨噬细胞密度在高脂饮食后进行性升高,并于第4周末达到高峰;巨噬细胞与增殖巨噬细胞密度百分比在高脂饮食后进行性升高,并于第6周末达到高峰;随着高脂饮食时间的增加Ly6G-CD11b+Ly Chi单核细胞亚群比例逐渐增大。结论在Apo E-/-动脉粥样硬化模型发展过程中,循环Ly6G-CD11b+Ly Chi单核细胞呈递增趋势,增殖巨噬细胞密度在第4周达到平台期。     

GLP-1通过调节巨噬细胞泡沫化抑制ApoE-/-小鼠动脉粥样硬化的作用机制研究

目的 研究胰高血糖素样肽1(GLP-1)是否能抑制高脂饮食喂养的载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化(AS)进程,从巨噬细胞泡沫化角度探讨相关作用机制.方法 选择6周龄雄性ApoE-/-小鼠40只,随机分为对照组(普通饮食)、模型组(高脂饮食)、GLP-1组(高脂饮食+GLP-1)和GLP-1阻断组(高...     

瑞舒伐他汀对ApoE-/-小鼠动脉粥样斑块中凋亡相关蛋白的影响

目的观察瑞舒伐他汀对Apo E-/-小鼠动脉粥样硬化斑块凋亡相关蛋白Bcl-2和Caspase-3表达的影响。方法 10只C57小鼠作为对照组,给予普通饮食,同品系22只Apo E-/-小鼠随机分为模型组(n=11)、干预组(n=11),高脂喂养8 w后,干预组给予瑞舒伐他汀悬液灌胃,模型组给予等量生理盐水。继续喂养12 w后所有老鼠处死,全自动生化仪检测血清血脂,光学显微镜观察各组小鼠主动脉斑块形态及面积,免疫组化法检测动脉粥样斑块Bcl-2和Caspase-3蛋白的表达。结果与对照组相比较,模型组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)明显升高(P0.05),高密度脂蛋白胆固醇(HDL-C)明显降低(P0.05);主动脉可见明显粥样斑块;Bcl-2表达明显减少,Caspase-3表达明显增多(P0.05)。与模型组比较,TC、TG、LDL-C明显降低(P0.05);干预组小鼠动脉粥样斑块面积减小(P0.05),Bcl-2表达明显增多,Caspase-3表达明显减少(P0.05)。结论高脂饮食可引起Apo E-/-小鼠主动脉凋亡相关蛋白Bcl-2和Caspase-3的变化,瑞舒伐他汀可以通过上调Bcl-2、下调Caspase-3的表达,抑制Apo E-/-小鼠动脉粥样硬化斑块的进展。     

Orai1在载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成中的表达

目的探讨Orai1在载脂蛋白E基因敲除(Apo E-/-)小鼠动脉粥样硬化斑块形成过程中的表达。方法选取7~8周龄雄性Apo E-/-小鼠及野生型C57BL/6J小鼠,高脂饲喂20、27和33周后,在各个时点处死动物。取主动脉制备连续切片,HE、Masson染色计算机图像分析仪测定斑块面积占管腔面积百分比,及胶原成分占斑块面积百分比;油红O染色分析斑块中脂质含量;免疫组织化学染色测定平滑肌细胞阳性表达Orai1的百分比;Western Blot定量分析Orai1在易损斑块形成过程中的动态表达。结果与同周龄C57BL/6J小鼠相比,Apo E-/-小鼠主动脉Orai1表达增高,且随着其周龄增加,Orai1在Apo E-/-小鼠主动脉的表达动态升高(P0.05)。结论 Orai1参与动脉粥样硬化斑块形成的病理过程,在其形成过程中其表达上调。     

维生素K2对ApoE－/－小鼠动脉粥样硬化内膜钙化和Toll样受体2及4表达的影响

目的探讨维生素K2对Apo E-/-小鼠动脉粥样硬化内膜钙化和Toll样受体2(TLR2)及TLR4表达的影响。方法 18只6周龄雄性Apo E-/-小鼠,随机分为模型组、维生素K2干预组及对照组,每组6只。模型组及维生素K2干预组小鼠予高脂饮食,对照组小鼠予普通饮食喂养。维生素K2干预组在高脂饮食基础上同时予维生素K2灌胃,每天1次,共12周。小鼠19周龄时处死,测定血清脂质水平;HE染色观察主动脉组织形态学变化,Von Kossa染色观察主动脉钙化;测定血管钙含量和碱性磷酸酶活性判断血管钙化程度;免疫组织化学法、实时定量PCR(qRT-PCR)分别检测主动脉TLR2、TLR4蛋白和mRNA的表达。结果模型组小鼠主动脉HE染色可见内膜显著增厚,有典型的动脉粥样硬化斑块形成,Von Kossa染色斑块纤维帽下可见灶状黑色钙化团块,维生素K2干预组小鼠主动脉可见粥样硬化斑块,但Von Kossa染色斑块内未见明显黑色钙盐沉积;定量分析显示,维生素K2干预组小鼠主动脉血管壁钙含量和碱性磷酸酶活性均明显低于模型组(P0.01);免疫组织化学染色显示TLR2、TLR4主要表达于粥样硬化斑块内,qRT-PCR证实模型组小鼠主动脉TLR2、TLR4表达均显著高于对照组(P0.05),维生素K2干预组小鼠主动脉TLR2、TLR4 mRNA及蛋白水平较模型组明显降低,差异有统计学意义(P0.05)。小鼠主动脉钙含量与TLR2 mRNA表达呈正相关(r=0.77,P0.001),与TLR4 mRNA表达亦呈正相关(r=0.79,P0.001)。结论维生素K2可降低高脂饮食Apo E-/-小鼠主动脉中钙含量和碱性磷酸酶活性,减少主动脉血管壁TLR2、TLR4的表达,维生素K2抑制内膜钙化的作用可能与下调TLR2、TLR4的表达有关。     

Autoantibody to factor VIII that has less reactivity to factor Vlll/von Willebrand Factor Complex

To determine the difference in reactivity of factor Vlll (FVIII) inhibitor to FVlll/von Willebrand Factor (vWF) complex and FVlll free of vWF, an autoantibody to FVlll light chain was tested. A patient (1-3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (1-3 IgG) was shown to be the C2 domain of FVlll light chain (2170-2332) by Western blotting using recombinant FVlll deletions expressed in Escherichia coli. The inhibitory effect on FVlll procoagulant activity (VIII :C) of 1-3 lgG was tested against a conventional FVlll concentrate; Haemate P, a monoclonal antibody-purified FVlll concentrate; Hemofil M, and a recombinant FVlll (rFVIII); Kogenate. 1-3 lgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mglgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the 1-3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVlll by forming a complex with vWF. from 22 BU/mglgG to o.5 BU/mgIgG. Fab from the 1-3 IgG had the same effect. In addition, vWF showed a protective effect on FVlll inactivation by the 1-3 IgG in a dose dependent manner. Fifty-nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with 1-3 lgG. These results suggested that vWF could compete with the 1-3 IgG for binding to FVIII. © 1995 Wiley-Liss, Inc.     

Further studies on factor VII padua defect: the report of the fourth homozygous patient from the same valley

Summary A new patient with factor VII Padua abnormality is presented. The proposita is an 11-year-old girl who showed a mild bleeding tendency and a laboratory pattern characterized by a prolonged prothrombin time corrected by normal serum, normal partial thromboplastin time and normal Thrombotest. Factor VII assay was 10% using rabbit brain thromboplastin and 100% of normal using ox brain thromboplastin. Factor VII cross-reaction material was normal. The parents were not consanguineous but both came from the same area and were found to be heterozygous for the abnormality. The discovery of the present patient, the fourth in three years, indicates that the defect might be more frequent than originally thought.Supported by grants from the M.P.I. (grant 1592–1980), Rome and from the Veneto Regional Government, Venice     

Large-scale production and properties of human plasma-derived activated Factor VII concentrate

BACKGROUND AND OBJECTIVES: An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. MATERIALS AND METHODS: FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. RESULTS: Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. CONCLUSIONS: We established a large-scale manufacturing process of human plasma-derived FVIIa concentrate with a high yield, making it possible to provide sufficient FVIIa concentrate for use in haemophiliacs with inhibitory antibodies.     

Factor VIII Structure and Function

Factor VIII, a non-covalent heterodimer comprised of a heavy chain (A1-A2-B domains) and light chain (A3-C1-C2 domains), circulates as an inactive procofactor in complex with von Willebrand factor. Metal ions are critical to the integrity of factor VIII, with Cu and Ca ions stabilizing the heterodimer and generating the active conformation, respectively. Activation of factor VIII catalyzed by thrombin appears dependent upon interactions with both anion-binding exosites I and II, and converts the heterodimer to the active cofactor, factor VIIIa. This protein, comprised of A1, A2, and A3-C1-C2 subunits, is labile due to weak affinity of the A2 subunit. Association of factor VIIIa with factor IXa to form the intrinsic factor Xase complex is membrane-dependent and involves multiple inter-protein contacts that remain poorly characterized. This complex catalyzes the conversion of factor X to factor Xa, a reaction that is essential for the propagation phase of coagulation. The role of factor VIIIa in this complex is to increase the catalytic efficiency for factor Xa generation by several orders of magnitude. Mechanisms for the down-regulation of factor Xase focus upon inactivation of the cofactor and include dissociation of the A2 subunit as well as activated protein C-catalyzed proteolysis.     

Factor VIII coagulant activity and factor Vlll-related antigen released from isolated perfused human spleens

Summary Eight human spleens were perfused for up to 65 h at normothermia and the coagulant Factor VIII activity measured in the perfusate. In addition, in three experiments Factor VIII-related antigen was determined in the perfusate. Although the spleens were pathologically enlarged and the normal structure involved by different diseases, all spleens released Factor VIII coagulant activity and Factor VIII-related antigen. On average the total amount of Factor VIII coagulant activity released was equivalent to that of 3.5 1 of human plasma.

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Zusammenfassung Bei der normothermen Langzeitperfusion von 8 menschlichen Milzen wurde ein Anstieg des Gerinnungsfaktors VIII im Perfusat gemessen und in 3 FÄllen die Konzentration des Faktor VIII-assoziierten Antigens bestimmt. Obwohl es sich um pathologisch verÄnderte Milzen handelte, stieg in allen FÄllen die Faktor-VIII-AktivitÄt und die Konzentration des Faktor-VIII-assoziierten Antigens an. Der Mittelwert des maximalen Gehalts an Faktor VIII entsprach der GerinnungsaktivitÄt von 3,5 1 menschlichen Plasmas.

     

Combined deficiencies of factor vlll (ahf) and factor xi (pta)

Combined deficiencies of Factor VIII and Factor XI associated with moderate degree of bleeding symptoms were found in 3 brothers. Examination of Factor VIII activity and Factor VIII-related antigen revealed that the Factor VIII activity/ Factor VIII-related antigen ratio was significantly decreased in their mother and maternal grandmother consistent with the carrier state of hemophilia. Factor XI deficiency was found in 2 siblings, the father, and 2 of his sisters. The paternal grandmother was thought to carry the abnormal Factor XI gene, although her Factor XI level was normal, because of a significant bleeding history. It was concluded that the combined Factor VIII and XI deficiencies in the 3 brothers represent the coincidental inheritance of 2 separate and independent abnormal genes.     

Hepatocyte growth factor,epidermal growth factor,and placenta growth factor concentrations in peripheral blood of pregnant women with alcohol abuse

BACKGROUND: Alcohol abuse during pregnancy compromises fetal development not only directly but also by abnormal placental function. Therefore, hepatocyte growth factor (HGF), epidermal growth factor (EGF), and placenta growth factor (PlGF), expressed in the placenta, may play a role in alcohol-induced placental dysfunction. METHODS: Peripheral venous blood samples were collected from 40 pregnant alcohol-abusing women and 42 abstinent pregnant women from gestational weeks 4 to 41. Plasma HGF and serum PlGF were assessed by enzyme-linked immunosorbent assays and serum EGF by an immunofluorometric assay. RESULTS: Plasma HGF concentrations were similar in alcohol-abusing and abstinent mothers, although in the latter women these concentrations increased with advancing pregnancy. Serum EGF concentrations were consistently higher in alcohol-abusing than in abstinent mothers. In the latter, these concentrations decreased with advancing pregnancy. Serum PlGF concentrations increased with advancing pregnancy in both groups and were higher in alcohol-abusing mothers during the second and third trimesters but not during the first. CONCLUSIONS: Alcohol abuse during pregnancy is associated with changes in maternal circulating EGF and PlGF but not HGF concentrations. The observed changes may be caused by alcohol per se or may be secondary to possible alcohol-induced changes in placental physiology.     

肝细胞生长因子、TGF-β1与脑动脉粥样硬化程度的关系

目的　检测脑动脉粥样硬化（CAs）患者血清肝细胞生长因子（HGF）和转化生长因子β1（TGF-β1）水平，探讨两者水平与CAs程度间的关系，为外源性HGF干预提供依据。方法　71例CAs患者及对照组患者33例，抽取血样，采用双抗体夹心酶联免疫吸附法（ELISA）检测血清中HGF、TGF-β1含量。结果　CAs组患者血清HGF水平显著低于对照组（P<0.05），不同CAs程度组患者间血清HGF水平相互比较差异有显著性（P<0.05），在CAs组内随CAs程度逐渐加重，HGF水平表现出一定程度上升趋势。CAs组患者血清TGF-β1水平显著高于对照组（P<0.001），不同CAs程度组患者血清TGF-β1水平相互比较差异有显著性（P<0.05），在CAs组内随CAs程度逐渐加重，TGF-β1水平表现出一定程度下降趋势。结论　HGF和TGF-β1之间存在动态互逆平衡关系，考虑未来给予外源性HGF治疗CAs所致缺血性脑血管病存在可行性。     

Expression of Hepatocyte Growth Factor and c-Met Receptor in Gastric Mucosa during Gastric Ulcer Healing

Background: Ethanol is generally believed to inhibit extracellular Ca 2+ influx, thereby inhibiting gastric muscle contraction. Recently, we observed that verapamil inhibited only the amplitude of spontaneous phasic contractions, whereas ethanol inhibited both amplitude and frequency. In our objective to investigate the mechanism of ethanol's inhibition of gastric motility, the involvement of various protein kinases in ethanol-inhibited spontaneous phasic contractions of the stomach muscle strips was tested. Methods: Circular muscle strips (2.0 × 0.2 cm) were prepared from the corpus of cat stomach in order to measure isometric contraction in a chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 °C) bubbled with 5% CO 2 in O 2. Results: Spontaneous phasic contraction was not affected by various receptor antagonists (1 μM atropine, 1 μM hexamethonium, 1 μM phentolamine and 1 μM propranolol) or 1 μM tetrodotoxin. EGTA and verapamil dose-dependently inhibited only the amplitude of spontaneous phasic contractions and not the frequency. Ethanol dose-dependently inhibited both the amplitude and frequency of phasic contractions. The amplitude and frequency of spontaneous phasic contractions were significantly inhibited by protein kinase C and tyrosine kinase inhibitors. However, neither protein kinase C activator nor various phosphatase inhibitors blocked the inhibitory effect of ethanol. Conclusions: Ethanol appears to inhibit spontaneous phasic contractions by a mechanism other than the inhibition of protein kinase C or tyrosine kinase or the inhibition of extracellular Ca 2+ influx.     

The effect of plasma caeruloplasmin levels on the sensitivity for activated protein C

The effect of caeruloplasmin levels on the sensitivity for activated protein C (APC), measured by a clotting assay based on the activated partial thromboplastin time, was investigated in a large group of healthy individuals without factor V Leiden. A modest inverse association between caeruloplasmin and normalized APC sensitivity ratio was found (regression coefficient beta = -0.33 x 10-2; 95% confidence interval, -0.42 x 10-2 to -0.24 x 10-2). After adjustment for sex and oral contraceptive use, this association weakened (beta = -0.19 x 10-2; 95% CI: -0.34 x 10-2 to -0.05 x 10-2). After additional adjustment for factor VIII levels, which are known to influence the assay, the effect of caeruloplasmin on APC sensitivity completely disappeared.