纳米粒子介导特异基因转染的实验研究

目的：观察纳米粒子携带特异性基因转染的可行性及其效率,方法：应用聚乳酸聚乙醇酸共聚物和聚乙烯醇包载特异性反义单核细胞趋化蛋白－1基因,制备纳米级粒子混合物。检测其包埋率,体外释放情况及粒度。以阳离子脂质体为对照,利用培养的平滑肌细胞,应用聚合酶链反应（PCR）观察其为真核细胞传递基因的可能性。采用移植静脉内膜增生动物模型,应用RNA斑点杂交和病理形态学分析。观察其在体内的基因转染、表达及生物学效应。结果：制备的纳米粒子－DNA粒度为150－300nm,包埋率为：0．9％,体外释放时间为2周左右。PCR结果提示：纳米粒子可将目的基因转移至平滑肌细胞中,体内实验显示：纳米粒子可实现体内局部基因转染,表达,发挥相应的效应。结论：纳米粒子可用于特异性基因的转染。     

Spätergebnisse nach transduodenaler Sphincterotomie und Sphincterplastik aufgrund der Erfahrungen von 18 Jahren (unter besonderer Berücksichtigung der Analyse unbefriedigender Resultate)

Zusammenfassung Die Verfasser haben in 18 Jahren 289 transduodenale Sphincterotomien und 87 Sphincterplastiken durchgeführt (295 Patienten bei der ersten und 81 Patienten bei weiteren Gallenoperationen). Im unmittelbaren postoperativen Stadium verstarben 20 Patienten (5,3%), die Sektionsergebnisse zeigen jedoch, daß die Sphincteroperation lediglich für den Tod von 10 Patienten (2,6%) verantwortlich gemacht werden kann. Von den anderen 356 Patienten konnten wir nur 270 (75,8%) 1–11 Jahre postoperativ untersuchen. Das Spätergebnis ist in 89,6% ausgezeichnet bzw. gut. Zur Klärung der unbefriedigenden Ergebnisse wurden klinische, labormedizinische, radiologische und endoskopische Untersuchungen durchgeführt. Die unbefriedigenden Ergebnisse können in 6,6% auf bilio-pankreatische, in 0,7% auf extrabiliäre organische und in 1,5% auf nicht-organische Ursachen zurückgeführt werden. Die Bedeutung der endoskopischen Untersuchung zur Klärung der Gründe der unbefriedigenden Operationsergebnisse nach Sphincteroperationen wird hervorgehoben.

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Late results of transduodenal sphincterotomy and sphincteroplasty based on 18 years of experience (with special respect to the analysis of unsatisfactory results)

Summary In the course of 18 years the authors performed transduodenal sphincterotomy on 289 and sphincteroplasty on 87 patients. The operations were connected, in 295 cases with prismary in 81 cases with repeated biliary surgery. Twenty of the patients (5.3%) died during the immediate postoperative period. However, on the grounds of autopsy data the death of only 10 patients (2.6%) can be attributed to the surgery of the sphincter. Out of the 356 surviving patients 270 were available for a follow-up study and were examined 1–11 years after the operation. Late results of the operation were found excellent or good in 89.6% of the patients. To clear up the unsatisfactory results clinical, laboratory, radiological, and endoscopic examinations were carried out. The unsatisfactory results can be explained by biliopancreatic (6.6%), organic extrabiliary (0.7%) and non-organic (1.5%) reasons. The authors emphasize the significance of endoscopic examinations following the surgery of the sphincter in the elucidation of the causes of unsatisfactory results.

     

Computational Study of Fluid Mechanical Disturbance Induced by Endovascular Stents

Arterial restenosis following stent deployment may be influenced by the local flow environment within and around the stent. We have used computational fluid dynamics to investigate the flow field in the vicinity of model stents positioned within straight and curved vessels. Our simulations have revealed the presence of flow separation and recirculation immediately downstream of stents. In steady flow within straight vessels, the extent of flow disturbance downstream of the stent increases with both Reynolds number and stent wire thickness but is relatively insensitive to stent interwire spacing. In curved vessels, flow disturbance downstream of the stent occurs along both the inner and outer vessel walls with the extent of disturbance dependent on the angle of vessel curvature. In pulsatile flow, the regions of flow disturbance periodically increase and decrease in size. Non-Newtonian fluid properties lead to a modest reduction in flow disturbance downstream of the stent. In more realistic stent geometries such as stents modeled as spirals or as intertwined rings, the nature of stent-induced flow disturbance is exquisitely sensitive to stent design. These results provide an understanding of the flow physics in the vicinity of stents and suggest strategies for stent design optimization to minimize flow disturbance.     

Treating atherosclerosis: local drug delivery from laboratory studies to clinical trials

Treating only the specific section of the vascular bed that is diseased appears to make sense. Giving drugs systematically to treat perhaps only a few centimetres of affected artery carries with it the risk of systemic side effects and reduced efficacy consequent on low concentrations of agent at the site of the problem. There has thus been great interest since the early 1990s in local drug delivery. Initial targets were the thrombotic response to plaque disruption but the problems arising from the incidental damage inflicted by devices used in interventional cardiology and the pathological consequences of this, namely smooth muscle cell initiated intimal hyperplasia, soon became the focus of pre-clinical studies. Problems to be overcome were the low efficiency of delivery of drugs and the low retention rates. Solutions to these problems included the development of strategies to target drugs, through the use of antibodies directed at antigens newly released at the site of damage. As it became clear that stents were becoming central to the attainment of a better clinical response to intervention by their inherent physical properties, it also became obvious that stents could be used to deliver agents. Issues such as which stent, how to load the drug onto the stent and what drug to use to inhibit the unwanted pathobiological response are ongoing issues.     

Percutaneous Interventions in Radiation-Associated Coronary In-Stent Restenosis

This study was performed to evaluate the outcome of percutaneous revascularization in edge restenoses developing after radioactive stent implantation in de novo and in-stent lesions. Twenty-one consecutive patients undergoing target lesion revascularization (TLR) at any follow-up after phosphorus-32 radioactive stent implantation were included in this study. We assessed the incidence of death, myocardial infarction, repeated TLR and recurrent angina over the following 18 months. After 6 months, TLR rate was 28.6%, and no stent thromboses, deaths or Q-wave myocardial infarctions occurred. Among the patients with TLR there were significantly more subjects who had received a radioactive stent in a previous in-stent restenosis (66.7% vs. 0% in patients without second restenosis; P < 0.001), or who had received two radioactive stents (83.3% vs. 33.3%; P = 0.038). After 18 months, TLR rate was 33.3%, and two patients (9.5%) had died. Restenosis after intravascular radiotherapy can be safely treated by percutaneous interventional techniques, yielding an acceptable clinical result within 18 months.     

Effect of antiproliferative agents on vascular function in normal and in vitro balloon-injured porcine coronary arteries

Local infusion of antiproliferative agents following coronary balloon angioplasty is used in vivo. This study examined the effects of the antiproliferative agents paclitaxel (5-beta, 20-Epoxy-1,2-alpha,4,7-beta,10-beta,13-alpha-Hexahydroxy-Tax-11-en-9-one 4,10-Diacetate 2_Benzoate 13-Ester with (2R,3S)-N-Benzoyl-3-Phenylisoserine; 10 and 50 microM), farnesyl protein transferase inhibitor III (FPT III, (E,E)-2-[2-Oxo-2-[(3,7,11-trimethyl-2,6,10-dodecatrienyl) oxy] amino] ethyl] phosphonic acid, (2,2-dimethyl-1-oxopropoxy) methyl ester, sodium); 10 and 25 microM), perillyl alcohol (4-isopropenyl-cyclohexenecarbinol; 1 and 2 mM) and Van 10/4 (Decahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulen-4-o-[2-(3-methylpent-2-enoyl)-fucopyranoside]; 10 and 25 microM) on normal and in vitro balloon-injured porcine coronary arteries. Short-term (30 min) incubation had no effect on contraction or relaxation. Overnight incubation with 25 microM Van 10/4-attenuated contraction while perillyl alcohol abolished contractility completely. Endothelium-dependent relaxation was significantly attenuated by the higher concentration of paclitaxel, FPT III and Van 10/4. Stretch injury significantly enhanced sensitivity to 3-morpholinosydnonimine (SIN-1) while attenuating relaxation to calcimycin. Drug incubation (15 min) had no effect on these responses. In conclusion, paclitaxel, FPT III and Van 10/4 have no detrimental effects on vascular function after short-term administration to normal or stretch-injured arteries.     

PARTNER~(TM)药物洗脱支架的临床应用

目的:评价PARTNERTM药物洗脱支架的临床疗效及安全性。方法:选择2006年1～12月111例冠心病患者,所有患者行经皮冠状动脉介入治疗置入PARTNERTM药物洗脱支架,术后对患者进行随访,观察有无胸痛复发、心电图改变及重要心血管不良事件的发生。结果:111例患者共180处病变置入196枚PARTNERTM药物洗脱支架,手术成功率100%,胸痛缓解无复发,术后无重要心血管不良事件发生。结论:PCI术中应用国产PARTNERTM雷帕霉素药物洗脱支架近期疗效满意,应用安全方便。     

冠状动脉支架置入术后的长期随访

冠状动脉支架置入术是治疗冠心病的一种安全、有效的方法。药物涂层支架的应用显著降低了支架内再狭窄的发生。作者简要介绍了冠状动脉支架置入术后长期随访的主要结果及其意义,并对其未来发展进行展望。     

兔髂动脉血管内照射的实验方法

目的用改进型后装治疗机进行血管内放疗的可行性研究。资料与方法用兔髂动脉行血管成形术,制成血管狭窄模型,用改进型后装治疗机及微型放射源１９２Ｉｒ进行兔髂动脉内放疗,预防血管成形术后再狭窄。结果６０只兔分为３组。１）放疗１０Ｇｙ组;２）放疗１８Ｇｙ组;３）对照组,只做球囊扩张血管损伤,不做放疗。放疗组及对照组均１００％成功。结论改进型后装治疗机在兔髂动脉扩张术后照射,安全可行。     

Efficiency of Dispatch ® and Infiltrator ® Cardiac Infusion Catheters in Arterial Localization of Nanoparticles in a Porcine Coronary Model of Restenosis

Localized intramural delivery of sustained release biodegradable nanoparticles containing an antiproliferative agent could provide prolonged drug effect at the site of vascular injury that could inhibit the proliferation of smooth muscle cells and hence restenosis. The efficiency of arterial localization of nanoparticles is crucial in maximizing the drug effect in the target tissue. Therefore, the objective of the present study was to determine the comparative efficiency of the Dispatch ® and the Infiltrator ® cardiac infusion catheters to localize nanoparticles in the arterial wall. Following a standard balloon angioplasty procedure on the left anterior descending artery (LAD) in a porcine coronary model of restenosis, a suspension of nanoparticles containing a fluorescent marker was infused at the site of injury using either the Dispatch ® or the Infiltrator ® catheter. One hour following the infusion, animals were sacrificed and the nanoparticle levels in the LAD and other tissue were analyzed. The Dispatch ® catheter resulted in 3.3 folds greater efficiency of nanoparticle localization in the LAD than the Infiltrator ® catheter (309 ± 124 vs. 93 ± 43 μ g/g of tissue, n =6 for Dispatch ® and n =5 for Infiltrator ®, p =0.082, t -test). It is estimated that about 2% of the arterial volume can be displaced with the nanoparticle infusion. Fluorescence microscopy of the cross-sections of the LAD revealed greater fluorescence activity in the intimal layer with both the catheters, however the arteries infused using the Dispatch ® catheter demonstrated relatively higher degree of fluorescence activity in the medial and adventitial layers. The transmission electron microscopy of the arterial sections demonstrated infiltration of nanoparticles in the arterial wall and the histological analysis of the sections demonstrated no apparent damage to the endothelium due to the infusion of nanoparticles.