Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Molecular interactions between anticancer drugs and iodinated contrast media: An in vitro spectroscopic study

Purpose: The purpose of this study is to assess molecular interactions between several anticancer drugs and an iodinated contrast medium by Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible spectroscopy (UV-Vis). Materials and Methods: Iopamidol (IPM) was used as an iodinated contrast medium, and mitomycin C (MTI), epirubicin hydrochloride (EPI), cisplatin (CDDP), 5-fluorouracil (5FU), irinotecan hydrochloride (CPT11), gemcitabine hydrochloride (dFdC), carboplatin (CBDCA), oxaliplatin (1OHP), paclitaxel hydrochloride (TAX) and docetaxel trihydrate (TXT) were used as anticancer drugs. For FT-IR, the purified IPM was mixed stoichiometrically with each anticancer drug as well as with a combination of MTI and EPI. After measuring each separated sample and the mixtures, the spectra of the mixtures were compared with the spectra of the sum of pure samples or the combination. For UV-Vis, IPM and anticancer drugs were dissolved in pure water;subsequently for the titration experiments, the mixtures were prepared by varying the molar ratio. IR absorption corresponds to stretching vibrations between atoms having covalent bonding, whereas UV-Vis spectra depend on molecular dynamics and shapes. Both UV-Vis and IR spectra change when there are molecular interactions such as aromatic ring stacking and hydrogen bonding. Result: IPM exhibited molecular interactions with MTI, EPI, CDDP, dFdC, CBDCA, 1OHP, TAX and TXT, as well as with the combination of MTI and EPI on FT-IR. However, molecular interactions were not observed on UV-Vis. Conclusion: Several anticancer drugs have molecular interactions with IPM, which could be clinically utilized for superselective intraarterial infusion chemotherapy.

Quantitative Assessment of Protective Effects of Antioxidant Agents against Drug-Induced Nephrotoxicity Using Dynamic Contrast-Enhanced Computed Tomography

Purpose: The purpose of this study was to develop a method for quantifying the extent of renal dysfunction due to drug-induced nephrotoxicity using dynamic contrast-enhanced computed tomography (DCE-CT) and to investigate the protective effects of various antioxidant agents against cis-dichlorodiammineplatinum (cisplatin)-induced nephrotoxicity in rats using this method. Materials and Methods: The DCE-CT studies were performed in 8-week-old male Sprague-Dawley rats. The CT scanning started 4 s before a bolus intravenous injection of iodinated contrast agent (CA) (150 mgI/kg) from the tail vein using an automatic injector and lasted 90 s at 1-s intervals. The contrast clearance per unit renal volume (K1) was estimated from the DCE-CT data using the Patlak model. The renal volume (V) was calculated by manually delineating the kidney on the CT image. The contrast clearance of the entire kid-ney (K) was obtained by . First, to investigate the effect of CA itself, the DCE-CT studies were performed without injecting cisplatin 2, 4, and 7 days after the first DCE-CT study on day 0. Second, to investigate the effect of injected dose of cisplatin, the DCE-CT study was performed after the intraperitoneal (i.p.) injection of cisplatin (1.8 mg/kg) and was repeated every other day for one week. Finally, to investigate the protective effects of antioxidant agents [L-arginine (300 mg/kg), N-acetylcysteine (500 or 1000 mg/kg), methimazole (40 mg/kg), captopril (60 mg/kg), and taurine (750 mg/kg)], the DCE-CT studies were performed on days 0, 2, 4, and 7 after the i.p. injection of cisplatin (3.6 mg/kg). For comparison, the DCE-CT data were also acquired without injecting the antioxidant agents (CDDP group). Results: When cisplatin was not injected, there were no significant changes in the K value as compared to that on day 0 within the studied period. The K valuesignificantly (p < 0.05) decreased with increasing dose of cisplatin. Although some differences were observed in the extent of change in the K value normalized by that on day 0, depending on the antioxidant agents and their injected dose and schedule, the normalized K values on day 7 in the groups injected with the antioxidant agents were significantly higher than those in the CDDP group, suggesting that the antioxidant agents studied here had protective effects against cisplatin-induced nephrotoxicity in varying degrees. Conclusion: Our method appears useful for quantitatively evaluating the protective effects of antioxidant agents against cisplatin-induced nephrotoxicity and for investigating the optimal injected dose and schedule of the agents, because it allows repeated measurements of split renal function in a single animal.

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Transdermal drug delivery （TDD） can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid （HA） in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers （e.g., their penetration depth and concentration） could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents （UCAs）. When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 p.m. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 p.m, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications （e.g., nanoparticle drug carriers, transdermal patches and cosmetics）, protocols and methods presented in this paper are potentially useful.

Usefulness of contrast enhanced ultrasound in monitoring therapeutic response after hepatocellular carcinoma treatment

In the last years, the development in the oncology field has been huge and rapid. In particular, the evaluation of response to anti-tumour treatments has been being object of intense research, producing significant changes. Response assessment after therapy in solid neoplasias has always used radiological imaging techniques, with tumour size reduction representing a presumed therapeutic efficacy. However, with the introduction of anti-angiogenetic drugs the evaluation of tumour size has become unsuitable because some tumours, under treatment, show only tumour perfusion changes rather than lesion shrinkage. Between different imaging techniques with contrast-enhancement, contrastenhanced ultrasound(CEUS) and, in particular, dynamic CEUS have arisen as a promising and non-invasive device for monitoring cancer treatments. Moreover, the introduction of perfusion software has even more refined the technique since it is able to provide quantitative parameters related to blood flow and blood volume that can be associated with tumour response and clinical outcome such as the progression free survival and the overall survival. Here, we give an overview of the current status of CEUS in monitoring hepatocellular carcinoma response to different kind of treatments.

鼓室给药临床实践指南

鼓室给药是一种常见的耳科局部给药方式,指通过将药物递送入中耳,经圆窗膜或卵圆窗扩散分布到内耳从而达到治疗或诊断效果。近年来,鼓室给药技术在耳科疾病的临床应用越来越广泛,主要包括突发性聋、梅尼埃病、分泌性中耳炎和自身免疫性内耳病等疾病的诊治。目前,国内外对鼓室给药的操作规范、适应证,尤其是给药时机及治疗方案尚未有统一标准。为了促进鼓室给药技术规范化,我们特组织了国内在鼓室给药领域经验丰富,有卓越建树中青年专家,基于临床经验和循证医学证据制定了鼓室给药临床实践指南。本指南从鼓室给药操作规范出发,系统总结了糖皮质激素鼓室给药、庆大霉素鼓室给药、鼓室内注射造影剂膜迷路MRI成像及其他药物鼓室给药四个方面,旨在指导并规范临床鼓室给药技术的应用。

碘对比剂全程化药学服务共识

目的探讨碘对比剂全程化药学服务模式,促进碘对比剂的临床合理使用。方法中国医药教育协会临床合理用药专业委员会和广东省药学会用药评价与临床科研专家委员会组织国内专家,成立《碘对比剂全程化药学服务共识》工作组,针对碘对比剂的发展历程、适应证、禁忌证、不良反应、药物相互作用、特殊人群用药、药学服务等进行文献检索、循证分析和研讨,梳理全程化药学服务的内容与流程,最终形成共识。结果制定的碘对比剂全程化药学服务共识包括检查前对患者、肾功能、合并用药和水化方案的评估,检查中有无发生对比剂外渗或发生(可疑)急性不良反应,检查后的观察时间点和随访等内容,以药学服务流程图展示各阶段的具体工作,并形成用药监护记录表用以记录工作情况。结论本共识构建了碘对比剂全程化药学服务体系,为临床医生、护理人员合理使用该类特殊药品提供了科学依据,也为药师进行相关药学服务提供了参考。

61例非离子型碘造影剂不良反应的回顾性分析

目的探讨心血管病专科医院非离子型碘造影剂不良反应(ADR)的特点及相关规律。方法将某心血管病专科医院2018年9月至2021年4月61例非离子型碘造影剂相关药品不良反应(ADR)报告中患者年龄、性别、ADR类型、用药情况、临床表现等进行分类统计、分析,并将结果与文献报道进行对比。结果该院不良反应发生率为0.267%,碘海醇注射液0.176%,碘普罗胺注射液0.667%,碘帕醇注射液0.230%,碘克沙醇注射液0.354%。严重不良反应3例,发生率0.0131%。48例急性ADR,构成比78.69%,迟发性ADR13例,构成比21.31%,无晚发性ADR。结论该心血管病专科医院非离子型碘造影剂ADR发生率低于文献报道,严重ADR发生率与国外报道的一致,迟发性ADR发生率低于大多数既往研究报道。

一种新型杀虫消毒合剂的药效实验研究

目的应用胶束微乳技术,研制杀虫和消毒功能的神网杀虫消毒合剂,通过与目前口岸常用杀虫和消毒剂对比,验证神网杀虫消毒合剂效果。方法采用密闭圆筒法,在口岸现场,用神网杀虫消毒合剂与雷达杀虫喷射剂比对测试杀虫效果;与泰胜消毒液对进境废纸、木托及集装箱进行喷洒测试消毒效果。结果杀虫实验结果表明,神网杀虫消毒合剂与0.17%雷达杀虫喷射剂对致倦库蚊、家蝇、德国小蠊的KT50及24h死亡率(%),前者优于后者。消毒实验结果表明,神网杀虫消毒合剂与泰胜消毒液对进境废纸、木托及集装箱所携带病菌的灭杀率均达到95%以上,二者无显著性差异(P>0.05)。结论神网杀虫消毒合剂是一种较好的卫生处理药剂,其杀虫和消毒功能基本能满足口岸卫生处理的需要。

包裹阿霉素的高分子材料微泡声学造影剂制备及显影效果实验研究

目的探索包裹药物的微泡声学造影剂制备方法,观察其体内外显影效果。方法采用在体内能生物降解的人工合成高分子聚合物乳酸/羟基乙酸共聚物(PLGA)作为成膜材料,通过双乳化法和冷冻干燥技术制备包裹阿霉素(ADM)和空气的PLGA微泡声学造影剂(ADM-PLGA声学造影剂)。光学显微镜进行形态学观察。体外和动物实验观察其显影效果。结果采用本法成功制备了ADM-PLGA声学造影剂;光镜观察其形态规则,呈球型,大小均匀,最大粒径<4μm;体内外显影效果好。结论通过本方法可以合成包裹水溶性药物的微泡声学造影剂,为应用超声波和微泡造影剂进行体内药物定位释放研究打下了基础。

正常兔肝脏二次谐波声学造影剂量与效应关系的声学定量分析

目的:利用实验性兔肝对二次谐波成像中的剂量-效应关系进行声学定量分析。方法:对10只健康新西兰大白兔进行二次谐波声学造影,造影剂经耳缘静脉注射,剂量分0.05,0.10,0.20,0.30ml?kg四个水平,造影增强后图像灰阶变化进行AD定量分析,测量指标有PI,AUC,HT,MTT。结果:各剂量水平肝实质AD曲线形态基本相似,呈单峰形态,近似直角三角形,但曲线高度不同。剂量从0.05ml?kg到0.20ml?kg,PI,AUC,HT,MTT测值均逐渐增大,造影效果逐渐增强;当剂量为0.30ml?kg时,因血管内声影的影响,PI,AUC,HT,MTT反而减低。结论:二次谐波造影增强效果与剂量有关,可随剂量增大而增强,但剂量过大时,造影效果反而减低。

比较两种制备载紫杉醇超声微泡的方法

目的比较能被超声击破的两种载紫杉醇超声微泡的制备方法,并评价其理化性质以及超声散射强度。方法用单纯紫杉醇法Ⅰ号和三醋酸甘油酯溶解法Ⅱ号分别制备载紫杉醇脂质超声微气泡,测定其包封率、载药量、粒径大小、分布和Zeta电位、pH值,并行超声击破试验及兔VX2皮下肿瘤显像试验。结果两种微泡显像无明显差异,可被低能量超声击破,但Ⅱ号(加入三醋酸甘油酯)脂质微泡较Ⅰ号(常规冷冻干燥法制备)载药微泡粒径显著减小[(1.07±0.38)μmvs(2.79±0.41)μm,P<0.01],表面电位增高[(19.10±0.32)mVvs(-5.90±0.21)mV,P<0.01],包封率和载药量显著增高[(95.00±1.22)%vs(36.10±4.74)%,P<0.01;(5.60±0.11)%vs(0.50±0.04)%,P<0.01]。结论三醋酸甘油酯溶解法制备的Ⅱ号微泡在局部药物释放中具有更大的应用价值。

载药脂质超声微泡造影剂的制备及应用研究

载药脂质微泡是近年来国内外研究的热点之一,目前已制备出微米级及纳米级载药脂质微泡,本文就载药脂质超声微泡造影剂的特点、制备、应用、现存的问题及发展前景做一综述。

携RGD肽靶向高分子造影剂的制备及体外靶向实验

目的制备携RGD肽的PLGA造影剂,并观察其在体外的靶向能力。方法采用双乳化法制备PLGA-COOH造影剂,利用碳二亚胺法将RGD肽与PLGA-COOH造影剂共价结合,制备出RGD-PLGA的靶向造影剂。用激光共聚焦检测FITC-RGD与PLGA造影剂的连接情况,并在光镜及荧光显微镜下对比观察RGD-PLGA与普通PLGA靶向SKOV-3细胞的能力,而后利用流式细胞检测技术对比RGD-PLGA与普通PLGA的靶向能力。结果连接FITC-RGD的PLGA显示出明显的绿光,体外靶向实验显示RGD-PLGA较普通PLGA更多地聚集在SKOV-3细胞的周围,流式细胞检测显示RGD-PLGA较普通PLGA有更好的靶向性。结论成功制备出RGD-PLGA,且在体外实验中对高表达整合素αvβ3的SKOV-3细胞有较强的结合能力。

微泡超声造影剂:一种新型的药物靶向载体

药物携载是目前重要的研究领域,如何使得药物安全、有效、靶向性地导入体内特定器官、组织并使其释放在靶细胞内是研究的重点。微泡超声造影剂作为一种新型的体内药物载体,受到国内外学者的广泛关注。本文对有关微泡超声造影剂作为药物载体的作用原理、制备要求、制备方法、特点和应用等方面的研究作了介绍。

MRI评价药物投递性能方法研究

采用MRI评价自制肝组织特异性非离子型高分子磁共振造影剂在小鼠体内药物投递效果.分别在注射造影剂后0.1h、6h、12h、24h及7天采集磁共振T1加权图像.所有扫描均在1.5T临床磁共振成像仪上完成,以固定体线圈为射频发射线圈,三英寸圆形表面线圈为信号接收线圈.数据分析前采用线圈非均匀性校正和信号非稳定性校正进行预处理.实验结果显示,线圈空间敏感性校正使得小鼠组织图像信号强度空间更加均匀,稳定性校正后使得图像数据更加准确可靠,MRI是一种在体评价顺磁性标记高分子化合物药物投递效果的有效方法.

磁性脂质体的制备及应用研究进展

综述了纳米磁性粒子和磁性脂质体的制备方法,同时简要介绍了磁性脂质体在磁性分离、靶向药物、热疗、组织工程和造影剂等领域的应用进展。

110例碘克沙醇药品不良反应分析

目的分析碘克沙醇在血管造影应用中发生药品不良反应(adverse drug reaction,ADR)的特点及规律,为减少临床用药风险提供参考。方法临床药师对我院心内科2018年7月1日至2019年5月31日使用碘克沙醇的415例患者进行药学监护,询问并记录患者使用碘克沙醇后ADR发生的时间、症状及程度,利用医院信息管理系统(HIS)检索患者其他信息,包括性别、年龄、体重、肌酐值等。结果415例患者中有359例患者录入ADR相关有效信息,发生ADR的患者共计110例,ADR总体发生率30.64%。其中急发ADR占不良反应总数的14.55%,迟发占85.45%;轻度占73.64%,中度占25.45%,重度占0.91%;按ADR累及系统-器官统计共计181例次,皮肤及其附件损害占25.41%,消化系统占27.62%,神经系统占24.31%,心血管系统占3.87%,呼吸系统占9.39%,泌尿系统占1.10%,全身ADR占8.29%。过敏性休克1例,对比剂所致的急性肾损伤(contrast induced acute kidney injury,CI-AKI)2例。结论碘克沙醇相关ADR发生率高于既往报道,应加强术前预防评估及各项措施,降低ADR发生率,提高用药安全性。

我院5年间冠脉介入术中碘造影剂过敏反应监测报告分析

目的研究和分析冠脉介入术中碘造影剂发生过敏反应的特点，为降低碘造影剂在冠脉介入手术中的使用风险提供参考。方法选用回顾性研究方法，对阜外心血管病医院2007～2012年住院冠脉介入手术（包括冠脉造影）中发生碘造影剂过敏反应病例资料，分别按照患者性别、年龄、临床表现以及引起过敏反应的碘造影剂种类等进行描述性统计分析。结果在79102监测到48例非离子型碘造影剂过敏反应，发生率0．61％o（48，78600）。其中男性患者为44例、女性患者为4例，男女比例11：1；涉及药品包括碘海醇、碘佛醇、碘帕醇、碘克沙醇、碘普罗胺等常用的非离子型碘造影剂，以碘普罗胺和碘克沙醇为多。过敏反应临床表现多样，以皮疹等皮肤黏膜表现最为常见，过敏性休克最为严重，其中死亡2例。结论在冠脉介入术中应用非离子型碘造影剂安全性良好，但仍需重视对其药品不良反应的监测、报告与分析；早期识别、早期干预，以提高用药安全与冠脉介入手术安全。

非离子型含碘造影剂不良反应Logistic回归分析

目的:探讨非离子造影剂不良反应发生的危险因素。方法:统计分析10 081例使用非离子造影剂调查表中不良反应发生情况。结果:本调查表中三种非离子造影剂的不良反应发生率为0.33%～0.67%;恶心、呕吐的不良反应发生率碘帕醇组远高于碘普罗胺及碘海醇组;碘浓度370组不良反应发生率最高为1.89%;注射速率5 ml·s^(-1)组不良反应发生率显著高于其他速度组。Logistic回归分析显示:碘普罗胺发生不良反应的危险因素是碘浓度、过敏体质、预加热;碘海醇发生不良反应的危险因素是注射速率(ml·s^(-1));碘帕醇发生不良反应的影响因素为注射速率(ml·s^(-1))、年龄、造影荆总量(ml)、预加热及检查部位。结论:非离子造影剂并非绝时安全,少数患者会发生不同程度的不良反应。