Our global hypothesis is that two-way exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMED CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to (I) hemorrhagic shock, (II), transfusion (III), mechanisms of anti-inflammatory resuscitation. The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Project. I focuses on lung injury induced by the cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to eicosanoid metabolism. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and dissect its components. Project. II undertakes a detailed analysis of lipids and proteins accruing in blood products, focusing on the acute coagulopathy of trauma with the aim of minimizing mortality by proper blood resuscitation. Project. Ill examines mechanism of reducing inflammation by regulating transcription factor activation with hypertonic solution and seeks to apply inhaled hypertonic saline to reduce lung inflammation in animals and humans. To validate these ideas, the Human Core is charged with supplying specimens, gathering data, and updating the Trauma MOF database while remaining in strict regulatory compliance. A vigorous Cell, Imaging &Proteomics Core will provide each project with commonly used human cells, equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies as well and advanced MS proteomics . These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions (Denver Health Medical Center, Belle Bonfils Blood Center, University of Colorado Health Sciences Center) to promulgate Trauma Research and improve patient care.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM049222-20
Application #
8678938
Study Section
Special Emphasis Panel (ZGM1-PPBC-5 (TR))
Program Officer
Somers, Scott D
Project Start
1997-04-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
20
Fiscal Year
2014
Total Cost
$1,918,240
Indirect Cost
$620,145
Name
University of Colorado Denver
Department
Surgery
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Brown, Joshua B; Cohen, Mitchell J; Minei, Joseph P et al. (2015) Pretrauma center red blood cell transfusion is associated with reduced mortality and coagulopathy in severely injured patients with blunt trauma. Ann Surg 261:997-1005
Stahel, Philip F; Moore, Ernest E (2014) Peer review for biomedical publications: we can improve the system. BMC Med 12:179
Silliman, C C; Bercovitz, R S; Khan, S Y et al. (2014) Antibodies to the HLA-A2 antigen prime neutrophils and serve as the second event in an in vitro model of transfusion-related acute lung injury. Vox Sang 107:76-82
Chin, Theresa L; Moore, Ernest E; Moore, Hunter B et al. (2014) A principal component analysis of postinjury viscoelastic assays: clotting factor depletion versus fibrinolysis. Surgery 156:570-7
Wohlauer, M; Kobeiter, H; Desgranges, P et al. (2014) Inferior Mesenteric Artery Stenting as a Novel Treatment for Chronic Mesenteric Ischemia in Patients with an Occluded Superior Mesenteric Artery and Celiac Trunk. Eur J Vasc Endovasc Surg 27:e21-e23
Stringham, John R; Moore, Ernest E; Gamboni, Fabia et al. (2014) Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock. J Trauma Acute Care Surg 76:1214-21
Jones, Edward L; Stovall, Robert T; Jones, Teresa S et al. (2014) Intra-abdominal injury following blunt trauma becomes clinically apparent within 9 hours. J Trauma Acute Care Surg 76:1020-3
Dzieciatkowska, Monika; D'Alessandro, Angelo; Moore, Ernest E et al. (2014) Lymph is not a plasma ultrafiltrate: a proteomic analysis of injured patients. Shock 42:485-98
Gonzalez, E; Moore, E E; Moore, H B et al. (2014) Trauma-Induced Coagulopathy: An Institution's 35 Year Perspective on Practice and Research. Scand J Surg 103:89-103
Moore, Ernest E; Chin, Theresa L; Chapman, Michael C et al. (2014) Plasma first in the field for postinjury hemorrhagic shock. Shock 41 Suppl 1:35-8

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