Effective attenuation of endotoxin-induced acute lung injury by 2,3-diacetyloxybenzoic acid in two independent animal models.

The pathology of acute lung injury (ALI) is often modeled in animal studies by the administration of lipopolysaccharide (LPS), which results in an endotoxemia with sequelae similar to that seen in acute respiratory distress syndrome (ARDS). Here we report the results of two studies designed to examine the efficacy of a novel agent, 2,3-diacetyloxybenzoic acid (2,3-DABA), in the treatment of LPS-induced ALI. In two separate animal models, 2,3-DABA was effective in significantly reducing lung microvascular permeability, a condition commonly seen in ARDS, which results in pulmonary edema and respiratory insufficiency. In each model, it is demonstrated that the mechanism by which 2,3-DABA exerts this effect occurs subsequent to the recruitment of neutrophils to the site of inflammation. Lung permeability was significantly decreased in both models by treatment with 2,3-DABA, suggesting that this agent, either alone or in combination therapy, may be useful in the treatment of ALI associated with ARDS.

Locally delivered plasmin: why should it be superior to plasminogen activators for direct thrombolysis?

With advances in the field of thrombolytic therapy, whereby clots are routinely treated locally via a catheter, traditional systemic thrombolytics such as plasminogen activators might not be the best drugs for this task. Plasmin represents a new class of thrombolytic agents that exhibit direct fibrinolytic activity, without the need for either plasminogen or a plasminogen activator. In contrast to plasminogen activators, this independence from plasminogen allows plasmin to efficiently dissolve long, retracted blood clots that are inherently deficient in plasminogen. Preclinical safety studies in rabbits demonstrate that plasmin, in contrast to tissue-type plasminogen activator, does not cause re-bleeding from preformed hemostatic plugs. These results predict that plasmin will prove to be both superior to, and safer than, plasminogen activators in the dissolution of long, retracted blood clots in humans.