The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars

Hypertrophic scar (HTS) is a fibrotic skin disorder that is marked by excessive inflammation and extracellular matrix deposition in response to cutaneous traumatic injuries such as burns, lacerations, incisions, and abrasions. HTS has various risk factors, available treatments, and treatment effectiveness. Research at the basic, translational, and clinical levels are in their infancy compared to fibrotic diseases in other organ systems. This chapter will review current in vitro and in vivo modeling, and highlight research needs to address gaps in the study of HTS. The following topics will be discussed in the chapter: a. Basic Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research b. Translational Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research c. Clinical Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research

Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

Inorganic polyphosphate (polyP) is a simple ancient polymer of linear chains of orthophosphate residues linked by high energy phospho-anhydride bonds ubiquitously found in all organisms. Despite its structural simplicity, it plays diverse functional roles. polyP is involved in myriad of processes including serving as microbial phosphagens, buffer against alkalis, Ca2+ storage, metal-chelating agents, pathogen virulence, cell viability and proliferation, structural component and chemical chaperones, and in the microbial stress response. In mammalian cells, polyP has been implicated in blood coagulation, inflammation, bone differentiation, cell bioenergetics, signal transduction, Ca2+-signaling, neuronal excitability, as a protein-stabilizing scaffold, and in wound healing, among others. This chapter will discuss (1) polyP metabolism and roles of polyP in prokaryotic and eukaryotic cells, (2) the contribution of polyP to survival, cell proliferation, and motility involved in wound healing in human skin keratinocytes, (3) the use of polyP-containing platelet-rich plasma (PRP) to promote wound healing in acute and chronic wounds, including burns, and (4) the use of polyP-containing PRP in excisional wound models to promote faster healing. While polyP shows promise as a therapeutic agent to accelerate healing for acute and chronic wounds, the molecular mechanisms as a potent modulator of the wound healing process remain to be elucidated

Results of a Pilot Multicenter Genotype-based Randomized Placebo-controlled Trial of Propranolol to Reduce Pain After Major Thermal Burn Injury

Results of previous studies suggest that β-adrenoreceptor activation may augment pain, and that β-adrenoreceptor antagonists may be effective in reducing pain, particularly in individuals not homozygous for the catechol-O-methyltransferase (COMT) high activity haplotype

Identification of a Transcytosis Epitope on Staphylococcal Enterotoxins

Staphylococcal enterotoxins (SE) are exoproteins produced by Staphylococcus aureus that act as superantigens and have been implicated as a leading cause of food-borne disease and toxic shock. Little is known about how these molecules penetrate the gut lining and gain access to both local and systemic immune tissues. To model movement in vitro of staphylococcal enterotoxins, we have employed a monolayer system composed of crypt-like human colonic T-84 cells. SEB and SEA showed comparable dose-dependent transcytosis in vitro, while toxic shock syndrome toxin (TSST-1) exhibited increased movement at lower doses. Synthetic peptides corresponding to specific regions of the SEB molecule were tested in vitro to identify the domain of the protein involved in the transcytosis of SE. A toxin peptide of particular interest contains the amino acid sequence KKKVTAQELD, which is highly conserved across all SE. At a toxin-to-peptide ratio of 1:10, movement of SEB across the monolayers was reduced by 85%. Antisera made against the SEB peptide recognized native SEB and also inhibited SEB transcytosis. Finally, the conserved 10-amino-acid peptide inhibited transcytosis of multiple staphylococcal enterotoxins, SEA, SEE, and TSST-1. These data demonstrate that this region of the staphylococcal enterotoxins plays a distinct role in toxin movement across epithelial cells. It has implications for the prevention of staphylococcal enterotoxin-mediated disease by design of a peptide vaccine that could reduce systemic exposure to oral or inhaled superantigens. Since the sequence identified is highly conserved, it allows for a single epitope blocking the transcytosis of multiple SE

General principles of resuscitation and supportive care: Burns

© 2017 by Taylor and Francis Group, LLC. In the United States, burn-related injuries are common among children, with the incidence being higher in children than adults. Each day about 300 children are seen in emergency departments in the United States for burn injuries, and two of these children will die from their injuries [1]. Burn injuries are consistently among the top causes of injury-related death in children under 15 years old [2]. Burn injury is the fifth most common cause of nonfatal injury in children and the eleventh most common cause of death worldwide [3]

General principles of resuscitation and supportive care: Burns

© 2017 by Taylor and Francis Group, LLC. In the United States, burn-related injuries are common among children, with the incidence being higher in children than adults. Each day about 300 children are seen in emergency departments in the United States for burn injuries, and two of these children will die from their injuries [1]. Burn injuries are consistently among the top causes of injury-related death in children under 15 years old [2]. Burn injury is the fifth most common cause of nonfatal injury in children and the eleventh most common cause of death worldwide [3]

Infection and Burn Injury

Burn injury is debilitating and among one of the most frequently occurring traumas. Critical care improvements have allowed for increasingly positive outcomes. However, infection, whether it be localized to the site of the wound or systemic in nature, remains a serious cause of morbidity and mortality. Immune suppression predisposes the burn population to the development of invasive infections; and this along with the possibility of inhalation injury puts them at a significant risk for mortality. Emerging multi-drug-resistant pathogens, including Staphylococcus aureus, Enterococcus, Pseudomonas, Acinetobacter, Enterobacter, and yeast spp., continue to complicate clinical care measures, requiring innovative therapies and antimicrobial treatment. Close monitoring of antimicrobial regimens, strict decontamination procedures, early burn eschar removal, adequate wound closure, proper nutritional maintenance, and management of shock and resuscitation all play a significant role in mitigating infection. Novel antimicrobial therapies such as ultraviolet light, cold plasma and topical antiseptics must continue to evolve in order to lower the burden of infection in burn