透皮给药研究的新进展

透皮给药安全可控，是无创给药的新途径，有着广阔的市场前景。现有的透皮药物限于小分子和低浓度，角质层屏障使大多数药物难以通过或难以达到有效浓度和有效速率。透皮给药的关键在于促进药物渗透，使药物透皮吸收进毛细血管。促渗手段有：使用化学促渗剂；对药物进行化学修饰制成前体药物；使用物理方法；将药物载入载体。这些方法的原理大致分为三种：改变角质层结构；外力驱动药物；将药物进行修饰或包裹。简要地介绍了增强药物透皮的物理方法和载体方法研究的新进展。     

Anatomic and physiologic development of the photoreceptor of the kitten

Summary The postnatal development of the photoreceptor of the cat was studied using physiological and anatomical methods. The late receptor potential (LRP) was recorded in vitro and the threshold and maximum amplitude determined. The same specimens used in the electrophysiological studies were then prepared for microscopy, and rod cell outer and inner segment length and diameter, photoreceptor density, and inter-receptor distance were determined. A small LRP was first recorded at 9–10 days, but only at very high stimulus intensities. Thereafter, there was a rapid decrease in the threshold and an increase in the amplitude of the LRP. The threshold reached adult values at 17–18 days, while the amplitude of the LRP was adultlike at 23–26 days. Of the anatomical parameters examined, inter-receptor spacing and rod cell diameters seem to be most clearly associated, respectively, with the attainment of adult LRP threshold and amplitude. Outer segment length was adult-like at 35–43 days of age and thus postdated physiological maturity of the photoreceptor. These observations suggest that the surface area of the rod cell outer segment tips is more critical in the development of the adult LRP than is the number of discs in the outer segment. In addition, changes over time in the mean diameter and length of rod cell inner segments follows the pattern of ontogenetic changes in LRP amplitude. These findings imply a close relationship during ontogeny between the metabolic functions of the inner segment and phototransduction at the outer segment disc.This study was supported by the Florida Lions Eye Bank (GST) and by a grant, 2-RO1-EY00376-08, from the National Eye Institute, National Institutes of Health, Bethesda, Maryland (DIH)Andrew Labbie and Joseph Muroff were participants in the Community Laboratory Research Programm sponsored by the Dade County Public School System, Miami, Florida     

胰腺电子计算机体层扫描增强扫描参数研究

目的 :研究不同扫描参数对胰腺电子计算机体层扫描 (CT)增强的影响 ,以得出合适的扫描方案。方法 :1预试验 10例 ,按 1.5 ml/ kg、3ml/ s注射造影剂 (Omnipaque 30 0 mg I/ m l)行胰腺薄层三期扫描 ,动脉期、胰腺期及门脉期的延迟时间各为 18s、40 s、70 s,分别测量平均胰腺 CT增强值并作比较。2将 40例患者按不同剂量和注射速度随机分成 4组 , 组 (1.5 ml/ kg、3.0ml/ s) , 组 (1.5 ml/ kg、2 .5 m l/ s) , 组 (1.0 ml/ kg、3.0 m l/ s) , 组 (1.0 ml/ kg、2 .5 ml/ s)每组各 10例 ,分别行胰腺期、门脉期扫描 ,分别测量平均胰腺 CT增强值并作比较。结果 :预试验中发现平均胰腺 CT增强值 ,胰腺期 [(6 9.5 6± 10 .6 ) Hu]比动脉期[(2 4.81± 14.98) Hu]高 (P<0 .0 5 ) ,胰腺期 [(6 9.5 6± 10 .6 ) Hu]比门脉期 [(5 4.38± 10 .34 ) Hu]高 (P<0 .0 5 )。40例对照研究中 ,胰腺期平均胰腺 CT增强值 : 组为 (71.0 5± 9.6 4) Hu, 组为 (6 2 .2 7± 12 .2 9) Hu, 组为 (42 .3± 11.75 ) Hu, 组为(44 .16± 11.2 7) Hu、 组与 组相比 (P<0 .0 5 )、 组与 组相比 (P<0 .0 5 )。 组与 组、 组与 组相比无明显差异。结论 :平均胰腺实质增强胰腺期比动脉期、门脉期好 ,以 1.5 ml/ kg剂量 ,2 .5～ 3.0 m l/ s     

49例造影剂副反应及急救体会

讨论了影像造影剂使用过程中副反应的发生率、发生原因、急救方法和预防措施。     

《午梦堂集》的文学成就

晚明时期 ,在吴江地区出现了一个以叶绍袁、沈宜修及其子女为核心的文学团体 ,成就杰出。特别是女性文学 ,更令人聒目相看 ,这与叶绍袁进步的女性文学观及其妻女杰出的文学才华密不可分 ;也与吴江地区高度的文学水平密不可分     

高分辨率MR血管壁成像测量壁强化指数评估颅内动脉瘤不稳定性

目的探讨高分辨率MR(HRMR)血管壁成像(VWI)所测壁强化指数(WEI)评估颅内动脉瘤不稳定性的价值。方法回顾性分析174例未破裂颅内动脉瘤患者。以3D-DSA观察动脉瘤大小、位置、形态。基于HRMR血管壁成像主观评估是否有动脉瘤壁强化(AWE),并采用软件计算WEI。采用ELAPSS及PHASES评分评估动脉瘤生长风险及破裂风险。以Spearman相关分析观察WEI与动脉瘤生长及破裂风险的相关性。结果 174例患者共248个无症状未破裂颅内囊状动脉瘤,HRMR VWI示AWE 78个、无AWE 170个。AWE与无AWE动脉瘤大小、位置、形态、ELAPSS评分、生长风险、PHASES评分、5年破裂风险差异均有统计学意义(P均0.05)。AWE动脉瘤WEI高于无AWE动脉瘤(P0.001)。Spearman相关分析显示,WEI与动脉瘤3年、5年生长风险(r_s=0.40、0.40,P均0.01)及5年破裂风险(r_s=0.24,P0.01)均呈正相关。结论 HRMR VWI所测WEI越高,提示动脉瘤不稳定性越高。     

Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques

Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection.     

Quantification and preservation of lectin binding by isolated cardiomyocytes

During preparation of cells for experimentation a considerable amount of bound substance is lost. Our aim was to develop a protocol which retained lectin binding to an extent similar to living cells. This procedure would use fixation procedures suited for fluorescent lectin conjugates and gold-conjugates to be visualized by light- and electron microscopy, respectively. We tested glutaraldehyde and paraformaldehyde in different concentrations before and after lectin binding, different buffers and divalent cations, as additives, to determine the effects on preservation of lectin binding. Lectin binding was visualized and semiquantitatively evaluated by image analysis in the light microscope after silver enhancement of lectin-gold conjugates and by using tetramethyl rhodaminyl isothiocyanate (TRITC)-conjugated lectins. Preservation of lectin binding was best visualized with fluorescent lectin conjugates, whereas during silver enhancement procedures of gold-conjugated lectins, a considerable amount of bound lectins was lost. In general, lectin binding to living cells followed by fixation is superior to fixation before lectin binding. Unfavourable combinations of fixatives and buffers can cause a loss of more than 90% bound lectin. In our experiments with freshly isolated guinea pig cardiomyocytes, lectin binding was best when we used Na-cacodylate buffer with glutaraldehyde fixation (0.1%) after binding of lectins to the living cells.     

Caffeine and nicotine improve visual tracking by rats: a comparison with amphetamine,cocaine and apomorphine

Psychomotor stimulant drugs such as caffeine, nicotine, amphetamine and cocaine, have been shown to improve vigilance in man under conditions of fatigue. Nicotine has also been shown to improve performance in some cognitive tests in patients with Alzheimer's disease. In rodents these drugs increase activity which may confound performance enhancing effects in rodent models. However, improvements have been found in a number of tests that do not seem to be directly dependent upon an enhancement of locomotor activation. In one example, Evenden and Robbins (1985) reported consistent improvements in a visual tracking test following amphetamine. The present study was undertaken to determine whether these performance enhancing effects of amphetamine could also be obtained with cocaine and apomorphine, which both have psychomotor stimulant effects through their actions as, respectively, indirect and direct dopamine agonists, and by caffeine and nicotine, which do not have a direct dopaminergic mechanism of action. The results of the study indicate that all five drugs improved tracking performance at one or more doses. The most consistent effects were obtained with amphetamine which, like cocaine and nicotine, improved tracking at a dose which did not produce other changes in behaviour. Taking into account previous studies (Evenden and Robbins 1983, 1985), these results were interpreted as indicating that psychomotor stimulant drugs produce ageneral activation of behaviour. At all but the highest doses of such drugs, the form of behaviour that is observed depends upon the environment. The results of this study support the conclusion that in the situation where stimuli are present which exert a strong control over behaviour in the undrugged state, then the stimulated behaviour will be directed towards those, and may result in an enhancement of performance.