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A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence

Descriptive Note:

[Technical Report, Final Report]

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State University of New York

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In year one our traumahemorrhagic shock THS injury model was highly effective at causing acute respiratory distress syndromeARDS in all Control groups. However, TRB-N0224 treatment, although it lowered both plasma and bronchoalveolar lavage BALF IL-6 levels, resulted in no significant improvement in clinical outcome, which was assessed by lung function i.e lung compliance or PaO2FiO2 ratio or histopathology. We postulated that there were two problems with the study 1 the stress of the gavage was an additional trauma in an already severe THS model and 2 the THS model causes severe damage to the gut, which significantly reduced TRB-N0224 adsorption. To solve these problems we requested a one-year no-cost extension to use an intravenous formulation of TRB-N0224 that, if our postulate was correct, would solve both of our problems. The results from these experiments were encouraging but not dramatic. The IP formulation of TRB-N0224 significantly reduced the Active and Total MMP-9 in the Bronchoalveolar Fluid BALF and Plasma and Interleukin-6 in the BALF and plasma, which translated into a reduction in lung histopathology. Although these are very positive results all of the rats in the TRBN0224treatment group died before the end of the 4-hr study period. It is possible that our THS model was too severe and that if we reduced the length of HS the positive molecular signal would result in reduced mortality.

Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology

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[A, Approved For Public Release]