title: Effect of gamma-hydroxybutyrate on keratinocytes proliferation: A preliminary prospective controlled study in severe burn patients.
abstract: BACKGROUND
  Hypermetabolism and hyposomatotropism related to severe burns lead to impaired wound healing. Growth hormone (GH) boosts wound healing notably following stimulation of the production of insulin-like growth factor-1 (IGF1), a mitogen factor for keratinocytes. Gamma-hydroxybutyrate (GHB) stimulates endogenous GH secretion.
  
  
  OBJECTIVE
  To assess effects of GHB sedation on keratinocytes proliferation (based on immunohistochemical techniques).
  
  
  METHODS
  Monocentric, prospective, controlled trial.
  
  
  METHODS
  Patients (aging 18-65 years, burn surface area >30%, expected to be sedated for at least one month) were alternately allocated, at the 5(th) day following injury, in three groups according to the intravenous GHB dose administered for 21 days: Evening bolus of 50 mg/kg (Group B), continuous infusion at the rate of 10 mg/kg/h (Group C), or absence of GHB (Group P). They all received local standard cares. Immunohistochemistry (Ki67/MIB-1, Ulex europaeus agglutinin-1 and Mac 387 antibodies) was performed at D21 on adjacent unburned skin sample for assessing any keratinocyte activation. Serum IGF1 levels were measured at initiation and completion of the protocol.
  
  
  METHODS
  Categorical variables were compared with Chi-square test. Comparisons of medians were made using Kruskal-Wallis test. Post hoc analyses were performed using Mann-Whitney test with Bonferroni correction for multiple comparisons. A P < 0.05 was considered to be statistically significant.
  
  
  RESULTS
  A total of 14 patients completed the study (Group B: n = 5, Group C: n = 5, Group P: n = 4). Continuous administration of GHB was associated with a significant higher Ki67 immunolabeling at D21 (P = 0.049) and with a significant higher increase in the IGF1 concentrations at D21 (P = 0.024). No adverse effects were disclosed.
  
  
  CONCLUSIONS
  Our preliminary data support a positive effect of GHB on keratinocyte proliferation and are encouraging enough to warrant large prospective studies.
authors.affiliation: Intensive Care Unit and Burn Centre, University Hospital, Liège, Belgium.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Rousseau
authors.affiliation: Burn Centre, Percy Military Teaching Hospital, Clamart, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bargues
authors.affiliation: Burn Centre, Percy Military Teaching Hospital, Clamart, France.
authors.forename: Hervé Le
authors.initials: HL
authors.lastname: Bever
authors.affiliation: Clinical Chemistry, Percy Military Teaching Hospital, Clamart, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vest
authors.affiliation: Clinical Chemistry, University Hospital, Liège, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Cavalier
authors.affiliation: Intensive Care Unit and Burn Centre, University Hospital, Liège, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Ledoux
authors.affiliation: Dermatopathology, University Hospital, Liège, Belgium.
authors.forename: Gérald E
authors.initials: GE
authors.lastname: Piérard
authors.affiliation: Intensive Care Unit and Burn Centre, University Hospital, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Damas
keywords: Burn injury; gamma-hydroxybutyrate; immunohistochemistry; keratinocyte