The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H 2 S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial cells (ECs) with H 2 S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel. Treatment of chicken chorioallantoic membranes (CAMS) with H 2 S increased vascular length. Exposure of ECs to H 2 S resulted in increased phosphorylation of Akt, ERK, and p38. The K ATP channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H 2 S-induced EC motility. Since glibenclamide inhibited H 2 S-triggered p38 phosphorylation, we propose that K ATP channels lay upstream of p38 in this process. When CAMs were treated with H 2 S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H 2 S serves as an endogenous stimulator of the angiogenic response. Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H 2 S release, while pharmacological inhibition of H 2 S production or K ATP channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs. These results implicate endothelial H 2 S synthesis in the pro-angiogenic action of VEGF. Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates. Finally, in vivo, topical administration of H 2 S enhanced wound healing in a rat model, while wound healing was delayed in CSE −/− mice. We conclude that endogenous and exogenous H 2 S stimulates EC-related angiogenic properties through a K ATP channel/MAPK pathway.

Objective To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial. Summary Background Data A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated. Methods Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. Results Average age was 8 ± 0.2 years, and average burn size was 56 ± 1% TBSA with 43 ± 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (−0.05% ± 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (−4.1% ± 1.9%); P < 0.05. Patients lost 3% ± 1% of their bone mineral content (BMC) and 2 ± 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 ± 0.2 infections and 17% sepsis. Conclusions In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with derangements that are greater and more protracted than previously thought.

Summary Improvements in acute burn care have enabled patients to survive massive burns which would have once been fatal. Now up to 70% of patients develop hypertrophic scars following burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. The current approach is to optimise the healing potential of the burn wound using targeted wound care and surgery in order to minimise the development of hypertrophic scarring. This approach often fails, and modulation of established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventative and therapeutic strategies.

Burn injuries have been more prevalent among low socioeconomic populations and in less developed regions. Incredible advances in burn care and social development over the recent decades, however, should have placed the incidence and severity of burns in a downwards trend. The aim of this review was to give an overview on current trends in burn epidemiology across the world. Also the socioeconomic development in countries that have published epidemiological data used in this study has been taken into account when comparing the results. There was a worldwide downwards trend of burn incidence, burn severity, length of hospital stay, and mortality rate. These findings were particularly pronounced in very highly developed countries. Data from highly and medium developed countries were more heterogeneous. No studies could be obtained from low developed countries. Comparisons between the different studies were compromised by the fact that studies emerged from specialized facilities on one hand and general hospitals on the other. Analyzed studies were also frequently focusing on limited patient populations such as “children” or “elderly”. Our findings indicate the need for an international burn database with a minimal data-set in order to obtain objective and comparable results in respect of burn epidemiology.