纳米级超声造影剂的研究进展

随着超声分子成像技术和生物纳米技术的迅猛发展，近年来出现了多种纳米级超声造影剂，包括纳米级脂质体造影剂、纳米级氟烷乳剂和纳米级微泡造影剂。本文就纳米级超声造影剂的研究背景、研究现状、现存的问题及发展前景做一综述。     

纳米级超声造影剂制备及成像的实验研究

目的 探讨纯度较高的纳米级超声微泡造影剂的理化性质及体内成像效果.方法 机械振荡法与低速离心法结合制备纳米级微泡,观察微泡形态,检测其平均粒径,并观察其增强正常兔肝显影的情况,并与微米级微泡造影剂进行比较.结果 光镜以及透射电镜观察,微泡呈圆形,分布均匀,无聚集现象.Zeta SIZIER 3000测定微泡粒径均值为623.4 nm,微泡表面电位均值1.3 mV.注射纳米级造影剂于新西兰大白兔体内能持续增强肝的显像效果,与微米级造影剂对比无明显差异.结论 纳米级的微泡造影剂大小合理,分布均匀,显像效果强,为下一步研制小型化靶向造影剂奠定了基础.     

自制纳米级超声微泡体外基本特性和肿瘤造影增强显影的实验研究

目的 探讨自制纳米级超声微泡的体内基本特性及体内造影增强显影效果.方法 机械振荡与低速离心法结合制备纳米级微泡,并对微泡粒径大小、分布、微观形态和稳定性进行研究.同时在裸鼠肝、肾及前列腺癌皮下移植瘤进行超声造影实验,与常规微米级造影剂对比造影效果.结果 所制备的微泡形态圆整,大小均一性较好,分布均匀无聚集,平均粒径(580.6±36.3)nm.该纳米级微泡能显著增强裸鼠肝肾及皮下移植瘤显影,与常规造影剂比较,不但增强强度相当,且显影时间显著延长.结论 自制纳米级超声微泡造影剂各项物理特性符合纳米级超声造影剂的要求,体内增强效果和稳定性较强,为下一步纳米级微泡在肿瘤显像和治疗中的应用提供实验依据.     

超声分子影像学研究进展

随着超声分子探针技术的兴起,超声分子成像成为当前医学影像学研究的热点之一.分子探针的设计是超声分子成像研究的重点和先决条件.靶向超声微泡(球)造影剂在分子影像中的研究、应用,愈来愈受到关注,而多学科的融合使其具有更大的发展空间.     

以HER2为靶点的靶向纳米级脂质微泡超声造影剂的制备及实验研究

目的 制备以HER2受体为靶点的靶向纳米级脂质微泡超声造影剂,并观察其体外寻靶能力及体外超声显像效果.方法 制备生物素化Herceptin单抗,检测其生物素化程度及生物学活性;薄膜水化-声振法制备生物素化纳米微泡,以生物素-亲和素为桥梁制备HER2为靶点的靶向纳米级脂质微泡超声造影剂,观察其对SKOV3卵巢癌细胞的体外寻靶能力及靶向结合的体外超声显像.结果 平均每分子Herceptin单抗可与16个生物素分子结合;与游离单抗相比,生物素化抗体的活性未见明显降低(P＞0.05).体外寻靶实验观察:靶向纳米微泡组SKOV3细胞表面有明显的红染纳米微泡与其牢固结合,沿细胞表面排列较规则;非靶向组SKOV3细胞表面未结合红染的纳米微泡.靶向纳米微泡体外超声显像:细胞爬片与靶向纳米微泡孵育后可明显增强超声显像效果,对照组均未见明显超声显像.结论 应用生物素-亲和素系统成功构建了以HER2为靶点的纳米级超声造影剂,与SKOV3细胞结合后有明显超声显像效果.     

纳米级超声微泡造影剂的制备及其性状的初步研究

目的制备适用于超声诊断的纳米级超声微泡造影剂,并对其性状进行初步研究。方法通过低速离心分级分离法制备纳米级的脂膜超声微泡,检测微泡大小形态、表面电位、粒径、分布,测试其与抗体结合情况,体外初步测试其增强显像效果。结果微泡呈圆形,分布均匀,粒径均值为623.4nm;微泡表面电位均值1.3mV,与抗体结合情况良好,体外初步测试能明显增强显像效果。结论通过低速离心分级分离法可以制备纯度较高的纳米级超声微泡,为超声造影剂的小型化和靶向性发展提供重要的工作平台。     

超声微泡造影剂的肿瘤靶向治疗研究进展

近几年,国内外着眼于靶向微泡造影剂的研究,利用超声波与微泡造影剂的相互作用及所产生的生物学效应,可实现微泡所携带的基因/药物等向目标组织的转移释放,介导肿瘤细胞的凋亡及肿瘤微血管的栓塞阻断等,从而起到靶向治疗的作用。随着各种兼具诊断治疗双重作用的超声探头和靶向微泡造影剂包括纳米级微泡造影剂的研制,以及对超声生物学效应的深入研究,超声微泡介导肿瘤靶向治疗将为临床肿瘤的治疗带来新的希望。     

纳米级分子靶向超声造影剂的制备及其体外肿瘤靶向性实验研究

目的制备针对肿瘤HER2分子的纯纳米粒径分子靶向超声造影剂,观测其理化特性,并在体外肿瘤细胞中验证其特异靶向性。方法利用改良的薄膜水化法直接制备纯纳米粒径微泡,鉴定其基本理化特性、形态学表现及体外超声造影成像效果;利用"亲和素-生物素法"构建"纳米微泡-Affibody",体外多种肿瘤细胞验证其特异靶向性,同时观察其稳定性。结果直接制备出了纯纳米级微泡,粒径为(498.7±55.0)nm,各项理化特性及超声成像效果良好;新构建的"纳米微泡-Affibody"在体外对多种HER2(+)肿瘤细胞具有特异靶向性。结论 "纳米微泡-Affibody"体外特异靶向性强,稳定性好,为进一步进行体内肿瘤分子靶向超声造影及抗肿瘤分子靶向治疗奠定了基础。     

靶向声学造影技术的研究现状与进展

超声造影剂 (ultrasoundcontrastagents ,UCA)是利用声波对气体反射比液体大近 10 0 0倍的原理 ,使用含气微泡后超声回声增强得到更高的对比分辨力 ,从而有利于疾病的诊断。至今 ,有关超声造影剂的研究已有近 3 0年的历史[1] 。过去几年中 ,靶向微泡的开发已取得可观进展。这种微泡对于靶向病变组织有一定亲和力 ,可以附着于某种疾病的特殊标记物 ,靶向微泡在病变组织的积聚可实现分子和细胞过程的无创性超声成像。本综述主要讨论靶向微泡分子成像的早期实验和对比增强超声分子成像具体应用的靶向方法。一、靶向炎症的对比超声成像血池中…     

纳米级造影剂在超声分子显像与靶向治疗中的研究进展

近年来，超声微泡类造影剂及其靶向技术已经在分子显像与靶向治疗领域取得了诸多研究成果。然而，由于微泡类造影剂直径为微米级，不能穿透血管内皮间隙，只能停留在血管内，发生血池内显影，因此限制了它们对血管外病变的探测能力。随着纳米技术与分子生物学的发展，另一类纳米级造影剂正日渐崛起，主要包括液态氟烷纳米粒／乳剂、具有声反射特性的脂质体等。这类造影剂以其分子小、穿透力强的突出特性，将有力地推动超声分子显像与靶向治疗向血管外领域拓展。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.     

Clinical Trial Updates and Hotline Sessions presented at the European Society of Cardiology Congress 2007

This article provides information and commentaries on trials which were presented at the Hotline and Clinical Trial Update Sessions at the European Society of Cardiology Congress 2007 in Vienna. The key presentations were performed by leading experts in the field with relevant positions in the trials or registries. It is important to note that unpublished reports should be considered as preliminary data, as the analysis may change in the final publications. The comprehensive summaries have been generated from the oral presentation and the webcasts of the European Society of Cardiology and should provide the readers with the most comprehensive information of relevant publications.     

Balance and Boundaries in Grief Counseling: An Intervention Framework for Volunteer Training

Volunteers or paraprofessional counselors are commonly used to provide supportive care to the bereaved. These counselors generally are trained in basic listening skills, providing a generic, nonspecific approach to intervention that remains to be proven effective. The present paper outlines a framework that provides paraprofessionals with a broader model for intervention with the bereaved. Attention to boundaries as a helper and balance in the grief recovery are central to the model. Interventions are described that provide the paraprofessional counselor with more options for tailoring their counseling strategy to the individual. These include techniques that are presumed to be more specific to the enhancement of grief recovery.     

Prospects for the control of neglected tropical diseases by mass drug administration

The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In spite of this and other striking successes, mass drug administration programs are faced with major challenges resulting from suboptimal coverage and lack of efficacy. At current suboptimal coverage rates, programs may need prolongation for an extended period, increasing costs and undermining sustainability. Community participation through health education and information appears to be crucial to improve coverage and to achieve sustainability. Implementation of complementary measures, such as vector control, improved hygiene and environmental sanitation, are important to further control transmission and to prevent re-emergence of the infection and, again, may only be achieved effectively through community-based initiatives. To reduce costs and to relieve pressure on the health system, combining neglected tropical disease programs in areas where diseases coexist and integration with existing control programs for malaria, tuberculosis and HIV/AIDS is advocated. The risk of developing drug resistance is of particular concern in view of the lack of alternative drugs, and reduced treatment efficacy due to emerging resistance is evident for the soil-transmitted helminths and onchocerciasis. Given the risk for the development of drug resistance and the need for a high degree of participation, close attention should be paid to the monitoring of the coverage and efficacy of the different program components.     

A new method for the simultaneous analysis of unmodified and modified urinary nucleosides and nucleobases by high performance liquid chromatography

Details are given of a new, rapid and simple pre-fractionation method and an isocratic high performance liquid chromatography system suitable for parallel analysis of nucleosides and nucleobases from urine and other biological fluids. The quantitative recovery and excellent reproducibility of the method is demonstrated by analysis of representative standard RNA catabolites. The advantage of this new method for application to biological samples is discussed.     

Adsorption of Charged Non-albumin Bound Drugs by Amorphous Silica

We investigated the in vitro drug adsorption of PQ 10150 sodium silicate gel (AIS, Santa Clara, CA) with particle size of 230 um and surface area of 400 nr/g. We observed 99% to 88% adsorption of gentamicin; a mean 91 % of disopyramide; a mean 89% of quinidine at low concentration, falling to 75% at higher concentration. Insulin was 88% adsorbed at low concentrations but less so (65%) at higher concentrations. We observed a mean 83 % adsorption of procainamide, a mean 84% of N-acetyl procainamide, 74% oflidocaine, 73% of amitriptyline; and 44% of desipramine. We found an average 14% reduction of total digoxin concentration when serum containing digoxin (2 to 33 ng/mL) was exposed to sodium silicate, while the reduction in free digoxin concentration was 16%. Five percent ethosuximide was also removed. The adsorption of theophylline, phenobarbital, acetaminophen, phenytoin, ethylene glycol, methotrexate, salicylate, thiocyanate and diazepam was minimal and not significant. We conclude that significant amounts of charged, non-albumin bound drugs can be removed by PQ 10150 sodium silicate gel.