caspase-8在支气管哮喘大鼠心肌细胞中的表达

目的 研究支气管哮喘心肌损害的机制及法医病理学实践中支气管哮喘猝死者的诊断指标.方法 建立大鼠支气管哮喘动物模型,运用免疫组化SP法染色,观察在不同实验条件下大鼠心肌细胞caspase-8表达的变化规律.结果 caspase-8在正常对照组及实验对照组心肌细胞中呈阴性或弱阳性表达,随着时间的延长免疫组化染色无明显的改变.各实验组第2周时caspase-8蛋白阳性面积和积分光密度比正常对照组及实验对照组明显升高(P＜0.01),随着时间的延长,阳性表达面积和积分光密度呈增加的趋势,第8周各实验组的阳性表达达到最高峰.肾上腺素氨茶碱联合给药组caspase-8表达阳性信号面积及积分光密度比不给药组低.组间比较,肾上腺素给药组caspase-8表达阳性信号面积及积分光密度比氨茶碱给药组在各时间段都明显增加.结论 支气管哮喘本身对心肌有一定的损害;肾上腺素药物可加重心肌损害;氨茶碱与肾上腺素联合使用可以减轻心肌损害;caspase-8可以作为支气管哮喘猝死的诊断辅助指标.     

SD大鼠支气管哮喘心肌HSP70表达研究

目的 探讨支气管哮喘心肌组织损害机制,为支气管哮喘猝死的法医学诊断提供形态学依据.方法 应用HE和免疫组化染色技术,对大鼠支气管哮喘模型不同药物治疗时心肌HSP70表达规律进行研究.结果 实验组心肌HSP70阳性表达明显高于对照组(P＜0.01),随哮喘时间延续,表达增强,至第八周最强.实验组中根据用药的不同,心肌HSP70表达强弱依次为肾上腺素治疗组＞肾上腺素 氨茶碱治疗组＞不使用药物治疗组＞氨茶碱治疗组.结论 支气管哮喘SD大鼠心肌损害机制与哮喘时心肌的缺血、缺氧密切相关.某些支气管哮喘治疗药物的使用可加重心肌细胞的损害,如肾上腺素的使用.HSP70免疫组化染色对支气管哮喘诱发的猝死的法医学诊断有一定的帮助.     

罗格列酮对糖尿病大鼠肺炎性病变的影响

目的 现察过氧化物酶体增殖体活化受体-r(PPAR-r)激动剂罗格列酮对链脲菌素诱导的糖尿病大鼠肺部炎性病变的影响.方法 30只10周龄SD大鼠随机分为正常对照组(C组,雌雄各5只)、糖尿病模型组(D组,雌雄各5只)、糖尿病罗格列酮处理组(DR组,雌雄各5只),采用链脲菌素诱导建立10周糖尿病大鼠模型.其中糖尿病罗格列酮处理组用马来酸罗格列酮1mg.kg-1.d-1灌胃治疗,对照组及糖尿病模型组用同体积0.9%氯化钠注射液代替.模型建立10周后,全部大鼠于氯胺酮35mg/kg和苯巴比妥50mg/kg腹腔内注射麻醉处死,并取肺组织.光学显微镜下现察肺组织炎症程度、检测杯状细胞的分布,免疫组织化学方法检测肺组织TNF-α表达的阳性面积百分比与平均积分光密度值(I0D).结果 ①肺部炎症观察:大多数正常对照组大鼠肺组织内未见炎症细胞.糖尿病模型组可见片状炎症细胞聚集,局部肺泡结构消失.罗格列酮处理组糖尿病大鼠肺组织炎症明显比模型组轻;②杯状细胞观察:在AB/PAS染色下,正常对照组大鼠各级气管上皮内均未见杯状细胞出现,糖尿病模型组在一级或二级支气管内出现较多的杯状细胞.罗格列酮处理组糖尿病大鼠在一级或二级支气管内也出现杯状细胞,但数量明显少于糖尿病模型组;③TNF-α的表达TNF-α主要表达于气管、血管周围的成纤维细胞内,糖尿病模型组、罗格列酮处理组还可见巨噬细胞胞浆内阳性表达.正常对照组肺组织阳性表达较其余两组弱,罗格列酮处理组阳性面积百分比及平均积分光密度值介于正常对照组和糖尿病模型组之间[其中阳性面积百分比(%)C:D:DR组为9.07±4.17vs23.75±5.66vs12.21±1.50(F=54.5,P<0.05;平均光密度C:D:DR组为0.60±0.03vs0.73±0.08vs0.66±0.04(F=22.73.P<0.05)],差异有统计学意义.结论 高血糖能引起肺部炎症及组织结构的破坏.罗格列酮能够保护糖尿病大鼠肺组织,该作用独立于降血糖之外. 内阳性表达.正常对照组肺组织阳性表达较其余两组弱,罗格列酮处理组阳性面积百分比及平均积分光密度值介于正常对照组和糖尿病模型组之间[其中阳性面积百分比(%)C:D:DR组为9.07±4.17vs23.75±5.66vs12.21±1.50(F=54.5,P<0.05;平均光密度C:D:DR组为0.60±0.03vs0.73±0.08vs0.66±0.04( =22.73.P<0.05)],差异有统计学意义.结论 高血糖能引起肺部炎症及组织结构的破坏.罗格列酮能够保护糖尿病大鼠肺组织,该作用独立于降血糖之外. 内阳性表达.正常对照组肺组织阳性表达较其余两组弱,罗格列酮处理组阳性面积百分比及平均积分光密度值介于正常对照组和糖尿病模型组之间[其中阳性面积百分比(%)C:D:DR组为9.07±4.17vs23.75±5.66vs12.21±1.50(F=54.5,P<0.05;平均光密度C:D:DR组为0.60±0.03vs0.73±0.08vs0.66±0.04( =22.73.P<0.05)],差异有统计学意义.结论 高血糖能引起肺部炎症及组织结构的破坏.罗格列酮能够保护糖尿病大鼠肺组织,该作用独立于降血糖之外. 内阳性表达.正常对照组肺组织阳性表达较其余两组弱,罗格列酮处理组阳性面积百分比及平均积分光密度值介于正常对照组和糖尿病模型组之间[其中阳性面积百分比(%)C:D:DR组为9.07±4.17vs23.75±5.     

小剂量氨茶碱对哮喘小鼠气道平滑肌细胞增殖及转化生长因子-β1表达的影响

目的:探讨小剂量氨茶碱干预对哮喘小鼠气道平滑肌细胞(ASMC)增殖及转化生长因子-β1(TGF-β1)表达的影响。方法:建立哮喘小鼠气道重塑模型,实验分为对照组、哮喘组、茶碱组。测定支气管肺泡灌洗液中嗜酸性粒细胞计数及活性TGF-β1表达的变化,行增殖细胞核抗原(PCNA)及TGF-β1免疫组化染色,图像分析测定管腔基底膜周长、气管壁总面积、气道平滑肌面积、ASMC核数及TGF-β1在ASMC的灰度值。结果:(1)哮喘组出现管壁、平滑肌层增厚及ASMC增殖等气道重塑的特征,与TGF-β1的表达呈正相关,嗜酸性粒细胞计数明显升高。(2)茶碱组与哮喘组比较炎症反应减轻,管壁、平滑肌层增厚及ASMC增殖减少,TGF-β1表达减弱;与对照组间比较差异无显著性。结论:反复的变应原吸入可导致气道重塑尤其是ASMC增殖,TGF-β1在ASMC增殖中可能具有重要作用,小剂量氨茶碱干预可能减缓气道重塑尤其是ASMC增殖的发生。     

烟雾暴露对卵白蛋白致敏的急性支气管哮喘大鼠模型肺组织激活素A mRNA和蛋白表达的影响

目的分析烟雾暴露对卵白蛋白致敏的急性支气管哮喘大鼠模型肺组织激活素A mRNA和蛋白表达的影响。方法取28只健康成年雄性SD大鼠,按照随机分配原则,分为空白对照组(正常大鼠,不采取任何处理)、阴性对照组(正常大鼠+烟雾暴露)、模型组(制备卵白蛋白致敏的急性支气管哮喘大鼠模型)、实验组(急性支气管哮喘大鼠+烟雾暴露),每组各7只。行苏木精-伊红染色,观察各组大鼠肺组织病理学改变;采用免疫印迹法检测大鼠肺组织中激活素A蛋白表达水平;根据实时荧光定量聚合酶链反应检测大鼠肺组织中激活素A mRNA相对表达量。结果经病理学染色结果可知,空白对照组肺组织病理学未见异常,而阴性对照组、模型组及实验组肺组织出现不同程度的病理学改变,且实验组更加明显。经免疫印迹法检测可知,阴性对照组、模型组及实验组肺组织中激活素A蛋白表达水平较空白对照组均明显升高(P <0. 05);模型组肺组织中激活素A蛋白表达水平较阴性对照组明显升高(P <0. 05);实验组肺组织中激活素A蛋白表达水平较阴性对照组和模型组明显升高(P <0. 05)。经实时荧光定量聚合酶链反应检测可知,相比空白对照组,阴性对照组、模型组及实验组肺组织中激活素A mRNA相对表达量均明显上调(P <0. 05);相比阴性对照组,模型组肺组织中激活素A mRNA相对表达量明显上调(P <0. 05);相比阴性对照组和模型组,实验组肺组织中激活素A mRNA相对表达量明显上调(P <0. 05)。结论在卵白蛋白致敏的急性支气管哮喘大鼠模型中,经烟雾暴露可促进大鼠肺组织激活素A蛋白表达,提高激活素A mRNA表达量,并进一步导致气道炎症加重。     

p53和Bcl-2基因mRNA在老年急性心肌梗死猝死者心肌细胞凋亡中作用的研究

目的探讨p53和Bcl-2基因在老年急性心肌梗死(AMI)猝死者心肌细胞凋亡中的作用.方法用TUNEL法检测15例老年AMI猝死者和10例心脏正常车祸死亡者的心肌细胞凋亡,用以cDNA为内参标准的逆转录-聚合酶链反应(RT-PCR)的方法检测心肌细胞内p53和Bcl-2基因mRNA表达量,并探讨它们之间的相互关系.结果TUNEL法发现,猝死者梗死区的每千个心肌细胞凋亡数老年AMI猝死组明显高于对照组(P=0.000);猝死者梗死区心肌细胞中p53基因mRNA表达量明显高于对照组(P=0.000),梗死区心肌细胞凋亡数与其中p53mRNA表达量的对数值成明显正相关性(r=0.883,P<0.001);Bcl-2基因mRNA表达量则明显低于对照组(P=0.000),且梗死区心肌细胞凋亡数与其内Bcl2mRNA表达量的对数值成明显负相关性(r=-0.907,P<0.001);猝死者p53和Bcl-2基因的mRNA表达量对数值之间呈明显的负相关性(r=-0.849,P<0.001).不同支数冠脉病变猝死者之间的比较1支、2支和3支病变者在心肌细胞凋亡数、p53和Bcl-2mRNA表达量方面,相互之间比较均无统计学上的差异(可能是因为例数少).结论老年AMI猝死者梗死区心肌细胞存在明显的凋亡现象,且受p53与Bcl-2两者相反调节其凋亡(p53基因上调、Bcl-2基因下调).     

星形细胞肿瘤中的细胞凋亡及其与p53、bcl—2的关系

目的探讨细胞凋亡在星形细胞肿瘤发展中的作用及其与p53、bcl-2的关系.方法对52例星形细胞肿瘤标本分别进行HE染色,TUNEL及PCNA、p53、bc1-2免疫组化染色.结果高级别星形细胞肿瘤的PI(增殖指数)显著高于低级别肿瘤(P＜0.01);高级别肿瘤和低级别肿瘤间的AI(凋亡指数)无显著性差异(P＞0.05).高级别星形细胞肿瘤p53的表达高于低级别肿瘤(0.01＜P＜0.05);p53阴性组和p53阳性组的AI(P＞0.05)和PI(P＞0.05)无显著性差异.低级别肿瘤中bcl-2的表达较高级别组肿瘤高(0.01＜P＜0.05);bc1-2免疫组化染色表达的阳性组与阴性组的AI(P＞0.05)和PI(P＞0.05)无显著性差异.结论与低级别星形细胞肿瘤相比,高级别肿瘤中的细胞凋亡受到了抑制;p53免疫组化染色结果可作为分析星形细胞肿瘤生物学行为的参考指标.星形细胞肿瘤中bcl-2的过表达对细胞凋亡未产生明显影响.     

N-乙酰半胱氨酸对急性肺损伤大鼠肺组织水通道蛋白-1表达的影响

目的:观察N-乙酰半胱氨酸(NAC)对急性肺损伤大鼠肺组织水通道蛋白-1(AQP-1)表达的影响,进一步探讨NAC对急性肺损伤肺组织的保护作用.方法:应用脂多糖诱导大鼠急性肺损伤模型,然后应用NAC进行干预.实验设对照组、模型组、NAC组,在肺损伤模型成功造模后24 h处死大鼠,取左叶肺组织.采用免疫组化染色,检测NAC对急性肺损伤大鼠肺组织中AQP-1的表达.利用HPIAS-2000图像分析系统测定AQP-1在以上各组中表达的平均光密度和平均阳性面积率.结果:对照组肺组织表达高水平AQP-1.模型组肺组织呈浅黄色染色,AQP-1表达较低.NAC组肺组织表达高水平AQP-1.对照组与模型组之间AQP-1的平均光密度及阳性面积率差异有显著性(P＜0.01),对照组与NAC组之间AQP-1的平均光密度及阳性面积率差异无显著性(P＞0.05).结论:NAC能使急性肺损伤组织中AQP-1呈高表达,对急性肺损伤组织有重要的保护作用.     

抗α1肾上腺素能受体自身抗体对糖尿病大鼠心肌TGF-β1和smads2/3表达的影响

目的 探讨抗α1-肾上腺素能受体自身抗体（抗α1-R抗体）对糖尿病（DM）大鼠心肌损害的作用机制.方法 （1）以抗α1-R抗体阳性的DM大鼠（抗体阳性组）为模型,设立抗α1-R抗体阴性DM大鼠（抗体阴性组）、正常Wistar大鼠（健康对照组）为对照.（2）用酶联免疫吸附试验法检测抗α1-R抗体.（3）用电子天秤称体重.（4）用免疫组织化学方法 检测左心室心肌组织的TGF-β1和smads2/3的表达,并在光镜下观察心脏病理变化,计算平均光密度值（MOD）.（5）在电镜下观察心脏超微结构的改变.结果 （1）实验结束时,DM抗体阳性组和抗体阴性组大鼠体重均明显低于实验前（均P〈0.01）,健康对照组大鼠体重明显高于实验前（P〈0.01）.（2）TGF-β1和smads2/3在抗体阳性组DM大鼠心肌组织中过度表达,MOD值明显高于抗体阴性组和健康对照组（分别P〈0.05,P〈0.01）.（3）心肌超微结构显示DM大鼠心肌纤维变性坏死,肌原纤维之间糖原减少,肌质网肿胀、扩张,线粒体大小悬殊,或肿胀或萎缩,微血管基底膜轻度增厚,其中抗体阳性组损伤更严重;健康对照组未见明显异常.结论 抗α1-R抗体可影响DM大鼠心肌组织的TGF-β1和smads2/3的表达,并且可能通过增加促纤维化生长因子TGF-β1的表达导致DM大鼠心肌损害的进展、加重.     

抑癌基因p53与p16及PCNA蛋白在皮肤增生期血管瘤中的表达及其对血管内皮细胞的干预

目的:应用免疫组化法检测抑癌基因p16,p53及DNA聚合酶δ的辅助蛋白PCNA在增生期血管瘤中的表达,及其对血管内皮细胞的影响。方法:实验选取2001-01/2005-04北京世纪坛医院病理科收集的手术切除皮肤增生期血管瘤组织标本36例作为增生期血管瘤组(患者术前均未经任何辅助性治疗),以痔静脉标本30例作为痔静脉对照组。患者均知情同意。①两组标本切片均采用DAKOEnvisions二步法进行免疫组化处理。切片以体积分数为0.03的过氧化氢消除内源性过氧化物酶,微波法抗原修复,92～95℃于pH6.0枸盐酸缓冲液浸泡10min;室温冷却10min,双蒸水洗涤,pH7.2磷酸盐缓冲液浸泡5min;体积分数为0.1的山羊血清(磷酸盐缓冲液稀释)封闭,去血清,加入Ⅰ抗,37℃浸泡30min;pH7.2磷酸盐缓冲液冲洗;Envision孵育,37℃下放置30min;二氨基联苯胺显色,苏木精复染后,脱水、透明、封固。免疫组化阴性对照以磷酸盐缓冲液代替Ⅰ抗,其他步骤维持不变,以确认试剂质量及控制染色效果。②p16,p53阳性信号为棕黄色,以内皮细胞浆和/或核染成棕黄色为阳性细胞。阴性对照除细胞核染成蓝色外,无棕黄色反应物。血管内皮细胞核内见棕黄色颗粒者为PCNA蛋白染色阳性。采用CMIAS高清晰彩色病理图像分析系统分别对两组切片p53,p16及PCNA蛋白的表达进行图像检测,测定每个视野下p16和p53阳性细胞的平均吸光度以及PCNA蛋白阳性表达指数。结果:实验选取手术切除皮肤增生期血管瘤组织标本36例,痔静脉标本30例,全部进入结果分析。①两组p53阳性表达检测及平均吸光度的比较:增生期血管瘤组内皮细胞核内有较多棕黄色颗粒,p53表达强;痔静脉对照组血管内皮细胞核内无棕黄色颗粒沉积,p53表达极弱。增生期血管瘤组p53阳性表达的平均吸光度明显强于痔静脉对照组(6.423±1.415,1.036±0.131,P<0.05)。②两组p16阳性表达检测及平均吸光度的比较:两组切片组织中除细胞核着色外,部分细胞浆有着色。p16的阳性表达在增生期血管瘤组和痔静脉对照组中基本相同,平均吸光度分别为1.241±0.373和1.206±0.267。③两组PCNA蛋白阳性表达指数的比较:PCNA蛋白阳性表达的细胞光镜下可见核内弥漫分布细小的棕黄色颗粒,这些内皮细胞围成血管腔及团块状,核椭圆,体积较大。增生期血管瘤组PCNA蛋白阳性表达指数明显高于痔静脉对照组(67.40±8.79,38.41±9.89,P<0.01)。结论:抑癌基因p53在增生期血管瘤组织中呈高表达,能够促进血管内皮细胞的增殖,但p16的表达与血管内皮细胞增殖的关系不明显。此外PCNA蛋白可作为增生期血管瘤的可靠标志物。     

心肌缺血日负荷对新西兰兔血管内皮生长因子表达的影响

要目的:观察心肌缺血日负荷对新西兰兔血管内皮生长因子(VEGF)表达的影响。方法:健康成年新西兰兔38只,体重2.0—2.5kg。根据日缺血次数随机分为2次/日组、4次/日组、6次/日组、假手术组以及正常组。将气囊梗阻器安装在冠状动脉左室支,制作间断性心肌缺血模型。缺血负荷为2min/h,缺血刺激4周。取缺血区心肌观察形态学变化;WesternBlotting方法检测VEGF蛋白在缺血区心肌的表达水平;取兔术前和缺血刺激前、后24h血清检测肌钙蛋白(cTnI)。结果:气囊充气可以有效、迅速地诱发心肌缺血;与假手术组和正常组相比,缺血刺激2次/日组、4次/日组、6次/日组缺血心肌VEGF表达升高(P<0.05),各缺血刺激组间的VEGF表达无差异;各组左室支支配区未见心肌坏死和血栓形成;兔缺血刺激后24h血清肌钙蛋白无明显升高。结论:持续4周的间断性心肌缺血对心肌无损伤,可以显著提高缺血区心肌VEGF表达增加,不同刺激频率对其表达无明显影响。     

扩张型心肌病心肌组织中组织蛋白酶L与心功能的关系

目的：探讨溶酶体组织蛋白酶L（cathepsin L）与扩张型心肌病发病的关系。方法：收集因终末期扩张型心肌病行心脏移植术的受体标本20例为心肌病组及脑死亡3h内排除心脏疾患的心脏标本5例为正常对照组，通过免疫组化及RT-PCR等方法半定量分析心肌组织中cathepsin L蛋白阳性颗粒及mRNA表达水平，并对cathepsin L mRNA表达水平的动态变化与心功能（EF值）的相关性进行分析。结果：心肌病组心肌组织中cathepsin L蛋白阳性颗粒及mRNA表达水平均明显高于对照组，均有极显著差异（P〈0．01）；心肌组织cathepsin L mRNA表达水平的变化与EF值的变化呈显著负相关（r=-0．544，P〈0．05）。结论：cathepsin L参与了扩张型心肌病的发生发展。     

Role of catecholamine oxidation in sudden cardiac death

Although sudden cardiac death is a leading cause of mortality, the mechanisms for its pathogenesis are poorly understood. Because overactivation of sympathetic nervous system is invariably seen in subjects with high risk for sudden cardiac death, elevated levels of circulating catecholamine levels are considered to result in lethal ventricular arrhythmias and subsequent sudden cardiac death. Such arrhythmogenic effects of catecholamines are generally believed to occur by their actions on α‐adrenoceptors in coronary arteries for inducing coronary spasm and subsequent myocardial ischemia as well as on β‐adrenoceptors in cardiomyocytes for increasing the concentration of cyclic AMP excessively and producing defects in intracellular Ca²⁺‐handling. Experimental evidence from our laboratory has revealed that excessive amounts of circulating catecholamines are oxidized to aminochromes, which are highly reactive quinine compounds. The oxidation products of catecholamines have been demonstrated to produce subcellular alterations, intracellular Ca²⁺‐overload, coronary spasm, myocardial cell damage, depletion of high energy stores, and ventricular arrhythmias. In addition, oxyradicals, which are known to generate oxidative stress and produce cardiotoxic effects, including arrhythmias, are formed during the oxidation of catecholamines. Accordingly, it is proposed that oxidation of catecholamines and the generation of oxidative stress under stressful conditions may play a critical role in the genesis of ventricular arrhythmias that may result in sudden cardiac death.     

中药通心络超微粉对糖尿病大鼠心肌细胞凋亡的干预作用

目的：探讨通心络超微粉对糖尿病大鼠心肌细胞凋亡的干预作用,为临床用药提供实验依据。方法：取SD大鼠随机分为3组：正常对照组、糖尿病心肌病变组（Diabetic Myocardi-opathy,DCM组）和通心络干预组（TXL组）。采用Tunel法检测光镜下观察心肌细胞凋亡指数,免疫组化法测定Bcl-2,Bax及P53基因蛋白表达。结果：TXL组大鼠较DCM组大鼠心肌细胞凋亡指数明显下降（P〈0.01）,Bcl-2表达明显增多（P〈0.01）,Bax及P53表达明显减少（P〈0.01）。结论：通心络超微粉可以通过多种途径有效减少糖尿病大鼠心肌细胞凋亡。     

Leukocyte filtration in the early reperfusion phase on cardiopulmonary bypass reduces myocardial injury

Improved myocardial protection and cardiopulmonary bypass (CPB) have limited, but not abolished, intraoperative myocardial damage due to surgical reperfusion injury after release of the aortic crossclamp. In this double-blind, randomized study, we evaluated whether short-term leukocyte filtration during reperfusion may further reduce myocardial damage. Thirty-eight patients with coronary artery disease were randomly assigned to CPB with (group I; n = 19) or without leukocyte filtration (group II; n = 19). There was no difference in bypass time or crossclamp time between the groups. No patient in group I required catecholamines, whereas three patients in group II were supported with adrenaline or dobutamine on the first and second postoperative day. In addition, troponin T plasma levels were lower in group I (p < 0.05), whereas other markers for tissue injury (CK, CK-MB, LDH, S-GOT and S100B) did not differ. In conclusion, leukocyte filtration during reperfusion may further improve CPB by reducing myocardial damage.     

Late expression of p53 from a replicating adenovirus improves tumor cell killing and is more tumor cell specific than expression of the adenoviral death protein

Gene transfer of p53 induces cell death in most cancer cells, and replication-defective adenoviral vectors expressing p53 are being evaluated in clinical trials. However, low transduction efficiency limits the efficacy of replication-defective vector systems for cancer therapy. The use of replication-competent vectors for gene delivery may have several advantages, holding the potential to multiply and spread the therapeutic agent after infection of only a few cells. However, expression of a transgene may adversely affect viral replication. We have constructed a replicating adenoviral vector (Adp53rc) that expresses high levels of p53 at a late time point in the viral life cycle and also contains a deletion of the adenoviral death protein (ADP). Adp53rc-infected cancer cells demonstrated high levels of p53 expression in parallel with the late expression pattern of the adenoviral fiber protein. p53 expression late in the viral life cycle did not impair effective virus propagation. Survival of several lung cancer cell lines was significantly diminished after infection with Adp53rc, compared with an identical p53-negative control virus. p53 expression also improved virus release and spread. Interestingly, p53 was more cytotoxic than the ADP in cancer cells but less cytotoxic than the ADP in normal cells. In conclusion, late expression of p53 from a replicating virus improves tumor cell killing and viral spread without impairing viral replication. In addition, in combination with a deletion of the ADP, specificity of tumor cell killing is improved.     

Sudden cardiac death: the lost fatty acid hypothesis

Evidence that an excess of plasma free fatty acids (FFA) might lead to primary ventricular fibrillation and sudden cardiac death has hardened over the 36 years since the hypothesis was proposed. When the sympathetic nervous system is stimulated during the onset of an acute coronary syndrome, catecholamine-induced tissue lipolysis occurs, with a surge of plasma FFA. This may overload the acutely ischaemic myocardium and impair glucose utilization. Myocardial oxygen consumption can increase in regional areas of ischaemia, and could lead to abnormal electrophysiological conduction and refractoriness, with irreversible ventricular arrhythmias. Efforts to combat the adverse effects of excess FFA include beta-blockade, increasing glucose availability and extraction, or inhibition of lipolysis. This last approach appears promising, but no method has yet been clearly shown to prevent primary ventricular fibrillation or sudden cardiac death. The hypothesis remains viable. More research is needed to derive treatment that can be applied as soon as the onset of acute myocardial ischaemia is suspected.     

Stress, coronary disease, and coronary death

Evidence of a positive association between cardiovascular illness and psychological stress presented in the literature is generally not totally convincing, which in part is due to methodological problems in defining and measuring psychophysiological and psychosocial variables. However, both reports in the literature and the clinical experience of most physicians present numerous examples of sudden, unexpected cardiac death, in which the event in all probability has been either induced or hastened by stressful life experiences. This applies to fatal and non fatal cardiac attacks, since both are often preceded by emotional stress. There is pathoanatomical evidence of specific myocardial damage induced by catecholamine release during stressful emotions. Histochemical studies have revealed copious amounts of noradrenaline stored in myocardium especially in patients with ischaemic heart disease. Epidemiological surveys on the relationships between life-stress and coronary mortality and morbidity have demonstrated certain positive associations in many cross-sectional studies as well as in certain prospective studies. Most positive evidence has been accumulated from studies on the influence of loneliness on cardiovascular morbidity and mortality. Animal experiments have demonstrated repeatedly that psychological stress evoked by aversive sensoric stimuli or unsuccessful social striving induce cardiovascular pathology including myocardial damage, hypertension, vascular changes and increased risk of sudden cardiac death.