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.

Satellite cell activation and apoptosis in skeletal muscle from severely burned children.

Abstract: Key points Severe burns result in profound skeletal muscle atrophy that hampers recovery. The activity of skeletal muscle stem cells, satellite cells, acutely following a severe burn is unknown and may contribute to the recovery of lean muscle. Severe burn injury induces skeletal muscle regeneration and myonuclear apoptosis. Satellite cells undergo concurrent apoptosis and activation acutely following a burn, with a net reduction in satellite cell content compared to healthy controls. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors. Abstract Severe burns result in profound skeletal muscle atrophy; persistent muscle loss and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma and we propose that an impaired muscle satellite cell response is key in the aetiology of burn-induced cachexia. Muscle biopsies from the m. vastus lateralis were obtained from 12 male pediatric burn patients (>30% total body surface area burn) and 12 young, healthy male subjects. Satellite cell content, activation and apoptosis were determined via immunohistochemistry, as were muscle fibre regeneration and myonuclear apoptosis. Embryonic myosin heavy chain expression and central nucleation, indices of skeletal muscle regeneration, were elevated in burn patients (P < 0.05). Myonuclear apoptosis, quantified by TUNEL positive myonuclei and cleaved caspase-3 positive myonuclei, was also elevated in burn patients (P < 0.05). Satellite cell content was reduced in burn patients, with approximately 20% of satellite cells positive for TUNEL staining, indicating DNA damage associated with apoptosis (P < 0.05). Additionally, a significant percentage of satellite cells in burn patients expressed Ki67, a marker for cellular proliferation (P < 0.05). Satellite cell activation was also observed in burn patients with increased expression of MyoD compared to healthy controls (P < 0.05). Robust skeletal muscle atrophy occurs after burn injury, even in muscles located distally to the site of injury. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors.

Insulin decreases inflammatory signal transcription factor expression in primary human liver cells after LPS challenge.

Abstract: Hepatic homeostasis is essential for survival in critically ill and burned patients. Insulin administration improves survival and decreases infections in these patients. To determine the molecular mechanisms, the aim of the present study was to establish a stress model using primary human hepatocytes (PHHs) and to study the effects of insulin on the hepatic inflammatory signaling cascade. Liver tissue was obtained from general surgical patients, and PHHs were isolated and maintained in culture. Primary hepatocyte cultures were challenged with various doses of lipopolysaccharide (LPS), and the inflammatory signal transcription cascade was determined by real-time PCR. In subsequent experiments, primary hepatocyte cultures were challenged with LPS and insulin was added in various doses. Glucose was determined by colorimetric assays. PHHs treated with 100 µg/mL LPS showed a profound inflammatory reaction with increased expression of interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF), and signal transducer and activator of transcription 5 (STAT-5). Insulin at 10 IU/mL significantly decreased IL-6, TNF, and IL-1β at pretranslational levels, an effect associated with decreased STAT-5 mRNA expression (P < 0.05). Glucose concentration and cellular metabolic activity were not different between controls and insulin-treated cells. Based on our results, we suggest that primary hepatocyte cultures can be used to study the effect of LPS on the inflammatory cascade. Insulin decreases hepatic cytokine expression, which is associated with decreased STAT-5 expression.

Amino Acid Supplementation for Reversing Bed Rest and Steroid Myopathies

Abstract: Muscular inactivity is inherent in many circumstances, including convalescence from serious illness or injury, spaceflight, and the progression of aging. Inactivity in a healthy individual leads to a decrease in whole-body protein turnover composed primarily of a decrease in muscle protein synthesis. The decrease in muscle protein synthesis leads to a substantial loss of lean body mass. We have demonstrated that this loss of lean mass is greater when inactivity is accompanied by stress, specifically hypercortisolemia. During convalescence from trauma or injury, the anabolic stimulus provided by nutrient ingestion represents a primary means of ameliorating the loss of muscle protein. We have previously demonstrated that ingestion of essential amino acids (EAAs), formulated to mimic the proportion of EAAs in muscle, provides a potent anabolic stimulus for muscle protein. Recently, we demonstrated that EAA supplementation throughout 28 d of bed rest stimulated net muscle protein synthesis. The repeated stimulation translated to maintenance of lean body mass and an amelioration of functional decrement compared to a placebo treatment. We have also demonstrated that this EAA supplement stimulates net protein synthesis during acute hypercortisolemia and are currently testing the effects during prolonged inactivity. Although EAAs promote muscle anabolism during hypercortisolemia, it is unlikely that a nutritional intervention alone would be effective in maintaining lean body mass during severe stress. It may be necessary to concomitantly reduce the catabolic influence of cortisol or provide another anabolic stimulus.

Practice guidelines for early ambulation of burn survivors after lower extremity grafts.

Abstract: The objective of this review was to systematically evaluate the available clinical evidence for early ambulation of burn survivors after lower extremity skin grafting procedures so that practice guidelines could be proposed. It provides evidence-based recommendations, specifically for the rehabilitation interventions required for early ambulation of burn survivors. These guidelines are designed to assist all healthcare providers who are responsible for initiating and supporting the ambulation and rehabilitation of burn survivors after lower extremity grafting. Summary recommendations were made after the literature, retrieved by systematic review, was critically appraised and the level of evidence determined according to Oxford Centre for Evidence-Based Medicine criteria. A formal consensus exercise was performed to address some of the identified gaps in the literature which were believed to be critical building blocks of clinical practice.