Relation between Respiratory Mechanics, Inflammation, and Survival in Experimental Mechanical Ventilation.

Low-tidal volume (Vt) ventilation might protect healthy lungs from volutrauma but lead to inflammation resulting from other mechanisms, namely alveolar derecruitment and the ensuing alveolar collapse and tidal reexpansion. We hypothesized that the different mechanisms of low- and high-volume injury would be reflected in different mechanical properties being associated with development of pulmonary inflammation and mortality: an increase of hysteresis, reflecting progressive alveolar derecruitment, at low Vt; an increase of elastance, as a result of overdistension, at higher Vt. Mice were allocated to "protective" (6 ml/kg) or "injurious" (15-20 ml/kg) Vt groups and ventilated for 16 hours or until death.

Molecular Imaging of Smoke-Induced Changes in Nuclear Factor-Kappa B Expression in Murine Tissues Including the Lung.

Many inflammatory responses are mediated by activation of the transcription factor, nuclear factor-kappa B (NF-κB), and a wide variety of human diseases involve abnormal regulation of its expression. In this investigation, we evaluated the effect of smoke inhalation injury on NF-κB expression in lung using two strains of NF-κB reporter mice. Groups of reporter mice with viral thymidine kinase (TK) or "fire fly" luciferase (Luc) genes under control by the NF-κB promoter (TK/NF-κB mice and Luc/NF-κB mice) were subjected to nonlethal smoke inhalation injury.

Single hind limb burn injury to mice alters nuclear factor-κB expression and [¹⁸F] 2-fluoro-2-deoxy-D-glucose uptake.

Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([18F] 2-fluoro-2-deoxy-D-glucose [18FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-κB activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on 18FDG uptake by NF-κB activity in vivo, and blood flow was determined by laser Doppler techniques.

Effect of exercise on burn-induced changes in tissue-specific glucose metabolism.

Exercise is a component of the clinical management for burn patients, to help reduce muscle wasting associated with prolonged hospitalization. In the present study the authors examined 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) uptake in mice subjected to burn injury with and without exercise. Mice had their the dorsums shaven, were placed in molds, and the exposed area was immersed in 90°C water for 9 seconds followed by resuscitation with saline (2 ml) to produce a 30% full-thickness burn injury.

Preliminary studies demonstrating acetoclastic methanogenesis in a rat colonic ring model.

Washed rat colonic rings were incubated in closed flasks under N2 at physiologic pH and temperature levels. In the absence of an exogenous substrate, negligible H2 but some CH4 concentrations were detected in vitro after one hour of incubation, but high concentrations (H2 > 100 ppm, CH4 > 10 ppm) of both gases were found after 24 hours of culture. Production of H2 and CH4 by the washed colonic rings was stimulated by lactose addition.

Combination of radiation and burn injury alters [¹⁸F] 2-fluoro-2-deoxy-D-glucose uptake in mice.

Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure on glucose metabolism in mice using [¹⁸F] 2-fluoro-2-deoxy-D-glucose (¹⁸FDG). Groups of male mice weighing approximately 30 g were studied.

Previous burn injury predisposes mice to lipopolysaccharide-induced changes in glucose metabolism.

In mice, it has been demonstrated that at 7 days after burn injury, injection of lipopolysaccharide (LPS) is more lethal than the same dose at 1 day after injury. In the present study, we examined the effect of LPS injection to mice burned 7 days previously on glucose metabolism ([(18)F] 2-fluoro-2-deoxy-D-glucose [(18)FDG] uptake) in vivo. CD-1 male mice (25-28 g, Charles River Breeding Laboratories, Wilmington, MA) were anesthetized, backs shaven, and subjected to dorsal full thickness burn on 25% TBSA.

Gram-negative bacterial infection in thigh abscess can migrate to distant burn depending on burn depth.

Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection.

In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.

Background: Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow.

In vivo molecular imaging of murine embryonic stem cells delivered to a burn wound surface via Integra® scaffolding.

It has been demonstrated that restoration of function to compromised tissue can be accomplished by transplantation of bone marrow stem cells and/or embryonic stem cells (ESCs). One limitation to this approach has been the lack of noninvasive techniques to longitudinally monitor stem cell attachment and proliferation. Recently, murine ESC lines that express green fluorescent protein (GFP), luciferase (LV), and herpes simplex thymidine kinase (HVTK) were developed for detection of actively growing cells in vivo by imaging.

Glucose metabolism during the early "flow phase" after burn injury.

Background: Burn injury (BI) is associated with insulin resistance (IR) and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of BI using a combination of positron emission tomography (PET) and stable isotope studies under euglycemic insulin clamp (EIC) conditions.

Materials And Methods: Twelve male rabbits were subjected to either full-thickness BI (B) or sham burn.

Association of heat production with 18F-FDG accumulation in murine brown adipose tissue after stress.

Previous studies have demonstrated that cold stress results in increased accumulation of (18)F-FDG in brown adipose tissue (BAT). Although it has been assumed that this effect is associated with increased thermogenesis by BAT, direct measurements of this phenomenon have not been reported. In the current investigation, we evaluated the relationship between stimulation of (18)F-FDG accumulation in BAT by 3 stressors and heat production measured in vivo by thermal imaging.

Evaluation of the antioxidant peptide SS31 for treatment of burn-induced insulin resistance.

After severe burn injury and other major traumas, glucose tolerance tests demonstrate delayed glucose disposal. This 'diabetes of injury' could be explained by insulin deficiency, and several studies have shown that soon after trauma (ebb phase) insulin concentrations are reduced in the face of hyperglycemia. After resuscitation of trauma patients (flow phase), β-cell responsiveness normalizes and plasma insulin levels are appropriate or even higher than expected, however, glucose intolerance and hyperglycemia persist.

Effects of burn injury, cold stress and cutaneous wound injury on the morphology and energy metabolism of murine brown adipose tissue (BAT) in vivo.

Aims: Cold stress has been shown to produce dramatic increases in 2-fluoro-2-deoxy-D-Glucose ((18)FDG) accumulation by brown adipose tissue (BAT) in rodents. However, neither the effects of other types of stress on (18)FDG accumulation nor the effects of stressors on the accumulation of tracers of other aspects of energy metabolism have been evaluated. In this report we studied the effects of cold stress, burn injury and cutaneous wounds on murine BAT at the macroscopic, microscopic and metabolic level.

Simvastatin treatment improves survival in a murine model of burn sepsis: Role of interleukin 6.

Infection is the most common and most serious complication of a major burn related to burn size. Recent studies have demonstrated that statin treatment can decrease mortality in murine or human sepsis. In the current study mice were anesthetized and subjected to a dorsal 30% TBSA scald burn.

Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance.

In addition to their primary role in lowering plasma cholesterol, statins have a variety of other actions. We studied the effect of simvastatin treatment on burn injury-induced changes in regional glucose metabolism. Groups of six CD-1 mice (male, approximately 25 g) were subjected to full thickness 30% total body surface area (TBSA) burn injury.

Farnesyltransferase inhibitor improved survival following endotoxin challenge in mice.

Endotoxemia plays an important role in the pathogenesis of sepsis and is accompanied by dysregulated apoptosis of immune and non-immune cells. Treatment with statins reduces mortality in rodent models of sepsis and endotoxemia. Inhibition of protein isoprenylation, including farnesylation, has been proposed as a mechanism to mediate the lipid-lowering-independent effects of statins.

Increased uncoupling protein 1 mRNA expression in mice brown adipose tissue after burn injury.

Brown adipose tissue (BAT) contains numerous mitochondria and is characterized by the presence of uncoupling protein 1 (UCP1). UCP1 is the main mediator of thermogenesis that plays an important role in the modulation of energy balance. The authors hypothesize that alterations in the expression of UCP1 might be involved in the major metabolic disorders occurring during burn trauma.

Burn-related metabolic and signaling changes in rat brain.

Postburn alterations in the morphology and metabolism of brain tissue have been previously reported. It was demonstrated in our previous study that thermal injury decreased glucose usage in rat brain during the ebb phase. The cellular and molecular signaling events that trigger the pathophysiologic alterations, however, have not yet been characterized.

Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates.

The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement (18)F-FDG. Copper-64 ((64)Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.

Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure.

Modulation of the immune system may be a viable alternative in the treatment of fulminant hepatic failure (FHF) and can potentially eliminate the need for donor hepatocytes for cellular therapies. Multipotent bone marrow-derived mesenchymal stem cells (MSCs) have been shown to inhibit the function of various immune cells by undefined paracrine mediators in vitro. Yet, the therapeutic potential of MSC-derived molecules has not been tested in immunological conditions in vivo.

Negative chemical ionization gas chromatography/mass spectrometry to quantify urinary 3-methylhistidine: application to burn injury.

A rapid method for measuring 3-methylhistidine (3MH) in rat and human urine with higher sensitivity and precision than any previously reported method is described using internal standard [1-(13)C]3MH (M+1) and negative chemical ionization (NCI) gas chromatography/mass spectrometry (GC/MS). Internal standard [1-(13)C]3MH (M+1) was added to rat and human urine samples, hydrolyzed, and absorbed onto cation exchange columns. The column eluent was dried and derivatized for GC/MS analysis.

Inflammation and infection: imaging properties of 18F-FDG-labeled white blood cells versus 18F-FDG.

Unlabelled: (18)F-FDG and (18)F-FDG-labeled white blood cells ((18)F-FDG-WBCs) are valuable radiopharmaceuticals for imaging focal sites of inflammation and infection. In the present study, the imaging properties of both radiotracers were compared in sterile and septic inflammation models.

Methods: Groups of adult male Sprague-Dawley rats (100-120 g) were injected in the left posterior thigh muscle with saline solution (group 1: controls, n = 15), 0.

Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: role of IRS phosphorylation.

Hyperglycemia, glucose intolerance and elevated insulin levels frequently occur in burned patients; however, the mechanism(s) for this insulin resistance has not been fully elucidated. One possible mechanism could involve alterations in the phosphorylation of serine 307 of the insulin receptor substrate-1 (IRS-1) via activation of stress kinase enzymes, including SAPK/JNK. In the present study we examined the time course of the effect of burn injury to mice on: levels of IRS-1 protein, phosphorylation of serine 307 of IRS-1, SAPK/JNK kinase levels and activity and Akt kinase activity in hind limb skeletal muscle.

Insulin resistance in thermally-injured rats is associated with post-receptor alterations in skeletal muscle, liver and adipose tissue.

Several of the possible molecular mechanisms that contribute to the insulin resistance associated with burn injury were examined in a rat model of thermal injury. Rats were subjected to full thickness scald injury (25% total body surface area, 10 sec burn) and resuscitated with saline. After 1, 2 and 3 weeks, urinary C-peptide excretion was measured in burned and sham-treated control animals.