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Metabolic anomalies exist in most severe injuries and chronic diseases such as cancer and AIDS. These abnormalities are often manifested as wasting syndromes leading to a severe loss of lean body mass, sometimes called cachexia. Our objective is to account quantitatively for the metabolic alterations produced by the inflammatory response to major injury or disease.
In these studies, the flow of substrates throughout the biochemical reaction network of an organ is experimentally determined under both normal and pathologic conditions. Model reaction schemes that describe the major characteristics of the metabolic reaction network are used to determine the distribution of flows of substrates. These analyses help identify the key differences between normal and pathologic conditions, give insight into the evolution of diseases, and suggest better nutritional therapies for patients with severe injuries and/or chronic diseases.
We are applying similar principles and techniques to modulate the metabolism of organs outside of the body, for example to recondition donor organs that are rejected from the donor pool because they are deemed unsuitable for transplantation. Rejected donor organs typically exhibit metabolic abnormalities, such as excessive fat content or prolonged lack of oxygen, which in principle can be overcome by perfusing these organs with appropriate solutions that restore the metabolic fluxes and promote repair processes. Our goal is that metabolically reconditioned donor organs can be returned to the donor pool, thus alleviating the shortage of donor organs for transplantation.
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