盐酸左氧氟沙星眼用凝胶对家兔眼刺激性试验

目的：观察家兔眼接触盐酸左氧氟沙星眼用凝胶后产生的刺激反应情况和恢复情况。方法：给家兔右眼滴用左氧氟沙星眼用凝胶，每天2次，连续7天后继续观察7天角膜、虹膜及结膜的反应情况和恢复情况。结果：家兔角膜、虹膜在各观察时间的刺激反应平均分值均为0，结膜有轻微反应，家兔眼刺激的综合平均分值在0～3．9范围内。结论：盐酸左氧氟沙星眼用凝胶对家兔眼无明显刺激反应．符合眼刺激试验要求。     

维生素C不同给药方式对早期兔角膜碱烧伤的疗效观察

目的比较结膜囊内放置维生素C药物棉片与常规点眼治疗兔角膜碱烧伤的效果。方法选取16只成年家兔制作右眼角膜碱烧伤模型并随机分为点眼组和棉片组,碱烧伤后0、12、24、36、48、60h荧光素钠染色,计算角膜上皮修复率;不同时点制作病理切片,光镜、电镜观察。结果24、36、48h棉片组角膜上皮修复率较点眼组高,差异有统计学意义(P<0.05);12h棉片组与点眼组比较,差异无统计学意义(P>0.05);60h角膜上皮均愈合。病理组织学结果显示:与点眼组比较,棉片组角膜上皮修复佳,基质层胶原纤维排列较整齐且炎症细胞浸润轻。结论结膜囊内放置维生素C药物棉片治疗角膜碱烧伤优于点眼。     

家兔口服司帕沙星后眼内组织分布及其药动学研究

目的 研究司帕沙星家兔口服后在其眼组织的分布及药动学.方法 给家兔灌服司帕沙星,不同时间点采集眼内各组织标本.以高效液相色谱法测定眼内各组织中的药物浓度,用3p97程序计算药动学参数.结果 给药后泪液、角膜、房水、虹膜-睫状体、晶状体4.0h达峰,玻璃体6.0h达峰.司帕沙星在泪液、角膜、房水、虹膜-睫状体、晶状体、玻璃体组织中cmax分别为(13.75±1.36)μg/ml、(3.25±0.32)μg/g、(2.06±0.14)μg/ml、(3.41±0.26)μg/g、(1.62±0.13)μg/g和(2.18±0.18)μg/ml;各眼组织中t1/2β分别为(8.18±0.70)、(9.94±3.90)、(5.05±0.66),(13.54±6.37)、(5.67±1.15)和(3.60±1.23)h;AUC0～t分别为(118.68±5.64)、(28.18±5.42)、(17.52±2.09)、(36.77±10.47)、(16.12±0.59)和(16.57±0.47)(μg·h)/ml.结论 司帕沙星家兔口服后在眼内各组织中分布广,浓度较高,可替代治疗眼病时肠外给药.     

家兔静注环丙沙星后血液与眼组织分布及其药代动力学研究

研究家兔静注环丙沙星 (CPL X)后血液与眼组织分布及药代动力学参数。用高效液相色谱法测定血液和眼内各组织中药物浓度。结果给药 30 min后泪液、角膜、房水、虹膜 -睫状体、晶状体和玻璃体组织内峰浓度值 (Cmax)分别为 (8.92± 2 .88)、(14 2 .84± 2 5 .0 2 )、(11.0 6± 2 .80 )、(99.32± 10 .6 0 )、(30 .2 8± 1.91)和(8.10± 1.71) μg/ ml或 μg/ g;其血液和各组织中消除半衰期 (T1 /2β)分别为 (1.2 1± 0 .2 3)、(1.4 8± 0 .97)、(1.6 6± 0 .13)、(2 .0 9± 0 .5 1)、(2 .0 1± 0 .4 4 )、(1.5 2± 0 .92 )和 (1.2 1± 0 .6 6 ) h。表明家兔静注 CPL X后能穿透到眼内各组织中。     

环丙沙星滴眼液滴眼的眼内组织分布及其药代动力学研究

对环丙沙星滴眼液滴眼后家兔眼各组织中药物浓度用高效液相色谱法进行测定。结果表明,环丙沙星滴眼液滴眼后迅速进入眼组织,其中角膜浓度最高,其次为虹膜—睫状体、房水、晶体和玻璃体。各组织中的药物消除半衰期(T_(1/2β))分别为泪液0.81h、晶体0.61h、玻璃体1.40h;峰浓度值(Cmax)分别为角膜19.43μg/g、房水1.58μg/g、虹膜—睫状体16.68μg/g、晶状体1.42μg/g、玻璃体0.96μg/ml。实验结果提示环丙沙星滴眼液滴眼后能在眼内达到较高的抗菌浓度。     

静注左氧氟沙星在兔血与眼组织中的药动学

目的:研究家兔静脉注射左旋氧氟沙星(LVFX)后在血液与眼组织中的分布以及药代动力学参数.方法:用高效液相色谱法测定给药后不同时点家兔血液和眼内各组织的药物浓度.结果:角膜、房水、虹膜-睫状体、晶状体和玻璃体内峰浓度值(Cmax)分别为(10.7±0.8)、(3.0±0.2)、(18.4±1.4)、(2.4±0.2)和(1.6±0.2)μg·g-1或mg·L-1.其血液和各组织中消除半衰期(T1/2β)分别为(3.2±0.4)、(9.2±2.9)、(9.1±1.9)、(7.7±1.1)、(6.2±1.3)和(5.5±1.0)h.结论:LVFX静脉注射后具有良好的眼内通透性,在眼组织中存留时间长,有助于维持眼内组织的有效血药浓度.     

电焊工角膜结膜改变的临床分析

目的探讨电焊工长期接触紫外线对结膜、角膜的损伤情况。方法电焊工种2人组(调查组)和其他职业组(对照组)均进行视力,结膜、角膜改变,以及角膜知觉检查。结果调查组75例视力,结膜、角膜损伤明显高于对照组。结论电焊对角膜、结膜的损害,特别是角膜的损害更为明显,且不同程度影响视力。     

缬沙坦胶囊灌胃给药后在兔眼组织的分布规律研究

目的:研究缬沙坦胶囊灌胃给药后在兔眼组织的分布规律。方法:取兔3只(6只眼),ig缬沙坦溶液,每次7.5 mg,每日2次,连用6 d。于末次给药后1 h处死兔,采集角膜、虹膜、房水、晶状体、玻璃体液、视网膜组织,采用高效液相色谱法测定各组织中缬沙坦的含量。结果:缬沙坦在视网膜、虹膜、角膜、房水、玻璃体液、晶状体中的含量依次为(4.274±1.75)、(2.233±0.72)、(0.871±0.66)、(0.713±0.49)、(0.177±0.07)、(0.083±0.06)μg/g。结论:连续多次给药后缬沙坦在兔眼内各组织中分布不均匀,以视网膜中的含量为最高,虹膜次之,晶状体、玻璃体液中的含量最低。     

碱性成纤维细胞生长因子对干眼小鼠模型眼表白细胞介素-10和白细胞介素-1β蛋白表达的影响北大核心CSCD

目的研究碱性成纤维细胞生长因子(b FGF)对干眼小鼠模型眼表白细胞介素-10(IL-10)和白细胞介素-1β(IL-1β)蛋白表达的影响。方法将30只BALB/c小鼠构建干眼小鼠模型,并将建模成功的25只小鼠分为模型组(n=8,16眼)、阳性对照组(n=8,16眼)和实验组(n=9,18眼),另选10只未给予任何处理的BALB/c小鼠作为正常组。实验组给予b FGF滴眼,每次5μL,每天3次,阳性对照组给予普拉洛芬滴眼,每次25μL,每天3次,模型组和正常组给予无菌生理盐水滴眼,连续干预5 d。观察小鼠干眼症状指标水平,用苏木精-伊红(HE)染色法观察小鼠眼球角膜组织病理变化;用过碘酸-希夫(PAS)染色法观察小鼠结膜杯状细胞数量;用酶联免疫吸附(ELISA)法检测小鼠眼表组织中IL-10和IL-1β蛋白表达。结果干预后,实验组角膜荧光素钠染色评分、角膜炎症指数、泪膜破裂时间(BUT)和泪液分泌实验(SIt)分别为(10.22±2.06)分,0.09±0.02,(4.52±0.26)s,(5.26±0.52)mm/5 min,模型组分别为(11.02±2.25)分,0.52±0.06,(2.02±0.21)s,(4.00±0.32)mm/5 min,差异均有统计学意义(均P<0.01)。实验组和阳性对照组角膜上皮细胞完整、光滑,结膜穹窿部杯状细胞数量较模型组明显增多。实验组小鼠眼表组织中IL-10和IL-1β蛋白含量分别为(573.15±22.13),(174.25±12.36)μg·g^(-1),模型组分别为(236.48±41.28),(223.51±23.48)μg·g^(-1),差异均有统计学意义(均P<0.01)。结论 b FGF对小鼠干眼模型具有一定的治疗作用,可缓解干眼小鼠临床症状,抑制眼表鳞状上皮化生,其机制可能与其能够调节干眼眼表炎症反应有关。     

家兔灌服左氧氟沙星后眼内组织分布及其药动学研究

目的:研究家兔单剂量灌服左氧氟沙星后的眼内组织分布及药动学。方法:27只家兔单剂量灌服左氧氟沙星(24mg·kg-1)后0.125、0.5、1.0、2.0、3.0、4.0、6.0、8.0、12h处死并取眼球各组织制备成匀浆,高效液相色谱法测定眼内各组织中药物浓度,3p97软件计算药动学参数。结果:给药后房水、角膜、虹膜-睫状体、玻璃体和晶体组织中cmax分别为(1.59±0.38)、(8.51±2.72)、(10.58±1.17)、(1.17±0.19)、(1.28±0.39)μg·g-1/μg·mL-1;tmax分别为(0.67±0.24)、(1.00±0.55)、(1.83±0.41)、(0.60±0.34)、(0.75±0.27)h;t1/2β分别为(2.68±0.70)、(3.87±1.24)、(5.73±1.66)、(4.44±1.53)、(4.43±1.78)h;AUC0～12h分别为(4.56±1.32)、(20.90±2.63)、(40.25±3.42)、(4.11±0.60)、(3.28±0.90)μg·h·g-1/μg·h·mL-1。药动学分布呈二室模型。结论:家兔单剂量灌服左氧氟沙星后在眼内各组织中分布较快,且有较高的药物浓度,消除较慢,维持时间较长。     

Ophthalmic Preservatives as Absorption Promoters for Ocular Drug Delivery

The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic β-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28·8 and 37·1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of β-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.     

Ocular miotic and irritative effects of aerosol and topically applied dichlorvos and propoxur insecticides on rabbit and monkey eyes

Abstract

Exposure of rabbit and monkey eyes to household aerosol insecticide sprays containing the cholinesterase inhibitors propoxur and dicahlorvos (DDVP) results in maximal pupillary constriction (pinpoint pupil) 10–30 min postexposure with complete recovery by 4 hr. Topical application of propoxur (0.1–1 %) or dichlorvos (0.2–2%) to rabbit eyes showed that the magnitude of the response is dose related but that recovery is complete by 4 hr at all doses. Ocular irritation in rabbits exposed topically to these substances consisted of mild conjunctival hyperemia, chemosis, and discharge. Exposure of monkey eyes to the aerosol products resulted in corneal epithelial erosion and corneal swelling. All ocular irritancy was entirely attributable to the effect of the 90% kerosene/10% isopropanol vehicle rather than the active ingredients. It can be predicted that accidental exposure of human eyes to household aerosol insecticides containing cholinesterase inhibitors will result in pupillary constriction by 30 min with recovery by 4 hr. Irritation of the ocular surface will consist of mild conjunctival irritation and possible corneal epithelial erosion.     

米诺环素对兔慢性高眼压视网膜功能的影响

目的研究米诺环素（minocycline）对兔慢性高眼压视网膜神经节细胞（retina／ganglia／cells,RGC）损伤的保护作用。方法成年健康色素兔30只随机分为A、B、C三组,每组各10只。A组为空白组;B组为模型组;C组为给药组。选B、C组右眼作高眼压模型,每眼抽取房水0．1ml,随后注射0．3％复方卡波姆溶液0．1ml。C组给予米诺环素（minocycline）口服给药,50mg／ks／24h,连续30d。用Schiotz眼压计测量并记录眼压,一周一次。30d时,A、B、C组右眼均行光学相干眼底断层扫描（OCT）检测视神经纤维层厚度。SPSS13．0统计学分析软件对结果进行统计学分析。结果眼压测量结果统计分析显示：B、C组眼压符合慢性高眼压造模标准,且差异无统计学意义（P〉0．05）,B、c组眼压较A组高,且差异有统计学意义（p〈0．05）。OCT所检测视神经纤维层厚度测量结果统计分析显示：视神经纤维层厚度由薄到厚B〈C〈A,差异均具有统计学意义（P〈0．05）。结论米诺环素对慢性高眼压下视网膜功能改变有保护作用。     

自体富血小板凝胶在眼表烧伤治疗中的应用

目的：观察自体富血小板凝胶治疗轻、中度眼表烧伤的疗效。方法选取该科收治的眼化学烧伤、热烧伤患者41例（54眼）为研究对象,按照数字随机法分为自体富血小板凝胶治疗组（APG组）和对照组,APG组19例（26眼）,对照组22例（28眼）。对照组采用常规局部和全身药物治疗,APG组在此基础上加用自体富血小板凝胶外用滴眼。比较两组患者平均创面的愈合时间、角膜新生血管的发生率及视力恢复情况。结果对照组6眼（21.4%）出现感染,APG组1眼（3.8%）;对照组平均愈合时间为（24.7±6.5） d,APG 组平均愈合时间为（19.1±3.5） d,APG 组平均愈合时间、感染率显著低于对照组（P〈0.05）。对照组3个月后各有1眼出现角膜斑翳和角膜云翳,6眼出现角膜新生血管;APG组未出现角膜斑翳和角膜云翳病例,2眼出现角膜新生血管。 APG组角膜新生血管发生率显著低于对照组（P〈0.05）。 APG组和对照组治疗后视力均得到不同程度的恢复,两组比较无显著差异（P〉0.05）。结论自体富血小板凝胶可缩短眼表修复时间,降低感染率和角膜新生血管发生率,不影响视力恢复,是轻、中度眼表烧伤治疗的新选择。     

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2?mg/L) vapor for 2.5, 5.0, 7.5 and 10.0?min and clinical progression of injury was observed for 28 days post-exposure (dose–response study), or exposed to same LEW dose for 2.5 and 7.5?min and clinical progression of injury was observed for up to 56 days post-exposure (time–response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6?h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1?day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22–35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.     

丹参酮对肺缺血再灌注损伤的保护作用

目的 探讨丹参酮对肺再灌注损伤的保护作用.方法 以离体兔肺模型为肺保护实验对象,以肺动脉灌洗再次肺动脉灌注为实验方法,以新西兰兔为实验动物,随机分为两组.一组用低钾右旋糖酐液行肺动脉灌洗和保存(对照组),另一组用丹参酮加LPD液组成实验组,用同样的方法灌洗和保存.保存18h后,观察病理形态并测量一氧化氮、超氧化物歧化酶及丙二醛的含量.结果 光镜下两组肺泡、支气管及毛细血管结构完整,高倍视野下对照组较实验组肺泡上皮及毛细血管上皮细胞肿胀、肥大,少部分组织可见肺泡内有红细胞渗出、间隔增宽等.实验组肺组织中一氧化氮[(2.16±2.15)μmol/g]及超氧化物歧化酶[(37.03±18.01)NU/mg]含量高于对照组[(0.68±0.33)μmol/g、(17.63±11.04)NU/mg](均P<0.05),丙二醛含量[(0.47±0.20)μmol/mg]低于对照组[(0.86±0.44)μmol/mg](P<0.05).结论 丹参酮能清除氧自由基,有较强的抗氧化性,能较明显地减轻肺的再灌注损伤.     

Conjunctival and corneal ulceration associated with nicorandil

Context/Objective: To report an association between conjunctival and corneal ulceration and nicorandil therapy for angina.

Methods: Review of the literature and spontaneous reports collected at the National Registry of Drug-Induced Ocular Side Effects (Portland, Oregon), the FDA Spontaneous Reporting System (Bethesda, Maryland) and the World Health Organization’s Uppsala Monitoring Center (Uppsala, Sweden).

Results: Thirteen case reports of adverse ocular reactions were collected. Abnormal vision (5 reports), corneal ulcer (4 reports) and conjunctival ulcer (4 reports) were associated with nicorandil. Eight subjects were male and 5 female with an average age of 75.4?±?8.3 years. The average duration of therapy to development of the ADR was 30.4 days ±3 days. Eleven case reports had positive dechallenge and the patients fully recovered. The average dose was 21.6?mg daily.

Conclusion: Using WHO classification for adverse drug reactions, the association between nicorandil and conjunctival and corneal ulceration is “possible”. The case reports indicate that, if recognized, withdrawing nicorandil will lead to resolution of the conjunctival or corneal ulceration. Advanced age and accumulation of nicotinic acid in tissues may be contributory to the risk of developing ocular ulcerations from nicorandil.     

颈内动脉系统急性脑梗死应用重组组织型纤溶酶原激活物溶栓治疗观察

目的 评价重组组织型纤溶酶原激活物(rtpA)用于颈内动脉系统急性脑梗死（6 h 内）静脉溶栓治疗的有效性与安全性。方法 选择2008年7月至2010年7月颈内动脉系统急性脑梗死患者80例,完全随机分为溶栓组和对照组,各40例。溶栓组接受rtPA 5 mg于1h内静脉推注,继以45 mg rtPA于1h内静脉滴注;溶栓后24h口服肠溶阿司匹林100 mg,1次/d。对照组应用常规改善循环、营养神经药物静脉滴注;人院后24h予肠溶阿司匹林100 mg口服,1次/d。所有患者治疗前均行头CT或MRI、凝血时间、血、尿常规及心电图检查,并记录既往史评分。治疗前后采用改良爱丁堡-斯堪的那维亚量表(MESSS)进行评定,记录溶栓前、溶栓后2、24h和3、7、14、30、90d的得分。记录2组不良反应及并发症情况。研究终点为治疗后90d。结果 溶栓组治疗后24h,3、7、14、30、90d的MESSS分值[分别为(14.43 ±11.61)、（9.88±10.44）、(9.27±9.66)、(8.27 ±9.54)、(7.79±9.13)、(5.13±6.75)分]均明显低于对照组[(24.23±6.23)、(21.37±4.12)、(21.17±3.68)、(18.53±3.55)、( 15.87±3.49)、(9.98±1.95)分],差异具有统计学意义(P＜0.05)。溶栓组发生非症状性脑出血1例,牙龈出血2例。结论 急性脑梗死6h内rtPA静脉溶栓治疗是有效、安全的。     

乌司他丁对百草枯中毒致兔肾损伤的保护作用

目的：探讨乌司他丁对百草枯中毒致兔肾损伤的保护作用。方法：30只健康新西兰白兔随机分为单纯百草枯染毒组、乌司他丁干预组、0．9％氯化钠溶液对照组,每组10只。单纯百草枯染毒组及乌司他丁干预组以35mg·kg^-1剂量一次性腹腔注射百草枯溶液;对照组注射等体积0．9％氯化钠溶液;干预组注射百草枯1h后于兔耳缘静脉缓慢注射乌司他丁100ku．kg^-1,以后每天注射1次。染毒3d后给予每只兔子行肾脏动态容积CT扫描,观察肾组织血流量（renalbloodflow,RBF）变化、肾组织病理学改变及经耳缘静脉采血2mL检测血清肌酐（Cr）。结果：与对照组和干预组相比,单纯百草枯染毒组RBF明显下降及Cr显著升高;与对照组相比,干预组RBF亦有下降、Cr亦有升高。光镜下单纯染毒组可见大量肾小球内皮细胞空泡变性、坏死等;干预组可见近端小管上皮细胞肿胀、空泡变性,肾小球内皮细胞无明显改变;对照组肾组织结构清晰。结论：乌司他丁通过改善肾脏循环以促进百草枯的排泄．产生对肾脏的保护作用。     

A Combination Drug Treatment Against Ocular Sulfur Mustard Injury

The eye is considered to be one of the most sensitive organs to sulfur mustard [bis(2‐chloroethyl) sulfide (SM)], with injuries ranging from mild conjunctivitis to advanced corneal disease. Even mild ocular involvement from sulfur mustard exposure can result in both physical and psychological incapacitation. In this study we explored the use of Food and Drug Administration (FDA) approved medications (prednisolone acetate ophthalmic suspension, triamcinolone, and cefazolin) as ocular treatments for sulfur mustard injury. Female New Zealand White rabbits were divided into a SM positive control group (n = 8) and a single treatment group (n = 7). At 10, 20, 30, 60, 90, and 120 min after SM exposure, two drops of prednisolone acetate ophthalmic suspension was administered to each treatment group rabbit while the control group received saline drops. At 120 min after SM exposure, each treatment group animal received a single 1.0 mL sub‐Tenon's injection containing 20 mg triamcinolone and 50 mg cefazolin. Control group rabbits did not receive an injection. Rabbits were observed for a total of 16 weeks after SM exposure. Corneal thickness, corneal stromal injury, neovascularization (NV), eyelid notching, and chemosis were recorded weekly for 6 consecutive weeks and on week 16 after exposure. The SM treatment group at weeks 2, 3, and 4 had a significantly lower index value for corneal thickness than the SM positive control group. For corneal stromal injury, NV, eyelid notching, and chemosis, significant evidence of a protective effect due to treatment was seen at weeks 4, 5, and 6. In addition, corneal stromal injury was reduced at weeks 2 and 3 and notching at week 2. By week 3, all SM positive control animals developed NV in contrast to 1 of 7 treatment animals. By week 6 all positive control animals still exhibited NV compared to 2 of 7 treatment animals. These data suggest that prednisolone acetate suspension dosed for the first 2 h after SM exposure followed by a single sub‐Tenon's injection of a triamcinolone/cefazolin combination is effective in treating the early stages of corneal injury from SM exposure.