Biomedical subjects
Dominique R Garrel
Publications and source records attributed to Dominique R Garrel.
Corticosterone binding globulin regulation and thymus changes after thermal injury in mice.
Thermal injury is extremely stressful, and data characterizing the systemic endocrine stress response to this injury are sparse. The objective of this study was to measure the effects of thermal injury on mice on corticosterone (Cort) levels in relation with corticosteroid-binding globulin (CBG) and thymus cell populations. The endocrine stress response was determined by measuring total Cort, free Cort, CBG binding capacity, liver CBG mRNA, and circulating CBG levels at 1, 2, 5, and 10 days postburn. Thymus cell populations were also analyzed. After thermal injury, a rapid increase of total Cort was observed in the first 48 h. This was associated with a decrease of hepatic CBG mRNA, protein levels, and binding capacity. Percentage of free Cort in the burn group peaked at day 2 postburn with a dramatic (+500%) increase. This correlated with a significant decrease of thymus cellularity (50% less). Phenotypic analyses showed that corticosensitive cells were significantly altered. After treatment (5 days), both endocrine and immune parameters returned to control levels. Our results demonstrate that, after a thermal injury, CBG is mainly responsible for Cort's action on corticosensitive immune cells.
Acute phase modulation of systemic insulin-like growth factor-1 and its binding proteins after major burn injuries.
OBJECTIVES: To provide a detailed, sequential analysis of insulin-like growth factor-1 and its binding proteins in adults during the acute phase after a major burn injury. DESIGN: Descriptive, repeated measurements for quantitation and characterization of insulin-like growth factor-1 and its binding proteins in adult burn survivors. SETTING: Burn center in a university hospital. PATIENTS: A total of 17 severely burned (>15% total body-surface area burned) adult patients. INTERVENTIONS: Venous blood was collected twice a day for 10 days and centrifuged, and the sera were stored at -80 degrees C until analysis. A series of 340 serum samples were analyzed by radioimmunoassay to determine the circulating concentration of insulin-like growth factor-1 and its major binding proteins (insulin-like growth factor-binding protein), by Western ligand blotting. To better understand the changes seen in systemic insulin-like growth factor-binding protein-3 levels by Western ligand blotting, a proteolysis assay was performed. MEASUREMENTS AND MAIN RESULTS: Insulin-like growth factor-1 levels were reduced from day 0 and correlated with insulin-like growth factor-binding protein-1 and -2 (p <.01), but not insulin-like growth factor-binding protein-3 and -4. Insulin-like growth factor-binding protein-3 was decreased relative to normal on day 0, declined further until day 3, and began recovering by day 6, but returned to only 35% of normal by day 10. Insulin-like growth factor-binding protein-1 and -2 were increased relative to normal and remained increased throughout the 10-day period. Insulin-like growth factor-binding protein-4 concentrations, however, were similar to normal at day 1 but gradually increased over time. Burn serum incubated with recombinant human glycosylated iodine-125 insulin-like growth factor-binding protein-3 did not demonstrate any proteolysis, although proteolysis of nonglycosylated iodine-125 insulin-like growth factor-binding protein-3 reached levels of approximately 40%. CONCLUSIONS: Insulin-like growth factor-binding protein-3 proteolysis does not seem to be the mechanism by which systemic insulin-like growth factor-1 levels are reduced in major burn survivors. In vitro proteolysis of recombinant human glycosylated and nonglycosylated iodine-125 insulin-like growth factor-binding protein-3 does not reflect the in vivo situation in major burn survivors.
Effects of dietary fatty acids on burn-induced immunosuppression.
Previous studies from our laboratory established that low-fat diets prevent immunosuppression and reduce oxidative stress after a thermal injury. The purpose of the present study was to test the hypothesis that the type of dietary fatty acid influences splenocyte proliferation and oxidative stress following a burn injury. Female C3H/HeN mice were fed ad libitum six experimental diets (5% w/w lipids) differing in fatty acid composition for 10 days following a burn injury. Compared to the controls, burned mice fed whichever diet showed lower lymphoproliferative responses to concanavalin-A (Con-A) and lipopolysaccharide (LPS) (p<0.01), but not to an anti-T cell receptor monoclonal antibody (H-57). In burned animals, nitric oxide (NO) concentration was negatively correlated to the proliferation induced by Con-A (p<0.01) or LPS (p<0.05). These results suggest that: (1) dietary fatty acid type does not influence the splenocyte proliferation or oxidative stress and (2) NO production is involved in the immunosuppression following burn injury.