经冠状动脉移植自体骨髓单个核细胞和间充质干细胞对急性心肌梗死模型心功能的改善

目的:为保护濒死心肌提供机会窗口,对比观察经冠脉移植自体骨髓单个核细胞或间充质干细胞后,实验性急性心肌梗死动物心功能变化及心肌组织核转录因子кB、心肌细胞凋亡情况。方法:实验于2005-03/2006-11在河北省人民医院实验中心完成。选用24只雄性冀中白猪,随机数字表法分为4组:正常对照组、模型组、单个核细胞组、间充质干细胞组,6只/组。①24只猪均以盐酸氯胺酮200mg臀部肌肉注射麻醉后,分别于各自右侧股骨抽取骨髓20mL,采用Fercoll法分离获得骨髓单个核细胞,加入胶体金溶液,培养12～16h待用。分离过程中取出含有骨髓单个核细胞成分的细胞层,常规培养传代,每3d换液1次,贴壁生长细胞即为骨髓间充质干细胞,加入胶体金溶液,培养24h待用。②除正常对照组外,其余各组均经导管球囊封闭第一对角支以远的前降支,复制猪急性心肌梗死模型。单个核细胞组、间充质干细胞组均于造模后立即开通前降支,分别经球囊注入预先分离的骨髓单个核细胞6×108个、间充质干细胞6×108个。模型组造模后于梗死1h开通前降支,经球囊注入磷酸盐缓冲液10mL。③各组分别于术前及术后4周经心脏超声检测心功能,取材行病理学检查、心肌组织核转录因子кB的免疫组织化学检测及心肌细胞凋亡检测。结果:24只雄性白猪均进入结果分析。①心功能变化:术前各组左心室收缩末内径、左心室舒张末内径、左心室射血分数、短轴缩短率基本相似。移植术后4周,正常对照组、单个核细胞组、间充质干细胞组左心室舒张末内径均明显低于模型组(F=4.68,P=0.01),左心室射血分数及短轴缩短率均明显高于模型组(F=5.14,P=0.01;F=3.32,P=0.04),各组左心室收缩末内径差异无显著性意义(F=1.64,P=0.21)。②心肌组织病理学改变:电镜下单个核细胞组、间充质干细胞组在梗死边缘区可见有胶体金颗粒的不成熟的心肌细胞,胞质中散在肌丝结构,肌丝排列紊乱不规则。③心肌组织核转录因子кB阳性率表达:与模型组比较,单个核细胞组、间充质干细胞组的梗死边缘区核转录因子кB阳性率明显降低(F=25.59,P=0.0001);正常心肌区核转录因子кB阳性率亦明显降低(F=18.20,P=0.0001)。④心肌细胞凋亡检测结果:与模型组比较,单个核细胞组、间充质干细胞组在心肌梗死区细胞凋亡率均明显降低(F=6.63,P=0.0027),梗死边缘区细胞凋亡率亦明显降低(F=36.07,P=0.0001)。正常心肌区单个核细胞组细胞凋亡率与模型组基本相似(F=9.69,P=0.004),但间充质干细胞组有所降低。⑤心功能与心肌细胞凋亡及心肌组织NF-кB的相关性:急性心肌梗死4周时,左心室射血分数与心肌细胞凋亡、心肌组织核转录因子кB均呈负相关(r=0.613,P=0.001;r=-0.437,P=0.033)。心肌细胞凋亡与心肌组织核转录因子кB呈正相关(r=0.672,P=0.002)。结论:经冠脉移植骨髓单个核细胞和间充质干细胞均可改善实验性急性心肌梗死动物的心功能,与梗死边缘区核转录因子кB表达降低及心肌细胞凋亡减少有关。骨髓单个核细胞移植的促血管增生作用优于间充质干细胞移植。     

补充蛋白质对健美运动员肌肉力量的影响

目的:为健美运动员补充蛋白质提供科学的饮食方法,以期增加其肌肉体积,达到发展肌肉力量的同时健美体形,对健美运动员补充蛋白质研究作一综述。资料来源:应用计算机检索http://www.chkd.cnki.net/index.htm/,http://www.highwire.org/1994/2007有关补充蛋白质和增加肌肉力量相关的论文,英文检索词为"protein,strength",并限定语种为English;中文检索词为"补充蛋白质,肌肉力量",并限定语种为中文;另外手工查找与补充蛋白质和增加肌肉力量有关的资料和书籍。资料选择:对资料进行初审,选取与补充蛋白质和增加肌肉力量相关的文献,所选择的文献为研究原著,排除重复研究。资料提炼:共收集到200篇补充蛋白质和增加肌肉力量的文献,在选择、分析的基础上,排除重复或类似研究,最终提炼出29篇文献进行分类整理用于综述。资料综合:①运动与蛋白质关系非常密切。当运动强度加大时,使运动员尿氮排出增加并出现尿负氮平衡,因此要适当的补充蛋白质。②补充蛋白质,可以增加肌肉生理横断面,肌纤维增粗,增加肌红蛋白、血红蛋白、酶和蛋白类激素的合成,有利于增加肌肉力量。结论:健美运动员高强度训练期间,为了恢复运动中的消耗、修复损伤的组织、提高健美训练效果,应给予高蛋白类膳食。同时,还需要保持均衡膳食,适当增加矿物质和维他命以及其他营养补剂的补充。     

新复合纤维蛋白胶可注射性磷酸钙人工骨的理学特性

目的:检测纤维蛋白胶复合β-磷酸三钙/磷酸二氢钙复合人工骨材料的物理学性能,评价纤维蛋白胶对β-磷酸三钙/磷酸二氢钙骨水泥性能的影响,以及其作为注射型复合人工骨用于修复骨缺损的可行性。方法:实验于2006-12/2007-06在南方医科大学珠江医院中心实验室和华南理工大学生物材料实验室完成。①材料:β-磷酸三钙由上海瑞邦生物材料有限公司提供,磷酸二氢钙为东泰化工赠,纤维蛋白胶购自广州倍绣生物技术有限公司。②复合材料制备:将β-磷酸三钙/磷酸二氢钙骨水泥按3∶1的比例充分混合后,与纤维蛋白胶按凝固后的体积2∶1体积比混合,制成复合人工骨材料。③观察指标:测定复合材料的凝固时间,抗压强度,抗稀散性能,并用扫描电镜观察其煅烧前后的显微结构特征,以未加纤维蛋白胶的磷酸钙水泥为对照(CPC组)。结果:复合人工骨材料的平均初凝时间长于CPC组(P<0.004),终凝时间在初凝时间后2～4 min;复合材料的抗压强度为(14.72±1.81)MPa。复合材料较CPC组有良好的抗稀散性能,扫描电镜发现,纤维蛋白胶贯穿于磷酸钙水泥晶体间,并将磷酸钙水泥晶体紧密连接。煅烧后复合材料的孔径有增大,空隙率为57.28%,并且微孔之间有空隙互相贯通。结论:该骨水泥复合材料凝固时间符合临床操作的需要;抗压强度达到松质骨强度的要求;煅烧后磷酸钙水泥的空隙率明显提高,有利于材料的降解。     

自体骨髓间充质干细胞移植后心肌缝隙连接蛋白43表达与室性心动过速发生的关系

目的:缝隙连接蛋白43对维持心肌细胞的连接通讯功能、电信号传导和正常的节律性收缩起重要作用,其表达和分布的异常是多种室性心律失常的解剖学基础,建立小型猪急性心肌梗死模型.观察自体骨髓间充质干细胞移植后室性心动过速的发生及心肌缝隙连接蛋白43的表达方法:实验于2006-01/2007-01在河北省人民医院导管室完成。①材料:选取8～12月龄小型猪22头,由河北医科大学实验动物中心提供,体质量20～30 kg,随机数字表法分为细胞移植组12头、模型对照组10头.实验过程中对动物的处置符合动物伦理学际准②实验方法:无菌条件下抽取猪双侧股骨骨髓20 mL,percoll法 贴壁法分离培养骨髓间充质干细胞,待细胞生长达75%融合时用胰酶消化传代。将传至第2代细胞加入终浓度为10μmol/L的5-氮胞苷进行诱导,用胶体金标记12 h后继续培养20 d用于移植:两组小型猪均采用球囊堵闭法建立急性心肌梗死模型.心电图监测示相关至少2个导联ST段抬高大于0.2 mV、术后血肌钙蛋白和肌酸磷酸激酶同工酶升高超过正常的两倍为建模成功标准:细胞移植组于造模成功后经OTW球囊于第一对角支远端1 cm处再次阻断血流,注入经胶体金标记的10×10~7个骨髓间充质干细胞。③实验评估:于细胞移植后2 h及4周行电生理程序刺激.观察室性心动过速的发生情况。末次电生理检查后、采用免疫组化染色法检测心肌缝隙连接蛋白43的表达.计算其积分吸光度值。结果:①模型建立指标检测:与术前比较.造模后所有小型猪血肌钙蛋白含量和肌酸磷酸激酶同工酶活性均增高,峰值浓度分别为(21.3±3.6)μg/L和(178.3×41.4)IU/L,术中心电图ST段平均抬高(10.67±1.43)mm.证明急性心肌梗死模型成功建立。②骨髓间充质干细胞移植后室性心动过速的发生情况:与模型对照组诱发出室性心动过速的动物数量比较,术后2 h细胞移植组无明显变化(X~2=0.201,P=0.650),术后4周细胞移植组明显降低(X~2=4.455.P=0.035)。②骨髓间充质干细胞移植后梗死心肌缝隙连接蛋白43的表达:术后4周移植到梗死心肌的骨髓间充质干细胞与宿主心肌生长为一体,移植部位颜色变黑,苏木精-伊红染色示移植细胞的胞浆呈紫红色。细胞移植组心肌梗死区缝隙连接蛋白43积分吸光度值明显高于模型对照组(t=16,82.P=0.00),细胞移植组中未发生室性心动过速小型猪的梗死心肌缝隙连接蛋白43的表达明显高于发生室性心动过速小型猪(t=5.06,P=0.00)。结论:自体骨髓间充质干细胞移植可促进急性心肌梗死猪心肌缝隙连接蛋白43的表达,其表达程度可能与急性心肌梗死室性心动过速的发生有关。     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.     

Quality of life in a heterogeneous sample of caregivers of cancer patients: an in‐depth interview study

MANCINI J., BAUMSTARCK‐BARRAU K., SIMEONI M.‐C., GROB J.‐J., MICHEL G., TARPIN C., LOUNDOU A.‐D., LAMBERT A., CLÉMENT A. & AUQUIER P. (2010) European Journal of Cancer Care
Quality of life in a heterogeneous sample of caregivers of cancer patients: an in‐depth interview study To establish the best approach to develop a quality of life (QoL) questionnaire for cancer‐patient caregivers, this study attempts to identify primary domains of QoL in terms of their impact on a purposive sample of caregivers. Seventy‐seven informal adult caregivers of cancer patients (breast cancer, paediatric haematological malignancies or melanoma) with different relationships with the patients (parents, children, spouses, siblings, and friends) were recruited at three specialised French centres and extensively interviewed. Caregivers' lives were altered in several domains: psychological well‐being, leisure and everyday activities, relationships with institutional caregivers, occupation and finances, relationships with family and friends, physical well‐being, and relationship with the patient. The relative importance of these domains varied mainly in association with the caregiver‐patient relationship. Multiple correspondence analysis identified two isolated clusters: children, and, most significantly, friends and siblings. The latter groups emphasised the repercussions on their psychological well‐being and their relationship with the patient, but were less willing to discuss the impact on their relationship with caregivers and on occupation, finances, leisure, and everyday activities. This study focuses on the caregiver's perspective and advocates the development of a short QoL core questionnaire. Additional modules should be cancer‐specific or dedicated to specifics of the caregiver‐patient relationship.     

Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon interaction with both receptor tyrosine kinases (RTK) and G- proteins resulting in the production of moieties involved in the inositol phospholipid signalling pathway. As G proteins, RTK and the inositol phospholipids have all been implicated in the human sperm acrosome reaction, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100 nM) and a polyclonal antibody raised against an extracellular region of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI 3- kinase is involved in the human sperm acrosome reaction. The levels of tyrosine phosphorylation of sperm proteins as detected by Western blotting using antiphosphotyrosine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase operates downstream of tyrosine phosphorylation in the signal transduction cascade which leads to the human sperm acrosome reaction.      

Magnetic resonance angiography

Pulse sequences that permit selective detection of moving spins in a magnetic resonance image have been developed. Experiments were performed by the authors to produce projected angiographic data without the use of contrast agents, with the intensity of each image pixel determined by the macroscopic velocity of the detected spins. With this method, suppression of nonmoving spins is essentially complete, yielding a high dynamic range in signal intensity for detected vessels. Selective detection of moving spins is not dependent on pulsatile flow. Consequently, not only arterial structures, but also venous structures can easily be visualized. High-resolution angiographic images can be obtained by combining the flow experiment with surface coil techniques.