Background and Objectives: Photodynamic therapy (PDT) appears to be endowed with several favorable features for the treatment of infections originated by microbial pathogens, including a broad spectrum of action, the efficient inactivation of antibiotic-resistant strains, the low mutagenic potential, and the lack of selection of photoresistant microbial cells. Therefore, intensive studies are being pursued in order to define the scope and field of application of this approach. Results: Optimal cytocidal activity against a large variety of bacterial, fungal, and protozoan pathogens has been found to be typical of photosensitizers that are positively charged at physiological pH values (e.g., for the presence of quaternarized amino groups or the association with polylysine moieties) and are characterized by a moderate hydrophobicity (n-octanol/water partition coefficient around 10). These photosensitizers in a micromolar concentration can induce a > 4-5 log decrease in the microbial population after incubation times as short as 5-10 minutes and irradiation under mild experimental conditions, such as fluence-rates around 50 mW/cm 2 and irradiation times shorter than 15 minutes. Conclusions: PDT appears to represent an efficacious alternative modality for the treatment of localized microbial infections through the in situ application of the photosensitizer followed by irradiation of the photosensitizer-loaded infected area. Proposed clinical fields of interest of antimicrobial PDT include the treatment of chronic ulcers, infected burns, acne vulgaris, and a variety of oral infections.

Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The development of alternative therapies against nosocomial infections caused by clinically relevant pathogens represents a major public health concern. RLP068/Cl is a novel Zn(II) phthalocyanine proposed as a photosensitizer suitable for antimicrobial photodynamic therapy (APDT) for localized infections. Its ability, following activation by light, to induce resistance in three major human pathogens after 20 daily passages was studied. Simultaneously for the same strains, the ability of daily sequential subcultures in subinhibitory concentrations of RLP068/Cl to develop resistant mutants without illumination was evaluated. We demonstrate that 20 consecutive APDT treatments with RLP068/Cl did not result in any resistant mutants and that, in dark conditions, only Staphylococcus aureus strains had increased MICs of RLP068/Cl. However, even in this case, the susceptibility of the mutated bacteria to APDT was not affected by their MIC increase.

Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process. Successive bioluminescence images of a representative mouse skin scratch model infected with 108 CFU MRSA.

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The results of the in vivo study demonstrated that APDT with RLP068/Cl may be useful in the management of chronic infected wounds, accelerating the repair process through a significant bacterial inhibition.

1 The ability to modify the pain threshold by the two M,-muscarinic agonists: AF-102B and by the specific M2-agonist arecaidine was examined in mice and rats by using three different noxious stimuli: chemical (writhing test), thermic (hot-plate test) and mechanical (paw pressure test).

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The effect of dietary fat, starch and cellulose on individual and total fecal bile acids was studied in mice after 4 wk of feeding diets containing different levels of fat (5 and 29%), starch (3, 36 and 57-65%) and cellulose (2 and 10%). Diet affected the fecal concentration of deoxycholic acid, beta-muricholic acid and total bile acids. Increasing dietary fat from 5 to 29% significantly increased the level of deoxycholic acid and total bile acids. An increase in dietary cellulose from 2 to 10% significantly decreased the level of deoxycholic acid, beta-muricholic acid and total bile acids. High levels of dietary starch (36 and 57-65%) did not significantly affect the excretion of deoxycholic, beta-muricholic and total fecal bile acids. Starch was able to bind bile acids in vitro and to affect the level of fecal free bile acids. In high fat diets, the level of free bile acids was lower in the feces of animals fed 36% starch diets than in those fed 3% starch diets. This reduction of free bile acids was accompanied by a reduction in colon proliferative activity. We suggest that free, rather than total, bile acids are the effective damaging agents for colon mucosa, and may represent a risk factor in the development of cancer.