Bull's eye missed by the magic bullet: preclinical investigations, publication bias, and promising new interventions.

摘要

Severe sepsis continues to have high incidence, mortality, and associated costs not only in the United States (1) but also in Europe (2) and Scandinavia (3). Thereby,from the clinical perspective, the efforts to discover safe and effective new treatments for severe sepsis and systemic inflammatory reaction are tremendously appreciated.Ethyl pyruvate (EP), with most-promising preclinical reports, has lined up to be one of the latest "magic bullets" in treatment of sepsis, inflammatory reaction, or ischemia and reperfusion. A simple esterification of pyruvate stabilizes the molecule in electrolyte solutions. Furthermore, with the molecular modification, the supposedly toxic endproduct of sodium pyruvate (parapyruvic acid) thus poses no further risk as a metabolic inhibitor. In addition, EP, being more lipophilic (than sodium pyruvate), enters the cells, or even mitochondria, more readily (4, 5). Indeed, as a number of preclinical trials showed, EP has potential for improving survival by reasonable mechanisms as characterized by different research groups. (See Fink (6) for review.).