Modelling drug elution from stents: effects of reversible binding in the vascular wall and degradable polymeric matrix

Today the most popular approach for the prevention of the restenosis consists in the use of the drug eluting stents. The stent acts as a source of drug, from a coating or from a reservoir, which is transported into and through the artery wall. In this study, the behaviour of a model of a hydrophilic drug (heparin) released from a coronary stent into the arterial wall is investigated. The presence of the specific binding site action is modelled using a reversible chemical reaction that explains the prolonged presence of drug in the vascular tissue. An axi-symmetric model of a single stent strut is considered. First an advection–diffusion problem is solved using the finite element method. Then a simplified model with diffusion only in the arterial wall is compared with: (i) a model including the presence of reversible binding sites in the vascular wall and (ii) a model featuring a drug reservoir made of a degradable polymeric matrix. The results show that the inclusion of a reversible binding for the drug leads to delayed release curves and that the polymer erosion affects the drug release showing a quicker elution of the drug from the stent.     

The evolution of an ideal stent design and its impact on the aortic endothelium during and after percutaneous replacement

Vascular support structures are important devices for treating valve stenosis. A large population of patients is treated for valvular disease and the preferred mode of treatment is percutaneous valve replacement. Stent devices are proving to be an improved technology in minimally invasive cardiac surgery. This new technology provides highly effective results at minimal cost and with a short duration of hospitalisation. Stents as a supporting structure for tissue valves have evolved over the years into remarkably useful and effective devices. During this process, a number of specific designs have come and gone, and a few have remained. Many design changes were successful, and many were not. This article describes the merits and demerits of various stent designs and details the specific reasons why a particular novel design is expected to be the most suitable implant during and after percutaneous aortic valve replacement.     

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.     

超声乳化白内障吸除、人工晶状体植入联合小梁切除术治疗白内障合并青光眼的临床疗效及安全性评价

目的：探讨超声乳化白内障吸除、人工晶状体植入联合小梁切除术治疗白内障合并青光眼的临床疗效及安全性。方法：将100例白内障合并青光眼患者按照抽签法随机地均分为对照组与观察组,对照组给予单纯超声乳化人工晶状体植入术,观察组在此基础上给予联合小梁切除术进行治疗。比较两组治疗前后相关指标以及术后并发症发生率等。结果：（1）对照组治疗前后IOP、ACD及AL均无统计学差异,观察组治疗前后IOP与CAD差异具有统计学意义（P〈0．05,P〈0．01）,但该组治疗前后AL无统计学差异;（2）两组术前与术后1周、1个月及3个月平均视野缺损值、平均模式标准差相比,差异均具有统计学意义,且观察组术后与对照组术后相比,差异均具有统计学意义;（3）对照组并发症发生率为20．00％,明显大于观察组（10．00％）。结论：超声乳化白内障吸除、人工晶状体植入联合小梁切除术治疗白内障合并青光眼,疗效显著,不良反应发生率低,值得加以推广并应用。     

The potential for biological control of stoats (Mustela erminea)

Abstract

Accelerating the mortality of stoats (Mustela erminea) using biological agents, or reducing their fertility using chemosterilants or biological agents, are increasingly seen as more sustainable and more humane than trapping and poisoning. Obligate delayed implantation in fertilised female stoats of all ages allows 10–11 months for an applied biological agent or chemosterilant to interfere with gestation. Two chemosterilants (cabergoline and mifepristone) disrupt pregnancy in some species and may be effective on stoats, although they are not species‐specific and are probably more expensive than poisoning. For the longer term, more recent fertility control research has explored potentially more species‐specific options for other species based on inducing an immune response to an animal's own reproductive hormones, gametes, or products from embryos. Conception will be difficult to disrupt in stoats because females are sexually mature and are mated in the nest during a short period before they are weaned. A large research effort will be required to determine which of the immunosterilants being developed could be suitable candidates for stoat control. There are fewer options apparent for using biological agents to increase stoat mortality, although species‐specific strains of canine distemper virus may be effective against stoats.

The greatest impediment to controlling stoat fertility will be effective delivery of sterilants. For the foreseeable future, it will probably be necessary to rely on baits, but they are unlikely to put all target stoats at risk, and will be incapable of delivery over larger scales than at present.

Before undertaking expensive field trials and development of anti‐fertility and biological agents, the effects of putative compensatory changes in demographics that may be associated with changes in stoat density should be modelled to see if the sterilisation and mortality rates that are required to achieve a given level of population control are realistic targets. Also, population control should be defined in terms of accrued benefit for wildlife by establishing the relationships between stoat densities and the viability of prey populations.

Biological control of fertility or mortality may never be suitable as stand‐alone control options for stoats, particularly when some native fauna survive only if stoats are reduced to very low densities. Biological control may have greater potential when integrated with conventional control.     

Controlled accumulation of vitellin in Bombyx eggs

Summary

Implantation of female fat body and ovary discs into the young male pupae brought about vitellin accumulation in the mature eggs developed in male hosts. The amounts of vitellin increased according to the increasing amounts of implanted fat body, and the vitellin synthesis activity of female fat body in male hosts was similar to that found in female hosts. When implanted into male pupae, larval fat body having no ability to produce vitellogenin in situ could bring about vitellin accumulation in the eggs. No accumulation of vitellin was induced by implantation of male fat body.     

Regulation of secretory activity in the albumen gland of the pulmonate snail Lymnaea stagnalis (L.)

The secretory activity of the albumen gland of the freshwater snail Lymnaea stagnalis was studied morphometrically (both at the light- and at the electron-microscope level) and biochemically under the following experimental conditions: (1) glandular tissue was implanted into acceptor snails and the glandular activity of the implants was compared to that of the glands of the donors and acceptors; (2) glandular activity was measured at various periods after oviposition; and (3) the activity was measured during a 24 h cycle (diurnal activity). The results indicate that cellular release of secretion material is regulated by a nervous mechanism, whereas synthetic activity is under hormonal control.     

Physiological and molecular determinants of embryo implantation

Embryo implantation involves the intimate interaction between an implantation-competent blastocyst and a receptive uterus, which occurs in a limited time period known as the window of implantation. Emerging evidence shows that defects originating during embryo implantation induce ripple effects with adverse consequences on later gestation events, highlighting the significance of this event for pregnancy success. Although a multitude of cellular events and molecular pathways involved in embryo–uterine crosstalk during implantation have been identified through gene expression studies and genetically engineered mouse models, a comprehensive understanding of the nature of embryo implantation is still missing. This review focuses on recent progress with particular attention to physiological and molecular determinants of blastocyst activation, uterine receptivity, blastocyst attachment and uterine decidualization. A better understanding of underlying mechanisms governing embryo implantation should generate new strategies to rectify implantation failure and improve pregnancy rates in women.     

哺乳期BALB/c小鼠胆道梗阻模型的探索

目的探讨新生BALB/c小鼠胆道梗阻模型的建立,并与报告的新生BALB/c小鼠感染猕猴轮状病毒(RRV)模型小鼠生存曲线进行比较。方法将出生后5～7 d的BALB/c小鼠随机分为实验组和对照组,实验组进行胆总管结扎,然后关腹。对照组打开腹部后关腹不结扎胆总管。实验完成后每天观察小鼠的体重变化、无毛区皮肤颜色变化、小鼠存活天数以及在术后第5、10天时分别取小鼠肝脏做病理及免疫组化。结果小鼠在结扎后随着时间的延长,小鼠的体重及肝体比、无毛区皮肤颜色、存活天数、肝脏病理等都存在一定变化。小鼠体重增长逐渐缓慢,术后第2天就会出现无毛区的皮肤变黄,在尿道口会有淡黄色的液体并随后出现陶土样便。在术后第5天及第10天时取肝脏做肝体比有统计学差异(P≤0.05),小鼠在术后第10天左右会出现死亡高峰。结论新生BALB/c小鼠胆总管结扎模型是研究胆道梗阻的可靠动物实验,其生存曲线与报告的猕猴轮状病毒致胆道闭锁大体类似。     

子宫动脉化疗栓塞术治疗胎盘植入61 例的临床分析

目的:探讨子宫动脉化疗栓塞术治疗胎盘植入的临床疗效及预后。方法:以胎盘植入患者61例为研究对象,按治疗方式不同分为保守治疗组31例和化疗栓塞组30例。保守治疗组仅单纯口服米非司酮治疗,而化疗栓塞组采用子宫动脉化疗栓塞术进行治疗。比较两组患者的临床疗效、手术时间、出血量、输血量、住院时间、胎盘排出和月经复潮时间,术后并发症的发生情况,并随访术后1年患者的月经情况和妊娠情况。结果:经子宫动脉化疗栓塞术后29例成功止血,有1例未能止血而行子宫切除术。栓塞术后未出现器官局部缺血坏死、神经损伤等严重并发症,发热、下腹痛为常见并发症。而保守治疗组的31例患者中,因治疗失败导致切除子宫的7例,仅24例有效保留子宫,成功率仅77.4%,严重影响患者以后的生育能力。6例发生宫腔感染,4例发生宫腔粘连。子宫动脉化疗栓塞组β-HCG恢复正常时间、输血量、胎盘完全清除时间、月经异常的发生情况均优于保守治疗组,差异有统计学意义(P0.05)。对子宫动脉化疗栓塞术组患者进行为期1年的随访,14例患者在术后1个月后有胎盘组织自阴道排出,有11例患者2个月后发现胎盘残留,予以清宫术,除3例失访病例,其余患者在随访时间内恢复正常月经,并有2例再次妊娠者。结论:采用子宫动脉化疗栓塞术治疗胎盘植入,其术前准备时间和手术时间均短,出血控制迅速且并发症少,有助于保留患者的子宫,提高患者的生活质量。