Complement activation by artificial blood substitute Fluosol: in vitro and in vivo studies

A perfluorocarbon blood substitute, Fluosol, is undergoing clinical trials as an adjunct to chemotherapy. The adverse effects associated with its administration have been postulated to result from complement activation. When gel electrophoresis and Western blotting of Fluosol are used after its incubation with serum, activated C3 and factors Bb and H are bound to the Fluosol particles in a time-dependent fashion, which suggests that complement activation with Fluosol, as does that with zymosan, occurs on the surface of the particles. Paradoxically, it is found, both by the measurement of Fluosol-bound C3d and by fluid-phase C5a, that lower concentrations of Fluosol cause greater amounts of complement activation, which suggests a complex interaction of activators and inhibitors that changes as the available surface area is decreased. Studies performed with bystander red cell-bound C3d demonstrated in vivo complement activation occurring in six patients receiving Fluosol as an adjunct to chemotherapy for colon cancer. In two patients, there was a marked increase in red cell-bound C3d after Fluosol infusion; these two patients also developed adverse reactions during Fluosol infusion. These studies suggest that the Fluosol surface plays a major role in the initiation and regulation of complement activation that is seen during Fluosol infusion.     

冠状动脉粥样硬化性心脏病患者升主动脉弹性与颈动脉内-中膜厚度的相关性

目的:观察冠状动脉粥样硬化性心脏病(简称冠心病)患者升主动脉弹性与颈动脉内膜-中层厚度及粥样斑块发生的相关性。方法:于2005-08/2006-04选择石河子大学医学院第一附属医院心内科行冠状动脉造影检查患者97例,根据冠状动脉造影结果分为正常对照组41例和冠心病组56例,对两组患者进行超声检查,分别测量升主动脉扩张性D、僵硬度指数β、测量升主动脉前壁收缩期S波以及舒张期E波、A波的速度、颈动脉内膜-中层厚度及粥样斑块发生率。僵硬度指数β=In(收缩压/舒张压)/[(收缩期内径-舒张期内径)/舒张期内径]。动脉扩张性D=2(收缩期内径-舒张期内径)/[舒张期内径(收缩压-舒张压)]×10-3m2/N。结果:纳入患者97例,均进入结果分析。①冠心病组升主动脉扩张性D低于正常对照组,差异有显著性意义[分别为(15.02±9.99)×10-4,(34.75±20.80)×10-3m2/N,P=0.001];僵硬度指数β高于正常对照组(分别为28.20±21.06,15.23±25.32,P=0.001);升主动脉前壁S波和E波速度低于正常对照组[分别为(0.08±0.01),(0.10±0.03)m/s;(0.05±0.01),(0.07±0.02)m/s,P=0.001];颈动脉内膜-中层厚度和颈动脉斑块发生率高于正常对照组[分别为(0.90±0.15),(0.66±0.09)mm;41.03%,5.88%,P=0.001]。②升主动脉前壁S波速度与扩张性呈正相关(r=0.43,P=0.003),与僵硬度指数呈负相关(r=-0.47,P=0.002)。升主动脉前壁E波速度与扩张性呈正相关(r=0.47,P=0.002),与僵硬度指数无相关性。升主动脉前壁A波速度与扩张性和僵硬度指数均无相关性。③升主动脉扩张性D与颈动脉内膜-中层厚度呈负相关(r=-0.49,P=0.004),而僵硬度指数β与内膜-中层厚度则呈正相关(r=0.46,P=0.003)。S波速度与内膜-中层厚度无相关性(r=-0.26,P=0.15)。结论:冠心病患者升主动脉弹性降低即动脉扩张性降低、僵硬度指数升高、升主动脉前壁S波速度下降,颈动脉内膜-中层厚度增厚及粥样斑块发生率增高,将这些参数结合可作为冠心病很有价值的预测指标。     

Demonstration by the monoclonal antibody-specific immobilization of erythrocyte antigens assay that a new red cell antigen belongs to the Kell blood group system

BACKGROUND: The Kell blood group system comprises 21 antigens residing on a red cell membrane glycoprotein of apparent M(r) 93,000. STUDY DESIGN AND METHODS: Serologic techniques were used to identify a new red cell antigen. The monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay was used to identify the red cell membrane component carrying that antigen. RESULTS: A new high-frequency red cell antigen was identified and provisionally named RAZ. RAZ is absent from K.o red cells and from red cells treated with 2-amino- ethylisothiouronium bromide and is expressed weakly on McLeod phenotype cells. It differs from all other Kell system antigens, and no depression of other Kell system antigens on RAZ+ red cells was noticed. The RAZ antigen was shown by the MAIEA assay to be located on the Kell glycoprotein. CONCLUSION: RAZ is a new high-frequency antigen located on the Kell glycoprotein. The MAIEA assay is a very effective method of demonstrating the membrane structure carrying a red cell antigen.     

重组结缔组织生长因子对体外培养成骨细胞核结合因子α1基因表达的影响

目的:研究发现,结缔组织生长因子可促进软骨细胞和成骨细胞的增殖及其表型的发生,在骨骼发育以及骨量维持方面发挥重要作用,但其对成骨细胞的作用机制目前尚不清楚。观察重组结缔组织生长因子对体外培养人成骨细胞核结合因子α1基因表达的影响。方法:实验于2006-01/2007-01在日照市人民医院完成。①实验材料:外科手术取正常成人髂骨松质骨,患者对试验知情同意。②实验方法:体外培养正常人成骨细胞,用不同浓度0,50,100,200,1000μg/L的重组结缔组织生长因子(0μg/L作为空白对照组)干预48h后,抽提细胞总RNA和总蛋白。③实验评估:采用半定量反转录-聚合酶链反应和蛋白免疫印迹分析方法观察不同浓度重组结缔组织生长因子对体外培养人成骨细胞核结合因子α1基因表达的影响。结果:半定量反转录-聚合酶链反应和蛋白免疫印迹结果显示,50,100,200,1000μg/L重组结缔组织生长因子干预后均可显著上调成骨细胞核结合因子α1的表达,并呈明显剂量依赖关系,与空白对照组比较,差异显著(P<0.01)。结论:重组结缔组织生长因子可剂量依赖性上调成骨细胞核结合因子α1基因的表达,核结合因子α1可能参与了结缔组织生长因子对成骨细胞增殖和分化的调节。     

Pace-Termination and Pacing for Prevention of Atrial Tachyarrhythmias: Results from a Multicenter Study with an Implantable Device for Atrial Therapy

INTRODUCTION: Patients with bradycardia requiring permanent pacing frequently suffer from additional atrial tachyarrhythmias (ATs). This study evaluated the safety and efficacy of atrial antitachycardia pacing (ATP) and the performance of pacing for AT prevention implemented into a new pacemaker. METHODS AND RESULTS: In patients with conventional indications for permanent pacing, an investigational DDDRP pacemaker (Medtronic AT500, model 7253) was implanted. The primary study objectives were to determine the safety of overall device functioning and its efficacy in terminating spontaneous AT. A secondary endpoint was to determine the reliability of AT detection. Pacemaker memory functions were used to analyze the impact of dedicated pacing algorithms on AT prevention. In 33 European and Canadian centers, 325 patients were enrolled (mean follow-up 2.3+/-1.3 months). Complication-free survival at 3 months was 88%. In 2,145 episodes stored with atrial electrograms, AT detection was confirmed in 97%. The algorithm for continuous overdrive pacing increased the percentage of atrial pacing to 97%. After ATP activation, 16,683 of 52,468 AT episodes were treated (120 patients). Of these, 8,903 episodes (53%) were terminated successfully by ATP. No proarrhythmic effect of preventive pacing or atrial ATP was observed. Preventive pacing algorithms increased the median percentage of atrial pacing from 62% to 97%. However, the number of AT/AF (atrial fibrillation) episodes (4.1 vs 4.1 per patient per day) and the time in AT/AF (13.7% vs 12.8%) was not significantly different before and after activation of preventive pacing. CONCLUSION: DDDRP pacing with a new system for AT therapy was safe and associated with successful pace-termination of AT in 53% of episodes. Preventive pacing and atrial ATP algorithms represent two new functions that can be implemented safely into pacemaker systems for nonpharmacologic treatment of ATs in patients requiring pacemaker therapy.     

四种中成药对气血双虚模型小鼠血象及免疫水平的影响

目的:为艾滋病抗病毒疗法所致的骨髓不良反应筛选疗效确切的中成药,观察分析参芪颗粒、复方阿胶浆、贞芪扶正颗粒、复方皂矾丸四种中成药对放血和注射环磷酰胺联合复制的气血双虚模型小鼠血象及免疫水平的影响。方法:实验于2005-08/09在河南中医学院药理实验室完成。①参芪颗粒(江西山高制药有限公司生产,批号040702);复方阿胶浆(山东东阿阿胶股份有限公司生产,批号050446);贞芪扶正颗粒(甘肃扶正药业科技股份有限公司生产,批号040803);复方皂矾丸(陕西郝其军制药有限责任公司生产,批号041014);当归补血口服液(郑州市协和制药厂生产,批号041122);环磷酰胺(上海华联制药有限公司生产,批号050101)。②选取清洁级昆明种小鼠150只,随机数字表法分为15组,10只/组:1～3组分别灌服参芪颗粒混悬液3,2,1g/kg;4～6组分别灌服复方阿胶浆30,20,10mL/kg;7～9组分别灌服贞芪扶正颗粒混悬液15,10,5g/kg;10～12组分别灌服复方皂矾丸混悬液2.4,1.6,0.8g/kg;第13组灌服当归补血口服液10g/kg;剩余2组为空白对照组和模型对照组,分别给于同体积生理盐水10g/kg。各组给药1次/d,连续给药10d。③除空白对照组外,其他各组从给药第1天开始建立气血双虚模型。每只鼠尾部放血0.25mL/10g,然后分别于第2,4,6,8天腹腔注射环磷酰胺80,40,40,40mg/kg。空白对照组同时间点仅腹腔注射等体积生理盐水。末次注射环磷酰胺后2h,眼眶取血,一部分用于血象测定,另一部分离心取血清,测定血细胞比容及血清中巨噬细胞集落刺激因子水平;解剖取胸腺和脾脏,检测胸腺皮质厚度、胸腺淋巴细胞数、脾小结大小、脾脏淋巴细胞数病理学指标的变化。结果:150只小鼠全部进入结果分析,放血和注射环磷酰胺并用可成功建立小鼠气血双虚模型。①与模型对照组比较,参芪颗粒3g/kg组、贞芪扶正颗粒10,5g/kg组、复方皂矾丸1.6g/kg组均可升高气血双虚模型小鼠白细胞水平(t=2.18～2.74,P<0.05),贞芪扶正颗粒15g/kg组作用更为显著(t=2.98,P<0.01);参芪颗粒1g/kg组、复方阿胶浆20mL/kg组、贞芪扶正颗粒15,10g/kg组均可升高红细胞水平(t=2.44～2.69,P<0.05),复方阿胶浆30mL/kg组、贞芪扶正颗粒5g/kg组、复方皂矾丸2.4,1.6g/kg组作用更为显著(t=2.91～3.66,P<0.01);当归补血口服液组、复方阿胶浆20mL/kg组、参芪颗粒3,1g/kg组、贞芪扶正颗粒15,10,5g/kg组均可升高血红蛋白水平(t=2.27～2.85,P<0.05),复方阿胶浆30mL/kg组、复方皂矾丸2.4,1.6g/kg组作用更为显著(t=3.07～4.04,P<0.01);当归补血口服液组、参芪颗粒3,2g/kg组均可升高血小板水平(t=2.20～2.41,P<0.05)。②与模型对照组比较,参芪颗粒2g/kg组、贞芪扶正颗粒5g/kg组均可升高气血双虚模型小鼠血细胞比容(t=2.01～2.62,P<0.05),参芪颗粒1g/kg组、复方阿胶浆30,20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4,1.6,0.8g/kg组作用更为显著(t=3.18～4.36,P<0.01);参芪颗粒2g/kg组、复方阿胶浆30,20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4,1.6g/kg组均可显著升高巨噬细胞集落刺激因子水平(t=3.60～6.80,P<0.01)。③与模型对照组比较,当归补血口服液组、参芪颗粒3,2,1g/kg组、复方阿胶浆30,20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4,1.6,0.8g/kg组均可显著增加气血双虚模型小鼠胸腺皮质厚度(t=3.71～9.34,P<0.01),增大脾小结(t=3.36～11.97,P<0.01),增加脾脏淋巴细胞数(t=4.29～10.44,P<0.01);复方阿胶浆30mL/kg组可明显增加小鼠胸腺淋巴细胞数(t=2.45,P<0.05),当归补血口服液组、参芪颗粒3,2,1g/kg组、复方阿胶浆20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4g/kg组作用更为显著(t=3.22～8.20,P<0.01)。结论:①四种中成药对气血双虚模型小鼠血红蛋白升高作用相近,以复方阿胶浆和贞芪扶正颗粒对白细胞和红细胞水平升高作用为强,以复方阿胶浆和贞芪扶正颗粒对血小板水平升高作用为优。②四种中成药对气血双虚模型小鼠血细胞比容的影响无差异,以贞芪扶正颗粒和复方皂矾丸对巨噬细胞集落刺激因子水平的升高作用为优。③以参芪颗粒、复方阿胶浆、贞芪扶正颗粒对胸腺皮质厚度和淋巴细胞数的促进作用为优,以参芪颗粒、贞芪扶正颗粒、复方皂矾丸对脾小结和脾脏淋巴细胞数的促进作用为优。     

贞芪扶正颗粒和复方阿胶浆干预再生障碍性贫血模型小鼠外周血及骨髓象的变化

目的:观察贞芪扶正颗粒和复方阿胶浆对苯油溶液致小鼠再生障碍性贫血模型的疗效。方法:实验于2005-06/09在河南中医学院药理实验室完成。①选用昆明种成年雄性小鼠90只。按随机数字表法将小鼠分为9组,每组10只:大、中、小剂量贞芪扶正颗粒组:按15,10,5g/kg剂量灌服贞芪扶正颗粒混悬液(主要成分:黄芪、女贞子;甘肃扶正药业科技股份有限公司生产;批号040803,15g/袋)。大、中、小剂量复方阿胶浆组:分别按10,20,30mL/kg剂量灌胃复方阿胶浆(主要成分:阿胶、熟地黄、党参、山楂、人参、蔗糖;山东东阿阿胶股份有限公司生产,批号050446,250mL/瓶),司坦唑醇组:按4mg/kg剂量灌胃司坦唑醇混悬液(司坦唑醇片,广西南宁百会药业集团有限公司生产,批号050306,30mg/片)。空白组和模型组:灌胃同体积的生理盐水(20mL/kg)。每天给药1次,连续给药14d。除空白组外,其余组小鼠皮下注射体积分数0.25苯的玉米油溶液4mL/kg复制苯油溶液致小鼠再生障碍性贫血模型,空白组皮下注射同体积玉米油。②各组小鼠分别于末次给药后24h,进行血常规检测。取右侧股骨,冲出骨髓细胞,采用BI-2000医学图像分析仪计数骨髓有核细胞数。③计量资料符合正态分布、方差齐者用t检验;方差不齐者用t’检验。结果:小鼠90只均进入结果分析。①血细胞测定结果比较:模型组小鼠血红细胞、白细胞、血小板计数和血红蛋白水平明显低于空白组(t=3.39～11.89,P<0.01)。司坦唑醇组3项血细胞计数和血红蛋白水平明显高于模型组(t=4.94～6.73,P<0.01)。大、中剂量贞芪扶正颗粒组和各剂量复方阿胶浆组血白细胞计数明显高于模型组(t=2.32～3.03,P<0.05￣0.01)。中剂量贞芪扶正颗粒组和各剂量复方阿胶浆组小鼠血红细胞计数明显高于模型组(t=2.15～4.84,P<0.05￣0.01)。大、中剂量贞芪扶正颗粒组和各剂量复方阿胶浆组血红蛋白水平明显高于模型组(t=2.33～4.45,P<0.05￣0.01)。大、中剂量贞芪扶正颗粒组和各剂量复方阿胶浆组血小板计数明显高于模型组(t=4.06～6.24,P<0.01)。②骨髓有核细胞数:模型组明显低于空白组(t=8.99,P<0.01)。司坦唑醇组、中剂量贞芪扶正颗粒组和小剂量复方阿胶浆组明显高于模型组(t=2.39～2.82,P<0.05)。结论:贞芪扶正颗粒、复方阿胶浆对皮下注射苯所致小鼠再生障碍性贫血模型血细胞状况及骨髓象均有较好的改善作用,以贞芪扶正颗粒有较为明显的剂量依赖关系。     

两种麻醉方法对单双肺通气期间能量代谢和呼吸氧价及应激反应的影响

目的:观察胸段硬膜外复合全静脉麻醉和全静脉麻醉对单、双肺通气能量代谢、呼吸氧价和应激反应的影响,比较两者的差异。方法:选择2004-07/2005-01徐州医学院附属医院心胸外科择期行食管癌根治术且需要单肺通气的患者40例,按随机数字表法分为硬膜外复合全静脉麻醉组(n=20)和全静脉麻醉组(n=20),经患者同意并签字后进入试验。分别在单肺通气和双肺通气时进行氧耗量、二氧化碳排出量、能量代谢和呼吸商测定,同时测量肾上腺素、去甲肾上腺素、皮质醇和血糖水平。结果:40例患者全部进入结果分析,无脱落。①在单、双肺通气时硬膜外复合全静脉麻醉组的氧耗量、二氧化碳排出量、能量代谢均高于全静脉麻醉组(P<0.05);两组患者单肺通气时段氧耗量、二氧化碳排出量、能量代谢低于双肺通气时段,但差异无显著性意义(P>0.05)。②在单、双肺通气时硬膜外复合全静脉麻醉组的肾上腺素、去甲肾上腺素、皮质醇和血糖水平均低于全静脉麻醉组(P<0.05);单、双肺通气相比,两组患者肾上腺素、去甲肾上腺素变化差异无显著性意义(P>0.05)。结论:与全静脉麻醉相比,胸段硬膜外阻滞复合全静脉麻醉能够增加胸科手术的氧耗量、能量代谢,减轻应激反应。单、双肺通气期间没有明显差异。