光动力作用对大鼠肠系膜微循环的影响

目的 观察不同浓度的光敏剂血啉甲醚(HMME)、竹红菌乙素(HB)所介导的光动力作用对大鼠肠系膜微循环的动态影响，了解光敏剂种类和浓度与微循环损伤程度之间的关系。方法 采用显微数码相机录像和IMAGE PRO图像处理系统，对52只Wistar大鼠肠系膜微循环在光动力作用过程中的改变进行实时观测并记录，通过对微血管红细胞流柱宽度、血流速度、血流状态3种指标反映微循环的动态变化。结果 光动力作用过程中、微血管内皮细胞肿胀、红细胞聚集、白细胞贴壁翻滚、附壁血栓形成，造成管腔狭窄、红细胞流径减小，并最终导致血流停滞，管腔闭塞。随光敏剂给药剂量的增加，微循环损伤出现时间提前，损伤程度加重。HMME的剂量为2．5、5、10、15和20mg／kg时，光动力作用后，红细胞流柱宽度百分比分别减少到照光前的51％、29%、19％、0%、0％，血流流速下降，分别为粒线流、粒流、粒摆流、停滞、停滞；HB的剂量为2、4、6和8mg／kg时，光动力作用后，红细胞流柱宽度百分比分别减少到照光前的88％、67％、14％、0％，血流流速分别下降为线粒流、粒流、粒摆流、停滞。血啉甲醚和竹红菌乙素所介导的光动力效应对微循环的损伤过程无明显差别，较小剂量的HB(8mg／kg)即能引起与较大剂量HMME(15mg／kg)相当的损伤效应。结论光动力作用对微循环的效应是复杂的动态过程，而内皮细胞的损伤是其重要环节，并可能引发微循环系统的进一步损伤过程。在光照剂量一定的情况下，该效应对微循环的作用强度与光敏剂给药剂量之间呈正相关关系。两种光敏剂所介导的光动力效应对微循环的作用机制基本一致，而竹红菌乙素所介导的光动力效应比血啉甲醚强。     

不同色素兔眼底对光动力治疗反应的实验研究

目的 观察不同色素兔眼底对维替泊芬(verteporfin)-光动力疗法(photodynamic therapy,PDT)的光敏反应及眼底组织损伤差别.方法 青紫蓝兔和新西兰白兔各42只,随机分为PDT治疗组、单纯激光组、单纯光敏剂组和空白对照组.其中PDT治疗组青紫蓝兔和新西兰白兔各20只,注射光敏剂10 min后接受功率密度为600 mW/cm2、波长为689 nm激光照射,照射时间15～83 s,能量密度15～50 J/cm2;单纯激光组青紫蓝兔和新西兰白兔各20只,不注射光敏剂,仅接受激光照射;单纯光敏剂组和空白对照组青紫蓝兔和新西兰白兔各1只.于PDT后第1、3、7、30和60天对兔眼行荧光素眼底血管造影术(fluorescence fundus angiography,FFA)、光镜、电镜、免疫组化检查,观察不同色素兔眼底的损伤是否存在差异.结果 PDT治疗组新西兰白兔接受能量密度25 J/cm2激光照射后1 d即出现视网膜下出血,出血量随能量增强明显增加;PDT后3～7 d,激光能量密度为20 J/cm2时新西兰白兔眼视网膜下亦可见出血,FFA检查光斑处可见明显的荧光素渗漏;PDT后30～60d,新西兰白兔视网膜下出血基本吸收,同时视网膜变薄,视网膜细胞减少,FFA检查光斑处呈片状低荧光.PDT治疗组青紫蓝兔接受能量密度30 J/cm2激光照射后1 d出现视网膜下出血,出血量随能最增强而增加;PDT后3～7 d激光能量密度25 J/cm2时受照青紫蓝兔眼视网膜下可见出血,FFA检查光斑边缘荧光素渗漏;PDT后30～60 d视网膜色素增加,FFA检查光斑区呈现斑驳状低荧光.免疫组织化学检查显示,凋亡细胞指数青紫蓝兔视网膜多于新西兰白兔,两者差异有显著意义(P＜0.05).电镜下青紫蓝兔视网膜色素上皮细胞胞质内空泡状改变较新西兰白兔明显.单纯激光组和单纯光敏剂组兔眼底未见明显改变.结论 PDT治疗后,新西兰白兔眼底的损伤以脉络膜为主,青紫蓝兔眼底的损伤以视网膜色素上皮细胞及其内视网膜为主,不同色素兔PDT治疗后眼底损伤部位存在差异.     

光动力作用对大鼠血小板释放血栓烷的影响

为了探讨光动力作用激活血小板的机制，对大鼠注射光敏剂血卟啉衍生物后，取血分离富含血小板血浆进行Ｈｅ－Ｎｅ激光照射。放射免疫测定发现，照光后血浆中ＴＸＢ２增加，ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ－１α的比值显著增高。提示光敏激活引起血小板释放血栓烷的改变可能对光敏引起的血管损伤、血流改变和凝血发生的机制有重要意义。这种现象可被消炎痛所抑制，提示临床工作中，对于正在用消炎痛或阿司匹林治疗的病人，应先停药数天后再作光动力治疗，以免影响疗效     

光照功率密度及照射方式对光动力疗法影响的研究进展

光照是光动力治疗中的重要因素。通过调节光照参数,可以使在同样用药方式和剂量等条件下的光动力治疗效果更好。近年来,该领域的众多研究者对光照参数对光动力疗法的影响以及作用的机制进行了深入的研究。这些研究集中在功率密度对光动力疗法的效果以及影响机制上。低功率密度的策略有助于产生充分的单线态氧,并可能对细胞死亡机制与免疫效应产生影响。同时,分段式光照等光照模式的采用也有可能弥补光动力治疗中的一些不足。但是由于目前尚缺乏系统的理论研究与技术手段,这些光照参数通过何种细胞生物学机制而产生作用有待进一步的研究。     

光动力作用与微循环损伤效应(二)

自Dougherty等首次报道光动力学疗法(photodynam-ictherapy,PDT)治疗恶性肿瘤以来,因其良好的组织选择性和作用强度的可控性在临床上受到普遍的重视。通过对治疗区瘤体的观察,发现光动力作用所致的微血管损坏效应甚为明显,这种现象启发人们将PDT用于良性血管增生性疾病的治疗。近年来,随着PDT基础研究的不断进展,对光动力作用的微血管效应认识进一步深入,PDT的适用范围已     

光动力作用与微循环损伤效应(一)

目前 ,随着光动力学疗法 (photodynamictherapy ,PDT)研究的逐步深入 ,其微循环系统损伤效应在治疗中的作用越来越受到重视。同时 ,新技术、新方法的不断涌现为更深入地研究和探讨微循环损伤机制提供了可能。现将近年来该领域的基础研究综述如下。一、概述在具体情况下 ,光动力     

光动力疗法与热损伤对正常大鼠胃损伤的研究

为了初步探讨ＰＤＴ与热损伤对正常胃损伤作用机制的差异，本实验以血卟啉衍生物及氩离子泵染料激光器为光敏剂及光源，观察了大鼠胃壁在单纯氩离子激光照射和ＰＤＴ时，照射部位的温度及组织学在照射后７２小时和二周的改变。结果：氩离子激光照射组和ＰＤＴ组胃壁温度均高于对照组（Ｐ＜０．０１），但ＰＤＴ组温度均低于３７℃。氩离子激光照射后的胃壁组织在７２小时各层组织均明显出血，炎细胞浸润，组织凝固坏死。电镜下见胶原纤维肿胀，排列紊乱，甚至溶解吸收。二周后损伤部位以纤维瘢痕组织修复。ＰＤＴ组在７２小时胃壁组织也有充血和炎细胞浸润，但仅有轻度组织坏死，损伤深度未超过粘膜下层。电镜下见胶原纤维结构基本正常。二周后损伤部位以组织再生修复，未留瘢痕。结论：ＰＤＴ与氩离子激光组织损伤及修复方式不同，ＰＤＴ不损伤胃粘膜下胶原纤维。     

光动力作用对人外周血中性粒细胞免疫影响的研究

目的：探讨光动力作用对人类外周血中性粒细胞免疫功能的影响。方法：采用酵母菌粘附试验,观察光动力作用对正常人中性粒细胞的粘附功能的影响,以及在光动力作用下,正常人红细胞对中性粒细胞吞噬功能的促进作用。实验将正常人的外周血中性粒细胞分离后、短时间暴露于小剂量的血卟啉衍生物及红光下,通过光镜观察活化的中性粒细胞与致敏酵母多糖的免疫粘附。结果：小剂量光动力作用可以显著增强中性粒细胞的免疫粘附功能,其Ｃ３ｂ受体花环率为（２２．５２±５．７９）％,明显大于对照组（１．３３±４．５６）％（Ｐ＜０．０１）,同时可增强红细胞促进中性粒细胞的粘附吞噬功能。结论：小剂量光动力作用可以促进人类外周血中性粒细胞及红细胞表面Ｃ３ｂ受体活性,增强其免疫粘附功能。     

鲜红斑痣光动力疗法治疗前后色差的研究

目的探讨光动力疗法治疗鲜红斑痣前后病灶颜色的变化规律,寻找客观、稳定的鲜红斑痣颜色变化评定系统。方法随机抽取鲜红斑痣患者34例34处病灶,根据国际照明委员会推荐的CIE1976L*A*B*系统,使用分光光度仪,测量病灶治疗前、治疗后即刻、治疗2～3个月的颜色参数,并分析其治疗前后的颜色参数L*、a*、b*、△E*的变化情况及相关的影响因素。结果光动力疗法治疗前,病灶与对侧正常部位的颜色比较,红绿度a*高,同时随着病变分型由P2至P6,色差值△E*明显增大;光动力疗法治疗后即刻明度L*明显下降,治疗部位肤色略变深;术后2～3个月与术前比较,治疗部位红绿度下降,且随临床疗效越显著,红绿度a*值降低越多,色差△E*升高越多;年龄、部位、疾病分型单个因素对一次治疗前后病灶颜色的变化不产生显著影响。结论 CIE标准色度系统测定光动力疗法治疗鲜红斑痣后病灶颜色的变化有较好的客观性,可将其作为临床上光动力疗法治疗鲜红斑痣疗效的评定标准之一。     

光动力疗法治疗消化道肿瘤的研究

光动力疗法 (ＰＤＴ)是继手术、放疗和化疗后又一治疗恶性肿瘤的手段 ,特别是对上述三种方法实施之后仍效果不佳的中晚期恶性肿瘤患者 ,仍可反复应用该疗法 ,现将我们1993年 2月至 1998年 8月应用ＰＤＴ治疗的 5 0例消化道肿瘤疗效观察报告如下。资料与方法1 临床资料　患者 5 0例 ,男性 40例 ,女性 10例 ;年龄5 5～ 75岁 ,平均 60岁。其中食管癌 2 8例 ,胃癌 12例 ,贲门癌10例。全部病例经上消化道钡餐透视、内镜及病理检查确诊 ,其中鳞癌 2 4例 ,腺癌 2 6例。患者均因年龄过大身体虚弱不能耐受手术 ,或肿瘤晚期无法切除 ,或手术、化疗、放…     

光动力学-微循环效应研究方法的建立与评价

目的改进活体微循环观测方法,建立更适合光动力学研究的微循环观察方法并加以验证。 方法采用Wistar大鼠肠系膜微循环观察模型,通过微循环血流流态、红细胞流柱宽度和血流流速三种指标评价该方法是否适合于光动力学-微循环效应的研究,并通过光敏剂介导的光动力学-微循环损伤效应予以验证。实验分为空白对照组、单纯激光组、单纯光敏剂HpD组、HpD-PDT组。每组Wistar大鼠10只。 结果实验观察120min,活体肠系膜微循环观察组血流流态正常,未见明显红细胞聚集、微血栓形成等改变,红细胞流柱宽度百分率未见明显下降（P〉0.05）,血流速度未见明显减慢（P〉0.05）。单纯激光组和单纯光敏剂组对微循环无明显影响,与观察的活体肠系膜微循环空白对照组比较差异无显著意义（单纯激光组P〉0.05;单纯光敏剂组P〉0.05）。在观察光动力学效应的HpD-PDT组,可见明确的光动力学损失效应,与空白对照组之间差异有显著意义（P〈0.05）。 结论改良大鼠肠系膜-活体微循环观察技术,方法可行,能够在较长时间内维持微循环正常的结构和循环动态,实现对微循环光动力学损伤效应的动态观察。     

光动力作用对鸡冠皮肤微循环影响的研究

目的观察光动力作用对鸡冠皮肤微循环结构和血流的影响。方法以来亨鸡鸡冠为实验动物模型。静脉注射HpD10mg/kg后,以波长为532nm、功率密度为100mW/cm2的倍频半导体激光照射。分别于照光5min后即刻、照光10min后即刻、照光20min后即刻、照光20min后第1天、照光20min后第3天分别取6只鸡冠行肉眼、活体显微镜、激光多普勒血流图、光镜和电镜检查,观察鸡冠激光照射处皮肤微循环结构和血流状态的动态变化。结果在本实验条件下,光动力作用5min时,微循环结构无改变,血流量增至对照组的1·17倍(P<0·05);光动力作用10min时,内皮细胞及管腔内血细胞轻度损伤改变,管腔扩张,血流量明显增加,为对照组的1·70倍(P<0·05);光动力作用20min时,微血管损伤明显,血流明显减慢,血流量为对照组的94·3%(P>0·05);光动力作用后第1天和第3天,微血管损伤加重,血流基本停滞,血流量分别为对照组的19·3%和21·6%(P<0·05)。结论光动力作用可造成鸡冠真皮乳头层毛细血管网损伤,初期微血管轻度扩张,血流加速,之后微血管损伤加重,血流紊乱。     

Role of antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: A systematic review

BackgroundThe aim was to assess the efficacy of antimicrobial photodynamic therapy (aPDT) in the treatment of aggressive periodontitis (AgP).MethodsThe addressed focused question was “Is aPDT effective in the treatment of AgP?” MEDLINE/PubMed, EMBASE, Scopus, ISI Web of knowledge and Google-Scholar databases were searched from 1977 till May 2015 using combinations of the following keywords: antimicrobial; photochemotherapy; photodynamic therapy; photosensitizing agents; AgP; scaling and root-planing (SRP). Reviews, case reports, commentaries, and articles published in languages other than English were excluded.ResultsSeven studies were included. In 5 studies, aPDT was performed as an adjunct to SRP. Laserwavelengths and duration of irradiation ranged between 660–690 nm and 60–120 s, respectively. Laser power output as reported in 2 studies was 75 mW. One study showed significant improvement in periodontal parameters for subjects receiving aPDT as an adjunct to SRP as compared to treatment with SRP alone at follow up. However, comparable periodontal parameters were reported when aPDT as an adjunct to SRP was compared to SRP alone in the treatment of AgP in one study. One study showed comparable outcomes when aPDT was compared to SRP in the treatment of AgP. In two studies, adjunctive antibiotic administration to SRP showed significantly better outcomes when compared to application of adjunctive use of aPDT to SRP.ConclusionaPDT is effective as an adjunct to SRP for the management of AgP, however, further randomized clinical trials with well defined control groups are needed in this regard.     

Photosensitizers in clinical PDT

Photosensitizers in photodynamic therapy allow for the transfer and translation of light energy into a type II chemical reaction. In clinical practice, photosensitizers arise from three families—porphyrins, chlorophylls, and dyes. All clinically successful photosensitizers have the ability to a greater or lesser degree, to target specific tissues or their vasculature to achieve ablation. Each photosensitizer needs to reliably activate at a high enough light wavelength useful for therapy. Their ability to fluoresce and visualize the lesion is a bonus. Photosensitizers developed from each family have unique properties that have so far been minimally clinically exploited. This review looks at the potential benefits and consequences of each major photosensitizer that has been tried in a clinical setting.     

Treatment of peritoneal carcinomatosis with photodynamic therapy: Systematic review of current evidence

BackgroundPeritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although therapy with intention-to-cure is offered to selective patients using cytoreductive surgery with chemotherapy, the prognosis remains poor for most of the patients. Photodynamic therapy (PDT) is a cancer-therapeutic modality where a photosensitiser is administered to patients and exerts a cytotoxic effect on cancer cells when excited by light of a specific wavelength. It has potential application in the treatment of peritoneal carcinomatosis.MethodsWe systematically reviewed the evidence of using PDT to treat peritoneal carcinomatosis in both animals and humans (Medline/EMBASE searched in June 2017).ResultsThree human and 25 animal studies were included. Phase I and II human trials using first-generation photosensitisers showed that applying PDT after surgical debulking in patients with peritoneal carcinomatosis is feasible with some clinical benefits. The low tumour-selectivity of the photosensitisers led to significant toxicities mainly capillary leak syndrome and bowel perforation. In animal studies, PDT improved survival by 15–300%, compared to control groups. PDT led to higher tumour necrosis values (categorical values 0–4 [4 = highest]: PDT 3.4 ± 1.0 vs. control 0.4 ± 0.6, p < 0.05) and reduced tumour size (residual tumour size is 10% of untreated controls, p < 0.001).ConclusionPDT has potential in treating peritoneal carcinomatosis, but is limited by its narrow therapeutic window and possible serious side effects. Recent improvement in tumour-selectivity and light delivery systems is promising, but further development is needed before PDT can be routinely applied for peritoneal carcinomatosis.     

Brain PDD and PDT unlocking the mystery of malignant gliomas

Malignant brain tumours (MBTs) have one of the worst outcomes of human cancers today and their incidence is on the increase. Current treatment failure is usually due to local recurrence of the tumour rather than distant metastasis. In the last three decades we have seen many novel and potentially effective treatment strategies rise rapidly to the rescue. Sadly, however, the majority of these approaches were not good enough to withstand the harsh reality of the sceptical gaze of the scientific eye or the stringent health economics of this millennium. PDD and PDT, however, is one of the few therapies fighting back and still standing today. The results of its randomised controlled trials are eagerly awaited. To date the literature suggests that both PDD and PDT significantly prolong the time to tumour progression, reduce local recurrence, increase radical resection and prolong overall survival of MBTs. PDD and PDT are well tolerated by patients and worthwhile pursuing.     

光动力治疗过程中组织内光衰减的实时测量

采用计算机辅助的光子计数装置实时测量了ＰＤＴ过程中实验肿瘤Ｓ１80内透射光密度的变化，结果观察到透射光密度呈下降趋势，应用ＨｐＤ的肿瘤内光密度变化与无ＨｐＤ肿瘤内光密度变化相比，有显著性差异（Ｐ＜０．０１）。     

Effect of photodynamic therapy with two photosensitizers on Streptococcus mutants: In vitro study

Background and objectivesStreptococcus mutans (S. mutans) colonizes the oral cavity and causes dental caries and periodontal diseases. Considering the importance of the treatments that decrease pathogenic microorganisms, the aim of the present research was the assessment of the antimicrobial effect of Photodynamic Therapy (PDT) with Methylene Blue (MB) and Indocyanine Green (IG) photosensitizers on S. mutans.Materials and methodsIn this In vitro experimental study, Sixty four caries-free first premolars were contaminated with 0.5 McFarland S.mutans suspension and were randomly assigned to 4 groups. The teeth in the first group were impregnated with 2% MB while the teeth in the second group were impregnated with 0.2% IG. The teeth in the first group were irradiated with continuous-wave 660 nm dod laser with 40 mw output power, energy density of 2.4 J/cm² and 100% duty cycle for 60 s, while the teeth in the second group were irradiated with continuous -wave 810 nm diode laser with 100 mw out power, density energy of 6 J/cm² and 100% duty cycle for 60 s in contact mode. In the third group, the teeth were suspended in 0.2% Chlorhexidine for 30 s. The fourth group was considered as the control. The teeth were sampled before and after the interventions and the samples were incubated in Blood Agar for 24 h. Afterwards, the number of S. mutans colonies were counted. Data were statistically analyzed by Kruskal-Wallis, Dunn's and Friedman tests.ResultsIn the groups treated with a combination of MB and IG and laser irradiation and also in the Chlorhexidine group, the final number of S. mutans colonies equaled zero. In “MB and IG groups without laser irradiation”, although the amount of microorganisms decreased, but the number of colonies did not reach zero. Pair comparisons by Dunn's test showed that there was a significant difference between “MB and IG groups without laser irradiation” and the other experimental groups p = 0.03).ConclusionPDT with MB and IG photosensitizers and also Chlorhexidine mouthwash, have the ability to completely eradicate S. mutans bacterial colonies.     

PDT experience in Brazil: A regional profile

The success of PDT and its establishment into the existent hall of therapeutic modalities depends on the collection of reported experiences from around the world. In that sense, it is important to report approaches taken by different countries and what their views are on the future of PDT. Following this idea, we present our clinical experience in photodynamic therapy (PDT) in Brazil, as well as the experimental advances coming up in parallel with clinical implementation. This report is a consequence of pioneering work in a collaborative program involving the Physics Institute in São Carlos, São Paulo State (SP), Brazil, the Medical School of the University of São Paulo, Ribeirão Preto, SP, Brazil and the Cancer Hospital Amaral Carvalho, Jaú, SP, Brazil. This collaborative program, begun in 1997, with the first patient treated in 1999, has treated over 400 patients by late 2004. About 80% of lesions were located in the head and neck or skin, but experience is being built in esophagus, bladder, gynecology, and cutaneous recurrence of breast cancer, among others. The overall results have shown to be compatible with previously reported data. Modifications, whose goal is to improve patient benefit and optimize results, are being implemented as we gain experience. In parallel with the clinical development, several laboratories have started studying experimental whose purpose is to analyze the clinical results and to contribute to the worldwide effort to bring PDT to the forefront of therapies offered to patients. We present the overall results of our 5 years experience as well as the whole implementation process.