EX-VIVO TREATMENT OF GASTRIC HELICOBACTER INFECTION BY PHOTODYNAMIC THERAPY

Attempts to develop PDT for eradication of Helicobacter infection have only been successful in vitro. We have investigated the effect of top ical sensitization (except ALA) of Helicobacter mustelae on explanted ferret gastric mucosa using one of five sensitizers ( methylene blue ( MB), toluidine blue O (TBO), phthalocyanine, haematoporphyrin derivati ve and 5-aminolavulinic acid), followed by irradiation with an appropr iately tuned copper vapour pumped dye laser. A 90% reduction in counts of bacteria sensitized with 0.75 mg TBO kg(-1) were seen after irradi ation with 200 J cm(-2). Concentrations of MB of 0.75 mg kg(-1) and 7. 5 mg kg(-1) were not toxic to H. mustelae, but the further addition of 20 J cm(-2) laser light reduced colony counts by more than 99%. MB at a concentration of 75 mg kg(-1) exhibited significant dark toxicity t owards H. mustelae, but further addition of 20 J cm(-2) laser light re sulted in near eradication of all colonies. The remaining three compou nds were ineffective. Finally, we studied the microscopic fluorescence distribution of MB (7.5 mg kg(-1)) on ferret gastric mucosa after top ical administration. Fluorescence was greatest in the superficial muco sal layer, upon which lies the bacteria. However, from experiments on rats, the energy required to kill the sensitized bacteria was insuffic ient to damage the underlying mucosa. We conclude that Helicobacter ca n be killed on host mucosal epithelium following topical administratio n of MB and subsequent exposure to laser light.