Mortality from sepsis and acute lung injury (ALI) remains unacceptably high despite recent advances in critical care including early goal-directed therapy and lung protective ventilator strategies. The overall goal of this Translational Program Project in Lung Diseases is to discover novel mechanisms and identify innovative molecular targets by which carbon monoxide (CO) gas exerts cytoprotection during sepsis and ALI. In order to achieve this Program Project's goals. Core D, the CO Delivery in Sepsis and ALI Core, will provide the expertise, resources, facilities, and quality control (QC) services for the delivery of CO in a standardized fashion in Projects 1-4. As the CO Delivery Core, we will provide coordinated resources and expertise to the Project investigators for the centralized delivery of CO in cell culture systems, preclinical animal models, and in subjects with sepsis-induced ALI in a Phase I Biosafety Clinical Trial. Specifically, Core D will develop and implement standardized protocols to administer CO and monitor CO concentrations in cell culture systems, animal models of sepsis and ALI, and in mechanically ventilated subjects with sepsis-induced ALI as a central service for Project investigators. A highly innovative feature of this proposal is the development and validation of a CO delivery protocol for critically ill patients requiring mechanical ventilation. Core D will also be responsible for standardizing the animal models of sepsis and ALI employed by investigators in all four Projects. By using the same highly trained and experienced personnel as well as standardized Good Laboratory Practice (GLP)-like protocols, we will ensure that all CO exposures are performed under uniform conditions, that CO exposures are strictly regulated, and that CO levels and animals are properly monitored throughout experiments. In our Phase I Biosafety Clinical Trial, Core D will provide the expertise required to standardize the CO administration protocol, ensure continuous real-time monitoring of CO concentrations in the inspiratory and expiratory gases, and assess carboxyhemoglobin (COHb) levels in subjects to assure high quality safety and monitoring standards. By consolidating and leveraging highly skilled and experienced staff, facilifies, and equipment in Core D and making them available to all Projects, we will greatly reduce the cost of producing high-quality data. This approach will facilitate and promote synergisfic interactions between investigators in the different Projects. Therefore, Core D, the CO Delivery in Sepsis and ALI Core, will play an integral role in the successful completion of the work proposed in this Program Project.
Core D will provide all four Projects with standardized methods, facilities, and personnel for delivery of carbon monoxide (CO) gas to cells in culture, to animals during experiments, and to people as part of a clinical trial. By centralizing these services, Core D will coordinate and facilitate interactions between the investigators of the four different Projects.
|Beitler, Jeremy R; Schoenfeld, David A; Thompson, B Taylor (2014) Preventing ARDS: progress, promise, and pitfalls. Chest 146:1102-13|
|Siempos, Ilias I; Lam, Hilaire C; Ding, Yan et al. (2014) Cecal ligation and puncture-induced sepsis as a model to study autophagy in mice. J Vis Exp :e51066|
|Suliman, Hagir B; Piantadosi, Claude A (2014) Mitochondrial biogenesis: regulation by endogenous gases during inflammation and organ stress. Curr Pharm Des 20:5653-62|
|Agrawal, Pankaj B; Pierson, Christopher R; Joshi, Mugdha et al. (2014) SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet 95:218-26|
|Nakahira, Kiichi; Cloonan, Suzanne M; Mizumura, Kenji et al. (2014) Autophagy: a crucial moderator of redox balance, inflammation, and apoptosis in lung disease. Antioxid Redox Signal 20:474-94|
|Schumacker, Paul T; Gillespie, Mark N; Nakahira, Kiichi et al. (2014) Mitochondria in lung biology and pathology: more than just a powerhouse. Am J Physiol Lung Cell Mol Physiol 306:L962-74|
|Colas, Romain A; Shinohara, Masakazu; Dalli, Jesmond et al. (2014) Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol 307:C39-54|
|Shinohara, Masakazu; Kibi, Megumi; Riley, Ian R et al. (2014) Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1. Am J Physiol Lung Cell Mol Physiol 307:L746-57|
|Ryter, Stefan W; Koo, Ja Kun; Choi, Augustine M K (2014) Molecular regulation of autophagy and its implications for metabolic diseases. Curr Opin Clin Nutr Metab Care 17:329-37|
|Kraft, Bryan D; Piantadosi, Claude A; Benjamin, Ashlee M et al. (2014) Development of a novel preclinical model of pneumococcal pneumonia in nonhuman primates. Am J Respir Cell Mol Biol 50:995-1004|
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