不同脂质体透皮机制的研究进展

脂质体作为药物载体进行透皮给药是一种很有发展前途的给药方式.目前常用的有普通脂质体、变形脂质体、乙醇脂质体等.脂质体促透的机理主要是影响皮肤角质层.作用于皮肤附属器以及改变药物的外在特性使之透过皮肤,从而提高药物透皮吸收的速率和总量.其促透机理有水合作用、穿透作用、变形作用和渗透压驱动作用等.脂质体在透皮方面有着广泛的应用前景.     

薄荷脑促扑热息痛透过胎儿皮肤实验的电镜观察及其助渗机制的探讨

主要研究了中药薄荷脑作为渗透促进剂对药物扑热息痛透过胎儿皮肤的影响.结果表明:在透皮吸收药理实验小,薄荷脑具有显著促进扑热息痛透皮吸收作用(P<0.01):扫描电镜观察显示,用薄荷脑实验组的胎儿皮肤表面绉折增多,角质层局部断裂脱屑、翻卷呈破棉絮状,表皮细胞间隙加宽,毛囊口扩展.毛干的毛小皮剥脱而变细.提示薄荷脑促扑热息痛透皮吸收的机制与改变皮肤表皮结构密切相关.     

TEMPO-NaBr-NaClO 体系对细菌纤维素的氧化过程研究

细菌纤维素是具有天然纳米网状结构的支架材料,选择性催化氧化可改善其降解性能。以NaClO、TEMPO和反应时间为变量,研究2,2,6,6-四甲基哌啶-1-氧化物自由基(TEMPO)/NaBr/NaClO体系对细菌纤维素的氧化。结果表明,在试验条件范围内,体系初始阶段的反应速率随NaClO用量的增加而减小;体系pH值是影响此阶段反应速率的主要因素且体系最大反应速率出现在pH＝10.50～11.00之间;TEMPO用量对此阶段反应速率的影响不明显。对整个反应过程而言,体系的反应速率和不溶性产物的羧基含量都随NaClO用量的增加而增大,其中NaClO用量在1～8 mL之间时,都呈现良好的线性关系;二者都随催化剂TEMPO用量的增加而增大。不溶性产物的羧基含量随反应时间的延长先逐渐减小后保持相对稳定在0.70～0.75 mol/kg。在不同反应阶段,TEMPO/NaBr/NaClO体系对BC的氧化规律存在明显差异,BC独特的结构特点可能是导致这种差异的主要原因。     

一种用于实体瘤诊断的磁共振成像(MRI)生物大分子对比增强剂的合成与鉴别

通过二步法成功地合成一系列N-(2-羟丙基)甲基丙烯酰胺(HPMA)聚合物-Proxyl接合物，以紫外可见分光光度法测定聚合物中Proxyl的含量，电子自旋共振图谱仪测定接合物的电子自旋共振图谱(ESR)，快速蛋白液相色谱仪(FPLC)测定分子大小分离图谱(Size exclusion chromatography)。结果表明，对比剂Proxyl确已连接于聚合物上，伴以HPMA大分子聚合物对实体瘤的靶向特性，说明此聚合物用于MRI具有一定的可行性。     

长期使用芬太尼透皮贴剂的疗效和安全性分析

 背景：芬太尼透皮贴剂与口服吗啡控释片的止痛效果相近,近年来已被广泛用于晚期癌痛止痛治疗,但与芬太尼相关的严重不良反应事件屡有报道,其长期使用的安全性受到某些质疑。 目的：探讨长期接受芬太尼透皮贴剂治疗对罹患晚期癌痛患者的临床疗效,并分析其安全性。 方法：纳入309例晚期癌痛患者,其中男143例,女166例,年龄26-72岁,前2周使用口服缓释吗啡止痛,第3周开始改用芬太尼透皮贴剂止痛,直至第12周。采用自身前后对照方法,比较两种药物的止痛效果、使用过程中的不良反应和毒性反应及患者的接受程度。 结果与结论：患者在使用口服缓释吗啡及芬太尼透皮贴剂期间疼痛均获得良好控制。使用口服吗啡缓释片治疗后,出现的不良反应依次为便秘、恶心、疲劳和食欲减退。在转换为芬太尼透皮贴后,便秘(χ²=5.22,P=0.02)、恶心(χ²=4.38,P=0.04)症状较口服吗啡缓释片治疗明显减轻,呕吐症状虽有所减轻但差异无显著性意义  (χ²=2.7,P=0.10);有2.3%患者出现皮肤反应,更换贴片区域后好转,皮肤反应在使用后2-10周时有所减轻,一些不常见的不良反应如头痛、腹泻、呼吸困难、出汗增多等症状在增加剂量后初期出现。与口服缓释吗啡相比,91%患者偏爱或强烈偏爱芬太尼透皮贴剂止痛治疗。说明芬太尼透皮贴剂可以稳定地控制疼痛,减轻口服药物的不良反应,具有良好的患者依从性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

瘢痕疙瘩局部皮肤微循环

目的:通过瘢痕疙瘩局部皮肤与正常皮肤微循环结构的比较,了解瘢痕疙瘩局部皮肤微循环的特征。方法:选取我院病理科2006-01—2013-12手术切除瘢痕疙瘩带皮组织32例(瘢痕疙瘩组)和正常皮肤组织18例(正常皮肤组),对比两组皮肤真皮乳头层微循环结构的真皮乳头个数、乳头层总面积、真皮乳头内层微血管密度等指标。并行低氧诱导因子-1(HIF-1)及血管内皮生长因子(VEGF)的免疫组织化学检查。统计学比较两组上述指标的差异。结果:与正常皮肤组相比,瘢痕疙瘩组真皮乳头个数明显减少(P0.05),乳头层面积增大(P0.05),真皮乳头内微血管密度降低(P0.05);瘢痕疙瘩局部皮肤HIF-1表达明显减弱,其下游基因VEGF表达亦明显降低(P0.05)。结论:瘢痕疙瘩形成与局部皮肤微循环改变有关,HIF-1及下游基因VEGF表达降低可能是局部皮肤微循环改变的原因之一。     

MRI技术中T1、T2的物理学意义及临床应用

磁共振成像(magnetic resonance imaging,MRI)是利用射频(radio frequency,RF)电磁波对置于磁场中的含有自旋不为零的原子核的物质进行激发,发生核磁共振(nuclear magnetic resonance,NMR),用感应线圈采集共振信号,经计算机处理,建立的数字图像.本文介绍MRI技术中,决定图像质量的组织特性重要参数T1、T2的物理学意义及临床应用.     

ALA和HMME水凝胶栓剂的制备和体内外释药研究

目的 制备光敏剂5-氨基酮戊酸(ALA)和血卟啉单甲醚(HMME)水凝胶栓剂,评价其对直肠肿瘤组织的光敏剂递送效率.方法 将皮下移植人直肠癌细胞SW837的BALB/c小鼠随机分为水凝胶栓剂直肠局部给药组、皮肤局部给药组、瘤内注射给药组和静脉注射给药组.用荧光光谱仪测量直肠壁、皮肤和皮下肿瘤中原卟啉(PpⅨ)和HMME的浓度,荧光光谱系统测定相应的光敏剂分布情况.结果 ALA水凝胶栓剂直肠局部给药组的PpⅨ浓度分别是皮肤局部给药组的9.76倍(1 h)和5.80倍(3 h),差异均具有统计学意义(均P＜0.05).皮肤局部给药后2h,ALA在肿瘤组织内达到最大穿透深度(3～6 mm).而HMME水凝胶栓剂直肠局部给药后,直肠壁中的HMME浓度极低,且皮肤局部给药后的最大肿瘤穿透深度不足2 mm.结论 与皮肤相比,ALA更易穿透黏膜屏障,以水凝胶栓剂形式直肠局部给药有望成为ALA用于光动力疗法治疗直肠癌的一种给药方式.     

丁丙诺啡透皮贴联合PCIA在全膝关节置换术后镇痛中的应用疗效

目的 探讨丁丙诺啡透皮贴联合自控静脉镇痛泵(PCIA)用于膝关节置换术后镇痛的疗效。方法 选取因膝关节骨性关节炎行单侧人工膝关节置换术的80例患者,将其随机分为治疗组(术前1 d采用丁丙诺啡透皮贴+PCIA)和对照组(单纯应用PCIA),每组40例。观察比较2组患者术后静态和动态VAS评分、PCIA按压次数、膝关节活动度、补救镇痛药物使用量以及药物不良反应发生率。结果 治疗组在术后6 h、12 h、1 d、2 d、3 d的静态和动态VAS评分均明显低于对照组,差异有统计学意义(P 0. 05);而术后4 d、7 d、14 d 2组静态和动态VAS评分比较差异无统计学意义(P 0. 05)。治疗组在术后2 d内PCIA按压次数、术后补救镇痛药物使用量均明显少于对照组,差异有统计学意义(P 0. 05)。治疗组患者术后3 d、4 d、7 d、14 d膝关节活动度明显大于对照组,差异有统计学意义(P 0. 05); 2组患者不良反应发生率比较差异无统计学意义(P 0. 05)。结论 丁丙诺啡透皮贴联合PCIA应用于膝关节置换术后镇痛是一种安全有效的镇痛方法,对术后疼痛的控制效果显著,可减少患者术后补救镇痛药物的使用,促进膝关节功能早期恢复,且不良反应少。     

胆酸盐对蟾蜍离体皮肤静息电位的作用

胆酸盐在食物脂肪代谢中超重要作用,这是大家公认的。但目前有一些研究证明,胆酸盐通过对细胞受体膜离子通道和Na—KATP酶的作用,影响细胞输运行为的进程。 为此我们以上海郊区产中华大蟾蜍离体皮肤为材料,皮肤的跨皮电位(Transepi-thelial Potential)为探针,着重研究了胆酸盐对皮肤上皮细胞透性和跨皮电位(以下简称TEP)变化的规律。所用动物雌雄兼     

TEMPO‐Labeled Viologen Dendrimers: Synthesis,Characterization, and Preliminary Distance Measurements

Viologen dendrimers (G₀* to G₂*) bearing (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) spin labels are successfully synthesized via a divergent approach. 4‐amino TEMPO is successfully grafted onto the periphery of the dendrimer moieties using Zincke reaction under dark conditions. The final products are characterized by cyclic voltammetry and the spin‐label efficiencies are characterized by electron paramagnetic resonance (EPR) measurements. Cyclic voltammetric studies show the coexistence of both viologen as well as TEMPO electroactive subunits, and evidence for the intramolecular electrocatalytic reduction of TEMPO by viologen subunit is presented. EPR measurements show moderate to good spin‐label efficiencies (72–85%), but the spin‐labeled samples are not stable in the presence of air and light. The measured spin‐label efficiency decreases with increasing dendrimer generation. Double electron resonance measurements provide interspin distances for zeroth generation G₀* dendrimers. MM⁺ calculations perform using Hyperchem show an averaged single spin distance (2.34 nm) for G₀* dendrimers and a more complex scenario of several possible interspin distances in the case of G₁* and G₂* dendrimers.     

Dimethyl sulfoxide enhances effectiveness of skin antiseptics and reduces contamination rates of blood cultures

Effective skin antisepsis is of central importance in the prevention of wound infections, colonization of medical devices, and nosocomial transmission of microorganisms. Current antiseptics have a suboptimal efficacy resulting in substantial infectious morbidity, mortality, and increased health care costs. Here, we introduce an in vitro method for antiseptic testing and a novel alcohol-based antiseptic containing 4 to 5% of the polar aprotic solvent dimethyl sulfoxide (DMSO). The DMSO-containing antiseptic resulted in a 1- to 2-log enhanced killing of Staphylococcus epidermidis and other microbes in vitro compared to the same antiseptic without DMSO. In a prospective clinical validation, blood culture contamination rates were reduced from 3.04% for 70% isopropanol-1% iodine (control antiseptic) to 1.04% for 70% isopropanol-1% iodine-5% DMSO (P < 0.01). Our results predict that improved skin antisepsis is possible using new formulations of antiseptics containing strongly polarized but nonionizing (polar aprotic) solvents.     

Liquid nitrogen storage of cultured T lymphocytes

The conditions required for storing and recovering IL-2-dependent T cell clones from liquid nitrogen were investigated. For maximum cell recovery, cultured T lymphocytes were precooled at 4 degrees C for 15 min in medium containing 10% DMSO and 20% FCS before storage in liquid nitrogen. This method allowed adequate time for DMSO to penetrate the cells before freezing.     

The effect of some environmental conditions and final-host- and parasite-related factors on the penetration ofSchistosoma mansoni cercariae into mice

Summary The capacity ofSchistosoma mansoni cercariae to penetrate mouse tail skin was studied under selected environmental exposure conditions and in relation to some parasite-and final-host-related factors. Mice were exposed to non-labelled or⁷⁵Se-methionine labelled cercariae using the tail immersion technique. The number of cercariae which penetrated of the amount of tail-bound radioactivity was used to express the host-penetrative capacity of the larvae under various experimental conditions.The minimum temperature for host-penetration was 7° C. The ability to penetrate increased significantly at 10° C and 12° C and the optimum number of cercariae which penetrated was in the range between 14° C and 36° C. At temperatures above 36° C the number of cercariae which penetrated was reduced dramatically. The skin-penetration capacity was unaltered up to a salinity level of 2.4 while at salinity levels above 2.4 the ability to penetrate gradually decreased. The host-finding capacity was reduced in distilled water and in water with high levels of turbidity. A comparison of cercarial exposure in six types of water revealed comparable skin-penetration capacity.Final-host-related factors such as strain of mice, weight, sex, exposure under anaesthesia, and fixation of the tail, in general did not influence cercarial penetration. Previous heterologous infections with the nematodeSyphacia sp. or the trematodeEchinostoma revolutum had no influence on penetration. The penetration capacity of cercariae into tails of dead mice was reduced.     

Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging

By use of a Fourier transform infrared (FTIR) spectroscopic imaging technique, we examine the dynamic optical clearing processes occurring in hyperosmotically biocompatible agents penetrating into skin tissue in vitro. The sequential collection of images in a time series provides an opportunity to assess penetration kinetics of dimethyl sulphoxide (DMSO) and glycerol beneath the surface of skin tissue over time. From 2-D IR spectroscopic images and 3-D false color diagrams, we show that glycerol takes at least 30 min to finally penetrate the layer of epidermis, while DMSO can be detected in epidermis after only 4 min of being topically applied over stratum corneum sides of porcine skin. The results demonstrate the potential of a FTIR spectroscopic imaging technique as an analytical tool for the study of dynamic optical clearing effects when the bio-tissue is impregnated by hyperosmotically biocompatible agents such as glycerol and DMSO.     

Use of glycerol as an optical clearing agent for enhancing photonic transference and detection of Salmonella typhimurium through porcine skin

The objective of this study was to evaluate glycerol (GLY) and GLY + dimethyl sulfoxide (DMSO) to increase photonic detection of transformed Salmonella typhimurium (S. typh-lux) through porcine skin. Skin was placed on 96-well plates containing S. typh-lux, imaged (5 min) using a CCD camera, and then completely immersed in PBS, GLY, DMSO, GLY+DMSO in a dose- and time-dependent manner and re-imaged (5 min). The percent of photonic emissions detected (treated or untreated skin relative to no skin controls) was used for analysis. Treatment for 4 h with 50% GLY-PBS and 50:30:20% GLY:DMSO:PBS increased photonic detection compared to untreated skin, 100% PBS, or 30:70% DMSO:PBS. Treatment with 50% GLY in the presence of 20 and 40% DMSO (v/v with PBS) increased photonic detection compared to 50% GLY alone and in the presence of 10% DMSO: 50% GLY (v/v with PBS). Data indicate that GLY and GLY+DMSO are effective optical clearing agents on porcine skin (2-3 mm thick) when treated for 4 h to increase detection of emitted photons. Clearing agents such as GLY have the potential to minimize effects of porcine skin tissue as one of the photon transmittance barriers (i.e., skin, fat, muscle, and visceral tissues) in vivo.     

The solvent dimethylsulfoxide (DMSO) does not induce aneuploidy in oocytes of Drosophila melanogaster

Both with a conventional method and with the "aneuploidy pattern method" we tested whether the solvent dimethylsulfoxide (DMSO) is able to induce aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster. DMSO was fed as a 2% solution to Drosophila females. No evidence for a mutagenic activity was obtained. This finding and the negative results reported by other authors for other types of mutation in Drosophila show that DMSO can be used as a solvent for chemical agents in mutagenicity screening in Drosophila melanogaster.     

The influence of the hair cycle on the thickness of mouse skin

The data on mouse skin thickness reported here was prompted by the need to know the true position of basal cells of the epidermis and hair follicles as these are important "cells at risk" for a variety of skin reactions including carcinogenesis following exposure to radiation. There is little reliable data in the literature and most previous reports have ignored the shrinkage of skin that occurs because of its natural elasticity. The values determined for mouse flank skin in telogen--the resting phase of the hair cycle for the different skin layers--are epidermis 10 micron, corium 250 micron, adipose layer 150 micron, and hair follicle depth 150 micron. Three days after chemical depilation which triggers the hair follicles into active cycle (anagen) the epidermis doubles in thickness, remains at this value for 7 days, and then gradually returns to telogen values by day 18. The corium and adipose layers also increase significantly to reach approximately 390 micron and approximately 260 micron, respectively, by day 10 and then return to control values from day 15 onward. The change in hair follicles depths are more dramatic with active follicle basal cells reaching approximately 450-550 micron into the adipose layer between days 7 and 15. One important finding is that chemical depilation does not affect the telogen thickness of skin-the teleogen values for the epidermis and dermis immediately prior to and immediately after depilation were similar to those 23 days later at the beginning of the next telogen phase.     

Dimethylsulfoxide (DMSO) blocks conduction in peripheral nerve C fibers: a possible mechanism of analgesia

Dimethylsulfoxide (DMSO) is readily absorbed through skin, and relieves musculoskeletal pain when applied topically to painful areas. We studied the effects of DMSO on C-type nerve fibers, which mediate pain sensation. DMSO was applied directly to exposed cat sural nerves. C fiber conduction velocity was slowed by DMSO, even in low concentrations (5–7% v/v). Higher concentrations completely blocked C fiber conduction, with a minimum blocking concentration of 9%. Onset of nerve block was almost immediate with 15% DMSO or higher concentrations. C fiber blockade may account for analgesia with DMSO.     

Cone of skin exists in rat: A “hypertrophic scarring free” animal

Cone of skin is deemed to be related to hypertrophic scarring and absent in such traditionally “hypertrophic scarring and keloid free” animals as rat. The purpose of our study is to determine whether the cone of skin exists in rat. If it was, why it was ignored, and what was the meaning of it. The depilation of left dorsum of 32 male Sprague‐Dawley rats was performed using a wax/rosin mixture. Skin samples were harvested on 0 d, 3 d, 9 d, 15 d, 21 d, 27 d, 33 d, and 39 d after depilation and stained by hematoxylin and eosin methods. Light microscopic observation of the dermis‐fat interface was studied at 25× magnification. It was observed that, “dome” like fat tissue bulged up into the dermis from 3 d to 27 d and hair follicle bulged down into the “dome” like fat tissue from 15 d to 27 d and a “cone” like structure was seen. Cone of skin exists in rat in certain stages of hair follicle cycle, which is a valuable addition to the scientific literature and might be a challenge to the relation between cone of skin and hypertrophic scarring. Anat Rec, 299:1140–1144, 2016. © 2016 Wiley Periodicals, Inc.