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Articles 1 - 2 of 2
Full-Text Articles in Medicine and Health Sciences
Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito
Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito
Physiology Faculty Publications
Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …
Pharmacology, Pharmacokinetics, And Metabolism Of The Dna-Decoy Ayx1 For The Prevention Of Acute And Chronic Post-Surgical Pain, Julien Mamet, Scott Harris, Michael Klukinov, David C. Yeomans, Renee R. Donahue, Bradley K. Taylor, Kelly Eddinger, Tony Yaksh, Donald C. Manning
Pharmacology, Pharmacokinetics, And Metabolism Of The Dna-Decoy Ayx1 For The Prevention Of Acute And Chronic Post-Surgical Pain, Julien Mamet, Scott Harris, Michael Klukinov, David C. Yeomans, Renee R. Donahue, Bradley K. Taylor, Kelly Eddinger, Tony Yaksh, Donald C. Manning
Physiology Faculty Publications
Background: AYX1 is an unmodified DNA-decoy designed to reduce acute post-surgical pain and its chronification with a single intrathecal dose at the time of surgery. AYX1 inhibits the transcription factor early growth response protein 1, which is transiently induced at the time of injury and triggers gene regulation in the dorsal root ganglia and spinal cord that leads to long-term sensitization and pain. This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord.
Results: The effects of ascending dose-levels of AYX1 on mechanical …