光对大鼠视网膜光化学损伤的动态观察

目的　观察可见光对大鼠视网膜光化学损伤动态变化过程。方法　对 Wistar大鼠进行持续 2 4h光照射 ,分别于光照前、光照后 12 h、3d、7d进行视网膜光镜形态学观察 ,外核层厚度及闪烁光视网膜电图(FERG)检测。结果　光照前视网膜形态正常 ,结构层次清晰 ,内外节排列整齐 ,色素上皮排列规则 ,光照后 12 h,视网膜外核层变薄 ,其厚度减少了 2 4.5 % ,内外节排列紊乱 ,光照后 3d,外核层更薄 ,其厚度减少了 5 3.1% ,光照后 7d,外核层进一步变薄 ,其厚度减少 6 3.3%。EFRG的 a波、b波振幅于光照后 12 h、3d、7d持续下降。结论　光对视网膜的损伤形态计量指标与视网膜功能变化呈正相关     

蓝光致棕色挪威大鼠慢性视网膜光损伤的实验研究

目的 通过构建蓝光致棕色挪威（Brown Norway,BN）大鼠慢性视网膜光损伤的模型，探究大鼠光感受器细胞及视网膜色素上皮细胞（RPEc）损伤的特点及可能损伤机制。方法 根据随机数字表法将大鼠分组为光照0 d（正常对照组）和光照1、3、7及14 d组，每组8只。正常对照组不进行光照；余各组每日暴露于光照强度为（1 000±100）Lux的LED蓝光光源环境中3 h，连续1、3、7及14 d，观察大鼠的行为活动；视网膜电流图（ERG）记录最大混合反应的a、b波振幅和潜伏期；进行眼底照相；HE染色观察视网膜组织；酶联免疫吸附试验（ELISA）检测大鼠视网膜组织的活性氧（ROS）含量。结果 与正常对照组比较，光照3 d组对光声刺激的反应迟钝，光照7 d及14 d组精神较萎靡，行动稍迟缓，对光声刺激反应更为迟钝；光照3 d组偶见视网膜出血点，RPEc层基底部色素颗粒增多，外核层可见轻度细胞核固缩；光照7 d组视网膜上见散在点状出血点、黄白色点状颗粒物，视网膜静脉迂曲扩张；光照14 d组视网膜上见大量黄白色点状渗出，视网膜动脉呈铜丝样甚至银丝样外观，视网膜静脉迂曲扩张；光照7、14 d组视网...     

即早基因在N-甲基-N-亚硝脲诱导SD大鼠视网膜变性中的表达

目的研究N-甲基-N-亚硝脲(N-m ethyl-N-n itrosourea,MNU)对SD大鼠视网膜毒性的分子机制。方法于♀SD大鼠出生后50 d,一次腹腔注射(ip)MNU 60 mg.kg-1。在MNU处理不同时间后,处死大鼠,取眼球。进行组织学检查;TUNEL试剂盒检测光感受器细胞凋亡;RT-PCR法检测基因c-jun和c-fos的表达。结果MNU作用24 h后,视网膜光感受器外节部定向紊乱;7 d后,外颗粒层和光感受层几乎完全消失。MNU作用12 h后,光感受器细胞开始发生凋亡,24 h达高峰。MNU可时间依赖性地上调即早基因的表达。结论MNU对视网膜的毒性作用是通过增加基因c-jun和c-fos的表达,从而诱导光感受器细胞发生凋亡。     

益气明目口服液对光化学损伤大鼠视网膜保护作用的研究

目的:研究益气明目口服液对光化学损伤大鼠视网膜的保护作用。方法:48只SD大鼠随机分为阴性对照组、模型组及益气明目口服液高、低剂量组。除阴性对照组外,各组大鼠接受(1 900±106.9)Lux绿色荧光灯24h持续光照射,制备大鼠视网膜光化学损伤模型。益气明目口服液高、低剂量组分别于光照前7d灌胃给药30、15mL.kg-1.d-1;阴性对照组及模型组予以等量生理盐水灌胃。光照后6h、6d、14d检测视网膜组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,并进行视网膜透视电子显微镜和光学显微镜的组织学观察。结果:光化学损伤后6d及14d,益气明目口服液高剂量组视网膜中SOD的活性显著高于模型组(P<0.05),益气明目口服液高、低剂量组视网膜中MDA的含量均显著低于模型组(P<0.05);通过视网膜透视电子显微镜和光学显微镜的组织学观察,益气明目口服液高、低剂量组的病理组织学损害较模型组显著减轻。结论:益气明目口服液对视网膜光化学损伤有显著的保护作用。     

红花黄色素滴眼液对大鼠光化学损伤后视网膜变性的保护作用

目的 探讨红花黄色素是否对大鼠光化学损伤引起的视网膜变性有保护作用.方法 选取48只健康SD大鼠并将其随机分为三组：A组为正常对照组、B组为光化学损伤模型组、C组为红花黄色素给药组.B组和C组大鼠在（1900.0±106.9） Lux绿色荧光灯下持续光照射24 h,建立大鼠视网膜光化学损伤模型,分别滴用溶剂对照液、红花黄色素滴眼液.在造模后第6小时、6天、14天,测定视网膜组织中的超氧化物歧化酶（SOD）活性以及丙二醛（MDA）含量,同时,造模后每隔7天对视网膜进行光学显微镜和透视电子显微镜的组织学观察.结果 光照后6d、14 d,红花黄色素滴眼液组视网膜中SOD活性高于模型对照组（P＜0.05）,MDA含量低于模型对照组（P＜0.05）;并且光照后7d,三组视网膜形态结构差异均有统计学意义（（P＜0.05））,红花黄色素滴眼液组病理组织学损害较模型组明显减轻.结论 红花黄色素滴眼液对视网膜光化学损伤有明显的保护作用.     

野菊花滴眼液对大鼠实验性视网膜光损伤的疗效观察

目的探讨润眼明目中药野菊花滴眼液治疗光化学损伤诱导的视网膜变性大鼠的疗效观察,为防治视网膜变性提供一种有价值的现代化中药。方法SD大鼠90只随机分为空白对照组、模型对照组、野菊花滴眼液组。视网膜变性动物模型采用光化学损伤模型,分别滴用溶剂对照液、野菊花滴眼液。光照后7、14、28d观察视网膜电图的改变,并进行视网膜透视电子显微镜和光学显微镜的组织学观察。结果正常对照组大鼠不同时间点视网膜电图（ERG）a波及b波的振幅差异无统计学意义（P〉0．05）;模型对照组在光照后ERGa波及b波的振幅均呈持续性、进行性下降,治疗后14d,野菊花滴眼液对实验大鼠光损伤后ERGa波及b波振幅的降低均有保护作用,通过视网膜透视电子显微镜和光学显微镜的组织学观察显示,野菊花滴眼液组的病理组织学损害较光损伤模型组明显减轻。结论野菊花滴眼液可明显减轻光化学损伤诱导的大鼠视网膜变性,促进光化学损伤诱导的大鼠视网膜光感受器细胞损伤的功能恢复。     

黄斑明目颗粒对N-甲基-N-亚硝脲诱导大鼠视网膜光感受器细胞损伤的防护作用

目的 探讨黄斑明目颗粒对N-甲基-N-亚硝脲(MNU)诱导的大鼠视网膜光感受器细胞变性动物模型的防护作用,为防治视网膜变性提供一种有价值的现代化中药.方法 将鼠龄为43 d的雌性SD大鼠33只随机分为3组.黄斑明目颗粒组(n=10)以黄斑明目颗粒溶解后灌胃,正常对照组(n=10)和模型对照组(n=10)以等量蒸馏水灌胃,bid,连续7 d.给药7 d后,黄斑明目颗粒组和模型对照组大鼠予MNU 40 mg/kg,ip;正常对照组注射等量生理盐水.观察MNU处理后12、24、48、72 h各组大鼠视网膜电图a波及b波的变化,并于MNU作用后7 d处死大鼠,取眼球测定视网膜全层及外核层厚度.结果 正常对照组大鼠不同时间点视网膜电图(ERG)a波及b波的振幅差异无统计学意义(P＞0.05);模型对照组在MNU处理后ERG a波及b波的振幅均呈持续性、进行性下降,黄斑明目颗粒可明显抑制ERG a波及b波振幅的降低(P＜0.05).眼病理结果,黄斑明目颗粒组与模型对照组比较,MNU诱导的大鼠视网膜光感受器细胞损伤明显减轻(P＜0.05).结论 黄斑明目颗粒可减轻MNU对大鼠视网膜光感受器细胞的损伤程度,促进MNU诱导的大鼠视网膜光感受器细胞损伤的功能恢复.     

地塞米松对视网膜光损伤防护作用的实验研究

目的 研究地塞米松（Dex）对手术显微镜光源致大鼠视网膜损伤的防护作用及其抗凋亡作用的机理。方法 采用手术显微镜光源（散射白光）照射成年Wistar大鼠眼，建立光损伤动物模型。光照前1h腹腔内给予Dex（52mg／kg），光照时间为60min，于光照后0，2，6，12，24，48h处死大鼠．取出被照射眼球。以TUNEL法进行原位凋亡检测，免疫组织化学方法检测C—FOS的表达。结果 光照后大鼠视网膜的外核层（ONL）和内核层（INL）均可见TUNEL染色阳性细胞，其阳性染色与时间变化有关，光照后0-24h逐渐升高，48h可观察到下降；试验组（Dex4-光照）与对照组（生理盐水＋光照）相比较，对应的时间点各细胞层凋亡指数具有显著性差异；免疫组织化学染色显示，C—FOS在视网膜INL细胞中有表达，其表达与时间变化有关，Dex对INL细胞中C—FOS的表达有明显下调作用。结论 Dex能减少视网膜上细胞的凋亡，对光致视网膜损伤有保护作用，而Dex抗凋亡作用可能与下调C—FOS表达有关。     

大鼠玻璃体腔内注射氯化钴后视网膜的病理学观察

目的 给予大鼠玻璃体腔注射氯化钴溶液,观察其视网膜病理学变化.方法 将20只SD大鼠随机分为正常对照组、观察1周组、观察2周组、观察3周组,正常对照组不给予任何处理,正常饲养,其他各组给予左眼玻璃体腔注射4μl 3mmol/L的氯化钴,右眼注射4μl的0.01M磷酸盐缓冲溶液(PBS)作为实验对照.分别于玻璃体腔注射后第1、2、3周末处死大鼠摘除眼球,利用常规病理切片HE染色及透射电镜观察视网膜组织损伤情况.结果 常规病理切片显示:玻璃体腔注射氯化钴的大鼠视网膜组织随着时间的延长,视网膜水肿,RGCs层变薄,RGCs细胞数量减少,细胞核皱缩,细胞排列紊乱;内、外核层细胞数量减少,细胞核皱缩;视锥、视杆细胞排列疏松、紊乱.透射电镜结果显示:视网膜内界膜水肿逐渐加重,外节膜盘结构逐渐紊乱,线粒体损伤严重.结论 大鼠玻璃体腔注射氯化钴可以造成视网膜组织的缺氧性损伤.     

不同光量子数蓝光对豚鼠视网膜超微结构的影响

目的:研究不同光量子数蓝光长期间断照射对豚鼠视网膜组织超微结构的影响。方法:将42只普通级英国短毛三色健康雄性豚鼠随即分成A、B、C、D、E、F组,给予不同强度的蓝光照射,光量子数分别为3.0、4.5、6.0、7.5、9.0、12.0μmol·m^-2·s^-1,20周后对各组豚鼠视网膜组织损伤情况进行电镜检测。结果:各组豚鼠视网膜组织均出现一定程度的超微结构改变,光感受器细胞变性、凋亡速度加快,如萎缩、变薄、溶解、断裂、凝固、空泡增多等,但并未发现某一组的损伤明显重于其他组的情况,也未观察到对蓝光吸收最强的视网膜光感受器细胞损伤程度明显高于其他层面的情况。结论:光量子数低于12μmol·m^-2·s^-1的蓝光长期间断照射对豚鼠的眼部发育是相对安全的,所造成的轻微损伤可能与幼龄豚鼠视网膜发育不健全有关。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.