Human erythrocyte fragmentation during ex-vivo pig organ perfusion.

Platelet sequestration is a common process during organ reperfusion after transplantation. However, instead of lower platelet counts, when using traditional hemocytometers and light microscopy, we observed physiologically implausible platelet counts in the course of ex-vivo lung and liver xenograft organ perfusion studies. We employed conventional flow cytometry (FC) and imaging FC (AMINS ImageStream X) to investigate the findings and found platelet-sized fragments in the circulation that are mainly derived from red blood cell membranes.

Standards in Biologic Lesions: Cutaneous Thermal Injury and Inhalation Injury Working Group 2018 Meeting Proceedings.

On August 27 and 28, 2018, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn and inhalation injury in Washington, DC. The goal of the meeting was to identify and discuss the existing knowledge, data, and modeling gaps related to understanding cutaneous thermal injury and inhalation injury due to exposure from a fire environment, and in addition, address two more areas proposed by the American Burn Association Research Committee that are critical to burn care but may have current translational research gaps (inflammatory response and hypermetabolic response). Representatives from the Underwriters Laboratories Firefighter Safety Research Institute and the Bureau of Alcohol, Tobacco, Firearms and Explosives Fire Research Laboratory presented the state of the science in their fields, highlighting areas that required further investigation and guidance from the burn community.

Early reduced bone formation following burn injury in rats is not inversely related to marrow adiposity.

Objectives: The objective of the study was to determine whether postburn reduction of bone formation occurred earlier than 2-3 weeks after burn injury and whether that reduction was inversely related to marrow adiposity.

Methods: Using a rat model of burn injury with sacrifice at 3 days postburn, we measured serum osteocalcin, a biomarker of bone formation, as well as a regulator of glucose metabolism, and counted tibial marrow adipocytes.

Results: Serum osteocalcin was reduced as early as 3 days postburn, coinciding with a trend toward decline in marrow adipocyte number rather than demonstrating an inverse relationship with adipocyte count.

Magnetization transfer contrast MRI in GFP‑tagged live bacteria.

Green fluorescent protein (GFP) is a widely utilized molecular reporter of gene expression. However, its use in in vivo imaging has been restricted to transparent tissue mainly due to the tissue penetrance limitation of optical imaging. Magnetization transfer contrast (MTC) is a magnetic resonance imaging (MRI) methodology currently utilized to detect macromolecule changes such as decrease in myelin and increase in collagen content.

Effects of Exendin-4 on pancreatic islets function in treating hyperglycemia post severe scald injury in rats.

Background: It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-cell apoptosis, increases insulin secretion, and improves glucose tolerance in scald injury. However, the effects of Exendin-4, a long-acting incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this study attempted to investigate whether Exendin-4 had similar effects by protecting the histology of pancreas in severely scalded rats.

The Role of Calcium in Inflammation-Associated Bone Resorption.

The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration.

The Role of Bone Secreted Factors in Burn-Induced Muscle Cachexia.

Purpose Of Review: Burn injury results in resorptive bone loss, failure to make new bone, and muscle protein breakdown resulting in cachexia. The purpose of this review is to examine the relationship between bone loss and muscle atrophy in burn injury with a view to understanding the process at work and how it may apply to other conditions that have similar features.

Recent Findings: We present data suggesting that the use of bisphosphonates in the first 10 days following the burn prevents not only the resorptive bone loss but also the muscle wasting.

Impact of Complete Spinal Cord Injury on Healing of Skin Ulcers in Mouse Models.

Pressure ulcers (PUs) are common debilitating complications of traumatic spinal cord injury (SCI) and tend to occur in soft tissues around bony prominences. There is, however, little known about the impact of SCI on skin wound healing because of the lack of suitable animal models for studies in controlled experimental settings. Herein, we describe a reproducible and clinically relevant mouse model of PUs in the context of complete SCI.

Stromal Cell-Derived Growth Factor-1 Alpha-Elastin Like Peptide Fusion Protein Promotes Cell Migration and Revascularization of Experimental Wounds in Diabetic Mice.

In previous work, we demonstrated the development of a novel fusion protein containing stromal cell-derived growth factor-1 alpha juxtaposed to an elastin-like peptide (SDF1-ELP), which has similar bioactivity, but is more stable in elastase than SDF1. Herein, we compare the ability of a single topical application of SDF1-ELP to that of SDF1 in healing 1 × 1 cm excisional wounds in diabetic mice. Human Leukemia-60 cells were used to demonstrate the chemotactic potential of SDF1-ELP versus SDF1 .

Why so little effort to study anti-oxidant therapy in burns?

Given that oxidative stress is an inherent response to burn injury, it is puzzling as to why investigation into anti-oxidant therapy as an adjunct to burn treatment has been limited. Both the inflammatory response and the stress response to burn injury involve oxidative stress, and there has been some limited success in studies using gamma tocopherol and selenium to improve certain consequences of burns. Much remains to be done to investigate the number, doses and combinations of anti-oxidants, their efficacy, and limitations in improving defined outcomes after burn injury.

Elastin-like polypeptides: A strategic fusion partner for biologics.

Elastin-like peptides (ELPs) are derivatives of tropoelastin with a unique property that allows them to stay soluble below a certain critical temperature but reversibly form aggregates above that temperature. Since they are derived from tropoelastin, ELPs are biocompatible, non-toxic, and non-immunogenic. The unique properties of ELPs have made them a desirable class of fusion tags used in several biomedical applications including targeted drug delivery and enhancing the half-life of protein drugs.

The development and characterization of SDF1α-elastin-like-peptide nanoparticles for wound healing.

Chronic skin wounds are characterized by poor re-epithelialization, angiogenesis and granulation. Previous work has demonstrated that topical stromal cell-derived growth factor-1 (SDF1) promotes neovascularization, resulting in faster re-epithelialization of skin wounds in diabetic mice. However, the clinical usefulness of such bioactive peptides is limited because they are rapidly degraded in the wound environment due to high levels of proteases.

THE EFFECT OF GLUCOCORTICOIDS ON BONE AND MUSCLE.

This article examines the current knowledge of the effects of both exogenous and endogenous glucocorticoids on bone and muscle. It demonstrates the similarity of effects of supraphysiologic loads of glucocorticoids regardless of whether they enter the body in the form of medication or are manufactured by the body in response to stimuli such as inflammation. The effects of endogenous glucocorticoids and the systemic inflammatory response resulting from pediatric burn injury are compared and the difficulty in sorting out which of the two factors is responsible for the ultimate effects on bone and muscle is pointed out.

Machine perfusion enhances hepatocyte isolation yields from ischemic livers.

Background: High-quality human hepatocytes form the basis of drug safety and efficacy tests, cell-based therapies, and bridge-to-transplantation devices. Presently the only supply of cells derives from an inadequate pool of suboptimal disqualified donor livers. Here we evaluated whether machine perfusion could ameliorate ischemic injury that many of these livers experience prior to hepatocyte isolation.

Ex Situ Normothermic Machine Perfusion of Donor Livers.

In contrast to conventional static cold preservation (0-4 °C), ex situ machine perfusion may provide better preservation of donor livers. Continuous perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic machine perfusion (37 °C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous perfusion of the portal vein.

Skin rejuvenation with non-invasive pulsed electric fields.

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields.

Insulin and bone: Recent developments.

While insulin-like growth factor I is a well-known anabolic agent in bone evidence is beginning to accumulate that its homologue, insulin, also has some anabolic properties for bone. There is specific evidence that insulin may work to stimulate osteoblast differentiation, which in turn would enhance production of osteocalcin, the osteoblast-produced peptide that can stimulate pancreatic β cell proliferation and skeletal muscle insulin sensitivity. It is uncertain whether insulin stimulates bone directly or indirectly by increasing muscle work and therefore skeletal loading.

Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures.

Background & Aims: The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation.

Methods: In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system.

No correlation between initial arterial carboxyhemoglobin level and degree of lung injury following ovine burn and smoke inhalation.

Fire victims often suffer from burn injury and concomitant inhalation trauma, the latter significantly contributing to the morbidity and mortality in these patients. Measurement of blood carboxyhemoglobin levels has been proposed as a diagnostic marker to verify and, perhaps, quantify the degree of lung injury following inhalation trauma. However, this correlation has not yet been sufficiently validated.

Perfusion defatting at subnormothermic temperatures in steatotic rat livers.

Hepatic steatosis is a major risk factor in liver transplantation. Use of machine perfusion to reduce steatosis has been reported previously at normothermic (37°C) temperatures, with minimal media as well as specialized defatting cocktails. In this work, we tested if subnormothermic (room temperature) machine perfusion, a more practical version of machine perfusion approach that does not require temperature control or oxygen carriers, could also be used to reduce fat content in steatotic livers.

Transesophageal echocardiography in the management of burn patients.

A systematic review was conducted to assess the level of evidence for the use of transesophageal echocardiography (TEE) in the management of burn patients. We searched any article published before and including June 30, 2013. Our search yielded 118 total publications, 11 met the inclusion criteria of burn injury and TEE.

Hydrogen sulfide-mediated stimulation of mitochondrial electron transport involves inhibition of the mitochondrial phosphodiesterase 2A, elevation of cAMP and activation of protein kinase A.

Although hydrogen sulfide (H₂S) is generally known as a mitochondrial poison, recent studies show that lower concentrations of H₂S play a physiological role in the stimulation of mitochondrial electron transport and cellular bioenergetics. This effect involves electron donation at Complex II. Other lines of recent studies demonstrated that one of the biological actions of H₂S involves inhibition of cAMP and cGMP phosphodiesterases (PDEs).

Healing efficacy of sea buckthorn (Hippophae rhamnoides L.) seed oil in an ovine burn wound model.

To investigate the efficacy of sea buckthorn (SBT) seed oil - a rich source of substances known to have anti-atherogenic and cardioprotective activity, and to promote skin and mucosa epithelization - on burn wound healing, five adult sheep were subjected to 3rd degree flame burns. Two burn sites were made on the dorsum of the sheep and the eschar was excised down to the fascia. Split-thickness skin grafts were harvested, meshed, and fitted to the wounds.

Strategies to rescue steatotic livers before transplantation in clinical and experimental studies.

The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications post-transplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies.