曲美他嗪治疗冠心病心力衰竭的临床观察

目的观察曲美他嗪治疗冠心病心力衰竭的临床疗效和安全性。方法选择冠心病心力衰竭患者86例,左心室射血分数(LVEF)均小于40%,NYHA心功能分级在Ⅲ~Ⅳ级。随机分成2组,对照组给予血管紧张素转换酶抑制剂(ACEI)或血管紧张素Ⅱ受体拮抗剂(ARB)、β-受体阻滞剂、利尿剂、醛固酮拮抗剂和洋地黄等基础药物治疗;治疗组在上述基础治疗上加用曲美他嗪20mg,3次/d治疗。观察时间为6个月。结果治疗组与对照组相比,3个月和6个月时LVEF、心功能分级及6min步行试验结果改善明显(P<0.05),且6个月较3个月时改善更明显,再住院次数亦明显减少,不良反应较少。结论曲美他嗪治疗冠心病心力衰竭的作用明显,是一种安全有效的新方法,其机制可能与改善缺血心肌的能量代谢有关。     

耳穴脉冲刺激对Oddi括约肌张力及肌电活动的影响

目的　探讨耳穴脉冲电刺激治疗胆石症 ,胆绞痛的机制 .方法　选用 15条成年杂种犬 ,进行耳穴体表脉冲刺激与缩胆素 (CCK)对在体狗胆囊张力 ,Oddi括约肌张力及肌电活动影响的对比研究 .结果　耳穴脉冲电刺激对胆囊张力无明显影响 [(1.2 7± 0 .2 6 ) k Pa与 (1.2 4± 0 .2 2 ) k Pa,P<0 .0 5 ],CCK注射液能明显提高胆囊张力 [(1.2 7± 0 .2 6 ) k Pa与 (1.91± 0 .39) k Pa,P<0 .0 5 ],CCK注射液能明显降低Oddi括约肌张力 [(2 .2 4± 0 .5 5 ) k Pa与 (1.5 8± 0 .5 6 ) k Pa,P>0 .0 5 ]及肌电活动 .结论　耳穴脉冲电刺激同 CCK一样 ,均对 Oddi括约肌的张力有显著的降低作用 ,并减少 Oddi括约肌的肌电峰电位爆发波的频率与电压值 ,推测其对胆绞痛有治疗作用 ,并有助于胆结石的排石过程 .     

淋巴瘤细胞转染GM-CSF 基因后生物学特性的变化

目的：制备高表达GM－CSF的淋巴瘤细胞系，观察淋巴瘤细胞转染GM－CSF基因后生物学特性的改变。方法：将小鼠GF－CSF真核表达质粒用电穿孔法导入小鼠淋巴瘤细胞系RMA，有限稀释法制备单个细胞克隆，经RT－PCR，骨髓祖细胞增殖实验和集落形成实验筛选相对高表达GM－CSF的RMA克隆，并观察其生物学特性的改变。结果：获得了高表达GM－CS的RMA细胞系,其同基因动物体内致瘤性降低。结论：淋巴瘤细胞系RMA转染GM－CSF基因后致瘤性降低。     

小鼠不完全性脑缺血、再灌注时脑膜血流量的变化及尼莫地平的作用

目的：观察双侧颈总动脉阻断后脑血流的变化。方法：结扎双侧颈总动脉观察小鼠不完全性脑缺血及其再灌注时脑膜血流量的变化。结果：结扎颈总动脉后小鼠脑膜血流量在几秒钟内骤然下降，血流量较结扎前降低约８５．９％±６．４５％。同时血管中红细胞运动近停滞状态，血管再通时脑血流处于低灌注状态，血流量下降３４．４７％±１１．６９％，此时脑缺血再灌后脑组织实际上处于一种慢性缺血状态。再灌注１０ｄ后，小鼠脑海马ＣＡ１区神经细胞数明显减少。尼莫地平可以解除再灌注时的脑血流低灌状态。并防止由此所引起的脑海马ＣＡ１区神经细胞的缺失。结论：缺血后及时给予尼莫地平具有积极的治疗意义。     

The 2.0-Å resolution crystal structure of a trimeric antibody fragment with noncognate VH–VL domain pairs shows a rearrangement of VH CDR3

The 2.0-Å resolution x-ray crystal structure of a novel trimeric antibody fragment, a “triabody,” has been determined. The trimer is made up of polypeptides constructed in a manner identical to that previously described for some “diabodies”: a V_L domain directly fused to the C terminus of a V_H domain—i.e., without any linker sequence. The trimer has three Fv heads with the polypeptides arranged in a cyclic, head-to-tail fashion. For the particular structure reported here, the polypeptide was constructed with a V_H domain from one antibody fused to the V_L domain from an unrelated antibody giving rise to “combinatorial” Fvs upon formation of the trimer. The structure shows that the exchange of the V_L domain from antibody B1-8, a V_λ domain, with the V_L domain from antibody NQ11, a V_κ domain, leads to a dramatic conformational change in the V_H CDR3 loop of antibody B1-8. The magnitude of this change is similar to the largest of the conformational changes observed in antibody fragments in response to antigen binding. Combinatorial pairing of V_H and V_L domains constitutes a major component of antibody diversity. Conformationally flexible antigen-binding sites capable of adapting to the specific CDR3 loop context created upon V_H–V_L pairing may be employed by the immune system to maximize the structural diversity of the immune response.     

As2O3处理前后K562细胞基因表达变化的基因芯片检测

目的应用基因芯片研究三氧化二砷(As2O3)处理前后K562细胞基因表达的变化.方法提取As2O3处理前后K562细胞的总RNA,纯化为mRNA后再反转录为cDNA.cDNA经限制性内切酶Sau3AI切割后,cDNA片段分别用Cy3和Cy5标记,与自制的包含348个基因片段的胎盘库芯片杂交.结果杂交结果经扫描和软件分析,发现了11个差异表达的基因片段,其中有3个基因片段与细胞凋亡密切相关.结论我们构建的胎盘库基因芯片可以成功地用于研究药物作用前后基因表达的变化.     

地塞米松对布比卡因诱导小鼠神经元毒性的影响

Objective To investigate the effect of dexamethasone on the toxicity of bupivacaine in murine neurons.Methods Murine neuroblastoma cell line N2a was obtained from ATCC cell bank (USA). The cells were cultured in 10% fetal cow serum/MEM culture medium and divided into 4 groups voup I control (Con); group II bupivacaine ( Bup); group Ⅲ dexamethasone (Dex) and group IV Dex + Bup. The culture medium contained bupivacaine 900 μmol/L in group Bup and dexamethasone 1 μmol/L in group Dex respectively. In group Dex + Bup ( IV ) Bup was added to the culture medium with a final concentration of 900 μmol/L at 12 h after pretreatment with Dex 1 μmol/L. The cells were inoculated in 24 well plates (0.5 ml in each well, 24 wells in each group) and 10 cm culture dishes (7 ml in each dish, 4 dishes in each group). The release rate of LDH was calculated and the morphology of the cells and nucleus condensation (by Hoechst 3334224 fluorescent staining) was detected at 9 h of incubation in 24 well plates. The mitochondrial transmembrane potential (by JC-1 assay) and phosphorylation of Akt and ERKs (by Western blot) were measured at 5 h of incubation in 24 well plates and in culture dishes respectively. ResultsBupivacaine caused severe damage to the N2a cells as evidenced by increase in LDH release and nucleus condensation (apoptosis), dephosphorylation of Akt and ERKs, decrease in mitochondrial transmembrane potential and severe morphological changes. Dexamethasone pretreatment significantly attenuated bupivacaine-induced neurotoxicity. Conclusion Dexamethasone can protect N2a cells from bupivacaine-induced neurotoxicity through stabilization of mitochondrial transmembrane potential and inhibition of dephosphorylation of Akt and ERKs.