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Parameter study of myocardial cell damage with photosensitization reaction under extracellular talaporfin sodium existence
Abstracts / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375
Conduction block recovery by photosensitization reaction under extracellular talaporfin sodium existence in a cardiomyocyte electrical conduction wire
Parameter study of myocardial cell damage with photosensitization reaction under extracellular talaporfin sodium existence
Mariko Kurotsu, Emiyu Ogawa, Tsunenori Arai
E. Ogawa, T. Arai
Graduate School of Science and Technology, Keio University, Japan
School of Fundamental Science and Technology, Graduate School of Science and Technology, Keio University, Japan
We studied the electrical conduction (EC) block recovery by photosensitization reaction (PR) under extracellular talaporfin sodium existence in a novel cardiomyocyte EC wire in vitro. Tachyarrhythmia can be cured by permanent block of abnormal EC. The EC block recovery sometimes occurs in the case of weak damage on myocardium. The pattern cultivation cover glass, which had 60 m width cultivation areas, was used to form the wires. The PR was operated to the wires for 600 s varying 3–120 mW/cm2 in 663 nm laser irradiances with 20 g/ml talaporfin sodium. The cardiomyocyte EC was evaluated by the cross correlation function of a fluorescence brightness of intracellular Ca2+ probe in a wire. In 30 and 60 mW/cm2 , the EC of 15 min after the PR was blocked significantly faster than the reported cardiomyocyte necrosis occurrence timing of the same PR conditions. Despite the EC block probabilities of 15 min and 2 h after the PR were almost 90% in 60 mW/cm2 , those in 30 mW/cm2 were approximately 90 and 60%, respectively. We think this temporary EC block might be caused by gap junction closure induced by intracellular Ca2+ increase. http://dx.doi.org/10.1016/j.pdpdt.2015.07.036 Light fractionation improves the response to BF-200 ALA-PDT in hairless mouse skin Henriëtte S. de Bruijn 1 , Sander Brooks 2 , Angèlique van der Ploeg-van den Heuvel 1 , Ellen R.M. de Haas 2 , Dominic J. Robinson 1 1
The Centre for Optical Diagnostics and Therapy, Department of Otolaryngology and Head & Neck Surgery, The Netherlands 2 Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands Fractionated illumination significantly enhances the effectiveness of 5-aminolevulinic-acid based photodynamic therapy (ALAPDT) but not of Methyl-AminoLevulinate (MAL). BF-200 ALA is a recently approved novel formulation of 10% ALA in a lecithin-based nanoemulsion. Here we compare the fluorescence kinetics, distribution and PDT induced response in hairless mice using BF-200 ALA, MAL and ALA. Comparable fluorescence kinetics was determined for MAL, ALA and BF-200 ALA. Cryo-sections were stained for CD31 and co-localization with PpIX fluorescence was significantly stronger after ALA and BF-200 ALA compared to MAL (p < 0.01). Intra-vital confocal microscopy showed no difference between ALA and BF-200 ALA at depth in skin. Vascular responses were not different as determined in the skin-fold chamber immediately after PDT or at day 1 in cryosections. Visual skin damage scored up to 14 days post PDT showed an significantly increased response to light fractionation for both ALA and BF-200 ALA. BF-200 ALA behaves like ALA in normal mouse skin. While light fractionated ALA-PDT was successfully translated to a treatment modality for human lesions our results suggest that ALA can be replaced by BF-200 ALA, marketed as Ameluz® in Europe, for the treatment of superficial BasalCell-Carcinoma and other skin lesions using light fractionation. http://dx.doi.org/10.1016/j.pdpdt.2015.07.037
333
We studied the myocardial cell damage of photosensitization reaction under extracellular talaporfin sodium existence with various photosensitization reaction parameters as talaporfin sodium concentration, radiant exposure, irradiance, albumin concentration, and temperature. We have proposed the application of the photosensitization reaction under extracellular talaporfin sodium existence in interstitial space to non-thermal myocardium electrical conduction block in atrial tachyarrhythmia treatment. To understand the effect and consider about the proper clinical conditions, we measured cell lethality by WST assay with various photosensitization reaction parameters as talaporfin sodium concentration (0–40 g/ml), radiant exposure (0–40 J/cm2 ), irradiance (0.03–0.65 W/cm2 ), albumin concentration (0–15 mg/ml), and temperature (27−37 ◦ C). We also measured the time response of the necrosis occurrence by intracellular Ca2+ concentration measurement with various talaporfin sodium concentrations, radiant exposures, and irradiances. We found that the photocytotoxicity decreased markedly over 0.65 mg/ml in albumin concentration. The photocytotoxicity had positive linear relation with talaporfin sodium concentration, radiant exposure, and temperature increased under 2.1 mg/ml albumin concentration. Necessary time to occur necrosis was about 200–500 min with 10–30 g/ml talaporfin sodium concentration, 10–40 J/cm2 radiant exposures, and 0.03–0.29 W/cm2 irradiance. The proper clinical photosensitization reaction parameter can be determined by these results. http://dx.doi.org/10.1016/j.pdpdt.2015.07.038 A combination regimen of 5-fluorouracil with ALA-PDT augments cell death by upregulating p53 in squamous cell carcinoma and actinic keratoses in mice and humans Sanjay Anand 1,2 , Kishore Rollakanti 1 , Tayyaba Hasan 3 , Edward Maytin 1,2,3 1
Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA 2 Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA 3 Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Combination PDT (cPDT) in which prodifferentiating agents are given prior to aminolevulinate (ALA)-PDT, is a recent approach developed in our laboratory. We have shown that methotrexate, vitamin D and 5-fluorouracil (5-FU) when given prior to PDT, make cancer cells more susceptible to cell death by enhancing the accumulation of Protoporphyrin (PpIX). In the current study using three experimental models; (i) carcinogen-induced murine SCC (ii) subcutaneous A431 tumors (human SCC) in nude mice, and (iii) actinic keratoses in human patients, we show that cPDT with 5-FU (a chemotherapeutic drug) results in significant enhancement of PpIX levels (confocal microscopy) and cell death (TUNEL and histomorphology) after PDT. As anticipated, the 5-FU pretreatment inhibited proliferation (Ki67) and stimulated cellu-
Conduction block recovery by photosensitization reaction under extracellular talaporfin sodium existence in a cardiomyocyte electrical conduction wire
Parameter study of myocardial cell damage with photosensitization reaction under extracellular talaporfin sodium existence
Mariko Kurotsu, Emiyu Ogawa, Tsunenori Arai
E. Ogawa, T. Arai
Graduate School of Science and Technology, Keio University, Japan
School of Fundamental Science and Technology, Graduate School of Science and Technology, Keio University, Japan
We studied the electrical conduction (EC) block recovery by photosensitization reaction (PR) under extracellular talaporfin sodium existence in a novel cardiomyocyte EC wire in vitro. Tachyarrhythmia can be cured by permanent block of abnormal EC. The EC block recovery sometimes occurs in the case of weak damage on myocardium. The pattern cultivation cover glass, which had 60 m width cultivation areas, was used to form the wires. The PR was operated to the wires for 600 s varying 3–120 mW/cm2 in 663 nm laser irradiances with 20 g/ml talaporfin sodium. The cardiomyocyte EC was evaluated by the cross correlation function of a fluorescence brightness of intracellular Ca2+ probe in a wire. In 30 and 60 mW/cm2 , the EC of 15 min after the PR was blocked significantly faster than the reported cardiomyocyte necrosis occurrence timing of the same PR conditions. Despite the EC block probabilities of 15 min and 2 h after the PR were almost 90% in 60 mW/cm2 , those in 30 mW/cm2 were approximately 90 and 60%, respectively. We think this temporary EC block might be caused by gap junction closure induced by intracellular Ca2+ increase. http://dx.doi.org/10.1016/j.pdpdt.2015.07.036 Light fractionation improves the response to BF-200 ALA-PDT in hairless mouse skin Henriëtte S. de Bruijn 1 , Sander Brooks 2 , Angèlique van der Ploeg-van den Heuvel 1 , Ellen R.M. de Haas 2 , Dominic J. Robinson 1 1
The Centre for Optical Diagnostics and Therapy, Department of Otolaryngology and Head & Neck Surgery, The Netherlands 2 Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands Fractionated illumination significantly enhances the effectiveness of 5-aminolevulinic-acid based photodynamic therapy (ALAPDT) but not of Methyl-AminoLevulinate (MAL). BF-200 ALA is a recently approved novel formulation of 10% ALA in a lecithin-based nanoemulsion. Here we compare the fluorescence kinetics, distribution and PDT induced response in hairless mice using BF-200 ALA, MAL and ALA. Comparable fluorescence kinetics was determined for MAL, ALA and BF-200 ALA. Cryo-sections were stained for CD31 and co-localization with PpIX fluorescence was significantly stronger after ALA and BF-200 ALA compared to MAL (p < 0.01). Intra-vital confocal microscopy showed no difference between ALA and BF-200 ALA at depth in skin. Vascular responses were not different as determined in the skin-fold chamber immediately after PDT or at day 1 in cryosections. Visual skin damage scored up to 14 days post PDT showed an significantly increased response to light fractionation for both ALA and BF-200 ALA. BF-200 ALA behaves like ALA in normal mouse skin. While light fractionated ALA-PDT was successfully translated to a treatment modality for human lesions our results suggest that ALA can be replaced by BF-200 ALA, marketed as Ameluz® in Europe, for the treatment of superficial BasalCell-Carcinoma and other skin lesions using light fractionation. http://dx.doi.org/10.1016/j.pdpdt.2015.07.037
333
We studied the myocardial cell damage of photosensitization reaction under extracellular talaporfin sodium existence with various photosensitization reaction parameters as talaporfin sodium concentration, radiant exposure, irradiance, albumin concentration, and temperature. We have proposed the application of the photosensitization reaction under extracellular talaporfin sodium existence in interstitial space to non-thermal myocardium electrical conduction block in atrial tachyarrhythmia treatment. To understand the effect and consider about the proper clinical conditions, we measured cell lethality by WST assay with various photosensitization reaction parameters as talaporfin sodium concentration (0–40 g/ml), radiant exposure (0–40 J/cm2 ), irradiance (0.03–0.65 W/cm2 ), albumin concentration (0–15 mg/ml), and temperature (27−37 ◦ C). We also measured the time response of the necrosis occurrence by intracellular Ca2+ concentration measurement with various talaporfin sodium concentrations, radiant exposures, and irradiances. We found that the photocytotoxicity decreased markedly over 0.65 mg/ml in albumin concentration. The photocytotoxicity had positive linear relation with talaporfin sodium concentration, radiant exposure, and temperature increased under 2.1 mg/ml albumin concentration. Necessary time to occur necrosis was about 200–500 min with 10–30 g/ml talaporfin sodium concentration, 10–40 J/cm2 radiant exposures, and 0.03–0.29 W/cm2 irradiance. The proper clinical photosensitization reaction parameter can be determined by these results. http://dx.doi.org/10.1016/j.pdpdt.2015.07.038 A combination regimen of 5-fluorouracil with ALA-PDT augments cell death by upregulating p53 in squamous cell carcinoma and actinic keratoses in mice and humans Sanjay Anand 1,2 , Kishore Rollakanti 1 , Tayyaba Hasan 3 , Edward Maytin 1,2,3 1
Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA 2 Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA 3 Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Combination PDT (cPDT) in which prodifferentiating agents are given prior to aminolevulinate (ALA)-PDT, is a recent approach developed in our laboratory. We have shown that methotrexate, vitamin D and 5-fluorouracil (5-FU) when given prior to PDT, make cancer cells more susceptible to cell death by enhancing the accumulation of Protoporphyrin (PpIX). In the current study using three experimental models; (i) carcinogen-induced murine SCC (ii) subcutaneous A431 tumors (human SCC) in nude mice, and (iii) actinic keratoses in human patients, we show that cPDT with 5-FU (a chemotherapeutic drug) results in significant enhancement of PpIX levels (confocal microscopy) and cell death (TUNEL and histomorphology) after PDT. As anticipated, the 5-FU pretreatment inhibited proliferation (Ki67) and stimulated cellu-