叶酸靶向超声造影剂的制备及体外寻靶实验研究

目的 制备偶联叶酸的靶向超声微泡造影剂,鉴定其基本性质,并探讨体外寻靶能力.方法 将DSPE-PEG(2000)Folate溶入微泡成膜材料中,制备叶酸靶向超声微泡造影剂.用DFY型超声图像定量分析诊断仪检测微泡粒径和浓度.通过光镜和激光共聚焦显微仪观察该靶向造影剂对SKOV3细胞的体外寻靶情况,以普通超声微泡作对照.结果 靶向超声微泡的大小、粒径及分布与普通超声微泡相似.体外寻靶试验显示,该靶向微泡可以较多并牢固地聚集到SKOV3细胞表面,而普通微泡对照组未见特异性结合.结论 成功制备出偶联叶酸的靶向超声微泡造影剂.该造影剂在体外对高表达叶酸受体的SKOV3细胞具有较强的特异性亲合力,有望成为靶向显像卵巢癌的理想造影剂.     

LHRHa靶向微泡造影剂的制备及体外寻靶实验

目的 制备人卵巢癌靶向超声造影剂,观察其体外寻靶能力。方法 采用生物素-链霉亲和素法制备促黄体生成素释放激素类似物(LHRHa)靶向脂质微泡,以免疫荧光染色验证LHRHa与脂质微泡的结合情况,并以普通脂质微泡作为对照,在倒置显微镜下观察LHRHa靶向脂质微泡对人卵巢癌A2780/DDP的体外寻靶能力。结果 LHRHa靶向脂质微泡免疫荧光阳性;体外寻靶实验显示LHRHa靶向脂质微泡能够与表面存在LHRH受体的A2780/DDP细胞特异性结合,而普通脂质微泡则不能结合。结论 利用生物素-链霉亲和素方法可成功制备LHRHa靶向脂质微泡造影剂,该靶向造影剂具有体外寻靶能力。     

载10-羟基喜树碱靶向脂质微泡的制备及体外寻靶能力实验研究

目的 制备携人肝癌单抗Hab18载10-羟基喜树碱的脂质微泡,并观察其体外寻靶能力.方法 制备生物素化抗人肝癌Hab18单克隆抗体,检测其生物素化程度;用机械振荡法制备载药脂质微泡,以生物素-亲和素桥连方式构建携人肝癌单抗Hab18载10-羟基喜树碱的脂质超声微泡,检测其一般特性、包封率和载药量,以免疫荧光法检测微泡与抗体的连接情况,在光镜下观察靶向载药微泡的寻靶能力,并与载药非靶向微泡进行比较.结果 每个单抗分子平均可与13个生物素分子结合.载药靶向脂质超声微泡分布均匀,平均粒径为1.52 μm,包封率为76.32%,载药量为21.81%.免疫荧光法显示微泡表面可见明亮的红色环状荧光,体外寻靶实验显示该载药靶向微泡可与人肝癌7721细胞牢固结合.结论 携人肝癌单抗Hab18载10-羟基喜树碱的脂质超声载药靶向微泡可成功制备,其包封率和载药量较高,具有较强的体外寻靶能力.     

携载PSMA单抗靶向前列腺癌的纳米级脂质微泡的制备及体外寻靶能力

目的制备携载PSMA单抗靶向人前列腺癌的纳米级脂质微泡,并观察其体外寻靶能力。方法利用静电吸附法制备携载PSMA单抗靶向前列腺癌的脂质纳米级微泡,检测其一般特性;免疫荧光法检测抗体与纳米级微泡的结合情况;用细胞免疫荧光分析鉴定PSMA的表达及其在细胞膜上的定位;普通光镜下观察靶向微泡对前列腺癌细胞的寻靶能力,同时以胃癌细胞作对照。结果携载PSMA单抗的靶向纳米级微泡分布均匀,平均粒径为(623.70±66.05)nm,免疫荧光法显示微泡表面可见绿色荧光,细胞免疫荧光检测前列腺癌细胞膜高表达PSMA,体外寻靶实验显示该靶向微泡可与人前列腺癌LNCAP及C4-2细胞牢固结合,而与胃癌MKN45细胞不结合。结论本实验成功制备的携载PSMA单抗靶向人前列腺癌的纳米级脂质微泡具有较强的体外寻靶能力,能特异性地与前列腺癌细胞结合。     

靶向纳米脂质超声造影剂制备及其体外寻靶能力实验研究

目的 制备一种靶向乳腺癌的纳米脂质超声造影剂,并观察其体外寻靶能力.方法 制备生物素化抗人乳腺癌细胞单克隆抗体Neu(F-11),并检测其生物素化程度和活性;通过生物素-亲和素系统制备靶向纳米脂质超声造影剂,用免疫荧光染色定性检测造影剂与抗体的连接情况,通过靶向造影剂与不同细胞的结合实验检测其寻靶能力.结果 每分子抗体可结合的生物素数目平均为7个,生物素化抗体的活性与游离单抗相比未见明显降低;免疫荧光染色显示靶向纳米脂质超声造影剂表面可见明亮的红色环状荧光,细胞结合实验显示其可与乳腺癌细胞特异性牢固结合.结论 生物素-亲和素系统可使造影剂与抗体牢固结合,所制得的靶向纳米脂质超声造影剂在体外具有较强的寻靶能力.     

PSMA单抗靶向人前列腺癌纳米级脂质微泡制备和体外寻靶能力实验研究

目的探究前列腺特异性膜抗原(PSMA)单抗靶向人前列腺癌纳米级脂质微泡的制备方法,对其体外寻靶能力予以观察。方法采用静电吸附法对PSMA单抗靶向人前列腺癌纳米级脂质微泡进行制备,观察其特性,对抗体与纳米级微泡结合情况予以免疫荧光法检测,采用细胞免疫荧光法对PSMA表达以及在细胞膜上的定位予以鉴定,观察靶向微泡对前列腺癌细胞的寻靶能力,并将胃癌细胞作为对照。结果 PSMA单抗靶向纳米级微泡呈现出均匀分布状态,平均粒径为(626.25±66.02)nm;经过免疫荧光法试验,显示微泡表面存在绿色荧光;对前列腺癌细胞膜给予细胞免疫荧光检测其PSMA呈现出高表达;体外寻靶实验显示靶向微泡能够实现与人前列腺癌LNCAP、C4-2细胞的结合,但其与胃癌MKN45细胞无法结合。结论 PSMA单抗靶向人前列腺癌纳米级脂质微泡体外寻靶能力强,能够实现与前列腺癌细胞的有机结合。     

结合链霉亲和素的高分子造影剂的制备及其初步应用

目的 制备一种结合链霉亲和素的高分子超声造影剂,并与生物素化抗体结合,考察其体外寻靶能力.方法 采用双乳化法制备高分子材料PLGA-COOH超声造影剂;并用碳二亚胺法将造影剂与亲和素耦联,制备出结合链霉亲和素的高分子超声造影剂.检测该造影剂一般特性;采用红外与免疫荧光检测亲和素与PLGA-COOH超声造影剂连接的情况.检测生物素-亲和素技术使该造影剂与生物素化抗体结合后其体外寻靶能力.结果 红外检测与免疫荧光检测显示亲和素被成功地连接在高分子造影剂上,并存在活性.体外寻靶实验显示,与生物素化单抗结合后的靶向高分子造影剂较多并牢固地聚集到肝癌细胞表面.结论 成功制备了结合链霉亲和素的高分子超声造影剂,该造影剂与生物素化抗体结合后于体外对肝癌细胞具有较强的亲和力.     

携Gelsolin单抗靶向超声造影剂的制备及体外靶向实验

目的 制备一种以肿瘤淋巴转移相关特异性膜抗原蛋白——凝溶胶蛋白（Gelsolin）为靶点的纳米级高分子造影剂，并观察其体外寻靶及显影能力。方法 通过改良的双乳化法制备高分子PLGA-COOH造影剂，以碳二亚胺法将造影剂与Gelsolin单抗连接，制备出GSN-PLGA靶向超声造影剂。检测该造影剂的一般性质，评估Gelsolin单抗与造影剂表面连接情况，评价其体外寻靶能力并进行体外显影实验。结果 GSN-PLGA靶向超声造影剂平均粒径为（575.67±4.71）nm，表面电位（-11.46±1.19）mV，造影剂表面GSN单抗结合率达96.93%。体外摄取实验显示细胞表面高表达Gelsolin抗体的小鼠腹水型肝癌高淋巴转移细胞株（Hca-F细胞）可较多摄取GSN-PLGA靶向造影剂。体外显像实验显示靶向超声造影剂体外显影效果较好。结论 GSN-PLGA靶向超声造影剂可与高表达Gelsolin的Hca-F细胞特异性结合，且体外显影效果较好。     

肝癌靶向液态氟碳脂质微球造影剂的体外寻靶实验研究

目的 制备液态氟碳脂质微球造影剂并研究其体外基本特性,再引入抗人肝癌细胞单克隆抗体,采用生物素亲和素法,进行体外靶向结合的研究.方法 采用旋转蒸发法和高压均质法制备一种纳米液态氟碳脂质微球造影剂,观察其外观、形态、大小及分布情况,计算其浓度,并测定其粒径、电位;制备生物素的抗人肝癌细胞单克隆抗体HAb18,用HABA/Avidin试剂盒检测抗体的生物素化程度;制备NBD标记的生物素化的微球,采用生物素亲和素法研究其体外靶向作用.结果 所制备的液态氟碳脂质微球造影剂外观呈乳白色的混悬液,镜下观察,微球形态圆整,大小均一,性质稳定,平均粒径171.9 nm;采用生物素亲和素法制备的NBD标记的生物素化的微球可靶向结合到靶细胞上.结论 成功制备出稳定的纳米液态氟碳脂质微球造影剂,并引入抗人肝癌细胞单克隆抗体,通过生物素亲和素系统可将其特异结合到靶细胞上.     

平行板流动腔法评价生物素化脂质微泡制备效果

目的 制备生物素化脂质微泡,并应用平行板流动腔检测流体切应力对生物素化脂质微泡与链亲和素结合稳定性的影响,为进一步开展超声分子成像研究奠定基础.方法 采用声振法制备出表面携有生物素分子的脂质微泡,与普通脂质微泡对照,应用平行板流动腔模型,设置不同流体剪切应力,观察与链亲和素靶向结合的生物素化微泡的黏附效果.结果 在不同浓度链亲和素包被的平行板流动腔中均见生物素化微泡结合;随着链亲和素包被浓度的提高,靶向结合的生物素化脂质微泡抗流体剪切应力能力明显提高.结论 应用平行板流动腔模型能成功检测生物素化微泡的靶向黏附效果,该模型可推广应用于其他靶向微泡制备成功后靶向黏附能力的体外检测.     

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.     

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.     

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.     

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.     

自动化酸碱平衡图在急诊社区获得性肺炎诊治中的应用

目的 探讨自动化酸碱平衡图在急诊科社区获得性肺炎(CAP)患者诊断中的价值.方法 根据病史、肺功能测定结果、慢性阻塞性肺疾病(COPD)诊断标准,将111例CAP患者分为单纯CAP组(56例)和COPD合并CAP组[即慢性阻塞性肺疾病急性加重(AECOPD)组,55例].询问患者病史后即刻抽取动脉血测血气并进行自动化酸碱平衡图分析.结果 血气分析结果显示,AECOPD组动脉血二氧化碳分压(PaCO2,kPa)、HCO3- (mmol/L)、剩余碱(BE,mmol/L)均显著高于CAP组(PaCO2:7.714±2.414比5.896±1.308,HCO3-:30.767±7.185比25.014±3.043,BE:4.345±5.371比-0.354±3.180,均P＜0.01).自动化酸碱平衡图分析结果显示,AECOPD组患者酸碱平衡紊乱高达89.1％,CAP组为66.1％.将AECOPD组和CAP组患者中正常(10.9％、33.9％)、急性呼吸性酸中毒(急性呼酸,12.7％、14.3％)、慢性呼吸性酸中毒(慢性呼酸,49.1％、10.7％)、呼吸性碱中毒(呼碱,7.3％、14.3％)、代谢性酸中毒(代酸,12.7％、17.9％)、代谢性碱中毒(代碱,12.7％、8.9％)综合进行x2分析,差异有统计学意义(x2=24.421,P=0.001),而将正常、急性呼酸、呼碱、代酸及代碱进行x2分析,差异无统计学意义(x2=5.280,P=0.260),提示AECOPD患者慢性呼酸的发生率较单纯CAP患者显著增加.结论 自动化酸碱平衡图能帮助急诊科医师快速识别CAP患者是否存在多重酸碱平衡紊乱,并可快速识别急、慢性呼吸系统疾病.