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  • In vivo infection in the mouse was established by inoculation of C. albicans yeast in the intradermal space of the ear pinna. Two days post-infection, 0.3?mg?ml?1 TMP-1363 was administered topically. Thirty minutes after TMP-1363 application, the ears were irradiated at 514?nm using a fluence of 90?J?cm?2 delivered at an irradiance of 50?mW?cm?2. The ears were excised 2?hours post-irradiation, homogenized, and the organism XAV-939 burden was determined by a CFU assay. In vivo wide field and confocal fluorescence imaging assessed the localization of the photosensitizer in relationship to C. albicans. Photosensitization with TMP-1363 resulted in a greater than three-log increase in killing of C. albicans in vitro compared to MB. In vivo fluorescence imaging demonstrated a high degree of selective labeling of C. albicans by TMP-1363. PDT of infection using TMP-1363 resulted in a significant reduction in CFU/ear relative to untreated controls. Infected ears subjected to PDT displayed complete healing over time see more with no observable damage to the pinna. Our in vitro and in vivo findings support TMP-1363-mediated PDT as a viable therapeutic approach for the PDT of candidiasis. Lasers Surg. Med. 43:324�C332, 2011. ? 2011 Wiley-Liss, Inc. ""We examined tumor response to methylene blue (MB)-mediated photodynamic therapy (PDT) in a murine tumor model. The goal was to investigate the effects of drug�Clight interval (DLI), injection vehicle, and fluence on tumor destruction. Fluorescence and reflectance spectroscopy informed our understanding. EMT6 tumor cells were implanted intradermally on the backs of female BALB/c mice and grown to ?4-mm diameter. Mice were given a 35??l, single site, intratumor injection of 500??g/ml MB administered in either a water or a 5% ethanol-5% Cremophor-90% saline tuclazepam vehicle. PDT was begun either immediately or after a 1-hour DLI with a fluence rate of 60?mW/cm2. Each animal received a fluence of 240 or 480?J/cm2. Fluorescence and reflectance spectra were captured before and during irradiation. A protocol consisting of the Cremophor-based vehicle, 0 DLI, and a fluence of 480?J/cm2 was the most effective, with a 55% cure rate as measured by no evidence of tumor 90 days after PDT. Use of the water vehicle with this fluence and DLI reduced the cure rate to 20%. Reducing the fluence to 240?J/cm2 similarly reduced treatment efficacy with 0 and 1-hour DLIs. Univariate Cox proportional hazards analysis identified increased fluence, 0 versus 1-hour DLI, and the Cremophor versus water vehicle as highly significant independent predictors of long term tumor control (P?<?0.01 in each case). Multivariate analysis with model selection revealed fluence and injection vehicle as the best predictors of survival hazards. Fluorescence spectroscopy in vivo showed that MB fluorescence decreased monotonically during a 2-hour dark interval but was restored by irradiation.</div>

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