title: Additive effect of pronase on the efficacy of eradication therapy against Helicobacter pylori.
abstract: BACKGROUND
  Helicobacter pylori (H. pylori) colonizes not only the surface of the surface mucous cells but also the surface mucous gel layer (SMGL). Thus, we examined the possible value of pronase, a mucolytic agent, as a potential eradication therapy.
  
  
  METHODS
  One hundred and thirty-five patients were randomly assigned to two treatment groups. Sixty-eight patients received 30 mg of lansoprazole once daily, 500 mg of amoxicillin and 250 mg of metronidazole thrice daily for 2 weeks (LAM group), while the other 67 patients received the same dosage of those agents plus 18,000 tyrosine units of pronase thrice daily for 2 weeks (LAMP group). Eradication was assessed 4-6 weeks after treatment by immunohistochemical tests and cultures. We also determined the in vitro activity of pronase against H. pylori, and evaluated the synergistic effects between pronase and the other three drugs. To investigate the effect of pronase on the structure of the SMGL, surgically removed stomachs obtained from patients who had taken pronase were examined histopathologically.
  
  
  RESULTS
  The cure rates for H. pylori infection in the LAMP group were significantly higher than those in the LAM group (intention to treat analysis: 94.0 vs. 76.5%, p =.0041). Pronase exhibited no antibacterial activity against H. pylori., and no in vitro synergistic effects were observed. In the patients who took pronase before surgery, the SMGL was thinner than in the patients who did not take pronase, and the structure of the SMGL was markedly disrupted.
  
  
  CONCLUSIONS
  Pronase has an additive effect in curing H. pylori infection. Pronase has no apparent in vitro activity against H. pylori, but may improve the local delivery of antibiotics by virtue of its removal and disruption of the SMGL.
authors.affiliation: The Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Gotoh
authors.forename: Taiji
authors.initials: T
authors.lastname: Akamatsu
authors.forename: Toshiki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Shimodaira
authors.forename: Taimei
authors.initials: T
authors.lastname: Kaneko
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Ishida
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ikeno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Katsuyama
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000382:microbiology; D005756:Gastritis / Q000188:drug therapy*; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011402:Pronase / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D064747:Lansoprazole; D008795:Metronidazole; D000658:Amoxicillin; D011402:Pronase; D009853:Omeprazole