PurposePosterior vitreous detachment (PVD) is implicated in numerous retinal pathologies. A necessary step in developing new therapies, an area of significant interest, is a quantifiable assessment of posterior vitreous adhesion (PVA) that is also clinically relevant.MethodsA 23-gauge vitrector was used at varying levels of vacuum to attempt PVD induction in a porcine eye model injected with either balanced salt solution (BSS) (control) or plasmin (2, 3, or 5 U), which can pharmacologically induce PVD.ResultsThe average minimum vacuum necessary to induce a PVD was 395 ± 28 mm Hg for BSS alone, 385 ± 58 mm Hg for 2 U of plasmin, 265 ± 53 mm Hg for 3 U of plasmin, and 145 ± 28 mm Hg for 5 U of plasmin. We demonstrated a dose-dependent response curve with increasing amounts of plasmin, leading to a statistically significantly lower minimum vacuum necessary to induce a PVD except between BSS and 2 U plasmin.ConclusionsA dose-dependent relationship between plasmin concentration and PVD was demonstrated. We believe that this model offers significant benefits over prior work as it minimizes confounding manipulations and offers a quantitative assessment that is translatable to in vivo surgical models.Translational RelevanceThis is the first methodology to quantitatively assess the degree of vitreous adhesion in situ.

2024-07-01·Stroke

Lack of Interactions Between Alteplase/Tenecteplase and the Adenosine A1R/A3R Agonist AST-004

Article

作者: Korinek, William S ; Lechleiter, James D ; Liston, Theodore E ; Holstein, Deborah ; Solt, Derek ; Lozano, Damian

BACKGROUND:AST-004, a small molecule agonist of the adenosine A1 and A3 receptors, is a potential cerebroprotectant for patients with acute stroke and is currently in clinical trials. Drug-drug interactions are critically important to assess in the context of acute stroke care. Lytic therapy with tPA (tissue-type plasminogen activator)–induced plasmin formation (alteplase) is the only available pharmacotherapy for acute stroke. Consequently, it is imperative to evaluate potential interactions between AST-004 and tPAs such as alteplase and tenecteplase.METHODS:The interactions between AST-004 and tPAs were evaluated in 3 ways in preparation for AST-004 phase II trials. First, the metabolic stability of AST-004 was determined in the presence of alteplase and plasmin. Second, the potential for AST-004 to influence the thrombolytic efficacy of alteplase and tenecteplase was evaluated with an in vitro assay system utilizing a fluorogenic substrate of plasmin. Finally, the potential for AST-004 to influence the thrombolytic efficacy of alteplase was also determined with an in vitro thrombolysis assay of human blood thrombi.RESULTS:Neither alteplase nor plasmin affected the stability of AST-004 in vitro. In 2 different in vitro systems, AST-004 had no effect on the ability of alteplase or tenecteplase to generate plasmin, and AST-004 had no effect on the thrombolytic efficacy of alteplase to lyse blood clots in human blood.CONCLUSIONS:These studies indicate that there will be no interactions between AST-004 and tPAs such as alteplase or tenecteplase in patients with stroke undergoing thrombolytic therapy.

2023-05-01·Experimental Eye Research

A novel recombinant human microplasminogen induced complete posterior vitreous detachment without morphological change of retina in juvenile rabbits

Article

作者: Liu, Rong-zeng ; Zhao, Bing ; Wang, Tian-fa ; Hu, Ya-jun ; Yu, Jin-chao ; Zhang, Yan-ling ; Yu, Min ; Wang, Yu-xiong

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhμPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhμPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh μPlg could be activated by t-PA to generate microplasmin (μPlm). Moreover, rhμPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 μg rhμPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhμPlg has a potential value in the treatment of vitreoretinopathy.

100 项与纤溶酶相关的药物交易

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适应症	国家/地区	公司	日期
脑梗塞	中国	吉林津升制药有限公司	2003-05-22
血栓闭塞性血管炎	中国	北京赛升药业股份有限公司	1999-01-01
血栓性脑梗塞	中国	北京赛升药业股份有限公司	1999-01-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


PA022 (AAO2008)	N/A	糖尿病性黄斑水肿	-	Intravitreal Plasmin	(鹹衊簾糧選蓋餘顧鏇衊) = 壓鬱積夢網夢衊糧襯繭膚壓憲餘鬱鹹簾醖鑰醖 (衊糧餘鑰築齋鬱蓋蓋壓, 0.24) 更多	积极	2008-11-09
ARVO2002	N/A	-	16	Plasmin 1U combined with hyaluronidase 20U	願餘遞範構遞鏇糧鑰齋(齋築築廠膚夢遞網遞廠) = 壓廠網艱艱顧壓憲積膚範膚築遞廠蓋範艱鑰餘 (膚襯積衊淵構選繭顧壓 )	积极	2002-12-01
				Plasmin 1U alone	願餘遞範構遞鏇糧鑰齋(齋築築廠膚夢遞網遞廠) = 遞壓簾築獵壓遞鹽顧選範膚築遞廠蓋範艱鑰餘 (膚襯積衊淵構選繭顧壓 )
AAO2000	N/A	糖尿病性视网膜病变	-	Autologous Plasmin Enzyme (APE)	(壓構觸淵顧齋夢壓鹹鏇) = 餘膚製觸襯壓艱鏇網簾鹹獵餘製淵齋鏇糧鏇鏇 (鏇襯簾選夢獵衊餘選選 )	积极	2000-10-23
				Autologous Plasmin Enzyme	(壓構觸淵顧齋夢壓鹹鏇) = 積齋憲鬱餘夢築鹽憲憲鹹獵餘製淵齋鏇糧鏇鏇 (鏇襯簾選夢獵衊餘選選 )