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辅助性组织型纤溶酶原激活剂(tPA)和脱氧核糖核酸酶(DNase)用于腹膜透析相关性腹膜炎的临床前评估。

Preclinical assessment of adjunctive tPA and DNase for peritoneal dialysis associated peritonitis.

作者信息

McGuire Amanda L, Bennett Sophia C, Lansley Sally M, Popowicz Natalia D, Varano della Vergiliana Julius F, Wong Daniel, Lee Y C Gary, Chakera Aron

机构信息

Translational Renal Research Group, Harry Perkins Institute of Medical Research, Perth, Australia; University of Western Australia, School of Medicine and Pharmacology, Perth, Australia.

Pleural Disease Unit, Lung Institute of Western Australia, Centre for Asthma, Allergy Respiratory Research, School of Medicine and Pharmacology, Perth, Australia.

出版信息

PLoS One. 2015 Mar 5;10(3):e0119238. doi: 10.1371/journal.pone.0119238. eCollection 2015.

Abstract

A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.

摘要

腹膜透析的一个主要并发症是腹膜炎的发生,这与技术失败和患者生存率降低有关。感染引发的炎症反应会导致腹膜腔内形成富含纤维蛋白和碎屑的环境,这可能会降低抗菌药物的疗效,并易引发感染的复发或再发。因此,增强对抗菌药物反应的策略有可能改善患者的预后。本研究提供了临床前数据,描述了组织型纤溶酶原激活剂(tPA)和脱氧核糖核酸酶(DNase)与用于治疗腹膜透析相关性腹膜炎的抗菌药物联合使用时的兼容性。tPA和DNase在标准透析液以及抗菌药物存在的情况下是稳定的,并且在小鼠模型中腹腔内给药时是安全的,没有局部或全身毒性的证据。辅助使用tPA和DNase可能在腹膜透析相关性腹膜炎患者的管理中发挥作用。

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