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Selectivity Mechanism Of PDT For PWS--An Elementary Study Of Photobleaching Hypothesis

Posted on:2003-08-25Degree:MasterType:Thesis
Country:ChinaCandidate:R TaoFull Text:PDF
GTID:2144360062985427Subject:Laser Medicine
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Objective In order to confirm that photobleaching hypothesis may be apossible mechanism in tissue selectivity of new photodynamic therapy (PDT) for port wine stain (PWS), the work is aimed to study the photobleaching characteristics of hematoporphyrin monomethyl ether (HMME) and hematoporphyrin derivative (HpD) in PWS skin tissue during PDT, changes in perfusion volumes of affected part during PDT, in vitro photobleaching characteristics of photosensitizers which had good tissue selectivity and the relationship between factors which could accelerate photobleaching and tissue selectivity of PDT.Methods and Results (1) Study of photobleaching characteristics of HMME and HpD in superficial layers of PWS skin during PDT:using an optical multichannel analyzer (DMA) to survey fluorescence spectrum of photosensitizers in affected part of skin tissue in 34 patients and protracting time-fluorescence intensity curves. The results revealed that the first facula curve of HpD rapidly ascended after medication and stopped while starting irradiation. There was a flat period during 30minute irradiation course.Curve slowly rised after ceasing irradiation. The first facula curve of HMME quickly reached maximum after injecting intravenously drug but dropped to trough by irradiation and rising a little after ceasi irradiation. The second facula curve of HpD rapidly failed after starting irradiation, dropping to 50% of maximum in 10 minutes after starting irradiation and descending slowly after this. The second facula curve of HMME dropped promptly to minimum after starting irradiation. (2)Study of changes in perfusion volumes of PWS skin and damage characteristics of affected part perfused abundantly after treatment: laser Doppler flowmetry was adopted to measure skin blood perfusion of affected part in 56 PWS sufferers. The comparative analysis of changes in PWS perfusion during and after treatment was carried out. The results revealed:perfusion volumes were increased a little in the first 10 minutes, dropped in 20 minutes and failed remarkably in 30 minutes after starting treatment. Perfusion volumes in groupl and group2 were 2. 55 and 3. 74 before treatment and dropped to 1. 56 and 1. 72, respectively after treatment. (3) Study of characteristics of photosensitized reaction and photobleaching of HMME and HpD in vitro: luminol chemiluminescence wasused in the study of the effect of 62 and radical oxygen species (ROS) in photosensitized reaction and traits as well as affecting factors of photosensitized reaction and self-sensitized photooxidation induced byHMME and HpD.Results revealed that 02 scavengers almost completelyrestrained chemiluminescence in photosensitized reaction induced by HMME and HpD. The maximum of chemiluminescence induced by HMME in 48 secondswas 509595 mV. Shape of HMME reaction curve was high and narrow. Area under HMME curve was 12230280. However, the maximum of HpD chemiluminescence in 235 seconds was 49000 mV. HpD curve shape was low and broad. Area under HpD curve was 5757500. With some scope, photosensitizers with high concentration , high fluence rate and short wavelength laser could shorten the time of photosensitized reaction and make curve of photosensitized reaction narrow. (4)Research of relationship between factors influencing photosensitizer photobleaching and tissue selectivity: a. Influencing factors of laser wavelength on photobleaching at the level of cells:MTT colorimetric assay was used to study cytotoxic effect of PDT on mouse lung endothelial cells. IC50, photobleaching characteristics and laser wavelength on cytotoxic effect were studied. Results showed: IC50 of HMME 桺DT and HpD-PDT were 1. 3749ug/ml and 1.07ug/ml with 510. 6nm laser irradiation, respectively. Cytotoxic effect of HpD-PDT was 1.28 times stronger than that of HMME-PDT, P>0. 05. While with 578. 2nm laser irradiation, IC50 of HMME-PDT and HpD-PDT were 2. 69688ug/ml and 2. 326055ug/ml, respectively. Cytotoxic effect of HpD-PDT was 1.15 times stronger than that of HMME-PDT, P>0. 05. b. Study...
Keywords/Search Tags:photodynamic therapy, port wine stain, hematoporphyrin monomethyl ether, hematoporphyrin derivative, photobleaching
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