Dystrophic heart failure blocked by membrane sealant poloxamer

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy. Heart failure is the second leading cause of fatalities in DMD. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease. Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy.     

基于遗传算法的发动机自寻优模糊控制

针对汽车发动机参数具有离散性、非线性和不确定性,采用传统控制模型难以精确控制瞬态过程的过量空气系数和点火时刻的问题,提出了一种基于遗传算法的发动机自寻优模糊控制模型.设计了实现该控制模型的嵌入式控制器,讨论了实时在线仿真基础上,采用遗传算法对模糊控制参数的自动寻优.实验表明,发动机动力性和经济性指标取得到了明显提高,以及控制模型在降低燃油消耗方面具有明显的优势.     

Se-scFv-B3对过氧化氢诱导的大鼠乳鼠心肌细胞损伤的保护作用

用H2O2损伤大鼠乳鼠的心肌细胞建立氧化应激损伤模型,考察谷胱甘肽过氧化物酶模拟物Se-scFv-B3对H2O2诱导的大鼠乳鼠心肌细胞氧化损伤的影响.结果表明,Se-scFv-B3能部分增加心肌细胞存活率,减少细胞凋亡,恢复线粒体膜电位,下调Caspase-3活力并降低细胞内活性氧的含量.表明Se-scFv-B3可以保护心肌细胞抵制H2O2诱导的氧化应激损伤.     

Kinetics, stoichiometry and role of the Na-Ca exchange mechanism in isolated cardiac myocytes

Compelling evidence has existed for more than a decade for a sodium/calcium (Na-Ca) exchange mechanism in the surface membrane of mammalian heart muscle cells which exchanges about three sodium ions for each calcium ion. Although it is known that cardiac muscle contraction is regulated by a transient increase in intracellular calcium ([Ca2+]i) triggered by the action potential, the contribution of the Na-Ca exchanger to the [Ca2+]i transient and to calcium extrusion during rest is unclear. To clarify these questions, changes in [Ca2+]i were measured with indo-1 in single cardiac myocytes which were voltage clamped and dialysed with a physiological level of sodium. We find that Ca entry through the Na-Ca exchanger is too slow to affect markedly the rate of rise of the normal [Ca2+]i transient. On repolarization, Ca extrusion by the exchanger causes [Ca2+]i to decline with a time constant of 0.5 s at -80 mV. The rate of decline can be slowed e-fold with a 77-mV depolarization. Calcium extrusion by the exchanger can account for about 15% of the rate of decline of the [Ca2+]i transient (the remainder being calcium resequestration by the sarcoplasmic reticulum (SR]. The ability of the cell to extrude calcium was greatly reduced on inhibiting the exchanger by removing external sodium, which itself led to an increase in resting [Ca2+]i. This finding is in contrast to the suggestion that calcium extrusion at rest is mediated mainly by a sarcolemmal Ca-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)     

三七总皂苷对心梗后心室重构大鼠增强抗氧化与改善心肌形态学作用

 为研究三七总皂苷(PNS)对急性心肌梗塞（AMI）后左室重构（LVRM）大鼠自由基损伤和心肌细胞形态学改变的作用, 采用结扎大鼠左冠状动脉前降支的方法,建立AMI模型,术后24 h后随机分为对照组和实验组,连续4周分别灌胃给予生理盐水和PNS低、中、高剂量,观察PNS和福辛普利对病鼠血清丙二醛（MDA）、c反应蛋白(CRP)、肌红蛋白-I（cTn-I）及肌酸激酶同工酶（CK-MB）、谷胱甘肽过氧化物酶（GSH-Px）、一氧化氮（NO）及心肌细胞形态病理结构和心脏指数改变等的影响。结果发现与对照组比较,PNS与福辛普利均能显著改善病鼠左室心肌细胞形态结构病理改变及心脏指数（P<0.01）,显著降低MDA、CRP、CK-MB与cTn-I、提高GSH-Px活性（P<0.01～0.05）,高剂量PNS可明显降低NO含量（P<0.05）。可见PNS可通过抑制脂质过氧化反应,减轻病鼠心肌细胞的病理损伤,增强抗氧化,具有抑制心肌肥大与改善心室重构心肌细胞形态学结构作用。     

不同产地丹参脂溶性成分对H9C2心肌细胞缺氧缺糖损伤保护作用的差异

通过HPLC谱图比较不同产地丹参脂溶性成分含量的差异,采用MTT染色法测定缺氧、缺糖1、2、3 h后H9C2心肌细胞的成活率以建立缺氧缺糖模型组,以低、中、高剂量的丹参脂溶性成分加入模型组细胞,观察细胞的状态确定加药浓度。检测各组的乳酸脱氢酶（LDH）含量、总抗氧化活力（T AC）和细胞存活率（SR）,以此作为考察丹参脂溶性成分保护作用差异的指标。结果表明,缺氧缺糖组以及不同产地丹参脂溶性成分治疗各组的SR与正常对照组相比有显著性差异（P＜0.05）,不同产地丹参脂溶性成分治疗各组的SR与缺氧缺糖组相比有显著性差异（P＜0.05）。缺氧缺糖组以及不同产地丹参脂溶性成分治疗各组的LDH与正常对照组相比有显著性差异（P＜0.05）,不同产地丹参脂溶性成分各组的LDH含量与缺氧缺糖组相比有显著性差异（P＜0.05）。缺氧缺糖组以及不同产地丹参脂溶性成分各组的T AC与正常对照组相比有显著性差异（P＜0.05）,不同产地丹参脂溶性成分各组的T AC与缺氧缺糖组相比有显著性差异（P＜0.05）。丹参脂溶性成分明显减少心肌细胞缺氧缺糖损伤后LDH的溢出,提高了心肌细胞的T AC和SR,其对缺氧缺糖损伤后心肌细胞确实有修复保护作用,不同产地丹参中脂溶性成分对心肌细胞缺氧缺糖保护作用确实存在药效差别。     

重复购买与市场变化下产品扩散实证研究

重复购买以及市场环境变化对产品扩散有影响作用,从而限制了基本产品扩散模型的应用.通过构建反映动态市场变化的环境变量集合,基于影响系数对产品扩散模型做出修正,同时考虑重复购买因素,得到重复购买与市场变化下的产品扩散模型.以我国汽车产品细分市场之一的微型交叉型乘用车产品扩散为实例,将超过使用年限后的重复购买因素与市场的燃油价格、产品价格、宏观政策等因素作为修正变量融入扩散模型,分析目标产品的扩散规律.研究结果表明,加入重复购买与动态市场因素后,模型计算结果拟合度提高13%,预测结果的误差平均绝对比率由23.93降低至5.5.由此可知,提出的扩展产品扩散模型在解释能力和预测能力上均优于基本模型。     

Effect of Calcium on Spontaneous Quantal Transmitter Secretion from ACh-Loaded Myocytes

Introduction Transmitter secretion requires specialized secretory or- ganelles, the synaptic vesicles, for the packaging, stor- age, and exocytotic release of the transmitters[1,2]. The neurotransmitter acetylcholine (ACh) is released at the neuromuscular…     

一种改进的有毒气体扩散高斯模型算法及仿真(英文)

高斯模型作为评价有毒气体泄漏后的扩散模型,因其计算量小、简单易用等特点而被广泛应用.文章对有毒气体扩散的时空特性进行了讨论,通过引入一种时间因子,对现有高斯烟团模型进行了改进,建立了以时间函数为动态变换基点的有毒气体扩散模型.将有限时间内的有毒气体连续释放过程表述为实源和一系列虚源在多个时间区段内的释放子过程的组合.根据改进的高斯模型,编程实现了基于GIS的、实时的有毒气体扩散动态仿真.仿真结果表明,该算法能够快速、准确地计算出有毒气体泄漏后的任意时间点的扩散浓度空间分布,能够较好地模拟有毒气体扩散的动态变换过程,对危险化学品泄漏事故现场的预测和评估具有很好的辅助决策作用.     

Study of transmembrane La3+ movement in rat ventricular myocytes by the patch-clamp technique

We have studied transmembrane La3+ movement in rat ventricular myocytes for the first time by using the whole-cell patch-clamp recording mode. La3+ (0.01-5.0 mmol/L) could not bring out inward currents through the L-type calcium channel in rat ventricular myocytes, while it could enter the cells by the same way carried by 1μmol/L ionomycin. When the outward Na+ concentration gradient is formed, La3+ can enter the cells via Na-Ca exchange, and the exchange currentsincrease with the increase of external La3+ concentrations. But compared with Na-Ca exchange currents in the same concentration, the former is only 14%-38% of the latter. The patch-clamp experiment indicates that La3+ normally can not enter ventricular myocytes through L-type calcium channel, but it can enter the cells via Na-Ca exchange.     

Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes

In heart cells, cyclic AMP-dependent protein kinase (PKA) regulates calcium- and potassium-ion current by phosphorylating the ion channels or closely associated regulatory proteins. We report here that isoprenaline induced large chloride-ion currents in voltage-clamped, internally-dialysed myocytes from guinea-pig ventricles. The Cl- current could be activated by intracellular dialysis with cAMP or the catalytic subunit of PKA, indicating regulation by phosphorylation. In approximately symmetrical solutions of high Cl- concentration, the macroscopic cardiac Cl- current showed little rectification, unlike the single-channel current in PKA-regulated Cl- channels of airway epithelial cells. But, like epithelial Cl- -channel currents, the cardiac Cl- current was sensitive to the distilbene,4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS). In the absence of kinase activation, cardiac sarcolemmal Cl- conductance was negligible. During beta-adrenergic stimulation of the heart, this novel Cl- conductance should accelerate action-potential repolarization and so protect impulse propagation in the face of the possibly arrhythmogenic increases in heart rate and in calcium entry into the cells.     

Se-scFv-B3对过氧化氢诱导的大鼠乳鼠心肌细胞损伤的保护作用

用H₂O₂损伤大鼠乳鼠的心肌细胞建立氧化应激损伤模型, 考察谷胱甘肽过氧化物酶模拟物Se-scFv-B3对H₂O₂诱导的大鼠乳鼠心肌细胞氧化损伤的影响. 结果表明, Se-scFv-B3能部分增加心肌细胞存活率, 减少细胞凋亡, 恢复线粒体膜电位, 下调Caspase-3活力并降低细胞内活性氧的含量. 表明Se-scFv-B3可以保护心肌细胞抵制H₂O₂诱导的氧化应激损伤.     

热等静压扩散连接反应层元素互扩散的动力学模拟计算

通过DICTRA-THERMO-CALC动力学和热力学联合计算软件对DD402单晶和Rene95粉末高温合金进行热等静压扩散连接反应层元素互扩散规律的模拟计算，计算结果表明，此种模拟计算方法可以较好地反应扩散偶中元素的互扩散规律，与实验结果基本吻合，在此基础上，分析了计算了温度和时间对扩散连接过程中Al元素互扩散规律的影响，最终得出此种模拟计算方法可以为热等静压扩散连接工艺的制定和优化提供较好的理论依据。     

基于时序模型的股指序列分析

根据计量经济时序模型,基于2005～2009年沪深两股市的数据和统计软件EVIEWS,将计量模型与分形维数相结合,利用股指的高维混沌特征,以L-P算法确定了分形维数。运用向量自回归VAR模型,对沪深两个股市进行了单位根检验,根据AIC和SC信息准则确定滞后阶数,并对股市的未来趋势进行了有效地动态和静态预测,得出了较为合理的结果。     

奇线性的动态投入-产出问题

本文从推导没有联合生产和生产时滞的动态投入产出模型出发,利用奇摄动方法处理了资本货物矩阵为奇异或近似奇异的情形。结果发现产品的初始产量向量应位于某稳定流形上,否则将出现边界层现象,从而经济系统将很快失去平衡。     

等离子体显示中基于边缘检测的动态误差扩散方法

针对交流等离子体显示器中的常规误差扩散方法因误差扩散系数固定导致反映图像细节轮廓损失的问题，提出了一种基于边缘检测的动态误差扩散方法．该方法在对每个像素的误差扩散处理过程中，先沿误差扩散方向进行边缘检测，再根据边缘检测结果动态地选择误差扩散系数组及调整各个方向的误差扩散系数，使得误差扩散系数与轮廓特征相关，减小了误差扩散过程中造成图像细节轮廓损失的累积误差．仿真结果表明，将新方法应用于交流等离子体显示器中，不仅能够减少因较少子场引起的假轮廓，同时还可以避免由于常规误差扩散方法中固定误差扩散系数引起的轮廓细节损失．     

改性硅藻土对重金属离子的吸附规律

 利用CaCO3对硅藻土矿物进行改性. 研究结果表明: 单组分体系中CaCO3改性的硅藻土对Cu2+,Pb2+,Cd2+和Zn2+的吸附动力学规律均符合伪二阶动力学模型, 吸附热力学规律符合Langmuir模型; 在混合组分体系中, Pb2+,Cd2+和Zn2+的吸附速率降低, Cu2+的吸附速率增加, 对金属离子的吸附动力学规律仍然符合伪二阶动力学模型, 但对金属离子的吸附量均明显降低, 仅Pb2+的吸附热力学规律符合Langmuir模型.     

新生大鼠心肌细胞原代培养方法的改进

探讨更为简单的SD大鼠心肌细胞原代培养的方法,使分离的心肌细胞达到理想的存活率和纯度,为临床应用建立心肌细胞模型.取出生24 h内SD大鼠的左心室,剪碎、消化、分离和纯化,进行培养,0.1 g/L胰酶消化,可以分离到形态完整、贴壁生长的心肌细胞.进一步通过离心、差速贴壁和化学试剂抑制非心肌细胞生长,纯化得到95%以上的心肌细胞.成功建立了心肌细胞体外培养模型,获得了高纯度的心肌细胞.     

DFO对心肌细胞铁代谢的影响

观察去铁胺(DFO)对原代培养的心肌细胞铁代谢的影响,探讨DFO对心肌细胞铁代谢的影响机制.用原代培养的乳鼠心肌细胞为材料,以不同浓度的DFO孵育细胞,然后检测心肌细胞存活率、搏动频率以及铁转运相关蛋白CP,HP,FP1的表达变化.结果表明:各剂量DFO对心肌细胞存活率无明显影响;心肌细胞搏动频率减慢,停止跳动的细胞数量明显增加,收缩幅度逐渐降低;随着DFO浓度的增加,心肌细胞CP和HP的表达增加而FP1表达减少.由此可以看出,DFO不影响心肌细胞的存活率,但影响细胞的生活状态,也影响心肌细胞内CP,HP和FP1蛋白的表达.     

Cyg X-1 X射线短暴特性与康普顿化模型的比较

为了解释致密天体高能辐射的时延现象和能谱等特征,多种致密天体X射线辐射源的理论模型先后被提出。但是,目前尚没有一种模型能够完全解释X射线的高能辐射现象,即现有的理论模型还不够完善。通过对X射线辐射源时延现象和短暴半高宽随能量变化这两个特性的讨论,并尝试将Cyg X-1的观测结果与康普顿化模型进行比较,对原模型给出更多的限制从而建立更为合理的新模型。