The Effect of Fluence Rate on Tumor and Normal Tissue Responses to Photodynamic Therapy

Photodynamic therapy (PDT), carried out at low fluence rates, may enhance tumor response as well as affect treatment selectivity. We have studied the effects of fluence rate on the response of the murine radiation-induced fibrosarcoma (RIF) to PDT using Photofrin® (5 mg/kg). Tumor response was tested over a large range of fluence rates (10-200 mW/cm²) and fluences (25-378 J/ cm²). Low fluence rates were more efficient; -60 J/cm2 at 10 mW/cm² was needed to achieve the same tumor growth delay as -100 J/cm² at 150 mW/cm² and -150 J/cm2 at 200 mW/cm². Despite this increased efficiency, lower fluence rates still required longer treatment times for equivalent anti-tumor effects: 95 min for 57 J/cm² at 10 mW/cm²versus 11 min for 100 J/cm² at 150 mW/cm². Effects of fluence rate on the PDT toxicity to normal tissue were examined through the response of the murine (C311) foot to Photofrin® PDT. Treatment with conditions that produced equivalent tumor responses, i.e. 57 J/cm² at 10 mW/cm² and 100 J/cm² at 150 mW/cm², resulted in a more severe foot response at the higher fluence rate (median peak response: 0.9 at 10 mW/cm², 1.5 at 150 mW/cm²) with more time required for tissue to return to normal (8 days at 10 mW/cm², at least 30 days at 150 mW/cm²). However, when feet were treated with an equal fluence of 100 J/cm2 at various fluence rates, longer healing times accompanied the lower fluence rate treatments. Overall, this paper demonstrates that lower PDT fluence rates are associated with increased efficiency of tumor response. If this increased efficiency is accounted for by lowering treatment fluence, lower fluence rates also may result in a more favorable normal tissue response to treatment.     

Suppression of Different Phases of Systemic Contact Hypersensitivity by Urocanic Acid Oxidation Productsfn1

On exposure to UV‐B, the epidermal component trans‐urocanic acid (UCA) is not only photoisomerized into cis‐ UCA but will also, at least in part, be photooxidized into UCA oxidation products (UOPs). We hypothesized that UOPs can mimic UV‐induced systemic immunosuppression comparable to the suppressive properties already established for cis‐UCA. A crude mixture of UOPs showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity (CHS) response to picryl chloride (PCI). Three of the UOPs were selected for this study: imidazole‐4‐carboxylic acid (ImCOOH), immidazole‐4‐carboxaldehyde (ImCHO) and imidazole‐4‐acetic acid (ImAc). Effects on the sensitization, elicitation and postelicitation phases of CHS to PCI in BALB/c mice were studied and compared with the effects of cis‐UCA. ImCHO was equally effective at suppressing the sensitization phase as cis‐UCA. The triplet combination of the imidazoles (1:1:1) showed more pronounced suppression than that induced by cis‐UCA. The most effective compounds for the suppression of the elicitation phase appeared to be ImAc and cis‐UCA. Significant suppression of the postelicitation phase was only obtained with the triplet combination of ImCHO, ImCOOH and ImAc, the combination that appeared to be effective at all three tested phases. Because these three UOPs are present in UV‐B‐exposed human stratum corvneum, these compounds may play a role in UV‐B‐induced immunosuppression.     

In Vivo Fluence Rate Effect in Photodynamic Therapy of Early Cancers with Tetra(m-hydroxyphenyl)chlorin

Abstract— Several parameters affect clinical trials in photodynamic therapy and influence the therapeutic outcome. Beside drug dose, light dose, drug-light interval and other variables, the fluence rate is a parameter that can influence the therapeutic results. In this study we have evaluated the fluence rate effect with a second-generation photosensitizer, tetra( m -hydroxyphenyl)chlorin (mTHPC) using a 7,12-dimethylbenz(a)anthracene induced early squamous cell carcinoma of the Syrian hamster cheek pouch as a tumor model. Following injection of 0.5 mg/kg of mTHPC, irradiation tests were performed at two drug-light intervals, 4 and 8 days. Wavelength and light dose were adapted from those applied routinely in clinical trials. Irradiations at 652 nm were carried out with fluences ranging from 8 to 20 J/cm² delivered at fluence rates of 15 and 150 mW/cm². Similar tests were also performed at 514 nm with a fluence of 80 J/cm² delivered at fluence rates ranging from 25 to 125 mW/cm². At both wavelengths and drug-light intervals for a given fluence, the higher fluence rates resulted in less tissue damage in tumor and healthy mucosae. However, the lower fluence rates yielded slightly less therapeutic selectivity. This study confirms that the fluence rate is of major importance in clinical PDT.     

Rethinking the Concepts of Fluence (UV Dose) and Fluence Rate: The Importance of Photon‐based Units – A Systemic Review

After a critical review of the fundamental equations describing photobiological and photochemical processes occurring in a medium exposed to a quasi‐collimated monochromatic UV light beam, the analysis in this review is extended to analogous processes driven by polychromatic UV light, such as that emitted by medium pressure mercury‐vapor arc lamps. The analysis is based on the Second Law of Photochemistry, namely that all photochemical events must be independent, and the rate of such events must be proportional to the rate of photon absorption. A consistent application of the Second Law of Photochemistry leads to a concept change; hence it is proposed herein to use photon fluence and photon fluence rate, rather than fluence (UV dose) and fluence rate, respectively, in the analysis and interpretation of photobiological and photochemical processes. As a consequence, many equations that have been used in the past must be revised, and some experimental information (e.g. action spectra) needs to be re‐analyzed.     

荧光法测定补骨脂素和异补骨脂素

以溴代十六烷基三甲胺（ＣＴＭＡＢ）为胶束试剂，β－环糊精（β－ＣＤ）为包含试剂，在优化实验条件下，用荧光光度法测定了补骨脂中补骨脂素和异补骨脂素．线性范围分别为２×１０－９～８×１０－６ｇ／ｍＬ，２×１０－９～８×１０－７ｇ／ｍＬ；检出限分别为２．６７×１０－１１ｇ／ｍＬ和１．１５×１０－１１ｇ／ｍＬ．     

应变率诱发镍纳米丝的非晶化

采用镶嵌原子法(EAM)作用势对镍纳米丝的拉伸过程进行了分子动力学模拟. 体系施加应变率范围在5×10^7 - 1×10^10 s^-1, 观察体系的应力-应变曲线、平均原子能量、原子轨迹, 偶相关函数随应变率的变化. 发现当应变率低于1×10^8 s^-1时, 体系发生塑性变形, 最终颈缩断裂, 偶相关函数表明体系一直保持晶体结构; 而当应变率高于1×10^9 s^-1时, 体系发生了由晶体向非晶的持续转变, 偶相关函数出现了典型的非晶峰, 高应变率诱发了Ni纳米丝的非晶化.     

Antioxidative Effect of Schiff Bases with o-Hydroxybenzylidene Groupon Free Radical Induced Hemolysis of Human Red Blood Cell

IntroductionThe recent development of free radical biologyand medicine has provided a great deal of clinicaland experimental evidence indicating that the freeradical induced peroxidation of membrane lipids isassociated with a variety of chronic healthproblems,such as cancer,atherosclerosis andageing[1,2 ] . Both natural and synthetic antioxidantshave been used to trap peroxyl radicals and/orinitiating radicals to protect the membrane lipidsagainst free radical chain reactions,and hence mayhave…     

Potentiation of Photodynamic Therapy Antitumor Activity in Mice by Nitric Oxide Synthase Inhibition Is Fluence Rate Dependent

The effects of systemic administration of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NNA) in combination with photodynamic therapy (PDT) on tumor response, tumor oxygenation and tumor and normal skin perfusion were studied in C3H mice bearing subcutaneous radiation-induced fibrosarcoma tumors. Photodynamic therapy was carried out using the photosensitizer Photofrin (5 mg/kg) in conjunction with a low fluence rate (30 mW/cm2) and a high fluence rate (150 mW/cm2) protocol at a total fluence of 100 J/cm2. Low fluence rate PDT produced approximately 15% tumor cures, a response not significantly altered by administration of 20 mg/kg L-NNA either 5 min before or after PDT. In contrast, high fluence rate PDT produced no tumor cures by itself, but addition of L-NNA either pre- or post-PDT resulted in approximately 30% and approximately 10% tumor cures, respectively. The L-NNA by itself tended to decrease tumor pO2 levels and perfusion, but statistically significant differences were reached only at one time point (1 h) with one of the oxygenation parameters measured (% values < 2 mm Hg). Photodynamic therapy by itself decreased tumor oxygenation and perfusion more significantly. Addition of L-NNA before PDT further potentiated this effect. The L-NNA exerted its most striking effects on the PDT response of the normal skin microvasculature. Low fluence rate PDT caused severe and lasting shut-down of skin microvascular perfusion. With high fluence rate PDT, skin perfusion was initially decreased but recovered to persistent normal levels within 1 h of treatment. Administration of L-NNA reversed this response, converting it to complete and lasting vascular shut-down identical to that achieved with low fluence rate PDT. This effect was somewhat L-NNA dose dependent but was still marked at a dose of 1 mg/kg. It occurred whether L-NNA was given before or after PDT. The L-NNA did not alter the long-term vascular response of skin to low fluence rate PDT. The ability of L-NNA to correspondingly improve tumor response and severely limit skin vascular perfusion following high fluence rate PDT, while providing no benefit for the low fluence rate protocol, suggests that vascular changes in the tumor surrounding normal tissue contribute to the enhanced tumor curability with adjuvant L-NNA treatment.     

Suppression of Delayed and Contact Hypersensitivity Responses in Mice Have Different UV Dose Responses

Although acute exposure to UV radiation suppresses the induction of delayed-type (DTH) and contact (CHS) hypersensitivity in mice, it is not clear whether the photo-biological mechanism(s) involved in suppressing these closely related immune reactions is the same. A careful examination of the UV dose responses and wavelength dependencies involved in suppressing CHS and DTH may provide important insights into the mechanisms involved. We compared the UV dose-response curves for suppressing four closely related immune reactions, local and systemic suppression of CHS to dinitrofluorobenzene, systemic suppression of DTH to Candida albicans and systemic suppression of DTH to alloantigen using three different UV spectra (FS40 sunlamps, Kodacel-filtered FS40 sunlamps and solar-simulated light). For each immune response studied, the amount of UVB radiation required to induce 50% immune suppression was lowest when FS40 sunlamps were used, highest with solar-simulated light and intermediate when Kodacel-filtered FS40 sunlamps were used, but the differences observed were not statistically significant. The UV dose-response curves for immune suppression differed significantly depending on the assay used, the site of antigenic sensitization and the antigen used. These findings suggest that the mechanisms by which UV radiation induces immune suppression differ for the four immunological reactions studied.     

数码成像比色法探究反应物浓度对化学反应速率的影响

利用数码成像比色法探究反应物浓度对化学反应速率的影响,采用紫红色溶液互补光"绿"通道的亮度值-时间的曲线变化表征反应物浓度与化学反应速率的关系。同时也利用分光光度计研究反应物浓度与反应速率的关系,测出透光率-时间的曲线变化。从实验结果比较分析,用数码成像比色法探究反应物浓度对化学反应速率的影响是非常简便可行的方法,同时让学生使用随身所带的电子产品开展实验研究,不仅使实验教学具有趣味性和科学性,而且能更好地培养学生的创新潜质。     

增加一种反应物浓度对反应物转化率影响的研究

通过建构模型探讨了多反应物平衡体系中增加反应物浓度对转化率的影响,并用曲线进行表征。模型表明,转化率的变化与反应物和生成物化学计量数相对大小关联紧密。文中结论澄清了某些错误认知,对中学化学教学有一定的指导意义。     

Protection of UV-induced Suppression of Skin Contact Hypersensitivity: A Common Feature of Flavonoids after Oral Administration?

In this study we investigated the effect of the dietary ingredients fruit and vegetable, green tea phenol extract (GTP) and the specific flavonoid components quercetin and chrysin on the UV-induced suppression of the con-tact hypersensitivity (CHS) response to picryl chloride (PCl). The SKH-1 mice were fed with test diet from 2 or 4 weeks before and during the UV irradiation (daily, 95 mJ/cm²) and tested for the CHS ear-swelling response 10 weeks after the onset of the irradiation. For the CHS, mice were immunized with PCl by epicutaneous application on nonirradiated sites. Four days after sensitization all mice were challenged on both sides of each ear by topical application of one drop PCl. In addition, from mice fed with the fruit and vegetable mixture the number of Langerhans cells (LC) were scored in the skin and from mice fed with quercetin, quercetin levels in plasma were measured at week 11 after the start of UV irradiation. It was found that fruit and vegetable (19% in the diet), GTP (0.1% and 0.01% in the drinking water), quercetin (1% in the diet) and chrysin (1% and 0.1% in the diet), prevented statistically significantly the UV-induced suppression of CHS to PCl. In the skin of mice fed with fruit and vegetables combined with UV irradiation the number of LC were comparable to the control mice, whereas the number of LC were significantly diminished in mice treated with UV only. This protective effect on the presence of LC in the epidermis after UV irradiation, which was also observed in a previous study with quercetin, may play a role in the prevention of UV-induced immunosuppression by the flavonoids tested. In conclusion, we found protection of flavonoids against UV-induced effects on CHS, which may be a common feature of most flavonoids.     

英美中学化学实验教学案例分析——探究浓度对化学反应速率的影响

“探究浓度对化学反应速率的影响”是中外高中典型的基础实验。实验内容类似,但教学方法大相径庭。我国侧重以实验结论学习化学原理。英美国家注重实验的过程和方法：设计控制变量,绘图,统计分析数据,注重后实验过程,考试评估巩固实验教学的行为过程。     

自制装置探究浓度与温度对化学反应速率的影响

利用光敏电阻型光敏传感器模块具有在环境光线亮度达不到设定阈值时,DO端输出高电平的特性,自制实验装置来探究温度和反应物浓度等对硫代硫酸钠与盐酸反应速率的影响。相关实验数据的图表表明利用自制装置与肉眼测定的结果相比较,准确度更高。     

升温速率对金属铅的熔化和过热行为的影响

采用分子动力学方法和QSC(quantum Sutton-Chen)力场研究了升温速率对金属铅的熔化和过热行为的影响.模拟中考虑了缺陷和表面对熔化和过热行为的作用.结果表明，升温速率对金属铅的熔化和过热行为影响很大，随着升温速率的升高，金属铅的熔点有所升高.快的升温速率会导致金属铅体系内部无序化程度增加，进而使体系能量增加，降低了熔化相变的能垒.升温速率导致的金属铅的过热极限大约为780 K.     

用荧光法研究补骨脂素与异补骨脂素的药代动力学

补骨脂素和异补骨脂素是补骨脂的主要有效成分。为了研究补骨脂素和异补骨脂素的药物代谢动力学,本文采用胶束荧光法对补骨脂素和异补骨脂素在兔体内的血药浓度进行２４ｈ监测,求出系列药动学参数。结果表明：补骨脂素的Ｋａ为３．２２５１ｈ－１,ｔ１／２（α）为 ０．１８４９ｈ,ｔ１／２（β）为１０．７０６５ｈ,Ｔ为０．８２００ｈ,ＡＵＣ为２１．６１０４ｍｇ·ｈ／Ｌ;异补骨脂素的Ｋａ为４．４３２９ｈ－１,ｔ１／２（Ｋａ）为０．１５６４ｈ,ｔ１／２（Ｋｅ）为２．１７７７ｈ,Ｔ为１．０９５５ｈ,ＡＵＣ为７．２４１８ｍｇ·ｈ／Ｌ。     

Suppression of Photocyclization: Stabilization of an Aggregation‐Induced Tetraaryldistyrylbenzene Emitter

The synthesis of 2,3,5,6‐tetrakis(2,6‐difluorophenyl)di(styryl)benzene by using a conventional synthetic sequence, including Diels–Alder and Horner reactions is reported. The target is an effective aggregation‐induced emitter. It is photostable with respect to electrocyclization, due to the presence of the fluorine substituents. This compound undergoes photochemical trans/cis isomerization of its styryl double bonds.     

探究实验教学中“控制单一变量”思想的培养——以“浓度对化学反应速率的影响”为例

控制单一变量思想是化学学科的本质之一,是探究实验中不可或缺的认知成分。针对人教版高中《化学反应原理》"浓度对化学反应速率的影响"一节,充分挖掘实验的定量价值,以3种不同层次浓度方案的设计和评价,生成控制单一变量思想的具体内涵。教学过程中以任务驱动的形式,充分激发学习兴趣,培养实验探究能力、深化思维水平。     

Effect of Concentration Gradient on the Morphology Development in Polymer Solutions Undergoing Thermally Induced Phase Separation

Anisotropic porous polymeric materials fabricated from the phase separation method via spinodal decomposition are used in various practical engineering applications. We studied the formation of anisotropic porous polymeric materials numerically, by imposing an initial linear concentration gradient across a model polymer solution. The initial concentration gradient is placed at three different regions of the polymer sample for comparison purposes. All the simulation results are in good agreement with published experimental observations, which are reported from the applications of porous polymeric membranes. The structure development shows that an anisotropic porous morphology forms when an initial linear concentration gradient is applied to the model polymer solution.