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PGC-1alpha (peroxisome proliferator-activated receptor [PPARgamma] coactivator-1alpha) activates PPARalpha and mitochondrial transcription factor A (Tfam), which regulate proteins, fatty acid and ATP metabolism (i.e., FAT/CD36, MCAD, and COX I). Recently we found that the salutary effects of estradiol (E2) on cardiac function following trauma-hemorrhage(More)
OBJECTIVE To determine whether the combined administration of adrenomedullin and adrenomedullin binding protein-1 (AM/AMBP-1) has any modulatory effects on the cardiovascular response during the progression of sepsis. SUMMARY BACKGROUND DATA Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Recent(More)
OBJECTIVE Our recent study indicates that administration of adrenomedullin (AM) in combination with AM-binding protein-1 (AMBP-1) before sepsis (i.e., pretreatment) maintains cardiovascular stability and reduces the mortality rate. The aim of the present study was to determine whether administration of AM/AMBP-1 after the onset of sepsis (posttreatment) has(More)
Stress-induced hyperglycemia is necessary for maximal rates of survival after severe hemorrhage; however, the responsible mechanisms are not clear. One consequence of hyperglycemia is an increase in hexosamine biosynthesis, which leads to increases in levels of O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) on nuclear and cytoplasmic proteins. This(More)
Hemeoxygenase (HO)-1 induction following adverse circulatory conditions is known to be protective, and precastrated males have less intestinal damage than sham-operated males following trauma-hemorrhage (T-H). Previous studies have also shown that administration of flutamide up-regulated estrogen receptor (ER) expression in males following T-H. We(More)
Trauma-hemorrhage (T-H) causes hypoxia and organ dysfunction. Mitochondrial dysfunction is a major factor for cellular injury due to T-H. Aging also has been known to cause progressive mitochondrial dysfunction. In order to study the effect of aging on T-H-induced mitochondrial dysfunction, we recently developed a rodent mitochondrial genechip with(More)
OBJECTIVE Although hepatic cytochrome P-450 protein concentrations are altered following endotoxin shock, changes in P-450 isoforms in sepsis have not been fully investigated. The aim of this study was to determine whether the major P-450 isoform in rat liver (i.e., CYP1A2) is down-regulated during the progression of sepsis and, if so, whether reduction of(More)
Although the mouse has been extensively used to study immune consequences of sepsis and other genetic anomalies, the changes in various cardiovascular parameters such as cardiac output, organ perfusion, as well as oxygen utilization have not been characterized in this species during sepsis. To determine this, polymicrobial sepsis was induced in male adult(More)
A prolonged depression of cardiovascular function occurs in males after trauma-hemorrhagic shock (T-H). Although a correlation between increased circulatory IL-6 levels and poor outcome has been reported after T-H, it remains unknown whether T-H increases IL-6 levels locally in cardiomyocytes and whether there is a correlation between altered cardiac(More)
We have previously demonstrated that in a rat model of trauma-hemorrhage (T-H), glucosamine administration during resuscitation improved cardiac function, reduced circulating levels of inflammatory cytokines, and increased tissue levels of O-linked N-acetylglucosamine (O-GlcNAc) on proteins. The mechanism(s) by which glucosamine mediated its protective(More)