Targeting the PAI-1 Mechanism with a Small Peptide Increases the Efficacy of Alteplase in a Rabbit Model of Chronic Empyema.
Targeting the PAI-1 Mechanism with a Small Peptide Increases the Efficacy of Alteplase in a Rabbit Model of Chronic Empyema.
复制标题
用较小的肽靶向PAI-1机理会增加慢性脓肿模型中高度倍增酶的功效。
DOI：
10.3390/pharmaceutics15051498
复制
发表时间：
2023-05-14
期刊：
影响因子：
5.4
通讯作者：
Komissarov AA
中科院分区：
文献类型：
--
作者：
Florova G;De Vera CJ;Emerine RL;Girard RA;Azghani AO;Sarva K;Jacob J;Morris DE;Chamiso M;Idell S;Komissarov AA
The incidence of empyema is increasing and associated with a mortality rate of 20% in patients older than 65 years. Since 30% of patients with advanced empyema have contraindications to surgical treatment, novel, low-dose, pharmacological treatments are needed. A Streptococcus pneumoniae-induced rabbit model of chronic empyema recapitulates the progression, loculation, fibrotic repair, and pleural thickening of human disease. Treatment with single chain (sc) urokinase (scuPA) or tissue type (sctPA) plasminogen activators in doses 1.0–4.0 mg/kg were only partially effective in this model. Docking Site Peptide (DSP; 8.0 mg/kg), which decreased the dose of sctPA for successful fibrinolytic therapy in acute empyema model did not improve efficacy in combination with 2.0 mg/kg scuPA or sctPA. However, a two-fold increase in either sctPA or DSP (4.0 and 8.0 mg/kg or 2.0 and 16.0 mg/kg sctPA and DSP, respectively) resulted in 100% effective outcome. Thus, DSP-based Plasminogen Activator Inhibitor 1-Targeted Fibrinolytic Therapy (PAI-1-TFT) of chronic infectious pleural injury in rabbits increases the efficacy of alteplase rendering ineffective doses of sctPA effective. PAI-1-TFT represents a novel, well-tolerated treatment of empyema that is amenable to clinical introduction. The chronic empyema model recapitulates increased resistance of advanced human empyema to fibrinolytic therapy, thus allowing for studies of muti-injection treatments.
登录
查看更多内容
影响因子：
64.8
作者：
CARRELL, RW;EVANS, DL;STEIN, PE
通讯作者：
STEIN, PE
DOI：
10.1152/ajplung.00579.2016
发表时间：
2018-01-01
影响因子：
4.9
作者：
Florova, Galina;Azghani, Ali O.;Komissarov, Andrey A.
通讯作者：
Komissarov, Andrey A.
DOI：
10.1165/rcmb.2014-0168oc
发表时间：
2015-04-01
影响因子：
6.4
作者：
Florova, Galina;Azghani, Ali;Komissarov, Andrey A.
通讯作者：
Komissarov, Andrey A.
影响因子：
2.5
作者：
Federici S;Bédat B;Hayau J;Gonzalez M;Triponez F;Krueger T;Karenovics W;Perentes JY
通讯作者：
Perentes JY
影响因子：
5.6
作者：
Karandashova S;Florova G;Idell S;Komissarov AA
通讯作者：
Komissarov AA