title: Clinical assessment of the effect of a matrix metalloproteinase inhibitor on aphthous ulcers.
abstract: OBJECTIVE
  Aphthous ulceration is a common form of recurrent ulceration of the oral mucosa. Numerous treatments have been tried as a means of relieving pain, disinfecting the ulcer base, and reducing inflammation, but with limited success. Tetracycline and its derivatives have been shown to be inhibitors of matrix metalloproteinases (MMPs), which are part of the inflammatory response and contribute to the breakdown of tissue in the ulcer. Of the commercially available tetracyclines, doxycycline has shown the best inhibition of the MMPs. The aim of this study was to test clinically whether the inhibitory effect of a low-dose doxycycline in a hydrogel on MMPs would speed the recovery of oral ulceration.
  
  
  METHODS
  Forty-nine patients participated in a randomized, double-blind, placebo-controlled trial.
  
  
  RESULTS
  Sixty-eight percent of ulcers had healed by the third day of treatment with the doxycycline gel, whereas only 25% of the patients receiving the placebo reported healing of their ulcers within 3 days. Patients treated with the docycline gel recounted faster reduction in pain during the treatment period than the placebo group did.
  
  
  CONCLUSIONS
  Incorporation of low-dose doxycycline in a muco-adhesive gel has been demonstrated to have potential in the treatment of recurrent oral ulceration. It is concluded that MMP enzymes can be inhibited by low doses of doxycycline below levels likely to disrupt the oral flora.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland. skulis@hi.is
authors.forename: Skuli
authors.initials: S
authors.lastname: Skulason
authors.forename: William Peter
authors.initials: WP
authors.lastname: Holbrook
authors.forename: Thordis
authors.initials: T
authors.lastname: Kristmundsdottir
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010147:Pain Measurement; D013281:Stomatitis, Aphthous / Q000188:drug therapy* / Q000201:enzymology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D005782:Gels; D061965:Matrix Metalloproteinase Inhibitors; D004318:Doxycycline