BACKGROUND & AIMS: :The purpose of this study was to compare the in vivo and in vitro phototoxicity potentials of 13 fragrances. We used the 3T3 neutral red uptake phototoxicity (3T3 NRU PT) test and the photohaemolysis test as in vitro phototoxicity assays. In the 3T3 NRU PT test, all of the fragrances were non-phototoxic. Six fragrances were phototoxic in the photohaemolysis test. Three of the six photohaemolytic fragrances were phototoxic in the guinea-pig photoirritation test. These phototoxic fragrances did not cause cellular phototoxicity, but showed a photohaemolytic reaction. The photohaemolysis test was more sensitive than the 3T3 NRU PT test for screening for the phototoxicity of fragrances. The accuracy of this in vitro phototoxicity test battery was 82%. It is thought that the major phototoxic mechanism of fragrances is cell membrane damage. We suggest that a battery composed of the 3T3 NRU PT test and the photohaemolysis test is a simple and effective model for the in vitro phototoxicity assay of fragrances.

背景与目标： : 这项研究的目的是比较13种香料的体内和体外光毒性潜力。我们使用3T3中性红摄取光毒性 (3T3 NRU PT) 试验和光溶血试验作为体外光毒性试验。在3T3 NRU PT测试中，所有香精都是无毒的。在光溶血试验中，六种香料具有光毒性。在豚鼠光刺激试验中，六种光致溶血香料中的三种具有光毒性。这些光毒性香料不会引起细胞光毒性，但显示出光致溶血反应。光溶血试验比3T3 NRU PT试验对筛选香料的光毒性更敏感。82% 了这种体外光毒性测试电池的准确性。人们认为香料的主要光毒性机制是细胞膜损伤。我们建议由3T3 NRU PT测试和光溶血测试组成的电池是用于香料体外光毒性测定的简单有效模型。

BACKGROUND & AIMS: A number of sulphonamide-derived oral antidiabetics (chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide) and diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chloratalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide) were investigated for phototoxicity in a cell culture model. Cell death dependent on ultraviolet A fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzyl-hydrochlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at 5x10(-5) M and higher concentrations, bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at 2.5x10(-4) M and higher concentrations, and the oral antidiabetics glibenclamide and gliquidone as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at 5(-4) M and higher concentrations. Electron microscopic investigations showed swelling of mitochondria and endoplasmic reticulum as well as aggregation of euchromatin when the cells were irradiated in the presence of photosensitizers.

背景与目标： 多种磺酰胺衍生的口服抗糖尿病药 (氯丙酰胺，格列吡嗪，格列吡嗪，格列喹酮，格列吡酮，格列美定，妥拉酰胺和甲苯磺丁酰胺) 和利尿剂在细胞培养模型中研究了三氯甲烷和xipamide) 的光毒性。在存在口服抗糖尿病药格列本脲和格列喹酮以及利尿剂贝甲替嗪，苄氟甲肼，苄基氢氯噻嗪，布美他尼，布替嗪，氢氯噻嗪，氢氟甲酰肼，吡咯烷，聚噻嗪和三氯甲烷的情况下，观察到细胞死亡取决于紫外线A通量和测试物质浓度。苯达氟甲肼在5x10(-5) M和更高浓度下具有光毒性，贝美齐，苄基氢氯噻嗪，布美他尼和氢氟甲肼在2.5x10(-4) M和更高浓度下具有光毒性，口服抗糖尿病药格列本脲和格列喹酮以及利尿剂布替齐特，氢氯噻嗪，吡拉他尼，聚噻嗪和三氯甲烷在5(-4) M和更高的浓度下具有光毒性。电子显微镜检查显示，在光敏剂存在下照射细胞时，线粒体和内质网肿胀以及常染色质聚集。

BACKGROUND & AIMS: :A gram negative bacteria Escherichia coli (Dh5alpha strain) was developed as an alternate test system of phototoxicity. Eight drugs (antibiotics) and cosmetic products (eight face creams) were examined for their phototoxicity using this test system. Five known phototoxic compounds were used to validate the test system. UVA-radiation induced phototoxicity of these compounds was tested by agar gel diffusion assay. Decrease in colony forming units (CFU) was taken as an end point of phototoxicity. The phototoxic compounds and antibiotics produced significant reduction in CFU (p<0.001) at 80 microg/ml concentrations under exposure to UVA-radiation (5.4-10.8 J/cm(2)). One face cream was found phototoxic and produced significant decrease in CFU of E. coli at 1.0mg/ml concentration under UVA exposure (10.8 J/cm(2)). The minimum effective concentration of tetracycline and dose of UVA-radiation were also determined by observing growth inhibition of E. coli through disc diffusion assay. The observations suggested that E. coli can be used as an alternative test system for phototoxicity evaluation of chemicals. A battery of test systems is required to conclude the toxic/phototoxic potential of a chemical agent. In view of the speed, easiness, sensitivity and low cost, E. coli is introduced as one of the alternate test system for phototoxicity studies in safety evaluation of various chemical ingredients or formulations used in cosmetics and drugs.

背景与目标： : 开发了革兰氏阴性菌大肠杆菌 (dh5α 菌株) 作为光毒性的替代测试系统。使用该测试系统检查了八种药物 (抗生素) 和化妆品 (八种面霜) 的光毒性。使用五种已知的光毒性化合物来验证测试系统。通过琼脂凝胶扩散测定法测试了UVA辐射诱导的这些化合物的光毒性。菌落形成单位 (CFU) 的减少被视为光毒性的终点。在暴露于UVA辐射 (5.4-10.8 J/cm(2)) 下，光毒性化合物和抗生素在80微克/毫升浓度下产生显著的CFU降低 (p<0.001)。发现一种面霜具有光毒性，并且在UVA暴露 (10.8 J/cm(2)) 下，在1.0mg/ml浓度下，大肠杆菌的CFU显着降低。通过圆盘扩散试验观察大肠杆菌的生长抑制，确定了四环素的最小有效浓度和UVA辐射剂量。观察结果表明，大肠杆菌可以用作化学物质光毒性评估的替代测试系统。需要一组测试系统来得出化学试剂的毒性/光毒性。鉴于大肠杆菌具有速度快、容易、灵敏度高、成本低等特点，将其作为用于化妆品和药品中各种化学成分或制剂安全性评价的光毒性研究的替代试验体系之一。

BACKGROUND & AIMS: BACKGROUND:Ultraviolet (UV) radiation is the main exogenous inductor of skin damage and so photoprotection is important to control skin disorders. The Antarctic moss Sanionia uncinata is an important source of antioxidants and the photoprotective activity of its organic extracts has been investigated. This study aimed to evaluate the potential photoprotection, cytotoxicity and embryotoxicity of residual aqueous fraction (AF) from the moss S. uncinata. METHODS:UV-visible spectrum and SPF (sun protection factor) were determined by spectrophotometry. Embryotoxicity potential was evaluated by Fish embryo-larval toxicity test using zebrafish (Danio rerio) as organism model. Cell death assays by water-soluble tetrazolium salt (WST-1) and lactate dehydrogenase (LDH) were investigated using HaCaT keratinocyte cell line cultured in monolayers and three dimensions (3D). Phototoxicity and association with UV-filters were performed by 3T3 neutral red uptake test. RESULTS:The AF showed sharp absorption bands in the UV region and less pronounced in the visible region. The SPF was low (2.5 ± 0.3), but the SPF values of benzophenone-3 and octyl-methoxycinnamate increased ~ 3 and 4 times more, respectively, in association with AF. The AF did not induce significant lethal and sublethal effects on zebrafish early-life stages. In monolayers, the HaCaT cell viability, evaluated by WST-1, was above 70% by ≤0.4 mg AF/mL after 48 and 72-h exposure, whereas ≤1 mg AF/mL after 24-h exposure. The LDH assay showed that the cell viability was above 70% by ≤0.4 mg AF/mL even after 72-h exposure, but ≤1 mg/mL after 24 and 48-h exposure. In 3D cell culture, an increased cell resistance to toxicity was observed, because cell viability of HaCaT cell by WST-1 and LDH was above ~ 90% when using ≤1 and 4 mg AF/mL, respectively. The AF demonstrated values of photo irritation factor < 2 and of photo effect < 0.1, even though in association with UV-filters. CONCLUSIONS:The residual AF absorbs UV-vis spectrum, increased SPF values of BP-3 and OMC and does not induce embryotoxicity to zebrafish early life-stage. The cell death assays allowed establishing non-toxic doses of AF and phototoxicity was not detected. AF of S. uncinata presents a good potential for skin photoprotection against UV-radiation.

背景与目标：

BACKGROUND & AIMS: :Genetically encoded photosensitizers are increasingly used as optogenetic tools to control cell fate or trigger intracellular processes. A monomeric red fluorescent protein called SuperNova has been recently developed, however, it demonstrates suboptimal characteristics in most phototoxicity-based applications. Here, we applied directed evolution to this protein and identified SuperNova2, a protein with S10R substitution that results in enhanced brightness, chromophore maturation and phototoxicity in bacterial and mammalian cell cultures.

背景与目标： : 基因编码的光敏剂越来越多地用作控制细胞命运或触发细胞内过程的光遗传学工具。最近开发了一种称为超新星的单体红色荧光蛋白，但是，它在大多数基于光毒性的应用中表现出次优的特性。在这里，我们对该蛋白进行了定向进化，并鉴定了SuperNova2，这是一种具有S10R取代的蛋白，可在细菌和哺乳动物细胞培养物中提高亮度，发色团成熟和光毒性。

BACKGROUND & AIMS: :Rhodamine 123 (R123) is a permeant, cationic, fluorescent dye that localizes preferentially within mitochondria of living carcinoma cells. MGH-U1 human bladder carcinoma cells incubated in vitro with 10 microM R123 for 30 min and then irradiated at 514.5 nm with an argon ion laser underwent selective, phototoxic injury to mitochondria. Ultrastructurally, treatment with R123 plus irradiation with 10 J/cm2 caused selective, progressive mitochondrial alterations consisting of disruption of cristae, vacuolization, swelling, increasing numbers of ring-shaped and angulated mitochondria at 4 to 8 h after irradiation, and obliteration of many mitochondria at 24 to 48 h. Confocal laser scanning microscopy after treatment with R123 plus irradiation with 10 to 30 J/cm2 demonstrated altered uptake and localization of subsequently administered R123, accompanied by striking mitochondrial fragmentation. Irradiation caused a dose-dependent depletion of extractable R123, due to a photosensitized efflux that began immediately and progressed by 4 h after irradiation with 10 to 30 J/cm2; further uptake after reincubation in the presence of R123 was also quantitatively impaired in cells previously irradiated with 30 J/cm2.

背景与目标： 罗丹明123 (R123) 是一种渗透的阳离子荧光染料，优先定位在活癌细胞的线粒体内。MGH-U1人膀胱癌细胞与10 microM R123体外孵育30分钟，然后用氩离子激光在514.5 nm照射，对线粒体进行选择性的光毒性损伤。在超微结构上，用R123加10 J/cm2辐照处理会导致选择性的进行性线粒体改变，包括cr破坏，空泡化，肿胀，照射后4至8小时环形和成角度的线粒体数量增加，以及在24至48小时内许多线粒体消失。用R123加10至30 J/cm2辐照处理后的共聚焦激光扫描显微镜显示，随后施用的R123的摄取和定位发生了改变，并伴有明显的线粒体断裂。辐照导致可提取的R123的剂量依赖性耗竭，这是由于光敏外排立即开始并在用10至30 J/cm2辐照后4小时内进展; 在先前用30 J/cm2辐照的细胞中，在R123存在下重新吸收后的进一步吸收也受到定量损害。

BACKGROUND & AIMS: :In this study, important H1 antihistaminic drugs, i.e., emedastine (EME), epinastine (EPI), and ketotifen (KET), were irradiated with UV/Vis light (300-800 nm) in solutions of different pH values. Next, they were analyzed by new high performance liquid chromatography (HPLC) methods, in order to estimate the percentage of degradation and respective kinetics. Subsequently, ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) was used to identify their photodegradation products and to propose degradation pathways. In addition, the peroxidation of linoleic acid and generation of singlet oxygen (SO) and superoxide anion (SA) were examined, together with the molar extinction coefficient (MEC) evaluation, to estimate their phototoxic risk. The photodegradation of all EME, EPI, and KET followed pseudo first-order kinetics. At pH values of 7.0 and 10.0, EPI was shown to be rather stable. However, its photostability was lower at pH 3.0. EME was shown to be photolabile in the whole range of pH values. In turn, KET was shown to be moderately labile at pH 3.0 and 7.0. However, it degraded completely in the buffer of pH 10.0. As a result, several photodegradation products were separated and identified using the UPLC-MS/MS method. Finally, our ROS assays showed a potent phototoxic risk in the following drug order: EPI < EME < KET. All of these results may be helpful for manufacturing, storing, and applying these substantial drugs, especially in their ocular formulations.

背景与目标： : 在这项研究中，在不同ph值的溶液中用UV/Vis光 (300-800 nm) 照射重要的H1抗组胺药物，即伊美斯汀 (EME) 、依平斯汀 (EPI) 和酮替芬 (KET)。接下来，通过新的高效液相色谱 (HPLC) 方法对它们进行分析，以估计降解百分比和相应的动力学。随后，使用超高效液相色谱串联质谱 (uplc-ms/MS) 鉴定其光降解产物并提出降解途径。此外，还检查了亚油酸的过氧化作用以及单线态氧 (SO) 和超氧阴离子 (SA) 的产生以及摩尔消光系数 (MEC) 的评估，以评估其光毒性风险。所有EME，EPI和KET的光降解均遵循伪一级动力学。在7.0和10.0的ph值下，EPI显示为相当稳定。然而，其在pH 3.0下的光稳定性较低。EME在整个ph值范围内均显示为光不稳定。反过来，KET显示在pH 3.0和7.0下适度不稳定。然而，它在pH 10.0的缓冲液中完全降解。结果，使用uplc-ms/MS方法分离并鉴定了几种光降解产物。最后，我们的ROS测定法按以下药物顺序显示出有效的光毒性风险: EPI < EME

BACKGROUND & AIMS: :We examined the mechanisms of quinolone phototoxicity in vivo and in vitro. Simultaneous p.o. administration of a quinolone and ultraviolet-A (UVA) irradiation for 4 h induced auricular skin inflammation in BALB/c mice, including edema and neutrophil infiltration in the dermis. Antioxidants inhibited the inflammation in the early stage and cyclooxygenase inhibitors did in both the early and later stages, whereas 5-lipoxygenase inhibitors or histamine antagonists had no effect. The phototoxic inflammation was also induced in mast cell-deficient WBB6F1-W/Wv mice. Corresponding to the in vivo results, incubation with a quinolone under UVA irradiation stimulated BALB/c 3T3 mouse fibroblast cells to release prostaglandin E2 (PGE2) and 6-keto-PGF1alpha, but not leukotriene B4. In contrast, UVA-pre-irradiated quinolones did not affect PG release from fibroblasts. The PGE2 release was inhibited by cyclooxygenase inhibitors, antioxidants, protein kinase C (PKC) inhibitors and a tyrosine kinase (TK) inhibitor, but not by antibodies against tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1). These results lead to a hypothesis that reactive oxygen species generated from quinolones under UVA irradiation trigger PG release from dermal fibroblasts via PKC and TK activation, resulting in skin inflammation and that 5-lipoxygenase products, histamine, TNF alpha or IL-1 is ruled out from the mechanism.

背景与目标： : 我们在体内和体外研究了喹诺酮的光毒性机制。同时p.o.给予喹诺酮和紫外线-a (UVA) 照射4小时会引起BALB/c小鼠的耳廓皮肤炎症，包括真皮中的水肿和中性粒细胞浸润。抗氧化剂在早期抑制炎症，在早期和晚期均抑制环氧合酶抑制剂，而5-脂氧合酶抑制剂或组胺拮抗剂则无效。在肥大细胞缺陷型WBB6F1-W/Wv小鼠中也诱导了光毒性炎症。与体内结果相对应，在UVA照射下与喹诺酮孵育刺激BALB/c 3T3小鼠成纤维细胞释放前列腺素E2 (PGE2) 和6-keto-pgf1α，但不释放白三烯b4。相反，UVA预辐照的喹诺酮类药物不会影响成纤维细胞中PG的释放。环氧合酶抑制剂，抗氧化剂，蛋白激酶C (PKC) 抑制剂和酪氨酸激酶 (TK) 抑制剂抑制了PGE2的释放，但不受针对肿瘤坏死因子 α (TNF α) 和interleukin-1 (IL-1) 的抗体的抑制。这些结果导致了一个假设，即在UVA照射下由喹诺酮类产生的活性氧物质通过PKC和TK激活触发真皮成纤维细胞释放PG，导致皮肤炎症，并且排除了5-脂氧合酶产物、组胺、TNF-α 或IL-1。

BACKGROUND & AIMS: Purpose:To evaluate the riboflavin (RF) concentration and distribution in the corneal stroma and the risk for endothelial photodamage during corneal crosslinking (CXL) following 10- and 30-minute impregnation. Methods:De-epithelialized rabbit corneas were subjected to impregnation for 10 and 30 minutes with different RF formulations. Human corneal endothelial cells (HCECs) were subjected to different RF concentrations and ultraviolet A (UVA) dosages. Assays included fluorescence imaging, absorption spectroscopy of corneal buttons and anterior chamber humor, and cell viability staining. Results:After 10 and 30 minutes of impregnation, respectively, anterior chamber fluid showed an RF concentration of (1.6 ± 0.21)•10-4% and (5.4 ± 0.21)•10-4%, and trans-corneal absorption reported an average corneal RF concentration of 0.0266% and 0.0345%. This results in a decrease in endothelial RF concentration from 0.019% to 0.0056%, whereas endothelial UVA irradiance increases by 1.3-fold when changing from 30 to 10 minutes of impregnation. HCEC viability in cultures exposed to UVA illumination and RF concentrations as concluded for the endothelium after 10- and 30-minute impregnation was nonstatistically different at 51.0% ± 3.9 and 41.3 ± 5.0%, respectively. Conclusions:The risk for endothelial damage in CXL by RF/UVA treatment does not increase by shortened impregnation because the 30% increase in light intensity is accompanied by a 3.4-fold decrease of the RF concentration in the posterior stroma. This is substantiated by similar endothelial cell toxicity seen in vitro, which in fact appears to favor 10-minute impregnation. Translational Relevance:This study offers compelling arguments for (safely) shortening RF impregnation duration, reducing patients' burden and costly operation room time.

背景与目标：

BACKGROUND & AIMS: :The poor selectivity of photosensitizers for tumor tissue remains a drawback in photodynamic therapy (PDT) and could be improved by adapted formulations. The cellular uptake, localization and phototoxicity of meta-tetra(hydroxyphenyl)chlorin (mTHPC) encapsulated in submicronic colloidal carriers have been studied in macrophage-like J774 cells and HT 29 human adenocarcinoma cells. Nanocapsules with an external layer made of poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG NCs), PLA coated with poloxamer 188 (polox PLA NCs) and oil/water nanoemulsion (NE) have been examined. The cellular uptake by J774, as determined by microspectroflorimetry, is reduced with mTHPC encapsulated into surface-modified NCs--PLA-PEG and polox PLA--compared with naked PLA, indicating a possible limitation of the clearance of such carriers by the reticuloendothelial system. Encapsulation also modifies the interaction between mTHPC and HT29 cells. Compared with the manufacturer's solution (PEG, ethanol, water), the cellular uptake is strongly reduced. However, the HT29 phototoxicity is much less affected and a protecting effect against plasma proteins is observed. Fluorescence microscopy reveals a specific punctate fluorescence pattern with PLA-PEG and polox PLA NCs in contrast to a more diffuse distribution with NE and solution, indicating that photodamage targeting could be different. These findings suggest that photosensitizers encapsulated into surface-modified nanocapsules could be a promising approach for improving PDT efficacy and this has to be confirmed in vivo.

背景与目标： : 光敏剂对肿瘤组织的选择性差仍然是光动力疗法 (PDT) 的缺点，并且可以通过调整配方来改善。已在巨噬细胞样J774细胞和HT 29人腺癌细胞中研究了封装在亚微离子胶体载体中的间四 (羟基苯基) 氯蛋白 (mTHPC) 的细胞摄取，定位和光毒性。已经检查了具有由聚 (D，L乳酸) (PLA NCs) 制成的外层的纳米胶囊，接枝聚乙二醇的PLA (PLA-PEG NCs)，涂有泊洛沙姆188的PLA (polox PLA NCs) 和油/水纳米乳液 (NE)。与裸露的PLA相比，通过显微分光光度法测定的J774的细胞摄取被封装在表面修饰的NCs (PLA-PEG和polox PLA) 中的mTHPC降低，这表明网状内皮系统可能限制了此类载体的清除。封装也改变了mTHPC和HT29细胞之间的相互作用。与制造商的溶液 (PEG，乙醇，水) 相比，细胞摄取大大减少。然而，HT29光毒性的影响要小得多，并且观察到对血浆蛋白的保护作用。荧光显微镜显示出PLA-PEG和polox PLA NCs具有特定的点状荧光模式，而NE和溶液具有更漫射的分布，表明光损伤靶向可能有所不同。这些发现表明，封装在表面改性的纳米胶囊中的光敏剂可能是改善PDT功效的有前途的方法，这必须在体内得到证实。

BACKGROUND & AIMS: :N-retinylidene-N-retinylethanolamine (A2E) accumulation in the retina is a prominent marker of retinal degenerative diseases. Blue light exposure is considered as an important factor contributing to dry age-related macular degeneration (AMD). Eggplant and its constituents have been shown to confer health benefits, but their therapeutic effects on dry AMD remain incompletely understood. In this study, we showed that an extract of Solanum melongena L. (EPX) protected A2E-laden ARPE-19 cells against blue light-induced cell death via attenuating reactive oxygen species. Transcriptomic analysis demonstrated that blue light modulated the expression of genes associated with stress response, inflammation, and cell death, and EPX suppressed the inflammatory pathway induced by blue light in A2E-laden ARPE-19 cells by inhibiting the nuclear translocation of nuclear factor kappa B and transcription of pro-inflammatory genes (CXCL8 and IL1B). The degradation of intracellular A2E was considered the major mechanism underlying the protective effect of EPX. Moreover, chlorogenic acid isolated from EPX exerted protective effects against blue light-induced cell damage in A2E-laden ARPE-19 cells. In vivo, EPX administration in BALB/c mice reduced the fundus damage and degeneration of the retinal layer in a blue light-induced retinal damage model. Collectively, our findings suggest the potential role of Solanum melongena L. extract for AMD treatment.

背景与目标： : 视网膜中N-亚黄基-N-视黄醇胺 (A2E) 的积累是视网膜退行性疾病的重要标志。蓝光暴露被认为是导致干性年龄相关性黄斑变性 (AMD) 的重要因素。茄子及其成分已被证明具有健康益处，但它们对干性AMD的治疗作用仍未完全了解。在这项研究中，我们证明了茄子的提取物。(EPX) 通过减弱活性氧来保护A2E-laden ARPE-19细胞免受蓝光诱导的细胞死亡。转录组分析表明，蓝光调节与应激反应、炎症和细胞死亡相关的基因的表达，EPX通过抑制核因子 κ B的核易位和促炎基因 (CXCL8和IL1B) 的转录来抑制A2E-laden ARPE-19细胞中由蓝光诱导的炎症途径。细胞内A2E的降解被认为是EPX保护作用的主要机制。此外，从EPX中分离出的绿原酸对A2E-laden ARPE-19细胞中的蓝光诱导的细胞损伤具有保护作用。在体内，在蓝光诱导的视网膜损伤模型中，在BALB/c小鼠中施用EPX可减少眼底损伤和视网膜层变性。总的来说，我们的发现表明茄属提取物在AMD治疗中的潜在作用。

BACKGROUND & AIMS: :Bituminous tars (Ichthammol and Ichthyol Pale) are widely used in pharmaceutical, veterinary and cosmetic industries for their anti-microbial, anti-inflammatory and anti-pruritic effects. In contrast to coal tar, no phototoxicity of bituminous tars has been reported in man, although both Ichthammol and Ichthyol Pale exhibit UV absorption which is higher and broader for the former. The validated 3T3 NRU phototoxicity test indicated phototoxic potential of both substances. The phototoxicity test in a 3D human skin model (EpiDerm) only confirmed phototoxicity for Ichthammol. Human data on Ichthammol phototoxicity are missing. A photopatch test in human volunteers was performed in order to clarify the discrepancy between the phototoxicity found in the skin model and the absence of reported human phototoxicity. Following 4h exposure to 5% and 10% aqueous solutions of Ichthammol and Ichthyol Pale the test sites were irradiated with a UVA dose of 5 J/cm(2). Early phototoxic reaction (erythema) within 4-6h after irradiation was only elicited by Ichthammol and not by Ichthyol Pale. These data correspond well with those from the 3D skin model test and suggest the necessity to employ several test systems for final phototoxicity assessment. In addition to the results obtained in 3T3 NRU PT, further testing on 3D skin models may better reflect bioavailability of a given chemical in the skin, relevant to the situation in humans.

背景与目标： : 沥青焦油 (鱼腥味和鱼腥味) 因其抗微生物，抗炎和止痒作用而广泛用于制药，兽医和化妆品行业。与煤焦油相反，尽管鱼炭和鱼炭都表现出紫外线吸收，但在人类中没有沥青焦油的光毒性，前者的紫外线吸收更高，更宽。经过验证的3T3 NRU光毒性测试表明两种物质的光毒性潜力。3D人类皮肤模型 (表皮) 中的光毒性测试仅证实了鱼酰胺的光毒性。关于鱼腥草素光毒性的人类数据缺失。为了澄清在皮肤模型中发现的光毒性与没有报告的人类光毒性之间的差异，对人类志愿者进行了光测试。暴露于5% 和10% 的鱼腥酚和鱼腥酚水溶液中4小时后，用5 j/cm(2) 的UVA剂量照射测试部位。辐照后4-6小时内的早期光毒性反应 (红斑) 仅由鱼胺酚引起，而不是由鱼鳞苍白引起。这些数据与3D皮肤模型测试中的数据非常吻合，并建议有必要使用几种测试系统进行最终的光毒性评估。除了在3T3 NRU PT中获得的结果外，在3D皮肤模型上进行的进一步测试可能会更好地反映皮肤中给定化学物质的生物利用度，与人类的情况有关。

BACKGROUND & AIMS: :Methoxsalen (8-methoxypsoralen) was used as the photoxic substance in the study of the properties of various vehicles in photoepicutaneous testing. Macrogols as such were relatively poor bases, and positive reactions were seen only occasionally at a concentration of 0.05% methoxsalen. Increasing amounts of water in macrogols brought forth more numerous and stronger reactions. The photoxicity also increased when ethanol was added. The reactions were, however, weaker than to those with aqueous bases. Wool fat and glycerol as vehicles usually reacted in the same way as polyethylene glycols when water was added. An explanation of the mechanism of the changes in the properties of vehicles due to the addition of water/ethanol requires further investigation.

背景与目标： : 甲氧沙林 (8-甲氧基补骨脂素) 被用作光氧化物质，用于研究光表皮测试中各种媒介物的特性。像这样的大分子是相对较差的碱基，并且仅在0.05% 甲氧沙林浓度下偶尔看到阳性反应。大分子中的水量增加会引起更多更强烈的反应。加入乙醇后，光x度也会增加。但是，该反应比具有水性碱的反应弱。当加入水时，作为载体的羊毛脂肪和甘油通常以与聚乙二醇相同的方式反应。对由于添加水/乙醇而导致车辆性能变化的机理的解释需要进一步研究。

BACKGROUND & AIMS: BACKGROUND:Near-infrared photoimmunotherapy (NIR-PIT) constitutes a new class of molecular-targeted theranostics utilizing monoclonal antibody (mAb)-photosensitizer conjugates and NIR light. In this study, we developed a new type of NIR-PIT targeting vascular endothelial growth factor receptor 2 (VEGFR-2) expressed on vascular endothelium in an experimental gastric cancer model and evaluated the feasibility by comparing conventional NIR-PIT targeting cancer cell membrane in vitro and in vivo. METHODS:HER2-positive human gastric cancer cells, NCI-N87, were used for the experiments. Anti-HER2 mAb, trastuzumab and anti-VEGFR-2 mAb, DC101 were conjugated to photosensitizer, IR700. Phototoxicity in response to NIR-PIT were investigated in vitro and in vivo. Microvessel densities, as an indicator of angiogenesis, were counted in harvested xenografts after NIR-PIT to elucidate the mechanism. RESULTS:DC101-IR700 did not induce phototoxic effect in vitro because of the absence of expression of VEGFR-2 in NCI-N87 cancer cells. However, it induced an antitumor effect in NCI-N87 xenograft tumors accompanied with damage in tumor neovasculature as determined by decreasing tumor microvessel density, which represents a different mechanism than that of conventional NIR-PIT targeting antigens expressed on the tumor cell membrane. CONCLUSION:We demonstrated a new approach of NIR-PIT utilizing a target on vascular endothelium, such as VEGFR-2, and this treatment might lead to the development of a new therapeutic strategy for human gastric cancer.

背景与目标：

BACKGROUND & AIMS: :Albino and pigmented (black-hooded) rats of the Sprague-Dawley and Long Evans strains, respectively, were compared in terms of their susceptibility to retinal damage by ultraviolet-A light. Anesthetized animals were exposed to ultraviolet-A light (lambda max = 360 nm) for 4 hr and retinal damage was assessed 1 week later by electroretinographic analysis and measurement of outer nuclear layer thickness. Albino and pigmented animals showed approximately the same severity of ultraviolet-A retinal damage as a function of exposure irradiance. Furthermore, both pigmentation strains showed swelling and vesiculation of rod inner segment mitochondria as an early manifestation of damage. An abbreviated study on a congenic rat strain (F344-c/+) of albino and pigmented littermates again demonstrated an equal susceptibility to ultraviolet-A phototoxicity for both pigmentation phenotypes. These findings provide evidence that melanin is not the mediator of short-wavelength phototoxicity to the retina, since damage readily occurred in albino animals completely lacking this chromophore.

背景与目标： : 分别比较了Sprague-Dawley和Long Evans品系的白化病大鼠和有色 (黑帽) 大鼠对紫外线A光对视网膜损伤的敏感性。将麻醉的动物暴露于紫外线A光 (最大 λ = 360 nm) 4小时，并在1周后通过视网膜电图分析和测量外核层厚度评估视网膜损伤。白化病和有色动物表现出与暴露辐照度有关的紫外线-视网膜损伤的严重程度大致相同。此外，两种色素沉着菌株均显示杆状内段线粒体肿胀和囊泡，这是损伤的早期表现。对白化病和有色同窝的同系大鼠品系 (F344-c/) 的简短研究再次表明，两种色素沉着表型对紫外线-a光毒性的敏感性相同。这些发现提供了证据，表明黑色素不是对视网膜短波长光毒性的介体，因为完全缺乏这种发色团的白化病动物很容易发生损害。