A Combination Drug Treatment Against Ocular Sulfur Mustard Injury

Michael C. Babin, K. M. Ricketts, M. Gazaway, R. Lee, R. Sweeney, J. Brozetti
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引用次数: 11

Abstract

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.
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联合用药治疗眼部硫芥菜损伤
眼睛被认为是对硫芥[双(2‐氯乙基)硫(SM)]最敏感的器官之一,其损伤范围从轻度结膜炎到晚期角膜疾病。即使轻微的眼受累从硫磺芥暴露可导致身体和心理上的丧失能力。在这项研究中,我们探讨了美国食品和药物管理局(FDA)批准的药物(醋酸泼尼松龙眼用混悬液、曲安奈德和头孢唑林)作为硫芥菜损伤的眼部治疗。将雌性新西兰大白兔分为SM阳性对照组(n = 8)和单一治疗组(n = 7),在SM暴露后10、20、30、60、90和120 min,每治疗组兔滴入醋酸泼尼松龙眼用混悬液2滴,对照组兔滴入生理盐水。在SM暴露后120分钟,每个处理组动物接受一次1.0 mL的亚Tenon注射剂,其中含有20 mg曲安奈德酮和50 mg头孢唑林。对照组家兔不注射。兔暴露于SM后共观察16周。连续6周和暴露后第16周,每周记录角膜厚度、角膜间质损伤、新生血管形成(NV)、眼睑切口和化脓情况。SM治疗组在第2、3、4周的角膜厚度指数值明显低于SM阳性对照组。对于角膜基质损伤、NV、眼睑切口和化脓,在第4、5和6周观察到明显的保护作用。此外,角膜基质损伤在第2周和第3周减轻,并在第2周出现切口。到第3周,所有SM阳性对照动物都发生了NV,而7只治疗动物中只有1只发生了NV。到第6周,所有阳性对照动物仍表现出NV,而7只治疗动物中有2只出现NV。这些数据表明,在SM暴露后的前2小时服用醋酸泼尼松龙混悬液,然后单次注射曲安奈德/头孢唑林联合药物,可有效治疗SM暴露引起的早期角膜损伤。
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