AbstractSphingolipids and their metabolites have emerged as a new class of lipid mediator of various cell functions. It has been over a decade since the sphingolipid, ceramide-1-phosphate, was described. Until recently, only sparse reports on possible biological functions for this lipid have been published. In the last few years, a large number of reports have surfaced demonstrating distinct biological mechanisms regulated by ceramide-1-phosphate. The following is a review of the current literature on this overlooked lipid, with emphasis on its newly discovered role in signal transduction.Key words: ApoptosisCalciumCeramide KinaseCeramide-1-PhosphateCytosolic Phospholipase A2αEicosanoidsInflammationPhagocytosis
Split-thickness skin grafting (STSG) is the standard of care for treating deep burns. They often contract, have unpredictable cosmetic outcomes, lack dermal appendages, and result in painful, conspicuous donor sites. An autologous homologous skin construct (AHSC) has been shown to produce full-thickness skin architecture. This study examined the safety profile, engraftment, and quality of healing of a pilot group of AHSC-treated burn wounds. Following IRB approval and informed consent, patients with deep-partial/full-thickness burns requiring grafting underwent side-by-side treatment with AHSC and STSG. A 2 cm2 fullthickness harvest was processed into AHSC at an FDA-registered facility, returned within 48 hours, and applied to a 4 cm2 area alongside a STSG. AHSC donor site was closed primarily. Wounds were evaluated for healing with digital photography and investigator assessments for 90 days. All adverse events (AEs) were recorded. Eight patients with average 13.3% TBSA [range 2-58%] burn wounds were treated: 5 Caucasian and 3 African American with an average body mass index (BMI) of 26.8. Injury was due to predominantly flame burn, with additional injury from grease, scald, contact, friction and flash. Mean time between injury and AHSC treatment was 11 days [range 5-35 days]. All patients had adequate engraftment and complete epithelialization by the end of the study. Patients required one application of AHSC and no other additional surgical procedures at the application sites. The most common AEs for STSG-treated wounds included hypertrophic scarring and pruritus. One non-infected AHSC harvest site experienced a dehiscence. There were no other AEs related to AHSC treatment. AHSC treatment is feasible in deep partial and fullthickness burn wounds warranting additional investigation.La greffe dermo- épidermique (GDE) est le traitement de référence des brûlures profondes. La zone traitée est sujette aux brides, n’a pas d’appendices dermiques, a un aspect esthétique aléatoire et le site donneur est indéniablement douloureux. Un hybride cutané autologue- homologue (HCAH) a montré être architecturalement proche de la peau. Cette étude a pour but d’évaluer l’innocuité, la qualité de prise et la qualité cicatricielle obtenues sur un groupe pilote de brûlés profonds. Après autorisation des tutelles et consentement éclairé, les patients, nécessitant une greffe ont reçu, côte à côte, une GDE et un HCAH. Ce dernier est préparé à partir d’un prélèvement de 2 cm² de peau totale (auto- fermant), en 48 h, dans une structure approuvée par la FDA. On obtient une structure de 4 cm², installée à côté d’une GDE. Les brûlures ont été évaluées cliniquement et photographiées pendant 90 j. Tous les événements indésirables (EI) ont été répertoriés. Huit patients brûlés sur 13,3 % (2-58) de SCT ont été inclus. Il s’agissait de 5 blancs et 3 noirs (je dois traduire même ceci, qui me semble foncièrement non éthique- NDRLF) ayant un IMC de 26,8. Les brûlures étaient liées à un flamme mais aussi à de la graisse, par ébouillantement, contact, flash ou dermabrasion. Le délai moyen de mise en place de l’HCAH était de 11 jours (5-53). L’intégration de la greffe a été bonne et tous les patients étaient cicatrisés à la fin de l’étude, sans nécessité de nouvelle greffe. Les EI les plus fréquents observés sur les zones GDE étaient des cicatrices hypertrophiques et un prurit. Une zone HCAH s’est désunie (hors infection), seul EI observé dans ce groupe. L’HCAH semble utilisables sur les brûlures profondes et doit être étudié plus avant.
Traumatic shock activates the hypothalamic-pituitary-adrenal axis (HPA) to mediate a cascade of defensive mechanisms that often include overwhelming inflammatory response and immunosuppression, which may lead to multiple organ failure. Androstenetriol (5 androstene, 3beta, 7beta, 17beta triol-AET) is a metabolite of dehydroepiandrosterone that markedly up regulates host immune response, prevents immune suppression, modulates inflammation and improves survival after lethal infections by pathogens and lethal radiation.AET-induced immune modulation will improve survival in a conscious rodent model of traumatic shock.A relevant traumatic shock rodent model that applies to both combat and civilian sectors was used. After creation of a midline laparotomy (soft tissue trauma), animals were hemorrhaged to a mean arterial pressure of 35-40 mm Hg. Resuscitation was initiated sixty minutes later with crystalloid fluid and packed red blood cells and animals were observed for two days. In a randomized and blinded fashion, AET or vehicle was administered subcutaneously at the beginning of resuscitation.In the vehicle group 5 out of 16 animals survived, (31%). In contrast, 9 out of 13 animals who received AET survived (69%), (Fisher Exact Test p < 0.05). Survival in the AET treatment group was associated with reduced levels of IL-6, IL-10, and IL-18, and enhanced IFN-gamma and IL-2 levels.: The results indicate that AET provides a significant protective effect and improves survival in a clinically relevant model of traumatic hemorrhagic shock. AET protective effects are associated with an elevation of Th1 and reduction of Th2 cytokines.
Abstract Introduction Split-thickness skin grafting (STSG) is the standard of care for treating deep burns. They often contract, have limited cosmesis, lack dermal appendages, and result in painful, conspicuous donor sites. An Autologous Homologous Skin Construct (AHSC) has been shown to result in full-thickness skin formation.1,2 This study examined the safety profile, graft take, and quality of healing of a pilot group of AHSC-treated burn wounds. Methods Following IRB approval and informed consent, patients with deep-partial/full-thickness burns requiring grafting underwent side-by-side treatment with AHSC and STSG. A 2cm2 full-thickness harvest was processed into AHSC at an FDA-registered facility, returned within 48 hours, and applied to a 4cm2 area alongside a STSG. AHSC donor site was closed primarily. Wounds were evaluated for healing with digital photography and investigator assessments for 90 days. All adverse events (AEs) were recorded. Results Eight patients with 12% TBSA [range 2–40%] burn wounds were treated; 5 Caucasian and 3 African American with an average BMI of 26.8. Injury was due to predominantly flame burn, with additional injury from grease, scald, contact, friction, and flash. Mean time between injury and AHSC treatment was 11 days [range 5–35 days]. All patients had graft take and complete epithelialization by the end of the study. Patients required one application of AHSC and no other additional surgical procedures at the application sites. The most common AEs for STSG-treated wounds included hypertrophic scarring, pruritus, and insomnia. One non-infected AHSC harvest site experienced a mechanical dehiscence. There were no other AEs related to AHSC treatment. Conclusions No related adverse events at the treatment sites were noted in this study. However, the size of the treatment area limited the ability to comment on the presence of complex dermal elements including hair follicles. Additional investigation with application to larger areas is warranted to evaluate the utility of AHSC for the treatment of acute burn wounds. Applicability of Research to Practice Novel therapy may provide an alternative treatment for burns requiring skin grafting however larger studies are needed.
