自主研制镍钛记忆合金左心耳封堵器封闭左心耳对实验动物左心功能的影响

目的:应用经胸彩色多普勒超声技术评价自主研制的镍钛记忆合金左心耳封堵器封闭左心耳对实验动物猪左心房、左心室功能的影响。方法:实验于2005-09/2006-08在南京医科大学第一附属医院江苏省实验动物中心完成。①实验分组:选用苏钟小型种猪17只,随机分为实验组12只和对照组5只。②实验干预:实验组12只苏钟小型种猪使用自主研制的左心耳封堵器(发明专利号码:200610037789.3,公开号CN1799521,由镍钛合金骨架、多聚四氟乙烯膜和传送连接部分等构成。其外观呈单盘状,封堵器的左心房面呈圆盘状,直接连接放入心耳内的圆柱体结构)行左心耳封堵,对照组5只手术步骤相同而不采用封堵器行左心耳封堵。③实验评估:两组动物分别于术前、术后1周、2周、4周采用经胸超声心动图检查观察心功能的改变,测量左心房内径、最大及最小容积、左房射血分数、左心房搏出量、血流分数等左房功能参数以及左室射血分数、左室短轴缩短率、Tei指数、E/A比值等指标。结果:①实验动物数量分析:在施行左心耳封堵后,1头猪于术中出血过多并出现室颤后死亡,1头猪因封堵器脱入左房,卡在二尖瓣口导致死亡。其余动物封堵效果良好。②两组动物术后1,2,4周左房功能指标各参数与术前比较无明显变化(P>0.05);与术前相比,实验组术后1周、2周左室射血分数、左心室短轴缩短率、E/A比值分别由术前的0.70±0.04、0.39±0.03、1.33±0.28降低至术后1周的0.59±0.05、0.31±0.03、0.95±0.11(P<均0.01)及术后2周的0.62±0.05、0.33±0.05、0.90±0.05(P<均0.01);Tei指数由术前的0.48±0.02增加至术后1周的0.59±0.03(P<0.01)及术后2周的0.58±0.04(P<0.01)。对照组手术前后左室功能指标差异无显著性。结论:自主研制左心耳封堵器可以有效的封堵左心耳;左心耳封堵后短期内对实验动物左房功能无明显影响;封堵后短期内对左心室功能具有短期的减弱,更长期的安全性有待于进一步研究。     

结缔组织生长因子在急性心肌梗死后心力衰竭大鼠心肌中表达与洛沙坦的调节

目的:观察结缔组织生长因子在急性心肌梗死后心力衰竭大鼠心肌中的表达特点和洛沙坦对其调节作用。方法:实验于2004-01/2005-03在华中科技大学同济医学院附属协和医院心血管病实验室完成。选择健康雌性SD大鼠60只,50只大鼠通过结扎大鼠左冠状动脉前降支制备急性心肌梗死后心力衰竭模型,术后6h存活的44只大鼠随机数字表法分为心力衰竭对照组24只,洛沙坦干预组20只。另设假手术组10只,相当于冠脉结扎部位穿线,但不结扎,然后立即缝合。洛沙坦干预组每天直接灌胃给予洛沙坦10mg/kg,2次/d;心力衰竭对照组及假手术组大鼠灌等量自来水,共计8周。治疗8周后行高频多普勒超声、血流动力学、心脏重塑指标、左室非梗死区心肌结缔组织生长因子蛋白免疫印迹测定。结果:纳入大鼠60只,去除死亡及梗死面积<35%和>55%的大鼠,最终进入结果分析32只。①大鼠左室结构和功能比较:多普勒超声检查提示,心力衰竭对照组的左室舒张末期内径、左室舒张末期容积、E峰、E峰减速度及E/A显著高于假手术组(P<0.01),左室短轴缩短率和射血分数显著低于假手术组(P<0.01)。洛沙坦干预组左室舒张末期内径、左室舒张末期容积、E峰、E峰减速度及E/A显著低于心力衰竭对照组[分别为(7.0±0.5),(8.7±0.6)mm;(421±26),(521±27)μL;(72±6),(95±7)cm/s;(26.5±2.6),(32.1±3.5)m/s2;4.9±0.5,10.3±0.8,P<0.01],左室短轴缩短率和射血分数显著高于心力衰竭对照组[分别为(26±4)%,(21±4)%;(39±4)%,(31±4)%,P<0.01]。②大鼠血流动力学和心室重塑指标改变:心力衰竭对照组平均动脉压明显低于假手术组(P<0.01),左室舒张末压、左心室心肌肥厚指数、右心室心肌肥厚指数和心肌胶原容积分数均显著高于假手术组(均为P<0.01)。洛沙坦干预组左室舒张末压、左心室心肌肥厚指数、右心室心肌肥厚指数和心肌胶原容积分数显著低于心力衰竭对照组[分别为(10.2±1.9),(20.1±2.5)mm Hg;2.30±0.11,2.45±0.12;0.69±0.07,0.92±0.11;(4.7±1.1)%,(8.2±1.2)%,P<0.01]。③大鼠左室心肌结缔组织生长因子蛋白表达的变化:心力衰竭对照组结缔组织生长因子蛋白表达高于假手术组(P<0.01)。洛沙坦干预组结缔组织生长因子蛋白表达低于心力衰竭对照组(分别为0.72±0.21,1.21±0.23,P<0.01)。结论:急性心肌梗死后心力衰竭大鼠左室非梗死区心肌结缔组织生长因子蛋白表达明显升高,洛沙坦对结缔组织生长因子蛋白表达的增加有抑制作用,并能明显减轻左室重塑和延缓心力衰竭进展。     

Intravascular ultrasound assessment of expansion of the sirolimus-eluting (cypher select) and paclitaxel-eluting (Taxus Express-2) stent in patients with diabetes mellitus

Patients with diabetes have a higher risk for in-stent restenosis after coronary stent implantation. Drug-eluting stents (DES) are highly effective in reducing in-stent restenosis. Once neointimal hyperplasia is suppressed with DES, the impact of stent underexpansion becomes magnified. The aim of this study was to evaluate DES expansion in patients with diabetes. Ninety-five patients with diabetes were randomized to Cypher Select (n = 48) or Taxus Express-2 (n = 47) stent implantation. Intravascular ultrasound was performed after stent implantation. Stent expansion was defined as the ratio of measured to predicted minimum stent diameter. There was a trend for lower stent expansion in the Cypher Select stent group (0.74 +/- 0.08 vs 0.78 +/- 0.11 in the Taxus Express-2 stent group, p = 0.061). Cypher Select stents achieved a final minimal stent cross-sectional area of 5.5 +/- 1. 8 mm2, compared with 6.4 +/- 1.9 mm2 for Taxus Express-2 stents (p = 0.015). For stents with nominal diameters > or =2.75 mm (Cypher Select n = 40, Taxus Express-2 n = 38), 42.5% of the Cypher Select stents and 10.5% of the Taxus Express-2 stents did not achieve a final minimum stent area of 5 mm2 (p = 0.002). Insulin treatment (relative risk 0.31, 95% confidence interval 0.10 to 0.95, p = 0.041) and stent type (relative risk 0.15, 95% CI 0.04 to 0.53, p = 0.003) were independent predictors of not achieving a minimum stent area >5.0 mm2. In conclusion, an important percentage of DES in patients with diabetes fail to achieve the manufacturers' predicted final minimal stent diameter. Cypher Select stent and insulin treatment were independent predictors of not achieving a minimum stent area >5.0 mm2.     

Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model

We investigated the effect of human bone marrow-derived mesenchymal stem cells on engraftment of human umbilical cord blood CD34⁺ cells and acute myelogenous leukemia cells and also assessed the homing capability of MSCs. Forty-two NOD/SCID mice were administered sublethal irradiation followed by various cell doses of intravenous UCB CD34⁺ cells with or without MSCs. Another 12 NOD/SCID mice were also sublethally irradiated followed by intravenous injection of AML cells with or without MSCs. In ten of these mice, MSCs were genetically modified with an adenoviral vector encoding eGFP gene for tracking purpose. Cotransplantation of UCB CD34⁺ cells and MSCs resulted in a significant increase in bone marrow engraftment after 6 weeks, and the engraftment promoting effect of MSCs was proportional to the dose of MSCs and obvious when low doses of UCB CD34⁺ cells were given. There was no effect of MSCs on AML cells engraftment. All of the ten mice transplanted with eGFP-transfected MSCs showed positive for eGFP in their major organs. These data demonstrate that MSCs promote engraftment of UCB CD34⁺cells in bone marrow, but exert no effect on engraftment of AML cells, and are capable of homing to the major organs including bone marrow following intravenous infusion. This investigation was supported by a CMB Yuhan Research Grant of Yonsei University College of Medicine for 2003.     

BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments

Recent microarray studies with stringent validating criteria identified Bcl-2-associated athanogene (BAG1) as a target for the actions of medications that are mainstays in the treatment of bipolar disorder (BPD). BAG1 is a Hsp70/Hsc70-regulating cochaperone that also interacts with glucocorticoid receptors (GRs) and attenuates their nuclear trafficking and function. Notably, glucocorticoids are one of the few agents capable of triggering both depressive and manic episodes in patients with BPD. As a nexus for the actions of glucocorticoids and bipolar medications, we hypothesized that the level of BAG1 expression would play a pivotal role in regulating affective-like behaviors. This hypothesis was investigated in neuron-selective BAG1 transgenic (TG) mice and BAG1 heterozygous knockout (+/-) mice. On mania-related tests, BAG1 TG mice recovered much faster than wild-type (WT) mice in the amphetamine-induced hyperlocomotion test and displayed a clear resistance to cocaine-induced behavioral sensitization. In contrast, BAG1+/- mice displayed an enhanced response to cocaine-induced behavioral sensitization. The BAG1 TG mice showed less anxious-like behavior on the elevated plus maze test and had higher spontaneous recovery rates from helplessness behavior compared with WT mice. In contrast, fewer BAG1+/- mice recovered from helplessness behavior compared with their WT controls. BAG1 TG mice also exhibited specific alterations of hippocampal proteins known to regulate GR function, including Hsp70 and FKBP51. These data suggest that BAG1 plays a key role in affective resilience and in regulating recovery from both manic-like and depression-like behavioral impairments.     

Ionic cellulose-stabilized gold nanoparticles and their application in the catalytic reduction of 4-nitrophenol

A novel strategy for the synthesis of highly stable gold nanoparticles (GNPs) was designed by reducing HAuCl₄ with NaBH₄ in an aqueous solution of water-soluble ionic cellulose composed of dimethylimidazolium cations and phosphite-bound cellulose anions. NMR and UV-Vis analysis along with the measurement of the zeta potential suggest that the exceptionally high stability of GNPs originates from the strong interaction of GNPs with the phosphite groups of the ionic cellulose. The thus prepared GNPs exhibit excellent catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol, a model hydrogenation reaction.

Gold nanoparticles (GNP) were highly stabilized by water soluble ionic cellulose by the strong interaction of GNP with the phosphite groups and showed extremely high catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol.     

人体蛞蝓假寄生1例

患者女性,50岁,黑龙江省七台河市新兴煤矿面包厂工人。2006年11月25日早饭后自觉腹胀,持续1d,因无食欲未再进食。次日清晨,患者呕吐活虫20余条,从中捡出7条置于小瓶中,来哈尔滨医科大学附属第二医院就诊。经胃肠钡餐造影,未见异物。经本教研室鉴定,7条虫体为蛞蝓(Li     

大鼠海马神经细胞体外缺糖缺氧模型制备方法的改进

目的:改进培养大鼠海马神经细胞体外缺糖缺氧模型制备方法,并通过兴奋性氨基酸N-甲基-D-天冬氨酸受体拮抗剂进行验证。方法:实验于2004-09/2005-06在南方医科大学基础医学院神经生物学教研室进行。实验材料:出生1d内清洁级SD大鼠,由南方医科大学实验动物中心提供(合格证号为粤证监字2004B023号)。N-甲基-D-天冬氨酸受体拮抗剂5-甲基二氢丙环庚烯亚胺马来酸(MK-801)和D-2-氨基-5-磷酰基戊酸(d-APV)购自Sigma公司。实验方法:取新生1dSD大鼠海马组织作神经细胞分散细胞原代培养,培养到13d时进行氧/葡萄糖剥夺模型的制备:将neurobasal培养基更换为不含葡萄糖的BSSo培养基,连续充以50mL/LCO2 950mL/LN2(体积比)混合气体。缺氧30,45,60,90min后取出细胞,更换为正常neurobasal培养基,恢复正常条件继续培养。将神经细胞随机分为正常对照组、单纯缺氧组、无糖缺氧组、MK-801组和d-APV组。将10μmol/LMK-801和500μmol/Ld-APV在通50mL/LCO2 950mL/LN2混合气前加入到BSSo培养基,缺氧结束后随BSSo培养基一起去掉。复氧24h后采用MTT比色法测神经细胞成活率及Hoechst荧光染料法测神经细胞凋亡率。结果:①随着氧/葡萄糖剥夺时间延长,神经细胞存活率下降。氧/葡萄糖剥夺30,45,60,90min再复氧24h,神经细胞存活率分别为(81.48±3.84)%、(63.14±3.14)%、(41.73±2.97)%和(16.78±2.12)%。②N-甲基-D-天冬氨酸受体拮抗剂MK-801(10μmol/L)和d-APV(500μmol/L)均能明显增加神经细胞存活率(P<0.05),并且两组细胞存活率与正常对照组比较,差异无统计学意义(P>0.05)。结论:实验制备的海马神经细胞短时间氧/葡萄糖剥夺模型可对神经细胞造成迟发性死亡,兴奋性氨基酸N-甲基-D-天冬氨酸受体拮抗剂可保护氧/葡萄糖剥夺诱导的神经细胞损伤,说明本实验建立的缺氧模型有效并简便可靠,并且缩短了缺氧时间。