Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Role of delayed enhancement MRI in patients with acute coronary syndrome and unobstructed coronary arteries: reply

We thank Coceani and L'Abbate for their comments on our paper.We concur that ‘pathophysiology cannot be inferred fromcoronary lumenography alone’, and this was one of thekey motivations in conducting the present study.     

64排螺旋CT冠状动脉造影与DSA的对照研究

目的:通过和冠脉造影对比,评价64排螺旋CT冠状动脉成像在冠状动脉狭窄中的临床应用价值。方法:28例患者同时行64排螺旋CT冠状动脉成像和有创性冠脉造影检查,依据AHA17段分段法,评价所有有效节段,并将两者进行对比。结果:冠脉造影显示阴性病例占7.1%(2例),单只病变占21.4%(6例),多支病变占71.4%(20例)。按节段分析,CT检出冠脉狭窄的敏感度,特异度,阳性预测值和阴性预测值分别为91.1%,94.6%,90.0和95.3%。结论:64排螺旋CT冠状动脉成像和传统的冠脉造影检查对检出正常冠脉节段以及狭窄节段具有很好的一致性。     

Renal Aspergilloma--A Case Illustrating the Problems of Medical Therapy

The second documented case of renal aspergilloma due to Aspergillusflavus is presented. The merits of the medical therapy thatfailed are discussed. Pathological examination showed a nidusof aspergillus around suture material persisting from a pyelolithotomyoperation 2 years before in India. We argue that this was thereason for the failure of the medical therapy. This is the firstcase of its kind reported.     

三氧化二砷纳米微粒对抑制兔血管平滑肌细胞增殖作用的实验研究

目的 了解纳米微粒与普通剂型的三氧化二砷（As2O3）对抑制体外培养的兔血管平滑肌细胞（VSMC）增殖作用的差别。方法 对照组为不加药物的细胞，实验组为3μmol／L纳米微粒和普通剂型的As2O3，干预体外培养的兔VSMC细胞72h，进行四唑氮盐（MTT）染色测定细胞吸光度（A）值。用流式细胞仪检测细胞凋亡情况，提取细胞DNA，进行凝胶电泳分析，将3组的结果进行比较。结果 3μmol／L纳米剂型的As2O3，干预细胞，细胞数量随作用时间的延长逐渐减少，细胞生长明显受抑制，而普通剂型干预细胞，生长受抑制程度较纳米剂型弱。24h时，对照组、3μmol／L普通剂型组与纳米组，A值分别为0．68±0．10、0．58±0．12、0．33±0．12，48h时分别为0．79±0．11、0．48±0．14、0．28±0．11，72h时分别为0．96±0．13、0．34±0．15、0．20士0．06，差异均有统计学意义（Ⅳ值分别为10．934、15．039、15．539，P值均〈0．01）。流式细胞仪检测，纳米剂型As2O3、普通剂型As2O3干预及对照组的细胞干预48h，细胞增殖率分别为44．97％、58．54％、74．02％，早期凋亡率分别为16．89％、11．27％、11．20％，晚期凋亡率分别为26．56％、23．60％、12．46％，坏死细胞分别为11．58％、6．59％、2．32％。DNA电泳，As2O3干预细胞，可见凋亡梯形条带，部分细胞坏死，呈模糊的无间隔片状条带。纳米剂型药物作用的细胞DNA条带，梯形条带更多、更模糊。结论 As2O3，可以抑制体外培养的VSMC增殖，且纳米剂型As2O3较普通剂型的As2O3，对细胞抑制作用更强。     

鼻咽癌CT灌注成像及其生物学相关性研究

目的研究鼻咽癌CT灌注值与肿瘤微血管密度（MVD）、肿瘤分期的关系，探讨多层螺旋CT灌注成像对鼻咽癌的临床应用价值。方法49例鼻咽部CT灌注检查中，鼻咽癌组30例，鼻咽癌放疗后组14例，正常鼻咽部5例，测量鼻咽癌和鼻咽黏膜位置的血流量（BF）、最大强化指数（PEI）、峰值到达时间（TTP）及血容量（BV）作为灌注指标，其中16例鼻咽癌活检组织行免疫组织化学CD34单抗染色后，Weidner方法计数MVD。各组灌注值比较行方差分析，CT灌注值、肿瘤分期与MVD之间行Spearman等级相关分析。结果49例中1例鼻咽癌灌注检查失败。鼻咽癌组（29例）肿瘤CT灌注值BF为（48．6±16．9）ml·100g^-1·min^-1，PEI为（32．3±7．9）HU，TTP为（17．5±4．9）s，BV为（12．8±4．4）ml·100g^-1；正常对照组（5例）BF、PEI、TTP、BV值分别为（15．9±5．9）ml·100g^-1·min^-1、（12.6±1．3）HU、（22．6±6．9）s、（3．5±0．5）ml·100g^-1；鼻咽癌放疗后组（14例）BF、PEI、TTP、BV值分别为（25．2±7．0）ml·100g^-1·min^-1、（19．8±5．9）HU、（22．6±4．3）s、（6．1±2．4）ml·100g^-1，三组各灌注值差异有统计学意义（P值均〈0．01）；相关分析显示，鼻咽癌组（29例）中TNM分期（其中Ⅰ期3例，Ⅱ期9例，Ⅲ期10例，Ⅳ期7例）与PEI和BV存在相关性（r值分别为0．48和0．50），与BF和TTP无明显相关性（r值分别为0．23和0．22）；16例鼻咽癌MVD为（30．8±12．6）个／高倍镜视野，与其BF（51．4±17．0）ml·100g^-1·min^-1、PEI（33．2±9．6）HU和TTP（16．3±4．1）8存在相关性（r值分别为0．85、0．60和0．78），与BV（13．2±5．6）ml·100g^-1弱相关（r=0．48）。结论鼻咽癌有着特征的CT灌注表现，多层螺旋CT灌注成像的灌注值可以反映鼻咽癌微血管密度特征，PEI和BV值与鼻咽癌的TNM分期存在一定的相关性。