Shriners Hospitals for Children - Galveston

About: Shriners Hospitals for Children - Galveston is a healthcare organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Burn injury & Lean body mass. The organization has 249 authors who have published 420 publications receiving 15311 citations.

H2S, a Bacterial Defense Mechanism against the Host Immune Response.

Abstract: The biological mediator hydrogen sulfide (H2S) is produced by bacteria and has been shown to be cytoprotective against oxidative stress and to increase the sensitivity of various bacteria to a range of antibiotic drugs. Here we evaluated whether bacterial H2S provides resistance against the immune response, using two bacterial species that are common sources of nosocomial infections, Escherichia coli and Staphylococcus aureus Elevations in H2S levels increased the resistance of both species to immune-mediated killing. Clearances of infections with wild-type and genetically H2S-deficient E. coli and S. aureus were compared in vitro and in mouse models of abdominal sepsis and burn wound infection. Also, inhibitors of H2S-producing enzymes were used to assess bacterial killing by leukocytes. We found that inhibition of bacterial H2S production can increase the susceptibility of both bacterial species to rapid killing by immune cells and can improve bacterial clearance after severe burn, an injury that increases susceptibility to opportunistic infections. These findings support the role of H2S as a bacterial defense mechanism against the host response and implicate bacterial H2S inhibition as a potential therapeutic intervention in the prevention or treatment of infections.

Metabolism modulators in sepsis: Propranolol

Abstract: Sepsis is accompanied by an enormous increase in catecholamine expression, leading to metabolism of lipids and glucose, changes in cardiovascular output, immunomodulatory effects, and changes in protein metabolism, all of which push the body into a catabolic state. Deleterious beta-adrenoceptor controlled responses to stress and sepsis are well documented; therefore, it would seem appropriate to use propranolol under such circumstances. There are arguments both for and against the use of beta-adrenoceptor blockade during episodes of stress and infection. The definition of sepsis itself is a clinical one in most cases. There are guidelines concerning the diagnosis of sepsis (systemic inflammatory response syndrome [SIRS] in the presence of significant infection). However, when the cause of SIRS is not infection, for example, in burn patients, is it not possible, and indeed preferable, to tackle the stress response in a more aggressive fashion? The effects of SIRS on the body are myriad and have been defined and illustrated in many fine reviews. The effects of sepsis on the body, as well, have been discussed in the world literature and are beyond the scope of this article. In this article we attempt to demonstrate the effects of sepsis (SIRS plus infection) on whole body metabolism, outline the mediators of these changes, and then show the ability of propranolol to attenuate the changes seen.

Post-burn hepatic insulin resistance is associated with endoplasmic reticulum (ER) stress.

Abstract: Insulin resistance with its associated hyperglycemias represents one significant contributor to mortality in burned patients. A variety of cellular stress-signaling pathways are activated as a consequence of burn. A key player in the cellular stress response is the endoplasmic reticulum (ER). Here, we investigated a possible role for ER-stress pathways in the progression of insulin function dysregulation post-burn. Rats received a 60% TBSA thermal injury and a laparotomy was performed at 24, 72 and 192 h post-burn. Liver was harvested before and 1 min after insulin injection (1 IU/kg) into the portal vein and expression patterns of various proteins known to be involved in insulin and ER-stress signaling were determined by Western blotting. mRNA expression of Glucose-6-Phosphatase (G-6-P) and Glucokinase (GK) were determined by RT-PCR and fasting serum glucose and insulin levels by standard enzymatic and ELISA techniques, respectively. Insulin resistance indicated by increased glucose and insulin levels occurred starting 24 h post-burn. Burn injury resulted in activation of ER stress pathways, reflected by significantly increased accumulation of phospho-PERK and phosphor-IRE-1 leading to an elevation of phospho-JNK and serine phosphorylation of IRS-1 post-burn. Insulin administration caused a significant increase in tyrosine phosphorylation of IRS-1 leading to activation of the PI3K/Akt pathway in normal liver. Post-burn tyrosine phosphorylation of IRS-1 was significantly impaired associated with an inactivation of signaling molecules acting downstream of IRS-1 leading to significantly elevated transcription of G-6-P and significantly decreased mRNA expression of GK. Activation of ER-stress signaling cascades may explain metabolic abnormalities involving insulin action following burn.