Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy

The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (P_BRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lenstransmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the P_BRB by multiple regression analysis. The P_brb was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p > 0.3]. The P_BRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (S_irma) and (2) new vessels (S_neo): p_brb = A – B.S_IRMA – C.S_neo with P_BRB in nm/sec, A = 1.5 ± 0.5, B = 0.9 ± 0.2 and C = 1.7 ± 0.4, R² = 0.65, p < 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.     

贲门癌的显微自体荧光研究

目的:探讨贲门癌显微自体荧光图象的特征表现。方法:采用激光扫描共聚焦显微镜,以氩离子(Ar+)激光(EX=488nm)和氦氖激光(He-Ne)(EX=543nm)为激发光的双通道法,对12例贲门癌手术标本包括贲门癌组织与同体胃体组织进行自体荧光检测,并进行显微图象分析和自体荧光强度的比较。结果:癌细胞的高度增生和浸润使组织原有结构被破坏。贲门癌组织癌细胞浸润区域的平均自体荧光强度绿光为62·03,红光为18·50,而正常胃体组织平均荧光强度为:绿光168·06,红光139·79。与正常组织各层分别比较,癌组织的自体荧光强度均明显减弱,差异有统计学意义,P值均<0·01。结论:贲门癌与正常胃体组织的显微自体荧光无论在形态、颜色和分布上,还是在荧光强度上都存在巨大的差异。     

荧光素三元共聚纳米微粒的合成及其荧光性质

目的：合成苯乙烯(St)、丙烯酰胺(AAm)和丙烯酸(AA)三元共聚荧光高分子微球并对其性质进行研究．方法：采用无皂乳液聚合法合成三元共聚荧光微球．利用正交设计表L18(3^7)考察温度、搅拌速度、pH值、离子强度和反应时间对聚合物性能的影响．用透射电镜和原子力显微镜观察微球形态及其分布，并测定其粒径大小．用荧光分光光度计测定荧光性质．结果：在75℃，搅拌速度300r／min，pH7．5，0．5g NaCl，反应4h时合成的胶乳呈单分散性，稳定性高，荧光性能好，其荧光最大激发波长为551．7nm，发射波长为554．2nm．当pH值为6．0时荧光微球的荧光强度最强．荧光素缓释实验显示胶乳在4℃下比25℃更稳定．结论：荧光素三元共聚纳米微粒的荧光性质良好．     

荧光淬灭法分析奈韦拉平含量

目的建立测定奈韦拉平含量的新方法。方法采用合成的荧光试剂[Ni(phen)2PHPIP].2ClO4],在激发波长226 nm,发射波长340 nm的条件下,用荧光淬灭法测定奈韦拉平。结果在pH 6.0的磷酸盐缓冲介质中,荧光试剂的荧光淬灭程度与奈韦拉平浓度呈良好的线性关系。奈韦拉平的线性范围为5.0×10-7~1.0×10-5mol/L,检测限为1.0×10-7mol/L,相关系数0.9946,奈韦拉平回收率102%(n=5),RSD 2.57%,日内及日间RSD分别为2.64%和3.77%(n=5)。结论测定奈韦拉平含量的荧光淬灭方法具有杂质干扰少、操作简便等优点。     

三磷酸腺苷生物荧光法检测肿瘤药敏的价值

目的探讨三磷酸腺苷生物荧光法(ATP-TCA)评估肿瘤药物敏感性和指导术后化疗的价值.方法以ATP-TCA法在体外分别检测了59例5种实体瘤细胞对6种化疗药物的耐药率和敏感率.结果5-FU、MMC、DDP等6种常用化疗药物的耐药率＞75%.胃肠肿瘤的化疗药物敏感性差异无显著意义,泰素、羟基喜树碱、丝裂霉素和吡柔比星对肝癌的敏感率分别为91.7%、60.0%、50.0%和42.8%;诺维本、博莱霉素对食管癌敏感率为85.7%、42.9%.结论ATP-TCA法用于检测肿瘤化疗药物敏感性较为可靠,可作为指导实体瘤术后序贯性化疗的药物筛选手段.     

A fluorophotometric study of the effect of topical timolol on aqueous humor dynamics

A modification of the fluorophotometric method of Jones and Maurice is described and used to measure the aqueous flow coefficient. The method was used to measure the effect of topical timolol on aqueous humor dynamics in 15 human subjects. It was found that the acute decrease in intraocular pressure caused by timolol can be explained entirely by its effect on the aqueous flow. The mean aqueous flow coefficient in the timolol treated eye was found to be 0·0126 min^?1 before timolol, and 0·0067 min^?1 after timolol. A small effect on the aqueous flow coefficient of the untreated eye was also observed.     

Anti-inflammatory effects of topical ocular MAXIDEX administration to rabbits following vitrectomy or lensectomy

We conducted a series of surgical studies (n=155) to find out the possible utility of the Dutch Belted rabbits as an ocular test model. Following either vitrectomy (n=59) or lensectomy (n=96) studies using either BSS or BSS Plus, we characterized the corresponding magnitude and duration of inflammatory response of selected endpoints over a one-week period. Preoperative Dutch Belted rabbits served as controls for baseline determination (n=27). Inflammatory endpoints included clinical inflammation, blood aqueous barrier (BAB) changes measured by particle-scatter and fluorophotometry, corneal edema, and prostaglandin-E2 (PGE2). Topical ocular 0.1% dexamethasone (MAXIDEX) served as a positive treatment group. We compared the inflammatory features (treated and untreated) to determine significance. Using either irrigating solution, the endpoints (n=101) were shown increased in both models. While the clinical scores were similar following both types of surgery (ns; p=0.51), the lensectomy study caused a more marked effect on corneal edema (p=0.0004) and PGE2 production (p=0.002) compared with the vitrectomy study. After the lensectomy procedure, BSS Plus (n=52) compared with BSS (n=24) showed a significant improvement (p=0.004) of clinical score during the recovery phase. Further improvement was gained over BSS Plus (n=52) using MAXIDEX treatment. Topical MAXIDEX (lensectomy, n=20/group; vitrectomy, n=12/group) reduced clinical score (p<0.001), decreased BAB breakdown to fluorescein (p<0.01), lessened particle flare (p<0.05), inhibited aqueous PGE2 levels (p<0.001), and reduced corneal edema (p=0.01) in the lensectomy group. The use of the rabbit model offers a convenient test to identify therapeutic agents that could lessen ocular complications after these common ocular surgeries.     

Vitreous fluorescein accumulation determined by in vivo fluorophotometry and by vitreous extraction in normal and diabetic rats

Summary Vitreous fluorophotometry was performed on pigmented male rats (Piebald strain) 2 weeks after induction of diabetes by streptozotocin. In vivo fluorophotometry data were compared with measurements obtained by direct extraction of the vitreous 60 min after an intravenous injection of sodium fluorescein. In addition, the rate of fluorescein disappearance from blood plasma, plasma protein binding of fluorescein and the effect of insulin treatment of diabetic animals were investigated. Age-matched nondiabetic animals served as controls. In vivo fluorophotometric measurements showed a good correlation with fluorescein determinations after direct extraction of the vitreous. Vitreous fluorescein concentrations were similar in diabetic and normal rats and were strongly related to the dye plasma levels within each group of animals. In the diabetic rats, however, the elimination of plasma fluorescein was accelerated and the percentage of free fluorescein, as determined by ultrafiltration and equilibrium dialysis, was consistently higher (130–150% of controls). The ratios of vitreous to total or free plasma fluorescein levels were elevated in diabetic rats. Experimental data indicate that plasma concentration of free fluorescein is crucial for vitreous dye accumulation. Insulin treatment of diabetic rats markedly improved their metabolic state and normalized the plasma fluorescein elimination and the vitreous to plasma fluorescein concentration ratios. It is concluded that vitreous fluorophotometry can be adequately applied to pigmented rats, provided that plasma fluorescein elimination rate and protein binding are considered in the interpretation of the results, since both influence the vitreous fluorescein accumulation and both may be altered by disease and drug treatment.     

Effect of piroxicam on the blood-retina barrier in experimentally induced diabetes in rats

The effect of piroxicam on the blood-retina barrier was evaluated in rats with experimentally induced diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ). Diabetic rats were divided into two equal groups: those treated with piroxicam, a long-acting platelet inhibitor, and an untreated control group. Vitreous fluorophotometry (VFP) was performed both before and two weeks after induction of diabetes and piroxicam intake. Streptozocin-induced diabetes caused an alteration in the blood-retinal barrier evidenced by an increase in vitreous fluorescein concentration in diabetic rats compared with normal rats. Piroxicam intake did not lead to significant change in vitreous fluorescein concentrations. However, the examination had to be terminated at two weeks because of cataract formation. The piroxicam treated group showed less incidence of lens opacity formation (59.1% compared to 81.8% in the untreated group, p = 0.0006). Piroxicam administration appears to protect the diabetic rat eye against lens opacification.This work was supported in part by U.S. Public Health Service Grants EY02377, EY07541 and EY08137 from the National Eye Institute, National Institutes of Health, Bethesda, MD and by the Juvenile Diabetes Foundation International and Pfizer, Inc.