NCA对受磷蛋白敲除小鼠心肌兴奋-收缩偶联的作用

 目的: 硝酰基(HNO)在轻微增加细胞内钙的基础上可以显著增加心肌肌丝对钙离子的反应性。本研究中,我们应用崭新的HNO供体乙酸1-亚硝基环己酯(NCA)来观察HNO对受磷蛋白敲除(PLB-KO)小鼠心室梳状肌的作用。方法: 小鼠右心室的完整梳状肌被连接在张力换能器与刺激电极之间,肌小节长度设定在2.2~2.3μm之间,K-H液表面灌流后,Fura-2经玻璃微电极负载进行离子透入法检测[Ca²⁺]_i,同时测定心肌收缩张力的变化。结果: PLB-KO小鼠心室梳状肌比野生型(WT)小鼠具有更高的钙瞬变及收缩力,同时展示负性收缩力-收缩频率相关性(FFR)。NCA(2.5μmol/L)在不同浓度细胞外钙([Ca²⁺]_o)条件下增加PLB-KO及WT小鼠心肌收缩力,但并不影响PLB-KO小鼠的负性FFR。稳态条件下2组小鼠去肌膜梳状肌的收缩力-钙离子相关性无显著性差异,NCA则增加去肌膜梳状肌的钙离子的反应性。结论: NCA提供的HNO通过增加PLB-KO及WT小鼠心肌肌丝对钙离子的反应性而增强心肌收缩力;心肌细胞内钙瞬变的增加伴随收缩力的增强表明HNO可改善钙离子活性,进一步证实HNO作为正性肌力药物的作用效果。     

Defective intracellular Ca2+ homeostasis contributes to myocyte dysfunction during ventricular remodelling induced by chronic volume overload in rats

1. Previous studies have demonstrated progressive ventricular hypertrophy, dilatation and contractile depression in response to chronic volume overload. Whether this decompensation was related to intrinsic myocyte dysfunction was not clear. The present study evaluated ventricular myocyte function at critical times during the progression of ventricular remodelling induced by volume overload. 2. Chronic volume overload was induced with an infrarenal aortocaval fistula in rats. Myocyte contraction and intracellular Ca(2+) concentrations ([Ca(2+)](i)) were evaluated using a fura-2 fluorescence and edge detection system. Protein levels of sarcoplasmic reticulum (SR) Ca(2+) transporters were determined by western blots. Progressive ventricular dilatation developed following creation of the fistula. Although myocyte function in 5 week fistula rats was comparable to that of the control group, myocytes from rats 10 weeks post-fistula demonstrated significant depression of cell shortening and peak [Ca(2+)](i). Application of isoproterenol (0.1 micromol/L) was not able to compensate for the functional deficiency in myocytes from 10 week fistula rats. Caffeine (10 mmol/L) induced SR Ca(2+) release, as well as protein expression of SR Ca(2+)-ATPase, and ryanodine receptors were reduced in myocytes obtained from the same group of 10 week fistula rats. 3. These data indicate that the transition to heart failure secondary to chronic volume overload is related to depressed myocyte contractility secondary to altered intracellular Ca(2+) homeostasis.     

大剂量阿司匹林并氟伐他汀钠治疗TIA效果

目的观察大剂量阿司匹林并氟伐他汀钠治疗短暂性脑缺血发作（TIA）安全性、效果以及对血小板计数、凝血功能、血脂的影响。方法将96例TIA病人随机分为2组，对照组口服阿司匹林肠溶片300mg，每日1次，连用10d，后改为阿司匹林肠溶片100mg，每日1次，长期服用。治疗组在对照组用药的基础上同时给予氟伐他汀钠40mg，每日1次，晚餐时口服。所有病人均辅以血塞通400mg加生理盐水250mL静脉滴注，并根据病情给予抗高血压、降血糖、抗心力衰竭等基础治疗。两组治疗前及治疗后第30天分别行血小板、凝血功能及血脂测定。结果两组病人疗效比较差异有显著性（Hc=6．73，P〈0．01）；两组病人治疗前后凝血功能测定值均在正常范围内，差异无显著性（P〉0．05）；两组病人治疗后TC、LDL—C、TG及HDL比较差异均有显著性（t=2．95～8．21，P〈0．01）。结论大剂量阿司匹林并氟伐他汀钠治疗TIA安全、有效。     

Three-Dimensional Fluid-Structure Interaction Simulation of Bileaflet Mechanical Heart Valve Flow Dynamics

The wall shear stress induced by the leaflet motion during the valve-closing phase has been implicated with thrombus initiation with prosthetic valves. Detailed flow dynamic analysis in the vicinity of the leaflets and the housing during the valve-closure phase is of interest in understanding this relationship. A three-dimensional unsteady flow analysis past bileaflet valve prosthesis in the mitral position is presented incorporating a fluid-structure interaction algorithm for leaflet motion during the valve-closing phase. Arbitrary Lagrangian-Eulerian method is employed for incorporating the leaflet motion. The forces exerted by the fluid on the leaflets are computed and applied to the leaflet equation of motion to predict the leaflet position. Relatively large velocities are computed in the valve clearance region between the valve housing and the leaflet edge with the resulting relatively large wall shear stresses at the leaflet edge during the impact-rebound duration. Negative pressure transients are computed on the surface of the leaflets on the atrial side of the valve, with larger magnitudes at the leaflet edge during the closing and rebound as well. Vortical flow development is observed on the inflow (atrial) side during the valve impact-rebound phase in a location central to the leaflet and away from the clearance region where cavitation bubbles have been visualized in previously reported experimental studies.     

Mitochondrial Ca uptake: Tortoise or hare?

Mitochondria are equipped with an efficient machinery for Ca²⁺ uptake and extrusion and are capable of storing large amounts of Ca²⁺. Furthermore, key steps of mitochondrial metabolism (ATP production) are Ca²⁺-dependent. In the field of cardiac physiology and pathophysiology, two main questions have dominated the thinking about mitochondrial function in the heart: 1) how does mitochondrial Ca²⁺ buffering shape cytosolic Ca²⁺ levels and affect excitation–contraction coupling, particularly the Ca²⁺ transient, on a beat-to-beat basis, and 2) how does mitochondrial Ca²⁺ homeostasis influence cardiac energy metabolism. To answer these questions, a thorough understanding of the kinetics of mitochondrial Ca²⁺ transport and buffer capacity is required. Here, we summarize the role of mitochondrial Ca²⁺ signaling in the heart, discuss the evidence either supporting or arguing against the idea that Ca²⁺ can be taken up rapidly by mitochondria during excitation–contraction coupling and highlight some interesting new areas for further investigation.     

北京市朝阳区结核病防治网络系统评价

目的对由区结防所在社区卫生服务中心内设立的肺结核病防治站（以下简称“防治站”）和社区卫生站聘任的结防督导员（以下简称“督导员”）组成的全区结核病防治网络（以下简称“建网”）在结核病控制工作中的作用进行评价。方法分析朝阳区2002年1月—2007年12月登记的肺结核病例资料,对建网前3年（2002年1月—2004年12月）与建网后3年（2005年1月—2007年12月）肺结核的病例发现、户籍人口和流动人口病例的DOTS管理和涂阳病例的治疗转归等情况进行比较。 结果建网前后比较：(1)病例发现由789例增至1322例,增加了533例（67.6%）。防治站发现病例占登记病例总数的40%以上。(2)涂阳病例DOTS管理率平均由63.0%提高到92.9%。(3)涂阳病例治疗成功率户籍人口平均由83.3%提高到92.4%,流动人口平均由65.5 %提高到80.7%。(4)建网后防治站与区结防所的涂阳病例治疗成功率比较无差异。结论在加强政府承诺的同时,建立地区结核病防治网络是解决结核病控制工作中的困难和提高质量的重要措施。     

Airway obstruction and airway wall instability in cystic fibrosis: the isolated and combined effect of theophylline and sympathomimetics

Multiple aspects of lung function were measured in 17 cystic fibrosis (CF) patients on four occasions: without therapy (0); with oral theophylline medication (Th); after inhalation of salbutamol (beta 2); and with combined medication (Th + beta 2). In addition to routine measurements, partial and maximum expiratory flow-volume (MEFV) curves were superimposed, and the flow transient equivalent of the MEFV curve was determined. Its volume dimension (volume of airway contribution, VACMEFV) partially reflects airway distensibility. Changes in airway compressibility--the other consequence of airway wall instability--were assessed by observing changes in end-expiratory flow rate. Airway resistance, expired volumes, and early expired flow rates, as well as VACMEFV improved significantly after beta 2 medication. Mean end-expiratory flow also increased after beta 2; in two patients, however, it decreased significantly, indicating that enhanced airway compression dominated over the release of bronchospasm. The alone had only minor effects on lung function. Early expired volume and flow rates as well as VACMEFV showed no significant difference between beta 2 alone and Th + beta 2; airway resistance even decreased significantly with this drug combination. End-expiratory flow rate, however, was significantly lower after Th + beta 2 than after beta 2 alone. Although theophylline does not alter lung function in most patients with CF, sympathomimetics relieve bronchospasm in many, but they enhance airway compressibility and thereby decrease peripheral expiratory airflow in some.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppressive effect of sustained low-contrast adaptation followed by transient high-contrast on peripheral target detection

We observed that presenting a low-contrast Gabor patch (2 cpd, 5 degrees eccentricity, contrast=4%) for 8 s and then flashing a 20-30 ms high-contrast patch over it could elicit the perceptual disappearance of a subsequent low-contrast stimulus, whereas neither low-contrast adaptation nor high-contrast flash alone had any considerable effect (p<0.00001). In other experiments we found (a) suppressive components are phase-insensitive, (b) the effect transfers between eyes, (c) suppression is selective for orientation, and (d) the induction by the transient high-contrast Gabor patch could be transferred to another previously adapted location up to a few degrees. Results indicate synergy between contrast and adaptation through a non-linear interaction between rapid gain adjustment to transient change and adaptation to sustained spatial patterns. Findings are compatible with non-local mechanisms presumably at the cortical level.     

Endometrial cancer in Asian migrants to the United States and their descendants

Objective: The purpose of this study was to determine the extent to which the incidence of endometrial cancer in Chinese, Japanese, and Filipino residents of the United States varies according to country of birth. Methods: Women 35–74 years diagnosed with endometrial cancer between 1973 and 1986 among residents of the San Francisco/Oakland (CA) metropolitan area, 13 counties of western Washington, and the state of Hawaii were identified by cancer registries serving these populations. From a special tabulation of the 1980 US census, we estimated the size of the population at risk in each of these three areas according to age, race, and country of birth.Results: The annual incidence of primary endometrial cancer was lower among Chinese–American (42.6/100,000) and Japanese–American (25.3/100,000) women born in Asia than among their counterparts who were born in the United States (57.2/100,000 and 51.2/100,000, respectively). No difference in incidence was observed between Filipino women born in Asia (27.4/100,000) and those born in the United States (25.4/100,000). The rate of endometrial cancer among US-born white women (77.0/100,000 women years) exceeded that in any of these Asian–American subgroups. Conclusions: These findings suggest that some clues to the aetiologies of endometrial cancer may be found in exposures whose prevalence differs between generations of Chinese and Japanese Americans.