title: Therapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole.
abstract: OBJECTIVE
  This study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers.
  
  
  METHODS
  The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 microg/kg) (12 ml/rat/day) or intraperitoneally (10 microg/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)].
  
  
  RESULTS
  Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine).
  
  
  CONCLUSIONS
  We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.
authors.affiliation: Department of Pharmacology, Medical School, University of Zagreb, Salata 11, 10000, Zagreb, Croatia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Skorjanec
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Dolovski
authors.forename: Ivan
authors.initials: I
authors.lastname: Kocman
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Alenka
authors.initials: A
authors.lastname: Blagaic Boban
authors.forename: Lovorka
authors.initials: L
authors.lastname: Batelja
authors.forename: Marjana
authors.initials: M
authors.lastname: Coric
authors.forename: Marko
authors.initials: M
authors.lastname: Sever
authors.forename: Robert
authors.initials: R
authors.lastname: Klicek
authors.forename: Lidija
authors.initials: L
authors.lastname: Berkopic
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.forename: Danijela
authors.initials: D
authors.lastname: Kolenc
authors.forename: Spomenko
authors.initials: S
authors.lastname: Ilic
authors.forename: Vedran
authors.initials: V
authors.lastname: Cesarec
authors.forename: Ante
authors.initials: A
authors.lastname: Tonkic
authors.forename: Ivan
authors.initials: I
authors.lastname: Zoricic
authors.forename: Stjepan
authors.initials: S
authors.lastname: Mise
authors.forename: Mario
authors.initials: M
authors.lastname: Staresinic
authors.forename: Mihovil
authors.initials: M
authors.lastname: Ivica
authors.forename: Martina
authors.initials: M
authors.lastname: Lovric Bencic
authors.forename: Tomislav
authors.initials: T
authors.lastname: Anic
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001285:Atropine / Q000494:pharmacology / Q000627:therapeutic use; D017577:Cutaneous Fistula / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005747:Gastric Fistula / Q000188:drug therapy* / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011506:Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D011506:Proteins; D001285:Atropine; D011899:Ranitidine; C083833:BPC 157; D009853:Omeprazole