包裹ICG的靶向阳离子纳米粒的制备及体外显像

目的 制备一种包裹ICG的靶向相变型阳离子脂质纳米粒(INP),连接CD105抗体,检测其光热效应、体外相变、光声及超声显像规律,并证实纳米粒抗体连接成功。方法 采用双乳化法制备包裹ICG及液态氟碳(PFP)的阳离子脂质纳米粒;链霉亲和素法连接CD105抗体,流式细胞量化及激光共聚焦下观察抗体连接情况;脉冲激光激发观察其光热效应及相变情况;体外Lifu辐照致相变后记录超声显影效果;光声仪检测光声显像能力。结果 制备的INP平均粒径(354.2±93.85nm),平均电位(25.2±3.29mv),与CD105抗体结合率为99.89%,纳米粒具有良好光热效应,一定浓度下2W/cm2激光辐照180s温度可升至63℃,可发生液气相变。体外超声及光声显影效果佳。结论 成功制备了包裹ICG的靶向相变型阳离子脂质纳米粒(INP),其光热效应好、光声显影及增强超声显影效果佳,纳米粒与CD105抗体结合率高。     

携Gelsolin单抗靶向相变型超声造影剂的制备及体外靶向实验

目的制备一种以凝溶胶蛋白(GSN)为靶点的包裹液态氟碳的纳米级PLGA高分子造影剂(GSN-PLGA-PFP),并评价其体外热致相变、靶向及显影能力。方法采用双乳化法及碳二亚胺法制备靶向相变型高分子超声造影剂。检测此造影剂的一般性质;显微镜加热板法进行热致相变;激光共聚焦显微镜体外观察GSN-PLGA-PFP被小鼠腹水型肝癌高淋巴道转移Hca-F细胞摄取的情况,初步评价其寻靶能力;体外低强度聚焦超声(LIFU)仪辐照后观察其超声显影效果。结果 GSN-PLGA-PFP的平均粒径为(328.59±3.82)nm,造影剂表面平均Zeta电位为(-10.36±1.34)mV,造影剂表面GSN单抗连接率高达98.31%,且于43.5℃时纳米粒开始发生相变;体外摄取实验显示Hca-F细胞可较多地摄取GSNPLGA-PFP,体外行LIFU辐照后可观察到显影效果明显增强。结论自制携Gelsolin单抗包载PFP的PLGA造影剂热致相变效果明显,可与Hca-F细胞特异度结合且体外显影效果较好。     

载替莫唑胺纳米粒联合低强度聚焦超声对人胶质瘤细胞的促凋亡作用

目的制备由聚乳酸-羟基乙酸共聚物(PLGA)包载全氟戊烷(PFP)与化疗药替莫唑胺(TMZ)的液气相变型纳米粒(TMZ/PFP/PLGA NPs), 联合低强度聚焦超声(LIFU)辐照, 探讨其体外超声显影能力及对人胶质瘤细胞的体外干预效果。方法采用复乳法制备TMZ/PFP/PLGA NPs, 检测其基本理化性质及药物包载能力, 观察纳米粒体外超声显影效果;CCK-8法检测纳米粒的体外细胞毒性及与LIFU协同干预对胶质瘤细胞存活率的影响;Western blot检测协同干预后细胞内凋亡相关蛋白Bcl-2、bax及caspase-3的表达水平变化。结果在透射电镜下, TMZ/PFP/PLGA NPs呈形态规则的类圆形核壳结构, 粒径(137.9±63.31) nm, 对TMZ的包封率为(83.01±5.57)%, 载药量(3.19±0.22)%;纳米粒与U251细胞共孵育24 h后细胞存活率仍可保持在70%以上, 在同时施加LIFU辐照的协同作用下, 可使细胞凋亡加速, 细胞存活率明显下降;Western blot检测结果显示, 协同干预可明显下调细胞内凋亡相关蛋白Bcl-2的表达, 同...     

载自杀基因的靶向超声分子探针的制备及超声显像的实验研究

目的:制备一种包裹液态氟碳，载肝癌治疗基因质粒，并具有叶酸分子靶向性的纳米级超声分子探针, 研究其基本特性及超声显像能力? 方法:通过聚乙二醇亚胺在PLGA表面连接叶酸（Fa）分子，制成靶向膜材料(PLGA-Fa)后,采用双乳化法制备载有PFP的纳米级靶向超声造影剂，将其与多聚赖氨酸孵育后，形成表面带正电荷的阳离子，利用正负电荷吸附作用，使纳米粒表面载上质粒C（PLGA-Fa-PFP-C）。 分别用加热及LIFU辐照的方式处理纳米粒，于显微镜下观察其相变情况，于超声造影模式下观察其体外显影效果。另同样用双乳法制备无叶酸的非靶向造影剂，将两者分别与肝癌细胞HepG2孵育，观察其寻靶能力。 结果: 成功制备了载有质粒、PFP的纳米级靶向超声造影剂(Fa-PLGA/PFP/C)，该纳米微粒大小均匀,形态圆整,分散性好，直径分布为200.5nm，平均电位为+37MV,当加热至50度时及用LIFU5档辐照后5分钟后，显微镜下可见较多的纳米粒相变，超声造影模式下亦可见显像;并在细胞实验中观察到该靶向造影剂有明显的靶向作用。 结论:本研究成功制备了一种载质粒及PFP的纳米级靶向超声造影剂(Fa-PLGA/PFP/C)，该纳米粒可用于超声造影显像，并具有肿瘤靶向性。     

靶向相变型载药纳米造影剂的制备及其基本性能和显像特性检测

目的制备一种叶酸靶向相变型载羟基喜树碱(HCPT)的纳米粒(FA-HCPT-Fe₃O₄-PFP NDs),检测其基本性能和多模态显像特性。方法采用旋转蒸发-超声法制备FA-HCPT-Fe₃O₄-PFP NDs。于制备后不同时间点使用电子显微镜测定纳米粒粒径以检测其稳定性;将纳米粒乳液加热后置于显微镜下观察其相变特性,高效液相色谱法检测纳米粒内药物(HCPT)的载药量。检测观察纳米粒对富含叶酸受体的SKOV3肿瘤细胞的寻靶能力。对不同浓度纳米粒制备成的凝胶块进行光声成像及MRI;使用低强度聚焦超声(LIFU)辐照纳米粒乳液后行超声成像,分别验证其增强光声、MRI及超声成像的能力。结果制备的FA-HCPT-Fe₃O₄-PFP NDs性质稳定,HCPT载药量为(8.33±0.57)%,包封率为(60.51±2.33)%,加热后可发生液气相变。体外寻靶实验证实该纳米粒对富含叶酸受体的SKOV3肿瘤细胞局部有良好的靶向性。体外多模态显像增强实验结果表明该纳米粒可以明显增强超声、光声及MRI的显影能力。结论本实验所制备的FA-HCPT-Fe₃O₄-PFP NDs具备多模态造影剂的功能,是一种极具潜力的分子探针。     

载紫杉醇的LHRH靶向相变型超声造影剂的制备及其一般特性

目的制备一种载紫杉醇的靶向相变型纳米级超声造影剂,并评价其一般特性。方法通过薄膜水化法、乳化法制备载紫杉醇的非靶向脂质纳米粒(PTX-LNP),通过生物素-亲和素法将生物素化的促黄体生成素释放激素(LHRH)连接于非靶向脂质微球制备载紫杉醇的LHRH靶向相变型脂质纳米粒(PTX-LNP-LHRH),检测PTX-LNP-LHRH的粒径以及表面电位,载药量及包封率,分别观察其声致相变及热致相变情况,检测纳米粒的LHRH靶连接率及其致人卵巢癌OVCAR3细胞的凋亡率。结果成功制备靶向相变型脂质纳米粒,LHRH的靶连接率为(98.85±0.75)%,共聚焦显微镜下可见PTX-LNP-LHRH聚集在OVCAR3细胞周围,PTX-LNP-LHRH组致OVCAR3细胞的凋亡率明显高于PTX-LNP组。结论成功制备靶连接率高且致靶细胞凋亡率较高的PTX-LNP-LHRH,其体外声致相变后可增强超声显影的效果。     

载ACE2激动剂的胶原靶向纳米粒的制备及体外显像与靶向研究

目的制备一种以心肌胶原蛋白标记物CNA35为靶点的载ACE2激动剂三氮脒(DIZE)的液态氟碳脂质纳米粒(CNA35/PFP/DIZE@NPs),评价其体外显像和寻靶能力。方法采用薄膜旋蒸联合乳化法将PFP和DIZE装载于脂质体内,碳二亚胺法连接CNA35。检测其一般性质及载药情况,LIFU辐照后评估超声显像能力,共聚焦显微镜观察其与兔心肌纤维化冰冻切片中胶原蛋白的结合,评估体外寻靶能力。结果制备的靶向载药纳米粒,形态均一,平均粒径为(302.90±4.89)nm,载药量4.00%±0.78%。体外LIFU辐照可增强现象,共聚焦下见纳米粒可与较多胶原结合。结论成功制备了CNA35/PFP/DIZE@NPs,具有良好的体外显像和胶原靶向能力。     

载10-羟基喜树碱液态氟碳纳米粒制备及其表征、体外增强超声显像效果观察

目的 研制一种包裹液态氟碳（PFP）的新型载药纳米级超声造影剂,考察其基本特性并观察其体外增强超声显像效果。方法 采用旋转蒸发和探头超声法制备载10-羟基喜树碱（10-HCPT）的液态氟碳（PFP）纳米粒,在光学显微镜和透射电镜下观察纳米粒形态,采用马尔文仪测量纳米粒粒径和电荷。采用紫外分光光度计测定纳米粒包封率,并应用低强度聚焦超声（LIFU）辐照载药液态氟碳纳米粒溶液,观察纳米粒相变情况及其增强超声显像效果。结果 制备的载药脂质纳米粒外观为乳白色混悬液,在油镜及透射电镜下观察,载药纳米粒形态规则,分布均一,平均粒径约（500.82±25.97）nm,表面平均电位为（-47.77±3.09）mV;在体外经LIFU辐照后,可见纳米粒发生液气相变形成微泡,在基波模式和谐波模式下,均可显著增强超声显影。结论 成功研制了包裹液态氟碳的载药脂质纳米粒,可望成为一种新型的多功能超声造影剂。     

载自杀基因靶向超声分子探针制备及其超声显像的实验研究

目的制备一种包裹液态氟碳及载肝癌治疗基因质粒,并具有叶酸分子靶向性的纳米级超声分子探针,研究其基本特性及超声显像能力。方法通过碳乙亚胺法在聚乳酸-羟基乙酸共聚物(PLGA)表面连接叶酸分子,制成靶向膜材料(FA-PLGA)后,采用双乳化法制备载有全氟戊烷(PFP)的纳米级靶向超声造影剂,将其与多聚赖氨酸孵育后,形成表面带正电荷的阳离子,利用正负电荷吸附作用,使纳米粒表面载上目标质粒S-HSV1-TK,得到S-HSV1-TK/PFP@FA-PLGA。使用低强度聚焦超声(LIFU)辐照的方式处理纳米粒,显微镜下观察其相变情况,于超声造影模式下观察其体外显影效果,流式细胞仪检测其连靶率;用PLGA代替FA-PLGA,使用相同方法制备无叶酸的非靶向造影剂,将靶向造影剂和非靶向造影剂分别与肝癌细胞HepG2孵育,观察其体外寻靶能力。结果成功制备了载有质粒及PFP的纳米级靶向超声造影剂S-HSV1-TK/PFP@FA-PLGA,该纳米粒大小均一,分散性好,平均粒径(200.50±66.34)nm,平均表面电位(37.40±7.08)mV。使用LIFU 5档辐照5 min后,显微镜下可见较多的纳米粒相变,超声造影模式下亦可见显像。流式细胞仪检测纳米粒连靶率约95%;体外细胞实验结果显示该靶向造影剂有明显的靶向作用。结论本实验成功制备了一种载质粒及PFP的纳米级靶向超声造影剂S-HSV1-TK/PFP@FA-PLGA;该纳米粒可用于超声造影显像,并具有肿瘤靶向性,为研究质粒的转染及肿瘤的治疗奠定了良好基础。     

裸鼠移植瘤相变型液态氟碳纳米粒超声显像实验研究

目的制备一种载超顺磁性氧化铁纳米粒(Fe3O4)包裹全氟正戊烷(PFP)的相变型液态氟碳超声造影剂PFP-MPLGA纳米粒,观察其在裸鼠移植瘤内发生相变及增强超声显像的效果,探讨其对肿瘤组织的作用。方法用单乳化法制备PFP-MPLGA纳米粒,检测其一般特性;对裸鼠移植瘤局部注射纳米粒,用近红外线照射肿瘤部位,用超声诊断仪观察纳米粒相变后增强超声显像的效果。结果成功制备出PFP-MPLGA纳米粒;裸鼠瘤内局部注射纳米粒后,近红外线照射可致其相变,显著增强超声显像;肿瘤组织HE染色观察到肿瘤组织内有大量空泡产生。结论 PFP-MPLGA纳米粒在近红外线照射下能在移植瘤内发生相变增强超声显像,且能起到消融肿瘤组织的作用。     

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.     

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.     

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.     

Bacterial meningitis: an update of new treatment options

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case–control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.