title: Dose response profiles of human growth hormone in subcutaneous wound chambers in rats.
abstract: OBJECTIVE
  To investigate dose response profiles of human growth hormone in soft connective tissue healing when it is given locally in subcutaneous wound chambers.
  
  
  METHODS
  Placebo controlled parallel study.
  
  
  METHODS
  Institute of Medical Anatomy, Denmark.
  
  
  METHODS
  36 male Sprague Dawley rats, in three group of 12.
  
  
  METHODS
  Stainless steel wire mesh cylinders 7 mm in diameter and 20 mm long were implanted subcutaneously in pairs in the upper and lower back on either side of the midline in three groups of male Sprague Dawley rats. Two groups were each given two different doses of growth hormone (group 1, 0.2 and 0.7 IU; and group 2, 0.02 and 2 IU) in two cylinders and vehicle alone in the two cylinders on the opposite side. Group 3 were given vehicle alone in two cylinders and needle puncture (sham) on the opposite side. Injections of growth hormone or vehicle (placebo) were given every three days for 16 days.
  
  
  METHODS
  Body weight, weight of granulation tissue, and concentrations of hydroxyproline and aminoterminal propeptide of procollagen type III.
  
  
  RESULTS
  The dose response curves for weight of granulation tissue and deposition of collagen were upward convex (ANOVA p < 0.001 and 0.001, respectively). Growth hormone in doses of 0.2 and 0.7 IU stimulated formation of granulation tissue to means of 180% (95% confidence interval (Cl) 149% to 210%) and 174% (95% Cl 148% to 200%) more than in the placebo treated cylinders (group 3) (p < 0.05 and < 0.01, respectively). Doses of 0.2 and 2 IU, however, had less effect. The placebo cylinders in animals in groups 1 and 2 contained a mean of 157% (95% Cl 137% to 177%) more granulation tissue than the cylinders in group 3, indicating that locally applied growth hormone also had a systemic effect.
  
  
  CONCLUSIONS
  The clinical use of topical growth hormone in wound healing may be complicated by the relatively narrow therapeutic interval.
authors.affiliation: Dept. of Surgery, Herlev Hospital, Copenhagen, Denmark.
authors.forename: L H
authors.initials: LH
authors.lastname: Rasmussen
authors.forename: C
authors.initials: C
authors.lastname: Garbarsch
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.forename: D
authors.initials: D
authors.lastname: Moe
authors.forename: K
authors.initials: K
authors.lastname: Hørslev-Pedersen
authors.forename: F
authors.initials: F
authors.lastname: Gottrup
authors.forename: H
authors.initials: H
authors.lastname: Steenfos
mesh_terms: D000818:Animals; D001835:Body Weight; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006097:Granulation Tissue / Q000187:drug effects / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D019382:Human Growth Hormone; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010446:Peptide Fragments / Q000097:blood; D010919:Placebos; D011347:Procollagen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013193:Stainless Steel; D013526:Surgical Mesh; D014945:Wound Healing / Q000187:drug effects
chemical_list: D010446:Peptide Fragments; D010919:Placebos; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D013193:Stainless Steel; D019382:Human Growth Hormone; D013006:Growth Hormone; D003094:Collagen; D006909:Hydroxyproline