Light fluence dosimetry in lung-simulating cavities

NASA Astrophysics Data System (ADS)

Zhu, Timothy C.; Kim, Michele M.; Padawer, Jonah; Dimofte, Andreea; Potasek, Mary; Beeson, Karl; Parilov, Evgueni

2018-02-01

Accurate light dosimery is critical to ensure consistent outcome for pleural photodynamic therapy (pPDT). Ellipsoid shaped cavities with different sizes surrounded by turbid medium are used to simulate the intracavity lung geometry. An isotropic light source is introduced and surrounded by turbid media. Direct measurements of light fluence rate were compared to Monte Carlo simulated values on the surface of the cavities for various optical properties. The primary component of the light was determined by measurements performed in air in the same geometry. The scattered component was found by submerging the air-filled cavity in scattering media (Intralipid) and absorbent media (ink). The light source was located centrally with the azimuthal angle, but placed in two locations (vertically centered and 2 cm below the center) for measurements. Light fluence rate was measured using isotropic detectors placed at various angles on the ellipsoid surface. The measurements and simulations show that the scattered dose is uniform along the surface of the intracavity ellipsoid geometries in turbid media. One can express the light fluence rate empirically as φ =4S/As*Rd/(1- Rd), where Rd is the diffuse reflectance, As is the surface area, and S is the source power. The measurements agree with this empirical formula to within an uncertainty of 10% for the range of optical properties studied. GPU voxel-based Monte-Carlo simulation is performed to compare with measured results. This empirical formula can be applied to arbitrary geometries, such as the pleural or intraperitoneal cavity.

Atomic Oxygen Fluence Monitor

NASA Technical Reports Server (NTRS)

Banks, Bruce A.

2011-01-01

This innovation enables a means for actively measuring atomic oxygen fluence (accumulated atoms of atomic oxygen per area) that has impinged upon spacecraft surfaces. Telemetered data from the device provides spacecraft designers, researchers, and mission managers with real-time measurement of atomic oxygen fluence, which is useful for prediction of the durability of spacecraft materials and components. The innovation is a compact fluence measuring device that allows in-space measurement and transmittance of measured atomic oxygen fluence as a function of time based on atomic oxygen erosion yields (the erosion yield of a material is the volume of material that is oxidized per incident oxygen atom) of materials that have been measured in low Earth orbit. It has a linear electrical response to atomic oxygen fluence, and is capable of measuring high atomic oxygen fluences (up to >10(exp 22) atoms/sq cm), which are representative of multi-year low-Earth orbital missions (such as the International Space Station). The durability or remaining structural lifetime of solar arrays that consist of polymer blankets on which the solar cells are attached can be predicted if one knows the atomic oxygen fluence that the solar array blanket has been exposed to. In addition, numerous organizations that launch space experiments into low-Earth orbit want to know the accumulated atomic oxygen fluence that their materials or components have been exposed to. The device is based on the erosion yield of pyrolytic graphite. It uses two 12deg inclined wedges of graphite that are over a grit-blasted fused silica window covering a photodiode. As the wedges erode, a greater area of solar illumination reaches the photodiode. A reference photodiode is also used that receives unobstructed solar illumination and is oriented in the same direction as the pyrolytic graphite covered photodiode. The short-circuit current from the photodiodes is measured and either sent to an onboard data logger, or

Preclinical studies of photodynamic therapy of intracranial tissues

NASA Astrophysics Data System (ADS)

Lilge, Lothar D.; Sepers, Marja; Park, Jane; O'Carroll, Cindy; Pournazari, Poupak; Prosper, Joe; Wilson, Brian C.

1997-05-01

The applicability and limitations of the photodynamic threshold model were investigated for an intracranial tumor (VX2) and normal brain tissues in a rabbit model. Photodynamic threshold values for four different photosensitizers, i.e., Photofrin, 5(delta) -aminolaevulinic acid (5(delta) -ALA) induced Protoporphyrin IX (PPIX), Tin Ethyl Etiopurpurin (SnET2), and chloroaluminum phthalocyanine (AlClPc), were determined based on measured light fluence distributions, macroscopic photosensitizer concentration in various brain structures, and histologically determined extent of tissue necrosis following PDT. For Photofrin, AlClPc, and SnET2, normal brain displayed a significantly lower threshold value than VX2 tumor. For 5(delta) -ALA induced PPIX and SnET2 no or very little white matter damage, equalling to very high or infinite threshold values, was observed. Additionally, the latter two photosensitizers showed significantly lower uptake in white matter compared to other brain structures and VX2 tumor. Normal brain structures lacking a blood- brain-barrier, such as the choroid plexus and the meninges, showed high photosensitizer uptake for all photosensitizers, and, hence, are at risk when exposed to light. Results to date suggest that the photodynamic threshold values iares valid for white matter, cortex and VX2 tumor. For clinical PDT of intracranial neoplasms 5(delta) -ALA induced PPIX and SnET2 appear to be the most promising for selective tumor necrosis.However, the photosensitizer concentration in each normal brain structure and the fluence distribution throughout the treatment volume and adjacent tissues at risk must be monitored to maximize the selectivity of PDT for intracranial tumors.

An improved analytic function for predicting light fluence rate in circular fields on a semi-infinite geometry

NASA Astrophysics Data System (ADS)

Zhu, Timothy C.; Lu, Amy; Ong, Yi-Hong

2016-03-01

Accurate determination of in-vivo light fluence rate is critical for preclinical and clinical studies involving photodynamic therapy (PDT). This study compares the longitudinal light fluence distribution inside biological tissue in the central axis of a 1 cm diameter circular uniform light field for a range of in-vivo tissue optical properties (absorption coefficients (μa) between 0.01 and 1 cm-1 and reduced scattering coefficients (μs') between 2 and 40 cm-1). This was done using Monte-Carlo simulations for a semi-infinite turbid medium in an air-tissue interface. The end goal is to develop an analytical expression that would fit the results from the Monte Carlo simulation for both the 1 cm diameter circular beam and the broad beam. Each of these parameters is expressed as a function of tissue optical properties. These results can then be compared against the existing expressions in the literature for broad beam for analysis in both accuracy and applicable range. Using the 6-parameter model, the range and accuracy for light transport through biological tissue is improved and may be used in the future as a guide in PDT for light fluence distribution for known tissue optical properties.

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

PubMed Central

Al-Qahtani, Ahmed; Alkahtani, Saad; Kolli, Bala; Tripathi, Pankaj; Dutta, Sujoy; Al-Kahtane, Abdullah A.; Jiang, Xiong-Jie; Ng, Dennis K. P.

2016-01-01

Photodynamic inactivation of Leishmania spp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency against Leishmania tropica promastigotes and axenic amastigotes in vitro. The uptake of these PCs by both Leishmania stages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation of Leishmania spp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitized Leishmania tropica strains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ∼650 nm) at a fluence of 1 to 2 J cm−2. Quantitative fluorescence assays based on the loss of GFP/CFSE from live Leishmania tropica showed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Leishmania tropica strains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC50s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation of Leishmania spp. for use as vaccines or vaccine carriers. PMID:26824938

TREATMENT OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION WITH RANIBIZUMAB COMBINED WITH KETOROLAC EYEDROPS OR PHOTODYNAMIC THERAPY.

PubMed

Semeraro, Francesco; Russo, Andrea; Delcassi, Luisa; Romano, Mario R; Rinaldi, Michele; Chiosi, Flavia; Costagliola, Ciro

2015-08-01

To evaluate whether ketorolac eyedrops plus intravitreal ranibizumab (IVR) or verteporfin photodynamic therapy plus IVR provides additional benefit over IVR monotherapy for treatment of choroidal neovascularization in age-related macular degeneration. This was a prospective, randomized, pilot study in 75 patients with naive choroidal neovascularization. Patients were randomized 1:1:1 into 3 groups: ranibizumab monotherapy (RM), ranibizumab plus ketorolac, or ranibizumab plus loading-phase reduced-fluence verteporfin photodynamic therapy (RV) groups. At 12 months, all groups showed significant improvement in both best-corrected visual acuity and central retinal thickness. The mean best-corrected visual acuity change from baseline to 12 months was -0.14 ± 0.52 logMAR (20/73 ± 20/29), -0.25 ± 0.60 logMAR (20/46 ± 20/27), and -0.10 ± 0.30 (20/97 ± 20/40) logMAR in RM, ranibizumab plus ketorolac, and RV groups, respectively. The mean central retinal thickness change from baseline to 12 months was -125 ± 15 μm, -141 ± 21 μm, and -130 ± 15 μm in RM, ranibizumab plus ketorolac, and RV groups, respectively. Both ranibizumab plus ketorolac and RV groups required fewer IVR treatments than RM. Compared with RM and ranibizumab plus verteporfin photodynamic therapy, the combination of 0.45% ketorolac eyedrops 3 times a day and ranibizumab in patients with choroidal neovascularization provided superior best-corrected visual acuity and central retinal thickness outcomes. Both combination regimens required fewer IVR injections than RM during the 12-month follow-up period.

New interplanetary proton fluence model

NASA Technical Reports Server (NTRS)

Feynman, Joan; Armstrong, T. P.; Dao-Gibner, L.; Silverman, S.

1990-01-01

A new predictive engineering model for the interplanetary fluence of protons with above 10 MeV and above 30 MeV is described. The data set used is a combination of observations made from the earth's surface and from above the atmosphere between 1956 and 1963 and observations made from spacecraft in the vicinity of earth between 1963 and 1985. The data cover a time period three times as long as the period used in earlier models. With the use of this data set the distinction between 'ordinary proton events' and 'anomalously large events' made in earlier work disappears. This permitted the use of statistical analysis methods developed for 'ordinary events' on the entire data set. The greater than 10 MeV fluences at 1 AU calculated with the new model are about twice those expected on the basis of models now in use. At energies above 30 MeV, the old and new models agree. In contrast to earlier models, the results do not depend critically on the fluence from any one event and are independent of sunspot number. Mission probability curves derived from the fluence distribution are presented.

Photodynamic treatment of endodontic polymicrobial infection in vitro

PubMed Central

Fimple, Jacob Lee; Fontana, Carla Raquel; Foschi, Federico; Ruggiero, Karriann; Song, Xiaoqing; Pagonis, Tom C.; Tanner, Anne C. R.; Kent, Ralph; Doukas, Apostolos G.; Stashenko, Philip P.; Soukos, Nikolaos S.

2008-01-01

We investigated the photodynamic effects of methylene blue (MB) on multi-species root canal biofilms comprising Actinomyces israelii, Fusobacterium nucleatum subspecies nucleatum, Porphyromonas gingivalis and Prevotella intermedia in experimentally infected root canals of extracted human teeth in vitro. The four test microorganisms were detected in root canals using DNA probes. Scanning electron microscopy (SEM) showed the presence of biofilms in root canals prior to therapy. Root canal systems were incubated with MB (25 µg/ml) for 10 minutes followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm2. Light was delivered from a diode laser via a 250 µm diameter polymethyl methacrylate optical fiber that uniformly distributed light at 360°. Photodynamic therapy (PDT) achieved up to 80% reduction of colony-forming unit counts. We conclude that PDT can be an effective adjunct to standard endodontic antimicrobial treatment when the PDT parameters are optimized. PMID:18498901

Half-Fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: Predisposing Factors for Visual Acuity Outcomes.

PubMed

Matušková, Veronika; Vysloužilová, Daniela; Uher, Michal

2017-12-18

Central serous chorioretinopathy (CSC) is characterised by a serous detachment of the neurosensory retina in the macula. Chronic CSC tends to affect older individuals with a less favourable visual outcome. Photodynamic therapy (PDT) with verteporfin is a possible therapeutic approach in cases of CSC with no tendency for spontaneous resorption. PDT has shown good anatomic and functional results in treating chronic CSC. For the purpose of diminishing side effects, modifications of the standard protocol were used. This is a retrospective study of 32 eyes with CSC of 32 patients treated by half-fluence PDT. The patients underwent complete ophthalmology examination. On optical coherence tomography (OCT) we measured central retinal thickness (CRT), the outer nuclear layer (ONL), presence of subfoveolar detachment of retinal pigment epithelium (PED), disturbance of external limiting membrane (ELM), morphological changes in the inner segment/outer segment (IS/OS) line and retinal pigment epithelium (RPE) atrophy. We evaluated at baseline, 3 and 12 months after PDT. The mean BCVA at baseline was 0.41 ± 0.23 log MAR, the mean BCVA at 3 months was 0.24 ± 0.20 and at the end of the follow-up it was 0.23 ± 0.200. We observed statistically significant improvements of visual acuity after 3 and 12 months (p < 0.001, Wilcoxon test). The mean central retinal thickness at baseline was 373 ± 87 µm, the mean CRT after 3 months was 234 ± 42 µm and after 12 months 223 ± 39 µm. A significant reduction from baseline was seen after 3 months and 12 months (p < 0.001, Wilcoxon test). Baseline ONL reached 80 ± 27 µm, after 3 months it was 78 ± 20 and after 12 months it was 74 ± 20 µm. We observed a statistically significant change in diminishing the amount of PED after PDT after 3 months and after 12 months (p = 0.021, McNemar's test). We observed that in patients with RPE ablation, there is lower chance for the restitution of the IS

Kinetics of tumor necrosis factor production by photodynamic-therapy-activated macrophages

NASA Astrophysics Data System (ADS)

Pass, Harvey I.; Evans, Steven; Perry, Roger; Matthews, Wilbert

1990-07-01

The ability of photodynamic therapy (PDT) to activate macrophages and produce cytokines, specifically tumor necrosis factor (TNF), is unknown. Three day thioglycolate elicited macrophages were incubated with 25 ug/mi Photofrin II (P11) for 2 hour, after which they were subjected to 630 nm light with fluences of 0-1800 J/m. The amount of TNF produced in the system as well as macrophage viability was measured 1, 3, 6, and 18 hours after POT. The level of TNF produced by the macrophages was significantly elevated over control levels 6 hours after POT and the absolute level of tumor necrosis factor production was influenced by the treatment energy and the resulting macrophage cytotoxicity. These data suggest that POT therapy induced cytotoxicity in vivo may be amplified by macrophage stimulation to secrete cytokines and these cytokines may also participate in other direct/indirect photodynamic therapy effects, i.e. immunosuppression, vascular effects.

Evaluation of Silicon Phthalocyanine 4 Photodynamic Therapy Against Human Cervical Cancer Cells In Vitro and in Mice

PubMed Central

Gadzinski, Jill A.; Guo, Jianxia; Philips, Brian J.; Basse, Per; Craig, Ethan K.; Bailey, Lisa; Comerci, John T.; Eiseman, Julie L.

2017-01-01

Background Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. Methods CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distrubtion were determined. For in vitro Pc 4 photodynamic therapy cells were irradiated at 667nm at a fluence of 2.5 J/cm2 at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight h after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm2. Results The IC50s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6μM and 0.016μM and >10μM and 0.026μM; as spheroids, IC50s of Pc 4 photodynamic therapy were, 0.26μM and 0.01μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay. Conclusions Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program. PMID:28890844

Chemical luminescence measurement of singlet oxygen generated by photodynamic therapy in solutions in real time

NASA Astrophysics Data System (ADS)

Luo, Shiming; Xing, Da; Zhou, Jing; Qin, Yanfang; Chen, Qun

2005-04-01

Photodynamic therapy (PDT) is a cancer therapy that utilizes optical energy to activate a photosensitizer drug in a target tissue. Reactive oxygen species (ROS), such as 1O2 and superoxide, are believed to be the major cytotoxic agents involved in PDT. Although current PDT dosimetry mostly involves measurements of light and photosensitizer doses delivered to a patient, the quantification of ROS production during a treatment would be the ultimate dosimetry of PDT. Technically, it is very difficult and expensive to directly measure the fluorescence from 1O2, due to its extreme short lifetime and weak signal strength. In this paper, Photofrin(R) and 635nm laser were used to generate 1O2 and superoxide in a PDT in solution. Compound 3,7- dihydro-6-{4-[2-(N"-(5-fluoresceinyl) thioureido) ethoxy] phenyl}-2- methylimidazo{1,2-a} pyrazin-3-one sodium salt,an Cyp- ridina luciferin analog commonly referred as FCLA, was used as a chemical reporter of ROS. The 532nm chemiluminescence (CL) from the reaction of the FCLA and ROS was detected with a photon multiplier tube (PMT) system operating at single photon counting mode. With the setup, we have made detections of ROS generated by PDT in real time. By varying the amount of conventional PDT dosage (photosensitizer concentration, light irradiation fluence and its delivery rate) and the amount of FCLA, the intensity of CL and its consumption rate were investigated. The results show that the intensity and temporal profile of CL are highly related to the PDT treatment parameters. This suggests that FCLA CL may provide a highly potential alternative for ROS detection during PDT.

Effect of Photodynamic Therapy with Posterior Sub-Tenon Triamcinolone Acetonide on Predominantly Classic Choroidal Neovascularization: One-Year Results

PubMed Central

Sertoz, Ayzin Deniz; Ates, Orhan; Keles, Sadullah; Kocer, Ibrahim; Kulacoglu, Destan Nil; Baykal, Orhan

2008-01-01

Objective: The aim of this study was to compare the results of monotherapy (photodynamic therapy) and combined therapy (photo-dynamic therapy with posterior sub-Tenon triamcinolone acetonide) in age-related macular degeneration (AMD). Materials and Methods: Forty eyes from forty patients with diagnosed neovascular AMD were enrolled in this study during March-2005 – October-2008. All patients were grouped in either the study or the control group. Both the study and control groups consisted of 20 eyes from 20 patients. The study group was treated with posterior sub-Tenon triamcinolone acetonide (PSTA) along with their initial photodynamic therapy (PDT) treatment. The control group members were treated with PDT alone. All patients were examined at 1, 3, 6 and 12 months. Visual acuity (VA), lesion size and number of treatment sessions were recorded during each examination. Results: The mean difference between pre- and post-treatment VA using the Snellen chart was +0.6 ± 1.7 in study group and −1.4 ± 1.7 in control. The difference for VA was significant in the study group as compared to control (p<0.05). The decrease in lesion size in the study group was 680±1195.2 µm, and the decrease was 32.75 ± 809.9 µm in the control. The difference with regard to the decrease in lesion sizes was significant in the study group as compared to the control (p<0.05). Total PDT treatment sessions were applied 1.2 times per patient in the study group and 1.9 times per patient in the control group. The difference was not significant (p>0.05). Conclusion: Our study showed that PSTA with PDT significantly reduces CNV growth, and improves VA at the 12-month follow-up in patients with AMD. PMID:25610041

Photodynamic Therapy for Cancer Cells Using a Flash Wave Light Xenon Lamp

NASA Astrophysics Data System (ADS)

Kimura, Makoto; Kashikura, Kasumi; Yokoi, Satomi; Koiwa, Yumiko; Tokuoka, Yoshikazu; Kawashima, Norimichi

We determined photodynamic therapy (PDT) efficacy using a flash wave (FW) and a continuous wave (CW) light, of which the fluence rate was 70 W/cm2, for murine thymic lymphoma cells (EL-4) cultivated in vitro. The irradiation frequency and the pulse width of the FW light were in the range of 1-32 Hz and less than one millisecond, respectively. 5-Aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) was used as a photosensitizer. When EL-4 with ALA administration was irradiated by the light for 4 h (irradiation fluence: 1.0J/cm2), the survival rate of EL-4 by the FW light was lower than that by the CW light, except for the FW light with irradiation frequency of 32 Hz, and decreased gradually with decreasing irradiation frequency. Moreover, the FW light, especially at lower irradiation frequency, was superior to the CW light for the generation of singlet oxygen in an aqueous PpIX solution. Therefore, thehigher PDT efficacy for EL-4 of the FW light would be caused by the greater generation of singlet oxygen in the cells.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Devos, Laura; Thecua, Elise; Vicentini, Claire; Mortier, Laurent; Mordon, Serge

2017-09-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol

Effect of photodynamic therapy on short-wavelength fundus autofluorescence in eyes with acute central serous chorioretinopathy.

PubMed

Hagen, Stefan; Ansari-Shahrezaei, Siamak; Smretschnig, Eva; Glittenberg, Carl; Krebs, Ilse; Steiner, Irene; Binder, Susanne

2015-02-01

To evaluate short-wavelength FAF as a parameter of retinal pigment epithelium function in eyes with acute symptomatic central serous chorioretinopathy after indocyanine green angiography-guided verteporfin photodynamic therapy with half-fluence rate. A retrospective review over a period of 1 year of short-wavelength FAF images of 15 consecutive patients treated with half-fluence rate (25 J/cm) indocyanine green angiography-guided verteporfin photodynamic therapy due to acute symptomatic central serous chorioretinopathy was performed. Short-wavelength (488 nm) FAF gray values were evaluated with a confocal scanning laser ophthalmoscope at a 350-μm diameter and a 1,200-μm diameter circle centered on the fovea. The change in short-wavelength (488 nm) FAF gray values for the 2 circles was evaluated by calculating the differences of respective values between the first month after treatment and the 3, 6, 9, and 12 months follow-up. Mean differences (95% confidence interval) in short-wavelength (488 nm) FAF gray values of the 350-μm and 1,200-μm diameter circle between the 1-month and the 3-month (n = 15) follow-up were -0.03 (-0.11 to 0.05) (P = 0.46) and -0.03 (-0.17 to 0.10) (P = 0.6). Respective differences between the 1 month and the 6 (n = 15), 9 (n = 14), and 12 months (n = 13) of follow-up were -0.03 (-0.11 to 0.05) (P = 0.42) and -0.04 (-0.16 to 0.08) (P = 0.5); -0.05 (-0.12 to 0.03) (P = 0.23) and -0.06 (-0.18 to 0.07) (P = 0.33); -0.03 (-0.12 to 0.07) (P = 0.57) and -0.07 (-0.20 to 0.05) (P = 0.22). Half-fluence rate (25 J/cm) indocyanine green angiography-guided verteporfin photodynamic therapy did not significantly affect short-wavelength FAF at a 350-μm diameter and a 1,200-μm diameter circle in eyes with resolved acute symptomatic central serous chorioretinopathy throughout 12 months of follow-up.

Optimization of light source parameters in the photodynamic therapy of heterogeneous prostate

NASA Astrophysics Data System (ADS)

Li, Jun; Altschuler, Martin D.; Hahn, Stephen M.; Zhu, Timothy C.

2008-08-01

The three-dimensional (3D) heterogeneous distributions of optical properties in a patient prostate can now be measured in vivo. Such data can be used to obtain a more accurate light-fluence kernel. (For specified sources and points, the kernel gives the fluence delivered to a point by a source of unit strength.) In turn, the kernel can be used to solve the inverse problem that determines the source strengths needed to deliver a prescribed photodynamic therapy (PDT) dose (or light-fluence) distribution within the prostate (assuming uniform drug concentration). We have developed and tested computational procedures to use the new heterogeneous data to optimize delivered light-fluence. New problems arise, however, in quickly obtaining an accurate kernel following the insertion of interstitial light sources and data acquisition. (1) The light-fluence kernel must be calculated in 3D and separately for each light source, which increases kernel size. (2) An accurate kernel for light scattering in a heterogeneous medium requires ray tracing and volume partitioning, thus significant calculation time. To address these problems, two different kernels were examined and compared for speed of creation and accuracy of dose. Kernels derived more quickly involve simpler algorithms. Our goal is to achieve optimal dose planning with patient-specific heterogeneous optical data applied through accurate kernels, all within clinical times. The optimization process is restricted to accepting the given (interstitially inserted) sources, and determining the best source strengths with which to obtain a prescribed dose. The Cimmino feasibility algorithm is used for this purpose. The dose distribution and source weights obtained for each kernel are analyzed. In clinical use, optimization will also be performed prior to source insertion to obtain initial source positions, source lengths and source weights, but with the assumption of homogeneous optical properties. For this reason, we compare the

Fast approximate delivery of fluence maps for IMRT and VMAT

NASA Astrophysics Data System (ADS)

Balvert, Marleen; Craft, David

2017-02-01

In this article we provide a method to generate the trade-off between delivery time and fluence map matching quality for dynamically delivered fluence maps. At the heart of our method lies a mathematical programming model that, for a given duration of delivery, optimizes leaf trajectories and dose rates such that the desired fluence map is reproduced as well as possible. We begin with the single fluence map case and then generalize the model and the solution technique to the delivery of sequential fluence maps. The resulting large-scale, non-convex optimization problem was solved using a heuristic approach. We test our method using a prostate case and a head and neck case, and present the resulting trade-off curves. Analysis of the leaf trajectories reveals that short time plans have larger leaf openings in general than longer delivery time plans. Our method allows one to explore the continuum of possibilities between coarse, large segment plans characteristic of direct aperture approaches and narrow field plans produced by sliding window approaches. Exposing this trade-off will allow for an informed choice between plan quality and solution time. Further research is required to speed up the optimization process to make this method clinically implementable.

Dosimetry study of PHOTOFRIN-mediated photodynamic therapy in a mouse tumor model

NASA Astrophysics Data System (ADS)

Qiu, Haixia; Kim, Michele M.; Penjweini, Rozhin; Zhu, Timothy C.

2016-03-01

It is well known in photodynamic therapy (PDT) that there is a large variability between PDT light dose and therapeutic outcomes. An explicit dosimetry model using apparent reacted 1O2 concentration [1O2]rx has been developed as a PDT dosimetric quantity to improve the accuracy of the predicted ability of therapeutic efficacy. In this study, this explicit macroscopic singlet oxygen model was adopted to establish the correlation between calculated reacted [1O2]rx and the tumor growth using Photofrin-mediated PDT in a mouse tumor model. Mice with radiation-induced fibrosarcoma (RIF) tumors were injected with Photofrin at a dose of 5 mg/kg. PDT was performed 24h later with different fluence rates (50, 75 and 150 mW/cm2) and different fluences (50 and 135 J/cm2) using a collimated light applicator coupled to a 630nm laser. The tumor volume was monitored daily after PDT and correlated with the total light fluence and [1O2]rx. Photophysical parameters as well as the singlet oxygen threshold dose for this sensitizer and the RIF tumor model were determined previously. The result showed that tumor growth rate varied greatly with light fluence for different fluence rates while [1O2]rx had a good correlation with the PDT-induced tumor growth rate. This preliminary study indicated that [1O2]rx could serve as a better dosimetric predictor for predicting PDT outcome than PDT light dose.

Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

Empirical assessment of the detection efficiency of CR-39 at high proton fluence and a compact, proton detector for high-fluence applications

DOE PAGES

Rosenberg, M. J.; Séguin, F. H.; Waugh, C. J.; ...

2014-04-14

CR-39 solid-state nuclear track detectors are widely used in physics and in many inertial confinement fusion (ICF) experiments, and under ideal conditions these detectors have 100% detection efficiency for ~0.5–8 MeV protons. When the fluence of incident particles becomes too high, the overlap of particle tracks leads to under-counting at typical processing conditions (5h etch in 6N NaOH at 80°C). Short etch times required to avoid overlap can cause under-counting as well, as tracks are not fully developed. Experiments have determined the minimum etch times for 100% detection of 1.7–4.3-MeV protons and established that for 2.4-MeV protons, relevant for detectionmore » of DD protons, the maximum fluence that can be detected using normal processing techniques is ≲3 ×10 6 cm -2. A CR-39-based proton detector has been developed to mitigate issues related to high particle fluences on ICF facilities. Using a pinhole and scattering foil several mm in front of the CR-39, proton fluences at the CR-39 are reduced by more than a factor of ~50, increasing the operating yield upper limit by a comparable amount.« less

Photodynamic therapy: computer modeling of diffusion and reaction phenomena

NASA Astrophysics Data System (ADS)

Hampton, James A.; Mahama, Patricia A.; Fournier, Ronald L.; Henning, Jeffery P.

1996-04-01

We have developed a transient, one-dimensional mathematical model for the reaction and diffusion phenomena that occurs during photodynamic therapy (PDT). This model is referred to as the PDTmodem program. The model is solved by the Crank-Nicholson finite difference technique and can be used to predict the fates of important molecular species within the intercapillary tissue undergoing PDT. The following factors govern molecular oxygen consumption and singlet oxygen generation within a tumor: (1) photosensitizer concentration; (2) fluence rate; and (3) intercapillary spacing. In an effort to maximize direct tumor cell killing, the model allows educated decisions to be made to insure the uniform generation and exposure of singlet oxygen to tumor cells across the intercapillary space. Based on predictions made by the model, we have determined that the singlet oxygen concentration profile within the intercapillary space is controlled by the product of the drug concentration, and light fluence rate. The model predicts that at high levels of this product, within seconds singlet oxygen generation is limited to a small core of cells immediately surrounding the capillary. The remainder of the tumor tissue in the intercapillary space is anoxic and protected from the generation and toxic effects of singlet oxygen. However, at lower values of this product, the PDT-induced anoxic regions are not observed. An important finding is that an optimal value of this product can be defined that maintains the singlet oxygen concentration throughout the intercapillary space at a near constant level. Direct tumor cell killing is therefore postulated to depend on the singlet oxygen exposure, defined as the product of the uniform singlet oxygen concentration and the time of exposure, and not on the total light dose.

Photodynamic therapy for endodontic disinfection.

PubMed

Soukos, Nikolaos S; Chen, Peter Shih-Yao; Morris, Jason T; Ruggiero, Karriann; Abernethy, Abraham D; Som, Sovanda; Foschi, Federico; Doucette, Stephanie; Bammann, Lili Luschke; Fontana, Carla Raquel; Doukas, Apostolos G; Stashenko, Philip P

2006-10-01

The aims of this study were to investigate the effects of photodynamic therapy (PDT) on endodontic pathogens in planktonic phase as well as on Enterococcus faecalis biofilms in experimentally infected root canals of extracted teeth. Strains of microorganisms were sensitized with methylene blue (25 microg/ml) for 5 minutes followed by exposure to red light of 665 nm with an energy fluence of 30 J/cm2. Methylene blue fully eliminated all bacterial species with the exception of E. faecalis (53% killing). The same concentration of methylene blue in combination with red light (222 J/cm2) was able to eliminate 97% of E. faecalis biofilm bacteria in root canals using an optical fiber with multiple cylindrical diffusers that uniformly distributed light at 360 degrees. We conclude that PDT may be developed as an adjunctive procedure to kill residual bacteria in the root canal system after standard endodontic treatment.

Photodynamic therapy on bacterial reduction in dental caries: in vivo study

NASA Astrophysics Data System (ADS)

Baptista, Alessandra; Araujo Prates, Renato; Kato, Ilka Tiemy; Amaral, Marcello Magri; Zanardi de Freitas, Anderson; Simões Ribeiro, Martha

2010-04-01

The reduction of pathogenic microorganisms in supragingival plaque is one of the principal factors in caries prevention and control. A large number of microorganisms have been reported to be inactivated in vitro by photodynamic therapy (PDT). The purpose of this study was to develop a rat model to investigate the effects of PDT on bacterial reduction in induced dental caries. Twenty four rats were orally inoculated with Streptococcus mutans cells (ATCC 25175) for three consecutive days. The animals were fed with a cariogenic diet and water with 10% of sucrose ad libitum, during all experimental period. Caries lesion formation was confirmed by Optical Coherence Tomography (OCT) 5 days after the beginning of the experiment. Then, the animals were randomly divided into two groups: Control Group: twelve animals were untreated by either light or photosensitizer; and PDT Group: twelve animals were treated with 100μM of methylene blue for 5min and irradiated by a Light Emitting Diode (LED) at λ = 640+/-30nm, fluence of 172J/cm2, output power of 240mW, and exposure time of 3min. Microbiological samples were collected before, immediately after, 3, 7 and 10 days after treatment and the number of total microaerophiles was counted. OCT images showed areas of enamel demineralization on rat molars. Microbiological analysis showed a significant bacterial reduction after PDT. Furthermore, the number of total microaerophiles in PDT group remained lower than control group until 10 days posttreatment. These findings suggest that PDT could be an alternative approach to reduce bacteria in dental caries.

Photodynamic effect of curcumin on Vibrio parahaemolyticus.

PubMed

Wu, Juan; Mou, Haijin; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

2016-09-01

Vibrio parahaemolyticus (V. parahaemolyticus) is currently a major cause of bacterial diarrhoea associated with seafood consumption. The objective of this study was to determine the inactivation effect of curcumin-mediated photodynamic action on V. parahaemolyticus. First of all, V. parahaemolyticus suspended in PBS buffer was irradiated by a visible light from a LED light source with an energy density of 3.6J/cm(2). Colony forming units (CFU) were counted and the viability of V. parahaemolyticus cells was calculated after treatment. Singlet oxygen ((1)O2) production after photodynamic action of curcumin was evaluated using 9,10-Anthracenediyl-bis (methylene) dimalonic acid (ADMA). Bacterial outer membrane protein was extracted and analyzed using electrophoresis SDS-PAGE. DNA and RNA of V. parahaemolyticus were also extracted and analyzed using agarose gel electrophoresis after photodynamic treatment. Finally, the efficacy of photodynamic action of curcumin was preliminarily evaluated in the decontamination of V. parahaemolyticus in oyster. Results showed that the viability of V. parahaemolyticus was significantly decreased to non-detectable levels over 6.5-log reductions with the curcumin concentration of 10 and 20μM. Photodynamic action of curcumin significantly increased the singlet oxygen level with the curcumin concentration of 10μM. Notable damage was found to bacterial outer membrane proteins and genetic materials after photodynamic treatment. Photodynamic action of curcumin reduced the number of V. parahaemolyticus contaminating in oyster to non-detectable level. Our findings demonstrated that photodynamic action of curcumin could be a potentially good method to inactivate Vibrio parahaemolyticus contaminating in oyster. Copyright © 2016 Elsevier B.V. All rights reserved.

Photodynamic therapy influence on anti-cancer immunity

NASA Astrophysics Data System (ADS)

Isaeva, O. G.; Osipov, V. A.

2010-02-01

The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.

Photodynamic therapy influence on anti-cancer immunity

NASA Astrophysics Data System (ADS)

Isaeva, O. G.; Osipov, V. A.

2009-10-01

The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.

Photodynamic Therapy Effectively Treats Actinic Keratoses Without Pre-Illumination Incubation Time.

PubMed

Gandy, Jessica; Labadie, Brian; Bierman, Dina; Zachary, Christopher

2017-03-01

BACKGROUND: Actinic keratoses (AKs) are dysplastic lesions of the epidermis that have the potential to progress to non-melanoma skin cancers (NMSC). Traditional photodynamic therapy (PDT) requires a pre-illumination incubation time, which adds to overall in-office time and has been linked to pain. Our group has found a novel protocol to effectively treat AKs with PDT that eliminates the pre-illumination incubation period and uses 2 back-to-back cycles of 16 minute 40 seconds.

METHODS: The patient was prepped with soapy water and isopropyl alcohol, and thick AKs were descaled with a curette. Next, 5-aminolevulinic acid (ALA) was applied to the treatment areas and the patient was immediately placed under the blue light for 33 minutes and 20 seconds (two cycles of 16m/40s).

RESULTS: During therapy, the patient reported no pain. At one week, treated areas revealed a good reaction. The procedure was repeated at one month to treat residual AKs. At a 4-month follow-up, the patient's face and scalp showed near clearance of any AKs.

CONCLUSION: During PDT, the photosensitizer aminolevulinic acid (ALA), or in Europe methyl aminolevulinate (MAL), is utilized as a synthetic precursor that preferentially accumulates in dysplastic cells. The precursor then converts to PpIX via the heme pathway and causes apoptosis of the cells when excited, most commonly by either blue-violet (400-430 nm) or red (630-635 nm) light. Shorter incubation times are associated with reduced pain because less PpIX will have accumulated in the treated tissue by the start of the exposure to the light. The doubling of the light exposure time allows comparable levels of the photosensitizing molecule to accumulate and be activated so as to produce an equivalent reaction. The associated reduction in pain along with a more convenient treatment schedule makes this PDT protocol more tolerable and convenient to some patients.

J Drugs Dermatol. 2017;16(3):275-278.

Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study

NASA Astrophysics Data System (ADS)

Qiu, Haixia; Kim, Michele M.; Penjweini, Rozhin; Zhu, Timothy C.

2016-08-01

Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates (φ). A macroscopic model was adopted to evaluate using calculated reacted singlet oxygen concentration ([) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma tumors, as singlet oxygen is the primary cytotoxic species responsible for cell death in type II PDT. Using a combination of fluences (50, 135, 200, and 250 J/cm2) and φ (50, 75, and 150 mW/cm2), tumor regrowth rate, k, was determined for each condition. A tumor cure index, CI=1-k/k, was calculated based on the k between PDT-treated groups and that of the control, k. The measured Photofrin concentration and light dose for each mouse were used to calculate PDT dose and [, while mean optical properties (μa=0.9 cm-1, μs‧=8.4 cm-1) were used to calculate φ for all mice. CI was correlated to the fluence, PDT dose, and [ with R2=0.35, 0.79, and 0.93, respectively. These results suggest that [ serves as a better dosimetric quantity for predicting PDT outcome.

WE-AB-209-10: Optimizing the Delivery of Sequential Fluence Maps for Efficient VMAT Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craft, D; Balvert, M

2016-06-15

Purpose: To develop an optimization model and solution approach for computing MLC leaf trajectories and dose rates for high quality matching of a set of optimized fluence maps to be delivered sequentially around a patient in a VMAT treatment. Methods: We formulate the fluence map matching problem as a nonlinear optimization problem where time is discretized but dose rates and leaf positions are continuous variables. For a given allotted time, which is allocated across the fluence maps based on the complexity of each fluence map, the optimization problem searches for the best leaf trajectories and dose rates such that themore » original fluence maps are closely recreated. Constraints include maximum leaf speed, maximum dose rate, and leaf collision avoidance, as well as the constraint that the ending leaf positions for one map are the starting leaf positions for the next map. The resulting model is non-convex but smooth, and therefore we solve it by local searches from a variety of starting positions. We improve solution time by a custom decomposition approach which allows us to decouple the rows of the fluence maps and solve each leaf pair individually. This decomposition also makes the problem easily parallelized. Results: We demonstrate method on a prostate case and a head-and-neck case and show that one can recreate fluence maps to high degree of fidelity in modest total delivery time (minutes). Conclusion: We present a VMAT sequencing method that reproduces optimal fluence maps by searching over a vast number of possible leaf trajectories. By varying the total allotted time given, this approach is the first of its kind to allow users to produce VMAT solutions that span the range of wide-field coarse VMAT deliveries to narrow-field high-MU sliding window-like approaches.« less

Reduction of thermal damage in photodynamic therapy by laser irradiation techniques.

PubMed

Lim, Hyun Soo

2012-12-01

General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per 10 J/cm2 was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within ± 0.2%, and specific wavelength shift was limited to ± 3 nm. Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.

Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy

PubMed Central

Mallidi, Srivalleesha; Anbil, Sriram; Bulin, Anne-Laure; Obaid, Girgis; Ichikawa, Megumi; Hasan, Tayyaba

2016-01-01

Photodynamic therapy (PDT) is a photochemistry based treatment modality that involves the generation of cytotoxic species through the interactions of a photosensitizer molecule with light irradiation of an appropriate wavelength. PDT is an approved therapeutic modality for several cancers globally and in several cases has proved to be effective where traditional treatments have failed. The key parameters that determine PDT efficacy are 1. the photosensitizer (nature of the molecules, selectivity, and macroscopic and microscopic localization etc.), 2. light application (wavelength, fluence, fluence rate, irradiation regimes etc.) and 3. the microenvironment (vascularity, hypoxic regions, stromal tissue density, molecular heterogeneity etc.). Over the years, several groups aimed to monitor and manipulate the components of these critical parameters to improve the effectiveness of PDT treatments. However, PDT is still misconstrued to be a surface treatment primarily due to the limited depths of light penetration. In this review, we present the recent advances, strategies and perspectives in PDT approaches, particularly in cancer treatment, that focus on increasing the 'damage zone' beyond the reach of light in the body. This is enabled by a spectrum of approaches that range from innovative photosensitizer excitation strategies, increased specificity of phototoxicity, and biomodulatory approaches that amplify the biotherapeutic effects induced by photodynamic action. Along with the increasing depth of understanding of the underlying physical, chemical and physiological mechanisms, it is anticipated that with the convergence of these strategies, the clinical utility of PDT will be expanded to a powerful modality in the armamentarium for the management of cancer. PMID:27877247

Photodynamic therapy for cancer

MedlinePlus

... Photoradiation therapy; Cancer of the esophagus - photodynamic; Esophageal cancer - photodynamic; Lung cancer - photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

Photodynamic therapy can induce non-specific protective immunity against a bacterial infection

NASA Astrophysics Data System (ADS)

Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Kinoshita, Manabu; Morimoto, Yuji; Hamblin, Michael R.

2012-03-01

Photodynamic therapy (PDT) for cancer is known to induce an immune response against the tumor, in addition to its well-known direct cell-killing and vascular destructive effects. PDT is becoming increasingly used as a therapy for localized infections. However there has not to date been a convincing report of an immune response being generated against a microbial pathogen after PDT in an animal model. We have studied PDT as a therapy for bacterial arthritis caused by Staphylococcus aureus infection in the mouse knee. We had previously found that PDT of an infection caused by injection of MRSA (5X107 CFU) into the mouse knee followed 3 days later by 1 μg of Photofrin and 635- nm diode laser illumination with a range of fluences within 5 minutes, gave a biphasic dose response. The greatest reduction of MRSA CFU was seen with a fluence of 20 J/cm2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. We then tested the hypothesis that the host immune response mediated by neutrophils was responsible for most of the beneficial antibacterial effect. We used bioluminescence imaging of luciferase expressing bacteria to follow the progress of the infection in real time. We found similar results using intra-articular methylene blue and red light, and more importantly, that carrying out PDT of the noninfected joint and subsequently injecting bacteria after PDT led to a significant protection from infection. Taken together with substantial data from studies using blocking antibodies we believe that the pre-conditioning PDT regimen recruits and stimulates neutrophils into the infected joint which can then destroy bacteria that are subsequently injected and prevent infection.

A Photosensitizer-Loaded DNA Origami Nanosystem for Photodynamic Therapy.

PubMed

Zhuang, Xiaoxi; Ma, Xiaowei; Xue, Xiangdong; Jiang, Qiao; Song, Linlin; Dai, Luru; Zhang, Chunqiu; Jin, Shubin; Yang, Keni; Ding, Baoquan; Wang, Paul C; Liang, Xing-Jie

2016-03-22

Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.

Plant Photodynamic Stress: What's New?

PubMed Central

Issawi, Mohammad; Sol, Vincent; Riou, Catherine

2018-01-01

In the 1970's, an unconventional stressful photodynamic treatment applied to plants was investigated in two directions. Exogenous photosensitizer treatment underlies direct photodynamic stress while treatment mediating endogenous photosensitizer over-accumulation pinpoints indirect photodynamic stress. For indirect photodynamic treatment, tetrapyrrole biosynthesis pathway was deregulated by 5-aminolevulenic acid or diphenyl ether. Overall, photodynamic stress involves the generation of high amount of reactive oxygen species leading to plant cell death. All these investigations were mainly performed to gain insight into new herbicide development but they were rapidly given up or limited due to the harmfulness of diphenyl ether and the high cost of 5-aminolevulinic acid treatment. Twenty years ago, plant photodynamic stress came back by way of crop transgenesis where for example protoporphyrin oxidases from human or bacteria were overexpressed. Such plants grew without dramatic effects of photodamage suggesting that plants tolerated induced photodynamic stress. In this review, we shed light on the occurrence of plant photodynamic stress and discuss challenging issues in the context of agriculture focusing on direct photodynamic modality. Indeed, we highlighted applications of exogenous PS especially porphyrins on plants, to further develop an emerged antimicrobial photodynamic treatment that could be a new strategy to kill plant pathogens without disturbing plant growth. PMID:29875786

Safety and efficacy of low fluence, high repetition rate versus high fluence, low repetition rate 810-nm diode laser for axillary hair removal in Chinese women.

PubMed

Li, Wenhai; Liu, Chengyi; Chen, Zhou; Cai, Lin; Zhou, Cheng; Xu, Qianxi; Li, Houmin; Zhang, Jianzhong

2016-11-01

High-fluence diode lasers with contact cooling have emerged as the gold standard to remove unwanted hair. Lowering the energy should result in less pain and could theoretically affect the efficacy of the therapy. To compare the safety and efficacy of a low fluence high repetition rate 810-nm diode laser to those of a high fluence, low repetition rate diode laser for permanent axillary hair removal in Chinese women. Ninety-two Chinese women received four axillae laser hair removal treatments at 4-week intervals using the low fluence, high repetition rate 810-nm diode laser in super hair removal (SHR) mode on one side and the high fluence, low repetition rate diode laser in hair removal (HR) mode on the other side. Hair counts were done at each follow-up visit and 6-month follow-up after the final laser treatment using a "Hi Quality Hair Analysis Program System"; the immediate pain score after each treatment session was recorded by a visual analog scale. The overall median reduction of hair was 90.2% with the 810-nm diode laser in SHR mode and 87% with the same laser in HR mode at 6-month follow-up. The median pain scores in SHR mode and in HR mode were 2.75 and 6.75, respectively. Low fluence, high repetition rate diode laser can efficiently remove unwanted hair but also significantly improve tolerability and reduce adverse events during the course of treatment.

New design of textile light diffusers for photodynamic therapy.

PubMed

Cochrane, Cédric; Mordon, Serge R; Lesage, Jean Claude; Koncar, Vladan

2013-04-01

A homogeneous and reproducible fluence delivery rate during clinical photodynamic therapy (PDT) plays a determinant role in preventing under- or overtreatment. PDT applied in dermatology has been carried out with a wide variety of light sources delivering a broad range of more or less adapted light doses. Due to the complexities of the human anatomy, these light sources do not in fact deliver a uniform light distribution to the skin. Therefore, the development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of plastic optical fiber (POF) into textile structures could offer an interesting alternative. In this article, a textile light diffuser (TLD) has been developed using POF and Polyester yarns. Predetermined POF macrobending leads to side emission of light when the critical angle is exceeded. Therefore, a specific pattern based on different satin weaves has been developed in order to improve light emission homogeneity and to correct the decrease of side emitted radiation intensity along POF. The prototyped fabrics (approximately 100 cm(2): 5×20 cm) were woven using a hand loom, then both ends of the POF were coupled to a laser diode (5 W, 635 nm). The fluence rate (mW/ cm(2)) and the homogeneity of light delivery by the TLD were evaluated. Temperature evolution, as a function of time, was controlled with an infrared thermographic camera. When using a power source of 5 W, the fluence rate of the TLD was 18±2.5 mw/cm(2). Due to the high efficiency of the TLD, the optical losses were very low. The TLD temperature elevation was 0.6 °C after 10 min of illumination. Our TLD meets the basic requirements for PDT: homogeneous light distribution and flexibility. It also proves that large (500 cm(2)) textile light diffusers adapted to skin, but also to peritoneal or pleural cavity, PDTs can be easily produced by textile manufacturing processes. Copyright © 2012 Elsevier B.V. All rights reserved.

Phthalocyanine-assisted photodynamic inactivation of pathogenic microorganisms

NASA Astrophysics Data System (ADS)

Mantareva, Vanya; Angelov, Ivan; Borissova, Ekaterina; Avramov, Latchezar; Kussovski, Vesselin

2007-03-01

The phthalocyanine zinc(II) and aluminum (III) complexes were studied to photoinactivate the bacterial strains, Staphylococcus aureus, methacillin-sensitive and methacillin-resistant, Pseudomonas aeruginosa and one yeast Candida albicans. The binding of phthalocyanines to bacteria and fungi cells was evaluated by the means of laserinduced fluorescence technique. The fluorescent spectra of dyes (650 - 800 nm) after direct excitation (635 nm) were measured as follows: 1. for the aqua supernatants obtained after 10 min cell incubation with the respected phthalocyanines (1.6 μmol.l -1), 2. for the washed from the unbound dye cells, and 3. for the organic extracts from the three times washed cells. Fluorescent intensities at the emission maximum (~690 nm) were compared to the spectra of the phthalocyanines in organic solutions. The phthalocyanines uptake data for bacteria and fungi were determined at different cell densities. Nevertheless the better fluorescence properties of AlPc (fluorescent quantum yield of 0.4 towards 0.3 for ZnPcs) the lower drug accumulation in microorganisms was obtained. PDI results indicated an intensive lowering of the bacterial survival of both strains of S. aureus treated with cationic ZnPcMe followed by the anionic ZnPcS, at irradiance of 100 mW cm -2 and fluence rate of 60 J cm -2. More resistant to phototreatment P. aeruginosa and morphologically complicated yeast C. albicans were successfully inactivated only with cationic ZnPcMe. These data indicate the promising future application of cationic phthalocyanine in photodynamic inactivation of pathogenic microorganisms.

Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins

PubMed Central

Solár, Peter; Chytilová, Mária; Solárová, Zuzana; Mojžiš, Ján; Ferenc, Peter; Fedoročko, Peter

2011-01-01

In this study we have focused on the response of SKBR-3 cells to both single 17-DMAG treatment as well as its combination with photodynamic therapy with hypericin. Low concentrations of 17-DMAG without any effect on survival of SKBR-3 cells significantly reduced metabolic activity, viability and cell number when combined with photodynamic therapy with hypericin. Moreover, IC10 concentation of 17-DMAG resulted in significant increase of SKBR-3 cells in G1 phase of the cell cycle, followed by an increase of cells in G2 phase when combined with photodynamic therapy. Furthermore, 17-DMAG already decreased HER2, Akt, P-Erk1/2 and survivin protein levels in SKBR-3 cells a short time after its application. In this regard, 17-DMAG protected also SKBR-3 cells against both P-Erk1/2 as well as survivin upregulations induced by photodynamic therapy with hypericin. Interestingly, IC10 concentration of 17-DMAG led to total depletion of Akt, P-Erk1/2 proteins and to decrease of survivin level at 48 h. On the other hand, 17-DMAG did not change HER2 relative expression in SKBR-3 cells, but caused a significant decrease of HER2 mRNA in MCF-7 cells characterized by low HER2 expression. These results show that targeting HSP90 client proteins increases the efficiency of antineoplastic effect of photodynamic therapy in vitro. PMID:27721334

Real time laser speckle imaging monitoring vascular targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Goldschmidt, Ruth; Vyacheslav, Kalchenko; Scherz, Avigdor

2017-02-01

Laser speckle imaging is a technique that has been developed to non-invasively monitor in vivo blood flow dynamics and vascular structure, at high spatial and temporal resolution. It can record the full-field spatio-temporal characteristics of microcirculation and has therefore, often been used to study the blood flow in tumors after photodynamic therapy (PDT). Yet, there is a paucity of reports on real-time laser speckle imaging (RTLSI) during PDT. Vascular-targeted photodynamic therapy (VTP) with WST11, a water-soluble bacteriochlorophyll derivative, achieves tumor ablation through rapid occlusion of the tumor vasculature followed by a cascade of events that actively kill the tumor cells. WST11-VTP has been already approved for treatment of early/intermediate prostate cancer at a certain drug dose, time and intensity of illumination. Application to other cancers may require different light dosage. However, incomplete vascular occlusion at lower light dose may result in cancer cell survival and tumor relapse while excessive light dose may lead to toxicity of nearby healthy tissues. Here we provide evidence for the feasibility of concomitant RTLSI of the blood flow dynamics in the tumor and surrounding normal tissues during and after WST11-VTP. Fast decrease in the blood flow is followed by partial mild reperfusion and a complete flow arrest within the tumor by the end of illumination. While the primary occlusion of the tumor feeding arteries and draining veins agrees with previous data published by our group, the late effects underscore the significance of light dose control to minimize normal tissue impairment. In conclusion- RTSLI application should allow to optimize VTP efficacy vs toxicity in both the preclinical and clinical arenas.

Myocardial electrical conduction blockade time dominated by irradiance on photodynamic reaction: in vitro and in silico study

NASA Astrophysics Data System (ADS)

Ogawa, Emiyu; Arai, Tsunenori

2018-02-01

The time for electrical conduction blockade induced by a photodynamic reaction was studied on a myocardial cell wire in vitro and an in silico simulation model was constructed to understand the necessary time for electrical conduction blockade for the wire. Vulnerable state of the cells on a laser interaction would be an unstable and undesirable state since the cells might progress to completely damaged or repaired to change significantly therapeutic effect. So that in silico model, which can calculate the vulnerable cell state, is needed. Understanding an immediate electrical conduction blockade is needed for our proposed new methodology for tachyarrhythmia catheter ablation applying a photodynamic reaction. We studied the electrical conduction blockade occurrence on the electrical conduction wire made of cultured myocardial cells in a line shape and constructed in silico model based on this experimental data. The intracellular Ca2+ ion concentrations were obtained using Fluo-4 AM dye under a confocal laser microscope. A cross-correlation function was used for the electrical conduction blockade judgment. The photodynamic reaction was performed under the confocal microscopy with 3-120 mW/cm2 in irradiance by the diode laser with 663 nm in wavelength. We obtained that the time for the electrical conduction blockade decreased with the irradiance increasing. We constructed a simulation model composed of three states; living cells, vulnerable cells, and blocked cells, using the obtained experimental data and we found the rate constant by an optimization using a conjugate gradient method.

Light emitting fabric technologies for photodynamic therapy.

PubMed

Mordon, Serge; Cochrane, Cédric; Tylcz, Jean Baptiste; Betrouni, Nacim; Mortier, Laurent; Koncar, Vladan

2015-03-01

Photodynamic therapy (PDT) is considered to be a promising method for treating various types of cancer. A homogeneous and reproducible illumination during clinical PDT plays a determinant role in preventing under- or over-treatment. The development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of optical fiber into flexible structures could offer an interesting alternative. This paper aims to describe different methods proposed to develop Side Emitting Optical Fibers (SEOF), and how these SEOF can be integrated in a flexible structure to improve light illumination of the skin during PDT. Four main techniques can be described: (i) light blanket integrating side-glowing optical fibers, (ii) light emitting panel composed of SEOF obtained by micro-perforations of the cladding, (iii) embroidery-based light emitting fabric, and (iv) woven-based light emitting fabric. Woven-based light emitting fabrics give the best performances: higher fluence rate, best homogeneity of light delivery, good flexibility. Copyright © 2014 Elsevier B.V. All rights reserved.

A robotic multi-channel platform for interstitial photodynamic therapy

PubMed Central

Sharikova, Anna V.; Finlay, Jarod C.; Dimofte, Andreea; Zhu, Timothy C.

2015-01-01

A custom-made robotic multichannel platform for interstitial photodynamic therapy (PDT) and diffuse optical tomography (DOT) was developed and tested in a phantom experiment. The system, which was compatible with the operating room (OR) environment, had 16 channels for independent positioning of light sources and/or isotropic detectors in separate catheters. Each channel’s motor had an optical encoder for position feedback, with resolution of 1.5 mm, and a maximum speed of 5 cm/s. Automatic calibration of detector positions was implemented using an optical diode beam that defined the starting position of each motor, and by means of feedback algorithms controlling individual channels. As a result, the accuracy of zero position of 0.1 mm for all channels was achieved. We have also employed scanning procedures where detectors automatically covered the appropriate range around source positions. Thus, total scan time for a typical optical properties (OP) measurement throughout the phantom was about 1.5 minutes with point sources. The OP were determined based on the measured light fluence rates. These enhancements allow a tremendous improvement of treatment quality for a bulk tumor compared to the systems employed in previous clinical trials. PMID:25914794

T-Opt: A 3D Monte Carlo simulation for light delivery design in photodynamic therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Honda, Norihiro; Hazama, Hisanao; Awazu, Kunio

2017-02-01

The interstitial photodynamic therapy (iPDT) with 5-aminolevulinic acid (5-ALA) is a safe and feasible treatment modality of malignant glioblastoma. In order to cover the tumour volume, the exact position of the light diffusers within the lesion is needed to decide precisely. The aim of this study is the development of evaluation method of treatment volume with 3D Monte Carlo simulation for iPDT using 5-ALA. Monte Carlo simulations of fluence rate were performed using the optical properties of the brain tissue infiltrated by tumor cells and normal tissue. 3-D Monte Carlo simulation was used to calculate the position of the light diffusers within the lesion and light transport. The fluence rate near the diffuser was maximum and decreased exponentially with distance. The simulation can calculate the amount of singlet oxygen generated by PDT. In order to increase the accuracy of simulation results, the parameter for simulation includes the quantum yield of singlet oxygen generation, the accumulated concentration of photosensitizer within tissue, fluence rate, molar extinction coefficient at the wavelength of excitation light. The simulation is useful for evaluation of treatment region of iPDT with 5-ALA.

A common fluence threshold for first positive and second positive phototropism in Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Janoudi, A.; Poff, K. L.

1990-01-01

The relationship between the amount of light and the amount of response for any photobiological process can be based on the number of incident quanta per unit time (fluence rate-response) or on the number of incident quanta during a given period of irradiation (fluence-response). Fluence-response and fluence rate-response relationships have been measured for second positive phototropism by seedlings of Arabidopsis thaliana. The fluence-response relationships exhibit a single limiting threshold at about 0.01 micromole per square meter when measured at fluence rates from 2.4 x 10(-5) to 6.5 x 10(-3) micromoles per square meter per second. The threshold values in the fluence rate-response curves decrease with increasing time of irradiation, but show a common fluence threshold at about 0.01 micromole per square meter. These thresholds are the same as the threshold of about 0.01 micromole per square meter measured for first positive phototropism. Based on these data, it is suggested that second positive curvature has a threshold in time of about 10 minutes. Moreover, if the times of irradiation exceed the time threshold, there is a single limiting fluence threshold at about 0.01 micromole per square meter. Thus, the limiting fluence threshold for second positive phototropism is the same as the fluence threshold for first positive phototropism. Based on these data, we suggest that this common fluence threshold for first positive and second positive phototropism is set by a single photoreceptor pigment system.

Comparison microbial killing efficacy between sonodynamic therapy and photodynamic therapy

NASA Astrophysics Data System (ADS)

Drantantiyas, Nike Dwi Grevika; Astuti, Suryani Dyah; Nasution, Aulia M. T.

2016-11-01

Biofilm is a way used by bacteria to survive from their environmental conditions by forming colony of bacteria. Specific characteristic in biofilm formation is the availability of matrix layer, known as extracellular polymer substance. Treatment using antibiotics may lead bacteria to be to resistant. Other treatments to reduce microbial, like biofilm, can be performed by using photodynamic therapy. Successful of this kind of therapy is induced by penetration of light and photosensitizer into target cells. The sonodynamic therapy offers greater penetrating capability into tissues. This research aimed to use sonodynamic therapy in reducing biofilm. Moreover, it compares also the killing efficacy of photodynamic therapy, sonodynamic therapy, and the combination of both therapeutic schemes (known as sono-photodynamic) to achieve higher microbial killing efficacy. Samples used are Staphylococcus aureus biofilm. Treatments were divided into 4 groups, i.e. group under ultrasound treatment with variation of 5 power levels, group of light treatment with exposure of 75s, group of combined ultrasound-light with variation of ultrasound power levels, and group of combined lightultrasound with variation of ultrasound power levels. Results obtained for each treatment, expressed in % efficacy of log CFU/mL, showed that the treatment of photo-sonodynamic provides greater killing efficacy in comparison to either sonodynamic and sono-photodynamic. The photo-sonodynamic shows also greater efficacy to photodynamic. So combination of light-ultrasound (photo-sonodynamic) can effectively kill microbial biofilm. The combined therapy will provide even better efficacy using exogenous photosensitizer.

Developing a treatment planning process and software for improved translation of photodynamic therapy

NASA Astrophysics Data System (ADS)

Cassidy, J.; Zheng, Z.; Xu, Y.; Betz, V.; Lilge, L.

2017-04-01

Background: The majority of de novo cancers are diagnosed in low and middle-income countries, which often lack the resources to provide adequate therapeutic options. None or minimally invasive therapies such as Photodynamic Therapy (PDT) or photothermal therapies could become part of the overall treatment options in these countries. However, widespread acceptance is hindered by the current empirical training of surgeons in these optical techniques and a lack of easily usable treatment optimizing tools. Methods: Based on image processing programs, ITK-SNAP, and the publicly available FullMonte light propagation software, a work plan is proposed that allows for personalized PDT treatment planning. Starting with, contoured clinical CT or MRI images, the generation of 3D tetrahedral models in silico, execution of the Monte Carlo simulation and presentation of the 3D fluence rate, Φ, [mWcm-2] distribution a treatment plan optimizing photon source placement is developed. Results: Permitting 1-2 days for the installation of the required programs, novices can generate their first fluence, H [Jcm-2] or Φ distribution in a matter of hours. This is reduced to 10th of minutes with some training. Executing the photon simulation calculations is rapid and not the performance limiting process. Largest sources of errors are uncertainties in the contouring and unknown tissue optical properties. Conclusions: The presented FullMonte simulation is the fastest tetrahedral based photon propagation program and provides the basis for PDT treatment planning processes, enabling a faster proliferation of low cost, minimal invasive personalized cancer therapies.

[Photodynamic therapy of urinary bladder cancer using a chlorin based photosensitizer].

PubMed

Iagudaev, D M; Martov, A G; Sorokatyĭ, A E; Geĭnits, A V

2006-01-01

Photodynamic therapy (PDT) is a modem, low-invasive method of urinary bladder (UB) cancer treatment. PDT can induce complete or partial destruction of the tumor, reduce recurrence rate, provide assistance to elderly patients with compromised somatic status who are not radically operable. A combined technique improves the results of photodynamic therapy in patients with surface and invasive UB cancer of stage T2 because photodynamic impact affects not only the tumor but also all UB mucosa by light fiber with cylindric diffusor introduced in a silicon balloon with water. This leads to tumor destruction and a recurrence rate decrease.

Intraoperative photodynamic treatment for high-grade gliomas

NASA Astrophysics Data System (ADS)

Dupont, C.; Reyns, N.; Deleporte, P.; Mordon, S.; Vermandel, M.

2017-02-01

Glioblastoma (GBM) is the most common primary brain tumor. Its incidence is estimated at 5 to 7 new cases each year for 100 000 inhabitants. Despite reference treatment, including surgery, radiation oncology and chemotherapy, GBM still has a very poor prognosis (median survival of 15 months). Because of a systematic relapse of the tumor, the main challenge is to improve local control. In this context, PhotoDynamic Therapy (PDT) may offer a new treatment modality. GBM recurrence mainly occurs inside the surgical cavity borders. Thus, a new light applicator was designed for delivering light during a PDT procedure on surgical cavity borders after Fluorescence Guided Resection. This device combines an inflatable balloon and a light source. Several experimentations (temperature and impermeability tests, homogeneity of the light distribution and ex-vivo studies) were conducted to characterize the device. An abacus was created to determine illumination time from the balloon volume in order to reach a therapeutic fluence value inside the borders of the surgical cavity. According to our experience, cavity volumes usually observed in the neurosurgery department lead to an acceptable average lighting duration, from 20 to 40 minutes. Thus, extra-time needed for PDT remains suitable with anesthesia constraints. A pilot clinical trial is planned to start in 2017 in our institution. In view of the encouraging results observed in preclinical or clinical, this intraoperative PDT treatment can be easily included in the current standard of care.

Hypericin-photodynamic therapy (PDT) using an alternative treatment regime suitable for multi-fraction PDT.

PubMed

Thong, Patricia Soo-Ping; Watt, Frank; Ren, Min Qin; Tan, Puay Hoon; Soo, Khee Chee; Olivo, Malini

2006-01-02

Photodynamic therapy (PDT) outcome depends on the conditions under which it is carried out. Maintaining the tumour tissue oxygen level is important for PDT efficacy and using a low fluence rate can improve outcome. In this work we studied the response of human nasopharyngeal carcinoma tumours in murine models to hypericin-PDT carried out under low fluence and fluence rate. A drug-light interval (DLI) of 1h or 6h was used for 1h-PDT and 6h-PDT, respectively. Evan's blue test was used to assess necrosis and TUNEL staining for apoptosis. Nuclear microscopy was used to quantify elemental concentrations in tumours. Serum vascular endothelial growth factor (VEGF) levels were also determined. TUNEL results showed that 6h-PDT induced significantly more apoptosis compared to 1h-PDT (p<0.01). This was supported by nuclear microscopy showing an increase in calcium and a decrease in zinc levels (both known triggers of apoptosis) in 6h-PDT tumours compared to non-PDT tumours (p<0.05). These results further imply a zinc-mediated pathway in hypericin-PDT induced apoptosis. 6h-PDT also resulted in a significant increase in copper concentrations compared to non-PDT tumours (p<0.05). Serum VEGF levels measured after 6h-PDT were lower than those obtained after 1h-PDT. Overall tumour response to hypericin-PDT under low fluence and fluence rate and using a 6h DLI showed increased apoptosis and lower serum VEGF levels. This treatment regime is suitable for the alternative approach of multi-fraction PDT in which the tumour can be exposed to multiple PDT fractions for complete tumour response. This alternative approach might yield improved outcome.

Zinc phthalocyanine-loaded PLGA biodegradable nanoparticles for photodynamic therapy in tumor-bearing mice.

PubMed

Fadel, Maha; Kassab, Kawser; Fadeel, Doa Abdel

2010-03-01

Nanoparticles formulated from the biodegradable copolymer poly(lactic-coglycolic acid) (PLGA) were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting of zinc(II) phthalocyanine (ZnPc) for photodynamic therapy. Three ZnPc nanoparticle formulations were prepared using a solvent emulsion evaporation method and the influence of sonication time on nanoparticle shape, encapsulation and size distribution, in vitro release, and in vivo photodynamic efficiency in tumor-bearing mice were studied. Sonication time did not affect the process yield or encapsulation efficiency, but did affect significantly the particle size. Sonication for 20 min reduced the mean particle size to 374.3 nm and the in vitro release studies demonstrated a controlled release profile of ZnPc. Tumor-bearing mice injected with ZnPc nanoparticles exhibited significantly smaller mean tumor volume, increased tumor growth delay and longer survival compared with the control group and the group injected with free ZnPc during the time course of the experiment. Histopathological examination of tumor from animals treated with PLGA ZnPc showed regression of tumor cells, in contrast to those obtained from animals treated with free ZnPc. The results indicate that ZnPc encapsulated in PLGA nanoparticles is a successful delivery system for improving photodynamic activity in the target tissue.

Development of Singlet Oxygen Luminescence Kinetics during the Photodynamic Inactivation of Green Algae.

PubMed

Bornhütter, Tobias; Pohl, Judith; Fischer, Christian; Saltsman, Irena; Mahammed, Atif; Gross, Zeev; Röder, Beate

2016-04-13

Recent studies show the feasibility of photodynamic inactivation of green algae as a vital step towards an effective photodynamic suppression of biofilms by using functionalized surfaces. The investigation of the intrinsic mechanisms of photodynamic inactivation in green algae represents the next step in order to determine optimization parameters. The observation of singlet oxygen luminescence kinetics proved to be a very effective approach towards understanding mechanisms on a cellular level. In this study, the first two-dimensional measurement of singlet oxygen kinetics in phototrophic microorganisms on surfaces during photodynamic inactivation is presented. We established a system of reproducible algae samples on surfaces, incubated with two different cationic, antimicrobial potent photosensitizers. Fluorescence microscopy images indicate that one photosensitizer localizes inside the green algae while the other accumulates along the outer algae cell wall. A newly developed setup allows for the measurement of singlet oxygen luminescence on the green algae sample surfaces over several days. The kinetics of the singlet oxygen luminescence of both photosensitizers show different developments and a distinct change over time, corresponding with the differences in their localization as well as their photosensitization potential. While the complexity of the signal reveals a challenge for the future, this study incontrovertibly marks a crucial, inevitable step in the investigation of photodynamic inactivation of biofilms: it shows the feasibility of using the singlet oxygen luminescence kinetics to investigate photodynamic effects on surfaces and thus opens a field for numerous investigations.

In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

PubMed

Liu, Y H; Hawk, R M; Ramaprasad, S

1995-01-01

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

Photodynamic therapy for the treatment of folliculitis decalvans.

PubMed

Castaño-Suárez, Esther; Romero-Maté, Alberto; Arias-Palomo, Dolores; Borbujo, Jesús

2012-04-01

Folliculitis decalvans is a chronic form of deep folliculitis that occurs on the scalp as patches of scarring alopecia at the expanding margins of which are follicular pustules. Treatment of folliculitis decalvans is extremely difficult with a resultant poor prognosis. Photodynamic therapy has been reported to be effective in disorders as acne or folliculitis. We report one patient with folliculitis decalvans who was successfully treated with photodynamic therapy. © 2012 John Wiley & Sons A/S.

Photodynamic immune modulation (PIM)

NASA Astrophysics Data System (ADS)

North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

1999-09-01

Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

A Common Fluence Threshold for First Positive and Second Positive Phototropism in Arabidopsis thaliana1

PubMed Central

Janoudi, Abdul; Poff, Kenneth L.

1990-01-01

The relationship between the amount of light and the amount of response for any photobiological process can be based on the number of incident quanta per unit time (fluence rate-response) or on the number of incident quanta during a given period of irradiation (fluence-response). Fluence-response and fluence rate-response relationships have been measured for second positive phototropism by seedlings of Arabidopsis thaliana. The fluence-response relationships exhibit a single limiting threshold at about 0.01 micromole per square meter when measured at fluence rates from 2.4 × 10−5 to 6.5 × 10−3 micromoles per square meter per second. The threshold values in the fluence rateresponse curves decrease with increasing time of irradiation, but show a common fluence threshold at about 0.01 micromole per square meter. These thresholds are the same as the threshold of about 0.01 micromole per square meter measured for first positive phototropism. Based on these data, it is suggested that second positive curvature has a threshold in time of about 10 minutes. Moreover, if the times of irradiation exceed the time threshold, there is a single limiting fluence threshold at about 0.01 micromole per square meter. Thus, the limiting fluence threshold for second positive phototropism is the same as the fluence threshold for first positive phototropism. Based on these data, we suggest that this common fluence threshold for first positive and second positive phototropism is set by a single photoreceptor pigment system. PMID:11537470

Explicit dosimetry for 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy: macroscopic singlet oxygen modeling.

PubMed

Penjweini, Rozhin; Liu, Baochang; Kim, Michele M; Zhu, Timothy C

2015-01-01

Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen ([(3)O2]), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen ([(1)O2]rx). We use an empirical macroscopic model based on four photochemical parameters for the calculation of [(1)O2]rx threshold concentration ([(1)O2]rx,sh) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100  J/cm and source power per unit length (LS) of 12 to 150  mW/cm was used to induce different radii of necrosis. Then the amount of [(1)O2]rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and [(1)O2]rx,sh. We provide evidence that [(1)O2]rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate.

Explicit dosimetry for 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy: macroscopic singlet oxygen modeling

PubMed Central

Penjweini, Rozhin; Liu, Baochang; Kim, Michele M.; Zhu, Timothy C.

2015-01-01

Abstract. Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen ([O32]), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen ([O12]rx). We use an empirical macroscopic model based on four photochemical parameters for the calculation of [O12]rx threshold concentration ([O12]rx,sh) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100  J/cm and source power per unit length (LS) of 12 to 150  mW/cm was used to induce different radii of necrosis. Then the amount of [O12]rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and [O12]rx,sh. We provide evidence that [O12]rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate. PMID:26720883

Explicit dosimetry for 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy: macroscopic singlet oxygen modeling

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Liu, Baochang; Kim, Michele M.; Zhu, Timothy C.

2015-12-01

Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen ([O]), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen ([]rx). We use an empirical macroscopic model based on four photochemical parameters for the calculation of []rx threshold concentration ([]rx,sh) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100 J/cm and source power per unit length (LS) of 12 to 150 mW/cm was used to induce different radii of necrosis. Then the amount of []rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and []rx,sh. We provide evidence that []rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate.

In vivo light dosimetry for pleural PDT

NASA Astrophysics Data System (ADS)

Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Culligan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

2009-02-01

In-vivo light Dosimetry for patients undergoing photodynamic therapy (PDT) is one of the important dosimetry quantities critical for predicting PDT outcome. This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area, and its accuracy as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here were enrolled in Phase II clinical trial of Photofrin-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. The ages of the patients studied varied from 34 to 69 year old. All patients were administered 2mg per kg body weight Photoprin 24 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with laser light with a light fluence of 60 J/cm^2 at 630nm. Fluence rate (mW/cm^2) and cumulative fluence (J/cm^2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 30%. The mean fluence rate delivery varied from 37.84 to 94.05 mW/cm^2 and treatment time varied from 1762 to 5232s. We have established a correlation between the treatment time and the treatment volume. The results are discussed using an integrating sphere theory and the measured tissue optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.

Inactivation of pathogenic bacteria in food matrices: high pressure processing, photodynamic inactivation and pressure-assisted photodynamic inactivation

NASA Astrophysics Data System (ADS)

Cunha, A.; Couceiro, J.; Bonifácio, D.; Martins, C.; Almeida, A.; Neves, M. G. P. M. S.; Faustino, M. A. F.; Saraiva, J. A.

2017-09-01

Traditional food processing methods frequently depend on the application of high temperature. However, heat may cause undesirable changes in food properties and often has a negative impact on nutritional value and organoleptic characteristics. Therefore, reducing the microbial load without compromising the desirable properties of food products is still a technological challenge. High-pressure processing (HPP) can be classified as a cold pasteurization technique, since it is a non-thermal food preservation method that uses hydrostatic pressure to inactivate spoilage microorganisms. At the same time, it increases shelf life and retains the original features of food. Photodynamic inactivation (PDI) is also regarded as promising approach for the decontamination of food matrices. In this case, the inactivation of bacterial cells is achieved by the cytotoxic effects of reactive oxygens species (ROS) produced from the combined interaction of a photosensitizer molecule, light and oxygen. This short review examines some recent developments on the application of HPP and PDI with food-grade photosensitizers for the inactivation of listeriae, taken as a food pathogen model. The results of a proof-of-concept trial of the use of high-pressure as a coadjutant to increase the efficiency of photodynamic inactivation of bacterial endospores is also addressed.

Monitoring of the Irradiated Neutron Fluence in the Neutron Transmutation Doping Process of Hanaro

NASA Astrophysics Data System (ADS)

Kim, Myong-Seop; Park, Sang-Jun

2009-08-01

Neutron transmutation doping (NTD) for silicon is a process of the creation of phosphorus impurities in intrinsic or extrinsic silicon by neutron irradiation to obtain silicon semiconductors with extremely uniform dopant distribution. HANARO has two vertical holes for the NTD, and the irradiation for 5 and 6 inch silicon ingots has been going on at one hole. In order to achieve the accurate neutron fluence corresponding to the target resistivity, the real time neutron flux is monitored by self-powered neutron detectors. After irradiation, the total irradiation fluence is confirmed by measuring the absolute activity of activation detectors. In this work, a neutron fluence monitoring method using zirconium foils with the mass of 10 ~ 50 mg was applied to the NTD process of HANARO. We determined the proportional constant of the relationship between the resistivity of the irradiated silicon and the neutron fluence determined by using zirconium foils. The determined constant for the initially n-type silicon was 3.126 × 1019 n·Ω/cm. It was confirmed that the difference between this empirical value and the theoretical one was only 0.5%. Conclusively, the practical methodology to perform the neutron transmutation doping of silicon was established.

Endodontic photodynamic therapy ex vivo

PubMed Central

Ng, Raymond; Singh, Fiza; Papamanou, Despoina A.; Song, Xiaoqing; Patel, Chitrang; Holewa, Colleen; Patel, Niraj; Klepac-Ceraj, Vanja; Fontana, Carla R.; Kent, Ralph; Pagonis, Tom C.; Stashenko, Philip P.; Soukos, Nikolaos S.

2010-01-01

Objective To evaluate the anti-microbial effects of photodynamic therapy (PDT) on infected human teeth ex vivo. Materials and Methods Fifty-two freshly extracted teeth with pulpal necrosis and associated periradicular radiolucencies were obtained from 34 subjects. Twenty-six teeth with 49 canals received chemomechanical debridement (CMD) with 6% NaOCl and twenty-six teeth with 52 canals received CMD plus PDT. For PDT, root canal systems were incubated with methylene blue (MB) at concentration of 50 µg/ml for 5 minutes followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm2. The contents of root canals were sampled by flushing the canals at baseline and following CMD alone or CMD+PDT and were serially diluted and cultured on blood agar. Survival fractions were calculated by counting colony-forming units (CFU). Partial characterization of root canal species at baseline and following CMD alone or CMD+PDT was performed using DNA probes to a panel of 39 endodontic species in the checkerboard assay. Results The Mantel-Haenszel chi-square test for treatment effects demonstrated the better performance of CMD+PDT over CMD (P=0.026). CMD+PDT significantly reduced the frequency of positive canals relative to CMD alone (P=0.0003). Following CMD+PDT, 45 of 52 canals (86.5%) had no CFU as compared to 24 of 49 canals (49%) treated with CMD (canal flush samples). The CFU reductions were similar when teeth or canals were treated as independent entities. Post-treatment detection levels for all species were markedly lower for canals treated by CMD+PDT than were for those treated by CMD alone. Bacterial species within dentinal tubules were detected in 17/22 (77.3%) and 15/29 (51.7%) of canals in the CMD and CMD+PDT group, respectively (P= 0.034). Conclusion Data indicate that PDT significantly reduces residual bacteria within the root canal system, and that PDT, if further enhanced by technical improvements, holds substantial promise as an adjunct to CMD. PMID

Photodynamic actinometry using microencapsulates: concepts and developmental approach

NASA Astrophysics Data System (ADS)

Bisland, Stuart K.; Austin, James; Wilson, Brian C.; Lilge, Lothar D.

2003-12-01

This study describes the development of novel, fluorescent-based actinometer encapsulates as a means of discerning volumetric Photodynamic therapy (PDT) dosimetry relative to the incident light and reactive oxygen species (ROS) production. PDT relies on three main ingredients; oxygen, light and photo-activatable commpounds, although, the PDT response is definately contingent on the site and level of ROS generation. Providing a localized, in situ measurement of luminance and ROS generation is therefore critical when deciphering targetd photodynamci therapy (PDT) protocols in vivo. Toward this end, alginate-poly-L-lysine-alginate encapsulates were made using ionotropic gelation of sodium alginate droplets ranging from 75 to 200 μm in diameter. Two candidate dyes, ADS680WS (ADS) and R-phycoerythrin (RPE) were chosen based on photochemistry, chemical stabilty and sensitivity to changing pH and oxygen environments. Alginate beads were constructed with ADS conjugated to the inside and RPE attached to the outside layer. The production of ROS was initiated either chemically using increasing concentrations of potassium perchromate or photochemically using tetra-sulphonated aluminium phosphorescence (AlPcS4). The generation of singlet oxygen was confirmed by the presence of a phosphorescence peak at 1270 nm. The resulting photodegradation and subsequent decrease in fluorescence of RPE was found to correlate very closely (p<0.001) with increasing perchromate or fluence respectively. This effect was independent of pH (6.5-8) and could be inhibited using sodium azide. RPA was not susceptible to photobleaching with light alone (675 nm; 150 J/cm2). Meanwhile, ADS680WS, which absorbs light at 670-690 nm, showed a direct correlation between diminished fluorescence (photobleaching) and incident fluence (675 nm; 0-100 J/cm2). This effect was independent of fluence rate (10-40 mW/cm2). We propose that actinometer encapsulates may prove useful for implanting into potential target

Acceleration Of Wound Healing Ny Photodynamic Therapy

DOEpatents

Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

2000-08-22

Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

Platinum(IV) complex-based two-in-one polyprodrug for a combinatorial chemo-photodynamic therapy.

PubMed

Guo, Dongbo; Xu, Shuting; Huang, Yu; Jiang, Huangyong; Yasen, Wumaier; Wang, Nan; Su, Yue; Qian, Jiwen; Li, Jing; Zhang, Chuan; Zhu, Xinyuan

2018-05-30

A combinatorial therapy that utilizes two or more therapeutic modalities is more effective in overcoming the limitations than each individual method used alone. Despite great advances have been achieved, the combination of chemotherapy and photodynamic therapy (PDT) still cannot satisfy the clinic requirements as the antitumor efficacy could be severely affected by tumor-associated hypoxia. Herein, for the first time, we reported a platinum(IV) complex-based polyprodrug that can in situ generate the highly toxic platinum(II) species as chemotherapeutics and simultaneously induce a high level of reactive oxygen species (ROS) in a PDT-like process without the use of photosensitizer and consumption of oxygen. By in situ polymerizing the platinum(IV) complex-based prodrug monomer (PPM) and 2-methacryloyloxy ethyl phosphorylcholine (MPC), nanosized hydrogel-like polyprodrug could be synthesized. Upon being exposed to light, Pt(IV) moieties in this photoactivable polyprodrug were reduced to generate Pt(II) species. At the meantime, a high level of ROS was generated without the presence of endogenous oxygen, which was confirmed by electron spin resonance (ESR) and fluorescence probes. With the unique nanosized architecture and photoresponsive feature, the as-synthesized polyprodrug exhibited the advantages of sustained drug release, long-term circulation, preferable tumor accumulation, and reversing drug resistance by downregulating the expression of multidrug resistance-associated protein 1 (MRP1) in the anticancer treatment. Copyright © 2018. Published by Elsevier Ltd.

Hypericin encapsulated in solid lipid nanoparticles: phototoxicity and photodynamic efficiency.

PubMed

Lima, Adriel M; Pizzol, Carine Dal; Monteiro, Fabíola B F; Creczynski-Pasa, Tânia B; Andrade, Gislaine P; Ribeiro, Anderson O; Perussi, Janice R

2013-08-05

The hydrophobicity of some photosensitizers can induce aggregation in biological systems, which consequently reduces photodynamic activity. The conjugation of photosensitizers with nanocarrier systems can potentially be used to overcome this problem. The objective of this study was to prepare and characterise hypericin-loaded solid lipid nanoparticles (Hy-SLN) for use in photodynamic therapy (PDT). SLN were prepared using the ultrasonication technique, and their physicochemical properties were characterised. The mean particle size was found to be 153 nm, with a low polydispersity index of 0.28. One of the major advantages of the SLN formulation is its high entrapment efficiency (EE%). Hy-SLN showed greater than 80% EE and a drug loading capacity of 5.22% (w/w). To determine the photodynamic efficiency of Hy before and after encapsulation in SLN, the rate constants for the photodecomposition of two (1)O2 trapping reagents, DPBF and AU, were determined. These rate constants exhibited an increase of 60% and 50% for each method, respectively, which is most likely due to an increase in the lifetime of the triplet state caused by the increase in solubility. Hy-SLN presented a 30% increase in cell uptake and a correlated improvement of 26% in cytotoxicity. Thus, all these advantages suggest that Hy-loaded SLN has potential for use in PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of Blue and White Lamp Light with Sunlight for Daylight-Mediated, 5-ALA Photodynamic Therapy, in vivo.

PubMed

Marra, Kayla; LaRochelle, Ethan P; Chapman, M Shane; Hoopes, P Jack; Lukovits, Karina; Maytin, Edward V; Hasan, Tayyaba; Pogue, Brian W

2018-04-16

Daylight-mediated photodynamic therapy (d-PDT) as a treatment for actinic keratosis (AK) is an increasingly common technique due to a significant reduction in pain, leading to better patient tolerability. While past studies have looked at different light sources and delivery methods, this study strives to provide equivalent PpIX-weighted light doses with the hypothesis that artificial light sources could be equally as effective as natural sunlight if their PpIX-weighted fluences were equalized. Normal mouse skin was used as the model to compare blue LED light, metal halide white light and natural sunlight, with minimal incubation time between topical ALA application and the onset of light delivery. A total PpIX-weighted fluence of 20 J eff cm -2 was delivered over 2 h, and the efficacy of response was quantified using three acute bioassays for PDT damage: PpIX photobleaching, Stat3 crosslinking and quantitative histopathology. These bioassays indicated blue light was slightly inferior to both sunlight and white light, but that the latter two were not significantly different. The results suggest that metal halide white light could be a reasonable alternative to daylight PDT, which should allow a more controlled treatment that is independent of weather and yet should have similar response rates with limited pain during treatment. © 2018 The American Society of Photobiology.

Application of 1,2-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Porter, John B.; Bown, Stephen G.

1995-03-01

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Davidson, Sean R. H.; Weersink, Robert A.; Haider, Masoom A.; Gertner, Mark R.; Bogaards, Arjen; Giewercer, David; Scherz, Avigdor; Sherar, Michael D.; Elhilali, Mostafa; Chin, Joseph L.; Trachtenberg, John; Wilson, Brian C.

2009-04-01

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately ±2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D90, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D90 less than 23 J cm-2 had complete biopsy response, while 8/13 (62%) of patients with a D90 greater than 23 J cm-2 had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

System and Method for Determining Fluence of a Substance

NASA Technical Reports Server (NTRS)

Banks, Bruce A. (Inventor)

2016-01-01

A system and method for measuring a fluence of gas are disclosed. The system has a first light detector capable of outputting an electrical signal based on an amount of light received. A barrier is positionable adjacent the first light detector and is susceptible to a change in dimension from the fluence of the gas. The barrier permits a portion of light from being received by the first light detector. The change in the dimension of the barrier changes the electrical signal output from the first light detector. A second light detector is positionable to receive light representative of the first light detector without the barrier. The system and method have broad application to detect fluence of gas that may cause erosion chemical reaction causing erosive deterioration. One application is in low orbit Earth for detecting the fluence of atomic oxygen.

Antimicrobial Photodynamic Inactivation and Antitumor Photodynamic Therapy with Fullerenes

NASA Astrophysics Data System (ADS)

de Freitas, Lucas F.

2016-04-01

This book provides detailed and current information on using fullerenes (bucky-balls) in photodynamic therapy (PDT), one of the most actively studied applications of photonic science in healthcare. This will serve as a useful source for researchers working in photomedicine and nanomedicine, especially those who are investigating PDT for cancer treatment and infectious disease treatment. The book runs the gamut from an introduction to the history and chemistry of fullerenes and some basic photochemistry, to the application of fullerenes as photosensitizers for cancer and antimicrobial inactivation.

Photodynamic therapy for recurrent respiratory papillomatosis.

PubMed

Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M

2014-06-05

Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.   We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23

Photodynamic therapy for basal cell carcinoma.

PubMed

Fargnoli, Maria Concetta; Peris, Ketty

2015-11-01

Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

Photodynamic inactivation of foodborne bacteria by eosin Y.

PubMed

Bonin, E; Dos Santos, A R; Fiori da Silva, A; Ribeiro, L H; Favero, M E; Campanerut-Sá, P A Z; de Freitas, C F; Caetano, W; Hioka, N; Mikcha, J M G

2018-06-01

The aim of this study was evaluate the effect of photodynamic inactivation mediated by eosin Y in Salmonella enterica serotype Typhimurium ATCC 14028, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778. Bacteria (10 7 CFU per ml) were incubated with eosin Y at concentrations ranging from 0·1 to 10 μmol l -1 , irradiated by green LED (λ max 490-570 nm) for 5, 10 and 15 min and the cellular viability was determined. Pseudomonas aeruginosa was completely inactivated when treated with 10 μmol l -1 eosin Y for 10 min. Treatments reduced B. cereus and Salm. Typhimurium counts to 2·7 log CFU per ml and 1·7 log CFU per ml, respectively. Escherichia coli counts were slightly reduced. Staphylococcus aureus presented the highest sensitivity, being completely inactivated by eosin Y at 5 μmol l -1 and 5 min of illumination. The reduction of cellular viability of photoinactivated Staph. aureus was also demonstrated by flow cytometry and morphological changes were observed by scanning electron microscopy. Eosin Y in combination with LED produced bacterial inactivation, being a potential candidate for photodynamic inactivation. This study evidenced the efficacy of photodynamic inactivation as a novel and promising alternative to bacterial control. © 2018 The Society for Applied Microbiology.

Isotopic Dependence of GCR Fluence behind Shielding

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wilson, John W.; Saganti, Premkumar; Kim, Myung-Hee Y.; Cleghorn, Timothy; Zeitlin, Cary; Tripathi, Ram K.

2006-01-01

In this paper we consider the effects of the isotopic composition of the primary galactic cosmic rays (GCR), nuclear fragmentation cross-sections, and isotopic-grid on the solution to transport models used for shielding studies. Satellite measurements are used to describe the isotopic composition of the GCR. For the nuclear interaction data-base and transport solution, we use the quantum multiple-scattering theory of nuclear fragmentation (QMSFRG) and high-charge and energy (HZETRN) transport code, respectively. The QMSFRG model is shown to accurately describe existing fragmentation data including proper description of the odd-even effects as function of the iso-spin dependence on the projectile nucleus. The principle finding of this study is that large errors (+/-100%) will occur in the mass-fluence spectra when comparing transport models that use a complete isotopic-grid (approx.170 ions) to ones that use a reduced isotopic-grid, for example the 59 ion-grid used in the HZETRN code in the past, however less significant errors (<+/-20%) occur in the elemental-fluence spectra. Because a complete isotopic-grid is readily handled on small computer workstations and is needed for several applications studying GCR propagation and scattering, it is recommended that they be used for future GCR studies.

cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy.

PubMed

Li, Wenjing; Tan, Sihai; Xing, Yutong; Liu, Qian; Li, Shuang; Chen, Qingle; Yu, Min; Wang, Fengwei; Hong, Zhangyong

2018-04-02

Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts its clinical applications. A higher accumulation of photosensitizers is very important for the treatment of deeply seated and larger tumors. The conjugation of Pyro with tumor-homing peptide ligands could be a very useful strategy to optimize the physical properties of Pyro. Herein, we reported our studies on the conjugation of Pyro with a cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, to develop highly tumor-specific photosensitizers for PDT application. To further reduce the nonspecific uptake and, thus, reduce the background distribution of the conjugates in normal tissues, we opted to add a highly hydrophilic polyethylene glycol (PEG) chain and an extra strongly hydrophilic carboxylic acid group as the linker to avoid the direct connection of the strongly hydrophobic Pyro macrocycle and cRGD ligand. We reported here the synthesis and characterization of these conjugates, and the influence of the hydrophilic modification on the biological function of the conjugates was carefully studied. The tumor-accumulation ability and photodynamic-induced cell-killing ability of these conjugates were evaluated through both in vitro cell-based experiment and in vivo distribution and tumor therapy experiments with tumor-bearing mice. Thus, the synthesized conjugate significantly improved the tumor enrichment and tumor selectivity of Pyro, as well as abolished the xenograft tumors in the murine model through a one-time PDT treatment.

Five years experience of photodynamic therapy with new chlorin photosensitizer

NASA Astrophysics Data System (ADS)

Privalov, Valery A.; Lappa, Alexander V.; Kochneva, Elena V.

2005-08-01

Clinical results of photodynamic therapy (PDT) with a novel natural second generation chlorin-type photosensitizer "Radachlorin", mainly consisting of sodium chlorine e6, are presented. This sensitizer possesses a number of advantages over sensitizers of hematoporphyrin and phthalocyanine types. In particular, Radachlorin is excreted from organism much faster (in 1-2 days), as a result the problem of patient light hypersensitivity for a few months is non-actual for Radachlorin. As light source there was used a 662 nm diode laser specially designed for PDT with Radachlorin. The 5 year clinical results of PDT application to 89 patients with different malignant tumors are summarized and analysed. It is shown in particular that PDT with Radachlorin is a radical high efficient method for treatment of basal cell carcinoma of skin. At intravenous introduction in drug dose 0.5 mg/kg with light fluence 300-350 J/cm2 or in dose 1 mg/kg with fluence 200-250 J/cm2 the method gives full recovery in almost 100% cases with excellent cosmetic effect. The method was successfully combined with surgical operations, laser ablations, radio- and chemotherapy. Preoperative and intraoperative PDT favors improvement of results in complex treatment of malignant tumors. The method has a potential as palliative measure; in a number of incurable cases it allowed us to achieve recanalization of obturated hollow organs, eliminate the inflammatory complications, and as a result to improve life quality.

PDT dose dosimetry for Photofrin-mediated pleural photodynamic therapy (pPDT)

NASA Astrophysics Data System (ADS)

Ong, Yi Hong; Kim, Michele M.; Finlay, Jarod C.; Dimofte, Andreea; Singhal, Sunil; Glatstein, Eli; Cengel, Keith A.; Zhu, Timothy C.

2018-01-01

Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its photobleaching. The temporal integral of the product of in vivo photosensitizer concentration and light fluence is called PDT dose, which is an important dosimetry quantity for PDT. However, the detected photosensitizer fluorescence may be distorted by variations in the absorption and scattering of both excitation and fluorescence light in tissue. Therefore, correction of the measured fluorescence for distortion due to variable optical properties is required for absolute quantification of photosensitizer concentration. In this study, we have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and photosensitizer fluorescence data. We measured PDT dose at four sites in the pleural cavity during pleural PDT. We have determined an empirical optical property correction function using Monte Carlo simulations of fluorescence for a range of physiologically relevant tissue optical properties. Parameters of the optical property correction function for Photofrin fluorescence were determined experimentally using tissue-simulating phantoms. In vivo measurements of photosensitizer fluorescence showed negligible photobleaching of Photofrin during the PDT treatment, but large intra- and inter-patient heterogeneities of in vivo Photofrin concentration are observed. PDT doses delivered to 22 sites in the pleural cavity of 8 patients were different by 2.9 times intra-patient and 8.3 times inter-patient.

Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling.

PubMed

Penjweini, Rozhin; Kim, Michele M; Liu, Baochang; Zhu, Timothy C

2016-12-01

Photodynamic therapy (PDT) is known as a non-invasive treatment modality that is based on photochemical reactions between oxygen, photosensitizer, and a special wavelength of light. However, a dosimetric predictor for PDT outcome is still elusive because current dosimetric quantities do not account for the differences in the PDT oxygen consumption rate for different fluence rates. In this study, we evaluate several dose metrics, total fluence, photobleaching ratio, PDT dose, and mean reacted singlet oxygen (mean [ 1 O 2 ] rx ) for predicting the PDT outcome and a clinically relevant tumor re-growth endpoint. For this reason, radiation-induced fibrosarcoma (RIF) mice tumors are treated with 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) and different in-air fluences (30 J/cm 2 , 50 J/cm 2 , 135 J/cm 2 , 250 J/cm 2 , and 350 J/cm 2 ) and in-air fluence rates (20, 50, 75, 150 mW/cm 2 ). Explicit measurements of HPPH and oxygen concentration as well as tissue optical properties are performed pre- and post-treatment. Then, this information is incorporated into a macroscopic model to calculate the photobleaching, PDT dose, and mean [ 1 O 2 ] rx . Changes in tumor volume are tracked following the treatment and compared with the dose metrics. The correlation demonstrates that mean [ 1 O 2 ] rx  serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor re-growth endpoint. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

2005-01-01

In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy.

PubMed

de Miguel, Guilherme Chohfi; Abrantes, Ana Margarida; Laranjo, Mafalda; Grizotto, Ana Yoshie Kitagawa; Camporeze, Bruno; Pereira, José Aires; Brites, Gonçalo; Serra, Arménio; Pineiro, Marta; Rocha-Gonsalves, António; Botelho, Maria Filomena; Priolli, Denise Gonçalves

2018-03-01

Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer. Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99m Tc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed. Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals. Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Photodynamic therapy--aspects of pain management.

PubMed

Fink, Christine; Enk, Alexander; Gholam, Patrick

2015-01-01

Topical photodynamic therapy (PDT) is a highly effective and safe treatment method for actinic keratoses with an excellent cosmetic outcome and is commonly used for the therapy of large areas of photodamaged skin with multiple clinically manifest and subclinical lesions. However, the major drawback of photodynamic therapy is the pain experienced during the treatment that can be intense and sometimes even intolerable for patients, requiring interruption or termination of the process. Several strategies for controlling pain during photodynamic therapy have been studied but few effective methods are currently available. Therefore, this review puts the spotlight on predictors on pain intensity and aspects of pain management during photodynamic therapy. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

A Comprehensive Tutorial on In Vitro Characterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms

PubMed Central

Maisch, Tim; Berneburg, Mark; Plaetzer, Kristjan

2013-01-01

In vitro research performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS) intended for application in photodynamic therapy (PDT) of cancer or photodynamic inactivation (PDI) of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performing in vitro experiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research. PMID:23762860

Results of photodynamic therapy in the combined treatment of choroidal metastasis

NASA Astrophysics Data System (ADS)

Likhvantseva, Vera G.; Osipova, Ekaterina V.; Petrenko, Mikhail V.; Merzlyakova, Oksana Y.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

2007-07-01

Choroidal metastasis (CM) are more and more spreading type of eye's neoplasma. The frequency of CM is increasing with prolonging of cancer patients' life. And it makes worse the quality of their life because blindness. Photodynamic therapy (PDT) is very delicate modality, which can be used for this purpose. The aim of this work was to open the possibility and to determine the efficacy of photodynamic therapy (PDT) in the treatment of patients with CM. PDT was performed simultaneously with standard chemotherapy in 8 oncological patients with CM. We used photosensitizer Photosens in doses of 0.3 mg/kg and light doses 150 J/cm2 (675 nm). PDT was performed in the some stances. Its are ranged from 7 to 10. Complete tumor regression was achieved in 6 cases. The high retina ablation was developed in one case. And in one case effect was not complete: tumor size reduced from 5 mm to 3 mm of thickness. We didn't notice any recurrence for 6-18 months follow-up. PDT is modality that could to be used in the in the combined treatment of the CM.

Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy

PubMed Central

Trigo Gutierrez, Jeffersson Krishan; Zanatta, Gabriela Cristina; Ortega, Ana Laura Mira; Balastegui, Maria Isabella Cuba; Sanitá, Paula Volpato; Pavarina, Ana Cláudia; Barbugli, Paula Aboud

2017-01-01

Curcumin (CUR) has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT). However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP) and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO) as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species) cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA) and non-parametric (Kruskal-Wallis) tests (α = 0.05). CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR. PMID:29107978

SU-G-JeP3-10: Update On a Real-Time Treatment Guidance System Using An IR Navigation System for Pleural PDT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Penjweini, R; Zhu, T

Purpose: Photodynamic therapy (PDT) is used in conjunction with surgical debulking of tumorous tissue during treatment for pleural mesothelioma. One of the key components of effective PDT is uniform light distribution. Currently, light is monitored with 8 isotropic light detectors that are placed at specific locations inside the pleural cavity. A tracking system with real-time feedback software can be utilized to improve the uniformity of light in addition to the existing detectors. Methods: An infrared (IR) tracking camera is used to monitor the movement of the light source. The same system determines the pleural geometry of the treatment area. Softwaremore » upgrades allow visualization of the pleural cavity as a two-dimensional volume. The treatment delivery wand was upgraded for ease of light delivery while incorporating the IR system. Isotropic detector locations are also displayed. Data from the tracking system is used to calculate the light fluence rate delivered. This data is also compared with in vivo data collected via the isotropic detectors. Furthermore, treatment volume information will be used to form light dose volume histograms of the pleural cavity. Results: In a phantom study, the light distribution was improved by using real-time guidance compared to the distribution when using detectors without guidance. With the tracking system, 2D data can be collected regarding light fluence rather than just the 8 discrete locations inside the pleural cavity. Light fluence distribution on the entire cavity can be calculated at every time in the treatment. Conclusion: The IR camera has been used successfully during pleural PDT patient treatment to track the motion of the light source and provide real-time display of 2D light fluence. It is possible to use the feedback system to deliver a more uniform dose of light throughout the pleural cavity.« less

Photoproduct formation of endogeneous protoporphyrin and its photodynamic activity

NASA Astrophysics Data System (ADS)

Koenig, Karsten; Schneckenburger, Herbert; Rueck, Angelika C.; Auchter, S.

1991-11-01

Human skin shows a strong autofluorescence in the red spectral region caused on the porphyrin production of the Gram positive lipophile skin bacterium Propionibacterium acnes. Irradiation of these bacteria reduces the integral fluorescence intensity and induces the formation of fluorescent photoproducts. The fluorescence band at around 670 nm and the decay times of around 1 ns and 5 ns are typical for protoporphyrin products. The photoproduct formation is connected with an increased absorption in the red spectral region. However the photodynamic activity of these photoproducts determined by scattering measurements on human erythrocytes is lower than that of protoporphyrin IX. 1:

Photodynamic application in neurosurgery: present and future

NASA Astrophysics Data System (ADS)

Kostron, Herwig

2009-06-01

Photodynamic techniques such as photodynamic diagnosis (PDD), fluorescence guided tumor resection (FGR) and photodynamic therapy (PDT) are currently undergoing intensive clinical investigations as adjunctive treatment for malignant brain tumours. This review provides an overview on the current clinical data and trials as well as on photosensitisers, technical developments and indications for photodynamic application in Neurosurgery. Furthermore new developments and clinical significance of FGR for neurosurgery will be discussed. Over 1000 patients were enrolled in various clinical phase I/II trials for PDT for malignant brain tumours. Despite various treatment protocols, variation of photosensitisers and light dose there is a clear trend towards prolonging median survival after one single PDT as compared to conventional therapeutic modalities. The median survival after PDT for primary glioblastoma multiforme WHO IV was 19 months and for recurrent GBM 9 months as compared to standard convential treatment which is 15 months and 3 months, respectively. FGR in combination with adjunctive radiation was significantly superior to standard surgical resection followed by radiation. The combination of FGR/PDD and intraoperative PDT increased significantly survival in recurrent glioblastoma patients. The combination of PDD/ FGR and PDT offers an exciting approach to the treatment of malignant brain tumours "to see and to treat." PDT was generally well tolerated and side effects consisted of occasionally increased intracranial pressure and prolonged skin sensitivity against direct sunlight. This review covers the current available data and draws the future potential of PDD and PDT for its application in neurosurgery.

Photodynamic therapy with Photofrin II by bronchial artery infusion

NASA Astrophysics Data System (ADS)

Okunaka, Tetsuya; Kato, Harubumi; Konaka, Chimori; Kinoshita, Komei; Yamada, Kimito

1993-03-01

Photodynamic therapy (PDT) utilizing Photofrin II is proving to be an effective modality in the treatment of early stage lung cancer. However, wider clinical application of Photofrin II as a photosensitizer for various cancers is hampered by the potentially serious and prolonged skin photosensitivity. To prevent these side effects and reduce the inpatient period, we recently tried to give reduced doses of Photofrin II by bronchial artery infusion (BAI). Six patients with endoscopically evaluated early stage carcinoma of the lung were given 0.7 mg/kg of Photofrin II by BAI 48 hours before PDT. Complete remission was obtained in all 6 cases, and there was no evidence of skin photosensitivity when exposed to outside light under careful surveillance at one week after PDT.

Photodynamic Therapy Using Intra-Articular Photofrin for Murine MRSA Arthritis: Biphasic Light Dose Response for Neutrophil-Mediated Antibacterial Effect

PubMed Central

Tanaka, Masamitsu; Kinoshita, Manabu; Yoshihara, Yasuo; Shinomiya, Nariyoshi; Seki, Shuhji; Nemoto, Koichi; Hamblin, Michael R.; Morimoto, Yuji

2011-01-01

Background and Objective Bacterial arthritis does not respond well to antibiotics and moreover multidrug resistance is spreading. We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin® in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated. Study Design/Materials and Methods The present study used an intra-articular injection of Photofrin® and optimized the light dosimetry in order to maximize bacterial killing and minimize killing of host neutrophils. MRSA (5 × 107 CFU) was injected into the mouse knee followed 3 days later by 1 μg of Photofrin® and 635-nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1–3, 5, and 7 days after PDT to determine MRSA colony-forming units (CFU), neutrophil numbers, and levels of cytokines. Results A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20 J cm−2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein-2, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20 J cm−2 compared to fluences of 5 or 70 J cm−2. Conclusion PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense. PMID:21412806

Fluence field modulated CT on a clinical TomoTherapy radiation therapy machine

NASA Astrophysics Data System (ADS)

Szczykutowicz, Timothy P.; Hermus, James

2015-03-01

Purpose: The multi-leaf collimator (MLC) assembly present on TomoTherapy (Accuray, Madison WI) radiation therapy (RT) and mega voltage CT machines is well suited to perform fluence field modulated CT (FFMCT). In addition, there is a demand in the RT environment for FFMCT imaging techniques, specifically volume of interest (VOI) imaging. Methods: A clinical TomoTherapy machine was programmed to deliver 30% imaging dose outside predefined VOIs. Four different size ROIs were placed at varying distances from isocenter. Projections intersecting the VOI received "full dose" while those not intersecting the VOI received 30% of the dose (i.e. the incident fluence for non VOI projections was 30% of the incident fluence for projections intersecting the VOI). Additional scans without fluence field modulation were acquired at "full" and 30% dose. The noise (pixel standard deviation) was measured inside the VOI region and compared between the three scans. Results: The VOI-FFMCT technique produced an image noise 1.09, 1.05, 1.05, and 1.21 times higher than the "full dose" scan for ROI sizes of 10 cm, 13 cm, 10 cm, and 6 cm respectively within the VOI region. Conclusions: Noise levels can be almost unchanged within clinically relevant VOIs sizes for RT applications while the integral imaging dose to the patient can be decreased, and/or the image quality in RT can be dramatically increased with no change in dose relative to non-FFMCT RT imaging. The ability to shift dose away from regions unimportant for clinical evaluation in order to improve image quality or reduce imaging dose has been demonstrated. This paper demonstrates that FFMCT can be performed using the MLC on a clinical TomoTherapy machine for the first time.

Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

NASA Astrophysics Data System (ADS)

Kim, Michele M.; Penjweini, Rozhin; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume <= 100 mm3 using four dose metrics: light fluence, photosensitizer photobleaching rate, PDT dose, and [1O2]rx. PDT dose was defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume <=100 mm3, for the four dose metrics light fluence, photosensitizer photobleaching rate, PDT dose and [1O2]rx. PDT dose is defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

Photodynamic therapy in endodontics: a literature review.

PubMed

Trindade, Alessandra Cesar; De Figueiredo, José Antônio Poli; Steier, Liviu; Weber, João Batista Blessmann

2015-03-01

Recently, several in vitro and in vivo studies demonstrated promising results about the use of photodynamic therapy during root canal system disinfection. However, there is no consensus on a standard protocol for its incorporation during root canal treatment. The purpose of this study was to summarize the results of research on photodynamic therapy in endodontics published in peer-reviewed journals. A review of pertinent literature was conducted using the PubMed database, and data obtained were categorized into sections in terms of relevant topics. Studies conducted in recent years highlighted the antimicrobial potential of photodynamic therapy in endodontics. However, most of these studies were not able to confirm a significant improvement in root canal disinfection for photodynamic therapy as a substitute for current disinfection methods. Its indication as an excellent adjunct to conventional endodontic therapy is well documented, however. Data suggest the need for protocol adjustments or new photosensitizer formulations to enhance photodynamic therapy predictability in endodontics.

Second generation photodynamic agents: a review.

PubMed

Sternberg, E D; Dolphin, D

1993-10-01

Over the last decade, laser treatment of neoplastic diseases has become routine. The ability of these light-induced therapies to effect positive results is increased with the utilization of photosensitizing dyes. The approval of Photofrin in Canada as a first generation photodynamic therapeutic agent for the treatment of some forms of bladder cancer is being followed by the development of other agents with improved properties. At this time a number of second generation photosensitizing dyes are under study in phase I/II clinical trials. A review of the status of these trials along with mechanistic aspects is reviewed in this article. In addition, a review of the status of lasers to be utilized for photodynamic therapy gives some indication of which instruments could be considered for this therapy in the future.

Mitochondria-targeting for improved photodynamic therapy

NASA Astrophysics Data System (ADS)

Ngen, Ethel J.

Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus

Endodontic photodynamic therapy ex vivo.

PubMed

Ng, Raymond; Singh, Fiza; Papamanou, Despina A; Song, Xiaoqing; Patel, Chitrang; Holewa, Colleen; Patel, Niraj; Klepac-Ceraj, Vanja; Fontana, Carla R; Kent, Ralph; Pagonis, Tom C; Stashenko, Philip P; Soukos, Nikolaos S

2011-02-01

The objective of this study was to evaluate the antimicrobial effects of photodynamic therapy (PDT) on infected human teeth ex vivo. Fifty-two freshly extracted teeth with pulpal necrosis and associated periradicular radiolucencies were obtained from 34 subjects. Twenty-six teeth with 49 canals received chemomechanical debridement (CMD) with 6% NaOCl, and 26 teeth with 52 canals received CMD plus PDT. For PDT, root canal systems were incubated with methylene blue (MB) at concentration of 50 μg/mL for 5 minutes, followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm(2). The contents of root canals were sampled by flushing the canals at baseline and after CMD alone or CMD+PDT and were serially diluted and cultured on blood agar. Survival fractions were calculated by counting colony-forming units (CFUs). Partial characterization of root canal species at baseline and after CMD alone or CMD+PDT was performed by using DNA probes to a panel of 39 endodontic species in the checkerboard assay. The Mantel-Haenszel χ(2) test for treatment effects demonstrated the better performance of CMD+PDT over CMD (P = .026). CMD+PDT significantly reduced the frequency of positive canals relative to CMD alone (P = .0003). After CMD+PDT, 45 of 52 canals (86.5%) had no CFUs as compared with 24 of 49 canals (49%) treated with CMD (canal flush samples). The CFU reductions were similar when teeth or canals were treated as independent entities. Post-treatment detection levels for all species were markedly lower for canals treated by CMD+PDT than they were for those treated by CMD alone. Bacterial species within dentinal tubules were detected in 17 of 22 (77.3%) and 15 of 29 (51.7%) canals in the CMD and CMD+PDT groups, respectively (P = .034). Data indicate that PDT significantly reduces residual bacteria within the root canal system, and that PDT, if further enhanced by technical improvements, holds substantial promise as an adjunct to CMD. Copyright © 2011 American

Skin photosensitivity as a model in photodynamic therapy

NASA Astrophysics Data System (ADS)

Richter, Anna M.; Jain, Ashok K.; Canaan, Alice J.; Meadows, Howard; Levy, Julia G.

1996-01-01

Skin photosensitivity is the most common side effect of photodynamic therapy (PDT) and in clinical situations needs to be avoided or at least minimized. However, because of the accessibility of skin tissue, skin photosensitivity represents a useful test system in vivo for evaluation of the pharmacokinetics of photosensitizers and light sources. Pig skin resembles in many aspects human skin and, therefore, is most suitable for these tests. Using pig skin photosensitivity as an end point, we evaluate the effect of cell loading with a photosensitizer, benzoporphyrin derivative (BPD verteporfin) following its intravenous administration either as a rapid bolus or slow infusion. Skin response to light activation indicated a very similar cell content of BPD. These results were in agrement with those obtained in an in vitro model. In addition, in the same pig skin photosensitivity model we compared the efficiency of activation of BPD with either laser (690 plus or minus 3 nm) or light-emitting diode (LED; 690 plus or minus 12 nm) light. Results indicated the equivalency of the two light sources in this test system, with LED light being slightly more efficient, due possibly to a fluence rate lower than laser light.

Molecular imaging of photodynamic therapy

NASA Astrophysics Data System (ADS)

Chang, Sung K.; Errabelli, Divya; Rizvi, Imran; Solban, Nicolas; O'Riordan, Katherine; Hasan, Tayyaba

2006-02-01

Recent advances in light sources, detectors and other optical imaging technologies coupled with the development of novel optical contrast agents have enabled real-time, high resolution, in vivo monitoring of molecular targets. Noninvasive monitoring of molecular targets is particularly relevant to photodynamic therapy (PDT), including the delivery of photosensitizer in the treatment site and monitoring of molecular and physiological changes following treatment. Our lab has developed optical imaging technologies to investigate these various aspects of photodynamic therapy (PDT). We used a laser scanning confocal microscope to monitor the pharmacokinetics of various photosensitizers in in vitro as well as ex vivo samples, and developed an intravital fluorescence microscope to monitor photosensitizer delivery in vivo in small animals. A molecular specific contrast agent that targets the vascular endothelial growth factor (VEGF) was developed to monitor the changes in the protein expression following PDT. We were then able to study the physiological changes due to post-treatment VEGF upregulation by quantifying vascular permeability with in vivo imaging.

Nontumor photodynamic therapy

NASA Astrophysics Data System (ADS)

van den Bergh, Hubert

1997-12-01

Photodynamic therapy (PDT) has become an approved treatment for different types of cancer in many countries over the last few years. As an example one might mention PDT of the early stages of bronchial or esophageal cancer which have been treated with only about 20% recurrence being observed over several years of follow-up. The low degree of invasion of PDT, as compared to most alternative treatments as well as minimal sided effects, and good repeatability, all speak for this treatment modality. Improved and cheap screening procedures, that are now being developed for the early stage disease, will lead to a more frequent application of PDT for these indications. Detailed studies of PDT showed that certain dyes, after systematic or topical application, could be taken up more in neoplastic tissue as compared to the surrounding normal tissue in the clinical context, thus leading to 'selective' or at least partially selective destruction of the tumor following light application. This selectivity of uptake of certain compounds in hyperproliferative tissue, as well as the observation that PDT can lead to blood vessel stasis, suggested that photodynamic therapy might be worth trying in non-tumor disease. Some of the diseases associated with hyperproliferation and/or neovascularization which are being considered for PDT are listed in table I.

Materials International Space Station Experiment-6 (MISSE-6) Atomic Oxygen Fluence Monitor Experiment

NASA Technical Reports Server (NTRS)

Banks, Bruce A.; Miller, Sharon K.; Waters, Deborah L.

2010-01-01

An atomic oxygen fluence monitor was flown as part of the Materials International Space Station Experiment-6 (MISSE-6). The monitor was designed to measure the accumulation of atomic oxygen fluence with time as it impinged upon the ram surface of the MISSE 6B Passive Experiment Container (PEC). This was an active experiment for which data was to be stored on a battery-powered data logger for post-flight retrieval and analysis. The atomic oxygen fluence measurement was accomplished by allowing atomic oxygen to erode two opposing wedges of pyrolytic graphite that partially covered a photodiode. As the wedges of pyrolytic graphite erode, the area of the photodiode that is illuminated by the Sun increases. The short circuit current, which is proportional to the area of illumination, was to be measured and recorded as a function of time. The short circuit current from a different photodiode, which was oriented in the same direction and had an unobstructed view of the Sun, was also to be recorded as a reference current. The ratio of the two separate recorded currents should bear a linear relationship with the accumulated atomic oxygen fluence and be independent of the intensity of solar illumination. Ground hyperthermal atomic oxygen exposure facilities were used to evaluate the linearity of the ratio of short circuit current to the atomic oxygen fluence. In flight, the current measurement circuitry failed to operate properly, thus the overall atomic oxygen mission fluence could only be estimated based on the physical erosion of the pyrolytic graphite wedges. The atomic oxygen fluence was calculated based on the knowledge of the space atomic oxygen erosion yield of pyrolytic graphite measured from samples on the MISSE 2. The atomic oxygen fluence monitor, the expected result and comparison of mission atomic oxygen fluence based on the erosion of the pyrolytic graphite and Kapton H atomic oxygen fluence witness samples are presented in this paper.

Biomedical applications of nano-titania in theranostics and photodynamic therapy.

PubMed

Rehman, F U; Zhao, C; Jiang, H; Wang, X

2016-01-01

Titanium dioxide (TiO2) is one of the most abundantly used nanomaterials for human life. It is used in sunscreen, photovoltaic devices, biomedical applications and as a food additive and environmental scavenger. Nano-TiO2 in biomedical applications is well documented. It is used in endoprosthetic implants and early theranostics of neoplastic and non-neoplastic maladies as a photodynamic therapeutic agent and as vehicles in nano-drug delivery systems. Herein, we focus on the recent advancements and applications of nano-TiO2 in bio-nanotechnology, nanomedicine and photodynamic therapy (PDT).

Effects of vegetation, a clay cap and environmental variables on 222Rn fluence rate from reclaimed U mill tailings.

PubMed

Morris, R C; Fraley, L

1989-04-01

We measured 222Rn fluence rate and several environmental variables on two plots with U mill tailings buried beneath 30 cm of overburden and 20 cm of topsoil. An additional 30 cm of clay covered the tailings on one plot and each plot was subdivided into bare soil and vegetated subplots. We used linear correlation, two-way ANOVA and stepwise multiple regression to analyze the effects of the plot characteristics and the environmental variables on 222Rn fluence rate. The most important effect on 222Rn fluence rates from these plots was the combination of a clay cap and a vegetated surface. The mean annual fluence rate from the plot having both of these characteristics (520 +/- 370 mBq m-2 s-1) was over three times that of the vegetated plot without a clay cap (170 +/- 130 mBq m-2 s-1) and 18 times that of the bare plot with a clay cap (29 +/- 13 mBq m-2 s-1). The interaction effect may have been due to the growth of roots in the moist clay and active transport of dissolved 222Rn to the surface in water. This speculation is supported by the observation that on vegetated plots with a clay cap, moisture in the clay enhanced the fluence rate.

Comparison of three light doses in the photodynamic treatment of actinic keratosis using mathematical modeling

NASA Astrophysics Data System (ADS)

Vignion-Dewalle, Anne-Sophie; Betrouni, Nacim; Tylcz, Jean-Baptiste; Vermandel, Maximilien; Mortier, Laurent; Mordon, Serge

2015-05-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm2, 75 mW/cm2, 500 s blue light dose, 10 J/cm2, 10 mW/cm2, 1000 s and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable.

Particle Test Fluence: What's the Right Number?

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.

2014-01-01

While we have been utilizing standard fluence levels such as those listed in the JESD57 document, we have begun revisiting what an appropriate test fluence is when it comes to qualifying a device for single events. Instead of a fixed fluence level or until a specific number of events occurs, a different thought process is required.

Photodynamic effects of pyropheophorbide-a methyl ester in nasopharyngeal carcinoma cells.

PubMed

Xu, Chuan Shan; Leung, Albert Wing Nang

2006-08-01

Nasopharyngeal carcinoma (NPC) is one of the most common cancers, and exploring novel therapeutic modalities will improve the clinical outcomes. It has been confirmed that photodynamic therapy can efficiently deactivate malignant cells. The aim of the present study was to explore the photodynamic effects of pyropheophorbide-a methyl ester (MPPa) in CNE2 nasopharyngeal carcinoma cells. CNE2 cells were subjected to photodynamic therapy with MPPa, in which the drug concentration was 0.25 to 4 microM and light energy 1 to 8 J/cm(2). Photodynamic toxicity was investigated 24 h after treatment. Apoptosis was determined using flow cytometry with annexin V-FITC and propidum iodine staining and with nuclear staining with Hoechst 33258. The mitochondrial membrane potential (DeltaPsim) was evaluated by Rhodamine 123 assay. There was no dark cytotoxicity of MPPa in the CNE2 cells at doses of 0.25-4 microM, and MPPa resulted in dose- and light-dependent phototoxicity. The apoptotic rate 8 h after PDT with MPPa (2 microM) increased to 16.43% under a light energy of 2 J/cm(2). Mitochondrial membrane potential (DeltaPsim) collapsed when the CNE2 cells were exposed to 2 microM MPPa for 20 h and then 2 J/cm(2) irradiation. Photodynamic therapy with MPPa significantly enhanced apoptosis and the collapse of DeltaPsim. This can be developed for treating nasopharyngeal carcinoma.

Photodynamic therapy for treatment subretinal neovascularization

NASA Astrophysics Data System (ADS)

Avetisov, Sergey E.; Budzinskaja, Maria V.; Kiseleva, Tatyana N.; Balatskaya, Natalia V.; Gurova, Irina V.; Loschenov, Viktor B.; Shevchik, Sergey A.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

2007-07-01

This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

Experimental evaluation of dual multiple aperture devices for fluence field modulated x-ray computed tomography

NASA Astrophysics Data System (ADS)

Mathews, A. J.; Gang, G.; Levinson, R.; Zbijewski, W.; Kawamoto, S.; Siewerdsen, J. H.; Stayman, J. W.

2017-03-01

Acquisition of CT images with comparable diagnostic power can potentially be achieved with lower radiation exposure than the current standard of care through the adoption of hardware-based fluence-field modulation (e.g. dynamic bowtie filters). While modern CT scanners employ elements such as static bowtie filters and tube-current modulation, such solutions are limited in the fluence patterns that they can achieve, and thus are limited in their ability to adapt to broad classes of patient morphology. Fluence-field modulation also enables new applications such as region-of-interest imaging, task specific imaging, reducing measurement noise or improving image quality. The work presented in this paper leverages a novel fluence modulation strategy that uses "Multiple Aperture Devices" (MADs) which are, in essence, binary filters, blocking or passing x-rays on a fine scale. Utilizing two MAD devices in series provides the capability of generating a large number of fluence patterns via small relative motions between the MAD filters. We present the first experimental evaluation of fluence-field modulation using a dual-MAD system, and demonstrate the efficacy of this technique with a characterization of achievable fluence patterns and an investigation of experimental projection data.

Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

NASA Astrophysics Data System (ADS)

Kumar, M. Suresh; Aruna, P.; Ganesan, S.

2018-03-01

One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

SU-F-T-261: Reconstruction of Initial Photon Fluence Based On EPID Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seliger, T; Engenhart-Cabillic, R; Czarnecki, D

2016-06-15

Purpose: Verifying an algorithm to reconstruct relative initial photon fluence for clinical use. Clinical EPID and CT images were acquired to reconstruct an external photon radiation treatment field. The reconstructed initial photon fluence could be used to verify the treatment or calculate the applied dose to the patient. Methods: The acquired EPID images were corrected for scatter caused by the patient and the EPID with an iterative reconstruction algorithm. The transmitted photon fluence behind the patient was calculated subsequently. Based on the transmitted fluence the initial photon fluence was calculated using a back-projection algorithm which takes the patient geometry andmore » its energy dependent linear attenuation into account. This attenuation was gained from the acquired cone-beam CT or the planning CT by calculating a water-equivalent radiological thickness for each irradiation direction. To verify the algorithm an inhomogeneous phantom consisting of three inhomogeneities was irradiated by a static 6 MV photon field and compared to a reference flood field image. Results: The mean deviation between the reconstructed relative photon fluence for the inhomogeneous phantom and the flood field EPID image was 3% rising up to 7% for off-axis fluence. This was probably caused by the used clinical EPID calibration, which flattens the inhomogeneous fluence profile of the beam. Conclusion: In this clinical experiment the algorithm achieved good results in the center of the field while it showed high deviation of the lateral fluence. This could be reduced by optimizing the EPID calibration, considering the off-axis differential energy response. In further progress this and other aspects of the EPID, eg. field size dependency, CT and dose calibration have to be studied to realize a clinical acceptable accuracy of 2%.« less

Antimicrobial Activity of Photodynamic Therapy Against Enterococcus faecalis Before and After Reciprocating Instrumentation in Permanent Molars.

PubMed

Pinheiro, Sérgio Luiz; Azenha, Giuliana Rodrigues; Democh, Yasmin Marialva; Nunes, Daniela Camila; Provasi, Silvia; Fontanetti, Giovana Masiero; Duarte, Danilo Antônio; Fontana, Carlos Eduardo; da Silveira Bueno, Carlos Eduardo

2016-12-01

The present study sought to evaluate the antimicrobial activity against Enterococcus faecalis of photodynamic therapy applied before and after reciprocating instrumentation of permanent molars. Apical extrusion of debris can cause flare-ups due to introduction of bacteria into the periapical tissues. Eighteen mesial roots from permanent mandibular molars were selected. The crowns were removed to obtain a standard root length of 15 mm. The included mesial roots had an angulation of 10°-40° and canals with independent foramina. The orifice of each mesiolingual canal was sealed with light-curing resin, and the working length was established visually, 1 mm short of the apical foramen. The roots were rendered impermeable and sterilized, and the mesiobuccal canals were contaminated with a standard strain of E. faecalis for 21 days. Specimens were randomly divided into three groups (n = 6): G1, photodynamic therapy performed before instrumentation and irrigation with 0.9% NaCl (saline) solution; G2, photodynamic therapy performed after instrumentation and irrigation with 0.9% NaCl; and G3 (control), instrumentation and irrigation with 2.5% NaOCl (sodium hypochlorite) solution. Canals were shaped with a WaveOne primary file (25.08) and irrigated with 0.9% NaCl. E. faecalis samples were collected before and after each procedure, and the results were analyzed using descriptive statistics and the Kruskal-Wallis and Wilcoxon tests. Significant reductions in E. faecalis were observed when photodynamic therapy was performed before and after instrumentation of the root canal system (p < 0.05). Reciprocating instrumentation significantly reduced E. faecalis colonies in experimentally contaminated root canal systems (p < 0.05). Photodynamic therapy was effective in removing E. faecalis from the root canal system, whether performed before or after reciprocating instrumentation.

[Photodynamic therapy for actinic cheilitis].

PubMed

Castaño, E; Comunión, A; Arias, D; Miñano, R; Romero, A; Borbujo, J

2009-12-01

Actinic cheilitis is a subtype of actinic keratosis that mainly affects the lower lip and has a higher risk of malignant transformation. Its location on the labial mucosa influences the therapeutic approach. Vermilionectomy requires local or general anesthetic and is associated with a risk of an unsightly scar, and the treatment with 5-fluorouracil or imiquimod lasts for several weeks and the inflammatory reaction can be very intense. A number of authors have used photodynamic therapy as an alternative to the usual treatments. We present 3 patients with histologically confirmed actinic cheilitis treated using photodynamic therapy with methyl aminolevulinic acid as the photosensitizer and red light at 630 nm. The clinical response was good, with no recurrences after 3 to 6 months of follow-up. Our experience supports the use of photodynamic therapy as a good alternative for the treatment of actinic cheilitis.

SU-E-T-436: Fluence-Based Trajectory Optimization for Non-Coplanar VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smyth, G; Bamber, JC; Bedford, JL

2015-06-15

Purpose: To investigate a fluence-based trajectory optimization technique for non-coplanar VMAT for brain cancer. Methods: Single-arc non-coplanar VMAT trajectories were determined using a heuristic technique for five patients. Organ at risk (OAR) volume intersected during raytracing was minimized for two cases: absolute volume and the sum of relative volumes weighted by OAR importance. These trajectories and coplanar VMAT formed starting points for the fluence-based optimization method. Iterative least squares optimization was performed on control points 24° apart in gantry rotation. Optimization minimized the root-mean-square (RMS) deviation of PTV dose from the prescription (relative importance 100), maximum dose to the brainstemmore » (10), optic chiasm (5), globes (5) and optic nerves (5), plus mean dose to the lenses (5), hippocampi (3), temporal lobes (2), cochleae (1) and brain excluding other regions of interest (1). Control point couch rotations were varied in steps of up to 10° and accepted if the cost function improved. Final treatment plans were optimized with the same objectives in an in-house planning system and evaluated using a composite metric - the sum of optimization metrics weighted by importance. Results: The composite metric decreased with fluence-based optimization in 14 of the 15 plans. In the remaining case its overall value, and the PTV and OAR components, were unchanged but the balance of OAR sparing differed. PTV RMS deviation was improved in 13 cases and unchanged in two. The OAR component was reduced in 13 plans. In one case the OAR component increased but the composite metric decreased - a 4 Gy increase in OAR metrics was balanced by a reduction in PTV RMS deviation from 2.8% to 2.6%. Conclusion: Fluence-based trajectory optimization improved plan quality as defined by the composite metric. While dose differences were case specific, fluence-based optimization improved both PTV and OAR dosimetry in 80% of cases.« less

Does supplemental photodynamic therapy optimize the disinfection of bacteria and endotoxins in one-visit and two-visit root canal therapy? A randomized clinical trial.

PubMed

Rabello, Diego G D; Corazza, Bruna J M; Ferreira, Luciana L; Santamaria, Mauro P; Gomes, Ana P M; Martinho, Frederico C

2017-09-01

To evaluate the effectiveness of supplemental photodynamic therapy (PDT) in optimizing the removal of bacteria and endotoxins from primarily infected root canals after one-visit and two-visit treatments. Twenty-four primarily infected root canals with apical periodontitis were selected and randomly divided into one-visit (n=12) and two-visit treatment groups (n=12). Chemo-mechanical preparation (CMP) was performed by using the single-file reciprocating technique+2.5% NaOCL and a final rinse with 17% EDTA. The photosensitizer agent (methylene blue 0.1mg/mL) was applied to root canals for 60s before application of laser with a potency of 60mW and energy density of 129J/cm 2 for 120s after CMP in the one-visit treatment and after 14-day inter-appointment medication with Ca(OH) 2 +Saline solution (SSL) in the two-visit treatment. Samples were collected before and after root canal procedures. Endotoxins were quantified by chromogenic limulus amebocyte lysate assay. Culture techniques were used to determine bacterial colony-forming unit counts. Bacteria and endotoxins were detected in 100% of the initial samples, with median values of 1.97×10 5 CFU/mL and 24.983EU/mL, respectively. The CMP using single-file reciprocating technique was effective in the reduction of bacteria and endotoxins (All, p<0.05). The supplemental PDT was effective in reducing bacterial load in the one-visit (p<0.05) but not in the two-visit treatment after use of Ca(OH) 2 medication for 14days (p>0.05). In the two-visit group, after 14days of inter-appointment medication with Ca(OH) 2 , a significant reduction in the median levels of endotoxins was found in comparison to CMP alone (from 1.041 to 0.094EU/mL) (p<0.05). Despite the type of treatment, the supplemental PDT was not effective against endotoxins (p>0.05). The photodynamic therapy optimized the disinfection of bacteria from root canals in one-visit but not for two visit treatment modality with the accomplishment of calcium hydroxide

Photodynamic therapy in treatment of severe oral lichen planus.

PubMed

Rabinovich, O F; Rabinovich, I M; Guseva, A V

2016-01-01

The aim of the study was to elaborate the rationale for the application of photodynamic therapy in complex treatment of patient with severe oral lichen planus. Complex clinical and laboratory examination and treatment was performed in 54 patients divided on 3 groups. Diagnosis of oral lichen planus was based on clinical, histological and immunohistochemical features. Group 1 received standard treatment, in the second group photodynamic therapy was conducted in addition to conventional treatment, patients in the third group received only photodynamic therapy. The study results proved photodynamic therapy to be useful tool in complex treatment of severe oral lichen planus.

Evaluation of antitumor efficiency of experimental interstitial photodynamic therapy on the model of M1 sarcoma.

PubMed

Skugareva, O A; Kaplan, M A; Malygina, A I; Mikhailovskaya, A A

2009-11-01

Antitumor efficiency of interstitial photodynamic therapy was evaluated in experiments on outbred albino rats with implanted M-1 sarcoma. Interstitial photodynamic therapy was carried out using one diffusor at different output power and duration of exposure. The percentage of complete regression of the tumors increased with increasing exposure parameters.

A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.

PubMed

Yao, Mengyu; Ma, Lun; Li, Lihua; Zhang, Junying; Lim, Rebecca; Chen, Wei; Zhang, Yu

2016-10-01

Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.

Conjugate of biotin with silicon(IV) phthalocyanine for tumor-targeting photodynamic therapy.

PubMed

Li, Ke; Qiu, Ling; Liu, Qingzhu; Lv, Gaochao; Zhao, Xueyu; Wang, Shanshan; Lin, Jianguo

2017-09-01

In order to improve the efficacy of photodynamic therapy (PDT), biotin was axially conjugated with silicon(IV) phthalocyanine (SiPc) skeleton to develop a new tumor-targeting photosensitizer SiPc-biotin. The target compound SiPc-biotin showed much higher binding affinity toward BR-positive (biotin receptor overexpressed) HeLa human cervical carcinoma cells than its precursor SiPc-pip. However, when the biotin receptors of HeLa cells were blocked by free biotin, >50% uptake of SiPc-biotin was suppressed, demonstrating that SiPc-biotin could selectively accumulate in BR-positive cancer cells via the BR-mediated internalization. The confocal fluorescence images further confirmed the target binding ability of SiPc-biotin. As a consequence of specificity of SiPc-biotin toward BR-positive HeLa cells, the photodynamic effect was also largely dependent on the BR expression level of HeLa cells. The photodynamic activities of SiPc-biotin against HeLa cells were dramatically reduced when the biotin receptors were blocked by the free biotin (IC 50 : 0.18μM vs. 0.46μM). It is concluded that SiPc-biotin can selectively damage BR-positive cancer cells under irradiation. Furthermore, the dark toxicity of SiPc-biotin toward human normal liver cell lines LO2 was much lower than that of its precursor SiPc-pip. The targeting photodynamic activity and low dark toxicity suggest that SiPc-biotin is a promising photosensitizer for tumor-targeting photodynamic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Photodynamic Antimicrobial Chemotherapy on Mono- and Multi-Species Cariogenic Biofilms: A Literature Review

PubMed Central

de Freitas, Maria Tayara Marques; Soares, Talyta Teixeira; Aragão, Maria Gerusa Brito; Lima, Ramille Araújo; Duarte, Simone

2017-01-01

Abstract Objective: The aim of this literature review is to study the effect of photodynamic antimicrobial chemotherapy (PACT) on mono- and multi-species cariogenic biofilms. Methods: To this purpose, the database, PubMed, was searched using the descriptors, photodynamic therapy, antimicrobial photodynamic chemotherapy, and photoinactivation, associated with the mandatory presence of the word biofilm. A total of 98 references published from 2003 to 2016 were selected. Moreover, literature reviews (15), investigations that did not have biofilms related to dental caries (65), and those that did not have Streptococcus mutans count as an outcome (7) were excluded, yielding a final amount of 11 publications. Results: The results revealed that Toluidine Blue O was the most used photosensitizer. Among the sources of light, light-emitting diode was the choice, and the biofilm models varied between in vitro and in situ. Multi-species biofilms were more resistant to the antimicrobial effects of PACT due to the thickness and complexity they have, which impede the penetration of the photosensitizer. This fact may also be associated with the type of photosensitizer used as well as with the light exposure time since the antimicrobial effect seems to be dose dependent. Despite this, in all the included publications, the therapy was effective in reducing S. mutans count. Conclusions: This review demonstrated that under different conditions, PACT is effective in reducing S. mutans count in monospecies biofilms. Multi-species biofilms were more resistant to the antimicrobial action of the therapy, possibly due to their thickness and complexity. PMID:28121497

Low versus High Fluence Parameters in the Treatment of Facial Laceration Scars with a 1,550 nm Fractional Erbium-Glass Laser

PubMed Central

Shim, Hyung-Sup; Jun, Dai-Won; Kim, Sang-Wha; Jung, Sung-No; Kwon, Ho

2015-01-01

Purpose. Early postoperative fractional laser treatment has been used to reduce scarring in many institutions, but the most effective energy parameters have not yet been established. This study sought to determine effective parameters in the treatment of facial laceration scars. Methods. From September 2012 to September 2013, 57 patients were enrolled according to the study. To compare the low and high fluence parameters of 1,550 nm fractional erbium-glass laser treatment, we virtually divided the scar of each individual patient in half, and each half was treated with a high and low fluence setting, respectively. A total of four treatment sessions were performed at one-month intervals and clinical photographs were taken at every visit. Results. Results were assessed using the Vancouver Scar Scale (VSS) and global assessment of the two portions of each individual scar. Final evaluation revealed that the portions treated with high fluence parameter showed greater difference compared to pretreatment VSS scores and global assessment values, indicating favorable cosmetic results. Conclusion. We compared the effects of high fluence and low fluence 1,550 nm fractional erbium-glass laser treatment for facial scarring in the early postoperative period and revealed that the high fluence parameter was more effective for scar management. PMID:26236738

Engineering a Cell-surface Aptamer Circuit for Targeted and Amplified Photodynamic Cancer Therapy

PubMed Central

Han, Da; Zhu, Guizhi; Wu, Cuichen; Zhu, Zhi; Chen, Tao; Zhang, Xiaobing

2013-01-01

Photodynamic therapy (PDT) is one of the most promising and noninvasive methods for clinical treatment of different malignant diseases. Here, we present a novel strategy of designing an aptamer-based DNA nanocircuit capable of the selective recognition of cancer cells, controllable activation of photosensitizer and amplification of photodynamic therapeutic effect. The aptamers can selectively recognize target cancer cells and bind to the specific proteins on cell membranes. Then the overhanging catalyst sequence on aptamer can trigger a toehold-mediated catalytic strand displacement to activate photosensitizer and achieve amplified therapeutic effect. The specific binding-induced activation allows the DNA circuit to distinguish diseased cells from healthy cells, reducing damage to nearby healthy cells. Moreover, the catalytic amplification reaction will only take place close to the target cancer cells, resulting in a high local concentration of singlet oxygen to selectively kill the target cells. The principle employed in this study demonstrated the feasibility of assembling a DNA circuit on cell membranes and could further broaden the utility of DNA circuits for applications in biology, biotechnology, and biomedicine. PMID:23397942

Cardiovascular photodynamic therapy: state of the art

NASA Astrophysics Data System (ADS)

Woodburn, Kathryn W.; Rockson, Stanley G.

2000-05-01

Photodynamic therapy (PDT) has been used traditionally for oncologic and ophthalmic indications. In addition, the enormous potential for the use of PDT agents in cardiovascular diseases is currently being translated into reality. Preclinical studies with various photosensitizers have demonstrated reduction in atheromatous plaque and prevention of intimal hyperplasia. With recent advances in light-based vascular devices and laser diode technology, the clinical use of cardiovascular photodynamic therapy is even more likely. Two photosensitizers, 5-aminolevulinic acid (ALA) and AntrinR (motexafin lutetium) Injection, are under clinical evaluation with many other agents in preclinical testing. Here, preclinical studies are reviewed and the clinical viability of cardiovascular photodynamic therapy is discussed.

Proton Particle Test Fluence: What's the Right Number?

NASA Technical Reports Server (NTRS)

LaBel, Kenneth A.; Ladbury, Raymond

2015-01-01

While we have been utilizing standard fluence levels such as those listed in the JESD57 document, we have begun revisiting what an appropriate test fluence is when it comes to qualifying a device for single events. Instead of a fixed fluence level or until a specific number of events occurs, a different thought process is required.

A method for radiological characterization based on fluence conversion coefficients

NASA Astrophysics Data System (ADS)

Froeschl, Robert

2018-06-01

Radiological characterization of components in accelerator environments is often required to ensure adequate radiation protection during maintenance, transport and handling as well as for the selection of the proper disposal pathway. The relevant quantities are typical the weighted sums of specific activities with radionuclide-specific weighting coefficients. Traditional methods based on Monte Carlo simulations are radionuclide creation-event based or the particle fluences in the regions of interest are scored and then off-line weighted with radionuclide production cross sections. The presented method bases the radiological characterization on a set of fluence conversion coefficients. For a given irradiation profile and cool-down time, radionuclide production cross-sections, material composition and radionuclide-specific weighting coefficients, a set of particle type and energy dependent fluence conversion coefficients is computed. These fluence conversion coefficients can then be used in a Monte Carlo transport code to perform on-line weighting to directly obtain the desired radiological characterization, either by using built-in multiplier features such as in the PHITS code or by writing a dedicated user routine such as for the FLUKA code. The presented method has been validated against the standard event-based methods directly available in Monte Carlo transport codes.

Photoluminescence and reflectivity of polymethylmethacrylate implanted by low-energy carbon ions at high fluences

NASA Astrophysics Data System (ADS)

Wang, Jun; Zhu, Fei; Zhang, Bei; Liu, Huixian; Jia, Guangyi; Liu, Changlong

2012-11-01

Polymethylmethacrylate (PMMA) specimens were implanted with 30 keV carbon ions in a fluence range of 1 × 1016 to 2 × 1017 cm-2, and photoluminescence (PL) and reflectivity of the implanted samples were examined. A luminescent band with one peak was found in PL spectra excited by 480 nm line, but its intensity did not vary in parallel with ion fluence. The strongest PL occurred at the fluence of 5 × 1016 cm-2. Results from visible-light-excited micro-Raman spectra indicated that the formation of hydrogenated amorphous carbon structures in subsurface layer and their evolutions with ion fluence could be responsible for the observed PL responses. Measurements of the small-angle reflectance spectra from both the implanted and rear surfaces of samples in the ultraviolet-visible (UV-vis) range demonstrated a kind of both fluence-dependent and wavelength-related reflectivity variations, which were attributed to the structural changes induced by ion implantation. A noticeable reflectivity modification, which may be practically used, could be found at the fluence of 1 × 1016 cm-2.

The effects of one-time inversion tillage on soil physical properties after long-term reduced tillage

NASA Astrophysics Data System (ADS)

Kuhwald, Michael; Augustin, Katja; Duttmann, Rainer

2017-04-01

The positive effects of reduced tillage on soil stability and on various soil functions such as infiltrability or saturated hydraulic conductivity are known in general. However, long-term employment of conservation tillage can increase weed pressure, damage by mice and soil compaction. Thus, the application of one-time inversion tillage (occasional or strategic tillage) is customarily used as a method for overcoming these drawbacks. Hitherto, the effects of one-time inversion tillage on soil physical properties have not been investigated. This study focuses on analysing whether the improved soil physical properties derived by long-term reduced tillage remain after one-time inversion tillage by mouldboard plough. The study was carried out in a 5.5 ha field in the southern part of Lower Saxony, Germany. Since 1996, this field has been subdivided into three plots, one managed conventionally by using a mouldboard plough (CT), while in the others a chisel plough (RT1) and a disk harrow (RT2) were employed. In October 2014, the entire field was ploughed by mouldboard plough to a depth of 30 cm. During the following year, four field studies were conducted to analyse the effects of this one-time inversion tillage on volumetric soil water content, bulk density, saturated hydraulic conductivity and infiltration rate. Additionally, penetration resistance measurements taken across the entire field were interpolated by kriging to analyse the spatial distribution of soil characteristics. The surveys of RT1 and RT2 were compared with CT and with analyses conducted before the one-time inversion tillage. This study shows that positive effects of long-term conservation tillage on several soil physical characteristics still remain after one-time mouldboard ploughing. Throughout the entire cropping season, the topsoil tilled under former conservation tillage practices revealed significantly higher (p < 0.05) values of saturated hydraulic conductivities and infiltration rates compared

A new proton fluence model for E greater than 10 MeV

NASA Technical Reports Server (NTRS)

Feynman, Joan; Armstrong, T. P.; Dao-Gibner, L.; Silverman, S.

1988-01-01

Researchers describe a new engineering model for the fluence of protons with energies greater than 10 MeV. The data set used is a combination of observations made primarily from the Earth's surface between 1956 and 1963 and observations made from spacecraft in the vicinity of Earth between 1963 and 1985. With this data set we find that the distinction between ordinary proton events and anomalously large proton events made in earlier work disappears. The greater than 10 MeV fluences at 1 AU calculated with the new model are about twice those expected on the basis of models now in use. In contrast to earlier models, results do not depend critically on the fluence from any one event.

Comparison of anatomy-based, fluence-based and aperture-based treatment planning approaches for VMAT

NASA Astrophysics Data System (ADS)

Rao, Min; Cao, Daliang; Chen, Fan; Ye, Jinsong; Mehta, Vivek; Wong, Tony; Shepard, David

2010-11-01

Volumetric modulated arc therapy (VMAT) has the potential to reduce treatment times while producing comparable or improved dose distributions relative to fixed-field intensity-modulated radiation therapy. In order to take full advantage of the VMAT delivery technique, one must select a robust inverse planning tool. The purpose of this study was to evaluate the effectiveness and efficiency of VMAT planning techniques of three categories: anatomy-based, fluence-based and aperture-based inverse planning. We have compared these techniques in terms of the plan quality, planning efficiency and delivery efficiency. Fourteen patients were selected for this study including six head-and-neck (HN) cases, and two cases each of prostate, pancreas, lung and partial brain. For each case, three VMAT plans were created. The first VMAT plan was generated based on the anatomical geometry. In the Elekta ERGO++ treatment planning system (TPS), segments were generated based on the beam's eye view (BEV) of the target and the organs at risk. The segment shapes were then exported to Pinnacle3 TPS followed by segment weight optimization and final dose calculation. The second VMAT plan was generated by converting optimized fluence maps (calculated by the Pinnacle3 TPS) into deliverable arcs using an in-house arc sequencer. The third VMAT plan was generated using the Pinnacle3 SmartArc IMRT module which is an aperture-based optimization method. All VMAT plans were delivered using an Elekta Synergy linear accelerator and the plan comparisons were made in terms of plan quality and delivery efficiency. The results show that for cases of little or modest complexity such as prostate, pancreas, lung and brain, the anatomy-based approach provides similar target coverage and critical structure sparing, but less conformal dose distributions as compared to the other two approaches. For more complex HN cases, the anatomy-based approach is not able to provide clinically acceptable VMAT plans while highly

Methylene blue internalization and photodynamic action against clinical and ATCC Pseudomonas aeruginosa and Staphyloccocus aureus strains.

PubMed

Pereira, André Henrique Correia; Pinto, Juliana Guerra; Freitas, Mirian Aparecida Alves; Fontana, Letícia Corrêa; Pacheco Soares, Cristina; Ferreira-Strixino, Juliana

2018-06-01

Bacterial infections have been a major challenge to health. Increasing resistance to antimicrobial agents, according to World Health Organization, could be the major cause of death until 2050. Photodynamic therapy emerges as an alternative in microbial inactivation, due to its selectivity and to decreasing or dismissing antibiotic use. This study aimed at evaluating, in vitro, the internalization of the Methylene Blue and its photodynamic activity against a clinical and ATCC strain of Pseudomonas aeruginosa and Staphyloccocus aureus. Thus, the strains were incubated with MB in concentrations of 100, 300 e 500 μg/ml and then irradiated with a LED (±660 nm) at fluence of 10 and 25 J/cm 2 . The MB internalization was evaluated using a confocal microscope (Zeiss LSM 700), to capture the MB and the DAPI (for DNA staining). It was possible to observe that the MB was internalized by the bacterial cells, in all concentrations tested. The CFU/ml count demonstrated significant reduction (p ≤ 0,01) at the average 5.0 logs comparing with control group for the two species in all the tested concentrations. In conclusion, the strains tested were capable of internalizing the MB. PDT with MB was able to decrease the growth of the tested strains in vitro, being a promising alternative to the future treatment of infections caused by these species. Copyright © 2018 Elsevier B.V. All rights reserved.

Inactivation of Vibrio parahaemolyticus by antimicrobial photodynamic technology using methylene blue.

PubMed

Deng, Xi; Tang, Shuze; Wu, Qian; Tian, Juan; Riley, William W; Chen, Zhenqiang

2016-03-30

Vibrio parahaemolyticus is the leading causative pathogen of gastroenteritis often related to contaminated seafood. Photodynamic inactivation has been recently proposed as a strategy for killing cells and viruses. The objective of this study was to verify the bactericidal effects caused by photodynamic inactivation using methylene blue (MB) over V. parahaemolyticus via flow cytometry, agarose gel electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Vibrio parahaemolyticus counts were determined using the most probable number method. A scanning electron microscope and a transmission electron microscope were employed to intuitively analyze internal and external cell structure. Combination of MB and laser treatment significantly inhibited the growth of V. parahaemolyticus. The inactivation rate of V. parahaemolyticus was >99.99% and its counts were reduced by 5 log10 in the presence of 0.05 mg mL(-1) MB when illuminated with visible light (power density 200 mW cm(-2)) for 25 min. All inactivated cells showed morphological changes, leakage of cytoplasm and degradation of protein and DNA. Results from this study indicated that photodynamic technology using MB produced significant inactivation of V. parahaemolyticus mainly brought about by the degradation of protein and DNA. © 2015 Society of Chemical Industry.

Treatment of complicated gangrene using infrared photodynamic therapy

NASA Astrophysics Data System (ADS)

Szabo, Robert

2018-04-01

Antimicrobial photodynamic therapy (aPDT) is one of the treatment options of local infections. Conventional aPDT systems have physical limitations such as low light penetration and the need for long irradiation time to achieve the necessary light dose. With new forming specific complex of methylene blue dye molecules it is possible to reach efficient excitation processes at 810nm. At 810nm, there is increased light penetration depth in comparison to 670nm. This means that we are now able to excite the sensitizer in deeper areas and activate it transgingivally. Purpose Preserving teeth with complicated gangrene is a great challenge if root canal is obstructed. Lacking the possibility to perform the conventional mechanical cleaning of root canals. we have used infrared photodynamic therapy for elimination radicular bacterial infiltration Materials and methods We investigated 14 cases with complicated gangrene and totally or partially obstructed root canal. We deposited the sensitizer - Photolase Photolase GMBH Germany - in the pulp chamber and closed it for a week. This procedure was repeated three times. After the sensitizer penetrated we applied the light. We used G-Box 810 nm laser - Gigaa Laser China - at 0,8W/cm2 , 40s buccal and 40s oral side. Results 6 month later we performed follow-up CBCT. Out of 14 cases significant healing was detected in 10. In 4 cases no change was observable. Discussion and conclusion Infrared aPDT seems effective in eliminating bacterial infiltrations in deeper areas. It can be a minimal invasive method in the case of obstructed root canals.

Imaging a photodynamic therapy photosensitizer in vivo with a time-gated fluorescence tomography system

NASA Astrophysics Data System (ADS)

Mo, Weirong; Rohrbach, Daniel; Sunar, Ulas

2012-07-01

We report the tomographic imaging of a photodynamic therapy (PDT) photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in vivo with time-domain fluorescence diffuse optical tomography (TD-FDOT). Simultaneous reconstruction of fluorescence yield and lifetime of HPPH was performed before and after PDT. The methodology was validated in phantom experiments, and depth-resolved in vivo imaging was achieved through simultaneous three-dimensional (3-D) mappings of fluorescence yield and lifetime contrasts. The tomographic images of a human head-and-neck xenograft in a mouse confirmed the preferential uptake and retention of HPPH by the tumor 24-h post-injection. HPPH-mediated PDT induced significant changes in fluorescence yield and lifetime. This pilot study demonstrates that TD-FDOT may be a good imaging modality for assessing photosensitizer distributions in deep tissue during PDT monitoring.

Fluence-field modulated x-ray CT using multiple aperture devices

NASA Astrophysics Data System (ADS)

Stayman, J. Webster; Mathews, Aswin; Zbijewski, Wojciech; Gang, Grace; Siewerdsen, Jeffrey; Kawamoto, Satomi; Blevis, Ira; Levinson, Reuven

2016-03-01

We introduce a novel strategy for fluence field modulation (FFM) in x-ray CT using multiple aperture devices (MADs). MAD filters permit FFM by blocking or transmitting the x-ray beam on a fine (0.1-1 mm) scale. The filters have a number of potential advantages over other beam modulation strategies including the potential for a highly compact design, modest actuation speed and acceleration requirements, and spectrally neutral filtration due to their essentially binary action. In this work, we present the underlying MAD filtration concept including a design process to achieve a specific class of FFM patterns. A set of MAD filters is fabricated using a tungsten laser sintering process and integrated into an x-ray CT test bench. A characterization of the MAD filters is conducted and compared to traditional attenuating bowtie filters and the ability to flatten the fluence profile for a 32 cm acrylic phantom is demonstrated. MAD-filtered tomographic data was acquired on the CT test bench and reconstructed without artifacts associated with the MAD filter. These initial studies suggest that MAD-based FFM is appropriate for integration in clinical CT system to create patient-specific fluence field profile and reduce radiation exposures.

Increase of bulk optical damage threshold fluences of KDP crystals by laser irradiation and heat treatment

DOEpatents

Swain, J.E.; Stokowski, S.E.; Milam, D.; Kennedy, G.C.; Rainer, F.

1982-07-07

The bulk optical damage threshold fluence of potassium dihydrogen phosphate (KDP) crystals is increased by irradiating the crystals with laser pulses of duration 1 to 20 nanoseconds of increasing fluence, below the optical damage threshold fluence for untreated crystals, or by baking the crystals for times of the order of 24 hours at temperatures of 110 to 165/sup 0/C, or by a combination of laser irradiation and baking.

Photodynamic therapy of HeLa cell cultures by using LED or laser sources.

PubMed

Etcheverry, María E; Pasquale, Miguel A; Garavaglia, Mario

2016-07-01

The photodynamic therapy (PDT) on HeLa cell cultures was performed utilizing a 637nm LED lamp with 1.06W power and m-tetrahydroxyphenyl chlorin (m-THPC) as photosensitizer and compared to a laser source emitting at 654nm with the same power. Intracellular placement of the photosensitizer and the effect of its concentration (CP), its absorption time (TA) and the illumination time (TI) were evaluated. It was observed that for CP>40μg/ml and TA>24h, m-THPC had toxicity on cells in culture, even in the absence of illumination. For the other tested concentrations, the cells remained viable if not subjected to illumination doses. No effect on cells was observed for CP<0.05μg/ml, TA=48h and TI=10min and they continued proliferating. For drug concentrations higher than 0.05μgml(-1), further deterioration is observed with increasing TA and TI. We evaluated the viability of the cells, before and after the treatment, and by supravital dyes, and phase contrast and fluorescence microscopies, evidence of different types of cell death was obtained. Tetrazolium dye assays after PDT during different times yielded similar results for the 637nm LED lamp with an illuminance three times greater than that of the 654nm laser source. Results demonstrate the feasibility of using a LED lamp as alternative to laser source. Here the main characteristic is not the light coherence but achieving a certain light fluence of the appropriate wavelength on cell cultures. We conclude that the efficacy was achieved satisfactorily and is essential for convenience, accessibility and safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Real time optical coherence tomography monitoring of Candida albicans biofilm in vitro during photodynamic treatment

NASA Astrophysics Data System (ADS)

Suzuki, Luis Cláudio; Araujo Prates, Renato; Raele, Marcus Paulo; Zanardi di Freitas, Anderson; Simões Ribeiro, Martha

2010-04-01

The biofilm formed by Candida albicans is the mainly cause of infections associated to medical devices such as catheters. Studies have shown that photodynamic antimicrobial therapy (PAT) has lethal effect on C. albicans, and it is based on photosensitizer (PS) in the presence of low intensity light to generate reactive oxygen species in biological systems. The aim of this study was to analyze in real time, by Optical Coherence Tomography (OCT), the alterations in C. albicans biofilm in vitro during PAT using methylene blue (MB) as a PS and red light. An OCT system with working at 930nm was used, sequential images of 2000×512 pixels were generated at the frame rate of 2.5frames/sec. The dimension of the analyzed sample was 6000μm wide by 1170μm of depth corrected by refraction index of 1.35. We recorded 1min. before and after the irradiation with LED for PAT, generating 8min. of video. For biofilm formation, discs were made from elastomeric silicone catheters. The PS was dissolved in PBS solution, and a final concentration of 1mM MB was applied on biofilm, followed by a red LED irradiation (λ=630nm+/-20nm) during 6min. We performed a curve of survival fraction versus time of irradiation and it was reduced by 100% following 6min. of irradiation. OCT was performed for measurement of biofilm thickness of 110μm when biofilm was formed. During irradiation, the variation of biofilm thickness was ~70μm. We conclude that OCT system is able to show real time optical changes provided by PAT in yeasts organized in biofilm.

Solar heavy ion Heinrich fluence spectrum at low earth orbit.

PubMed

Croley, D R; Spitale, G C

1998-01-01

Solar heavy ions from the JPL Solar Heavy Ion Model have been transported into low earth orbit using the Schulz cutoff criterion for L-shell access by ions of a specific charge to mass ratio. The NASA Brouwer orbit generator was used to get L values along the orbit at 60 second time intervals. Heavy ion fluences of ions 2 < or = Z < or = 92 have been determined for the LET range 1 to 130 MeV-cm2/mg by 60, 120 or 250 mils of aluminum over a period of 24 hours in a 425 km circular orbit inclined 51 degrees. The ion fluence is time dependent in the sense that the position of the spacecraft in the orbit at the flare onset time fixes the relationship between particle flux and spacecraft passage through high L-values where particles have access to the spacecraft.

Nitric oxide-mediated activity in anti-cancer photodynamic therapy.

PubMed

Rapozzi, Valentina; Della Pietra, Emilia; Zorzet, Sonia; Zacchigna, Marina; Bonavida, Benjamin; Xodo, Luigi Emilio

2013-04-01

Cell recurrence in cancer photodynamic therapy (PDT) is an important issue that is poorly understood. It is becoming clear that nitric oxide (NO) is a modulator of PDT. By acting on the NF-κB/Snail/RKIP survival/anti-apoptotic loop, NO can either stimulate or inhibit apoptosis. We found that pheophorbide a/PDT (Pba/PDT) induces the release of NO in B78-H1 murine amelanotic melanoma cells in a concentration-dependent manner. Low-dose PDT induces low NO levels by stimulating the anti-apoptotic nature of the above loop, whereas high-dose PDT stimulates high NO levels inhibiting the loop and activating apoptosis. When B78-H1 cells are treated with low-dose Pba/PDT and DETA/NO, an NO-donor, intracellular NO increases and cell growth is inhibited according to scratch-wound and clonogenic assays. Western blot analyses showed that the combined treatment reduces the expression of the anti-apoptotic NF-κB and Snail gene products and increases the expression of the pro-apoptotic RKIP gene product. The combined effect of Pba and DETA/NO was also tested in C57BL/6 mice bearing a syngeneic B78-H1 melanoma. We used pegylated Pba (mPEG-Pba) due to its better pharmacokinetics compared to free Pba. mPEG-Pba (30 mg/Kg) and DETA/NO (0.4 mg/Kg) were i.p. injected either as a single molecule or in combination. After photoactivation at 660 nM (fluence of 193 J/cm(2)), the combined treatment delays tumor growth more efficiently than each individual treatment (p<0.05). Taken together, our results showed that the efficacy of PDT is strengthened when the photosensitizer is used in combination with an NO donor. Copyright © 2013 Elsevier Inc. All rights reserved.

The effect of standard and high-fluence corneal cross-linking (CXL) on cornea and limbus.

PubMed

Richoz, Olivier; Tabibian, David; Hammer, Arthur; Majo, François; Nicolas, Michael; Hafezi, Farhad

2014-07-22

When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross-linking with UV-A and riboflavin (CXL) must be applied eccentrically to the periphery of the lower cornea, partly irradiating the corneal limbus. Here, we investigated the effect of standard and double-standard fluence corneal cross-linking with riboflavin and UV-A (CXL) on cornea and corneal limbus in the rabbit eye in vivo. Epithelium-off CXL was performed in male New Zealand White rabbits with two irradiation diameters (7 mm central cornea, 13 mm cornea and limbus), using standard fluence (5.4 J/cm(2)) and double-standard fluence (10.8 J/cm(2)) settings. Controls were subjected to epithelial removal and riboflavin instillation, but were not irradiated with UV-A. Following CXL, animals were examined daily until complete closure of the epithelium, and at 7, 14, 21, and 28 days. Animals were killed and a corneoscleral button was excised and processed for light microscopy and immunohistochemistry. For both irradiation diameters and fluences tested, no signs of endothelial damage or limbal vessel thrombosis were observed, and time to re-epithelialization was similar to untreated controls. Histological and immunohistochemical analysis revealed no differences in the p63 putative stem cell marker expression pattern. Even when using fluence twice as high as the one used in current clinical CXL settings, circumferential UV-A irradiation of the corneal limbus does not alter the regenerative capacity of the limbal epithelial cells, and the expression pattern of the putative stem cell marker p63 remains unchanged. This suggests that eccentric CXL may be performed safely in PMD. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Near-infrared photodynamic inactivation of S. pneumoniae and its interaction with RAW 264.7 macrophages.

PubMed

Leite, Ilaiáli S; Geralde, Mariana C; Salina, Ana C G; Medeiros, Alexandra I; Dovigo, Lívia N; Bagnato, Vanderlei S; Inada, Natalia M

2018-01-01

Pneumonia is the main cause of children mortality worldwide, and its major treatment obstacle stems from the microorganisms increasing development of resistance to several antibiotics. Photodynamic therapy has been presenting, for the last decades, promising results for some subtypes of cancer and infections. In this work we aimed to develop a safe and efficient in vitro protocol for photodynamic inactivation of Streptococcus pneumoniae, one of the most commonly found bacteria in pneumonia cases, using two near-infrared light sources and indocyanine green, a FDA approved dye. Photodynamic inactivation experiments with bacteria alone allowed to determine the best parameters for microbial inactivation. Cytotoxicity assays with RAW 264.7 macrophages evaluated the safety of the PDI. To determine if the photodynamic inactivation had a positive or negative effect on the natural killing action of macrophages, we selected and tested fewer indocyanine green concentrations and 10 J/cm 2 on macrophage-S. pneumoniae co-cultures. We concluded that ICG has potential as a photosensitizer for near-infrared photodynamic inactivation of S. pneumoniae, producing minimum negative impact on RAW 264.7 macrophages and having a positive interaction with the immune cell's microbicidal action. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photodynamic inactivation of Escherichia coli - Correlation of singlet oxygen kinetics and phototoxicity.

PubMed

Müller, Alexander; Preuß, Annegret; Röder, Beate

2018-01-01

Photodynamic inactivation (PDI) of bacteria may play a major role in facing the challenge of the ever expanding antibiotic resistances. Here we report about the direct correlation of singlet oxygen luminescence kinetics and phototoxicity in E. coli cell suspension under PDI using the widely applied cationic photosensitizer TMPyP. Through direct access to the microenvironment, the time resolved investigation of singlet oxygen luminescence plays a key role in understanding the photosensitization mechanism and inactivation pathway. Using the homemade set-up for highly sensitive time resolved singlet oxygen luminescence detection, we show that the cationic TMPyP is localized predominantly outside the bacterial cells but in their immediate vicinity prior to photodynamic inactivation. Throughout following light exposure, a clear change in singlet oxygen kinetics indicates a redistribution of photosensitizer molecules to at least one additional microenvironment. We found the signal kinetics mirrored in cell viability measurements of equally treated samples from same overnight cultures conducted in parallel: A significant drop in cell viability of the illuminated samples and stationary viability of dark controls. Thus, for the system investigated in this work - a Gram-negative model bacteria and a well-known PS for its PDI - singlet oxygen kinetics correlates with phototoxicity. This finding suggests that it is well possible to evaluate PDI efficiency directly via time resolved singlet oxygen detection. Copyright © 2017 Elsevier B.V. All rights reserved.

Current Concepts in Gastrointestinal Photodynamic Therapy

PubMed Central

Webber, John; Herman, Mark; Kessel, David; Fromm, David

1999-01-01

Objective To review current concepts of photodynamic therapy (PDT) applied to the treatment of tumors of the gastrointestinal tract. Summary Background Data PDT initially involves the uptake or production of a photosensitive compound by tumor cells. Subsequent activation of the photoreactive compound by a specific wavelength of light results in cell death, either directly or as a result of vascular compromise and/or apoptosis. Methods The authors selectively review current concepts relating to photosensitization, photoactivation, time of PDT application, tissue selectivity, sites of photodynamic action, PDT effects on normal tissue, limitations of PDT, toxicity of photosensitizers, application of principles of PDT to tumor detection, and current applications of PDT to tumors of the gastrointestinal tract. Results PDT is clearly effective for small cancers, but it is not yet clear in which cases such treatment is more effective than other currently acceptable approaches. The major side effect of PDT is cutaneous photosensitization. The major limitation of PDT is depth of tumor kill. As data from current and future clinical trials become available, a clearer perspective of where PDT fits in the treatment of cancers will be gained. Many issues regarding pharmacokinetic data of photosensitizers, newer technology involved in light sources, optimal treatment regimens that take advantage of the pharmacophysiology of photoablation, and light dosimetry still require solution. One can foresee application of differing sensitizers and light sources depending on the specific clinical situation. As technologic advances occur, interstitial PDT may have significant application. Conclusions PDT has a potentially important role either as a primary or adjuvant mode of treatment of tumors of the gastrointestinal tract. PMID:10400031

Fluorescence detection and photodynamic activity of endogenous protoporphyrin in human skin

NASA Astrophysics Data System (ADS)

Koenig, Karsten; Rueck, Angelika C.; Schneckenburger, Herbert

1992-07-01

Human skin shows a strong autofluorescence in the red spectral region with main peaks around 600, 620, and 640 nm caused by the porphyrin production of the gram positive lipophile skin bacterium Propionibacterium acnes. Irradiation of these bacteria reduces the integral fluorescence intensity and induces the formation of photoproducts with fluorescence bands around 670 nm and decay times of about 1 and 5 ns. The photoproduct formation is connected with an increased absorption in the red spectral region. The endogenous fluorescent porphyrins act as photosensitizers. Photodestruction of Propionibacteria acnes by visible light appears therefore to be a promising therapy. The photodynamic activity of the photoproducts was lower than that of protoporphyrin IX.

Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum*

PubMed Central

Ramos, Rogério Rodrigo; Kozusny-Andreani, Dora Inês; Fernandes, Adjaci Uchôa; Baptista, Mauricio da Silva

2016-01-01

BACKGROUND Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring. PMID:27192510

Comparative survival study of glial cells and cells composing walls of blood vessels in crustacean ventral nerve cord after photodynamic treatment

NASA Astrophysics Data System (ADS)

Kolosov, Mikhail S.; Shubina, Elena

2015-03-01

Photodynamic therapy is a prospective treatment modality of brain cancers. It is of importance to have information about relative survival rate of different cell types in nerve tissue during photodynamic treatment. Particularly, for development of sparing strategy of the photodynamic therapy of brain tumors, which pursuits both total elimination of malignant cells, which are usually of glial origin, and, at the same time, preservation of normal blood circulation as well as normal glial cells in the brain. The aim of this work was to carry out comparative survival study of glial cells and cells composing walls of blood vessels after photodynamic treatment, using simple model object - ventral nerve cord of crustacean.

Global Mental Health in Action: Reducing Disparities One Community at a Time.

PubMed

Bischoff, Richard J; Springer, Paul R; Taylor, Nathan

2017-04-01

There are great disparities in mental health care around the world. Traditional approaches to mental health care have not been found to be transferrable to many parts of the world and are inadequate to address these disparities. Unconventional approaches are needed that match the traditions of care-seeking and care-giving within the communities where they are delivered. The authors review the global mental health literature and discuss how marriage and family therapists are in a particularly good position to have worldwide impact on mental health disparities. Five principles of global mental health are presented along with an example of how these principles are applied through the Reducing Mental Health Disparities One Community at a Time (RD1CT) model. © 2016 American Association for Marriage and Family Therapy.

Practical new method of measuring thermal-neutron fluence

NASA Technical Reports Server (NTRS)

Siebold, J. R.; Warman, E. A.

1967-01-01

Thermoluminescence dosimeter technique measures thermal-neutron fluence by encapsulating lithium flouride phosphor powder and exposing it to a neutron environment. The capsule is heated in a dosimeter reader, which results in light emission proportional to the neutron fluence.

Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

PubMed Central

Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

2012-01-01

Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

Physics of the Isotopic Dependence of Galactic Cosmic Ray Fluence Behind Shielding

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Saganti, Premkumar B.; Hu, Xiao-Dong; Kim, Myung-Hee Y.; Cleghorn, Timothy F.; Wilson, John W.; Tripathi, Ram K.; Zeitlin, Cary J.

2003-01-01

For over 25 years, NASA has supported the development of space radiation transport models for shielding applications. The NASA space radiation transport model now predicts dose and dose equivalent in Earth and Mars orbit to an accuracy of plus or minus 20%. However, because larger errors may occur in particle fluence predictions, there is interest in further assessments and improvements in NASA's space radiation transport model. In this paper, we consider the effects of the isotopic composition of the primary galactic cosmic rays (GCR) and the isotopic dependence of nuclear fragmentation cross-sections on the solution to transport models used for shielding studies. Satellite measurements are used to describe the isotopic composition of the GCR. Using NASA's quantum multiple-scattering theory of nuclear fragmentation (QMSFRG) and high-charge and energy (HZETRN) transport code, we study the effect of the isotopic dependence of the primary GCR composition and secondary nuclei on shielding calculations. The QMSFRG is shown to accurately describe the iso-spin dependence of nuclear fragmentation. The principal finding of this study is that large errors (plus or minus 100%) will occur in the mass-fluence spectra when comparing transport models that use a complete isotope grid (approximately 170 ions) to ones that use a reduced isotope grid, for example the 59 ion-grid used in the HZETRN code in the past, however less significant errors (less than 20%) occur in the elemental-fluence spectra. Because a complete isotope grid is readily handled on small computer workstations and is needed for several applications studying GCR propagation and scattering, it is recommended that they be used for future GCR studies.

Chlorophyll mediated photodynamic inactivation of blue laser on Streptococcus mutans

NASA Astrophysics Data System (ADS)

Astuti, Suryani Dyah; Zaidan, A.; Setiawati, Ernie Maduratna; Suhariningsih

2016-03-01

Photodynamic inactivation is an inactivation method in microbial pathogens that utilize light and photosensitizer. This study was conducted to investigate photodynamic inactivation effects of low intensity laser exposure with various dose energy on Streptococcus mutans bacteria. The photodynamic inactivation was achieved with the addition of chlorophyll as photosensitizers. To determine the survival percentage of Streptococcus mutans bacteria after laser exposure, the total plate count method was used. For this study, the wavelength of the laser is 405 nm and variables of energy doses are 1.44, 2.87, 4.31, 5.74, 7.18, and 8.61 in J/cm2. The results show that exposure to laser with energy dose of 7.18 J/cm2 has the best photodynamic inactivation with a decrease of 78% in Streptococcus

Linear feasibility algorithms for treatment planning in interstitial photodynamic therapy

NASA Astrophysics Data System (ADS)

Rendon, A.; Beck, J. C.; Lilge, Lothar

2008-02-01

Interstitial Photodynamic therapy (IPDT) has been under intense investigation in recent years, with multiple clinical trials underway. This effort has demanded the development of optimization strategies that determine the best locations and output powers for light sources (cylindrical or point diffusers) to achieve an optimal light delivery. Furthermore, we have recently introduced cylindrical diffusers with customizable emission profiles, placing additional requirements on the optimization algorithms, particularly in terms of the stability of the inverse problem. Here, we present a general class of linear feasibility algorithms and their properties. Moreover, we compare two particular instances of these algorithms, which are been used in the context of IPDT: the Cimmino algorithm and a weighted gradient descent (WGD) algorithm. The algorithms were compared in terms of their convergence properties, the cost function they minimize in the infeasible case, their ability to regularize the inverse problem, and the resulting optimal light dose distributions. Our results show that the WGD algorithm overall performs slightly better than the Cimmino algorithm and that it converges to a minimizer of a clinically relevant cost function in the infeasible case. Interestingly however, treatment plans resulting from either algorithms were very similar in terms of the resulting fluence maps and dose volume histograms, once the diffuser powers adjusted to achieve equal prostate coverage.

Photodynamic treatment of a secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher syndrome type I.

PubMed

Osman, Saatci A; Aylin, Yaman; Arikan, Gul; Celikel, Harika

2007-03-01

Vasoproliferative tumours may be primary or secondary and present with severe exudation leading to marked visual loss. We describe a 47-year-old man with unilateral secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher I syndrome who was successfully treated with a single session of photodynamic treatment. Standard treatment protocol was used except that the treatment duration was doubled. A year after the treatment, the angioma-like tumour vanished and exudation was dramatically reduced. Photodynamic therapy seems to be a minimally invasive and safe technique in eyes with secondary vasoproliferative tumours.

Antimicrobial photodynamic therapy for infectious stomatitis in snakes: Clinical views and microbiological findings.

PubMed

Grego, Kathleen Fernandes; Carvalho, Marcelo Pires Nogueira de; Cunha, Marcos Paulo Vieira; Knöbl, Terezinha; Pogliani, Fabio Celidonio; Catão-Dias, José Luiz; Sant'Anna, Sávio Stefanini; Ribeiro, Martha Simões; Sellera, Fábio Parra

2017-12-01

Antimicrobial photodynamic therapy (APDT) has been broadly investigated as an alternative to treat localized infections, without leading to the selection of resistant microorganisms. Infectious stomatitis is a multifactorial disease frequently reported in captive snakes characterized by infection of the oral mucosa and surrounding tissues. In this study, we investigated methylene blue (MB)-mediated APDT to treat infectious stomatitis in snakes and verified the resistance phenotype and genotype before and after APDT. Three Boid snakes presented petechiae, edema and caseous material in their oral cavities. MB (0.01%) was applied on the lesions and after 5min they were irradiated using a red laser (λ=660nm), fluence of 280J/cm 2 , 8J and 80s per point, 100mW, spot size 0.028cm 2 and fluence rate of 3.5W/cm 2 . APDT was repeated once a week during 3 months. Samples of the lesions were collected to identify bacteria and antibiotic resistance profiles. To analyze the clonality of bacterial isolates before and after APDT, isolates were subjected to ERIC PCR analysis. Snakes presented clinical improvement such as reduction of inflammatory signs and caseous material. Pseudomonas aeruginosa and Escherichia coli were present in all snakes; Klebsiella pneumoniae and Morganella morganii were also identified in some animals. We also observed that the oral microbiota was completely replaced following APDT. However, K. pneumoniae isolates before and after APDT were a single clone with 100% of genetic similarity that lost resistance phenotype for seven antibiotics of four classes. These results show that APDT can be used to treat infectious stomatitis in snakes. Copyright © 2017 Elsevier B.V. All rights reserved.

Photodynamic therapy can kill Cryptococcus neoformans in in vitro and in vivo models

NASA Astrophysics Data System (ADS)

Prates, Renato A.; da Silva, Eriques G.; Chaves, Priscila F.; Santos, Antônio José S.; Paula, Claudete R.; Ribeiro, Martha S.

2009-02-01

Cryptococcosis is an infection caused by the encapsulated yeast Cryptococcus neoformans and the most afflicted sites are lung, skin and central nervous system. A range of studies had reported that photodynamic therapy (PDT) can inactivate yeast cells; however, the in vivo experimental models of cryptococcosis photoinactivation are not commonly reported. The aim of this study was to investigate the ability of methylene blue (MB) combined with a low-power red laser to inactivate Cryptococcus neoformans in in vitro and in vivo experimental models. To perform the in vitro study, suspension of Cryptococcus neoformans ATCC-90112 (106cfu/mL) was used. The light source was a laser (Photon Lase III, DMC, SÃ#o Carlos, Brazil) emitting at λ660nm with output power of 90mW for 6 and 9min of irradiation, resulting fluences at 108 and 162J/cm². As photosensitizer, 100μM MB was used. For the in vivo study, 10 BALB/c mice had the left paw inoculated with C. neoformans ATCC-90112 (107cfu). Twenty-four hours after inoculation, PDT was performed using 150μM MB and 100mW red laser with fluence at 180J/cm2. PDT was efficient in vitro against C. neoformans in both parameters used: 3 log reduction with 108J/cm² and 6 log reduction with 162J/cm². In the in vivo experiment, PDT was also effective; however, its effect was less expressive than in the in vitro study (about 1 log reduction). In conclusion, PDT seems to be a helpful alternative to treat dermal cryptococcosis; however, more effective parameters must be found in in vivo studies.

Porphyrin-laser photodynamic induction of focal brain necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stroop, W.G.; Battles, E.J.; Townsend, J.J.

A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and bymore » edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.« less

Fluence-dependent singlet exciton dynamics in length-sorted chirality-enriched single-walled carbon nanotubes.

PubMed

Park, Jaehong; Deria, Pravas; Olivier, Jean-Hubert; Therien, Michael J

2014-02-12

We utilize individualized, length-sorted (6,5)-chirality enriched single-walled carbon nanotubes (SWNTs) having dimensions of 200 and 800 nm, femtosecond transient absorption spectroscopy, and variable excitation fluences that modulate the exciton density per nanotube unit length, to interrogate nanotube exciton/biexciton dynamics. For pump fluences below 30 μJ/cm(2), transient absorption (TA) spectra of (6,5) SWNTs reveal the instantaneous emergence of the exciton to biexciton transition (E11 → E11,BX) at 1100 nm; in contrast, under excitation fluences exceeding 100 μJ/cm(2), this TA signal manifests a rise time (τ rise ∼ 250 fs), indicating that E11 state repopulation is required to produce this signal. Femtosecond transient absorption spectroscopic data acquired over the 900-1400 nm spectral region of the near-infrared (NIR) region for (6,5) SWNTs, as a function of nanotube length and exciton density, reveal that over time delays that exceed 200 fs exciton-exciton interactions do not occur over spatial domains larger than 200 nm. Furthermore, the excitation fluence dependence of the E11 → E11,BX transient absorption signal demonstrates that relaxation of the E11 biexciton state (E11,BX) gives rise to a substantial E11 state population, as increasing delay times result in a concomitant increase of E11 → E11,BX transition oscillator strength. Numerical simulations based on a three-state model are consistent with a mechanism whereby biexcitons are generated at high excitation fluences via sequential SWNT ground- and E11-state excitation that occurs within the 980 nm excitation pulse duration. These studies that investigate fluence-dependent TA spectral evolution show that SWNT ground → E11 and E11 → E11,BX excitations are coresonant and provide evidence that E11,BX → E11 relaxation constitutes a significant decay channel for the SWNT biexciton state over delay times that exceed 200 fs, a finding that runs counter to assumptions made in previous

Internalization of the PDZ and its photodynamic effect on the growth of ATCC and clinical strains of E. coli and S. aureus

NASA Astrophysics Data System (ADS)

Rodrigues da Silva, Gislene; Henrique Correia Pereira, André; Guerra Pinto, Juliana; José Raniero, Leandro; Ferreira-Strixino, Juliana

2016-09-01

The treatment of bacterial infections has been a challenge after the end of the ‘era of antibiotics’. Bacteria are capable of causing many infectious diseases; therefore, with the increasing number of bacteria becoming resistant, development of alternative therapies is needed to minimize, or even eliminate the use of antibiotics. Photodynamic therapy (PDT) is a promising alternative to fight microorganism. In view of the increasing emergence of resistant bacteria and the limitations of conventional treatment, this study evaluated the effect of photodynamic therapy with photodithazine (PDZ) in inactivating bacterial strains of E. coli and S. aureus in vitro, comparing the behavior of clinical and ATCC strains. Confocal microscopy analysis was performed to determine the internalization of the PS and spectrophotometric technique was used to determine the growth of bacteria in vitro. PDT using PDZ was able to reduce the growth of S. aureus strains using the incubation time of 24 h, whereas no satisfactory results were obtained with 15 min incubation. The E. coli strains, tested at two incubation times, did not affectively reduce bacterial growth. Therefore, it is concluded that PDT using PDZ is viable when applied to the S. aureus strains, when suitable incubation times are used.

Determination of atomic oxygen fluence using spectrophotometric analysis of infrared transparent witness coupons for long duration exposure tests

NASA Technical Reports Server (NTRS)

Podojil, Gregg M.; Jaworske, Donald A.

1993-01-01

Atomic oxygen degradation is one of several major threats to the durability of spaceborne systems in low Earth orbit. Ground-based simulations are conducted to learn how to minimize the adverse effects of atomic oxygen exposure. Assessing the fluence of atomic oxygen in test chambers such as a plasma asher over long periods of time is necessary for accurate determination of atomic oxygen exposure. Currently, an atomic oxygen susceptible organic material such as Kapton is placed next to samples as a witness coupon and its mass loss is monitored and used to determine the effective atomic oxygen fluence. However, degradation of the Kapton witness coupons occurs so rapidly in plasma ashers that for any long term test many witness coupons must be used sequentially in order to keep track of the fluence. This necessitates opening vacuum to substitute fresh coupons. A passive dosimetry technique was sought to monitor atomic oxygen exposure over longer periods without the need to open the plasma asher to the atmosphere. This paper investigates the use of spectrophotometric analysis of durable IR transparent witness coupons to measure atomic oxygen exposure for longer duration testing. The method considered would be conductive to making in situ measurements of atomic oxygen fluence.

Effects of high thermal and high fast fluences on the mechanical properties of type 6061 aluminum in the HFBR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weeks, J.R.; Czajkowski, C.J.; Tichler, P.R.

The High Flux Beam Reactor (HFBR) at Brookhaven National Laboratory (BNL) is an epithermal, externally moderated (by D/sub 2/O) facility designed to produce neutron beams for research. Type 6061 T-6 aluminum was used for the beam tubes, pressure vessel, fuel cladding, and most other components in the high flux area. The HFBR has operated since 1965. The epithermal, external moderation of the HFBR means that materials irradiated in different areas of the facility receive widely different flux spectra. Thus, specimens from a control rod drive follower tube (CRDF) have received 1.5 /times/ 10/sup 22/ n/cm/sup 2/ (E > 0.1 MeV)more » and 3.2 /times/ 10/sup 23/ n/cm/sup 2/ thermal fluence, while those from a vertical thimble flow shroud received 1.9 /times/ 10/sup 23/ n/cm/sup 2/ (E > 0.1 MeV) and 1.0 /times/ 10/sup 23/ n/cm/sup 2/ thermal. These numbers correspond to fast to thermal fluence ratios ranging from 0.05 to 1.9. Irradiations are occurring at approximately 333/degree/K. The data indicate that the increase in tensile strength and decrease in ductility result primarily from the thermal fluence, i.e., the transmutation of aluminum to silicon. These effects appear to be saturating at fluences above approximately 1.8 /times/ 10/sup 23/ n/cm/sup 2/ thermal at values of 90,000 psi (6700 Kg/mm/sup 2/) and 9%, respectively. The specimens receiving the highest fluence ratios appear to have less increase in tensile strength and less decrease in ductility than specimens with a lower fast to thermal fluence ratio and the same thermal fluence, suggesting a possible beneficial effect of the high energy neutrons in preventing formation of silicon crystallites. 7 refs., 11 figs., 3 tabs.« less

The ratio of the spherical and flat Detectors at tissue surfaces during pleural photodynamic therapy.

PubMed

Zhu, Timothy C; Friedberg, Joseph S; Dimofte, Andrea; Miles, Jeremy; Metz, James; Glatstein, Eli; Hahn, Stephen M

2002-06-06

An isotropic detector-based system was compared with a flat photodiode-based system in patients undergoing pleural photodynamic therapy. Isotropic and flat detectors were placed side by side in the chest cavity, for simultaneous in vivo dosimetry at surface locations for twelve patients. The treatment used 630nm laser to a total light irradiance of 30 J/cm 2 (measured with the flat photodiodes) with photofrin® IV as the photosensitizer. Since the flat detectors were calibrated at 532nm, wavelength correction factors (WCF) were used to convert the calibration to 630nm (WCF between 0.542 and 0.703). The mean ratio between isotropic and flat detectors for all sites was linear to the accumulated fluence and was 3.4±0.6 or 2.1±0.4, with or without the wavelength correction for the flat detectors, respectively. The μ eff of the tissues was estimated to vary between 0.5 to 4.3 cm -1 for four sites (Apex, Posterior Sulcus, Anterior Chest Wall, and Posterior Mediastinum) assuming μ s ' = 7 cm -1 . Insufficient information was available to estimate μ eff directly for three other sites (Anterior Sulcus, Posterior Chest Wall, and Pericardium) primarily due to limited sample size, although one may assume the optical penetration in all sites to vary in the same range (0.5 to 4.3 cm -1 ).

Photodynamic inactivation of microorganisms which cause pulmonary diseases with infrared light: an in vitro study

NASA Astrophysics Data System (ADS)

Leite, Ilaiáli S.; Geralde, Mariana C.; Salina, Ana C.; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.; Inada, Natalia M.

2014-03-01

Lower respiratory infections are among the leading causes of death worldwide. In this study, it was evaluated the interaction of indocyanine green, a photosensitizer activated by infrared light, with alveolar macrophages and the effectiveness of the photodynamic therapy using this compound against Streptococcus pneumoniae . Initial experiments analyzed indocyanine green toxicity to alveolar macrophages in the dark with different drug concentrations and incubation times, and macrophage viability was obtained with the MTT method. The average of the results showed viability values below 90% for the two highest concentrations. Experiments with Streptococcus pneumoniae showed photodynamic inactivation with 10 μM indocyanine green solution. Further experiments with the bacteria in co-culture with AM will be conducted verifying the photodynamic inactivation effectiveness of the tested drug concentrations and incubation periods using infrared light.

Electrochemical microsensor system for cancer research on photodynamic therapy in vitro

NASA Astrophysics Data System (ADS)

Marzioch, J.; Kieninger, J.; Sandvik, J. A.; Pettersen, E. O.; Peng, Q.; Urban, G.

2016-10-01

An electrochemical microsensor system to investigate photodynamic therapy of cancer cells in vitro was developed and applied to monitor the cellular respiration during and after photodynamic therapy. The redox activity and therefore influence of the photodynamic drug on the sensor performance was investigated by electrochemical characterization. It was shown, that appropriate operation conditions avoid cross-sensitivity of the sensors to the drug itself. The presented system features a cell culture chamber equipped with microsensors and a laser source to photodynamically treat the cells while simultaneous monitoring of metabolic parameter in situ. Additionally, the optical setup allows to read back fluorescence signals from the photosensitizer itself or other marker molecules parallel to the microsensor readings.

Photodynamic effect of radiation with the wavelength 405 nm on the cells of microorganisms sensitised by metalloporphyrin compounds

NASA Astrophysics Data System (ADS)

Korchenova, M. V.; Tuchina, E. S.; Shvayko, V. Y.; Gulkhandanyan, A. G.; Zakoyan, A. A.; Kazaryan, R. K.; Gulkhandanyan, G. V.; Dzhagarov, B. M.; Tuchin, V. V.

2016-06-01

We have studied the photodynamic activity of photosensitisers based on metalloporphyrins. New metalloporphyrin compounds are synthesised and characterised, the quantum yields of the singlet oxygen formation are analysed. It is shown that when the photodynamic effect is implemented using the metalloporphyrins with Zn ions and butyl radical in the 3rd and 4th positions of the pyridine ring, the number of opportunistic bacteria, such as Staphylococcus aureus (antibiotic-sensitives and antibiotic-resistant strains), Staphylococcus simulans and Escherichia coli is efficiently reduced by 90% - 99%.

MS2 bacteriophage as a delivery vessel of porphyrins for photodynamic therapy

NASA Astrophysics Data System (ADS)

Cohen, Brian A.; Kaloyeros, Alain E.; Bergkvist, Magnus

2011-02-01

Challenges associated with photodynamic therapy (PDT) include the packaging and site-specific delivery of therapeutic agents to the tissue of interest. Nanoscale encapsulation of PDT agents inside targeted virus capsids is a novel concept for packaging and site-specific targeting. The icosahedral MS2 bacteriophage is one potential candidate for such a packaging-system. MS2 has a porous capsid with an exterior diameter of ~28 nm where the pores allow small molecules access to the capsid interior. Furthermore, MS2 presents suitable residues on the exterior capsid for conjugation of targeting ligands. Initial work by the present investigators has successfully demonstrated RNA-based self-packaging of a heterocyclic PDT agent (meso-tetrakis(para-N-trimethylanilinium)porphine, TMAP) into the MS2 capsid. Packaging photoactive compounds in confined spaces could result in energy transfer between the molecules upon photoactivation, which could in turn reduce the production of radical oxygen species (ROS). ROS are key components in photodynamic therapy, and a reduced production could negatively impact the efficacy of PDT treatment. Here, findings are presented from an investigation of ROS generation of TMAP encapsulated within the MS2 capsid compared to free TMAP in solution. Monitoring of ROS production upon photoactivation via a specific singlet oxygen assay revealed the impact on ROS generation between packaged porphyrins as compared to free porphyrin in an aqueous solution. Follow on work will study the ability of MS2-packaged porphyrins to generate ROS in vitro and subsequent cytotoxic effects on cells in culture.

Epidermal protection with cryogen spray cooling during high fluence pulsed dye laser irradiation: an ex vivo study.

PubMed

Tunnell, J W; Nelson, J S; Torres, J H; Anvari, B

2000-01-01

Higher laser fluences than currently used in therapy (5-10 J/cm(2)) are expected to result in more effective treatment of port wine stain (PWS) birthmarks. However, higher incident fluences increase the risk of epidermal damage caused by absorption of light by melanin. Cryogen spray cooling offers an effective method to reduce epidermal injury during laser irradiation. The objective of this study was to determine whether high laser incident fluences (15-30 J/cm(2)) could be used while still protecting the epidermis in ex vivo human skin samples. Non-PWS skin from a human cadaver was irradiated with a Candela ScleroPlus Laser (lambda = 585 nm; pulse duration = 1.5 msec) by using various incident fluences (8-30 J/cm(2)) without and with cryogen spray cooling (refrigerant R-134a; spurt durations: 40-250 msec). Assessment of epidermal damage was based on histologic analysis. Relatively short spurt durations (40-100 msec) protected the epidermis for laser incident fluences comparable to current therapeutic levels (8-10 J/cm(2)). However, longer spurt durations (100-250 msec) increased the fluence threshold for epidermal damage by a factor of three (up to 30 J/cm(2)) in these ex vivo samples. Results of this ex vivo study show that epidermal protection from high laser incident fluences can be achieved by increasing the cryogen spurt duration immediately before pulsed laser exposure. Copyright 2000 Wiley-Liss, Inc.

Photodynamic therapy and the treatment of neoplastic diseases of the larynx

NASA Astrophysics Data System (ADS)

Biel, Merrill A.

1995-05-01

Photodynamic therapy (PDT) is an innovative treatment involving the use of light-sensitive drugs to selectively identify and destroy diseased cells. Therefore, photodynamic therapy has the potential to treat and cure precancerous and early cancerous lesions (carcinoma in situ (CIS), T1 and T2) of the larynx while preserving normal tissue. Twenty-four patients with recurrent leukoplakia and carcinomas of the larynx were treated with PDT with follow-up to 60 months. Fourteen patients with T1 squamous cell carcinomas of the vocal cord, 2 patients with a T2 squamous cell carcinoma of the vocal cord failing radiotherapy, and 6 patients with CIS and sever atypia were treated with PDT and obtained a complete response and are disease free. One patient with a T3 carcinoma of the larynx was treated with PDT but died 5 weeks post-treatment of unrelated causes and could not be assessed. Photodynamic therapy is a promising therapy for treatment of precancerous and cancerous lesions of the larynx. This therapy may be particularly beneficial for the treatment of recurrent carcinomas of the larynx that have failed conventional radiotherapy, thereby preserving voice and eliminating the need for destructive laryngeal surgery.

Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

NASA Astrophysics Data System (ADS)

Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

2007-02-01

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

Time-resolved luminescence measurements of the magnetic field effect on paramagnetic photosensitizers in photodynamic reactions

NASA Astrophysics Data System (ADS)

Mermut, O.; Bouchard, J.-P.; Cormier, J.-F.; Desroches, P.; Diamond, K. R.; Fortin, M.; Gallant, P.; Leclair, S.; Marois, J.-S.; Noiseux, I.; Morin, J.-F.; Patterson, M. S.; Vernon, M.

2008-02-01

The development of multimodal molecular probes and photosensitizing agents for use in photodynamic therapy (PDT) is vital for optimizing and monitoring cytotoxic responses. We propose a combinatorial approach utilizing photosensitizing molecules that are both paramagnetic and luminescent with multimodal functionality to perturb, control, and monitor molecular-scale reaction pathways in PDT. To this end, a time-domain single photon counting lifetime apparatus with a 400 nm excitation source has been developed and integrated with a variable low field magnet (0- 350mT). The luminescence lifetime decay function was measured in the presence of a sweeping magnetic field for a custom designed photosensitizing molecule in which photoinduced electron transfer was studied The photosensitizer studied was a donor-acceptor complex synthesized using a porphyrin linked to a fullerene molecule. The magneto-optic properties were investigated for the free-base photosensitizer complex as well as those containing either diamagnetic (paired electron) or paramagnetic (unpaired electron) metal centers, Zn(II) and Cu(II). The magnetic field was employed to affect and modify the spin states of radical pairs of the photosensitizing agents via magnetically induced hyperfine and Zeeman effects. Since the Type 1 reaction pathway of an excited triplet state photosensitizer involves the production of radical species, lifetime measurements were conducted at low dissolved oxygen concentration (0.01ppm) to elucidate the dependence of the magnetic perturbation on the photosensitization mechanistic pathway. To optimize the magnetic response, a solvent study was performed examining the dependence of the emission properties on the magnetic field in solutions of varying dielectric constants. Lastly, the cytotoxicity in murine tumor cell suspensions was investigated for the novel porphyrin-fullerene complex by inducing photodynamic treatments and determining the associated cell survival.

Photodynamic action of methylene blue in osteosarcoma cells in vitro.

PubMed

Guan, Jiemin; Lai, Xiaoping; Wang, Xinna; Leung, Albert Wingnang; Zhang, Hongwei; Xu, Chuanshan

2014-03-01

Osteosarcoma is a common malignant bone tumor which threatens the life of young people worldwide. To explore alternative strategy for combating osteosarcoma, a light-emitting diode (LED) that activates methylene blue (MB) was used in the present study to investigate cell death of osteosarcoma-derived UMR106 cells. Photocytotoxicity in UMR106 cells was investigated 24h after photodynamic activation of MB using sulforhodamine B (SRB) assay and light microscopy. Apoptosis induction was observed 24h after photodynamic treatment using a confocal laser scanning microscopy (CLSM) with Hoechst 33342 staining. The change in mitochondrial membrane potential (MMP) was analyzed using a flow cytometry with rhodamine 123 staining. MB under red light irradiation caused a drug-concentration (0-100μM) and light-dose (0-32J/cm(2)) dependent cytotoxicity in UMR106 cells. The SRB assay and light microscopy observed a significant decrease in the number of UMR106 cells attached to the bottom of culture well after LED light-activated MB (100μM, 32J/cm(2)). Nuclear shrinkage, chromatin condensation and fragmentation were found in the treated cells by nuclear staining. In addition, flow cytometry showed that the MMP in UMR106 cells was rapidly reduced by photo-activated MB (100μM, 32J/cm(2)). Photodynamic action of MB under LED irradiation could remarkably kill osteosarcoma cells and induce cell apoptosis as well as MMP collapse. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Suppression of cucurbit scab on cucumber leaves by photodynamic dyes

USDA-ARS?s Scientific Manuscript database

The goal of this study was to test the ability of the photodynamic dyes bengal rose, toluidine blue, and methylene blue, to protect systemically cucumber plants from cucurbit scab. At the stage of one true leaf, water or aqueous solutions of the dyes were applied to the leaf as droplets. When the se...

Anisotropy of the neutron fluence from a plasma focus.

NASA Technical Reports Server (NTRS)

Lee, J. H.; Shomo, L. P.; Kim, K. H.

1972-01-01

The fluence of neutrons from a plasma focus was measured by gamma spectrometry of an activated silver target. This method results in a significant increase in accuracy over the beta-counting method. Multiple detectors were used in order to measure the anisotropy of the fluence of neutrons. The fluence was found to be concentrated in a cone with a half-angle of 30 deg about the axis, and to drop off rapidly outside of this cone; the anisotropy was found to depend upon the total yield of neutrons. This dependence was strongest on the axis. Neither the axial concentration of the fluence of neutrons nor its dependence on the total yield of neutrons is explained by any of the currently proposed models. Some other explanations, including the possibility of an axially distributed source, are considered.

A Review of Progress in Clinical Photodynamic Therapy

PubMed Central

Huang, Zheng

2005-01-01

Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators world-wide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases. PMID:15896084

Evaluation of the efficacy of photodynamic therapy for the treatment of actinic cheilitis.

PubMed

Chaves, Yuri N; Torezan, Luis Antonio; Lourenço, Silvia Vanessa; Neto, Cyro Festa

2017-01-01

Actinic cheilitis (AC) is a lip intraepithelial neoplasia, whose cells present alterations similar to those presented by invasive squamous cell carcinomas (SCCs). To conduct clinical and laboratory evaluation by histopathology and immunohistochemistry of the efficacy of actinic cheilitis treatment using photodynamic therapy (PDT) with methyl aminolevulinate (MAL) and noncoherent red light. Patients with actinic cheilitis detected by histopathological examination were submitted to two sessions of photodynamic therapy with a two-week interval between them. They were examined immediately after the sessions, four, six, and twelve weeks after beginning treatment when a new biopsy was carried out. Clinical histopathological and immunohistochemical parameters were evaluated before and after treatment. Of the 23 patients who underwent biopsy, 16 completed two photodynamic therapy sessions and the material of one patient was insufficient for immunohistochemistry. Complete clinical response was achieved in 62.5% (10 of 16 patients) and 37.5% still remained with clinical evidence of AC. In spite of this, no case of cure by histopathological analysis was found. There was no significant statistical change among the values of Ki-67, survivin, and p53 observed before and after treatment. Photodynamic therapy, as carried out in this trial, was not an efficacious therapeutic option for treating patients with actinic cheilitis included in this sample. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of axial ligands on the molecular configurations, stability, reactivity, and photodynamic activities of silicon phthalocyanines.

PubMed

Luan, Liqiang; Ding, Lanlan; Shi, Jiawei; Fang, Wenjuan; Ni, Yuxing; Liu, Wei

2014-12-01

To demonstrate the effect of axial ligands on the structure-activity relationship, a series of axially substituted silicon phthalocyanines (SiPcs) have been synthesized with changes to the axial ligands. The reactivity of the axial ligand upon shielding by the phthalocyanine ring current, along with their stability, photophysical, and photodynamic therapy (PDT) activities were compared and evaluated for the first time. As revealed by single-crystal XRD analysis, rotation of the axial -OMe ligands was observed in SiPc 3, which resulted in two molecular configurations coexisting synchronously in both the solid and solution states and causing a split of the phthalocyanine α protons in the (1)H NMR spectra that is significantly different from all SiPcs reported so far. The remarkable photostability, good singlet oxygen quantum yield, and efficient in vitro photodynamic activity synergistically show that compound 3 is one of the most promising photosensitizers for PDT. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of photodynamic treatment efficiency on glioblastoma cells received from malignant lesions: initial studies

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Kyurkchiev, Dobroslav; Tumangelova-Yuzeir, Kalina; Angelov, Ivan; Genova-Hristova, Tsanislava; Semyachkina-Glushkovskaya, Oxana; Minkin, Krassimir

2018-04-01

Photodynamic therapy is well-established and extensively used method in treatment of different cancer types. This research reveals its potential in the treatment of cultivated human glioblastoma cells with adherent morphology. As the blood-brain barrier (BBB) permeability of the drugs is a significant problem that could not be solved easily for large biomolecules, we search for an appropriate low-molecular weight photosensitizer that could be applied for photodynamic treatment of glioblastoma cells. We used delta-aminolevulinic acid (5-ALA), which could pass BBB and plays the role of precursor of a protoporphyrin IX (PpIX) - photosensitizer, that is accumulated selectively in the tumour cells and could be a proper tool in PDT of glioblastoma. However, differences from patient to patient and between the cell activities could also lead to different effectiveness of the PDT treatment of the tumour areas. Therefore in our study we investigated not only the effect of using different fluence rates and light doses, but aims to establish more efficient values for further clinical applications for each sub-type of the GBM lesions. For the needs of PDT application an illumination device was developed in Laboratory of Biophotonics, BAS based on light-emitting diode (LED) matrix light sources for therapeutic application emitting at 635 nm. The device is optimized for PDT in combination with aminolevulinic acid/protoporphyrin IX applied as a photosensitizer drug. By the means of FACSCalibur flow cytometer (Becton Dickinson, USA) and Cell Quest Software was made evaluation of PDT effect on used human glioblastoma cells. Treatment of glioblastoma tumours continues to be a very serious issue and there is growing need in development of new concepts, methods and cancer-fighting strategies. PDT may contribute in accomplishing better results in cancer treatment and can be applied as well in combination with other techniques.

Study of diffusion of indocyanine green as a photodynamic dye into skin using backscattering spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genina, E A; Bashkatov, A N; Tuchin, V V

One of the lines of development of modern medicine is theranostics consisting in simultaneous diagnosis and laser treatment with the use of multifunctional agents such as fluorescent indocyanine green that has photodynamic and photothermal properties. Diffusion of indocyanine green dissolved in water and aqueous solutions of alcohols (glycerol, propylene glycol and ethanol) into the dermis is studied by using backscattering spectroscopy. The coefficients of the dye diffusion into the dermis are obtained for the first time by using these solvents. (laser biophotonics)

High Fluence Synchrotron Radiation Microprobe Effects on Stardust Interstellar Dust Candidates

NASA Astrophysics Data System (ADS)

Simionovici, A.; Allen, C.; Bajt, S.; Bastien, R.; Bechtel, H.; Borg, J.; Brenker, F. E.; Bridges, J. C.; Brownlee, D. E.; Burchell, M. J.; Burghammer, M.; Butterworth, A.; Cloetens, P.; Davis, A. M.; Floss, C.; Flynn, G.; Frank, D.; Gainsforth, Z.; Grün, E.; Heck, P. R.; Hillier, J.; Hoppe, P.; Howard, L.; Huss, G. R.; Huth, J.; Kearsley, A. T.; King, A. J.; Lai, B.; Leitner, J.; Lemelle, L.; Leroux, H.; Lettieri, R.; Marchant, W.; Nittler, L.; Ogliore, R.; Postberg, F.; Sandford, S.; Sans Tresseras, J. A.; Schoonjans, T.; Schmitz, S.; Silversmit, G.; Srama, R.; Stadermann, F. J.; Stephan, T.; Stodolna, J.; Stroud, R. M.; Sutton, S.; Tucoulou, R.; Trieloff, M.; Tsou, P.; Tsuchiyama, A.; Tyliczszak, T.; Vekemans, B.; Vincze, L.; Westphal, A. J.; Zevin, D.; Zolensky, M. E.; 29,000 Stardust@Home Dusters

2011-03-01

We are presenting for the first time damage effects produced by focused high-fluence synchrotron beams on Stardust interstellar dust candidates. The damage produced on submicrometer grains shows up as particle smearing. We attribute this mainly to charging effects.

A laser-spectroscopy complex for fluorescent diagnostics and photodynamic therapy of age-related macula degeneration

NASA Astrophysics Data System (ADS)

Shevchik, S. A.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Kharnas, Sergey S.; Loschenov, Victor B.

2004-06-01

A laser-spectroscopy complex was developed for fluorescent diagnostics and photodynamic therapy of age related macula degeneration using the Russian photosensitizer Photosense. The complex is based on slit lamp which was additionally equipped with an optical adapter, and the video adapter allows to combine the procedure of photodynamic therapy and the control of its carrying in the frame work of one procedure. The sensitivity and spatial resolution of the complex were investigated using a special test object. The availability of the developed complex and Photosense itself was examined on experimental animals.

Availability of tissue rinse liquid-based cytology for the rapid diagnosis of sentinel lymph node metastasis and improved bilateral detection by photodynamic eye camera.

PubMed

Kato, Hidenori; Ohba, Yoko; Yamazaki, Hiroyuki; Minobe, Shin-Ichiro; Sudo, Satoko; Todo, Yukiharu; Okamoto, Kazuhira; Yamashiro, Katsushige

2015-08-01

On sentinel lymph node navigation surgery for early invasive cervical cancers, to gain high sensitivity and specificity, the sentinel nodes should be detected bilaterally and pathological diagnosis should be sensitive to detect micrometastasis. To improve these problems, we tried tissue rinse liquid-based cytology and the photodynamic eye. From 2005 to 2013, 102 patients with Stage Ib1 uterine cervical cancer were subjected to sentinel lymph node navigation surgery with Technetium-99 m colloid and blue dye. For the recent 11 patients with whom bilateral sentinel node detection was not available, the photodynamic eye was selectively examined. The detected sentinel node was cut along the minor axis into 2 mm slices, soaked in 10 ml CytoRich red and then subjected to tissue rinse liquid-based cytology at the time of surgery. With the accumulation of 102 Ib1 patients subjected to sentinel lymph node navigation surgery, the bilateral sentinel node detection rate was 67.7%. The photodynamic eye was examined for the recent 11 patients who did not have bilateral signals. Out of the 11, 10 patients obtained bilateral signals successfully. During the period of examining the photodynamic eye, a total of 34 patients were subjected to sentinel lymph node navigation surgery. Thus, the overall bilateral detection rate increased to 97% in this subset. Two hundred and five lymph nodes were available as sentinel nodes. The sensitivity of tissue rinse liquid-based cytology was 91.7%, and the specificity was 100%. False positivity was 0% and false negativity was 8.3%. Detection failure was observed only with one micrometastasis and one case of isolated tumor cells. Combination of photodynamic eye detection and tissue rinse liquid-based cytology pathology can be a promising method for more rewarding sentinel node detection. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Endodontic treatment associated with photodynamic therapy: Case report.

PubMed

Firmino, Ramon Targino; Brandt, Lorenna Mendes Temóteo; Ribeiro, Gustavo Leite; Dos Santos, Katia Simone Alves; Catão, Maria Helena Chaves de Vasconccelos; Gomes, Daliana Queiroga de Castro

2016-09-01

The complete elimination of bacteria inside the root canal is a difficult task, and inconsistent removal of the innermost layer of contaminated dentin leaves bacteria behind. PDT is an adjunct to conventional endodontic treatment due to its potential to reduce bacteria and its biocompatibility. Report a case of endodontic treatment associated with Photodynamic Therapy (PDT). A patient with chronic dentoalveolar abscess with radiolucent lesion next to the apexes of teeth 11 and 21 was submitted to conventional endodontic treatment associated with PDT. The canals were filled after two PDT sessions with an interval of 15days between applications. After six months, total regression of apical periodontitis and no fistula or associated symptoms were observed. The treatment proposed is a viable option for the clinician as it is easy to perform, has relatively low-cost and allows the improvement of symptoms in a short period of time. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

PubMed

Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

2015-09-01

Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of laser fluence non-uniformity on ambient-temperature soot measurements using the auto-compensating laser-induced incandescence technique

NASA Astrophysics Data System (ADS)

Liu, Fengshan; Rogak, Steven; Snelling, David R.; Saffaripour, Meghdad; Thomson, Kevin A.; Smallwood, Gregory J.

2016-11-01

Multimode pulsed Nd:YAG lasers are commonly used in auto-compensating laser-induced incandescence (AC-LII) measurements of soot in flames and engine exhaust as well as black carbon in the atmosphere. Such lasers possess a certain degree of fluence non-uniformity across the laser beam even with the use of beam shaping optics. Recent research showed that the measured volume fraction of ambient-temperature soot using AC-LII increases significantly, by about a factor of 5-8, with increasing the laser fluence in the low-fluence regime from a very low fluence to a relatively high fluence of near sublimation. The causes of this so-called soot volume fraction anomaly are currently not understood. The effects of laser fluence non-uniformity on the measured soot volume fraction using AC-LII were investigated. Three sets of LII experiments were conducted in the exhaust of a MiniCAST soot generator under conditions of high elemental carbon using Nd:YAG lasers operated at 1064 nm. The laser beams were shaped and relay imaged to achieve a relatively uniform fluence distribution in the measurement volume. To further homogenize the laser fluence, one set of LII experiments was conducted by using a diffractive optical element. The measured soot volume fractions in all three sets of LII experiments increase strongly with increasing the laser fluence before a peak value is reached and then start to decrease at higher fluences. Numerical calculations were conducted using the experimental laser fluence histograms. Laser fluence non-uniformity is found partially responsible for the soot volume fraction anomaly, but is insufficient to explain the degree of soot volume fraction anomaly observed experimentally. Representing the laser fluence variations by a histogram derived from high-resolution images of the laser beam energy profile gives a more accurate definition of inhomogeneity than a simple averaged linear profile across the laser beam.

Molecular analysis of apoptosis pathway after photodynamic therapy in breast cancer: Animal model study.

PubMed

Silva, Luciana C; Ferreira-Strixino, Juliana; Fontana, Letícia C; Rocha Gonsalves, António M d'A; Serra, Arménio C; Pineiro, Marta; Canevari, Renata A

2016-06-01

Molecular investigation of breast tumors has permitted better understanding about interaction of genes and pathways involved in tumor progression. The aim of this study was to evaluate the association between genes belonging to the pathway of apoptosis with tumor response to photodynamic therapy. The mammary tumors were induced in twenty-four Spraguey-Dawley female rats by oral gavage of 7,12-dimethylbenz(a)anthracene (8mg/Kg body weight). Animals were divided into three groups: G1 (normal tissue), G2 (tumors without treatment), G3 (animals euthanized 48h after treatment). The photosensitizer used was a chlorin, 5,15-bis-(2-bromo-5-hydroxyphenyl) chlorin in the dose of 8mg/kg for each animal. Light source of diode laser at a wavelength of 660nm, fluence rate of 100mW/cm, and light dose of 100J/cm was delivery to lesions for treatment. A sample from each animal was investigated by quantitative real time PCR using Rat Apoptosis RT(2) Profiler™ PCR Array platform. Pro-apoptotic BAK1, CARD6, CASP8, CIDEA, CIDEB, DAPK1, TNF, TNFRSF10B, FASLG, LOC687813, and TP73 genes showed increased expression, and CD40 anti-apoptotic gene showed decreased expression in the group who underwent PDT (G3) in relation to G2. The results indicated that these genes are involved more directly with cellular apoptosis induced by PDT using the Chlorin photosensitizer. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative study between the effects of photodynamic therapy and conventional therapy on microbial reduction in ligature-induced peri-implantitis in dogs.

PubMed

Hayek, Ricardo R A; Araújo, Ney S; Gioso, Marco A; Ferreira, Jonathan; Baptista-Sobrinho, Carlos A; Yamada, Aécio M; Ribeiro, Martha S

2005-08-01

Progressive peri-implant bone losses, which are accompanied by inflammatory lesions in the soft tissues, are referred to as peri-implantitis. The aim of this study was to compare the effects of photodynamic therapy (PDT) and conventional technique on microbial reduction in ligature-induced peri-implantitis in dogs. Eighteen third premolars from nine Labrador retriever dogs were extracted and the implants were submerged. After osseointegration, peri-implantitis was induced. After 4 months, ligature was removed and natural bacterial plaque was allowed to form for another 4 months. The animals were then randomly divided into two groups. In the conventional group, they were treated using mucoperiosteal flaps for scaling the implant surface and chlorexidine (conventional) irrigation. In the PDT group, only mucoperiosteal scaling was carried out before photodynamic therapy. Inside the peri-implant pocket, a paste-based azulene photosensitizer was placed and then a GaAlAs low-power laser (lambda=660 nm, P=40 mW, E=7.2 J for 3 minutes) was used. Microbiological samples were obtained before and immediately after treatment. Before treatment, one implant was removed and analyzed by scanning electron microscopy to validate the contamination. The results of this study showed that Prevotella sp., Fusobacterium sp., and S. Beta-haemolyticus were significantly reduced for both groups. After treatment, no significant differences were observed between the groups. These findings suggest that photodynamic therapy is a non-invasive method that could be used to reduce microorganisms in peri-implantitis. J Periodontol 2005;76:1275-1281.

Neutron Fluence And DPA Rate Analysis In Pebble-Bed HTR Reactor Vessel Using MCNP

NASA Astrophysics Data System (ADS)

Hamzah, Amir; Suwoto; Rohanda, Anis; Adrial, Hery; Bakhri, Syaiful; Sunaryo, Geni Rina

2018-02-01

In the Pebble-bed HTR reactor, the distance between the core and the reactor vessel is very close and the media inside are carbon and He gas. Neutron moderation capability of graphite material is theoretically lower than that of water-moderated reactors. Thus, it is estimated much more the fast neutrons will reach the reactor vessel. The fast neutron collisions with the atoms in the reactor vessel will result in radiation damage and could be reducing the vessel life. The purpose of this study was to obtain the magnitude of neutron fluence in the Pebble-bed HTR reactor vessel. Neutron fluence calculations in the pebble-bed HTR reactor vessel were performed using the MCNP computer program. By determining the tally position, it can be calculated flux, spectrum and neutron fluence in the position of Pebble-bed HTR reactor vessel. The calculations results of total neutron flux and fast neutron flux in the reactor vessel of 1.82x108 n/cm2/s and 1.79x108 n/cm2/s respectively. The fast neutron fluence in the reactor vessel is 3.4x1017 n/cm2 for 60 years reactor operation. Radiation damage in stainless steel material caused by high-energy neutrons (> 1.0 MeV) will occur when it has reached the neutron flux level of 1.0x1024 n/cm2. The neutron fluence results show that there is no radiation damage in the Pebble-bed HTR reactor vessel, so it is predicted that it will be safe to operate at least for 60 years.

Probabilistic Forecast of Solar Particle Fluence for Mission Durations and Exposure Assessment in Consideration of Integral Proton Fluence at High Energies

NASA Astrophysics Data System (ADS)

Kim, M. Y.; Tylka, A. J.; Dietrich, W. F.; Cucinotta, F. A.

2012-12-01

The occasional occurrence of solar particle events (SPEs) with large amounts of energy is non-predictable, while the expected frequency is strongly influenced by solar cycle activity. The potential for exposure to large SPEs with high energy levels is the major concern during extra-vehicular activities (EVAs) on the Moon, near Earth object, and Mars surface for future long duration space missions. We estimated the propensity for SPE occurrence with large proton fluence as a function of time within a typical future solar cycle from a non-homogeneous Poisson model using the historical database for measurements of protons with energy > 30 MeV, Φ30. The database includes a comprehensive collection of historical data set for the past 5 solar cycles. Using all the recorded proton fluence of SPEs, total fluence distributions of Φ30, Φ60, and Φ100 were simulated ranging from its 5th to 95th percentile for each mission durations. In addition to the total particle intensity of SPEs, the detailed energy spectra of protons, especially at high energy levels, were recognized as extremely important for assessing the radiation cancer risk associated with energetic particles for large events. For radiation exposure assessments of major SPEs, we used the spectral functional form of a double power law in rigidity (the so-called Band function), which have provided a satisfactory representation of the combined satellite and neutron monitor data from ~10 MeV to ~10 GeV. The dependencies of exposure risk were evaluated as a function of proton fluence at a given energy threshold of 30, 60, and 100 MeV, and overall risk prediction was improved as the energy level threshold increases from 30 to 60 to 100 MeV. The results can be applied to the development of approaches of improved radiation protection for astronauts, as well as the optimization of mission planning and shielding for future space missions.

Reducing Energy Consumption and CO2 One Street Lamp at a Time

NASA Astrophysics Data System (ADS)

Somssich, Peter

2011-11-01

Why wait for federal action on incentives to reduce energy use and address Greenhouse Gas (GHG) reductions (e.g. CO2), when we can take personal actions right now in our private lives and in our communities? One such initiative by private citizens working with Portsmouth NH officials resulted in the installation of energy reducing lighting products on Court St. and the benefits to taxpayers are still coming after over 4 years of operation. This citizen initiative to save money and reduce CO2 emissions, while only one small effort, could easily be duplicated in many towns and cities. Replacing old lamps in just one street fixture with a more energy efficient (Non-LED) lamp has resulted after 4 years of operation (˜15,000 hr. life of product) in real electrical energy savings of > 43. and CO2 emission reduction of > 465 lbs. The return on investment (ROI) was less than 2 years. This is much better than any financial investment available today and far safer. Our street only had 30 such lamps installed; however, the rest of Portsmouth (population 22,000) has at least another 150 street lamp fixtures that are candidates for such an upgrade. The talk will also address other energy reduction measures that green the planet and also put more green in the pockets of citizens and municipalities.

Investigation of photodynamic effect caused by MPPa-PDT on breast cancer Investigation of photodynamic effect caused by MPPa-PDT

NASA Astrophysics Data System (ADS)

Tian, Y. Y.; Hu, X. Y.; Leung, W. N.; Yuan, H. Q.; Zhang, L. Y.; Cui, F. A.; Tian, X.

2012-10-01

Breast cancer is the common malignant tumor, the incidence increases with age. Photodynamic therapy (PDT) is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. Pyropheophorbide-a methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. We are exploring the photodynamic effect caused by MPPa-PDT on breast cancer. The in vitro and in vivo experiments indicate that MPPa is a comparatively ideal photosensitizer which can induce apoptosis in breast cancer.

Fighting fish parasites with photodynamically active chlorophyllin.

PubMed

Häder, D-P; Schmidl, J; Hilbig, R; Oberle, M; Wedekind, H; Richter, P

2016-06-01

Water-soluble chlorophyll (chlorophyllin) was used in a phototoxic reaction against a number of fish ectoparasites such as Ichtyobodo, Dactylogyrus, Trichodina, and Argulus. Chlorophyllin is applied to the water at concentrations of several micrograms per milliliter for a predefined incubation time, and afterwards, the parasites are exposed to simulated solar radiation. Application in the dark caused only little damage to the parasites; likewise, light exposure without the addition of the photosensitizer was ineffective. In Ichthyobodo, 2 μg/mL proved sufficient with subsequent simulated solar radiation to almost quantitatively kill the parasites, while in Dactylogyrus, a concentration of about 6 μg/mL was necessary. The LD50 value for this parasite was 1.02 μg/mL. Trichodina could be almost completely eliminated at 2 μg/mL. Only in the parasitic crustacean Argulus, no killing could be achieved by a photodynamic reaction using chlorophyllin. Chlorophyllin is non-toxic, biodegradable, and can be produced at low cost. Therefore, we propose that chlorophyllin (or other photodynamic substances) are a possible effective countermeasure against several ectoparasites in ponds and aquaculture since chemical remedies are either forbidden and/or ineffective.

Photodynamic action of the red laser on Propionibacterium acnes*

PubMed Central

Ramos, Rogério Rodrigo; de Paiva, Jeferson Leandro; Gomes, José Paulo Franco dos Santos; Boer, Nagib Pezati; de Godoy, José Maria Pereira; Batigalia, Fernando

2017-01-01

Background Photodynamic therapy is a therapeutic modality that has consolidated its activity in the photooxidation of organic matter, which arises from the activity of reactive oxygen species. Objective To evaluate the effect of red laser 660nm with the photosensitizer methylene blue on Propionibacterium acnes in vitro. Method The experimental design was distributed into four groups (1 - control group without the application of light and without photosensitizer, 2 - application of light, 3 - methylene blue without light, and 4 - methylene blue with light). Tests were subjected to red laser irradiation 660nm by four cycles of 5 minutes at 3-minute intervals. Results It was evidenced the prominence of the fourth cycle (20 minutes) groups 2, 3 and 4. Study limitations Despite the favorable results, the laser irradiation time photosensitizer associated with methylene blue were not sufficient to to completely inhibit the proliferation of bacteria. Conclusion Further studies in vitro are recommended to enable the clinical application of this photosensitizer in photodynamic therapy. PMID:29166495

New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

NASA Astrophysics Data System (ADS)

Hanušová, T.; Vondráček, V.; Badraoui-Čuprová, K.; Horáková, I.; Koniarová, I.

2015-01-01

A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

Multifunctional nanoplatform for enhanced photodynamic cancer therapy and magnetic resonance imaging.

PubMed

Hao, Yongwei; Zhang, Bingxiang; Zheng, Cuixia; Niu, Mengya; Guo, Haochen; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Wang, Lei; Zhang, Yun

2017-03-01

Co-delivery of photosensitizers and synergistic agents by one single nanoplatform is interesting for enhancing photodynamic therapy (PDT) of cancer. Here, a multifunctional nanoplatform for enhanced photodynamic therapy and magnetic resonance imaging of cancer was constructed. The poly (lactide-co-glycolide) (PLGA) nanoparticles (NPs) loaded with hematoporphyrin monomethyl ether (HMME) were coated with multifunctional manganese dioxide (MnO 2 ) shells, which were designed as PLGA/HMME@MnO 2 NPs. Once the NPs were effectively taken up by tumor cells, the intracellular H 2 O 2 was catalysed by the MnO 2 shells to generate O 2 . Meanwhile, the higher glutathione (GSH) promoted the degradation of MnO 2 into Mn 2+ ions with the ability of magnetic resonance (MR) imaging. After the degradation of outer layer, the release of photosensitizer was promoted. Under irradiation, the released HMME produced cytotoxic reactive oxygen species (ROS) to damage the tumor cells when the O 2 was generated in the hypoxic tumor site. Furthermore, the decreased GSH level further inhibited the consumption of the produced ROS, which greatly enhanced the PDT efficacy. Therefore, this study suggested that this multifunctional system has the potential for enhanced photodynamic therapy and magnetic resonance imaging. Copyright © 2016 Elsevier B.V. All rights reserved.

Poster - 52: Smoothing constraints in Modulated Photon Radiotherapy (XMRT) fluence map optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGeachy, Philip; Villarreal-Barajas, Jose Eduardo

Purpose: Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has recently shown dosimetric improvement in comparison to conventional IMRT. That said, the degree of smoothness of resulting fluence maps (FMs) has yet to be investigated and could impact the deliverability of XMRT. This study looks at investigating FM smoothness and imposing smoothing constraint in the fluence map optimization. Methods: Smoothing constraints were modeled in the XMRT algorithm with the sum of positive gradient (SPG) technique. XMRT solutions, with and without SPG constraints, were generated for a clinical prostate scan using standard dosimetricmore » prescriptions, constraints, and a seven coplanar beam arrangement. The smoothness, with and without SPG constraints, was assessed by looking at the absolute and relative maximum SPG scores for each fluence map. Dose volume histograms were utilized when evaluating impact on the dose distribution. Results: Imposing SPG constraints reduced the absolute and relative maximum SPG values by factors of up to 5 and 2, respectively, when compared with their non-SPG constrained counterparts. This leads to a more seamless conversion of FMS to their respective MLC sequences. This improved smoothness resulted in an increase to organ at risk (OAR) dose, however the increase is not clinically significant. Conclusions: For a clinical prostate case, there was a noticeable improvement in the smoothness of the XMRT FMs when SPG constraints were applied with a minor increase in dose to OARs. This increase in OAR dose is not clinically meaningful.« less

[Cost-effectiveness of photodynamic therapy in age-related macular degeneration].

PubMed

Muslera, E; Natal, C

2006-04-01

The aim of this study was to estimate the public health service cost of visual acuity improvement or maintenance with photodynamic therapy in patients with age-related macular degeneration (ARMD). This illness is the most frequent cause of blindness in elderly patients in western countries. A cost-effectiveness analysis was carried out to compare photodynamic therapy versus no treatment. The analysis point of view was that of the health service. The improvement or maintenance of visual acuity and contrast sensitivity were considered efficacy results. Direct costs were estimated by means of cost accountancy. Quality adjusted costs per visual acuity life year gained (QACVAG) were calculated through utility values from other studies. The cost per year of maintenance of visual acuity in a two-year period was 36,530 euro for women and 34,804 euro for men. If this cost was estimated for life expectancy in Asturias, it would be reduced to 4,298 euro for women and 5,354 euro for men. If costs of the QACVAG, in a two-year period, were considered, photodynamic therapy would cost 66,931 euro for women and 70,249 euro for men. This cost-effectiveness analysis allows decisions to be made about public financing. Some research in our country suggests that public health financing should be provided for interventions whose cost-effectiveness is less than 30,000 euro of CVAQA. The treatment evaluated here far exceeds this value. It is recommended that the use of more restrictive patient selection, incorporating diagnostic criteria and patient autonomy indicators, could improve the results of this intervention.

SWIMRT: A graphical user interface using the sliding window algorithm to construct a fluence map machine file

PubMed Central

Chow, James C.L.; Grigorov, Grigor N.; Yazdani, Nuri

2006-01-01

A custom‐made computer program, SWIMRT, to construct “multileaf collimator (MLC) machine” file for intensity‐modulated radiotherapy (IMRT) fluence maps was developed using MATLAB® and the sliding window algorithm. The user can either import a fluence map with a graphical file format created by an external treatment‐planning system such as Pinnacle3 or create his or her own fluence map using the matrix editor in the program. Through comprehensive calibrations of the dose and the dimension of the imported fluence field, the user can use associated image‐processing tools such as field resizing and edge trimming to modify the imported map. When the processed fluence map is suitable, a “MLC machine” file is generated for our Varian 21 EX linear accelerator with a 120‐leaf Millennium MLC. This machine file is transferred to the MLC console of the LINAC to control the continuous motions of the leaves during beam irradiation. An IMRT field is then irradiated with the 2D intensity profiles, and the irradiated profiles are compared to the imported or modified fluence map. This program was verified and tested using film dosimetry to address the following uncertainties: (1) the mechanical limitation due to the leaf width and maximum traveling speed, and (2) the dosimetric limitation due to the leaf leakage/transmission and penumbra effect. Because the fluence map can be edited, resized, and processed according to the requirement of a study, SWIMRT is essential in studying and investigating the IMRT technique using the sliding window algorithm. Using this program, future work on the algorithm may include redistributing the time space between segmental fields to enhance the fluence resolution, and readjusting the timing of each leaf during delivery to avoid small fields. Possible clinical utilities and examples for SWIMRT are given in this paper. PACS numbers: 87.53.Kn, 87.53.St, 87.53.Uv PMID:17533330

Assessment of photodynamic damage on Escherichia coli via atomic force microscopy

NASA Astrophysics Data System (ADS)

Núñez, Silvia Cristina; Simões Ribeiro, Martha; Silva Garcez, Aguinaldo; Miyakawa, Walter

2010-04-01

Photodynamic antimicrobial therapy (PAT) may become a useful clinical tool to treat microbial infections, overcoming microbial resistance that is a major problem nowadays. The aim of our work was to verify the damage caused by photosensitization over a Escherichia col) via atomic force microscopy (AFM), looking for structural changes that might occur in cells after PAT. Cells culture were grown until a stationary phase to reach a concentration of approximately 108 cells/mL allowing the production of extracellular slime in a biofilm-like structure. The cells including the extracellular matrix were put in a slide and its structure was observed using AFM; subsequently a water solution of methylene blue at 60μM was applied over the cells and a pre-irradiation time of 3 minutes was waited and followed by illumination with a diode laser (λ=660nm, power 40mW, 3min, fluence 180J/cm2, beam diameter 0.04cm2). The same cells were observed and the images stored. A second set of experiments was performed with a smaller number of cells/area and without extracellular slime, using the parameters abovementioned. The results showed alterations on cellular scaffold markedly dependent on the number of cells and the presence of extracellular slime. The slime is targeted by the photosensitizer, and after irradiation a destruction of the matrix was observed; when fewer cells were evaluated the destruction is much more evident. The images suggested rupture of the cellular membrane and cellular fragments were observed. Our findings indicate that AFM seems is a useful tool to investigate parameters linked with photodestruction of microorganisms.

Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)

NASA Astrophysics Data System (ADS)

Spring, Bryan Q.; Sears, R. Bryan; Zheng, Lei Z.; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

2016-03-01

We introduce photoactivatable multi-inhibitor nanoliposomes (PMILs) for photodynamic tumor cell and microvessel damage in synchrony with photo-initiation of tumor-confined, multikinase inhibitor release. The PMIL is a biodegradable delivery system comprised of a nanoliposome carrying a photoactivable chromophore (benzoporphyrin derivative monoacid A, BPD) in its bilayer. A multikinase inhibitor-loaded PEG-PLGA nanoparticle is encapsulated within the liposome, which acts a barrier to nanoparticle erosion and drug release. Following intravenous PMIL administration, near infrared irradiation of tumors triggers photodynamic therapy and initiates tumor-confined drug release from the nanoparticle. This talk presents promising preclinical data in mouse models of pancreatic cancer utilizing this concept to suppress the VEGF and MET signaling pathways—both critical to cancer progression, metastasis and treatment escape. A single PMIL treatment using low doses of a multikanse inhibitor (cabozantinib, XL184) achieves sustained tumor reduction and suppresses metastatic escape, whereas combination therapy by co-administration of the individual agents has significantly reduced efficacy. The PMIL concept is amenable to a number of molecular inhibitors and offers new prospects for spatiotemporal synchronization of combination therapies whilst reducing systemic drug exposure and associated toxicities.

The role of singlet oxygen and oxygen concentration in photodynamic inactivation of bacteria

PubMed Central

Maisch, Tim; Baier, Jürgen; Franz, Barbara; Maier, Max; Landthaler, Michael; Szeimies, Rolf-Markus; Bäumler, Wolfgang

2007-01-01

New antibacterial strategies are required in view of the increasing resistance of bacteria to antibiotics. One promising technique involves the photodynamic inactivation of bacteria. Upon exposure to light, a photosensitizer in bacteria can generate singlet oxygen, which oxidizes proteins or lipids, leading to bacteria death. To elucidate the oxidative processes that occur during killing of bacteria, Staphylococcus aureus was incubated with a standard photosensitizer, and the generation and decay of singlet oxygen was detected directly by its luminescence at 1,270 nm. At low bacterial concentrations, the time-resolved luminescence of singlet oxygen showed a decay time of 6 ± 2 μs, which is an intermediate time for singlet oxygen decay in phospholipids of membranes (14 ± 2 μs) and in the surrounding water (3.5 ± 0.5 μs). Obviously, at low bacterial concentrations, singlet oxygen had sufficient access to water outside of S. aureus by diffusion. Thus, singlet oxygen seems to be generated in the outer cell wall areas or in adjacent cytoplasmic membranes of S. aureus. In addition, the detection of singlet oxygen luminescence can be used as a sensor of intracellular oxygen concentration. When singlet oxygen luminescence was measured at higher bacterial concentrations, the decay time increased significantly, up to ≈40 μs, because of oxygen depletion at these concentrations. This observation is an important indicator that oxygen supply is a crucial factor in the efficacy of photodynamic inactivation of bacteria, and will be of particular significance should this approach be used against multiresistant bacteria. PMID:17431036

Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

PubMed

Kusuzaki, Katsuyuki; Matsubara, Takao; Murata, Hiroaki; Logozzi, Mariantonia; Iessi, Elisabetta; Di Raimo, Rossella; Carta, Fabrizio; Supuran, Claudiu T; Fais, Stefano

2017-12-01

Photodynamic molecules represent an alternative approach for cancer therapy for their property (i) to be photo-reactive; (ii) to be not-toxic for target cells in absence of light; (iii) to accumulate specifically into tumour tissues; (iv) to be activable by a light beam only at the tumour site and (v) to exert cytotoxic activity against tumour cells. However, to date their clinical use is limited by the side effects elicited by systemic administration. Extracellular vesicles are endogenous nanosized-carriers that have been recently introduced as a natural delivery system for therapeutic molecules. We have recently shown the ability of human exosomes to deliver photodynamic molecules. Therefore, this review focussed on extracellular vesicles as a novel strategy for the delivery of photodynamic molecules at cancer sites. This completely new approach may enhance the delivery and decrease the toxicity of photodynamic molecules, therefore, represent the future for photodynamic therapy for cancer treatment.

Singlet oxygen production by combining erythrosine and halogen light for photodynamic inactivation of Streptococcus mutans.

PubMed

Fracalossi, Camila; Nagata, Juliana Yuri; Pellosi, Diogo Silva; Terada, Raquel Sano Suga; Hioka, Noboru; Baesso, Mauro Luciano; Sato, Francielle; Rosalen, Pedro Luiz; Caetano, Wilker; Fujimaki, Mitsue

2016-09-01

Photodynamic inactivation of microorganisms is based on a photosensitizing substance which, in the presence of light and molecular oxygen, produces singlet oxygen, a toxic agent to microorganisms and tumor cells. This study aimed to evaluate singlet oxygen quantum yield of erythrosine solutions illuminated with a halogen light source in comparison to a LED array (control), and the photodynamic effect of erythrosine dye in association with the halogen light source on Streptococcus mutans. Singlet oxygen quantum yield of erythrosine solutions was quantified using uric acid as a chemical-probe in an aqueous solution. The in vitro effect of the photodynamic antimicrobial activity of erythrosine in association with the halogen photopolimerizing light on Streptococcus mutans (UA 159) was assessed during one minute. Bacterial cultures treated with erythrosine alone served as negative control. Singlet oxygen with 24% and 2.8% degradation of uric acid in one minute and a quantum yield of 0.59 and 0.63 was obtained for the erythrosine samples illuminated with the halogen light and the LED array, respectively. The bacterial cultures with erythrosine illuminated with the halogen light presented a decreased number of CFU mL(-1) in comparison with the negative control, with minimal inhibitory concentrations between 0.312 and 0.156mgmL(-1). The photodynamic response of erythrosine induced by the halogen light was capable of killing S. mutans. Clinical trials should be conducted to better ascertain the use of erythrosine in association with halogen light source for the treatment of dental caries. Copyright © 2016 Elsevier B.V. All rights reserved.

[Application of photodynamic therapy in dentistry – literature review].

PubMed

Oruba, Zuzanna; Chomyszyn-Gajewska, Maria

Photodynamic therapy (PDT) is based on the principle that the target cells are destroyed by means of toxic reactive oxygen species generated upon the interaction of a photosensitizer, light and oxygen. This method is nowadays widely applied in various branches of medicine, mainly in oncology and dermatology. It is also applied in dentistry in the treatment of oral potentially malignant disorders (like lichen planus or leukoplakia) and infectious conditions (periodontitis, herpetic cheilitis, root canal disinfection). The application of the photodynamic therapy in the abovementioned indications is worth attention, as the method is noninvasive, painless, and the results of the published studies seem promising. The present article aims at presenting the principle of the photodynamic therapy and, based on the literature, the possibilities and results of its application in dentistry.

Progress toward development of photodynamic vaccination against infectious/malignant diseases and photodynamic mosquitocides

NASA Astrophysics Data System (ADS)

Chang, Kwang Poo; Kolli, Bala K.; Fan, Chia-Kwung; Ng, Dennis K. P.; Wong, Clarence T. T.; Manna, Laura; Corso, Raffaele; Shih, Neng-Yao; Elliott, Robert; Jiang, X. P.; Shiao, Shin-Hong; Fu, Guo-Liang

2018-02-01

Photodynamic therapy (PDT) uses photosensitizers (PS) that are excited with light to generate ROS in the presence of oxygen for treating various diseases. PS also has the potential use as photodynamic insecticides (PDI) and for light-inactivation of Leishmania for photodynamic vaccination (PDV). PDT-inactivated Leishmania are non-viable, but remain immunologically competent as whole-cell vaccines against leishmaniasis, and as a universal carrier for delivery of add-on vaccines against other infectious and malignant diseases. We have screened novel PS, including Zn- and Si-phthalocyanines (PC) for differential PDT activities against Leishmania, insect and mammalian cells in vitro to assess their PDI and PDV potential. Here, Zn-PC were conjugated with various functional groups. The conjugates were examined for uptake by cells as a prerequisite for their susceptibility to light-inactivation. PDT sensitivity was found to vary with cell types and PS used. PDI potential of several PS was demonstrated by their mosquito larvicidal PDT activities in vitro. PDT-inactivated Leishmania were stored frozen for PDV in several ongoing studies: [1] Open label trial with 20 sick dogs for immunotherapy of canine leishmaniasis after chemotherapy in Naples, Italy. Clinical follow-up for >3 years indicate that the PDV prolongs their survival; [2] PDV of murine models with a human lung cancer vaccine showed dramatic tumor suppression; [3] Open label trial of multiple PDV via compassionate access to 4 advanced cancer patients showed no clinically adverse effects. Two subjects remain alive. Genetic modifications of Leishmania are underway to further enhance their safety and efficacy for PDV by installation of activable mechanisms for self-destruction and spontaneous light-emission.

Investigating multi-objective fluence and beam orientation IMRT optimization

NASA Astrophysics Data System (ADS)

Potrebko, Peter S.; Fiege, Jason; Biagioli, Matthew; Poleszczuk, Jan

2017-07-01

Radiation Oncology treatment planning requires compromises to be made between clinical objectives that are invariably in conflict. It would be beneficial to have a ‘bird’s-eye-view’ perspective of the full spectrum of treatment plans that represent the possible trade-offs between delivering the intended dose to the planning target volume (PTV) while optimally sparing the organs-at-risk (OARs). In this work, the authors demonstrate Pareto-aware radiotherapy evolutionary treatment optimization (PARETO), a multi-objective tool featuring such bird’s-eye-view functionality, which optimizes fluence patterns and beam angles for intensity-modulated radiation therapy (IMRT) treatment planning. The problem of IMRT treatment plan optimization is managed as a combined monolithic problem, where all beam fluence and angle parameters are treated equally during the optimization. To achieve this, PARETO is built around a powerful multi-objective evolutionary algorithm, called Ferret, which simultaneously optimizes multiple fitness functions that encode the attributes of the desired dose distribution for the PTV and OARs. The graphical interfaces within PARETO provide useful information such as: the convergence behavior during optimization, trade-off plots between the competing objectives, and a graphical representation of the optimal solution database allowing for the rapid exploration of treatment plan quality through the evaluation of dose-volume histograms and isodose distributions. PARETO was evaluated for two relatively complex clinical cases, a paranasal sinus and a pancreas case. The end result of each PARETO run was a database of optimal (non-dominated) treatment plans that demonstrated trade-offs between the OAR and PTV fitness functions, which were all equally good in the Pareto-optimal sense (where no one objective can be improved without worsening at least one other). Ferret was able to produce high quality solutions even though a large number of parameters

An efficient method to determine double Gaussian fluence parameters in the eclipse™ proton pencil beam model.

PubMed

Shen, Jiajian; Liu, Wei; Stoker, Joshua; Ding, Xiaoning; Anand, Aman; Hu, Yanle; Herman, Michael G; Bues, Martin

2016-12-01

To find an efficient method to configure the proton fluence for a commercial proton pencil beam scanning (PBS) treatment planning system (TPS). An in-water dose kernel was developed to mimic the dose kernel of the pencil beam convolution superposition algorithm, which is part of the commercial proton beam therapy planning software, eclipse™ (Varian Medical Systems, Palo Alto, CA). The field size factor (FSF) was calculated based on the spot profile reconstructed by the in-house dose kernel. The workflow of using FSFs to find the desirable proton fluence is presented. The in-house derived spot profile and FSF were validated by a direct comparison with those calculated by the eclipse TPS. The validation included 420 comparisons of the FSFs from 14 proton energies, various field sizes from 2 to 20 cm and various depths from 20% to 80% of proton range. The relative in-water lateral profiles between the in-house calculation and the eclipse TPS agree very well even at the level of 10 -4 . The FSFs between the in-house calculation and the eclipse TPS also agree well. The maximum deviation is within 0.5%, and the standard deviation is less than 0.1%. The authors' method significantly reduced the time to find the desirable proton fluences of the clinical energies. The method is extensively validated and can be applied to any proton centers using PBS and the eclipse TPS.

Effectiveness of 5-aminolevulinic acid photodynamic therapy in the treatment of hidradenitis suppurativa: a report of 5 cases.

PubMed

Andino Navarrete, R; Hasson Nisis, A; Parra Cares, J

2014-01-01

Hidradenitis suppurativa has been described as a chronic, recurrent, and disabling inflammatory disease involving the entire hair follicle. Several treatments, including photodynamic therapy, have been used, but the results have been inconsistent and recurrence is high. In this prospective study, we evaluated disease severity, quality of life, and treatment tolerance in 5 patients with moderate to severe hidradenitis suppurativa treated with photodynamic therapy using 5-aminolevulinic acid and a 635-nm light source. Treatment effectiveness was evaluated using the Sartorius severity score, the Dermatology Life Quality Index, and a visual analog scale for pain and disease activity. Significant improvements were observed with all 3 instruments and the effects remained visible at 8 weeks. Our results suggest that photodynamic therapy with 5-aminolevulinic acid and a light wavelength of 635 nm could reduce disease severity and improve quality of life in patients with difficult-to-treat hidradenitis suppurativa. Copyright © 2013 Elsevier España, S.L. y AEDV. All rights reserved.

Impact of Mg-ion implantation with various fluence ranges on optical properties of n-type GaN

NASA Astrophysics Data System (ADS)

Tsuge, Hirofumi; Ikeda, Kiyoji; Kato, Shigeki; Nishimura, Tomoaki; Nakamura, Tohru; Kuriyama, Kazuo; Mishima, Tomoyoshi

2017-10-01

Optical characteristics of Mg-ion implanted GaN layers with various fluence ranges were evaluated. Mg ion implantation was performed twice at energies of 30 and 60 keV on n-GaN layers. The first implantation at 30 keV was performed with three different fluence ranges of 1.0 × 1014, 1.0 × 1015 and 5.0 × 1015 cm-2. The second implantation at an energy of 60 keV was performed with a fluence of 6.5 × 1013 cm-2. After implantation, samples were annealed at 1250 °C for 1 min under N2 atmosphere. Photoluminescence (PL) spectrum of the GaN layer with the Mg ion implantation at the fluence range of 1.0 × 1014 cm-2 at 30 keV was similar to the one of Mg-doped p-GaN layers grown by MOVPE (Metal-Organic Vapor Phase Epitaxy) on free-standing GaN substrates and those at the fluence ranges over 1.0 × 1015 cm-2 were largely degraded.

Investigation of photodynamic activity of water-soluble porphyrins in vitro and in vivo

NASA Astrophysics Data System (ADS)

Gyulkhandanyan, Grigor V.; Ghambaryan, Sona S.; Amelyan, Gayane V.; Ghazaryan, Robert K.; Arsenyan, Flora H.; Gyulkhandanyan, Aram G.

2006-02-01

Photodynamic therapy (PDT) is the method of photosensitized tumor treatment. It is based on the photosensitizer (PS) selective accumulation in tumors, its subsequent activation under the light influence and oxygen active form formation that results in tumor destruction. Photodynamic action of some new water-soluble porphyrins was investigated in our laboratory. Dose-dependent effect of these porphyrins was shown on PC-12 murine pheochromocytoma cell line. The results revealed that the efficiency of the investigated porphyrins decreased in the following way: TOEPyP (meso-tetra-(4-N-oxyethylpyridyl)porphyrin) > Zn-TOEPyP > Ag-TOEPyP. It was shown that TOEPyP possessed nearly the same photodynamic activity (LD50) as well-known photosensitizer chlorin e6. These porphyrins have also demonstrated quite high photodynamic activity in vivo. The results were obtained in the experiments on white mice with engrafted C-180 (Croker's sarcoma). Antitumor activity of these porphyrins in the dark was 30-40%, whereas photodynamic activity was 45-60%.

Photodynamic-induced inactivation of Propionibacterium acnes

NASA Astrophysics Data System (ADS)

Koenig, Karsten; Teschke, M.; Eick, Stephen G.; Pfister, W.; Meyer, Herbert; Halbhuber, Karl-Juergen

1998-05-01

We report on photodynamically induced inactivation of the skin bacterium Propionibacterium acnes (P. acnes) using endogenous as well as exogenous photosensitizers and red light sources. P. acnes is involved in the pathogenesis of the skin disease acne vulgaris. The skin bacterium is able to synthesize the metal-free fluorescent porphyrins protoporphyrin IX (PP) and coproporphyrin (CP) as shown by in situ spectrally-resolved detection of natural autofluorescence of human skin and bacteria colonies. These naturally occurring intracellular porphyrins act as efficient endogenous photosensitizers. Inactivation of P. acnes suspensions was achieved by irradiation with He-Ne laser light in the red spectral region (632.8 nm). We monitored the photodynamically-induced death of single bacteria using a fluorescent viability kit in combination with confocal laser scanning microscopy. In addition, the photo-induced inactivation was calculated by CFU (colony forming units) determination. We found 633 nm-induced inactivation (60 mW, 0.12 cm2 exposure area, 1 hour irradiation) of 72% in the case of non-incubated bacteria based on the destructive effect of singlet oxygen produced by red light excited endogenous porphyrins and subsequent energy transfer to molecular oxygen. In order to achieve a nearly complete inactivation within one exposure procedure, the exogenous photosensitizer Methylene Blue (Mb) was added. Far red exposure of Mb-labeled bacteria using a krypton ion laser at 647 nm and 676 nm resulted in 99% inactivation.

Photodynamic therapy toward selective endometrial ablation

NASA Astrophysics Data System (ADS)

Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.

1993-05-01

Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.

Spectral distribution of particle fluence in small field detectors and its implication on small field dosimetry.

PubMed

Benmakhlouf, Hamza; Andreo, Pedro

2017-02-01

Correction factors for the relative dosimetry of narrow megavoltage photon beams have recently been determined in several publications. These corrections are required because of the several small-field effects generally thought to be caused by the lack of lateral charged particle equilibrium (LCPE) in narrow beams. Correction factors for relative dosimetry are ultimately necessary to account for the fluence perturbation caused by the detector. For most small field detectors the perturbation depends on field size, resulting in large correction factors when the field size is decreased. In this work, electron and photon fluence differential in energy will be calculated within the radiation sensitive volume of a number of small field detectors for 6 MV linear accelerator beams. The calculated electron spectra will be used to determine electron fluence perturbation as a function of field size and its implication on small field dosimetry analyzed. Fluence spectra were calculated with the user code PenEasy, based on the PENELOPE Monte Carlo system. The detectors simulated were one liquid ionization chamber, two air ionization chambers, one diamond detector, and six silicon diodes, all manufactured either by PTW or IBA. The spectra were calculated for broad (10 cm × 10 cm) and narrow (0.5 cm × 0.5 cm) photon beams in order to investigate the field size influence on the fluence spectra and its resulting perturbation. The photon fluence spectra were used to analyze the impact of absorption and generation of photons. These will have a direct influence on the electrons generated in the detector radiation sensitive volume. The electron fluence spectra were used to quantify the perturbation effects and their relation to output correction factors. The photon fluence spectra obtained for all detectors were similar to the spectrum in water except for the shielded silicon diodes. The photon fluence in the latter group was strongly influenced, mostly in the low-energy region, by

Photodynamic therapy for periodontal disease

NASA Astrophysics Data System (ADS)

Weersink, Robert A.

2002-05-01

Periodontal disease is a family of chronic inflammatory conditions caused by bacterial infections.' It is manifested in red, swollen gingiva (gums) and can lead to destruction of the connective tissue and bone that hold teeth in place. Conventional treatments typically require some form of invasive surgery, depending on the disease stage at time of detection. Photodynamic Therapy (PDT) is the use of light-activated drugs (photosensitizers) for treatment of a variety of conditions 2 such as solid tumors, pre-malignancies, macular degeneration and actinic keratitis. There have been a number of studies of PDT as an antibacterial agent. 3'4 Depending on the photosensitizer and strain of bacteria, significant killing (several LOGS) can be achieved.

[Photophysical properties and photodynamic activity of nanostructured aluminium phthalocyanines].

PubMed

Udartseva, O O; Lobanov, A V; Andeeva, E R; Dmitrieva, G S; Mel'nikov, M Ia; Buravkova, L B

2014-01-01

We developed water-soluble supramolecular complexes of aluminium phthalocyanine based on mesoporous silica nanoparticles and polyvinylpirrolidone containing rare photoactive nanoaggregates. Radiative lifetimes, extinction coefficients and energy of electronic transitions of isolated and associated metal phthalocyanine complexes were calculated. Nontoxic concentrations of synthesized nanocomposite photosensibilizers were in vitro determined. In present study we compared photodynamic treatment efficacy using different modifications of aluminium phthalocyanine (Photosens®, AlPc-nSiO2 and AlPc-PVP). Mesenchymal stromal cells were used as a model for photodynamic treatment. Intracellular accumulation of aluminium phthalocyanine based on mesoporous silica nanoparticles AlPc-nSiO2 was the most efficient. Illumination of phthalocyanine-loaded cells led to reactive oxygen species generation and subsequent apoptotic cell death. Silica nanoparticles provided a significant decrease of effective phthalocyanine concentration and enhanced cytotoxicity of photodynamic treatment.

Regulation of porphyrin synthesis and photodynamic therapy in heavy metal intoxication.

PubMed

Grinblat, Borislava; Pour, Nir; Malik, Zvi

2006-01-01

Protoporphyrin IX (PpIX) synthesis by malignant cells is successfully exploited for photodynamic therapy (PDT) following administration of 5-aminolevulinic acid (ALA) and light irradiation. The influence of two environmental heavy metal poisons, lead and gallium, on PpIX-synthesis and ALA-PDT was studied in two neu-ronal cell lines, SH-SY5Y neuroblastoma and PC12 pheochromocytoma. The heavy metal intoxication affected two of the heme-synthesis enzymes, ALA-dehydratase (ALAD) and porphobilinogen deaminase (PBGD). The present results show that lead poisoning significantly decreased the PBGD cellular level and inhibited its enzymatic activity, whereas the effects of gallium were less prominent. Although, the protein levels were reduced, the mRNA levels of PBGD remained unchanged during metal intoxication. These findings show additional inhibitory activity of lead on top of its classical effect on ALAD. Proteasome activity was enhanced during lead treatment, as measured by the AMC fluorigenic proteasome assay. The reduction in PBGD levels was not a consequence of PBGD mRNA reduced synthesis, which remained unchanged as shown by RT-PCR analysis. As a result of the lead poisoning, marked alterations in the cell cycle were observed, including a decreased G1 phase and an increased number of S phase cells. The efficacy of ALA-PDT was reduced in correlation with decreased activities of the enzymes during lead intoxication. We may conclude that lead poisoning adversely affects the outcome of ALA photodynamic therapy of cancer.

Photodynamic hyperthermal chemotherapy with indocyanine green: a novel cancer therapy for 16 cases of malignant soft tissue sarcoma

PubMed Central

Onoyama, Masaki; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Minami, Saburo; Azuma, Kazuo; Kawashima, Kazuhiko; Ishi, Hiroshi; Takayama, Takahiro; Ogawa, Nobuhiko

2014-01-01

Sixteen cases of malignant soft tissue sarcoma (STS; 10 canines and six felines) were treated with a novel triple therapy that combined photodynamic therapy, hyperthermia using indocyanine green with a broadband light source, and local chemotherapy after surgical tumor resection. This triple therapy was called photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin was insufficient. In one feline case, PHCT was performed without surgical resection. PHCT was performed over an interval of 1 to 2 weeks and was repeated three to 21 times. No severe side effects, including severe skin burns, necrosis, or skin suture rupture, were observed in any of the animals. No disease recurrence was observed in seven out of 10 (70.0%) dogs and three out of six (50.0%) cats over the follow-up periods ranging from 238 to 1901 days. These results suggest that PHCT decreases the risk of STS recurrence. PHCT should therefore be considered an adjuvant therapy for treating companion animals with STS in veterinary medicine. PMID:24136207

Photodynamic therapy in dentistry: a literature review.

PubMed

Gursoy, Hare; Ozcakir-Tomruk, Ceyda; Tanalp, Jale; Yilmaz, Selçuk

2013-05-01

The purpose of this review was to summarize recent developments regarding photodynamic therapy (PDT) in the field of dentistry. A review of pertinent literature was carried out in PubMED to determine the current position of PDT applications in dentistry. One hundred thirteen relevant articles were retrieved from PubMED by inserting the keywords "photodynamic therapy", "dentistry", "periodontology", "oral surgery", and "endodontics". It is anticipated that this overview will create a specific picture in the practitioner's mind regarding the current status and use of PDT. In spite of different results and suggestions brought about by different researchers, PDT can be considered as a promising and less invasive technique in dentistry. PDT seems to be an effective tool in the treatment of localized and superficial infections. Within the limitations of the present review, it can be concluded that although PDT cannot replace antimicrobial therapy at its current stage, it may be used as an adjunctive tool for facilitating the treatment of oral infections. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry.

Photodynamic Therapy in Treatment of Oral Lichen Planus

PubMed Central

Mostafa, Diana; Tarakji, Bassel

2015-01-01

Oral lichen planus (OLP) is a relatively common chronic immunologic mucocutaneous disorder. Although there are many presenting treatments, some of them proved its failure. Recently, the use of photodynamic therapy (PDT) has been expanding due to its numerous advantages, as it is safe, convenient, and non-invasive and has toxic effect towards selective tissues. This article provides comprehensive review on OLP, its etiology, clinical features and recent non-pharmacological treatments. We also describe the topical PDT and its mechanisms. Our purpose was to evaluate the efficacy of PDT in treatment of OLP through collecting the data of the related clinical studies. We searched in PubMed website for the clinical studies that were reported from 2000 to 2014 using specific keywords: “photodynamic therapy” and “treatment of oral lichen planus”. Inclusion criteria were English publications only were concerned. In the selected studies of photodynamic treatment, adult patients (more than 20 years) were conducted and the OLP lesions were clinically and histologically confirmed. Exclusion criteria were classical and pharmacological treatments of OLP were excluded and also the using of PDT on skin lesions of lichen planus. We established five clinical studies in this review where all of them reported improvement and effectiveness of PDT in treatment of OLP lesions. The main outcome of comparing the related clinical studies is that the photodynamic is considered as a safe, effective and promising treatment modality for OLP. PMID:25883701

Subcellular localization and photodynamic activity of Photodithazine (glucosamine salt of chlorin e6) in murine melanoma B16-F10: an in vitro and in vivo study

NASA Astrophysics Data System (ADS)

Ono, Bruno Andrade; Pires, Layla; Nogueira, Marcelo Saito; Kurachi, Cristina; Pratavieira, Sebastião.

2018-02-01

Photodynamic therapy (PDT) is already a good option for the clinical treatment of several lesions, including mainly nonmelanoma skin cancers. However, cutaneous melanoma treatment remains a challenge when using PDT. One of the reasons for its reduced efficacy is the high pigmentation of melanoma cells. The object of our study is to evaluate the feasibility of the Photodithazine as a photosensitizer for melanoma. Photodithazine is already used in some malignant tumors with satisfactory results and has significant absorption band around 660 nm where the absorption of melanin is low. In this study, we measured the subcellular localization and photodynamic activity of Photodithazine (PDZ) in murine melanoma B16-F10 cell culture. Additionally, a PDT procedure was applied in an animal melanoma model. This first result demonstrates that Photodithazine is more localized at mitochondria in B16F10 cell culture and the cell viability is reduced to less than 90% using 1 µg/mL (PDZ) and 2 J/cm2. We also noticed a rapid PDZ (less than one hour) accumulation in a murine melanoma model. The treatment of melanoma resulted in 20 % more animal survival after one session of PDT compared with the control group. More studies are required to evaluate the cytotoxic effects of Photodithazine at human melanoma.

Fullerene C60 and graphene photosensibiles for photodynamic virus inactivation

NASA Astrophysics Data System (ADS)

Belousova, I.; Hvorostovsky, A.; Kiselev, V.; Zarubaev, V.; Kiselev, O.; Piotrovsky, L.; Anfimov, P.; Krisko, T.; Muraviova, T.; Rylkov, V.; Starodubzev, A.; Sirotkin, A.; Grishkanich, A.; Kudashev, I.; Kancer, A.; Kustikova, M.; Bykovskaya, E.; Mayurova, A.; Stupnikov, A.; Ruzankina, J.; Afanasyev, M.; Lukyanov, N.; Redka, D.; Paklinov, N.

2018-02-01

A solid-phase photosensitizer based on aggregated C60 fullerene and graphene oxide for photodynamic inactivation of pathogens in biological fluids was studied. The most promising technologies of inactivation include the photodynamic effect, which consists in the inactivation of infectious agents by active oxygen forms (including singlet oxygen), formed when light is activated by the photosensitizer introduced into the plasma. Research shows features of solid-phase systems based on graphene and fullerene C60 oxide, which is a combination of an effective inactivating pathogens (for example, influenza viruses) reactive oxygen species formed upon irradiation of the photosensitizer in aqueous and biological fluids, a high photostability fullerene coatings and the possibility of full recovery photosensitizer from the biological environment after the photodynamic action.

Femtosecond laser fluence based nanostructuring of W and Mo in ethanol

NASA Astrophysics Data System (ADS)

Bashir, Shazia; Rafique, Muhammad Shahid; Nathala, Chandra Sekher; Ajami, Ali Asghar; Husinsky, Wolfgang

2017-05-01

The effect of femtosecond laser fluence on nanostructuring of Tungsten (W) and Molybdenum (Mo) has been investigated after ablation in ethanol environment. A Ti: Sapphire laser (800 nm, 30 fs) at fluences ranging from 0.6 to 5.7 J cm-2 was employed to ablate targets. The growth of structures on the surface of irradiated targets is investigated by Field Emission Scanning Electron Microscope (FESEM) analysis. The SEM was performed for both central as well as the peripheral ablated regions. It is observed that both the development and shape of nanoscale features is dependent upon deposited energies to the target surface as well as nature of material. Nanostructures grown on Mo are more distinct and well defined as compared to W. At central ablated areas of W, unorganized Laser Induced Periodic Surface Structures (LIPSS) are grown at low fluences, whereas, nonuniform melting along with cracking is observed at higher fluences. In case of Mo, well-defined and organized LIPSS are observed for low fluences. With increasing fluence, LIPSS become unorganized and broken with an appearance of cracks and are completely vanished with the formation of nanoscale cavities and conical structures. In case of peripheral ablated areas broken and bifurcated LIPSS are grown for all fluences for both materials. The, ablated diameter, ablation depth, ablation rate and the dependence of periodicity of LIPSS on the laser fluence are also estimated for both W and Mo. Parametric instabilities of laser-induced plasma along with generation and scattering of surface plasmons is considered as a possible cause for the formation of LIPSS. For ethanol assisted ablation, the role of bubble cavitation, precipitation, confinement and the convective flow is considered to be responsible for inducing increased hydrodynamic instabilities at the liquid-solid interface.

Photodynamic toxicity of hematoporphyrin derivatives to human keratinocytes in culture.

PubMed

Kappus, H; Reinhold, C; Artuc, M

Human keratinocytes in culture were able to take up hematoporphyrin derivatives (HPDs) used during photodynamic chemotherapy of tumors. In the absence of light, HPDs showed no cytotoxic effects to keratinocytes. However, after irradiation with visible light, HPDs induced immediate cytotoxicity as measured by the neutral red uptake assay. On the other hand, cell attachment as measured by protein estimation was not affected. When the cells treated with HPDs and irradiated with light were cultured for a further 72 h, they partially lost their ability to attach to the collagen surface. Most of the cells remaining attached after 72 h were no longer viable following treatment with HPDs and light. All parameters measured depended on the intracellular concentration of HPDs used (7-50 ng/10(5) cells) and the time of irradiation (0-30 min). These results suggest that human keratinocytes are a good model to study cytotoxic effects of photodynamically active drugs. Further, keratinocytes were unable to recover after damage caused by HPDs and light.

Preparation of a chlorophyll derivative and investigation of its photodynamic activities against cholangiocarcinoma.

PubMed

Wu, Zhong-Ming; Wang, Li; Zhu, Wei; Gao, Ying-Hua; Wu, Hai-Ming; Wang, Mi; Hu, Tai-Shan; Yan, Yi-Jia; Chen, Zhi-Long

2017-08-01

Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma. Published by Elsevier Masson SAS.

Photodynamic inactivation of antigenic determinants of single-stranded DNA bacteriophage phiX174

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, N.C.; Poddar, R.K.

1974-05-01

Bacteriophage phi X174 when photodynamically inactivated (i.e., when rendered unable to produce plaques as a result of exposure to visible light in air in the presence of proflavine) progressively lost their capacity to bind efficiently with homologous antiserum. Such loss of serum-blocking power was evident with heat-inactivated but not with uv-irradiated phage. The ability of the phages to adsorb to host cells, however, remained practically unaltered even after photodynamic inactivation. It thus appears that photodynamic damages in the so-called ''jacket'' component of the phi X174 coat proteins are partly responsible for the loss of plaque-forming ability, whereas the ''spikes'' aremore » either poor antigens or insensitive to photodynamic treatment. (auth)« less

Predictive analysis of photodynamic therapy applied to esophagus cancer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

2008-04-01

The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

PubMed

Li, Jian-Wei; Wu, Zhong-Ming; Magetic, Davor; Zhang, Li-Jun; Chen, Zhi-Long

2015-12-01

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

In vivo light dosimetry for HPPH-mediated pleural PDT

NASA Astrophysics Data System (ADS)

Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Cullighan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

2010-02-01

This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area. The accuracy of treatment delivery is analyzed as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. Patients are administered 4mg per kg body weight HPPH 24-48 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with light therapy with a fluence of 15-60 J/cm2 at 661nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) is monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors are used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 15%. The mean fluence rate delivery and treatment time are recorded. A correlation between the treatment time and the treatment volume is established. The result can be used as a clinical guideline for future pleural PDT treatment.

Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment.

PubMed

Jain, Manish; Zellweger, Matthieu; Frobert, Aurélien; Valentin, Jérémy; van den Bergh, Hubert; Wagnières, Georges; Cook, Stéphane; Giraud, Marie-Noelle

2016-01-01

Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Visudyne® (100, 200, and 500 ng/ml) was perfused for 5-30 min in atherosclerotic aorta isolated from ApoE(-/-) mice. The fluorescence Intensity (FI) after 15 min of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 ± 2.5) to 10 min (FI-23.3 ± 3.0) and 15 min (FI-42.9 ± 3.4) before reaching saturation at 30 min (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm(2), irradiance-334 mW/cm(2)) was applied immediately after Visudyne® perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL; 2.5 ± 1.6, 41.3 ± 15.3, 58.9 ± 6%), mainly plaque macrophages (immunostaining; 0.3 ± 0.2, 37.6 ± 6.4, 45.3 ± 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm(2). Limited apoptosis was observed in the medial wall (0.5 ± 0.2, 8.5 ± 4.7, 15.3 ± 12.7%). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short-time

A retrospective review of pain control by a two-step irradiance schedule during topical ALA-photodynamic therapy of non-melanoma skin cancer.

PubMed

Zeitouni, Nathalie C; Paquette, Anne D; Housel, Joseph P; Shi, Yi; Wilding, Gregory E; Foster, Thomas H; Henderson, Barbara W

2013-02-01

Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here, we present a retrospective review of recent clinical experience in a broad patient population. This was a retrospective review of an existing dermatology database. Fourteen caucasion patients-nine men and five women, ages 18-80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions-were included. ALA was applied to each lesion for approximately 4 hours. Lesions received an initial irradiance of 30-50 mW/cm(2) for 20 J/cm(2) , followed by 150 mW/cm(2) for a total fluence of 200-300 J/cm(2) . Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. Copyright © 2013 Wiley Periodicals, Inc.

A Retrospective Review of Pain Control by a Two-Step Irradiance Schedule During Topical ALA-Photodynamic Therapy of Non-melanoma Skin Cancer

PubMed Central

Zeitouni, Nathalie C.; Paquette, Anne D.; Housel, Joseph P.; Shi, Yi; Wilding, Gregory; Foster, Thomas H.; Henderson, Barbara W.

2013-01-01

Background and Objective Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here we present a retrospective review of recent clinical experience in a broad patient population. Study Design/Materials and Methods This was a retrospective review of an existing dermatology data base. Fourteen caucasion patients - 9 men and 5 women, ages 18 to 80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions – were included. ALA was applied to each lesion for approximately 4h. Lesions received an initial irradiance of 30 - 50 mW/cm2 for 20 J/cm2, followed by 150 mW/cm2 for a total fluence of 200-300 J/cm2. Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Results Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. Conclusions A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. PMID:23390058

Solid-state track recorder dosimetry device to measure absolute reaction rates and neutron fluence as a function of time

DOEpatents

Gold, Raymond; Roberts, James H.

1989-01-01

A solid state track recording type dosimeter is disclosed to measure the time dependence of the absolute fission rates of nuclides or neutron fluence over a period of time. In a primary species an inner recording drum is rotatably contained within an exterior housing drum that defines a series of collimating slit apertures overlying windows defined in the stationary drum through which radiation can enter. Film type solid state track recorders are positioned circumferentially about the surface of the internal recording drum to record such radiation or its secondary products during relative rotation of the two elements. In another species both the recording element and the aperture element assume the configuration of adjacent disks. Based on slit size of apertures and relative rotational velocity of the inner drum, radiation parameters within a test area may be measured as a function of time and spectra deduced therefrom.

Low dose mTHPC photodynamic therapy for cholangiocarcinoma

NASA Astrophysics Data System (ADS)

Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

2013-06-01

Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

Photodynamic inactivation requires innovative approach concerning numerous bacterial isolates and multicomponent sensitizing agents.

PubMed

Nakonieczna, Joanna; Grinholc, Mariusz

2012-12-01

It is known that Staphylococcus aureus is susceptible to photodynamic inactivation in general, but the significant variation among particular strains in the response to the treatment exists. However, factors that determine the observed phenomenon remain unclear. This study was aimed to explore the PDI effect of two sensitizers (protoporphyrin diarginate and toluidine blue O) against clinical as well as reference strains of S. aureus. Obtained results indicate that the same isolate could be characterized as highly resistant or highly sensitive to PDI according to a sensitizer used. Moreover, the same sensitizing agent could be successfully used for total eradication of some isolates and could be non-effective in the case of other strains. Additionally, changing the photosensitizer, we are able to reverse the PDI "resistant" phenotype into "sensitive" one. Thus, one could conclude that photoinactivation involving several sensitizing agents and several isolates of the same bacterial species should be undertaken to make antimicrobial photodynamic inactivation reliable. Copyright © 2012 Elsevier B.V. All rights reserved.

A randomized, split-face clinical trial of low-fluence Q-switched neodymium-doped yttrium aluminum garnet (1,064 nm) laser versus low-fluence Q-switched alexandrite laser (755 nm) for the treatment of facial melasma.

PubMed

Fabi, Sabrina G; Friedmann, Daniel P; Niwa Massaki, Ane B; Goldman, Mitchel P

2014-09-01

Melasma is distressing for patients and challenging for physicians to treat. Clinical data from controlled comparative studies is lacking to support the efficacy, longevity, and safety of laser treatments for melasma. Compare the efficacy and safety of low fluence Q-switched neodymium-doped yttrium aluminum garnet (1,064 nm) laser (Nd:YAG) versus low-fluence Q-switched alexandrite laser (755 nm) (QSAL) for the treatment of facial melasma. Twenty male and female subjects with moderate to severe mixed-type melasma on both sides of the face were randomized to six, weekly treatments with the low-fluence Q-switched Nd:YAG laser on one side and the low-fluence QSAL to the other side. Two independent investigators conducted Modified Melasma Area and Severity Index (MMASI) evaluations and subjects completed self-assessment questionnaires at baseline, after three treatments and each follow-up visit 2, 12, and 24 weeks after the last treatment. Standardized digital photographs were taken at baseline and at each subsequent follow-up visit. One male and fifteen females, mean age of 43.4 (range 32-64) years, completed the 29-week study. Both laser treated sides showed a significant improvement in MMASI evaluations after two treatments (22% improvement on the QS-Nd:YAG, 17% QSAL) and each follow-up visit 2 (36% QS-Nd:YAG; 44% QSAL), 12 (27% QS-Nd:YAG; and 24% QSAL), and 24 weeks (27% QS-Nd:YAG; and 19% QSAL) after the last treatment, but no significant difference was seen between study groups at any visit. There was also no significant difference in subject evaluation of improvement between both treatment sides at any visit. Both laser treated sides were tolerated well, and no serious adverse events were noted. Only one subject was taken out of the study due to development of post-inflammatory hyperpigmentation bilaterally. Both low-fluence Q-switched Nd:YAG and low-fluence QSAL were equally effective at improving moderate to severe mixed-type facial melasma. This was a

Optimizing fluence and debridement effects on cutaneous resurfacing carbon dioxide laser surgery.

PubMed

Weisberg, N K; Kuo, T; Torkian, B; Reinisch, L; Ellis, D L

1998-10-01

To develop methods to compare carbon dioxide (CO2) resurfacing lasers, fluence, and debridement effects on tissue shrinkage and histological thermal denaturation. In vitro human or in vivo porcine skin samples received up to 5 passes with scanner or short-pulsed CO2 resurfacing lasers. Fluences ranging from 2.19 to 17.58 J/cm2 (scanner) and 1.11 to 5.56 J/cm2 (short pulsed) were used to determine each laser's threshold energy for clinical effect. Variable amounts of debridement were also studied. Tissue shrinkage was evaluated by using digital photography to measure linear distance change of the treated tissue. Tissue histological studies were evaluated using quantitative computer image analysis. Fluence-independent in vitro tissue shrinkage was seen with the scanned and short-pulsed lasers above threshold fluence levels of 5.9 and 2.5 J/cm2, respectively. Histologically, fluence-independent thermal depths of damage of 77 microns (scanner) and 25 microns (pulsed) were observed. Aggressive debridement of the tissue increased the shrinkage per pass of the laser, and decreased the fluence required for the threshold effect. In vivo experiments confirmed the in vitro results, although the in vivo threshold fluence level was slightly higher and the shrinkage obtained was slightly lower per pass. Our methods allow comparison of different resurfacing lasers' acute effects. We found equivalent laser tissue effects using lower fluences than those currently accepted clinically. This suggests that the morbidity associated with CO2 laser resurfacing may be minimized by lowering levels of tissue input energy and controlling for tissue debridement.

Effect of high fluence neutron irradiation on transport properties of thermoelectrics

NASA Astrophysics Data System (ADS)

Wang, H.; Leonard, K. J.

2017-07-01

Thermoelectric materials were subjected to high fluence neutron irradiation in order to understand the effect of radiation damage on transport properties. This study is relevant to the NASA Radioisotope Thermoelectric Generator (RTG) program in which thermoelectric elements are exposed to radiation over a long period of time in space missions. Selected n-type and p-type bismuth telluride materials were irradiated at the High Flux Isotope Reactor with a neutron fluence of 1.3 × 1018 n/cm2 (E > 0.1 MeV). The increase in the Seebeck coefficient in the n-type material was partially off-set by an increase in electrical resistivity, making the power factor higher at lower temperatures. For the p-type materials, although the Seebeck coefficient was not affected by irradiation, electrical resistivity decreased slightly. The figure of merit, zT, showed a clear drop in the 300-400 K range for the p-type material and an increase for the n-type material. Considering that the p-type and n-type materials are connected in series in a module, the overall irradiation damages at the device level were limited. These results, at neutron fluences exceeding a typical space mission, are significant to ensure that the radiation damage to thermoelectrics does not affect the performance of RTGs.

Molecular photosensitisers for two-photon photodynamic therapy.

PubMed

Bolze, F; Jenni, S; Sour, A; Heitz, V

2017-11-30

Two-photon excitation has attracted the attention of biologists, especially after the development of two-photon excited microscopy in the nineties. Since then, new applications have rapidly emerged such as the release of biologically active molecules and photodynamic therapy (PDT) using two-photon excitation. PDT, which requires a light-activated drug (photosensitiser), is a clinically approved and minimally invasive treatment for cancer and for non-malignant diseases. This feature article focuses on the engineering of molecular two-photon photosensitisers for PDT, which should bring important benefits to the treatment, increase the treatment penetration depth with near-infrared light excitation, improve the spatial selectivity and reduce the photodamage to healthy tissues. After an overview of the two-photon absorption phenomenon and the methods to evaluate two-photon induced phototoxicity on cell cultures, the different classes of photosensitisers described in the literature are discussed. The two-photon PDT performed with historical one-photon sensitisers are briefly presented, followed by specifically engineered cyclic tetrapyrrole photosensitisers, purely organic photosensitisers and transition metal complexes. Finally, targeted two-photon photosensitisers and theranostic agents that should enhance the selectivity and efficiency of the treatment are discussed.

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy.

PubMed

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P; Alexiou, Christoph; Janko, Christina

2017-06-29

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications.

Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions

NASA Astrophysics Data System (ADS)

Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

2012-02-01

Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 μL/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

Dependence of the phototropic response of Arabidopsis thaliana on fluence rate and wavelength

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konjevic, R.; Steinitz, B.; Poff, K.L.

1989-12-01

In the phototropic response of Arabidopsis thaliana seedlings, the shape of the fluence-response relation depends on fluence rate and wavelength. At low fluence rates, the response to 450-nm light is characterized by a single maximum at about 0.3 {mu}mol{center dot}m{sup {minus}2}. At higher fluence rates, the response shows two distinct maxima, I and II, at 0.3 and 3.5 {mu}mol{center dot}m{sup {minus}2}, respectively. The response to 500-nm light shows a single maximum at 2 {mu}mol{center dot}m{sup {minus}2}, and the response to 510-nm light shows a single maximum at 4.5 {mu}mol{center dot}m{sup {minus}2}, independent of fluence rate. The response to 490-nm lightmore » shows a maximal at 4.5 {mu}mol{center dot}m{sup {minus}2} and a shoulder at about 0.6 {mu}mol{center dot}m{sup {minus}2}. Preirradiation with high-fluence 510-nm light from above, immediately followed by unilateral 450-nm light, eliminates maximum II but not maximum I. Preirradiation with high-fluence 450-nm light from above eliminates the response to subsequent unilateral irradiation with either 450-nm or 510-nm light. The recovery of the response following high-fluence 450-nm light is considerably slower than the recovery following high-fluence 510-nm light. Unilateral irradiation with low-fluence 510-nm light followed by 450-nm light results in curvature that is approximately the sum of those produced by either irradiation alone. Based on these results, it is proposed that phototropism in A. thaliana seedlings is mediated by at least two blue-light photoreceptor pigments.« less

Task-Driven Optimization of Fluence Field and Regularization for Model-Based Iterative Reconstruction in Computed Tomography.

PubMed

Gang, Grace J; Siewerdsen, Jeffrey H; Stayman, J Webster

2017-12-01

This paper presents a joint optimization of dynamic fluence field modulation (FFM) and regularization in quadratic penalized-likelihood reconstruction that maximizes a task-based imaging performance metric. We adopted a task-driven imaging framework for prospective designs of the imaging parameters. A maxi-min objective function was adopted to maximize the minimum detectability index ( ) throughout the image. The optimization algorithm alternates between FFM (represented by low-dimensional basis functions) and local regularization (including the regularization strength and directional penalty weights). The task-driven approach was compared with three FFM strategies commonly proposed for FBP reconstruction (as well as a task-driven TCM strategy) for a discrimination task in an abdomen phantom. The task-driven FFM assigned more fluence to less attenuating anteroposterior views and yielded approximately constant fluence behind the object. The optimal regularization was almost uniform throughout image. Furthermore, the task-driven FFM strategy redistribute fluence across detector elements in order to prescribe more fluence to the more attenuating central region of the phantom. Compared with all strategies, the task-driven FFM strategy not only improved minimum by at least 17.8%, but yielded higher over a large area inside the object. The optimal FFM was highly dependent on the amount of regularization, indicating the importance of a joint optimization. Sample reconstructions of simulated data generally support the performance estimates based on computed . The improvements in detectability show the potential of the task-driven imaging framework to improve imaging performance at a fixed dose, or, equivalently, to provide a similar level of performance at reduced dose.

Photodynamic Antimicrobial Polymers for Infection Control

PubMed Central

McCoy, Colin P.; O’Neil, Edward J.; Cowley, John F.; Carson, Louise; De Baróid, Áine T.; Gdowski, Greg T.; Gorman, Sean P.; Jones, David S.

2014-01-01

Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting. PMID:25250740

In vivo photodynamic inactivation of Psuedomonas aeruginosa in burned skin in rats

NASA Astrophysics Data System (ADS)

Hirao, Akihiro; Sato, Shunichi; Terakawa, Mitsuhiro; Saitoh, Daizoh; Shinomiya, Nariyoshi; Ashida, Hiroshi; Obara, Minoru

2010-02-01

Control of infection in wounds is critically important to avoid transition to sepsis; however, recent rise of drug-resistant bacteria makes it difficult. Thus, antimicrobial photodynamic therapy (APDT) has recently received considerable attention. In this study, we examined methylene blue (MB)-mediated photodynamic inactivation of Psuedomonas aeruginosa in rat burned skin. Two days after infection, the wound surface was contacted with a MB solution at different concentrations, and thereafter the wound was irradiated with cw 665-nm light at a constant power density of 250 mW/cm2 for different time durations. We obtained a two orders of magnitude decrease in the number of bacteria by PDT with a 2-h contact of 0.5-mM MB solution and a illumination of 480 J/cm2, demonstrating the efficacy of PDT against infection with Ps. aeruginosa in burns.

Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds

PubMed Central

Caffarel-Salvador, Ester; Kearney, Mary-Carmel; Mairs, Rachel; Gallo, Luigi; Stewart, Sarah A.; Brady, Aaron J.; Donnelly, Ryan F.

2015-01-01

Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed “photodynamic antimicrobial chemotherapy” (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez® AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1–2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for

Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

NASA Astrophysics Data System (ADS)

Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

2014-11-01

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor-stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor-stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

Influence of monte carlo variance with fluence smoothing in VMAT treatment planning with Monaco TPS.

PubMed

Sarkar, B; Manikandan, A; Nandy, M; Munshi, A; Sayan, P; Sujatha, N

2016-01-01

The study aimed to investigate the interplay between Monte Carlo Variance (MCV) and fluence smoothing factor (FSF) in volumetric modulated arc therapy treatment planning by using a sample set of complex treatment planning cases and a X-ray Voxel Monte Carlo-based treatment planning system equipped with tools to tune fluence smoothness as well as MCV. The dosimetric (dose to tumor volume, and organ at risk) and physical characteristic (treatment time, number of segments, and so on) of a set 45 treatment plans for all combinations of 1%, 3%, 5% MCV and 1, 3, 5 FSF were evaluated for five carcinoma esophagus cases under the study. Increase in FSF reduce the treatment time. Variation of MCV and FSF gives a highest planning target volume (PTV), heart and lung dose variation of 3.6%, 12.8% and 4.3%, respectively. The heart dose variation was highest among all organs at risk. Highest variation of spinal cord dose was 0.6 Gy. Variation of MCV and FSF influences the organ at risk (OAR) doses significantly but not PTV coverage and dose homogeneity. Variation in FSF causes difference in dosimetric and physical parameters for the treatment plans but variation of MCV does not. MCV 3% or less do not improve the plan quality significantly (physical and clinical) compared with MCV greater than 3%. The use of MCV between 3% and 5% gives similar results as 1% with lesser calculation time. Minimally detected differences in plan quality suggest that the optimum FSF can be set between 3 and 5.

A virtual photon energy fluence model for Monte Carlo dose calculation.

PubMed

Fippel, Matthias; Haryanto, Freddy; Dohm, Oliver; Nüsslin, Fridtjof; Kriesen, Stephan

2003-03-01

The presented virtual energy fluence (VEF) model of the patient-independent part of the medical linear accelerator heads, consists of two Gaussian-shaped photon sources and one uniform electron source. The planar photon sources are located close to the bremsstrahlung target (primary source) and to the flattening filter (secondary source), respectively. The electron contamination source is located in the plane defining the lower end of the filter. The standard deviations or widths and the relative weights of each source are free parameters. Five other parameters correct for fluence variations, i.e., the horn or central depression effect. If these parameters and the field widths in the X and Y directions are given, the corresponding energy fluence distribution can be calculated analytically and compared to measured dose distributions in air. This provides a method of fitting the free parameters using the measurements for various square and rectangular fields and a fixed number of monitor units. The next step in generating the whole set of base data is to calculate monoenergetic central axis depth dose distributions in water which are used to derive the energy spectrum by deconvolving the measured depth dose curves. This spectrum is also corrected to take the off-axis softening into account. The VEF model is implemented together with geometry modules for the patient specific part of the treatment head (jaws, multileaf collimator) into the XVMC dose calculation engine. The implementation into other Monte Carlo codes is possible based on the information in this paper. Experiments are performed to verify the model by comparing measured and calculated dose distributions and output factors in water. It is demonstrated that open photon beams of linear accelerators from two different vendors are accurately simulated using the VEF model. The commissioning procedure of the VEF model is clinically feasible because it is based on standard measurements in air and water. It is

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy.

PubMed

Zhang, Xin; Yan, Qi; Mulatihan, Di Naer; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

2018-06-22

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy

NASA Astrophysics Data System (ADS)

Zhang, Xin; Yan, Qi; Naer Mulatihan, Di; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

2018-06-01

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Smart Photosensitizer: Tumor-Triggered Oncotherapy by Self-Assembly Photodynamic Nanodots.

PubMed

Jia, Yuhua; Li, Jinyu; Chen, Jincan; Hu, Ping; Jiang, Longguang; Chen, Xueyuan; Huang, Mingdong; Chen, Zhuo; Xu, Peng

2018-05-09

Clinical photosensitizers suffer from the disadvantages of fast photobleaching and high systemic toxicities because of the off-target photodynamic effects. To address these problems, we report a self-assembled pentalysine-phthalocyanine assembly nanodots (PPAN) fabricated by an amphipathic photosensitizer-peptide conjugate. We triggered the photodynamic therapy effects of photosensitizers by precisely controlling the assembly and disintegration of the nanodots. In physiological aqueous conditions, PPAN exhibited a size-tunable spherical conformation with a highly positive shell of the polypeptides and a hydrophobic core of the π-stacking Pc moieties. The assembly conformation suppressed the fluorescence and the reactive oxygen species generation of the monomeric photosensitizer molecules (mono-Pc) and thus declined the photobleaching and off-target photodynamic effects. However, tumor cells disintegrated PPAN and released the mono-Pc molecules, which exhibited fluorescence for detection and the photodynamic effects for the elimination of the tumor tissues. The molecular dynamics simulations revealed the various assembly configurations of PPAN and illustrated the assembly mechanism. At the cellular level, PPAN exhibited a remarkable phototoxicity to breast cancer cells with the IC 50 values in a low nanomolar range. By using the subcutaneous and orthotopic breast cancer animal models, we also demonstrated the excellent antitumor efficacies of PPAN in vivo.

Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres.

PubMed

Li, Wei; Guo, Xiaomeng; Kong, Fenfen; Zhang, Hanbo; Luo, Lihua; Li, Qingpo; Zhu, Chunqi; Yang, Jie; Du, Yongzhong; You, Jian

2017-07-28

Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Monoglycoconjugated phthalocyanines: effect of sugar and linkage on photodynamic activity.

PubMed

Lafont, Dominique; Zorlu, Yunus; Savoie, Huguette; Albrieux, Florian; Ahsen, Vefa; Boyle, Ross W; Dumoulin, Fabienne

2013-09-01

Click chemistry can be advantageously used to graft carbohydrates on phthalocyanines which are potent photosensitisers, but the effect of the presence of triazole moieties on photodynamic efficiency was not investigated systematically to date. The nature and linkage of the sugar were investigated in order to define structure-activity relationships. Two sets of monoglycoconjugated water-soluble phthalocyanines have been designed and their photodynamic activity and uptake investigated in HT-29 human colon adenocarcinoma cells. Carbohydrates: galactose, mannose or lactose were grafted onto Zn(II) phthalocyanines either by glycosylation or by click reaction. The triazole linkage formed by click conjugation lowered the biological efficiency for mannose and galactose, compared to classical glycosylation grafting. The mannose conjugate formed by glycosylation was the most photodynamically active, without correlation with the photosensitiser cell uptake. Copyright © 2012 Elsevier B.V. All rights reserved.

Preparation, characterization, and cellular studies of photosensitizer-loaded lipid nanoparticles for photodynamic therapy

NASA Astrophysics Data System (ADS)

Navarro, Fabrice P.; Bechet, Denise; Delmas, Thomas; Couleaud, Pierre; Frochot, Céline; Verhille, Marc; Kamarulzaman, Ezatul; Vanderesse, Régis; Boisseau, Patrick; Texier, Isabelle; Gravier, Julien; Vinet, Françoise; Barberi-Heyob, Muriel; Couffin, Anne Claude

2011-02-01

PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for different kinds of cancer. Among various attempts to enhance the therapeutics efficacy of PDT, the specific delivery of the PhotoSensitizer (PS) in the tumor is expected to increase its clinical applications, since unwanted accumulation, especially in the skin, impairs the patients' quality of life (prolonged cutaneous photosensitivity). The aim of this study was to engineer Lipid Nanoparticles (LNP) with different sizes and various PS contents, using simple, solvent-free and easily scale up manufacturing processes. Meso-tetra (hydroxyphenyl) chlorin (mTHPC) is one of the most potent photoactive compounds for clinical use and it has been successfully applied in the treatment of various indications, such as the head and neck, prostate and pancreatic cancers. Here, a derivative of mTHPC was efficiently incorporated into the lipid core of LNP, leading to a large range of stable and reproducible mTHPC-loaded LNP with narrow size distribution. The photophysical and photochemical properties of mTHPC-loaded LNP were studied by measuring absorbance and fluorescence spectra, colloidal stability, particle size and zeta potential, as well as singlet oxygen luminescence. The photocytotoxicity of three selected mTHPC-loaded LNP (25 nm, 45 nm and 95 nm of diameter, respectively) was evaluated on MCF-7 cells, in comparison to free mTHPC, under irradiation at 652 nm with a range of light fluence from 1 to 5 J/cm2. All the physico-chemical, photophysical and biological measurements allow us to conclude that LNP is a promising nano-drug delivery system for PDT.

Photodynamic therapy versus ultrasonic irrigation: interaction with endodontic microbial biofilm, an ex vivo study.

PubMed

Muhammad, Omid H; Chevalier, Marlene; Rocca, Jean-Paul; Brulat-Bouchard, Nathalie; Medioni, Etienne

2014-06-01

Photodynamic therapy was introduced as an adjuvant to conventional chemo-mechanical debridement during endodontic treatment to overcome the persistence of biofilms. The aim of this study was to evaluate the ability of photodynamic therapy (PDT) to disrupt an experimental microbial biofilm inside the root canal in a clinically applicable working time. Thirty extracted teeth were prepared and then divided in three groups. All samples were infected with an artificially formed biofilm made of Enterococcus faecalis, Streptococcus salivarius, Porphyromonas gingivalis and Prevotella intermedia bacteria. First group was treated with Aseptim Plus® photo-activated (LED) disinfection system, second group by a 650 nm Diode Laser and Toluidine blue as photosensitizer, and the third group, as control group, by ultrasonic irrigation (PUI) using EDTA 17% and NaOCl 2.6% solutions. The working time for all three groups was fixed at 3 min. Presence or absence of biofilm was assessed by aerobic and anaerobic cultures. There was no statistically significant difference between results obtained from groups treated by Aseptim Plus® and Diode Laser (P<0.6267). In cultures of both groups there was a maximal bacterial growth. The group that was treated by ultrasonic irrigation and NaOCl and EDTA solutions had the best results (P<0.0001): there was a statistically significant reduction of bacterial load and destruction of microbial biofilm. Under the condition of this study, Photodynamic therapy could not disrupt endodontic artificial microbial biofilm and could not inhibit bacterial growth in a clinically favorable working time. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis of axially disubstituted silicon phthalocyanines and investigation of photodynamic effects on HCT-116 colorectal cancer cell line.

PubMed

Sarı, Ceren; Eyüpoğlu, Figen Celep; Değirmencioğlu, İsmail; Bayrak, Rıza

2018-05-15

Photodynamic therapy is one of the hot topics in cancer studies recently. Basically, photosensitizing chemical substrates which are stimulated by light having a specific wavelength cause fatal effect on different kind of cells in photodynamic therapy. In this study, axially 4-{[(1E)-2-furylmethylene]amino}phenol, 4-{[(1E)-2-thienylmethylene]amino}phenol and 4-{[(1E)-(4-nitro-2-thienyl)methylene]amino}phenol disubstituted silicon phthalocyanines were synthesized as Photosensitizers for photodynamic therapy in cancer treatment for the first time. The structural characterizations of these novel compounds were performed by a combination of FT-IR, 1 H-NMR, UV-vis and mass. All these newly prepared compounds did not show aggregation at the concentration range of 2 × 10 -6 -12 × 10 -6 M in tetrahydrofurane and also did not show aggregation in different organic solvents at 2 × 10 -6 M concentration. Phthalocyanines which are synthesized in this study are tested on HCT-116 colorectal cancer cells and stimulated by light has wavelength of 680 nm. The toxic effects on cancer cells which are caused by different concentrations of photosensitizing molecules have been examined and compared with the toxic effects on cancer cells that were kept in the dark. It is confirmed that these molecules caused toxic effects on colorectal cancer cells when they were stimulated by light but there was no toxic effect in the dark. Copyright © 2018. Published by Elsevier B.V.

Light delivery over extended time periods enhances the effectiveness of photodynamic therapy.

PubMed

Seshadri, Mukund; Bellnier, David A; Vaughan, Lurine A; Spernyak, Joseph A; Mazurchuk, Richard; Foster, Thomas H; Henderson, Barbara W

2008-05-01

The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high-irradiance treatments, recent preclinical and clinical studies have focused on low-irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose, and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model. Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations was evaluated. Magnetic resonance imaging and oxygen tension measurements were done along with the Evans blue exclusion assay to assess vascular response, oxygenation status, and tumor necrosis. In contrast to high-incident laser power (150 mW), low-power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens using treatment times of 120 to 240 min showed marked reduction in signal intensity in T2-weighted magnetic resonance images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared with short-duration (6-11 min) regimens. Significantly greater reductions in pO(2) were observed with extended exposures, which persisted after completion of treatment. These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor, and suggest that duration of light treatment (time) may be an important new treatment variable.

Light Delivery Over Extended Time Periods Enhances the Effectiveness of Photodynamic Therapy

PubMed Central

Seshadri, Mukund; Bellnier, David A.; Vaughan, Lurine A.; Spernyak, Joseph A.; Mazurchuk, Richard; Foster, Thomas H.; Henderson, Barbara W.

2009-01-01

Purpose The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high irradiance treatments, recent preclinical and clinical studies have focused on low irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model. Experimental Design Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations were evaluated. Magnetic resonance imaging (MRI) and oxygen tension measurements were performed along with the Evans blue exclusion assay to assess vascular response, oxygenation status and tumor necrosis. Results In contrast to high incident laser power (150 mW), low power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens utilizing treatment times of 120–240 mins showed marked reduction in signal intensity in T2-weighted MR images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared to short duration (6–11 mins) regimens. Significantly greater reductions in pO2 were observed with extended exposures, which persisted after completion of treatment. Conclusions These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor and suggest that duration of light treatment (time) may be an important new treatment parameter. PMID:18451247

Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets

NASA Astrophysics Data System (ADS)

Liu, Teng; Wang, Chao; Cui, Wei; Gong, Hua; Liang, Chao; Shi, Xiaoze; Li, Zhiwei; Sun, Baoquan; Liu, Zhuang

2014-09-01

Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic

Photodynamic therapy: a review of applications in neurooncology and neuropathology

NASA Astrophysics Data System (ADS)

Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

2015-06-01

Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

Potentiation of antimicrobial photodynamic inactivation by inorganic salts.

PubMed

Hamblin, Michael R

2017-11-01

Antimicrobial photodynamic inactivation (aPDI) involves the use of non-toxic dyes excited with visible light to produce reactive oxygen species (ROS) that can destroy all classes of microorganisms including bacteria, fungi, parasites, and viruses. Selectivity of killing microbes over host mammalian cells allows this approach (antimicrobial photodynamic therapy, aPDT) to be used in vivo as an alternative therapeutic approach for localized infections especially those that are drug-resistant. Areas covered: We have discovered that aPDI can be potentiated (up to 6 logs of extra killing) by the addition of simple inorganic salts. The most powerful and versatile salt is potassium iodide, but potassium bromide, sodium thiocyanate, sodium azide and sodium nitrite also show potentiation. The mechanism of potentiation with iodide is likely to be singlet oxygen addition to iodide to form iodine radicals, hydrogen peroxide and molecular iodine. Another mechanism involves two-electron oxidation of iodide/bromide to form hypohalites. A third mechanism involves a one-electron oxidation of azide anion to form azide radical. Expert commentary: The addition of iodide has been shown to improve the performance of aPDT in several animal models of localized infection. KI is non-toxic and is an approved drug for antifungal therapy, so its transition to clinical use in aPDT should be straightforward.

A supramolecular photosensitizer system based on the host-guest complexation between water-soluble pillar[6]arene and methylene blue for durable photodynamic therapy.

PubMed

Yang, Kui; Wen, Jia; Chao, Shuang; Liu, Jing; Yang, Ke; Pei, Yuxin; Pei, Zhichao

2018-06-05

A supramolecular photosensitizer system WP6-MB was synthesized based on water-soluble pillar[6]arene and the photosensitizer methylene blue (MB) via host-guest interaction. MB can complex with WP6 directly with a high complex constant without further modification. In particular, WP6-MB can reduce the dark toxicity of MB remarkably. Furthermore, it can efficiently overcome photobleaching and extend the time for singlet oxygen production of MB upon light irradiation, which is significant for durable photodynamic therapy.

Novel photosensitisers derived from pyropheophorbide-a: uptake by cells and photodynamic efficiency in vitro.

PubMed

Stamati, Ioanna; Kuimova, Marina K; Lion, Mattia; Yahioglu, Gokhan; Phillips, David; Deonarain, Mahendra P

2010-07-30

Photodynamic Therapy (PDT) is a minimally invasive procedure used for treating a range of neoplastic diseases, which utilises combined action of light and a PDT drug called a photosensitiser. The efficiency of this treatment depends crucially on the properties of the photosensitiser used, namely on its efficient uptake by cells or by the surrounding vasculature, intracellular localisation, minimal dark toxicity and substantial phototoxicity. In this report we compare the spectroscopic properties, cell uptake and in vitro phototoxicity of two novel hydrophilic photosensitisers derived from pyropheophorbide-a (PPa). Both new photosensitisers have the potential to form bioconjugates with antibody fragments for targeted PDT. We find that the photophysical properties of both new photosensitisers are favourable compared to the parent PPa, including enhanced absorption in the red spectral region and substantial singlet oxygen quantum yields. Both molecules show efficient cellular uptake, but display a different intracellular localisation. Both new photosensitisers exhibit no significant dark-toxicity at concentrations of up to 100 microM. The phototoxicity of the two photosensitisers is strikingly different, with one derivative being 13 times more efficient than the parent PPa and another derivative being 18 times less efficient in SKOV3 ovarian cancer cells. We investigate the reasons behind such drastic differences in phototoxicity using confocal fluorescence microscopy and conclude that intracellular localisation is a crucial factor in the photodynamic efficiency of pheophorbide derivatives. These studies highlight the underlying factors behind creating more potent photosensitisers through synthetic manipulation.

Plasma-based beam combiner for very high fluence and energy

DOE PAGES

Kirkwood, R. K.; Turnbull, D. P.; Chapman, T.; ...

2017-10-02

Extreme optical fluences, much beyond the damage threshold of conventional optics, are of interest for a range of high-energy-density physics applications. Nonlinear interactions of multiple beams in plasmas have the potential to produce optics that operate at much higher intensity and fluence than is possible in solids. In inertial confinement fusion experiments indirectly driven with lasers, many beams overlap in the plasma inside a hohlraum, and cross-beam energy transfer by Brillouin scattering has been employed to redistribute energy between laser beams within the target. Here in this paper, we show that in a hot, under-dense plasma the energy of manymore » input beams can be combined into a single well-collimated beam. The emerging beam has an energy of 4 kJ (over 1 ns) that is more than triple that of any incident beam, and a fluence that is more than double. Because the optic produced is plasma, and is diffractive, it is inherently capable of generating higher fluences in a single beam than solid-state refractive or reflective optics.« less

Photodynamic inactivation of multiresistant bacteria (KPC) using zinc(II)phthalocyanines.

PubMed

Miretti, Mariana; Clementi, Romina; Tempesti, Tomas C; Baumgartner, María T

2017-09-15

The worldwide increase in antibiotic resistance has led to search of alternatives anti-microbial therapies such as photodynamic inactivation. The aim of this paper was to evaluate the photodynamic activity in vitro of a neutral and two cationic Zn phthalocyanines. Their photokilling activity was tested on Escherichia coli ATCC 25922 and Klebsiella pneumoniae Carbapenemase (KPC)-producing. After treating bacteria with phthalocyanines, the cultures were irradiated with white light. As a result, the bacteria were inactivated in presence of cationic phthalocyanines. The photoinactivation was dependent of the irradiation time and phthalocyanine concentration. The most effective photosensitizer on KPC-producing was Zinc(II)tetramethyltetrapyridino[2,3-b:2',3'-g:2″,3″-l:2‴,3‴-q]porphyrazinium methylsulfate (ZnTM2,3PyPz). After irradiation using the water soluble ZnTM2,3PyPz (3μM) the viability of KPC (30min of irradiation) and E. coli (10min of irradiation) decreased ≈99.995%. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of high fluence neutron irradiation on transport properties of thermoelectrics

DOE PAGES

Wang, H.; Leonard, K. J.

2017-07-25

Thermoelectric materials were subjected to high fluence neutron irradiation in order to understand the effect of radiation damage on transport properties. This paper is relevant to the NASA Radioisotope Thermoelectric Generator (RTG) program in which thermoelectric elements are exposed to radiation over a long period of time in space missions. Selected n-type and p-type bismuth telluride materials were irradiated at the High Flux Isotope Reactor with a neutron fluence of 1.3 × 10 18 n/cm 2 (E > 0.1 MeV). The increase in the Seebeck coefficient in the n-type material was partially off-set by an increase in electrical resistivity, makingmore » the power factor higher at lower temperatures. For the p-type materials, although the Seebeck coefficient was not affected by irradiation, electrical resistivity decreased slightly. The figure of merit, zT, showed a clear drop in the 300–400 K range for the p-type material and an increase for the n-type material. Considering that the p-type and n-type materials are connected in series in a module, the overall irradiation damages at the device level were limited. Finally, these results, at neutron fluences exceeding a typical space mission, are significant to ensure that the radiation damage to thermoelectrics does not affect the performance of RTGs.« less

Effect of high fluence neutron irradiation on transport properties of thermoelectrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, H.; Leonard, K. J.

Thermoelectric materials were subjected to high fluence neutron irradiation in order to understand the effect of radiation damage on transport properties. This paper is relevant to the NASA Radioisotope Thermoelectric Generator (RTG) program in which thermoelectric elements are exposed to radiation over a long period of time in space missions. Selected n-type and p-type bismuth telluride materials were irradiated at the High Flux Isotope Reactor with a neutron fluence of 1.3 × 10 18 n/cm 2 (E > 0.1 MeV). The increase in the Seebeck coefficient in the n-type material was partially off-set by an increase in electrical resistivity, makingmore » the power factor higher at lower temperatures. For the p-type materials, although the Seebeck coefficient was not affected by irradiation, electrical resistivity decreased slightly. The figure of merit, zT, showed a clear drop in the 300–400 K range for the p-type material and an increase for the n-type material. Considering that the p-type and n-type materials are connected in series in a module, the overall irradiation damages at the device level were limited. Finally, these results, at neutron fluences exceeding a typical space mission, are significant to ensure that the radiation damage to thermoelectrics does not affect the performance of RTGs.« less

Early and Late Onset Side Effects of Photodynamic Therapy

PubMed Central

Borgia, Francesco; Giuffrida, Roberta; Caradonna, Emanuela; Guarneri, Fabrizio; Cannavò, Serafinella P.

2018-01-01

Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations. PMID:29382133

Intraperitoneal photodynamic therapy of the rat CC531 adenocarcinoma.

PubMed Central

Veenhuizen, R. B.; Marijnissen, J. P.; Kenemans, P.; Ruevekamp-Helmers, M. C.; 't Mannetje, L. W.; Helmerhorst, T. J.; Stewart, F. A.

1996-01-01

The goal of this study was to investigate the efficacy of photodynamic therapy (PDT) of a single tumour growing intraperitoneally. For this purpose the CC531 colon carcinoma, implanted in an intraperitoneal fat pad of Wag/RijA rats, was treated with intraperitoneal photodynamic therapy (IPPDT) using Photofrin as the photosensitiser. Two illumination techniques have been compared. An invasive illumination technique using Perspex blocks to illuminate 30 cm2 of the lower abdomen gave a significant delay in tumour growth with 25 J cm-2 applied 1 day after Photofrin. A minimally invasive illumination technique using a balloon catheter to illuminate 14 cm2 resulted in an equivalent growth delay with 75 J cm-2. The route of administration of the photosensitiser did not influence regrowth times of the tumour. Mitomycin C (MMC), a bioreductive agent, was used to exploit the known PDT-induced hypoxia. The combination of IPPDT with MMC resulted in an increased tumoricidal effect. In conclusion, IPPDT led to a significant growth delay for a single tumour implanted intraperitoneally and repetition of the PDT treatment was possible using a minimally invasive illumination technique. Repeated treatments resulted in increased tumour response. PMID:8645584

Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for magnetically amplified photothermal and photodynamic cancer therapy.

PubMed

Bhana, Saheel; Lin, Gan; Wang, Lijia; Starring, Hunter; Mishra, Sanjay R; Liu, Gang; Huang, Xiaohua

2015-06-03

We present the synthesis and application of a new type of dual magnetic and plasmonic nanostructures for magnetic-field-guided drug delivery and combined photothermal and photodynamic cancer therapy. Near-infrared-absorbing gold nanopopcorns containing a self-assembled iron oxide cluster core were prepared via a seed-mediated growth method. The hybrid nanostructures are superparamagnetic and show great photothermal conversion efficiency (η=61%) under near-infrared irradiation. Compact and stable nanocomplexes for photothermal-photodynamic therapy were formed by coating the nanoparticles with near-infrared-absorbing photosensitizer silicon 2,3-naphthalocyannie dihydroxide and stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. The nanocomplex showed enhanced release and cellular uptake of the photosensitizer with the use of a gradient magnetic field. In vitro studies using two different cell lines showed that the dual mode photothermal and photodynamic therapy with the assistance of magnetic-field-guided drug delivery dramatically improved the therapeutic efficacy of cancer cells as compared to the combination treatment without using a magnetic field and the two treatments alone. The "three-in-one" nanocomplex has the potential to carry therapeutic agents deep into a tumor through magnetic manipulation and to completely eradicate tumors by subsequent photothermal and photodynamic therapies without systemic toxicity.

Pulse fluence dependent nanograting inscription on the surface of fused silica

NASA Astrophysics Data System (ADS)

Liang, Feng; Vallée, Réal; Leang Chin, See

2012-06-01

Pulse fluence dependent nanograting inscription on the surface of fused silica is investigated. The nanograting period is found to decrease with the increase of the incident pulse fluence. Local intensity distribution and incubation effect are responsible for the change of the nanograting period.

Induction of chromosomal aberrations at fluences of less than one HZE particle per cell nucleus.

PubMed

Hada, Megumi; Chappell, Lori J; Wang, Minli; George, Kerry A; Cucinotta, Francis A

2014-10-01

The assumption of a linear dose response used to describe the biological effects of high-LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high-energy charged (HZE) nuclei. Human fibroblast and lymphocyte cells were irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with oxygen (77 keV/μm), silicon (99 keV/μm) or Fe (175 keV/μm), Fe (195 keV/μm) or Fe (240 keV/μm) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Nonlinear regression models were used to evaluate possible linear and nonlinear dose-response models based on these data. Dose responses for simple exchanges for human fibroblasts irradiated under confluent culture conditions were best fit by nonlinear models motivated by a nontargeted effect (NTE). The best fits for dose response data for human lymphocytes irradiated in blood tubes were a linear response model for all particles. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low-particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high-LET radiation at the relevant range of low doses.

Photodynamic therapy of cervical intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

The Role of Photodynamic Therapy in the Treatment of Vulvar Intraepithelial Neoplasia

PubMed Central

Tosti, Giulio; Iacobone, Anna Daniela; Preti, Eleonora Petra; Vaccari, Sabina; Barisani, Alessia; Pennacchioli, Elisabetta

2018-01-01

Background: vulvar intraepithelial neoplasia is a non-invasive precursor lesion found in 50–70% of patients affected by vulvar squamous cell carcinoma. In the past, radical surgery was the standard treatment for vulvar intraepithelial neoplasia, however, considering the psychological and physical morbidities related to extensive surgery, several less aggressive treatment modalities have been proposed since the late 1970s. Photodynamic therapy is an effective and safe treatment for cutaneous non-melanoma skin cancer, with favorable cosmetic outcomes. Methods: in the present paper, the results of selected studies on photodynamic therapy in the treatment of vulvar intraepithelial neoplasia are reported and discussed. Results: Overall, complete histological response rates ranged between 20% and 67% and symptom response rates ranged between 52% and 89% according to different studies and case series. Conclusions: the real benefit of photodynamic therapy in the setting of vulvar intraepithelial neoplasia lies in its ability to treat multi-focal disease with minimal tissue destruction, preservation of vulvar anatomy and excellent cosmetic outcomes. These properties explain why photodynamic therapy is an attractive option for vulvar intraepithelial neoplasia treatment. PMID:29393881

Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets of NAND Flash Memory

NASA Technical Reports Server (NTRS)

Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Kim, Hak; Phan, Anthony; Seidleck, Christina; LaBel, Kenneth

2016-01-01

We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found the single-event upset (SEU) cross section varied inversely with fluence. The SEU cross section decreased with increasing fluence. We attribute the effect to the variable upset sensitivities of the memory cells. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, heavy ion irradiation of devices with variable upset sensitivity distribution using typical fluence levels may underestimate the cross section and on-orbit event rate.

Two solar proton fluence models based on ground level enhancement observations

NASA Astrophysics Data System (ADS)

Raukunen, Osku; Vainio, Rami; Tylka, Allan J.; Dietrich, William F.; Jiggens, Piers; Heynderickx, Daniel; Dierckxsens, Mark; Crosby, Norma; Ganse, Urs; Siipola, Robert

2018-01-01

Solar energetic particles (SEPs) constitute an important component of the radiation environment in interplanetary space. Accurate modeling of SEP events is crucial for the mitigation of radiation hazards in spacecraft design. In this study we present two new statistical models of high energy solar proton fluences based on ground level enhancement (GLE) observations during solar cycles 19-24. As the basis of our modeling, we utilize a four parameter double power law function (known as the Band function) fits to integral GLE fluence spectra in rigidity. In the first model, the integral and differential fluences for protons with energies between 10 MeV and 1 GeV are calculated using the fits, and the distributions of the fluences at certain energies are modeled with an exponentially cut-off power law function. In the second model, we use a more advanced methodology: by investigating the distributions and relationships of the spectral fit parameters we find that they can be modeled as two independent and two dependent variables. Therefore, instead of modeling the fluences separately at different energies, we can model the shape of the fluence spectrum. We present examples of modeling results and show that the two methodologies agree well except for a short mission duration (1 year) at low confidence level. We also show that there is a reasonable agreement between our models and three well-known solar proton models (JPL, ESP and SEPEM), despite the differences in both the modeling methodologies and the data used to construct the models.

RELATIVE DISTRIBUTIONS OF FLUENCES OF {sup 3}He AND {sup 4}He IN SOLAR ENERGETIC PARTICLES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrosian, Vahe; Jiang Yanwei; Liu Siming

2009-08-10

Solar energetic particles show a rich variety of spectra and relative abundances of many ionic species and their isotopes. A long-standing puzzle has been the extreme enrichments of {sup 3}He ions. The most extreme enrichments are observed in low-fluence, the so-called impulsive, events which are believed to be produced at the flare site in the solar corona with little scattering and acceleration during transport to the Earth. In such events, {sup 3}He ions show a characteristic concave curved spectra in a log-log plot. In two earlier papers of Liu et al., we showed how such extreme enrichments and spectra canmore » result in the model developed by Petrosian and Liu, where ions are accelerated stochastically by plasma waves or turbulence. In this paper, we address the relative distributions of the fluences of {sup 3}He and {sup 4}He ions presented by Ho et al., which show that while the distribution of {sup 4}He fluence (which we believe is a good measure of the flare strength) like many other extensive characteristics of solar flare is fairly broad, the {sup 3}He fluence is limited to a narrow range. These characteristics introduce a strong anticorrelation between the ratio of the fluences and the {sup 4}He fluence. One of the predictions of our model presented in the 2006 paper was the presence of steep variation of the fluence ratio with the level of turbulence or the rate of acceleration. We show here that this feature of the model can reproduce the observed distribution of the fluences with very few free parameters. The primary reason for the success of the model in both fronts is because fully ionized {sup 3}He ion, with its unique charge-to-mass ratio, can resonantly interact with plasma modes not accessible to {sup 4}He and be accelerated more readily than {sup 4}He. Essentially in most flares, all background {sup 3}He ions are accelerated to few MeV/nucleon range, while this happens for {sup 4}He ions only in very strong events. A much smaller fraction

Retrospective analysis of melasma treatment using a dual mode of low-fluence Q-switched and long-pulse Nd:YAG laser vs. low-fluence Q-switched Nd:YAG laser monotherapy.

PubMed

Choi, Chun Pil; Yim, Seon Mi; Seo, Soo Hong; Ahn, Hyo Hyun; Kye, Young Chul; Choi, Jae Eun

2015-02-01

Despite the effectiveness of low-fluence Q-switched Nd:YAG laser (QSNY) treatment in melasma, adverse events, including mottled hypopigmentation (MH) and rebound hyperpigmentation (RH) have been reported. To compare the effectiveness and safety of combination therapy using low-fluence QSNY and long-pulse Nd:YAG laser (LPNY) (Dual toning), with low-fluence QSNY monotherapy (QS toning), in Asian melasma patients. Patients were treated for 10 sessions at 1-week intervals with QSNY (6 mm spot); 2.5-3.0 J/cm(2) for QS toning (n = 177) or 2.1-2.5 J/cm(2) for dual toning (n = 183). The dual toning group was immediately treated with LPNY (7 mm spot, 15-17 J/cm(2)). The results were evaluated using the modified Melasma Area and Severity Index (mMASI) score and the physician's global assessment. MH or RH were significantly lower (1.1% vs. 14.1%) and the treatment efficacy was improved (median decrease of mMASI, 3.6 vs. 3.0) in the dual toning group compared with the QS toning group. Periorbital melasma showed distinctively high rates of adverse events in the QS toning group (23.9% vs. 5.7%), which were significantly reduced in the dual toning group (2.9%). Dual toning could represent a safe and effective treatment for Asian melasma patients, as it is associated with minimal adverse events and improved treatment efficacy compared with QS toning monotherapy.

Effects of continuous wave and fractionated diode laser on human fibroblast cancer and dermal normal cells by zinc phthalocyanine in photodynamic therapy: A comparative study.

PubMed

Navaeipour, Farzaneh; Afsharan, Hadi; Tajalli, Habib; Mollabashi, Mahmood; Ranjbari, Farideh; Montaseri, Azadeh; Rashidi, Mohammad-Reza

2016-08-01

In this experimental study, cancer and normal cells behavior during an in vitro photodynamic therapy (PDT) under exposure of continuous wave (CW) and fractionated mode of laser with different irradiation power and time intervals was compared and investigated. At the first, human fibroblast cancer cell line (SW 872) and human dermal normal (HFFF2) cell line were incubated with different concentrations of zinc phthalocyanine (ZnPc), as a PDT drug. The cells, then, were irradiated with a 675nm diode laser and the cell viability was evaluated using MTT assay. Under optimized conditions, the viability of the cancer cells was eventually reduced to 3.23% and 13.17%, and that of normal cells was decreased to 20.83% and 36.23% using CW and fractionated diode lasers, respectively. In general, the ratio of ZnPc LD50 values for the normal cells to the cancer cells with CW laser was much higher than that of the fractionated laser. Subsequently, cancer cells in comparison with normal ones were found to be more sensitive toward the photodynamic damage induced by ZnPc. In addition, treatment with CW laser was found to be more effective against the cancer cells with a lower toxicity to the normal cells compared with the fractionated diode laser. Copyright © 2016 Elsevier B.V. All rights reserved.

Individual Members of the Cab Gene Family Differ Widely in Fluence Response.

PubMed Central

White, M. J.; Kaufman, L. S.; Horwitz, B. A.; Briggs, W. R.; Thompson, W. F.

1995-01-01

Chlorophyll a/b-binding protein genes (Cab genes) can be extremely sensitive to light. Transcript accumulation following a red light pulse increases with fluence over 8 orders of magnitude (L.S. Kaufman, W.F. Thompson, W.R. Briggs [1984] Science 226: 1447-1449). We have constructed fluence-response curves for individual Cab genes. At least two Cab genes (Cab-8 and AB96) show a very low fluence response to a single red light pulse. In contrast, two other Cab genes (AB80 and AB66) fail to produce detectable transcript following a single pulse of either red or blue light but are expressed in continuous red light. Thus, very low fluence responses and high irradiance responses occur in the same gene family. PMID:12228352

The Antimicrobial Photodynamic Therapy in the Treatment of Peri-Implantitis

PubMed Central

Libotte, Fabrizio; Sabatini, Silvia; Grassi, Felice Roberto

2016-01-01

Introduction. The aim of this study is to demonstrate the effectiveness of addition of the antimicrobial photodynamic therapy to the conventional approach in the treatment of peri-implantitis. Materials and Methods. Forty patients were randomly assigned to test or control groups. Patients were assessed at baseline and at six (T1), twelve (T2), and twenty-four (T3) weeks recording plaque index (PlI), probing pocket depth (PPD), and bleeding on probing (BOP); control group received conventional periodontal therapy, while test group received photodynamic therapy in addition to it. Result. Test group showed a 70% reduction in the plaque index values and a 60% reduction in PD values compared to the baseline. BOP and suppuration were not detectable. Control group showed a significative reduction in plaque index and PD. Discussion. Laser therapy has some advantages in comparison to traditional therapy, with faster and greater healing of the wound. Conclusion. Test group showed after 24 weeks a better value in terms of PPD, BOP, and PlI, with an average pocket depth value of 2 mm, if compared with control group (3 mm). Our results suggest that antimicrobial photodynamic therapy with diode laser and phenothiazine chloride represents a reliable adjunctive treatment to conventional therapy. Photodynamic therapy should, however, be considered a coadjuvant in the treatment of peri-implantitis associated with mechanical (scaling) and surgical (grafts) treatments. PMID:27429618

Highly efficient photodynamic therapy colloidal system based on chloroaluminum phthalocyanine/pluronic micelles.

PubMed

Py-Daniel, Karen R; Namban, Joy S; de Andrade, Laise R; de Souza, Paulo E N; Paterno, Leonardo G; Azevedo, Ricardo B; Soler, Maria A G

2016-06-01

Phthalocyanine derivatives comprise the second generation of photosensitizer molecules employed in photodynamic therapy (PDT) and have attracted much attention due to their outstanding photosensitizing performance. Most phthalocyanines are hydrophobic compounds that require association to drug delivery systems for clinical use. In this study, formulations of Pluronic F127 micelles incorporated with chloroaluminum phthalocyanine, or else F127/AlClPc, were produced at optimized conditions aiming at efficient and biocompatible PDT colloidal systems. Absorption/emission spectroscopies, as well as dynamic light scattering were performed to evaluate the optimum conditions for the F127 micelle formation and AlClPc incorporation. The micelles formation was attained with F127 concentrations ranging from 50 to 150mgmL(-1). At these conditions, AlClPc photosensitizer molecules were encapsulated into the hydrophobic micelle core and, therefore, readily solubilized in physiological medium (PBS pH 7.2). Encapsulation efficiency of about 90% resulted from different AlClPc concentrations. Identification of singlet oxygen production by irradiated F127/AlClPc formulations indicated good applicability for PDT. In vitro tests conducted with A549 human lung carcinoma cell line incubated with the F127/AlClPc formulations, at different AlClPc loadings, followed by only 18min of light irradiation (660nm LED, fluence of 25.3J/cm(2)), showed a cellular damage as high as 90% for rather low dosages of AlClPc (0.1-5.0μgmL(-1)). Further, no cytotoxicity occurred on non-irradiated cells. These findings suggest those F127/AlClPc formulations are highly promising for PDT applications, since they are easily prepared and the incubation and irradiation times are significantly shortened. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of fluence-to-dose conversion coefficients for deuterons, tritons and helions.

PubMed

Copeland, Kyle; Friedberg, Wallace; Sato, Tatsuhiko; Niita, Koji

2012-02-01

Secondary radiation in aircraft and spacecraft includes deuterons, tritons and helions. Two sets of fluence-to-effective dose conversion coefficients for isotropic exposure to these particles were compared: one used the particle and heavy ion transport code system (PHITS) radiation transport code coupled with the International Commission on Radiological Protection (ICRP) reference phantoms (PHITS-ICRP) and the other the Monte Carlo N-Particle eXtended (MCNPX) radiation transport code coupled with modified BodyBuilder™ phantoms (MCNPX-BB). Also, two sets of fluence-to-effective dose equivalent conversion coefficients calculated using the PHITS-ICRP combination were compared: one used quality factors based on linear energy transfer; the other used quality factors based on lineal energy (y). Finally, PHITS-ICRP effective dose coefficients were compared with PHITS-ICRP effective dose equivalent coefficients. The PHITS-ICRP and MCNPX-BB effective dose coefficients were similar, except at high energies, where MCNPX-BB coefficients were higher. For helions, at most energies effective dose coefficients were much greater than effective dose equivalent coefficients. For deuterons and tritons, coefficients were similar when their radiation weighting factor was set to 2.

Laser fluence dependence on emission dynamics of ultrafast laser induced copper plasma

DOE PAGES

Anoop, K. K.; Harilal, S. S.; Philip, Reji; ...

2016-11-14

The characteristic emission features of a laser-produced plasma strongly depend strongly on the laser fluence. We investigated the spatial and temporal dynamics of neutrals and ions in femtosecond laser (800 nm, ≈ 40 fs, Ti:Sapphire) induced copper plasma in vacuum using both optical emission spectroscopy (OES) and spectrally resolved two-dimensional (2D) imaging methods over a wide fluence range of 0.5 J/cm 2-77.5 J/cm 2. 2D fast gated monochromatic images showed distinct plume splitting between the neutral and ions especially at moderate to higher fluence ranges. OES studies at low to moderate laser fluence regime confirm intense neutral line emission overmore » the ion emission whereas this trend changes at higher laser fluence with dominance of the latter. This evidences a clear change in the physical processes involved in femtosecond laser matter interaction at high input laser intensity. The obtained ion dynamics resulting from the OES, and spectrally resolved 2D imaging are compared with charged particle measurement employing Faraday cup and Langmuir probe and results showed good correlation.« less

Expected neutrino fluence from short Gamma-Ray Burst 170817A and off-axis angle constraints

NASA Astrophysics Data System (ADS)

Biehl, D.; Heinze, J.; Winter, W.

2018-05-01

We compute the expected neutrino fluence from SGRB 170817A, associated with the gravitational wave event GW 170817, directly based on Fermi observations in two scenarios: structured jet and off-axis (observed) top-hat jet. While the expected neutrino fluence for the structured jet case is very small, large off-axis angles imply high radiation densities in the jet, which can enhance the neutrino production efficiency. In the most optimistic allowed scenario, the neutrino fluence can reach only 10-4 of the sensitivity of the neutrino telescopes. We furthermore demonstrate that the fact that gamma-rays can escape limits the baryonic loading (energy in protons versus photons) and the off-axis angle for the internal shock scenario. In particular, for a baryonic loading of 10, the off-axis angle is more strongly constrained by the baryonic loading than by the time delay between the gravitational wave event and the onset of the gamma-ray emission.

Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2016-03-01

Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

Fluence compensated photoacoustic tomography in small animals (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hussain, Altaf; Pool, Martin; Daoudi, Khalid; de Vries, Liesbeth G.; Steenbergen, Wiendelt

2017-03-01

Light fluence inside turbid media can be experimentally mapped by measuring ultrasonically modulated light (Acousto-optics). To demonstrate the feasibility of fluence corrected Photoacoustic (PA) imaging, we have realized a tri-modality (i.e. photoacoustic, acousto-optic and ultrasound) tomographic small animal imaging system. Wherein PA imaging provides high resolution map of absorbed optical energy density, Acousto-optics yields the fluence distribution map in the corresponding PA imaging plane and Ultrasound provides morphological information. Further, normalization of the PA image with the acousto-optically measured fluence map results in an image that directly represents the optical absorption. Human epidermal growth factor receptor 2 (HER2) is commonly found overexpressed in human cancers, among which breast cancers, resulting in a more aggressive tumor phenotype. Identification of HER2-expression is clinically relevant, because cancers overexpressing this marker are amenable to HER2-directed therapies, among which antibodies trastuzumab and pertuzumab. Here, we investigate the feasibility and advantage of acousto-optically assisted fluence compensated PA imaging over PA imaging alone in visualizing and quantifying HER2 expression. For this experiment, nude mice were xenografted with human breast cancer cell lines SKBR3 and BT474 (both HER2 overexpressing), as well as HER2-negative MDA-MB-231. To visualize HER2 expression in these mice, HER2 monoclonal antibody pertuzumab (Perjeta®, Roche), was conjugated to near-infrared dye IRDye 800CW (800CW, LICOR Biosciences) at a ratio of 1∶2 antibody to 800CW. When xenograft tumors measured ≥ 100 mm3, mice received 100 µg 800CW-pertuzumab intravenously. Three days post injection, mice were scanned for fluorescence signal with an IVIS scanner. After fluorescence scans, mice were euthanized and imaged in our PA tomographic imaging system.

Pulmonary decontamination for photodynamic inactivation with extracorporeal illumination

NASA Astrophysics Data System (ADS)

Geralde, Mariana C.; Leite, Ilaiáli S.; Inada, Natalia M.; Grecco, Clóvis; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

Infectious pneumonia is a major cause of morbidity and mortality, despite advances in diagnostics and therapeutics in pulmonary infections. One of the major difficulties associated with the infection comes from the high rate of antibiotic resistant microorganisms, claiming for the use of alternative techniques with high efficiency and low cost. The photodynamic inactivation (PDI) is emerging as one of the great possibilities in this area, once its action is oxidative, not allowing microorganism develops resistance against the treatment. PDI for decontamination pulmonary has potential for treatment or creating better conditions for the action of antibiotics. In this study, we are developing a device to implement PDI for the treatment of lung diseases with extracorporeal illumination. To validate our theory, we performed measurements in liquid phantom to simulate light penetration in biological tissues at various fluency rates, the temperature was monitored in a body of hairless mice and the measurements of light transmittance in this same animal model. A diode laser emitting at 810 nm in continuous mode was used. Our results show 70% of leakage at 0.5 mm of thickness in phantom model. The mouse body temperature variation was 5.4 °C and was observed light transmittance through its chest. These results are suggesting the possible application of the extracorporeal illumination using infrared light source. Based on these findings, further studies about photodynamic inactivation will be performed in animal model using indocyanine green and bacteriochlorin as photosensitizers. The pulmonary infection will be induced with Streptococcus pneumoniae and Klebsiella pneumoniae.

[Screening method for angle closure and angle closure glaucoma using scanning laser polarimeter GDxVCC and photodynamic gonioscopy in a darkened room. One-year outcomes of systematic peripheral iridotomy].

PubMed

Malek-Chehire, N; Renard, G; Dreyfus, J-F; Lebuisson, D A; Pierre-Kahn, V

2013-12-01

Angle closure glaucoma, a recognized major world health issue disproportionately affecting women and Asians, is not often considered in our European populations, normotensive subjects, myopic patients, or subjects with a deep anterior chamber. Early diagnosis is worthwhile, as laser peripheral iridotomy (LPI) is an effective one-step treatment of the causal mechanism. We have performed a retrospective study of patients who underwent an LPI, the indication for which was based on "photodynamic" gonioscopy in a darkened room showing iridotrabecular contact in darkness. Such photodynamic gonioscopy was motivated by the presence of even minute defects in the nerve fiber layer as seen on the GDxVCC or the presence of a Van Herick sign (narrow limbal anterior chamber depth). One hundred and three eyes of 103 patients underwent LPI and a minimum 1-year follow-up (mean follow-up almost 2 years). Mean age was 63.7±11.8 years, and women accounted for 63.1% of cases. The vast majority (78.6%) of patients had neither glaucoma nor ocular hypertension. There were 60.1% hyperopes and 39.9% myopes. Over half (57%) had a deep or a very deep anterior chamber. After LPI, there was immediate deepening of the limbal depth of the anterior chamber in 100% of cases. The aqueous humor that flowed forward was almost always viscous-looking. After 1 year, the IOP was 1.3mm Hg±2.4 lower (P<.001) (t test). All patients who had experienced morning headaches (44% of patients) were relieved of this symptom. GDxVCC after 1 year was clearly improved in 18% of cases, slightly improved in 20%, stable in 50%, slightly worse in 11% of cases, and clearly worse in 1%. Cases treated at an earlier stage had a better improvement in GDxVCC. Our study shows frequent chronic angle closure in our European population even with deep anterior chambers. Absence of a Van Herick sign does not rule out angle closure at night. A photodynamic gonioscopy with the Goldmann three-lens mirror (to avoid unintentional

Virucidal efficacy of treatment with photodynamically activated curcumin on murine norovirus bio-accumulated in oysters.

PubMed

Wu, Juan; Hou, Wei; Cao, Binbin; Zuo, Tao; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

2015-09-01

Norovirus (NoV) is one of the most important seafood- and water-borne viruses, and is a major cause of acute gastroenteritis outbreaks. In the present study we investigated the effect of curcumin as a sensitizer to photodynamic treatment both in buffer and in oysters against murine norovirus 1 (MNV-1), a surrogate of NoV. MNV-1 cultured in buffer and MNV-1 bio-accumulated in oysters were irradiated with a novel LED light source with a wavelength of 470nm and an energy of 3.6J/cm(2). Inactivation of MNV-1 was investigated by plaque assays. After virus was extracted from the gut of oysters treated over a range of curcumin concentrations, the ultrastructural morphology of the virus was observed using electron microscopy, and the integrity of viral nucleic acids and stability of viral capsid proteins were also determined. Results showed that the infectivity of MNV-1 was significantly inhibited by 1-3logPFU/ml, with significant damage to viral nucleic acids in a curcumin dose-dependent manner after photodynamic activation. Virus morphology was altered after the photodynamic treatment with curcumin, presumably due to the change of the viral capsid protein structures. The data suggest that treatment of oysters with photodynamic activation of curcumin is a potentially efficacious and cost-effective method to inactivate food-borne NoV. Further studies are necessary to evaluate the toxicology of this approach in detail and perform sensory evaluation of the treated product. Copyright © 2015 Elsevier B.V. All rights reserved.

Blue laser system for photo-dynamic therapy

NASA Astrophysics Data System (ADS)

Dabu, R.; Carstocea, B.; Blanaru, C.; Pacala, O.; Stratan, A.; Ursu, D.; Stegaru, F.

2007-03-01

A blue laser system for eye diseases (age related macular degeneration, sub-retinal neo-vascularisation in myopia and presumed ocular histoplasmosis syndrome - POHS) photo-dynamic therapy, based on riboflavin as photosensitive substance, has been developed. A CW diode laser at 445 nm wavelength was coupled through an opto-mechanical system to the viewing path of a bio-microscope. The laser beam power in the irradiated area is adjustable between 1 mW and 40 mW, in a spot of 3-5 mm diameter. The irradiation time can be programmed in the range of 1-19 minutes. Currently, the laser system is under clinic tests.

Effect of photodynamic therapy using benzoporphyrin derivative on the cutaneous immune response

NASA Astrophysics Data System (ADS)

Simkin, Guillermo O.; Obochi, Modestus; Hunt, David W. C.; Chan, Agnes H.; Levy, Julia G.

1995-05-01

In this study, the effect of transdermal photodynamic therapy (PDT) using benzoporphyrin derivative monoacid ring A (BPD) on the development of the immunologically mediated contact hypersensitivity (CHS) response against the hapten dinitrofluorobenzene (DNFB) and on the duration of skin allograft acceptance has been evaluated. In the CHS model it was found that the treatment of hairless strain mice with whole-body transdermal PDT using BPD (1 mg/kg) and LED light (15 J/cm2) resulted in a profound suppression of the CHS reaction if treatment was applied either 48 or 24 hours prior or up to 72 hours after sensitization of abdominal skin with DNFB. Less inhibition of the CHS response was observed if PDT was given one day before the ear challenge with DNFB which was applied 5 days following the initial DNFB sensitization. However, DNFB-exposed, PDT-treated mice retained the capacity to respond maximally to the unrelated contact sensitizer oxazolone. These results are consistent with other models of experimentally induced immune tolerance. allogeneic skin graft studies demonstrated that pretreatment of skin with BPD and light, at levels that did not cause significant tissue damage, significantly enhanced the length of engraftment. Using a separate protocol, photodynamic treatment of recipient mice at various times after transplant had no significant effect on allograft acceptance. Irradiation of skin in the presence of BPD may significantly inhibit the initiation of certain immunological responses within these tissues.

Reflectance and fluorescence spectroscopies in photodynamic therapy

NASA Astrophysics Data System (ADS)

Finlay, Jarod C.

In vivo fluorescence spectroscopy during photodynamic therapy (PDT) has the potential to provide information on the distribution and degradation of sensitizers, the formation of fluorescent photoproducts and changes in tissue autofluorescence induced by photodynamic treatment. Reflectance spectroscopy allows quantification of light absorption and scattering in tissue. We present the results of several related studies of fluorescence and reflectance spectroscopy and their applications to photodynamic dosimetry. First, we develop and test an empirical method for the correction of the distortions imposed on fluorescence spectra by absorption and scattering in turbid media. We characterize the irradiance dependence of the in vivo photobleaching of three sensitizers, protoporphyrin IX (PpIX), Photofrin and mTHPC, in a rat skin model. The photobleaching and photoproduct formation of PpIX exhibit irradiance dependence consistent with singlet oxygen (1O2)-mediated bleaching. The bleaching of mTHPC occurs in two phases, only one of which is consistent with a 1O 2-mediated mechanism. Photofrin's bleaching is independent of irradiance, although its photoproduct formation is not. This can be explained by a mixed-mechanism bleaching model. Second, we develop an algorithm for the determination of tissue optical properties using diffuse reflectance spectra measured at a single source-detector separation and demonstrate the recovery of the hemoglobin oxygen dissociation curve from tissue-simulating phantoms containing human erythrocytes. This method is then used to investigate the heterogeneity of oxygenation response in murine tumors induced by carbogen inhalation. We find that while the response varies among animals and within each tumor, the majority of tumors exhibit an increase in blood oxygenation during carbogen breathing. We present a forward-adjoint model of fluorescence propagation that uses the optical property information acquired from reflectance spectroscopy to

Explicit macroscopic singlet oxygen modeling for benzoporphyrin derivative monoacid ring A (BPD)-mediated photodynamic therapy.

PubMed

Kim, Michele M; Penjweini, Rozhin; Liang, Xing; Zhu, Timothy C

2016-11-01

Photodynamic therapy (PDT) is an effective non-ionizing treatment modality that is currently being used for various malignant and non-malignant diseases. In type II PDT with photosensitizers such as benzoporphyrin monoacid ring A (BPD), cell death is based on the creation of singlet oxygen ( 1 O 2 ). With a previously proposed empirical five-parameter macroscopic model, the threshold dose of singlet oxygen ([ 1 O 2 ] rx,sh ]) to cause tissue necrosis in tumors treated with PDT was determined along with a range of the magnitude of the relevant photochemical parameters: the photochemical oxygen consumption rate per light fluence rate and photosensitizer concentration (ξ), the probability ratio of 1 O 2 to react with ground state photosensitizer compared to a cellular target (σ), the ratio of the monomolecular decay rate of the triplet state photosensitizer (β), the low photosensitizer concentration correction factor (δ), and the macroscopic maximum oxygen supply rate (g). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated interstitially with a linear light source at 690nm with total energy released per unit length of 22.5-135J/cm and source power per unit length of 12-150mW/cm to induce different radii of necrosis. A fitting algorithm was developed to determine the photochemical parameters by minimizing the error function involving the range between the calculated reacted singlet oxygen ([ 1 O 2 ] rx ) at necrosis radius and the [ 1 O 2 ] rx,sh . [ 1 O 2 ] rx was calculated based on explicit dosimetry of the light fluence distribution, the tissue optical properties, and the BPD concentration. The initial ground state oxygen concentration ([ 3 O 2 ] 0 ) was set to be 40μM in this study. The photochemical parameters were found to be ξ=(55±40)×10 -3 cm 2 mW -1 s -1 , σ=(1.8±3)×10 -5 μM -1 , and g=1.7±0.7μMs -1 . We have taken the literature values for δ=33μM, and β=11.9μM. [ 1 O 2 ] rx has shown promise to be a more effective

Photodynamic treatment with phenothiazinium photosensitizers kills both ungerminated and germinated microconidia of the pathogenic fungi Fusarium oxysporum, Fusarium moniliforme and Fusarium solani.

PubMed

de Menezes, Henrique Dantas; Tonani, Ludmilla; Bachmann, Luciano; Wainwright, Mark; Braga, Gilberto Úbida Leite; von Zeska Kress, Marcia Regina

2016-11-01

The search for alternatives to control microorganisms is necessary both in clinical and agricultural areas. Antimicrobial photodynamic treatment (APDT) is a promising light-based approach that can be used to control both human and plant pathogenic fungi. In the present study, we evaluated the effects of photodynamic treatment with red light and four phenothiazinium photosensitizers (PS): methylene blue (MB), toluidine blue O (TBO), new methylene blue N (NMBN) and the phenothiazinium derivative S137 on ungerminated and germinated microconidia of Fusarium oxysporum, F. moniliforme, and F. solani. APDT with each PS killed efficiently both the quiescent ungerminated microconidia and metabolically active germinated microconidia of the three Fusarium species. Washing away the unbound PS from the microconidia (both ungerminated and germinated) before red light exposure reduced but did not prevent the effect of APDT. Subcelullar localization of PS in ungerminated and germinated microconidia and the effects of photodynamic treatment on cell membranes were also evaluated in the three Fusarium species. APDT with MB, TBO, NMBN or S137 increased the membrane permeability in microconidia and APDT with NMBN or S137 increased the lipids peroxidation in microconidia of the three Fusarium species. These findings expand the understanding of photodynamic inactivation of filamentous fungi with phenothiazinium PS. Copyright © 2016 Elsevier B.V. All rights reserved.

Photodynamic therapy (PDT) utilizing PhotofrinR for treatment of early esophageal cancer

NASA Astrophysics Data System (ADS)

Overholt, Bergein F.; Panjehpour, Masoud; Teffeteller, Elmeria; Rose, S. Mark

1993-06-01

Four lesions of early carcinoma of the esophagus found during endoscopic biopsies in three patients were treated with photodynamic therapy. Follow-up biopsies over 9 - 24 months remain negative for carcinoma. Endoscopic ultrasonography is essential for proper staging and treatment planning for these patients. Photodynamic therapy may provide an alternative to surgical resection for early esophageal carcinoma or severe dysplasia in Barrett's esophagus.

Photodynamic therapy for actinic cheilitis: a systematic review.

PubMed

Yazdani Abyaneh, Mohammad-Ali; Falto-Aizpurua, Leyre; Griffith, Robert D; Nouri, Keyvan

2015-02-01

Actinic cheilitis (AC) is a premalignant lesion of the lips that can progress to squamous cell carcinoma and metastasize. Actinic cheilitis is difficult to treat because surgical treatments have significant adverse effects whereas less invasive procedures have uncertain efficacy. Photodynamic therapy (PDT) may offer a noninvasive yet effective treatment option for AC. To systematically review the safety and efficacy of PDT for AC. The terms "photodynamic," "actinic," "solar," "cheilitis," and "cheilosis" were used in combinations to search the PubMed database. Studies were considered for inclusion based on eligibility criteria, and specific data were extracted from all studies. The authors identified 15 eligible case series encompassing a total of 242 treated subjects. Among studies that evaluated subjects for complete clinical response, 139 of 223 subjects (62%) showed complete response at final follow-ups ranging from 3 to 30 months. Among studies that evaluated subjects for histological outcome, 57 of 121 subjects (47%) demonstrated histological cure at final follow-ups ranging from 1.5 to 18 months. Cosmetic outcomes were good to excellent in the majority of subjects, and adverse events were well tolerated. Photodynamic therapy is safe and has the potential to clinically and histologically treat AC, with a need for future randomized controlled trials.

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy

PubMed Central

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P.; Alexiou, Christoph; Janko, Christina

2017-01-01

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient’s body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications. PMID:28661430

Fluence inhomogeneities due to a ripple filter induced Moiré effect.

PubMed

Ringbæk, Toke Printz; Brons, Stephan; Naumann, Jakob; Ackermann, Benjamin; Horn, Julian; Latzel, Harald; Scheloske, Stefan; Galonska, Michael; Bassler, Niels; Zink, Klemens; Weber, Uli

2015-02-07

At particle therapy facilities with pencil beam scanning, the implementation of a ripple filter (RiFi) broadens the Bragg peak, so fewer energy steps from the accelerator are required for a homogeneous dose coverage of the planning target volume (PTV). However, sharply focusing the scanned pencil beams at the RiFi plane by ion optical settings can lead to a Moiré effect, causing fluence inhomogeneities at the isocenter. This has been experimentally proven at the Heidelberg Ionenstrahl-Therapiezentrum (HIT), Universitätsklinikum Heidelberg, Germany. 150 MeV u(-1) carbon-12 ions are used for irradiation with a 3 mm thick RiFi. The beam is focused in front of and as close to the RiFi plane as possible. The pencil beam width is estimated to be 0.78 mm at a 93 mm distance from the RiFi. Radiographic films are used to obtain the fluence profile 30 mm in front of the isocenter, 930 mm from the RiFi. The Monte Carlo (MC) code SHIELD-HIT12A is used to determine the RiFi-induced inhomogeneities in the fluence distribution at the isocenter for a similar setup, pencil beam widths at the RiFi plane ranging from σχ(RiFi to 1.2 mm and for scanning step sizes ranging from 1.5 to 3.7 mm. The beam application and monitoring system (BAMS) used at HIT is modelled and simulated. When the width of the pencil beams at the RiFi plane is much smaller than the scanning step size, the resulting inhomogeneous fluence distribution at the RiFi plane interfers with the inhomogeneous RiFi mass distribution and fluence inhomogeneity can be observed at the isocenter as large as an 8% deviation from the mean fluence. The inverse of the fluence ripple period at the isocenter is found to be the difference between the inverse of the RiFi period and the inverse of the scanning step size. We have been able to use MC simulations to reproduce the spacing of the ripple stripes seen in films irradiated at HIT. Our findings clearly indicate that pencil beams sharply focused near the RiFi plane result in

Measurement of trapped proton fluences in main stack of P0006 experiment

NASA Technical Reports Server (NTRS)

Nefedov, N.; Csige, I.; Benton, E. V.; Henke, R. P.; Benton, E. R.; Frigo, L. A.

1995-01-01

We have measured directional distribution and Eastward directed mission fluence of trapped protons at two different energies with plastic nuclear track detectors (CR-39 with DOP) in the main stack of the P0006 experiment on LDEF. Results show arriving directions of trapped protons have very high anisotropy with most protons arriving from the West direction. Selecting these particles we have determined the mission fluence of Eastward directed trapped protons. We found experimental fluences are slightly higher than results of the model calculations of Armstrong and Colborn.

Spectral matching technology for light-emitting diode-based jaundice photodynamic therapy device

NASA Astrophysics Data System (ADS)

Gan, Ru-ting; Guo, Zhen-ning; Lin, Jie-ben

2015-02-01

The objective of this paper is to obtain the spectrum of light-emitting diode (LED)-based jaundice photodynamic therapy device (JPTD), the bilirubin absorption spectrum in vivo was regarded as target spectrum. According to the spectral constructing theory, a simple genetic algorithm as the spectral matching algorithm was first proposed in this study. The optimal combination ratios of LEDs were obtained, and the required LEDs number was then calculated. Meanwhile, the algorithm was compared with the existing spectral matching algorithms. The results show that this algorithm runs faster with higher efficiency, the switching time consumed is 2.06 s, and the fitting spectrum is very similar to the target spectrum with 98.15% matching degree. Thus, blue LED-based JPTD can replace traditional blue fluorescent tube, the spectral matching technology that has been put forward can be applied to the light source spectral matching for jaundice photodynamic therapy and other medical phototherapy.

Equivalent electron fluence for solar proton damage in GaAs shallow junction cells

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Stock, L. V.

1984-01-01

The short-circuit current reduction in GaAs shallow junction heteroface solar cells was calculated according to a simplified solar cell damage model in which the nonuniformity of the damage as a function of penetration depth is treated explicitly. Although the equivalent electron fluence was not uniquely defined for low-energy monoenergetic proton exposure, an equivalent electron fluence is found for proton spectra characteristic of the space environment. The equivalent electron fluence ratio was calculated for a typical large solar flare event for which the proton spectrum is PHI(sub p)(E) = A/E(p/sq. cm) where E is in MeV. The equivalent fluence ratio is a function of the cover glass shield thickness or the corresponding cutoff energy E(sub c). In terms of the cutoff energy, the equivalent 1 MeV electron fluence ratio is r(sub p)(E sub c) = 10(9)/E(sub c)(1.8) where E(sub c) is in units of KeV.

An IR Navigation System for Pleural PDT

NASA Astrophysics Data System (ADS)

Zhu, Timothy; Liang, Xing; Kim, Michele; Finlay, Jarod; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Friedberg, Joseph; Cengel, Keith

2015-03-01

Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

PubMed

Wang, Sheng; Zhang, Lei; Dong, Chunhong; Su, Lin; Wang, Hanjie; Chang, Jin

2015-01-01

A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.

Temperature, illumination, and fluence dependence of current and voltage in electron irradiated solar cells

NASA Technical Reports Server (NTRS)

Faith, T. J.; Obenschain, A. F.

1974-01-01

Empirical equations have been derived from measurements of solar cell photovoltaic characteristics relating light-generated current and open circuit voltage to cell temperature, intensity of illumination and 1-MeV electron fluence. Both 2-ohm-cm and 10-ohm-cm cells were tested over the temperature range from 120 to 470 K, the illumination intensity range from 5 to 1830 mW/sq cm, and the electron fluence range from 1 x 10 to the 13th to 1 x 10 to the 16th electrons/sq cm. The normalized temperature coefficient of the light generated current varies as the 0.18 power of the fluence for temperatures above approximately 273 K and is independent of fluence at lower temperatures. At 140 mW/sq cm, a power law expression was derived which shows that the light-generated current decreases at a rate proportional to the 0.153 power of the fluence for both resistivities. The coefficient of the expression is larger for 2-ohm-cm cells; consequently, the advantage for 10-ohm-cm cells increased with increasing fluence.

Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

NASA Astrophysics Data System (ADS)

Rollakanti, Kishore Reddy

Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

ALA-PDT of the normal rat esophagus: efficiency and safety largely depends on the timing of illumination

NASA Astrophysics Data System (ADS)

van den Boogert, Jolanda; de Bruin, Ron W. F.; van Staveren, Hugo J.; Siersema, Peter D.; van Hillegersberg, Richard

1999-02-01

Photodynamic therapy (PDT) is an experimental treatment modality for (pre)malignant oesophageal lesions. 5- Aminolevulinic acid (ALA)-induced, protoporphyrin IX (PpIX)- mediated photo-sensitization could be very useful as ALA- induced porphrin accumulation selectively occurs in the oesophageal epithelium. The present study aimed to optimize the time between illumination and the administration of ALA. 200 mg/kg ALA was given orally to 24 rats (allocated to 6 groups of 4 animals each). Four animals served as controls and received phosphate buffered saline orally. The animals were illuminated at various time-points (either 1, 2, 3, 4, 6, or 12 hours) after ALA administration. Illumination was performed with a cylindrical diffuser placed in a balloon catheter. The device was originally made for percutaneous transluminal coronary angioplasty and consisted of a semi-flexible catheter and an inflatable cylindric optically clear balloon. The diffuser was placed centrally in the catheter. The same illumination parameters (633 nm, 25 J radiant energy/cm diffuser, power output 100 mW/cm diffuser) were used for each animal. During illumination, fluorescence measurements and light dosimetry were performed. The animals were sacrificed at 48 hours after PDT for histological assessment. Highest PpIX fluorescence was found at 2, 3, and 4 hours after ALA administration. Dosimetric measurements showed a 2 - 3 times higher in vivo fluence rate compared to the estimated fluence rate. Histology at 48 hours after PDT showed diffuse epithelial damage at the laser site only in rats illuminated at 2 hours after ALA administration. Illumination at 3, 4, and 6 hours after ALA administration resulted in diffuse epithelial damage in only one of four rats. In none of the rats illuminated at 1 and 12 hours after administration of ALA epithelial damage was found. These results show that illumination at 2 hours after oral ALA administration provides an efficient and safe scheme for ALA-PDT in the

Comparative study of the bactericidal effects of indocyanine green- and methyl aminolevulinate-based photodynamic therapy on Propionibacterium acnes as a new treatment for acne.

PubMed

Choi, Seung-Hwan; Seo, Jeong-Wan; Kim, Ki-Ho

2018-05-03

Acne vulgaris is one of the most common dermatological problems, and its therapeutic options include topical and systemic retinoids and antibiotics. However, increase in problems associated with acne treatment, such as side-effects from conventional agents and bacterial resistance to antibiotics, has led to greater use of photodynamic therapy. The purpose of this study was to compare the bactericidal effects of indocyanine green- and methyl aminolevulinate-based photodynamic therapy on Propionibacterium acnes. P. acnes were cultured under anaerobic conditions; then they were divided into three groups (control, treated with indocyanine green and treated with methyl aminolevulinate) and illuminated with different lights (630-nm light-emitting diode, 805-nm diode laser and 830-nm light-emitting diode). The bactericidal effects were evaluated by comparing each group's colony-forming units. The cultured P. acnes were killed with an 805-nm diode laser and 830-nm light-emitting diode in the indocyanine green group. No bactericidal effects of methyl aminolevulinate-based photodynamic therapy were identified. The clinical efficacy of indocyanine green-based photodynamic therapy in 21 patients was retrospectively analyzed. The Korean Acne Grading System was used to evaluate treatment efficacy, which was significantly decreased after treatment. The difference in the efficacy of the 805-nm diode laser and 830-nm light-emitting diode was not statistically significant. Although the methyl aminolevulinate-based photodynamic therapy showed no bactericidal effect, the indocyanine green-based photodynamic therapy has bactericidal effect and clinical efficacy. © 2018 Japanese Dermatological Association.

SU-F-T-540: Comprehensive Fluence Delivery Optimization with Multileaf Collimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weppler, S; Villarreal-Barajas, J; Department of Medical Physics, Tom Baker Cancer Center, Calgary, Alberta

2016-06-15

Purpose: Multileaf collimator (MLC) leaf sequencing is performed via commercial black-box implementations, on which a user has limited to no access. We have developed an explicit, generic MLC sequencing model to serve as a tool for future investigations of fluence map optimization, fluence delivery optimization, and rotational collimator delivery methods. Methods: We have developed a novel, comprehensive model to effectively account for a variety of transmission and penumbra effects previously treated on an ad hoc basis in the literature. As the model is capable of quantifying a variety of effects, we utilize the asymmetric leakage intensity across each leaf tomore » deliver fluence maps with pixel size smaller than the narrowest leaf width. Developed using linear programming and mixed integer programming formulations, the model is implemented using state of the art open-source solvers. To demonstrate the versatility of the algorithm, a graphical user interface (GUI) was developed in MATLAB capable of accepting custom leaf specifications and transmission parameters. As a preliminary proof-ofconcept, we have sequenced the leaves of a Varian 120 Leaf Millennium MLC for five prostate cancer patient fields and one head and neck field. Predetermined fluence maps have been processed by data smoothing methods to obtain pixel sizes of 2.5 cm{sup 2}. The quality of output was analyzed using computer simulations. Results: For the prostate fields, an average root mean squared error (RMSE) of 0.82 and gamma (0.5mm/0.5%) of 91.4% were observed compared to RMSE and gamma (0.5mm/0.5%) values of 7.04 and 34.0% when the leakage considerations were omitted. Similar results were observed for the head and neck case. Conclusion: A model to sequence MLC leaves to optimality has been proposed. Future work will involve extensive testing and evaluation of the method on clinical MLCs and comparison with black-box leaf sequencing algorithms currently used by commercial treatment planning

Photodynamics of the small BLUF protein BlrB from Rhodobacter sphaeroides.

PubMed

Zirak, P; Penzkofer, A; Schiereis, T; Hegemann, P; Jung, A; Schlichting, I

2006-06-01

The BLUF protein BlrB from the non-sulphur anoxyphototrophic purple bacterium Rhodobacter sphaeroides is characterized by absorption and emission spectroscopy. BlrB expressed from E. coli binding FAD, FMN, and riboflavin (called BrlB(I)) and recombinant BlrB containing only FAD (called BlrB(II)) are investigated. The dark-adapted proteins exist in two different receptor conformations (receptor states) with different sub-nanosecond fluorescence lifetimes (BLUF(r,f) and BLUF(r,sl)). Some of the flavin-cofactor (ca. 8%) is unbound in thermodynamic equilibrium with the bound cofactor. The two receptor conformations are transformed to putative signalling states (BLUF(s,f) and BLUF(s,sl)) of decreased fluorescence efficiency and shortened fluorescence lifetime by blue-light excitation. In the dark at room temperature both signalling states recover back to the initial receptor states with a time constant of about 2s. Quantum yields of signalling state formation of about 90% for BlrB(II) and about 40% for BlrB(I) were determined by intensity dependent transmission measurements. Extended blue-light excitation causes unbound flavin degradation (formation of lumichrome and lumiflavin-derivatives) and bound cofactor conversion to the semiquinone form. The flavin-semiquinone further reduces and the reduced flavin re-oxidizes back in the dark. A photo-dynamics scheme is presented and relevant quantum efficiencies and time constants are determined.

Photodynamic evaluation of tetracarboxy-phthalocyanines in model systems.

PubMed

Alonso, Lais; Sampaio, Renato N; Souza, Thalita F M; Silva, Rodrigo C; Neto, Newton M Barbosa; Ribeiro, Anderson O; Alonso, Antonio; Gonçalves, Pablo J

2016-08-01

The present work reports the synthesis, photophysical and photochemical characterization and photodynamic evaluation of zinc, aluminum and metal free-base tetracarboxy-phthalocyanines (ZnPc, AlPc and FbPc, respectively). To evaluate the possible application of phthalocyanines as a potential photosensitizer the photophysical and photochemical characterization were performed using aqueous (phosphate-buffered solution, PBS) and organic (dimethyl sulfoxide, DMSO) solvents. The relative lipophilicity of the compounds was estimated by the octanol-water partition coefficient and the photodynamic activity evaluated through the photooxidation of a protein and photohemolysis. The photooxidation rate constants (k) were obtained and the hemolytic potential was evaluated by the maximum percentage of hemolysis achieved (Hmax) and the time (t50) to reach 50% of the Hmax. Although these phthalocyanines are all hydrophilic and possess very low affinity for membranes (log PO/W=-2.0), they led to significant photooxidation of bovine serum albumin (BSA) and photohemolysis. Our results show that ZnPc was the most efficient photosensitizer, followed by AlPc and FbPc; this order is the same as the order of the triplet and singlet oxygen quantum yields (ZnPc>AlPc>FbPc). Furthermore, together, the triplet, fluorescence and singlet oxygen quantum yields of zinc tetracarboxy-phthalocyanines suggest their potential for use in theranostic applications, which simultaneously combines photodiagnosis and phototherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Block copolymer nanoassemblies for photodynamic therapy and diagnosis.

PubMed

Dickerson, Matthew; Bae, Younsoo

2013-11-01

Light can be a powerful therapeutic and diagnostic tool. Light-sensitive molecules can be used to develop locally targeted cancer therapeutics. This approach is known as photodynamic therapy (PDT). Similarly, it is possible to diagnose diseases and track the course of treatment in vivo using ligh-sensitive molecules. This methodology is referred to as photodynamic diagnosis (PDD). Despite the potential, many PDT and PDD agents have imperfect physiochemical properties for their successful clinical application. Nanotechnology may solve these issues by improving the viability of PDT and PDD. This review summarizes the current state of PDT and PDD development, the integration of nanotechnology in the field, and the prospective future applications, demonstrating the potential of PDT and PDD for improved cancer treatment and diagnosis.

In vitro Cellular Uptake and Dimerization of Signal Transducer and Activator of Transcription-3 (STAT3) Identify the Photosensitizing and Imaging-Potential of Isomeric Photosensitizers Derived from Chlorophyll-a and Bacteriochlorophyll-a

PubMed Central

Srivatsan, Avinash; Wang, Yanfang; Joshi, Penny; Sajjad, Munawwar; Chen, Yihui; Liu, Chao; Thankppan, Krishnakumar; Missert, Joseph R.; Tracy, Erin; Morgan, Janet; Rigual, Nestor; Baumann, Heinz; Pandey, Ravindra K.

2011-01-01

Among the photosensitizers investigated, both ring-D and ring-B reduced chlorins containing the m-iodobenzyloxyethyl group at position-3 and a carboxylic acid functionality at position-172 showed highest uptake by tumor cells and light-dependent photo reaction that correlated with maximal tumor-imaging [positron emission tomography (PET) and fluorescence] and long-term photodynamic therapy (PDT) efficacy in BALB/c mice bearing Colon26 tumors. However, among the ring-D reduced compounds, the isomer containing 1′-m-iobenzyloxyethyl group at position-3 was more effective than the corresponding 8-(1′-m-iodobenzyloxyethyl) derivative. All photosensitizers showed maximum uptake by tumor tissue 24h after injection and the tumors exposed with light at low fluence and fluence rates (128 J/cm2, 14 mW/cm2) produced significantly enhanced tumor eradication than those exposed at higher fluence and fluence rate (135 J/cm,2 75mW/cm2). Interestingly, dose-dependent cellular uptake of the compounds and light-dependent STAT3 dimerization have emerged as sensitive rapid indicators for PDT efficacy in vitro and in vivo and could be used as in vitro/in vivo biomarkers for evaluating and optimizing the in vivo treatment parameters of the existing and new PDT candidates. PMID:21842893

Diketopyrrolopyrrole-based carbon dots for photodynamic therapy.

PubMed

He, Haozhe; Zheng, Xiaohua; Liu, Shi; Zheng, Min; Xie, Zhigang; Wang, Yong; Yu, Meng; Shuai, Xintao

2018-06-01

The development of a simple and straightforward strategy to synthesize multifunctional carbon dots for photodynamic therapy (PDT) has been an emerging focus. In this work, diketopyrrolopyrrole-based fluorescent carbon dots (DPP CDs) were designed and synthesized through a facile one-pot hydrothermal method by using diketopyrrolopyrrole (DPP) and chitosan (CTS) as raw materials. DPP CDs not only maintained the ability of DPP to generate singlet oxygen (1O2) but also have excellent hydrophilic properties and outstanding biocompatibility. In vitro and in vivo experiments demonstrated that DPP CDs greatly inhibited the growth of tumor cells under laser irradiation (540 nm). This study highlights the potential of the rational design of CDs for efficient cancer therapy.

A Comparison of Singlet Oxygen Explicit Dosimetry (SOED) and Singlet Oxygen Luminescence Dosimetry (SOLD) for Photofrin-Mediated Photodynamic Therapy

PubMed Central

Kim, Michele M.; Penjweini, Rozhin; Gemmell, Nathan R.; Veilleux, Israel; McCarthy, Aongus; Buller, Gerald S.; Hadfield, Robert H.; Wilson, Brian C.; Zhu, Timothy C.

2016-01-01

Accurate photodynamic therapy (PDT) dosimetry is critical for the use of PDT in the treatment of malignant and nonmalignant localized diseases. A singlet oxygen explicit dosimetry (SOED) model has been developed for in vivo purposes. It involves the measurement of the key components in PDT—light fluence (rate), photosensitizer concentration, and ground-state oxygen concentration ([3O2])—to calculate the amount of reacted singlet oxygen ([1O2]rx), the main cytotoxic component in type II PDT. Experiments were performed in phantoms with the photosensitizer Photofrin and in solution using phosphorescence-based singlet oxygen luminescence dosimetry (SOLD) to validate the SOED model. Oxygen concentration and photosensitizer photobleaching versus time were measured during PDT, along with direct SOLD measurements of singlet oxygen and triplet state lifetime (τΔ and τt), for various photosensitizer concentrations to determine necessary photophysical parameters. SOLD-determined cumulative [1O2]rx was compared to SOED-calculated [1O2]rx for various photosensitizer concentrations to show a clear correlation between the two methods. This illustrates that explicit dosimetry can be used when phosphorescence-based dosimetry is not feasible. Using SOED modeling, we have also shown evidence that SOLD-measured [1O2]rx using a 523 nm pulsed laser can be used to correlate to singlet oxygen generated by a 630 nm laser during a clinical malignant pleural mesothelioma (MPM) PDT protocol by using a conversion formula. PMID:27929427

A Comparison of Singlet Oxygen Explicit Dosimetry (SOED) and Singlet Oxygen Luminescence Dosimetry (SOLD) for Photofrin-Mediated Photodynamic Therapy.

PubMed

Kim, Michele M; Penjweini, Rozhin; Gemmell, Nathan R; Veilleux, Israel; McCarthy, Aongus; Buller, Gerald S; Hadfield, Robert H; Wilson, Brian C; Zhu, Timothy C

2016-12-06

Accurate photodynamic therapy (PDT) dosimetry is critical for the use of PDT in the treatment of malignant and nonmalignant localized diseases. A singlet oxygen explicit dosimetry (SOED) model has been developed for in vivo purposes. It involves the measurement of the key components in PDT-light fluence (rate), photosensitizer concentration, and ground-state oxygen concentration ([³ O ₂])-to calculate the amount of reacted singlet oxygen ([¹ O ₂] rx ), the main cytotoxic component in type II PDT. Experiments were performed in phantoms with the photosensitizer Photofrin and in solution using phosphorescence-based singlet oxygen luminescence dosimetry (SOLD) to validate the SOED model. Oxygen concentration and photosensitizer photobleaching versus time were measured during PDT, along with direct SOLD measurements of singlet oxygen and triplet state lifetime ( τ Δ and τ t ), for various photosensitizer concentrations to determine necessary photophysical parameters. SOLD-determined cumulative [¹ O ₂] rx was compared to SOED-calculated [¹ O ₂] rx for various photosensitizer concentrations to show a clear correlation between the two methods. This illustrates that explicit dosimetry can be used when phosphorescence-based dosimetry is not feasible. Using SOED modeling, we have also shown evidence that SOLD-measured [¹ O ₂] rx using a 523 nm pulsed laser can be used to correlate to singlet oxygen generated by a 630 nm laser during a clinical malignant pleural mesothelioma (MPM) PDT protocol by using a conversion formula.

Photodynamic research at Baylor University Medical Center Dallas, Texas

NASA Astrophysics Data System (ADS)

Gulliya, Kirpal S.; Matthews, James Lester; Sogandares-Bernal, Franklin M.; Aronoff, Billie L.; Judy, Millard M.

1993-03-01

We received our first CO2 laser at Baylor University Medical Center in December 1974, following a trip to Israel in January of that year. Discussion with the customs office of the propriety of charging an 18% import tax lasted for nine months. We lost that argument. Baylor has been using lasers of many types for many procedures since that time. About ten years ago, through the kindness of Tom Dougherty and Roswell Park, we started working with photodynamic therapy, first with hematoporphyrin I and later with dihematoporphyrin ether (II). In February 1984, we were invited to a conference at Los Alamos, New Mexico, U.S.A. on medical applications of the free electron laser as part of the Star Wars Program. A grant application from Baylor was approved that November, but funding did not start for many months. This funding contributed to the development of a new research center as part of Baylor Research Institute. Many of the projects investigated at Baylor dealt with applications of the free electron laser (FEL), after it became available. A staff was assembled and many projects are still ongoing. I would like to outline those which are in some way related to photodynamic therapy.

Attempted photodynamic therapy against patagial squamous cell carcinoma in an African rose-ringed parakeet (Psittacula krameri).

PubMed

Suedmeyer, Wm Kirk; Henry, Carolyn; McCaw, Dudley; Boucher, Magalie

2007-12-01

A 5-yr-old female African rose-ringed parakeet (Psittacula krameri) presented with an ulcerated mass in the medial postpatagial area of the right wing. Biopsy specimens of the mass demonstrated a well-differentiated squamous cell carcinoma. Photodynamic therapy resulted in tumor cell necrosis and initial reduction in tumor burden, but complete remission was not achieved. Based on this and other avian cases, it appears that photodynamic therapy designed to eradicate squamous cell carcinoma in avian species using protocols modeled after canine, feline, and human photodynamic therapy protocols may not be useful. It is hypothesized that differences in light penetration, photosensitizing agent pharmacokinetics, and wound healing properties in avian species necessitate alteration of photodynamic therapy protocols if this treatment modality is to be effective in avian oncology.

Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.

PubMed

Srinivasan, Supriya; Bhardwaj, Vinay; Nagasetti, Abhignyan; Fernandez-Fernandez, Alicia; McGoron, Anthony J

2016-12-01

This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.

One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial.

PubMed

Lulic, Martina; Leiggener Görög, Isabelle; Salvi, Giovanni E; Ramseier, Christoph A; Mattheos, Nikolaos; Lang, Niklaus P

2009-08-01

Single photodynamic therapy (PDT) has been effective in initial periodontal therapy, but only improved bleeding on probing (BoP) in maintenance patients after a single use. Repeated PDT has not been addressed. To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance. Ten maintenance patients with 70 residual pockets [probing pocket depth (PPD)>or=5 mm] were randomly assigned for treatment five times in 2 weeks (Days 0, 1, 2, 7, 14) with PDT (test) or non-activated laser (control) following debridement. The primary outcome variable was PPD, and the secondary variables were clinical attachment level (CAL) and BoP. These were assessed at 3, 6 and 12 months following the interventions. Greater PPD reductions were observed in the test (-0.67 +/- 0.34; p=0.01) compared with the control patients (-0.04 +/- 0.33; NS) after 6 months. Significant CAL gain (+0.52 +/- 0.31; p=0.01) was noted for the test, but not in the control (-0.27 +/- 0.52; NS) patients after 6 months. BoP percentages decreased significantly in test (97-64%, 67%, 77%), but not control patients after 3, 6 and 12 months. Repeated (five times) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients. The effects were best documented after 6 months.

Selective accumulation of PpIX and photodynamic effect after aminolevulinic acid treatment of human adenomyosis xenografts in nude mice.

PubMed

Suzuki-Kakisaka, Haruka; Murakami, Takashi; Hirano, Toru; Terada, Yukihiro; Yaegashi, Nobuo; Okamura, Kunihiro

2008-10-01

To evaluate the effect of photodynamic therapy with aminolevulinic acid (ALA) on human adenomyosis xenografts in a mouse model. Human adenomyosis tissues were implanted SC into nude mice. We measured 5-aminolevulinic acid pharmacokinetics in these mice by analyzing tissue sections 1 to 6 hours after intraperitoneal administration. Twenty-four hours after photodynamic therapy, we evaluated tissue morphologic features. Department of obstetrics and gynecology at a university hospital in Japan. Immunodeficient mice. Tissue grafts were taken from women with adenomyosis attending a university hospital. Photodynamic treatment. Peak fluorescence after intraperitoneal ALA administration and tissue histological changes 24 hours after photodynamic therapy. Peak fluorescence was observed 3 hours after intraperitoneal administration. Histological studies revealed decreased numbers of epithelial and stromal cells in adenomyosis models after therapy. Photodynamic therapy with ALA caused extensive cell death in human adenomyosis tissues implanted into nude mice. Photodynamic treatment using ALA is a potential treatment for patients with adenomyosis uteri.

Laser Fluence Recognition Using Computationally Intelligent Pulsed Photoacoustics Within the Trace Gases Analysis

NASA Astrophysics Data System (ADS)

Lukić, M.; Ćojbašić, Ž.; Rabasović, M. D.; Markushev, D. D.; Todorović, D. M.

2017-11-01

In this paper, the possibilities of computational intelligence applications for trace gas monitoring are discussed. For this, pulsed infrared photoacoustics is used to investigate SF6-Ar mixtures in a multiphoton regime, assisted by artificial neural networks. Feedforward multilayer perceptron networks are applied in order to recognize both the spatial characteristics of the laser beam and the values of laser fluence Φ from the given photoacoustic signal and prevent changes. Neural networks are trained in an offline batch training regime to simultaneously estimate four parameters from theoretical or experimental photoacoustic signals: the laser beam spatial profile R(r), vibrational-to-translational relaxation time τ _{V-T} , distance from the laser beam to the absorption molecules in the photoacoustic cell r* and laser fluence Φ . The results presented in this paper show that neural networks can estimate an unknown laser beam spatial profile and the parameters of photoacoustic signals in real time and with high precision. Real-time operation, high accuracy and the possibility of application for higher intensities of radiation for a wide range of laser fluencies are factors that classify the computational intelligence approach as efficient and powerful for the in situ measurement of atmospheric pollutants.

Photodynamic therapy of diseased bone

NASA Astrophysics Data System (ADS)

Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

2005-08-01

Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support

Homogeneous Photodynamical Analysis of Kepler's Multiply-Transiting Systems

NASA Astrophysics Data System (ADS)

Ragozzine, Darin

To search for planets more like our own, NASA s Kepler Space Telescope ( Kepler ) discovered thousands of exoplanet candidates that cross in front of ( transit ) their parent stars (e.g., Twicken et al. 2016). The Kepler exoplanet data represent an incredible observational leap forward as evidenced by hundreds of papers with thousands of citations. In particular, systems with multiple transiting planets combine the determination of physical properties of exoplanets (e.g., radii), the context provided by the system architecture, and insights from orbital dynamics. Such systems are the most information-rich exoplanetary systems (Ragozzine & Holman 2010). Thanks to Kepler s revolutionary dataset, understanding these Multi-Transiting Systems (MTSs) enables a wide variety of major science questions. In conclusion, existing analyses of MTSs are incomplete and suboptimal and our efficient and timely proposal will provide significant scientific gains ( 100 new mass measurements and 100 updated mass measurements). Furthermore, our homogeneous analysis enables future statistical analyses, including those necessary to characterize the small planet mass-radius relation with implications for understanding the formation, evolution, and habitability of planets. The overarching goal of this proposal is a complete homogeneous investigation of Kepler MTSs to provide detailed measurements (or constraints) on exoplanetary physical and orbital properties. Current investigations do not exploit the full power of the Kepler data; here we propose to use better data (Short Cadence observations), better methods (photodynamical modeling), and a better statistical method (Bayesian Differential Evolution Markov Chain Monte Carlo) in a homogenous analysis of all 700 Kepler MTSs. These techniques are particularly valuable for understanding small terrestrial planets. We propose to extract the near-maximum amount of information from these systems through a series of three research objectives

Endoscopic and Photodynamic Therapy of Cholangiocarcinoma.

PubMed

Meier, Benjamin; Caca, Karel

2016-12-01

Most patients with cholangiocarcinoma (CCA) have unresectable disease. Endoscopic bile duct drainage is one of the major objectives of palliation of obstructive jaundice. Stent implantation using endoscopic retrograde cholangiography is considered to be the standard technique. Unilateral versus bilateral stenting is associated with different advantages and disadvantages; however, a standard approach is still not defined. As there are various kinds of stents, there is an ongoing discussion on which stent to use in which situation. Palliation of obstructive jaundice can be augmented through the use of photodynamic therapy (PDT). Studies have shown a prolonged survival for the combinations of PDT and different stent applications as well as combinations of PDT and additional systemic chemotherapy. More well-designed studies are needed to better evaluate and standardize endoscopic treatment of unresectable CCA.

Control of burn wound sepsis in rats by methylene blue-mediated photodynamic treatment

NASA Astrophysics Data System (ADS)

Hasegawa, Hiroyuki; Sato, Shunichi; Kawauchi, Satoko; Saitoh, Daizoh; Shinomiya, Nariyoshi; Ashida, Hiroshi; Terakawa, Mitsuhiro

2012-02-01

Control of wound sepsis is an important challenge in traumatology. However, increase in the drug-resistant bacteria makes this challenge considerably difficult in recent years. In this study, we attempted to control burn wound sepsis in rats by photodynamic treatment, which has been reported to be effective against some drug-resistant bacteria. A 20% TBSA (total body surface area) full-thickness burn was made in rat dorsal skin, and five days after injury, a suspension of P. aeruginosa was applied to the wound surface. At 30 min after infection, a methylene blue (MB) solution was applied to the wound surface; 5 min afterwards, the wound was illuminated with a 665-nm light emitting diode (LED) array for 10 min. This treatment (application of MB and illumination) was repeated 3 times successively. The averaged light intensity on the wound surface was 3.3 mW/cm2, the corresponding total light dose being 5.9 J/cm2. One week after injury, the numbers of bacteria in the blood and liver were counted by colony forming assay. In the liver, the number of bacteria of the treated group was significantly lower than that of the sham control group without photodynamic treatment. In the blood, no bacteria were detected in the treated group, while a certain amount of bacteria was detected in the control group. These results demonstrate the efficacy of MB-mediated PDT with a red LED array to control burn wound sepsis.

Determination of Ground-Laboratory to In-Space Effective Atomic Oxygen Fluence for DC 93?500 Silicone

NASA Technical Reports Server (NTRS)

deGroh, Kim K.; Banks, Bruce A.; Ma, David

2004-01-01

The objective of this research was to calibrate the ground-to-space effective atomic oxygen fluence for DC 93-500 silicone in a thermal energy electron cyclotron resonance (ECR) oxygen plasma facility. Silicones, commonly used spacecraft materials, do not chemically erode with atomic oxygen attack like other organic materials but form an oxidized hardened silicate surface layer. Therefore, the effective atomic oxygen fluence in a ground test facility should not be determined based on mass loss measurements, as they are with organic polymers. A technique has been developed at the Glenn Research Center to determine the equivalent amount of atomic oxygen exposure in an ECR ground test facility to produce the same degree of atomic oxygen damage as in space. The approach used was to compare changes in the surface hardness of ground test (ECR) exposed DC 93-500 silicone with DC 93-500 exposed to low Earth orbit (LEO) atomic oxygen as part of a shuttle flight experiment. The ground to in-space effective atomic oxygen fluence correlation was determined based on the fluence in the ECR source that produced the same hardness for the fluence in-space. Nanomechanical hardness versus contact depth measurements were obtained for five ECR exposed DC 93-500 samples (ECR exposed for 18 to 40 hrs, corresponding to Kapton effective fluences of 4.2 x 10(exp 20) to 9.4 x 10(exp 20) atoms/sq cm, respectively) and for space exposed DC 93-500 from the Evaluation of Oxygen Interactions with Materials III (EOIM III) shuttle flight experiment, exposed to LEO atomic oxygen for 2.3 x 10(exp 20) atoms/sq cm. Pristine controls were also evaluated. A ground-to-space correlation value was determined based on correlation values for four contact depths (150, 200, 250, and 300 nm), which represent the near surface depth data. The results indicate that the Kapton effective atomic oxygen fluence in the ECR facility needs to be 2.64 times higher than in LEO to replicate equivalent exposure damage in the

PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

PubMed Central

Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

2011-01-01

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154

Design of dual multiple aperture devices for dynamical fluence field modulated CT.

PubMed

Mathews, Aswin John; Tilley, Steven; Gang, Grace; Kawamoto, Satomi; Zbijewski, Wojciech; Siewerdsen, Jeffrey H; Levinson, Reuven; Webster Stayman, J

2016-07-01

A Multiple Aperture Device (MAD) is a novel x-ray beam modulator that uses binary filtration on a fine scale to spatially modulate an x-ray beam. Using two MADs in series enables a large variety of fluence profiles by shifting the MADS relative to each other. This work details the design and control of dual MADs for a specific class of desired fluence patterns. Specifically, models of MAD operation are integrated into a best fit objective followed by CMA-ES optimization. To illustrate this framework we demonstrate the design process for an abdominal phantom with the goal of uniform detected signal. Achievable fluence profiles show good agreement with target fluence profiles, and the ability to flatten projections when a phantom is scanned is demonstrated. Simulated data reconstruction using traditional tube current modulation (TCM) and MAD filtering with TCM are investigated with the dual MAD system demonstrating more uniformity in noise and illustrating the potential for dose reduction under a maximum noise level constraint.

Dye adsorption mechanisms in TiO2 films, and their effects on the photodynamic and photovoltaic properties in dye-sensitized solar cells.

PubMed

Hwang, Kyung-Jun; Shim, Wang-Geun; Kim, Youngjin; Kim, Gunwoo; Choi, Chulmin; Kang, Sang Ook; Cho, Dae Won

2015-09-14

The adsorption mechanism for the N719 dye on a TiO2 electrode was examined by the kinetic and diffusion models (pseudo-first order, pseudo-second order, and intra-particle diffusion models). Among these methods, the observed adsorption kinetics are well-described using the pseudo-second order model. Moreover, the film diffusion process was the main controlling step of adsorption, which was analysed using a diffusion-based model. The photodynamic properties in dye-sensitized solar cells (DSSCs) were investigated using time-resolved transient absorption techniques. The photodynamics of the oxidized N719 species were shown to be dependent on the adsorption time, and also the adsorbed concentration of N719. The photovoltaic parameters (Jsc, Voc, FF and η) of this DSSC were determined in terms of the dye adsorption amounts. The solar cell performance correlates significantly with charge recombination and dye regeneration dynamics, which are also affected by the dye adsorption amounts. Therefore, the photovoltaic performance of this DSSC can be interpreted in terms of the adsorption kinetics and the photodynamics of oxidized N719.

Neutron fluence-to-dose conversion coefficients for embryo and fetus.

PubMed

Chen, Jing; Meyerhof, Dorothy; Vlahovich, Slavica

2004-01-01

A problem of concern in radiation protection is the exposure of pregnant women to ionising radiation, because of the high radiosensitivity of the embryo and fetus. External neutron exposure is of concern when pregnant women travel by aeroplane. Dose assessments for neutrons frequently rely on fluence-to-dose conversion coefficients. While neutron fluence-to-dose conversion coefficients for adults are recommended in International Commission on Radiological Protection publications and International Commission on Radiological Units and Measurements reports, conversion coefficients for embryos and fetuses are not given in the publications. This study undertakes Monte Carlo calculations to determine the mean absorbed doses to the embryo and fetus when the mother is exposed to neutron fields. A new set of mathematical models for the embryo and fetus has been developed at Health Canada and is used together with mathematical phantoms of a pregnant female developed at Oak Ridge National Laboratory. Monoenergetic neutrons from 1 eV to 10 MeV are considered in this study. The irradiation geometries include antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT) and isotropic (ISO) geometries. At each of these standard irradiation geometries, absorbed doses to the fetal brain and body are calculated; for the embryo at 8 weeks and the fetus at 3, 6 or 9 months. Neutron fluence-to-absorbed dose conversion coefficients are derived for the four age groups. Neutron fluence-to-equivalent dose conversion coefficients are given for the AP irradiations which yield the highest radiation dose to the fetal body in the neutron energy range considered here. The results indicate that for neutrons <10 MeV more protection should be given to pregnant women in the first trimester due to the higher absorbed dose per unit neutron fluence to the fetus.

In-situ second harmonic generation by cancer cell targeting ZnO nanocrystals to effect photodynamic action in subcellular space.

PubMed

Gu, Bobo; Pliss, Artem; Kuzmin, Andrey N; Baev, Alexander; Ohulchanskyy, Tymish Y; Damasco, Jossana A; Yong, Ken-Tye; Wen, Shuangchun; Prasad, Paras N

2016-10-01

This paper introduces the concept of in-situ upconversion of deep penetrating near infrared light via second harmonic generation from ZnO nanocrystals delivered into cells to effect photo activated therapies, such as photodynamic therapy, which usually require activation by visible light with limited penetration through biological tissues. We demonstrated this concept by subcellular activation of a photodynamic therapy drug, Chlorin e6, excited within its strong absorption Soret band by the second harmonic (SH) light, generated at 409 nm by ZnO nanocrystals, which were targeted to cancer cells and internalized through the folate-receptor mediated endocytosis. By a combination of theoretical modeling and experimental measurements, we show that SH light, generated in-situ by ZnO nanocrystals significantly contributes to activation of photosensitizer, leading to cell death through both apoptotic and necrotic pathways initiated in the cytoplasm. This targeted photodynamic action was studied using label-free Coherent Anti-Stokes Raman Scattering imaging of the treated cells to monitor changes in the distribution of native cellular proteins and lipids. We found that initiation of photodynamic therapy with upconverted light led to global reduction in the intracellular concentration of macromolecules, likely due to suppression of proteins and lipids synthesis, which could be considered as a real-time indicator of cellular damage from photodynamic treatment. In prospective applications this in-situ photon upconversion could be further extended using ZnO nanocrystals surface functionalized with a specific organelle targeting group, provided a powerful approach to identify and consequently maximize a cellular response to phototherapy, selectively initiated in a specific cellular organelle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Photodynamic therapy for Barrett's esophagus using a 20-mm diameter light-delivery balloon

NASA Astrophysics Data System (ADS)

Panjehpour, Masoud; Overholt, Bergein F.; Phan, Mary N.; Haydek, John M.; Robinson, Amy R.

2002-06-01

Background and Objective: Patients with high grade dysplasia (HGD) in Barrett's esophagus are at a high risk for developing esophageal adenocarcinoma. Esophagectomy is the standard treatment for such patients. The objective of this study was to evaluate the safety and efficacy of photodynamic therapy (PDT) using an improved light delivery balloon for ablation of Barrett's esophagus with high grade dysplasia and/or early cancer. Materials and Methods: 20 patients with HGD or early cancer (19 with HGD, 1 with T1 cancer) received 2 mg/kg of porfimer sodium, intravenously. Two to three days after the injection, laser light was delivered using a cylindrical diffuser inserted inside a 20-mm diameter reflective esophageal PDT balloon. Initially, the balloon was inflated to a pressure of 80 mm Hg. The balloon pressure was gradually reduced to 30 mm Hg. A KTP/dye laser at 630 nm was used as the light source. Light dose of 115 J/cm was delivered at an intensity of 270 mw/cm. Nodules were pre- treated with an extra 50 J/cm using a short diffuser inserted through the scope. Patients were maintained on PPI therapy to keep the gastric pH higher than 4. Eighteen patients required one treatment, while two patients were treated twice. Follow-up consisted of endoscopy with four quadrant biopsies at every 2 cm of the treated area. Thermal ablation was used to treat small residual islands on the follow-ups. The follow-up endoscopies ranged from 6 to 17 months. Results: On follow-up endoscopy, 12 patients had complete replacement of their Barrett's mucosa with neosquamous mucosa. Five patients had residual non-dysplastic Barrett's mucosa, one had indefinite dysplasia, two had low grad dysplasia. There were no residual HGD or cancers. The average length of Barrett's was reduced from 5.4 cm to 1.2 cm. High balloon pressure resulted in wide variation in PDT response among patients. Lower balloon pressures resulted in more consistent destruction of Barrett's mucosa among patients. Five

Photodynamic therapy for polypoidal choroidal vasculopathy secondary to choroidal nevus.

PubMed

Wong, James G; Lai, Xin Jie; Sarafian, Richard Y; Wong, Hon Seng; Smith, Jeremy B

2017-01-01

We report a case of a Caucasian female who developed active polypoidal choroidal vasculopathy (PCV) at the edge of a stable choroidal nevus and was successfully treated with verteporfin photodynamic therapy. No active polyp was detectable on indocyanine green angiography 2 years after treatment, and good vision was maintained. Indocyanine green angiography is a useful investigation to diagnose PCV and may be underutilized. Unlike treatment of choroidal neovascularization secondary to choroidal nevus, management of PCV secondary to nevus may not require intravitreal anti-vascular endothelial growth factor therapy. Photodynamic monotherapy may be an effective treatment of secondary PCV.

Photodynamic treatment of herpes simplex virus during its replicative cycle.

PubMed Central

Khan, N C; Melnick, J L; Biswal, N

1977-01-01

Photodynamic treatment of herpes simplex virus type 1-infected hamster embryo fibroblasts (LSH strain) with a low concentration of proflavine (0.08 mug/10(5) cells per ml), a 3-9-diamine acridine dye, inhibited production not only of infectious progeny but also of virion particles. However, there was no appreciable inhibition of viral or cellular DNA synthesis, even when the infected cells were repeatedly exposed to this low concentration of dye and light during the replication cycle of the virus. It thus appears that photodynamic treatment of infected cells interferes with the processes involved in virus maturation. PMID:189063

Drug Carrier for Photodynamic Cancer Therapy

PubMed Central

Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

2015-01-01

Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

NASA Technical Reports Server (NTRS)

Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

2014-01-01

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

Acidity-Triggered Tumor Retention/Internalization of Chimeric Peptide for Enhanced Photodynamic Therapy and Real-Time Monitoring of Therapeutic Effects.

PubMed

Han, Kai; Zhang, Wei-Yun; Ma, Zhao-Yu; Wang, Shi-Bo; Xu, Lu-Ming; Liu, Jia; Zhang, Xian-Zheng; Han, He-You

2017-05-17

Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated PDT systems with improved tumor accumulation/internalization and timely therapeutic feedback. Here, we report a tumor-acidity-responsive chimeric peptide for enhanced PDT and noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies revealed that a tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate anions in chimeric peptide, which led to increased ζ potential, improved hydrophobicity, controlled size enlargement, and precise morphology switching from sphere to spherocylinder shape of the chimeric peptide. All of these factors realized superfast accumulation and prolonged retention in the tumor region, selective cellular internalization, and enhanced PDT against the tumor. Meanwhile, this chimeric peptide could further generate reactive oxygen species and initiate cell apoptosis during PDT. The subsequent formation of caspase-3 enzyme hydrolyzed the chimeric peptide, achieving a high signal/noise ratio and timely fluorescence feedback. Importantly, direct utilization of the acidity responsiveness of a biofunctional Asp-Glu-Val-Asp-Gly (DEVDG, caspase-3 enzyme substrate) peptide sequence dramatically simplified the preparation and increased the performance of the chimeric peptide furthest.

Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with CuII as the Active Center.

PubMed

Zhang, Wei; Lu, Jun; Gao, Xiaonan; Li, Ping; Zhang, Wen; Ma, Yu; Wang, Hui; Tang, Bo

2018-02-16

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano-metal-organic framework (Cu II -metalated nano-MOF {CuL-[AlOH] 2 } n (MOF-2, H 6 L=mesotetrakis(4-carboxylphenyl)porphyrin)) based on Cu II as the active center for PDT. This MOF-2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF-2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF-2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF-2 as a promising new PDT candidate and anticancer drug. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immune Response Following Photodynamic Therapy For Bladder Cancer

NASA Astrophysics Data System (ADS)

Raymond K.

1989-06-01

This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

Study of tissue oxygen supply rate in a macroscopic photodynamic therapy singlet oxygen model

NASA Astrophysics Data System (ADS)

Zhu, Timothy C.; Liu, Baochang; Penjweini, Rozhin

2015-03-01

An appropriate expression for the oxygen supply rate (Γs) is required for the macroscopic modeling of the complex mechanisms of photodynamic therapy (PDT). It is unrealistic to model the actual heterogeneous tumor microvascular networks coupled with the PDT processes because of the large computational requirement. In this study, a theoretical microscopic model based on uniformly distributed Krogh cylinders is used to calculate Γs=g (1-[O]/[]0) that can replace the complex modeling of blood vasculature while maintaining a reasonable resemblance to reality; g is the maximum oxygen supply rate and [O]/[]0 is the volume-average tissue oxygen concentration normalized to its value prior to PDT. The model incorporates kinetic equations of oxygen diffusion and convection within capillaries and oxygen saturation from oxyhemoglobin. Oxygen supply to the tissue is via diffusion from the uniformly distributed blood vessels. Oxygen can also diffuse along the radius and the longitudinal axis of the cylinder within tissue. The relations of Γs to [3O2]/] are examined for a biologically reasonable range of the physiological parameters for the microvasculature and several light fluence rates (ϕ). The results show a linear relationship between Γs and [3O2]/], independent of ϕ and photochemical parameters; the obtained g ranges from 0.4 to 1390 μM/s.

Efficacy of antimicrobial photodynamic therapy in the disinfection of acrylic denture surfaces: A systematic review.

PubMed

Varela Kellesarian, Sergio; Abduljabbar, Tariq; Vohra, Fahim; Malmstrom, Hans; Yunker, Michael; Varela Kellesarian, Tammy; Romanos, Georgios E; Javed, Fawad

2017-03-01

The aim of the present systematic review was to assess the efficacy of antimicrobial photodynamic therapy (aPDT) in the disinfection of acrylic denture surfaces. IN order to address the focused question: "Is aPDT more effective in decontaminating denture surfaces compared with traditional denture-disinfection techniques?" an electronic search without time or language restrictions was conducted up to November 2016 in indexed databases using different key words. The exclusion criteria included qualitative and/or quantitative reviews, case reports, case series, commentaries, letters to the editor, interviews, and updates. A total of 14 studies were included and processed for data extraction, out of which 1 study was a randomized clinical trial and 13 studies were performed in vitro. Results from 12 experimental studies reported that aPDT was effective in reducing bacteria and/or yeast cultured in single or multispecies biofilm growth on acrylic resin specimens. One experimental study reported selective microorganism reduction on acrylic resin after aPDT. One clinical randomized control trial reported that aPDT presented similar microorganism reduction compared with oral antifungal medication for the disinfection of denture surfaces. The role of aPDT in the disinfection of acrylic resin surfaces is unclear. From a clinical perspective further randomized control trials are needed to assess the efficacy of aPDT in the disinfection of acrylic resin surfaces. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature, illumination and fluence dependence of current and voltage in electron irradiated solar cells

NASA Technical Reports Server (NTRS)

Obenschain, A. F.; Faith, T. J.

1973-01-01

Emperical equations have been derived from measurements of solar cell photovoltaic characteristics relating light generated current, IL, and open circuit voltage, VO, to cell temperature, T, intensity of illumination, W, and 1 Mev electron fluence, phi both 2 ohm-cm and 10 ohm-cm cells were tested. The temperature dependency of IL is similar for both resistivities at 140mw/sq cm; at high temperature the coefficient varies with fluence as phi 0.18, while at low temperatures the coefficient is relatively independent of fluence. Fluence dependent degration causes a decrease in IL at a rate proportional to phi 0.153 for both resistivities. At all intensities other than 560 mw/sq cm, a linear dependence of IL on illumination was found. The temperature coefficient of voltage was, to a good approximation, independent of both temperature and illumination for both resistivities. Illumination dependence of VOC was logarithmic, while the decrease with fluence of VOC varied as phi 0.25 for both resistivities.

Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells

PubMed Central

Lee, Ming-Jen; Hung, Shih-Hsuan; Huang, Mu-Ching; Tsai, Tsuimin

2017-01-01

Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous disorders. Some NF1 patients develop benign large plexiform neurofibroma(s) at birth, which can then transform into a malignant peripheral nerve sheath tumor (MPNST). There is no curative treatment for this rapidly progressive and easily metastatic neurofibrosarcoma. Photodynamic therapy (PDT) has been developed as an anti-cancer treatment, and 5-aminolevulinic (ALA) mediated PDT (ALA-PDT) has been used to treat cutaneous skin and oral neoplasms. Doxycycline, a tetracycline derivative, can substantially reduce the tumor burden in human and animal models, in addition to its antimicrobial effects. The purpose of this study was to evaluate the effect and to investigate the mechanism of action of combined doxycycline and ALA-PDT treatment of MPNST cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the combination of ALA-PDT and doxycycline significantly reduce MPNST survival rate, compared to cells treated with each therapy alone. Isobologram analysis showed that the combined treatment had a synergistic effect. The increased cytotoxic activity could be seen by an increase in cellular protoporphyrin IX (PpIX) accumulation. Furthermore, we found that the higher retention of PpIX was mainly due to increasing ALA uptake, rather than activity changes of the enzymes porphobilinogen deaminase and ferrochelatase. The combined treatment inhibited tumor growth in different tumor cell lines, but not in normal human Schwann cells or fibroblasts. Similarly, a synergistic interaction was also found in cells treated with ALA-PDT combined with minocycline, but not tetracycline. In summary, doxycycline can potentiate the effect of ALA-PDT to kill tumor cells. This increased potency allows for a dose reduction of doxycycline and photodynamic radiation, reducing the occurrence of toxic side effects in vivo. PMID:28558025

Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells.

PubMed

Lee, Ming-Jen; Hung, Shih-Hsuan; Huang, Mu-Ching; Tsai, Tsuimin; Chen, Chin-Tin

2017-01-01

Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous disorders. Some NF1 patients develop benign large plexiform neurofibroma(s) at birth, which can then transform into a malignant peripheral nerve sheath tumor (MPNST). There is no curative treatment for this rapidly progressive and easily metastatic neurofibrosarcoma. Photodynamic therapy (PDT) has been developed as an anti-cancer treatment, and 5-aminolevulinic (ALA) mediated PDT (ALA-PDT) has been used to treat cutaneous skin and oral neoplasms. Doxycycline, a tetracycline derivative, can substantially reduce the tumor burden in human and animal models, in addition to its antimicrobial effects. The purpose of this study was to evaluate the effect and to investigate the mechanism of action of combined doxycycline and ALA-PDT treatment of MPNST cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the combination of ALA-PDT and doxycycline significantly reduce MPNST survival rate, compared to cells treated with each therapy alone. Isobologram analysis showed that the combined treatment had a synergistic effect. The increased cytotoxic activity could be seen by an increase in cellular protoporphyrin IX (PpIX) accumulation. Furthermore, we found that the higher retention of PpIX was mainly due to increasing ALA uptake, rather than activity changes of the enzymes porphobilinogen deaminase and ferrochelatase. The combined treatment inhibited tumor growth in different tumor cell lines, but not in normal human Schwann cells or fibroblasts. Similarly, a synergistic interaction was also found in cells treated with ALA-PDT combined with minocycline, but not tetracycline. In summary, doxycycline can potentiate the effect of ALA-PDT to kill tumor cells. This increased potency allows for a dose reduction of doxycycline and photodynamic radiation, reducing the occurrence of toxic side effects in vivo.

Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

PubMed Central

Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

2014-01-01

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2 + AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

Hypericin-loaded lipid nanocapsules for photodynamic cancer therapy in vitro

NASA Astrophysics Data System (ADS)

Barras, Alexandre; Boussekey, Luc; Courtade, Emmanuel; Boukherroub, Rabah

2013-10-01

Hypericin (Hy), a naturally occurring photosensitizer (PS), is extracted from Hypericum perforatum plants, commonly known as St. John's wort. The discovery of the in vitro and in vivo photodynamic activities of hypericin as a photosensitizer generated great interest, mainly to induce a very potent antitumoral effect. However, this compound belongs to the family of naphthodianthrones which are known to be poorly soluble in physiological solutions and produce non-fluorescent aggregates (A. Wirz et al., Pharmazie, 2002, 57, 543; A. Kubin et al., Pharmazie, 2008, 63, 263). These phenomena can reduce its efficiency as a photosensitizer for the clinical application. In the present contribution, we have prepared, characterized, and studied the photochemical properties of Hy-loaded lipid nanocapsule (LNC) formulations. The amount of singlet oxygen (1O2) generated was measured by the use of p-nitroso-dimethylaniline (RNO) as a selective scavenger under visible light irradiation. Our results showed that Hy-loaded LNCs suppressed aggregation of Hy in aqueous media, increased its apparent solubility, and enhanced the production of singlet oxygen in comparison with free drug. Indeed, encapsulation of Hy in LNCs led to an increase of 1O2 quantum yield to 0.29-0.44, as compared to 0.02 reported for free Hy in water. Additionally, we studied the photodynamic activity of Hy-loaded LNCs on human cervical carcinoma (HeLa) and Human Embryonic Kidney (HEK) cells. The cell viability decreased radically to 10-20% at 1 μM, reflecting Hy-loaded LNC25 phototoxicity.Hypericin (Hy), a naturally occurring photosensitizer (PS), is extracted from Hypericum perforatum plants, commonly known as St. John's wort. The discovery of the in vitro and in vivo photodynamic activities of hypericin as a photosensitizer generated great interest, mainly to induce a very potent antitumoral effect. However, this compound belongs to the family of naphthodianthrones which are known to be poorly soluble in

Efficient photodynamic therapy against gram-positive and gram-negative bacteria using THPTS, a cationic photosensitizer excited by infrared wavelength.

PubMed

Schastak, Stanislaw; Ziganshyna, Svitlana; Gitter, Burkhard; Wiedemann, Peter; Claudepierre, Thomas

2010-07-20

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to kill antibiotic-resistant bacteria uses light in combination with a photosensitizer to induce a phototoxic reaction. Concentrations of 1, 10 and 100microM of tetrahydroporphyrin-tetratosylat (THPTS) and different incubation times (30, 90 and 180min) were used to measure photodynamic efficiency against two Gram-positive strains of S.aureus (MSSA and MRSA), and two Gram-negative strains of E.coli and P.aeruginosa. We found that phototoxicity of the drug is independent of the antibiotic resistance pattern when incubated in PBS for the investigated strains. Also, an incubation with 100microM THPTS followed by illumination, yielded a 6lg (> or =99.999%) decrease in the viable numbers of all bacteria strains tested, indicating that the THPTS drug has a high degree of photodynamic inactivation. We then modulated incubation time, photosensitizer concentration and monitored the effect of serum on the THPTS activity. In doing so, we established the conditions to obtain the strongest bactericidal effect. Our results suggest that this new and highly pure synthetic compound should improve the efficiency of photodynamic therapy against multiresistant bacteria and has a significant potential for clinical applications in the treatment of nosocomial infections.

The Meteoroid Fluence at Mars Due to Comet C/2013 A1 (Siding Spring)

NASA Technical Reports Server (NTRS)

Moorhead, A.; Wiegert, P.; Blaauw, R.; McCarty, C.; Kingery, A.; Cooke, W.

2014-01-01

Long-period comet C/2013 A1 (Siding Spring) will experience a close encounter with Mars on 2014 Oct 19. A collision between the comet and the planet has been ruled out, but the comet's coma may envelop Mars and its man-made satellites. By the time of the close encounter, five operational spacecraft will be present near Mars. Characterizing the coma is crucial for assessing the risk posed to these satellites by meteoroid impacts. We present an analytic model of cometary comae that describes the spatial and size distributions of cometary dust and meteoroids. This model correctly reproduces, to within an order of magnitude, the number of impacts recorded by Giotto near 1P/Halley [1] and by Stardust near comet 81P/Wild 2 [2]. Applied to Siding Spring, our model predicts a total particle fluence near Mars of 0.02 particles per square meter. In order to determine the degree to which Siding Spring's coma deviates from a sphere, we perform numerical simulations which take into account both gravitational effects and radiative forces. We take the entire dust component of the coma and tail continuum into account by simulating the ejection and evolution of dust particles from comet Siding Spring. The total number of particles simulated is essentially a free parameter and does not provide a check on the total fluence. Instead, these simulations illustrate the degree to which the coma of Siding Spring deviates from the perfect sphere described by our analytic model (see Figure). We conclude that our analytic model sacrifices less than an order of magnitude in accuracy by neglecting particle dynamics and radiation pressure and is thus adequate for order-of-magnitude fluence estimates. Comet properties may change unpredictably and therefore an analytic coma model that enables quick recalculation of the meteoroid fluence is highly desirable. NASA's Meteoroid Environment Office is monitoring comet Siding Spring and taking measurements of cometary brightness and dust production. We

Ultrafast Spectroscopy of Fano-Like Resonance between Optical Phonon and Excitons in CdSe Quantum Dots: Dependence of Coherent Vibrational Wave-Packet Dynamics on Pump Fluence

PubMed Central

Aybush, Arseniy; Gostev, Fedor; Shelaev, Ivan; Titov, Andrey; Umanskiy, Stanislav; Cherepanov, Dmitry

2017-01-01

The main goal of the present work is to study the coherent phonon in strongly confined CdSe quantum dots (QDs) under varied pump fluences. The main characteristics of coherent phonons (amplitude, frequency, phase, spectrogram) of CdSe QDs under the red-edge pump of the excitonic band [1S(e)-1S3/2(h)] are reported. We demonstrate for the first time that the amplitude of the coherent optical longitudinal-optical (LO) phonon at 6.16 THz excited in CdSe nanoparticles by a femtosecond unchirped pulse shows a non-monotone dependence on the pump fluence. This dependence exhibits the maximum at pump fluence ~0.8 mJ/cm2. At the same time, the amplitudes of the longitudinal acoustic (LA) phonon mode at 0.55 THz and of the coherent wave packet of toluene at 15.6, 23.6 THz show a monotonic rise with the increase of pump fluence. The time frequency representation of an oscillating signal corresponding to LO phonons revealed by continuous wavelet transform (CWT) shows a profound destructive quantum interference close to the origin of distinct (optical phonon) and continuum-like (exciton) quasiparticles. The CWT spectrogram demonstrates a nonlinear chirp at short time delays, where the chirp sign depends on the pump pulse fluence. The CWT spectrogram reveals an anharmonic coupling between optical and acoustic phonons. PMID:29113056

Lifetime Neutron Fluence Analysis of the Ringhals Unit 1 Boiling Water Reactor

NASA Astrophysics Data System (ADS)

Kulesza, Joel A.; Roudén, Jenny; Green, Eva-Lena

2016-02-01

This paper describes a neutron fluence assessment considering the entire commercial operating history (35 cycles or ˜ 25 effective full power years) of the Ringhals Unit 1 reactor pressure vessel beltline region. In this assessment, neutron (E >1.0 MeV) fluence and iron atom displacement distributions were calculated on the moderator tank and reactor pressure vessel structures. To validate those calculations, five in-vessel surveillance chain dosimetry sets were evaluated as well as material samples taken from the upper core grid and wide range neutron monitor tubes to act as a form of retrospective dosimetry. During the analysis, it was recognized that delays in characterizing the retrospective dosimetry samples reduced the amount of reactions available to be counted and complicated the material composition determination. However, the comparisons between the surveillance chain dosimetry measurements (M) and calculated (C) results show similar and consistent results with the linear average M/C ratio of 1.13 which is in good agreement with the resultant least squares best estimate (BE)/C ratios of 1.10 for both neutron (E >1.0 MeV) flux and iron atom displacement rate.

Photodynamic inactivation of contaminated blood with Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Corrêa, Thaila Q.; Inada, Natalia M.; Pratavieira, Sebastião.; Blanco, Kate C.; Kurachi, Cristina; Bagnato, Vanderlei S.

2016-03-01

The presence of bacteria in the bloodstream can trigger a serious systemic inflammation and lead to sepsis that cause septic shock and death. Studies have shown an increase in the incidence of sepsis over the years and it is mainly due to the increased resistance of microorganisms to antibiotics, since these drugs are still sold and used improperly. The bacterial contamination of blood is also a risk to blood transfusions. Thus, bacteria inactivation in blood is being studied in order to increase the security of the blood supply. The purpose of this study was to decontaminate the blood using the photodynamic inactivation (PDI). Human blood samples in the presence of Photogem® were illuminated at an intensity of 30 mW/cm2, and light doses of 10 and 15 J/cm2. Blood counts were carried out for the quantitative evaluation and blood smears were prepared for qualitative and morphological evaluation by microscopy. The results showed normal viability values for the blood cells analyzed. The light doses showed minimal morphological changes in the membrane of red blood cells, but the irradiation in the presence of the photosensitizer caused hemolysis in red blood cells at the higher concentrations of the photosensitizer. Experiments with Staphylococcus aureus, one of the responsible of sepsis, showed 7 logs10 of photodynamic inactivation with 50 μg/mL and 15 J/cm2 and 1 log10 of this microorganism in a co-culture with blood.

Optimization of singlet oxygen production from photosensitizer-incorporated, medically relevant hydrogels.

PubMed

De Baróid, Áine T; McCoy, Colin P; Craig, Rebecca A; Carson, Louise; Andrews, Gavin P; Jones, David S; Gorman, Sean P

2017-02-01

Photodynamic therapy and photodynamic antimicrobial chemotherapy are widely used, but despite this, the relationships between fluence, wavelength of irradiation and singlet oxygen ( 1 O 2 ) production are poorly understood. To establish the relationships between these factors in medically relevant materials, the effect of fluence on 1 O 2 production from a tetrakis(4-N-methylpyridyl)porphyrin (TMPyP)-incorporated 2-hydroxyethyl methacrylate: methyl methacrylate: methacrylic acid (HEMA: MMA:MAA) copolymer, a total energy of 50.48 J/cm 2 , was applied at varying illumination power, and times. 1 O 2 production was characterized using anthracene-9,10-dipropionic acid, disodium salt (ADPA) using a recently described method. Using two light sources, a white LED array and a white halogen source, the LED array was found to produce less 1 O 2 than the halogen source when the same power (over 500 - 600 nm) and time conditions were applied. Importantly, it showed that the longest wavelength Q band (590 nm) is primarily responsible for 1 O 2 generation, and that a linear relationship exists between increasing power and time and the production of singlet oxygen. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 320-326, 2017. © 2015 The Authors Journal Of Biomedical Materials Research Part B: Applied Biomaterials Published By Wiley Periodicals, Inc.

Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid.

PubMed

Koizumi, Noriaki; Harada, Yoshinori; Minamikawa, Takeo; Tanaka, Hideo; Otsuji, Eigo; Takamatsu, Tetsuro

2016-01-21

Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.

Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

PubMed

Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

2010-12-01

A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area.

Device for fluorescent control and photodynamic therapy of age-related macula degeneration

NASA Astrophysics Data System (ADS)

Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

2004-07-01

Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

[Effect of M007 mediated photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro].

PubMed

Zhou, Yu-Kai; Wu, Wen-Zhi; Zhang, Lan; Yang, Chun-Hui; Wang, Yan-Ping

2012-01-01

To investigate the effect of a new photosensitizer, M007 mediated photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro. Human osteosarcoma MG63 cells were prepared as 1 x 10(6) /mL single-cell suspension, and 1 mL cells were transferred into 60 mL culture dish, then treated with 5 different gradient dosages (0, 2, 4, 8, 16 micromol/L) of M007 followed by photodynamic therapy or dark reaction for 10 min. The survival rate of the cells and the mode of cell death were detected by flow cytometry with the stain of Annexin V-FITC/PI. The effect on proliferation of survival cells was observed by MTT assay and colony-forming assay. M007 mediated photodynamic therapy induced the inactivation of MG63 human osteosarcoma cells in the way of late apoptosis/necrosis or becoming naked nucleus predominately. More than 90% MG63 cells in M007-PDT group were dead under the treatment of 2-16 micromol/L M007. The survival rates of 4-16 micromol/L M007-PDT group were steadily less than 1%. The optical densities did not increase with extension of culture time in 2-8 micromol/L M007-PDT group (P > 0.05). There were 16 survival alive cells found occasionally in 2 micromol/L M007-PDT group, but no colonies found in other groups. M007 mediated photodynamic therapy totally inactivated human osteosarcoma MG63 cells in vitro with the dosage more than 4 micromol/L.

Can nanotechnology potentiate photodynamic therapy?

PubMed Central

Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Chung, Hoon; Yaroslavsky, Anastasia; Garcia-Diaz, Maria; Chang, Julie; Chiang, Long Y.

2015-01-01

Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nano-technology potentiate PDT?” PMID:26361572

Correlating Fast Fluence to dpa in Atypical Locations

NASA Astrophysics Data System (ADS)

Drury, Thomas H.

2016-02-01

Damage to a nuclear reactor's materials by high-energy neutrons causes changes in the ductility and fracture toughness of the materials. The reactor vessel and its associated piping's ability to withstand stress without brittle fracture are paramount to safety. Theoretically, the material damage is directly related to the displacements per atom (dpa) via the residual defects from induced displacements. However in practice, the material damage is based on a correlation to the high-energy (E > 1.0 MeV) neutron fluence. While the correlated approach is applicable when the material in question has experienced the same neutron spectrum as test specimens which were the basis of the correlation, this approach is not generically acceptable. Using Monte Carlo and discrete ordinates transport codes, the energy dependent neutron flux is determined throughout the reactor structures and the reactor vessel. Results from the models provide the dpa response in addition to the high-energy neutron flux. Ratios of dpa to fast fluence are calculated throughout the models. The comparisons show a constant ratio in the areas of historical concern and thus the validity of the correlated approach to these areas. In regions above and below the fuel however, the flux spectrum has changed significantly. The correlated relationship of material damage to fluence is not valid in these regions without adjustment. An adjustment mechanism is proposed.

Endoscopic and Photodynamic Therapy of Cholangiocarcinoma

PubMed Central

Meier, Benjamin; Caca, Karel

2016-01-01

Background Most patients with cholangiocarcinoma (CCA) have unresectable disease. Endoscopic bile duct drainage is one of the major objectives of palliation of obstructive jaundice. Methods/Results Stent implantation using endoscopic retrograde cholangiography is considered to be the standard technique. Unilateral versus bilateral stenting is associated with different advantages and disadvantages; however, a standard approach is still not defined. As there are various kinds of stents, there is an ongoing discussion on which stent to use in which situation. Palliation of obstructive jaundice can be augmented through the use of photodynamic therapy (PDT). Studies have shown a prolonged survival for the combinations of PDT and different stent applications as well as combinations of PDT and additional systemic chemotherapy. Conclusion More well-designed studies are needed to better evaluate and standardize endoscopic treatment of unresectable CCA. PMID:28229075

Photodynamic therapy of endometriosis with HpD (Photosan III) in a new in vitro model

NASA Astrophysics Data System (ADS)

Viereck, Volker; Werter, Wiebke; Rueck, Angelika C.; Steiner, Rudolf W.; Keckstein, J.

1994-07-01

As a new treatment model for endometriosis, photodynamic therapy was applied to endometriotic and endometrial cultures. It could be demonstrated that both endometrial components (epithelium and stroma) were present in the cultures, proved by immunocytology and electron microscopy. No major differences were seen between endometriotic and endometrial cells. The cultures were treated by HpD-sensitized PDT. Incubation time was 24 h and concentrations of 5 and 10 (mu) g/ml were used. Irradiation was performed by an argon-pumped dye laser at 630 nm with a power density of 80 mW/cm2. Evaluation both morphologically and by trypan blue exclusion test, was effected 24 h after irradiation. Toxicity in endometriotic and endometrial cultures was practically identical. Stroma cells were more sensitive to photodynamic treatment than epithelial cells. Complete stromal cell destruction was reached at 15 J/cm2, whereas epithelial cells showed 100 lethality at 40 J/cm2 (10(mu) g/ml HpD). These and subsequent results demonstrate that the sensitivity of stromal cells was about seven times higher than that of epithelial cells.

Interstitial photodynamic therapy for the prostate: a canine feasibility study

NASA Astrophysics Data System (ADS)

Shetty, Sugandh D.; Sirls, Larry T.; Chen, Qun; Hetzel, Fred W.; Cerny, Joseph C.

1996-05-01

Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.

Towards dosimetry for photodynamic diagnosis with the low-level dose of photosensitizer.

PubMed

Buzalewicz, Igor; Hołowacz, Iwona; Ulatowska-Jarża, Agnieszka; Podbielska, Halina

2017-08-01

Contemporary medicine does not concern the issue of dosimetry in photodynamic diagnosis (PDD) but follows the photosensitizer (PS) producers recommendation. Most preclinical and clinical PDD studies indicate a considerable variation in the possibility of visualization and treatment, as e.g. in case of cervix lesions. Although some of these variations can be caused by the different histological subtypes or various tumor geometries, the issue of varying PS concentration in the tumor tissue volume is definitely an important factor. Therefore, there is a need to establish the objective and systematic PDD dosimetry protocol regarding doses of light and photosensitizers. Four different irradiation sources investigated in PDD (literature) were used for PS excitation. The PS luminescence was examined by means of the non-imaging (spectroscopic) and imaging (wide- and narrow-field of view) techniques. The methodology for low-level intensity photoluminescence (PL) characterization and dedicated image processing algorithm for PS luminescence images analysis were proposed. Further, HeLa cells' cultures penetration by PS was studied by a confocal microscopy. Reducing the PS dose with the choice of proper photoexcitation conditions decreases the PDD procedure costs and the side effects, not affecting the diagnostic efficiency. We determined in vitro the minimum incubation time and photosensitizer concentration of Photolon for diagnostic purposes, for which the Photolon PL can still be observed. It was demonstrated that quantification of PS concentration, choice of proper photoexcitation source, appropriate adjustment of light dose and PS penetration of cancer cells may improve the low-level luminescence photodynamic diagnostics performance. Practical effectiveness of the PDD strongly depends on irradiation source parameters (bandwidth, maximum intensity, half-width) and their optimization is the main conditioning factor for low-level intensity and low-cost PDD. Copyright © 2017

SU-E-T-238: Monte Carlo Estimation of Cerenkov Dose for Photo-Dynamic Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chibani, O; Price, R; Ma, C

Purpose: Estimation of Cerenkov dose from high-energy megavoltage photon and electron beams in tissue and its impact on the radiosensitization using Protoporphyrine IX (PpIX) for tumor targeting enhancement in radiotherapy. Methods: The GEPTS Monte Carlo code is used to generate dose distributions from 18MV Varian photon beam and generic high-energy (45-MV) photon and (45-MeV) electron beams in a voxel-based tissueequivalent phantom. In addition to calculating the ionization dose, the code scores Cerenkov energy released in the wavelength range 375–425 nm corresponding to the pick of the PpIX absorption spectrum (Fig. 1) using the Frank-Tamm formula. Results: The simulations shows thatmore » the produced Cerenkov dose suitable for activating PpIX is 4000 to 5500 times lower than the overall radiation dose for all considered beams (18MV, 45 MV and 45 MeV). These results were contradictory to the recent experimental studies by Axelsson et al. (Med. Phys. 38 (2011) p 4127), where Cerenkov dose was reported to be only two orders of magnitude lower than the radiation dose. Note that our simulation results can be corroborated by a simple model where the Frank and Tamm formula is applied for electrons with 2 MeV/cm stopping power generating Cerenkov photons in the 375–425 nm range and assuming these photons have less than 1mm penetration in tissue. Conclusion: The Cerenkov dose generated by high-energy photon and electron beams may produce minimal clinical effect in comparison with the photon fluence (or dose) commonly used for photo-dynamic therapy. At the present time, it is unclear whether Cerenkov radiation is a significant contributor to the recently observed tumor regression for patients receiving radiotherapy and PpIX versus patients receiving radiotherapy only. The ongoing study will include animal experimentation and investigation of dose rate effects on PpIX response.« less

Comparison of IMRT planning with two-step and one-step optimization: a strategy for improving therapeutic gain and reducing the integral dose

NASA Astrophysics Data System (ADS)

Abate, A.; Pressello, M. C.; Benassi, M.; Strigari, L.

2009-12-01

The aim of this study was to evaluate the effectiveness and efficiency in inverse IMRT planning of one-step optimization with the step-and-shoot (SS) technique as compared to traditional two-step optimization using the sliding windows (SW) technique. The Pinnacle IMRT TPS allows both one-step and two-step approaches. The same beam setup for five head-and-neck tumor patients and dose-volume constraints were applied for all optimization methods. Two-step plans were produced converting the ideal fluence with or without a smoothing filter into the SW sequence. One-step plans, based on direct machine parameter optimization (DMPO), had the maximum number of segments per beam set at 8, 10, 12, producing a directly deliverable sequence. Moreover, the plans were generated whether a split-beam was used or not. Total monitor units (MUs), overall treatment time, cost function and dose-volume histograms (DVHs) were estimated for each plan. PTV conformality and homogeneity indexes and normal tissue complication probability (NTCP) that are the basis for improving therapeutic gain, as well as non-tumor integral dose (NTID), were evaluated. A two-sided t-test was used to compare quantitative variables. All plans showed similar target coverage. Compared to two-step SW optimization, the DMPO-SS plans resulted in lower MUs (20%), NTID (4%) as well as NTCP values. Differences of about 15-20% in the treatment delivery time were registered. DMPO generates less complex plans with identical PTV coverage, providing lower NTCP and NTID, which is expected to reduce the risk of secondary cancer. It is an effective and efficient method and, if available, it should be favored over the two-step IMRT planning.

Intracellular Targeting Specificity of Novel Phthalocyanines Assessed in a Host-Parasite Model for Developing Potential Photodynamic Medicine

PubMed Central

Dutta, Sujoy; Ongarora, Benson G.; Li, Hairong; Vicente, Maria da Graca H.; Kolli, Bala K.; Chang, Kwang Poo

2011-01-01

Photodynamic therapy, unlikely to elicit drug-resistance, deserves attention as a strategy to counter this outstanding problem common to the chemotherapy of all diseases. Previously, we have broadened the applicability of this modality to photodynamic vaccination by exploiting the unusual properties of the trypanosomatid protozoa, Leishmania, i.e., their innate ability of homing to the phagolysosomes of the antigen-presenting cells and their selective photolysis therein, using transgenic mutants endogenously inducible for porphyrin accumulation. Here, we extended the utility of this host-parasite model for in vitro photodynamic therapy and vaccination by exploring exogenously supplied photosensitizers. Seventeen novel phthalocyanines (Pcs) were screened in vitro for their photolytic activity against cultured Leishmania. Pcs rendered cationic and soluble (csPcs) for cellular uptake were phototoxic to both parasite and host cells, i.e., macrophages and dendritic cells. The csPcs that targeted to mitochondria were more photolytic than those restricted to the endocytic compartments. Treatment of infected cells with endocytic csPcs resulted in their accumulation in Leishmania-containing phagolysosomes, indicative of reaching their target for photodynamic therapy, although their parasite versus host specificity is limited to a narrow range of csPc concentrations. In contrast, Leishmania pre-loaded with csPc were selectively photolyzed intracellularly, leaving host cells viable. Pre-illumination of such csPc-loaded Leishmania did not hinder their infectivity, but ensured their intracellular lysis. Ovalbumin (OVA) so delivered by photo-inactivated OVA transfectants to mouse macrophages and dendritic cells were co-presented with MHC Class I molecules by these antigen presenting cells to activate OVA epitope-specific CD8+T cells. The in vitro evidence presented here demonstrates for the first time not only the potential of endocytic csPcs for effective photodynamic therapy

Apoptosis triggered by pyropheophorbide-α methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

NASA Astrophysics Data System (ADS)

Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

2014-06-01

A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-α methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

One-step preparation of a water-soluble carbon nanohorn/phthalocyanine hybrid for dual-modality photothermal and photodynamic therapy.

PubMed

Jiang, Bang-Ping; Hu, Lan-Fang; Shen, Xing-Can; Ji, Shi-Chen; Shi, Zujin; Liu, Chan-Juan; Zhang, Li; Liang, Hong

2014-10-22

The biomedical applications of carbon nanomaterials, especially integrating noninvasive photothermal therapy (PTT) and photodynamic therapy (PDT), into a single system have enormous potential in cancer therapy. Herein, we present a novel and facile one-step method for the preparation of water-soluble single-walled carbon nanohorns (SWNHs) and metal phthalocyanines (MPc) hybrid for PTT and PDT. The hydrophilic MPc, tetrasulfonic acid tetrasodium salt copper phthalocyanine (TSCuPc), is coated on the surface of SWNHs via noncovalent π-π interaction using the sonication method. In this PTT/PDT nanosystem, SWNHs acts as a photosensitizer carrier and PTT agent, while TSCuPc acts as a hydrophilic and PDT agent. The EPR results demonstrated that the generated reactive oxygen species (ROS) not only from the photoinduced electron transfer process from TSCuPc to SWNHs but also from SWNHs without exciting TSCuPc to its excited state. The test of photothermal conversion proved that not only do SWNHs contribute to the photothermal therapy (PTT) effect, TSCuPc probably also contributes to that when it coats on the surface of SWNHs upon exposure to a 650-nm laser. More importantly, the results of in vitro cell viability revealed a significantly enhanced anticancer efficacy of combined noninvasive PTT/PDT, indicating that the SWNHs-TSCuPc nanohybrid is a hopeful candidate material for developing an efficient and biocompatible nanoplatform for biomedical application.

Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy.

PubMed

Hammerer, Fabien; Poyer, Florent; Fourmois, Laura; Chen, Su; Garcia, Guillaume; Teulade-Fichou, Marie-Paule; Maillard, Philippe; Mahuteau-Betzer, Florence

2018-01-01

The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Light dosimetry and dose verification for pleural PDT

NASA Astrophysics Data System (ADS)

Dimofte, Andreea; Sharikova, Anna V.; Meo, Julia L.; Simone, Charles B.; Friedberg, Joseph S.; Zhu, Timothy C.

2013-03-01

In-vivo light dosimetry for patients undergoing photodynamic therapy (PDT) is critical for predicting PDT outcome. Patients in this study are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. They are administered 4mg per kg body weight HPPH 48 hours before the surgery and receive light therapy with a fluence of 15-45 J/cm2 at 661 and 665nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) are monitored at 7 sites during the light treatment delivery using isotropic detectors. Light fluence (rate) delivered to patients is examined as a function of treatment time, volume and surface area. In a previous study, a correlation between the treatment time and the treatment volume and surface area was established. However, we did not include the direct light and the effect of the shape of the pleural surface on the scattered light. A real-time infrared (IR) navigation system was used to separate the contribution from the direct light. An improved expression that accurately calculates the total fluence at the cavity wall as a function of light source location, cavity geometry and optical properties is determined based on theoretical and phantom studies. The theoretical study includes an expression for light fluence rate in an elliptical geometry instead of the spheroid geometry used previously. The calculated light fluence is compared to the measured fluence in patients of different cavity geometries and optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.

Photodynamic therapy: Theoretical and experimental approaches to dosimetry

NASA Astrophysics Data System (ADS)

Wang, Ken Kang-Hsin

Singlet oxygen (1O2) is the major cytotoxic species generated during photodynamic therapy (PDT), and 1O 2 reactions with biological targets define the photodynamic dose at the most fundamental level. We have developed a theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O 2) consumption and transport and microscopic 1O 2 dose deposition during PDT in vivo. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O 2 saturation within vessels, irreversible photosensitizer degradation due to photobleaching, therapy-induced blood flow decrease and the microscopic distributions of 3O2 and 1O 2 dose deposition under various irradiation conditions. mTHPC, a promising photosensitizer for PDT, is approved in Europe for the palliative treatment of head and neck cancer. Using the theoretical model and informed by intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions for mTHPC-PDT. Our results demonstrate that the 1O 2 dose to the tumor volume does not track even qualitatively with long-term tumor responses. Thus, in this evaluation of mTHPC-PDT, any PDT dose metric that is proportional to singlet oxygen creation and/or deposition would fail to predict the tumor response. In situations like this one, other reporters of biological response to therapy would be necessary. In addition to the case study of mTHPC-PDT, we also use the mathematical model to simulate clinical photobleaching data, informed by a possible blood flow reduction during treatment. In a recently completed clinical trial at Roswell Park Cancer Institute, patients with superficial basal cell carcinoma received topical application of 5-aminolevulinic acid (ALA) and were irradiated with 633 nm light at 10-150 mW cm-2 . Protoporphyrin IX (PpIX) photobleaching in the lesion and the adjacent perilesion normal margin was monitored by

Enhancement of the photokilling effect of TiO2 in photodynamic therapy by conjugating with reduced graphene oxide and its mechanism exploration.

PubMed

Shang, Hongyuan; Han, Dong; Ma, Min; Li, Sha; Xue, Wenting; Zhang, Aiping

2017-12-01

As a promising next-generation photodynamic therapy (PDT) photosensitizer, TiO 2 nanoparticles (NPs) has gained great attention due to its higher efficiency. Yet, its application in PDT is strongly limited by its UV light response range. In this work, TiO 2 NPs conjugated with reduced graphene oxide (RGO-TiO 2 ) composites were successfully prepared by hydrothermal reduction method. They were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET), UV-vis spectroscopy and X-ray photoelectron spectroscopy (XPS). Superior adsorption and killing efficiency under UV-A light or visible light were achieved in the presence of the RGO rather than that of unmodified TiO 2 . The optimal photocatalytic activity was obtained when modified proportion was 0.2 (RGO:TiO 2 ). Dark cytotoxicity was observed using 0-500μgmL -1 RGO-TiO 2 during long incubation time. In parallel, following exposure of human hepatocellular carcinoma cell line (HepG2 cells) to RGO-TiO 2 and UV-A or visible light irradiation, a marked decrease in the ratio of the super-coiled DNA, mitochondrial membrane potential (MMP), and the oxidative damage effects, as well as increased the apoptosis rate and intracellular calcium concentration were observed. Moreover, photocatalytic RGO-TiO 2 composites killed the HepG2 cells by apoptosis pathway. The results suggested that RGO-TiO 2 composites were an excellent candidate as a PDT photosensitizer in the near future. Copyright © 2017. Published by Elsevier B.V.

Tissue effects of Ho:YAG laser with varying fluences and pulse widths

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; van der Veen, Maurits J.; Pergadia, Vani R.; Shi, Wei-Qiang; Duffy, J. T.; Weiss, Andrew B.; Fishbein, Michael C.; Grundfest, Warren S.

1994-02-01

We investigated the effect of varying fluence and pulse width on the ablation rate and consequent thermal damage of the Ho:YAG (2.130 micrometers ) laser. The rate of ablation on fresh bovine knee joint tissues, fibrous cartilage, hyaline cartilage, and bone in saline was determined after varying the fluence (160 - 640 J/cm2) and pulse width (150, 250, 450 microsecond(s) ec, FWHM) at a repetition rate of 2 Hz. A 400/440 micrometers fiber was used. The ablation rate increased linearly with the fluence. In fibrocartilage, different pulse durations generated significant changes in the ablation rates, but showed minor effects on hyaline cartilage and bone. The heat of ablation for all three tissue types decreased after lengthening the pulse.

Study of titania nanorod films deposited by matrix-assisted pulsed laser evaporation as a function of laser fluence

NASA Astrophysics Data System (ADS)

Caricato, A. P.; Belviso, M. R.; Catalano, M.; Cesaria, M.; Cozzoli, P. D.; Luches, A.; Manera, M. G.; Martino, M.; Rella, R.; Taurino, A.

2011-11-01

Chemically synthesized brookite titanium dioxide (TiO2) nanorods with average diameter and length dimensions of 3-4 nm and 35-50 nm, respectively, were deposited by the matrix-assisted pulsed laser evaporation technique. A toluene nanorod solution was frozen at the liquid-nitrogen temperature and irradiated with a KrF excimer laser ( λ=248 nm, τ=20 ns) at the repetition rate of 10 Hz, at different fluences (25 to 350 mJ/cm2). The deposited films were structurally characterized by high-resolution scanning and transmission electron microscopy. <100> single-crystal Si wafers and carbon-coated Cu grids were used as substrates. Structural analyses evidenced the occurrence of brookite-phase crystalline nanospheres coexisting with individually distinguishable TiO2 nanorods in the films deposited at fluences varying from 50 to 350 mJ/cm2. Nanostructured TiO2 films comprising only nanorods were deposited by lowering the laser fluence to 25 mJ/cm2. The observed shape and phase transitions of the nanorods are discussed taking into account the laser-induced heating effects, reduced melting temperature and size-dependent thermodynamic stability of nanoscale TiO2.

Optoacoustic imaging of tissue blanching during photodynamic therapy of esophageal cancer

NASA Astrophysics Data System (ADS)

Jacques, Steven L.; Viator, John A.; Paltauf, Guenther

2000-05-01

Esophageal cancer patients often present a highly inflamed esophagus at the time of treatment by photodynamic therapy. Immediately after treatment, the inflamed vessels have been shut down and the esophagus presents a white surface. Optoacoustic imaging via an optical fiber device can provide a depth profile of the blanching of inflammation. Such a profile may be an indicator of the depth of treatment achieved by the PDT. Our progress toward developing this diagnostic for use in our clinical PDT treatments of esophageal cancer patients is presented.

Photodynamic damage of glial cells in crayfish ventral nerve cord

NASA Astrophysics Data System (ADS)

Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

2011-03-01

Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

Fluence map optimization (FMO) with dose-volume constraints in IMRT using the geometric distance sorting method.

PubMed

Lan, Yihua; Li, Cunhua; Ren, Haozheng; Zhang, Yong; Min, Zhifang

2012-10-21

A new heuristic algorithm based on the so-called geometric distance sorting technique is proposed for solving the fluence map optimization with dose-volume constraints which is one of the most essential tasks for inverse planning in IMRT. The framework of the proposed method is basically an iterative process which begins with a simple linear constrained quadratic optimization model without considering any dose-volume constraints, and then the dose constraints for the voxels violating the dose-volume constraints are gradually added into the quadratic optimization model step by step until all the dose-volume constraints are satisfied. In each iteration step, an interior point method is adopted to solve each new linear constrained quadratic programming. For choosing the proper candidate voxels for the current dose constraint adding, a so-called geometric distance defined in the transformed standard quadratic form of the fluence map optimization model was used to guide the selection of the voxels. The new geometric distance sorting technique can mostly reduce the unexpected increase of the objective function value caused inevitably by the constraint adding. It can be regarded as an upgrading to the traditional dose sorting technique. The geometry explanation for the proposed method is also given and a proposition is proved to support our heuristic idea. In addition, a smart constraint adding/deleting strategy is designed to ensure a stable iteration convergence. The new algorithm is tested on four cases including head-neck, a prostate, a lung and an oropharyngeal, and compared with the algorithm based on the traditional dose sorting technique. Experimental results showed that the proposed method is more suitable for guiding the selection of new constraints than the traditional dose sorting method, especially for the cases whose target regions are in non-convex shapes. It is a more efficient optimization technique to some extent for choosing constraints than the dose

Enhanced plasmonic resonance energy transfer in mesoporous silica-encased gold nanorod for two-photon-activated photodynamic therapy.

PubMed

Chen, Nai-Tzu; Tang, Kuo-Chun; Chung, Ming-Fang; Cheng, Shih-Hsun; Huang, Ching-Mao; Chu, Chia-Hui; Chou, Pi-Tai; Souris, Jeffrey S; Chen, Chin-Tu; Mou, Chung-Yuan; Lo, Leu-Wei

2014-01-01

The unique optical properties of gold nanorods (GNRs) have recently drawn considerable interest from those working in in vivo biomolecular sensing and bioimaging. Especially appealing in these applications is the plasmon-enhanced photoluminescence of GNRs induced by two-photon excitation at infrared wavelengths, owing to the significant penetration depth of infrared light in tissue. Unfortunately, many studies have also shown that often the intensity of pulsed coherent irradiation of GNRs needed results in irreversible deformation of GNRs, greatly reducing their two-photon luminescence (TPL) emission intensity. In this work we report the design, synthesis, and evaluation of mesoporous silica-encased gold nanorods (MS-GNRs) that incorporate photosensitizers (PSs) for two-photon-activated photodynamic therapy (TPA-PDT). The PSs, doped into the nano-channels of the mesoporous silica shell, can be efficiently excited via intra-particle plasmonic resonance energy transfer from the encased two-photon excited gold nanorod and further generates cytotoxic singlet oxygen for cancer eradication. In addition, due to the mechanical support provided by encapsulating mesoporous silica matrix against thermal deformation, the two-photon luminescence stability of GNRs was significantly improved; after 100 seconds of 800 nm repetitive laser pulse with the 30 times higher than average power for imaging acquisition, MS-GNR luminescence intensity exhibited ~260% better resistance to deformation than that of the uncoated gold nanorods. These results strongly suggest that MS-GNRs with embedded PSs might provide a promising photodynamic therapy for the treatment of deeply situated cancers via plasmonic resonance energy transfer.

Protocol for Determining Ultraviolet Light Emitting Diode (UV-LED) Fluence for Microbial Inactivation Studies.

PubMed

Kheyrandish, Ataollah; Mohseni, Madjid; Taghipour, Fariborz

2018-06-15

Determining fluence is essential to derive the inactivation kinetics of microorganisms and to design ultraviolet (UV) reactors for water disinfection. UV light emitting diodes (UV-LEDs) are emerging UV sources with various advantages compared to conventional UV lamps. Unlike conventional mercury lamps, no standard method is available to determine the average fluence of the UV-LEDs, and conventional methods used to determine the fluence for UV mercury lamps are not applicable to UV-LEDs due to the relatively low power output, polychromatic wavelength, and specific radiation profile of UV-LEDs. In this study, a method was developed to determine the average fluence inside a water suspension in a UV-LED experimental setup. In this method, the average fluence was estimated by measuring the irradiance at a few points for a collimated and uniform radiation on a Petri dish surface. New correction parameters were defined and proposed, and several of the existing parameters for determining the fluence of the UV mercury lamp apparatus were revised to measure and quantify the collimation and uniformity of the radiation. To study the effect of polychromatic output and radiation profile of the UV-LEDs, two UV-LEDs with peak wavelengths of 262 and 275 nm and different radiation profiles were selected as the representatives of typical UV-LEDs applied to microbial inactivation. The proper setup configuration for microorganism inactivation studies was also determined based on the defined correction factors.

Photodynamic therapy of normal rat arteries after photosensitisation using disulphonated aluminium phthalocyanine and 5-aminolaevulinic acid.

PubMed Central

Grant, W. E.; Speight, P. M.; MacRobert, A. J.; Hopper, C.; Bown, S. G.

1994-01-01

Photodynamic therapy of cancer exposes adjacent arteries to the risk of injury and the possibility of haemorrhage and thrombosis. The nature of photodynamic injury to normal arteries has not been satisfactorily defined, and the ability of arteries to recover with time is unclear. To clarify these issues, we have investigated the effects of PDT on rat femoral arteries, using a second-generation photosensitiser, disulphonated aluminium phthalocyanine, and a new method of photosensitisation, using endogenous synthesis of protoporphyrin IX following systemic administration of 5-aminolaevulinic acid (ALA). Pharmacokinetic studies of sensitiser fluorescence were carried out to determine peak levels of sensitiser. Subsequently photodynamic therapy at times corresponding to maximal fluorescence was performed using two light doses, 100 and 250 J cm-2. The nature of injury sustained and recovery over a 6 month period was investigated. Three days following PDT, all vessels treated showed complete loss of endothelium, with death of all medial smooth muscle cells, leaving an acellular flaccid artery wall. No vascular occlusion, haemorrhage or thrombosis was found. A striking feature was the lack of inflammatory response in the vessel wall at any time studied. Re-endothelialisation occurred in all vessels by 2 weeks. The phthalocyanine group showed repopulation of the media with smooth muscle cells to be almost complete by 3 months. However, the ALA group failed to redevelop a muscular wall and remained dilated at 6 months. Luminal cross-sectional area of the ALA-treated group was significantly greater than both control and phthalocyanine groups at 6 months. All vessels remained patent. This study indicates that arteries exposed to PDT are not at risk of catastrophic haemorrhage or occlusion, a finding that is of significance for both the local treatment of tumours and the use of PDT as an intraoperative adjunct to surgery for the ablation of microscopic residual malignant

Femtosecond laser ablation of dentin and enamel: relationship between laser fluence and ablation efficiency.

PubMed

Chen, Hu; Liu, Jing; Li, Hong; Ge, Wenqi; Sun, Yuchun; Wang, Yong; Lü, Peijun

2015-02-01

The objective was to study the relationship between laser fluence and ablation efficiency of a femtosecond laser with a Gaussian-shaped pulse used to ablate dentin and enamel for prosthodontic tooth preparation. A diode-pumped thin-disk femtosecond laser with wavelength of 1025 nm and pulse width of 400 fs was used for the ablation of dentin and enamel. The laser spot was guided in a line on the dentin and enamel surfaces to form a groove-shaped ablation zone under a series of laser pulse energies. The width and volume of the ablated line were measured under a three-dimensional confocal microscope to calculate the ablation efficiency. Ablation efficiency for dentin reached a maximum value of 0.020 mm3∕J when the laser fluence was set at 6.51 J∕cm2. For enamel, the maximum ablation efficiency was 0.009 mm3∕J at a fluence of 7.59 J∕cm2.Ablation efficiency of the femtosecond laser on dentin and enamel is closely related to the laser fluence and may reach a maximum when the laser fluence is set to an appropriate value. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

The impact of antimicrobial photodynamic therapy on Streptococcus mutans in an artificial biofilm model

NASA Astrophysics Data System (ADS)

Schneider, Martin; Kirfel, Gregor; Krause, Felix; Berthold, Michael; Brede, Olivier; Frentzen, Matthias; Braun, Andreas

2010-02-01

The aim of the study was to assess the impact of laser induced antimicrobial photodynamic therapy on the viability of Streptococcus mutans cells employing an aritificial biofilm model. Employing sterile chambered coverglasses, a salivary pellicle layer formation was induced in 19 chambers. Streptococcus mutans cells were inoculated in a sterile culture medium. Using a live/dead bacterial viability kit, bacteria with intact cell membranes stain fluorescent green. Test chambers containing each the pellicle layer and 0.5 ml of the bacterial culture were analyzed using a confocal laser scan microscope within a layer of 10 μm at intervals of 1 μm from the pellicle layer. A photosensitizer was added to the test chambers and irradiated with a diode laser (wavelength: 660 nm, output power: 100 mW, Helbo) for 2 min each. Comparing the baseline fluorescence (median: 13.8 [U], min: 3.7, max: 26.2) with the values after adding the photosensitizer (median: 3.7, min: 1.1, max: 9), a dilution caused decrease of fluorescence could be observed (p<0.05). After irradiation of the samples with a diode laser, an additional 48 percent decrease of fluorescence became evident (median: 2.2, min: 0.4, max: 3.4) (p<0.05). Comparing the samples with added photosensitizer but without laser irradiation at different times, no decrease of fluorescence could be measured (p>0.05). The present study indicates that antimicrobial photodynamic therapy can reduce living bacteria within a layer of 10 μm in an artificial biofilm model. Further studies have to evaluate the maximum biofilm thickness that still allows a toxic effect on microorganisms.

Density and fluence dependence of lithium cell damage and recovery characteristics

NASA Technical Reports Server (NTRS)

Faith, T. J.

1971-01-01

Experimental results on lithium-containing solar cells point toward the lithium donor density gradient dN sub L/dw as being the crucial parameter in the prediction of cell behavior after irradiation by electrons. Recovery measurements on a large number of oxygen-rich and oxygen-lean lithium cells have confirmed that cell recovery speed is directly proportional to the value of the lithium gradient for electron fluences. Gradient measurements have also been correlated with lithium diffusion schedules. Results have shown that long diffusion times (25 h) with a paint-on source result in large cell-to-cell variations in gradient, probably due to a loss of the lithium source with time.

Equivalent electron fluence for space qualification of shallow junction heteroface GaAs solar cells

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Stock, L. V.

1984-01-01

It is desirable to perform qualification tests prior to deployment of solar cells in space power applications. Such test procedures are complicated by the complex mixture of differing radiation components in space which are difficult to simulate in ground test facilities. Although it has been shown that an equivalent electron fluence ratio cannot be uniquely defined for monoenergetic proton exposure of GaAs shallow junction cells, an equivalent electron fluence test can be defined for common spectral components of protons found in space. Equivalent electron fluence levels for the geosynchronous environment are presented.

Measured Thermal and Fast Neutron Fluence Rates for ATF-1 Holders During ATR Cycle 157D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Larry Don; Miller, David Torbet

This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 157D which were measured by the Radiation Measurements Laboratory (RML) as requested by the Power Reactor Programs (ATR Experiments) Radiation Measurements Work Order. This report contains measurements of the fluence rates corresponding to the particular elevations relative to the 80-ft. core elevation. The data in this report consist of (1) a table of the ATR power history and distribution, (2) a hard copy listing of all thermal and fast neutron fluence rates, and (3) plots ofmore » both the thermal and fast neutron fluence rates. The fluence rates reported are for the average power levels given in the table of power history and distribution.« less

Treatment of canine hemangiopericytomas with photodynamic therapy.

PubMed

McCaw, D L; Payne, J T; Pope, E R; West, M K; Tompson, R V; Tate, D

2001-01-01

Canine hemangiopericytomas are a commonly occurring neoplasm with a clinical course of recurrence after surgical removal. This study sought to evaluate Photochlor (HPPH) photodynamic therapy (HPPH-PDT) as an adjuvant therapy to prevent recurrence of tumor after surgical removal. Sixteen dogs with naturally occurring hemangiopericytomas were treated with surgical removal of the tumor followed by PDT using Photochlor as the photosensitizer. Photochlor was injected intravenously at a dose of 0.3 mg/kg. Forty-eight hours later the treatment consisted of surgical removal of the tumor followed by HPPH-PDT. Nine dogs (56%) had recurrence of tumor from 2 to 29 (median 9) months after treatment. These results are comparable or not as good as other forms of therapy. Photochlor photodynamic therapy applied after surgery appears to have no advantage over other forms of therapy in regards to preventing recurrence. Delayed wound healing and infections are problematic and make HPPH-PDT an undesirable addition to surgery for the treatment of this tumor type. Copyright 2001 Wiley-Liss, Inc.

Experimental and Monte Carlo studies of fluence corrections for graphite calorimetry in low- and high-energy clinical proton beams.

PubMed

Lourenço, Ana; Thomas, Russell; Bouchard, Hugo; Kacperek, Andrzej; Vondracek, Vladimir; Royle, Gary; Palmans, Hugo

2016-07-01

The aim of this study was to determine fluence corrections necessary to convert absorbed dose to graphite, measured by graphite calorimetry, to absorbed dose to water. Fluence corrections were obtained from experiments and Monte Carlo simulations in low- and high-energy proton beams. Fluence corrections were calculated to account for the difference in fluence between water and graphite at equivalent depths. Measurements were performed with narrow proton beams. Plane-parallel-plate ionization chambers with a large collecting area compared to the beam diameter were used to intercept the whole beam. High- and low-energy proton beams were provided by a scanning and double scattering delivery system, respectively. A mathematical formalism was established to relate fluence corrections derived from Monte Carlo simulations, using the fluka code [A. Ferrari et al., "fluka: A multi-particle transport code," in CERN 2005-10, INFN/TC 05/11, SLAC-R-773 (2005) and T. T. Böhlen et al., "The fluka Code: Developments and challenges for high energy and medical applications," Nucl. Data Sheets 120, 211-214 (2014)], to partial fluence corrections measured experimentally. A good agreement was found between the partial fluence corrections derived by Monte Carlo simulations and those determined experimentally. For a high-energy beam of 180 MeV, the fluence corrections from Monte Carlo simulations were found to increase from 0.99 to 1.04 with depth. In the case of a low-energy beam of 60 MeV, the magnitude of fluence corrections was approximately 0.99 at all depths when calculated in the sensitive area of the chamber used in the experiments. Fluence correction calculations were also performed for a larger area and found to increase from 0.99 at the surface to 1.01 at greater depths. Fluence corrections obtained experimentally are partial fluence corrections because they account for differences in the primary and part of the secondary particle fluence. A correction factor, F(d), has been

Database of episode-integrated solar energetic proton fluences

NASA Astrophysics Data System (ADS)

Robinson, Zachary D.; Adams, James H.; Xapsos, Michael A.; Stauffer, Craig A.

2018-04-01

A new database of proton episode-integrated fluences is described. This database contains data from two different instruments on multiple satellites. The data are from instruments on the Interplanetary Monitoring Platform-8 (IMP8) and the Geostationary Operational Environmental Satellites (GOES) series. A method to normalize one set of data to one another is presented to create a seamless database spanning 1973 to 2016. A discussion of some of the characteristics that episodes exhibit is presented, including episode duration and number of peaks. As an example of what can be understood about episodes, the July 4, 2012 episode is examined in detail. The coronal mass ejections and solar flares that caused many of the fluctuations of the proton flux seen at Earth are associated with peaks in the proton flux during this episode. The reasoning for each choice is laid out to provide a reference for how CME and solar flares associations are made.

Successful treatment of recalcitrant folliculitis barbae and pseudofolliculitis barbae with photodynamic therapy.

PubMed

Diernaes, Jon Erik Fraes; Bygum, Anette

2013-12-01

Folliculitis and pseudofolliculitis barbae typically affects men with curly hair who shave too close. Treatment modalities vary in effectiveness and include improved hair removal methods, topical corticosteroids, topical and oral antibiotics, and retinoids as well as laser surgery. We report a novel treatment of recalcitrant pseudofolliculitis barbae and confirm effectiveness in recalcitrant folliculitis in a 58-year old man who responded completely following photodynamic therapy with methyl aminolevulinate. Photodynamic therapy should be considered in recalcitrant folliculitis and pseudofolliculitis barbae. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of He+ fluence on surface morphology and ion-irradiation induced defect evolution in 7075 aluminum alloys

NASA Astrophysics Data System (ADS)

Ni, Kai; Ma, Qian; Wan, Hao; Yang, Bin; Ge, Junjie; Zhang, Lingyu; Si, Naichao

2018-02-01

The evolution of microstructure for 7075 aluminum alloys with 50 Kev helium ions irradiation were studied by using optical microscopy (OM), scanning electron microscopy (SEM), x-ray diffraction (XRD) and transmission electron microscopy (TEM). The fluences of 1 × 1015, 1 × 1016 and 1 × 1017 ions cm-2 were selected, and irradiation experiments were conducted at room temperatures. The transmission process of He+ ions was simulated by using SRIM software, including distribution of ion ranges, energy losses and atomic displacements. Experimental results show that irradiated pits and micro-cracks were observed on irradiation sample surface, and the size of constituent particles (not including Mg2Si) decreased with the increasing dose. The x-ray diffraction results of the pair of peaks is better resolved in irradiated samples might indicate that the stressed structure consequence due to crystal defects (vacancies and interstitials) after He+ implantation. TEM observation indicated that the density of MgZn2 phase was significantly reduced after helium ion irradiation which is harmful to strength. Besides, the development of compressive stress produced a large amount of dislocation defects in the 1015 ions cm-2 sample. Moreover, higher fluence irradiation produced more dislocations in sample. At fluence of 1016 ions cm-2, dislocation wall formed by dislocation slip and aggregation in the interior of grains, leading to the refinement of these grains. As fluence increased to 1017 ions cm-2, dislocation loops were observed in pinned dislocation. Moreover, dislocation as effective defect sink, irradiation-induced vacancy defects aggregated to these sinks, and resulted in the formation of helium bubbles in dislocation.

SU-F-J-214: Dose Reduction by Spatially Optimized Image Quality Via Fluence Modulated Proton CT (FMpCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Angelis, L; Landry, G; Dedes, G

Purpose: Proton CT (pCT) is a promising imaging modality for reducing range uncertainty in image-guided proton therapy. Range uncertainties partially originate from X-ray CT number conversion to stopping power ratio (SPR) and are limiting the exploitation of the full potential of proton therapy. In this study we explore the concept of spatially dependent fluence modulated proton CT (FMpCT), for achieving optimal image quality in a clinical region of interest (ROI), while reducing significantly the imaging dose to the patient. Methods: The study was based on simulated ideal pCT using pencil beam (PB) scanning. A set of 250 MeV protons PBsmore » was used to create 360 projections of a cylindrical water phantom and a head and neck cancer patient. The tomographic images were reconstructed using a filtered backprojection (FBP) as well as an iterative algorithm (ITR). Different fluence modulation levels were investigated and their impact on the image was quantified in terms of SPR accuracy as well as noise within and outside selected ROIs, as a function of imaging dose. The unmodulated image served as reference. Results: Both FBP reconstruction and ITR without total variation (TV) yielded image quality in the ROIs similar to the reference images, for modulation down to 0.1 of the full proton fluence. The average dose was reduced by 75% for the water phantom and by 40% for the patient. FMpCT does not improve the noise for ITR with TV and modulation 0.1. Conclusion: This is the first work proposing and investigating FMpCT for producing optimal image quality for treatment planning and image guidance, while simultaneously reducing imaging dose. Future work will address spatial resolution effects and the impact of FMpCT on the quality of proton treatment plans for a prototype pCT scanner capable of list mode data acquisition. Acknowledgement: DFG-MAP DFG - Munich-Centre for Advanced Photonics (MAP)« less

A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light.

PubMed

Turan, Ilke Simsek; Yildiz, Deniz; Turksoy, Abdurrahman; Gunaydin, Gurcan; Akkaya, Engin U

2016-02-18

The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SU-F-T-258: Efficacy of Exit Fluence-Based Dose Calculation for Prostate Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siebers, J; Gardner, J; Neal, B

Purpose: To investigate the efficacy of exit-fluence-based dose computation for prostate radiotherapy by determining if it estimates true dose more accurately than the original planning dose. Methods: Virtual exit-fluencebased dose computation was performed for 19 patients, each with 9–12 repeat CT images. For each patient, a 78 Gy treatment plan was created utilizing 5 mm CTV-to-PTV and OAR-to-PRV margins. A Monte Carlo framework was used to compute dose and exit-fluence images for the planning image and for each repeat CT image based on boney-anatomyaligned and prostate-centroid-aligned CTs. Identical source particles were used for the MC dose-computations on the planning andmore » repeat CTs to maximize correlation. The exit-fluence-based dose and image were computed by multiplying source particle weights by FC(x,y)=FP(x,y)/FT(x,y), where (x,y) are the source particle coordinates projected to the exit-fluence plane and we denote the dose/fluence from the plan by (DP,FP), from the repeat-CT as (DT,FT), and the exit-fluence computation by (DFC,FFC). DFC mimics exit-fluence backprojection through the planning image as FT=FFC. Dose estimates were intercompared to judge the efficacy of exit-fluence-based dose computation. Results: Boney- and prostate-centroid aligned results are combined as there is no statistical difference between them, yielding 420 dose comparisons per dose-volume metric. DFC is more accurate than DP for 46%, 33%, and 44% of cases in estimating CTV D98, D50, and D2 respectively. DFC improved rectum D50 and D2 estimates 54% and 49% respectively and bladder D50 and D2 47 and 49% respectively. While averaged over all patients and images DFC and DP were within 3.1% of DT, they differed from DT by as much as 22% for GTV D98, 71% for the Bladder D50, 17% for Bladder D2, 19% for Rectum D2. Conclusion: Exit-fluence based dose computations infrequently improve CTV or OAR dose estimates and should be used with caution. Research supported in part by

Functional manganese dioxide nanosheet for targeted photodynamic therapy and bioimaging in vitro and in vivo

NASA Astrophysics Data System (ADS)

Kim, Seongchan; Ahn, Seong Min; Lee, Ji-Seon; Kim, Tae Shik; Min, Dal-Hee

2017-06-01

Photodynamic therapy (PDT) has been widely studied as a promising non-invasive therapeutic strategy for the treatment of cancer. However, the poor solubility of photosensitizer (PS) in aqueous solution and inefficient cell-penetrating capability have limited the target-specific PDT. Herein, we develop a novel targeted photodynamic therapeutic and bioimaging system based on folic acid (FA)-conjugated MnO2 (FA-MnO2) nanosheet as a new carrier of PS, zinc phthalocyanine (ZnPc). ZnPc loaded FA-MnO2 nanosheet (FA-MnO2/ZnPc) complex is successfully formed by electrostatic interaction and coordination. We find that FA-MnO2/ZnPc complex exhibits excellent targeted delivery of ZnPc into folate receptor positive cancer cells and the ZnPc is released out from the complex via endogenous glutathione (GSH) stimulus, facilitating simultaneous bioimaging and targeted PDT by singlet oxygen (SO) generation upon light irradiation, showing high efficacy with only one tenth of conventional PS dosage in vitro and in vivo.

Encapsulation of photosensitizer into multilayer microcapsules by combination of spontaneous deposition and heat-induced shrinkage for photodynamic therapy.

PubMed

Han, Yuanyuan; Bu, Jing; Zhang, Yuying; Tong, Weijun; Gao, Changyou

2012-10-01

Annealing of PDADMAC/PSS multilayer microcapsules assembled on PSS-doped CaCO(3) particles at 80 °C for 30 min reduces their size dramatically from 6.9 ± 0.3 to 3.1 ± 0.5 µm. Methylene blue molecules are encapsulated by spontaneous deposition and post-annealing with a concentration of 22 mg · mL(-1), which is 1000 times higher than the feeding value. The unreleased MB molecules are retained stably for a long time, which are then protected by the capsules against reductive enzymes and keep their photodynamic activity. The viability of HeLa cells incubated with the MB-loaded capsules decreases sharply from ≈ 75 (dark cytotoxicity) to ≈ 20% after irradiation with a laser at 671 nm and 60 J · cm(-2) for 75 s. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photochemical predictive analysis of photodynamic therapy with non-homogeneous topical photosensitizer distribution in dermatological applications

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.

2010-04-01

Photodynamic Therapy (PDT) is a therapeutic technique widely used in dermatology to treat several skin pathologies. It is based in topical or systemic delivery of photosensitizing drugs followed by irradiation with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell necrosis. In this work we present a PDT model that tries to predict the photodynamic effect on the skin with a topically administered photosensitizer. The time dependent inhomogeneous distribution of the photoactive compound protoporphyrin IX (PpIX) is calculated after obtaining its precursor distribution (Methyl aminolevulinate, MAL) which depends on the drug permeability, diffusion properties of the skin, incubation time and conversion efficiency of MAL to PpIX. Once the optical energy is obtained by means of the Beer Lambert law, a photochemical model is employed to estimate the concentration of the different molecular compounds taking into account the electronic transitions between molecular levels and particles concentrations. The results obtained allow us to know the evolution of the cytotoxic agent in order to estimate the necrotic area adjusting parameters such as the optical power, the photosensitizer concentration, the incubation and exposition time or the diffusivity and permeability of the tissue.

Physiological considerations acting on triplet oxygen for explicit dosimetry in photodynamic therapy.

PubMed

Sánchez, Víctor; Romero, María Paulina; Pratavieira, Sebastião; Costa, César

2017-09-01

The aims of this study were to determine the spatial and temporal theoretical distribution of the concentrations of Protoporphyrin IX, 3 O 2 and doses of 1 O 2 . The type II mechanism and explicit dosimetry in photodynamic therapy were used. Furthermore, the mechanism of respiration and cellular metabolism acting on 3 O 2 were taken into account. The dermis was considered as an absorbing and a scattering medium. An analytical solution was used for light diffusion in the skin. The photophysical, photochemical and biological effects caused by PDT with the initial irradiances of 20, 60 and 150mW/cm 2 were studied for a time of exposure of 20min and a maximum depth of 0.5cm. We found that the initial irradiance triples its value in 0.02cm and that almost 100% of PpIX is part of the dynamics of reactions in photodynamic therapy. Additionally, with about 40μMof 3 O 2 there is a balance between the consumed and supplied oxygen. Finally, we determined that with 60mW/cm 2 , the highest dose of 1 O 2 is obtained. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanistic aspects of the photodynamic inactivation of Candida albicans induced by cationic porphyrin derivatives.

PubMed

Quiroga, Ezequiel D; Cormick, M Paula; Pons, Patricia; Alvarez, M Gabriela; Durantini, Edgardo N

2012-12-01

Photodynamic inactivation of Candida albicans produced by 5-(4-trifluorophenyl)-10,15,20-tris(4-N,N,N-trimethylammoniumphenyl)porphyrin (TFAP(3+)), 5,10,15,20-tetrakis(4-N,N,N-trimethylammoniumphenyl)porphyrin (TMAP(4+)) and 5,10,15,20-tetrakis(4-N-methylpyridyl)porphyrin (TMPyP(4+)) was investigated to obtain insight about the mechanism of cellular damage. In solution, absorption spectroscopic studies showed that these cationic porphyrins interact strongly with calf thymus DNA. The electrophoretic analysis indicated that photocleavage of DNA induced by TFAP(3+) took place after long irradiation periods (>5 h). In contrast, TMAP(4+) produced a marked reduction in DNA band after 1 h irradiation. In C. albicans, these cationic porphyrins produced a ∼3.5 log decrease in survival when the cell suspensions (10(7) cells/mL) were incubated with 5 μM photosensitizer and irradiated for 30 min with visible light (fluence 162 J/cm(2)). After this treatment, modifications of genomic DNA isolated from C. albicans cells were not found by electrophoresis. Furthermore, transmission electron microscopy showed structural changes with appearance of low density areas into the cells and irregularities in cell barriers. However, the photodamage to the cell envelope was insufficient to cause the release of intracellular biopolymers. Therefore, modifications in the cytoplasmic biomolecules and alteration in the cell barriers could be mainly involved in C. albicans photoinactivation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Reducing Design Cycle Time and Cost Through Process Resequencing

NASA Technical Reports Server (NTRS)

Rogers, James L.

2004-01-01

In today's competitive environment, companies are under enormous pressure to reduce the time and cost of their design cycle. One method for reducing both time and cost is to develop an understanding of the flow of the design processes and the effects of the iterative subcycles that are found in complex design projects. Once these aspects are understood, the design manager can make decisions that take advantage of decomposition, concurrent engineering, and parallel processing techniques to reduce the total time and the total cost of the design cycle. One software tool that can aid in this decision-making process is the Design Manager's Aid for Intelligent Decomposition (DeMAID). The DeMAID software minimizes the feedback couplings that create iterative subcycles, groups processes into iterative subcycles, and decomposes the subcycles into a hierarchical structure. The real benefits of producing the best design in the least time and at a minimum cost are obtained from sequencing the processes in the subcycles.

Real-Time Monitoring of Singlet Oxygen and Oxygen Partial Pressure During the Deep Photodynamic Therapy In Vitro.

PubMed

Li, Weitao; Huang, Dong; Zhang, Yan; Liu, Yangyang; Gu, Yueqing; Qian, Zhiyu

2016-09-01

Photodynamic therapy (PDT) is an effective noninvasive method for the tumor treatment. The major challenge in current PDT research is how to quantitatively evaluate therapy effects. To our best knowledge, this is the first time to combine multi-parameter detection methods in PDT. More specifically, we have developed a set of system, including the high-sensitivity measurement of singlet oxygen, oxygen partial pressure and fluorescence image. In this paper, the detection ability of the system was validated by the different concentrations of carbon quantum dots. Moreover, the correlation between singlet oxygen and oxygen partial pressure with laser irradiation was observed. Then, the system could detect the signal up to 0.5 cm tissue depth with 660 nm irradiation and 1 cm tissue depth with 980 nm irradiation by using up-conversion nanoparticles during PDT in vitro. Furthermore, we obtained the relationship among concentration of singlet oxygen, oxygen partial pressure and tumor cell viability under certain conditions. The results indicate that the multi-parameter detection system is a promising asset to evaluate the deep tumor therapy during PDT. Moreover, the system might be potentially used for the further study in biology and molecular imaging.

Synthesis and photonic property study of ZnO nanowires for a real time photodynamic therapy monitoring probe

NASA Astrophysics Data System (ADS)

Sridhar, D.; Xie, Jining; Abraham, Jose K.; Varadan, Vijay K.

2007-04-01

In this paper, we present how the photonic properties of zinc oxide (ZnO) nanowires can be used to potentially advance the effectiveness of Photodynamic therapy (PDT), one of the most recent and promising approaches among cancer therapies. Presently, PDT employs laser light to activate intravenously or topically administered photosensitizers to give rise to highly reactive singlet oxygen which has a very short lifetime and is capable of biochemical damage to cell membranes of the tumor. A probe that can monitor in real time the penetration depth of the laser in the tumor and also the evolution of the singlet oxygen, which is critical for tumor eradication, is capable of improving the efficacy of PDT quite significantly. Such a probe, by providing real time feedback, can help us determine whether to increase or decrease the light exposure dose and also if further local administration of photosensitizers is required or not. ZnO nanowires are known to be photoconductive and recent research also demonstrated the temperature dependence of the photocurrent in the nanowires. They are also sensitive to blue and other near UV spectra which is same range of activation wavelengths of most photosensitizers, and hence making them a good candidate for a potential PDT monitoring probe. ZnO nanowires were fabricated on silicon substrates by vapor phase deposition using e-beam evaporated gold as a catalyst. Control of the dimensions of the nanowires could be achieved by varying the dimensions of the catalyst by means of e-beam evaporation process. Photoluminescence properties of ZnO nanowires were investigated at UV and near UV wavelengths. Further, ZnO is also known for its antimicrobial properties, thereby ruling out any possibility of bacterial infection because of the implanted probe. This study was done to compliment the existing expertise of our research group in the design and fabrication of several nanowire based probes and microsensors specifically for neuroelectronic and

Activation of photodynamic therapy in vitro with Cerenkov luminescence generated from Yttrium-90 (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hartl, Brad A.; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R.

2016-03-01

Translation of photodynamic therapy to the clinical setting has primarily been limited to easily accessible and/or superficial diseases where traditional light delivery can be performed noninvasively. Cerenkov luminescence, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively in order to overcome this depth limitation. We report on the use of Cerenkov luminescence generated from Yttrium-90 as a means to active the photodynamic therapy process in monolayer tumor cell cultures. The current study investigates the utility of Cerenkov luminescence for activating both the clinically relevant aminolevulinic acid at 1.0 mM and also the more efficient photosensitizer TPPS2a at 1.2 µM. Cells were incubated with aminolevulinic acid for 6 hours prior to radionuclide addition, as well as additional daily treatments for three days. TPPS2a was delivered as a single treatment with an 18 hour incubation time before radionuclide addition. Experiments were completed for both C6 glioma cells and MDA-MB-231 breast tumor cells. Although aminolevulinic acid proved ineffective for generating a therapeutic effect at any activity for either cell line, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 µCi/well for the C6 cell line. Current results demonstrate that it may be possible to generate a therapeutic effect in vivo using Cerenkov luminescence to activate the photodynamic therapy process with clinically relevant photosensitizers.

Local photodynamic therapy delays recurrence of equine periocular squamous cell carcinoma compared to cryotherapy.

PubMed

Giuliano, Elizabeth A; Johnson, Philip J; Delgado, Cherlene; Pearce, Jacqueline W; Moore, Cecil P

2014-07-01

(i) To report the successful treatment of 10 cases of equine periocular squamous cell carcinoma (PSCC) with surgical excision and photodynamic therapy (PDT) using verteporfin. (ii) To evaluate time to first tumor recurrence between PDT-treated horses and horses treated with surgical excision and cryotherapy. A total of 24 equine PSCC cases were included: group 1 (n = 14) had excision and cryotherapy (1993–2003), group 2 (n = 10), excision and local PDT (2006–2010). Evaluated data: signalment, treatment method, tumor location, size, and time to first recurrence. Groups were compared via chi-square test for categorical variables and Wilcoxon rank-sum test for numeric variables. Time to tumor recurrence was examined using Kaplan–Meier product-limit survival analysis. Of 24 cases, nine breeds were affected. Mean age at treatment in years: 14 (range 5–24) in group 1; 11 (range 8–18) in group 2. Median tumor size: 163 mm2 (range 20–625 mm2) in group 1; 195 mm2 (range 45–775 mm2) in group 2. Signalment, tumor laterality, and size were not significantly different between groups. Time to recurrence was significantly different between groups (Logrank test, P = 0.0006). In group 1, 11/14 horses had tumor regrowth with median time to recurrence in months: 10 (range 1–44). In group 2 (minimum follow-up of 25 months; range 25–50), no horse demonstrated tumor recurrence after one treatment with excision and PDT. This represents the first report of local PDT using verteporfin for treatment of equine PSCC. Following surgery, the likelihood of tumor recurrence was significantly reduced with local PDT compared with cryotherapy. © 2013 American College of Veterinary Ophthalmologists.

Comparing clinical effects of photodynamic therapy as a novel method with topical corticosteroid for treatment of Oral Lichen Planus.

PubMed

Bakhtiari, Sedigheh; Azari-Marhabi, Saranaz; Mojahedi, Seyyed Masoud; Namdari, Mahshid; Rankohi, Zahra Elmi; Jafari, Soudeh

2017-12-01

Oral lichen planus is an autoimmune disorder with several challenges in treatment. Photodynamic therapy has been proposed as a new treatment option for the disease. The present study compared the clinical effects of photodynamic therapy to dexamethasone mouthwash in the treatment of oral lichen planus lesions. In this randomized clinical trial, 30 patients with oral lichen planus were included.15 patients were treated with 5% methylene blue mediated photodynamic therapy using Fotosan device for 30s (630nm wavelength and 7.2-14.4J/cm 2 dose) for 4 sessions in the days 1, 4, 7, 14. In another group, the treatment was done on 15 patients by 0.5mg tab dexamethasone solution in 5cc water, rinsed 4 times in a day within two weeks. The sign score, symptoms scores (pain), clinical severity and treatment efficacy were measured at the days 15, 30, 60, 90 after beginning of the treatment. The results were subjected to Mann-whitney U test in both groups. No significant difference existed between the two modalities regarding the treatment efficacy index, sign score, symptom score and clinical severity on the 15, 30, 60 and 90 post-treatment days. Decreases in patient's symptoms were statistically significant in both groups. Photodynamic therapy was as effective as the dexamethasone mouth wash in the treatment of oral lichen planus. It could be used as a safe modality in the treatment of oral lichen planus lesions without identified side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

PubMed Central

Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

2015-01-01

Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

Electron fluence correction factors for various materials in clinical electron beams.

PubMed

Olivares, M; DeBlois, F; Podgorsak, E B; Seuntjens, J P

2001-08-01

Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at dmax in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase-space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than +/- 1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between 0.83+/-0.01 and 1.55+/-0.02 for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from -1.6% to +0.2% at 9 MeV and from -1.9% to +0.2% at 15 MeV and is not significant at the 1sigma level. Excluding the data for Cu, electron

Photodynamic therapy as a novel treatment for halitosis in adolescents: study protocol for a randomized controlled trial.

PubMed

Lopes, Rubia Garcia; de Godoy, Camila Haddad Leal; Deana, Alessandro Melo; de Santi, Maria Eugenia Simões Onofre; Prates, Renato Araujo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Bussadori, Sandra Kalil

2014-11-14

Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% and systemic in 10% of cases. The unpleasant odor is mainly the result of volatile sulfur compounds produced by Gram-negative bacteria. However, it has recently been found that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the presence of amino acids, such as cysteine. Light, both with and without the use of chemical agents, has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by photosensitizing dye. The aim of the present study is to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using gas chromatography and microbiological analysis of coated tongue. A quantitative clinical trial will be carried out involving 60 adolescents randomly divided into the following groups: group 1 will receive treatment with a tongue scraper, group 2 will receive photodynamic therapy applied to the posterior two-thirds of the dorsum of the tongue, and group 3 will receive combined treatment (tongue scraper and photodynamic therapy). Gas chromatography (OralChromaTM) and microbiological analysis will be used for the diagnosis of halitosis at the beginning of the study. Post-treatment evaluations will be conducted at one hour and 24 hours after treatment. The statistical analysis will include the Shapiro-Wilk test for the determination of the distribution of the data. If normal distribution is demonstrated, analysis of variance followed by Tukey's test will be used to compare groups. The Kruskal-Wallis test followed by the Student-Newman-Keuls test will be used for data with non-normal distribution. Either the paired t-test or the Wilcoxon test will be used to compare data before and after treatment, depending on the distribution of the data. The

Study on accumulated crystallization characteristics of amorphous Ge2Sb2Te5 induced by multi-pulsed laser irradiations with different fluences

NASA Astrophysics Data System (ADS)

Fan, T.; Liu, F. R.; Li, W. Q.; Guo, J. C.; Wang, Y. H.; Sun, N. X.; Liu, F.

2018-07-01

Accumulated crystallization characteristics of amorphous Ge2Sb2Te5 (a-GST) films induced by multi-pulsed laser irradiations with different fluences were investigated by x-ray diffraction (XRD), Raman spectroscopy and spectrophotometer. Solid-state transformation was performed at low fluence (LF, 30.5 mJ cm‑2), whereas melting-cooling transformation dominated at medium and high fluence (MF, 45.7 and HF, 61 mJ cm‑2). Solid-state transformation induced by subsequent LF pulses promoted the growth and coalescence of grains, linearly increasing the average grain size, accordingly causing blue-shifts of the Raman spectral peaks. For MF/HF pulse irradiated films, the relatively high laser fluence increased the melting depth and reduced the volume fraction of the crystalline state induced by individual pulses, thereby increasing the threshold of laser pulse numbers for XRD detectable crystallization. However, the remelting depth induced by subsequent MF/HF laser pulse progressively decreased. The remelting-recrystallization process refined grain sizes, which improved the red-shifts of Raman spectral peaks. Moreover, optical contrast increased dramatically compared to single laser irradiation and five-level storage could be realized for a linear increase of optical contrast. The present study is fundamental for realizing the potential of multi-level devices.

Structural and magnetic fluence dependence in cobalt titanate thin films synthesized by pulse laser deposition

NASA Astrophysics Data System (ADS)

Prisbrey, Shon Thomas

Knowledge of the fundamental structure and magnetic characteristics of dilute magnetic semiconductors (DMSs) is an essential step towards the development of spin-polarized electronics (spintronics). Recently (2001), the report of ferromagnetism in cobalt-doped anatase titania films synthesized by pulse laser deposition (PLD) elicited interest as a possible DMS oxide. Other investigations of the CoxTi1-xO2-delta material system, utilizing a myriad of deposition techniques, yielded conflicting results as to the source of magnetism and the local environment of the deposited cobalt. No complete characterization of PLD synthesized films has been reported. This dissertation quantifies the effect of laser fluence on film morphology, structure, and magnetic properties by fully characterizing CoxTi1-x O2-delta films grown under optimal PLD deposition conditions that were identified separately in prior published work. The construction of a custom PLD system that provided repeatable laser/target interaction via a combination of fluence and target movement is addressed. A brief outline of magnetism and its relation to structure is also given. The remainder of the dissertation details the effect of laser fluence on Co0.049Ti0.951O2-delta and Co 0.038Ti0.962O2-delta films. Film structure, morphology, and magnetic properties were determined for illumination conditions corresponding to laser fluences varying from 0.57 to 1.37 J/cm2. The local cobalt environment is strongly correlated with laser fluence. Cobalt in 4.9% concentration films grown with a laser fluence between 0.7 and 0.93 J/cm2 were octahedrally coordinated, as were 3.8% films grown with a fluence less than 0.93 J/cm2. Departure of the laser fluence from these ranges results in a multitude of cobalt environments in the films. The film magnetization is observed to be a function of laser fluence with a maximum moment of ˜3.19 muB per cobalt atom occurring at 0.93 J/cm2 in the 4.9% films and ˜1.9 muB per cobalt atom at

Hypertrichosis in Becker's nevus: effective low-fluence laser hair removal.

PubMed

Lapidoth, M; Adatto, M; Cohen, S; Ben-Amitai, D; Halachmi, S

2014-01-01

Becker's nevus is cosmetically bothersome both due to the hyperpigmentation and due to the hypertrichosis which can accompany it, particularly in males. Laser hair removal can be considered, but the pigmented background of the Becker's nevus makes the treatment more challenging. Fifteen patients with Becker's nevus underwent eight sessions of hair removal with low-fluence high-repetition-rate diode lasers (808-810 nm). All participants experienced significant hair reduction at 6 and 12 months. No adverse events were reported. The study supports the use of low fluence with high-repetition-rate diode laser hair removal as a safe and effective method for the management of hypertrichosis in Becker's nevus.

A Cell-targeted Photodynamic Nanomedicine Strategy for Head & Neck Cancers

PubMed Central

Master, Alyssa; Malamas, Anthony; Solanki, Rachna; Clausen, Dana M.; Eiseman, Julie L.; Gupta, Anirban Sen

2013-01-01

Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. To this end, we report on a cell-targeted nanomedicine approach for the photosensitizer silicon phthalocyanine-4 (Pc 4), by packaging it within polymeric micelles that are surface-decorated with GE11-peptides to promote enhanced cell-selective binding and receptor-mediated internalization in EGFR-overexpressing H&N cancer cells. Using fluorescence spectroscopy and confocal microscopy, we demonstrate in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N SCC-15 cells. We further demonstrate that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, we demonstrate that the EGFR-targeted Pc 4-nanoformulation results in significant intra-tumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas. PMID:23531079

Mechanistics and photo-energetics of macrocycles and photodynamic therapy: An overview of aspects to consider for research.

PubMed

Horne, Tamarisk K; Cronjé, Marianne J

2017-02-01

Research within the field of photodynamic therapy has escalated over the past 20 years. The required conjunctional use of photosensitizers, particularly of the macrocycle structure, has lead to a vast repertoire of derivatives that branch classes and subclasses thereof. Each exhibits a differential range of physiochemical properties that influence their potential applications within the larger phototherapy field for use in either diagnostics, photodynamic therapy, both or none. Herein, we provide an overview of these properties as they relate to photodynamic therapy and to a lesser extent diagnostics. By summarizing the mechanistics of photodynamic therapy coupled to the photo-energetics displayed by macrocycle photosensitizers, we aimed to highlight the critical aspects any researcher should be aware of and consider when selecting and performing research for therapeutic application purposes. These include photosensitizer, photophysical and structural properties, synthesis design and subsequent attributes, main applications within research, common shortcomings exhibited and the current methods practiced to overcome them. © 2017 John Wiley & Sons A/S.

Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With Pseudomonas aeruginosa and Fusarium spp.

PubMed

Aspiroz, C; Sevil, M; Toyas, C; Gilaberte, Y

Photodynamic therapy (PDT) is a therapeutic modality with significant antimicrobial activity. We present 2 cases of chronic lower limb ulcers in which fungal and bacterial superinfection complicated management. PDT with methylene blue as the photosensitizer led to clinical and microbiological cure with no significant adverse effects. PDT with methylene blue is a valid option for the management of superinfected chronic ulcers, reducing the use of antibiotics and the induction of resistance. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Space Environment Effects: Model for Emission of Solar Protons (ESP): Cumulative and Worst Case Event Fluences

NASA Technical Reports Server (NTRS)

Xapsos, M. A.; Barth, J. L.; Stassinopoulos, E. G.; Burke, E. A.; Gee, G. B.

1999-01-01

The effects that solar proton events have on microelectronics and solar arrays are important considerations for spacecraft in geostationary and polar orbits and for interplanetary missions. Designers of spacecraft and mission planners are required to assess the performance of microelectronic systems under a variety of conditions. A number of useful approaches exist for predicting information about solar proton event fluences and, to a lesser extent, peak fluxes. This includes the cumulative fluence over the course of a mission, the fluence of a worst-case event during a mission, the frequency distribution of event fluences, and the frequency distribution of large peak fluxes. Naval Research Laboratory (NRL) and NASA Goddard Space Flight Center, under the sponsorship of NASA's Space Environments and Effects (SEE) Program, have developed a new model for predicting cumulative solar proton fluences and worst-case solar proton events as functions of mission duration and user confidence level. This model is called the Emission of Solar Protons (ESP) model.

Space Environment Effects: Model for Emission of Solar Protons (ESP)--Cumulative and Worst-Case Event Fluences

NASA Technical Reports Server (NTRS)

Xapsos, M. A.; Barth, J. L.; Stassinopoulos, E. G.; Burke, Edward A.; Gee, G. B.

1999-01-01

The effects that solar proton events have on microelectronics and solar arrays are important considerations for spacecraft in geostationary and polar orbits and for interplanetary missions. Designers of spacecraft and mission planners are required to assess the performance of microelectronic systems under a variety of conditions. A number of useful approaches exist for predicting information about solar proton event fluences and, to a lesser extent, peak fluxes. This includes the cumulative fluence over the course of a mission, the fluence of a worst-case event during a mission, the frequency distribution of event fluences, and the frequency distribution of large peak fluxes. Naval Research Laboratory (NRL) and NASA Goddard Space Flight Center, under the sponsorship of NASA's Space Environments and Effects (SEE) Program, have developed a new model for predicting cumulative solar proton fluences and worst-case solar proton events as functions of mission duration and user confidence level. This model is called the Emission of Solar Protons (ESP) model.

Chemical modification of normal tissue damage induced by photodynamic therapy.

PubMed Central

Sigdestad, C. P.; Fingar, V. H.; Wieman, T. J.; Lindberg, R. D.

1996-01-01

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses. PMID:8763855

Photodynamic method used for the treatment of malignant melanoma and Merkel cell carcinoma

NASA Astrophysics Data System (ADS)

Domaniecki, Janusz; Stanowski, Edward; Graczyk, Alfreda; Kalczak, M.; Struzyna, Jerzy; Kwasny, Miroslaw; Mierczyk, Zygmunt; Najdecki, M.; Krupa, J.

1997-10-01

A photodynamic method is successfully applied for tumor diagnosis treatment. We used such a method for a dozen or so patients with primary and metastatic skin tumors. As photosensitizers HpD (Arg)2 and PP(Ala)2(Arg)2 were used in concentration of 1 mg/ml. The photosensitizers wee administered directly into tumors with a does of 0.1 divided by 0.2 ml. As a result of tumor irradiation by means of the He-Cd laser, a tumor intensively luminates what makes it possible to determine accurately its size and shape. Next, we applied a series of irradiation by means of He-Ne laser during the successive three days and patients received full dose of 150 J/cm2 per tumor surface. For extensive tumors such an irradiation series was repeated after 7 days. The patients were divided into three groups depending on tumor size. The first group of patients with tumors of 0.5 cm of diameter showed very good treatment results just after the first series of irradiation. The second group of patients with tumors of 0.5-1.5 cm showed very good treatment results after two series of irradiation. The third group of patients with tumors of diameter over 1.0 cm showed acceptable treatment results after two series of irradiations, determined as sufficient ones. The patients from the third group wee operated on after 7 divided by 10 days from the time of the completed irradiation. The photodynamic method can be used as a method for tumor diagnosis and skin tumor treatment as well as a supplementary method for surgical intervention.

Performance improvement: one model to reduce length of stay.

PubMed

Chisari, E; Mele, J A

1994-01-01

Dedicated quality professionals are tired of quick fixes, Band-Aids, and other first-aid strategies that offer only temporary relief of nagging problems rather than a long-term cure. Implementing strategies that can produce permanent solutions to crucial problems is a challenge confronted by organizations striving for continuous performance improvement. One vehicle, driven by data and customer requirements, that can help to solve problems and sustain success over time is the storyboard. This article illustrates the use of the storyboard as the framework for reducing length of stay--one of the most important problems facing healthcare organizations today.

Interventions to reduce waiting times for elective procedures.

PubMed

Ballini, Luciana; Negro, Antonella; Maltoni, Susanna; Vignatelli, Luca; Flodgren, Gerd; Simera, Iveta; Holmes, Jane; Grilli, Roberto

2015-02-23

Long waiting times for elective healthcare procedures may cause distress among patients, may have adverse health consequences and may be perceived as inappropriate delivery and planning of health care. To assess the effectiveness of interventions aimed at reducing waiting times for elective care, both diagnostic and therapeutic. We searched the following electronic databases: Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946-), EMBASE (1947-), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), ABI Inform, the Canadian Research Index, the Science, Social Sciences and Humanities Citation Indexes, a series of databases via Proquest: Dissertations & Theses (including UK & Ireland), EconLit, PAIS (Public Affairs International), Political Science Collection, Nursing Collection, Sociological Abstracts, Social Services Abstracts and Worldwide Political Science Abstracts. We sought related reviews by searching the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE). We searched trial registries, as well as grey literature sites and reference lists of relevant articles. We considered randomised controlled trials (RCTs), controlled before-after studies (CBAs) and interrupted time series (ITS) designs that met EPOC minimum criteria and evaluated the effectiveness of any intervention aimed at reducing waiting times for any type of elective procedure. We considered studies reporting one or more of the following outcomes: number or proportion of participants whose waiting times were above or below a specific time threshold, or participants' mean or median waiting times. Comparators could include any type of active intervention or standard practice. Two review authors independently extracted data from, and assessed risk of bias of, each included study, using a standardised form and the EPOC 'Risk

Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets in a NAND Flash Memory

NASA Technical Reports Server (NTRS)

Chen, Dakai; Wilcox, Edward; Ladbury, Raymond L.; Kim, Hak; Phan, Anthony; Seidleck, Christina; Label, Kenneth

2016-01-01

We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found that the single-event upset (SEU) cross section varied inversely with cumulative fluence. We attribute the effect to the variable upset sensitivities of the memory cells. Furthermore, the effect impacts only single cell upsets in general. The rate of multiple-bit upsets remained relatively constant with fluence. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, traditional SEE testing techniques may underestimate the on-orbit event rate for a device with variable upset sensitivity.

Physiological oxygen concentration alters glioma cell malignancy and responsiveness to photodynamic therapy in vitro.

PubMed

Albert, Ina; Hefti, Martin; Luginbuehl, Vera

2014-11-01

The partial pressure of oxygen (pO2) in brain tumors ranges from 5 to 15%. Nevertheless, the majority of in vitro experiments with glioblastoma multiforme (GBM) cell lines are carried out under an atmospheric pO2 of 19 to 21%. Recently, 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), has been introduced to neurosurgery to allow for photodynamic diagnosis and photodynamic therapy (PDT) in high-grade gliomas. Here, we investigate whether low pO2 affects GBM cell physiology, PpIX accumulation, or PDT efficacy. GBM cell lines (U-87 MG and U-251 MG) were cultured under atmospheric (pO2  =  19%) and physiological (pO2  =  9%) oxygen concentrations. PpIX accumulation and localization were investigated, and cell survival and cell death were observed following in vitro PDT. A physiological pO2 of 9% stimulated GBM cell migration, increased hypoxia-inducible factor (HIF)-1 alpha levels, and elevated resistance to camptothecin in U-87 MG cells compared to cultivation at a pO2 of 19%. This oxygen reduction did not alter 5-ALA-induced intracellular PpIX accumulation. However, physiological pO2 changed the responsiveness of U-87 MG but not of U-251 MG cells to in vitro PDT. Around 20% more irradiation light was required to kill U-87 MG cells at physiological pO2, resulting in reduced lactate dehydrogenase (LDH) release (one- to two-fold) and inhibition of caspase 3 activation. Reduction of oxygen concentration from atmospheric to a more physiological level can influence the malignant behavior and survival of GBM cell lines after in vitro PDT. Therefore, precise oxygen concentration control should be considered when designing and performing experiments with GBM cells.

The synergistic effect of photodynamic therapy and photothermal therapy in the presence of gold-gold sulfide nanoshells conjugated Indocyanine green on HeLa cells.

PubMed

Ghorbani, Farzaneh; Attaran-Kakhki, Neda; Sazgarnia, Ameneh

2017-03-01

Photodynamic therapy (PDT) and photothermal therapy (PTT) are two known optical remedies of cancer. PTT can be combined with other therapies. One of the limitations of optical therapies is the penetration of light into biological tissues, which reduces its effectiveness due to usage of photosensitizers and PTT agents, which are absorbed in the NIR region that provides the maximum penetration. For instance, Indocyanine green (ICG) serves as a photosensitizer and Gold nanostructures as agents for PTT. GGS is a gold nanoshell with two absorption peaks in the NIR and visible regions. The aim of this study is to evaluate the synergistic effect of PDT and PTT in the presence of GGS conjugated with ICG. After synthesizing GGS, ICG was conjugated with GGS. The specifications and cytotoxicity of agents were identified. Cells were irradiated by an 808nm laser with or without the agents and three laser outputs were achieved, with each having four different exposure times. The viability of treated cells was determined via MTT assay. The irradiation of the laser did not produce any significant effect by itself or in the presence of GGS. The maximum cell death recorded for GGS, ICG and GGS-ICG were 15±7%, 50±3% and 31±3% respectively. ICG and GGS-ICG differs significantly for exposures higher than 2250J/cm 2 . The conjugate was provided through a simple process and a greater chemical stability compared to GGS was achieved. Moreover, it induced a stronger photodynamic and photothermal effect on the cells. This is a promising result which can help enhance the effectiveness of a minimally invasive treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy of Intense Pulsed Light Therapy in the Treatment of Facial Acne Vulgaris: Comparison of Two Different Fluences

PubMed Central

Patidar, Monika V; Deshmukh, Ashish Ramchandra; Khedkar, Maruti Yadav

2016-01-01

Background: Acne vulgaris is the most common disease of the skin affecting adolescents and young adults causing psychological distress. The combination of antibiotic resistance, adverse effects of topical and systemic anti acne medications and desire for high tech approaches have all led to new enthusiasm for light based acne treatment. Intense pulse light (IPL) therapy has three modes of action in acne vulgaris i.e., photochemical, photo thermal and photo immunological. Aims: (1) to study efficacy of IPL therapy in facial acne vulgaris. (2) To compare two fluences - one normal and other subnormal on right and left side of face respectively. Methods: (Including settings and design and statistical analysis used). Total 45 patients in age group 16 to 28 years with inflammatory facial acne vulgaris were included in prospective study. Baseline data for each patient was recorded. All patients were given 4 sittings of IPL at 2 weeks interval and were followed for 2 months every 2 weeks. Fluence used was 35J/cm2 on right and 20J/cm2 on left side. Percentage reduction in lesion count was calculated at each sitting and follow up and graded as mild (0-25%), moderate (26-50%), good (51-75%) and excellent (76-100%). Side effects were noted. The results were analysed using Mann-Whitney Test. Results: On right side, excellent results were achieved in 10(22%), good in 22(49%) and moderate in 13(29%) patients. On left side excellent were results achieved in 7(15%), good in 19(42%) and moderate in 16(43%) patients. There was no statically significant difference noted in efficacy of two fluences used in treatment of facial acne vulgaris. Conclusions: IPL is a effective and safe option for inflammatory acne vulgaris with minimal reversible side effects. Subnormal fluence is as effective as normal fluence in Indian skin. PMID:27688446

Efficacy of Intense Pulsed Light Therapy in the Treatment of Facial Acne Vulgaris: Comparison of Two Different Fluences.

PubMed

Patidar, Monika V; Deshmukh, Ashish Ramchandra; Khedkar, Maruti Yadav

2016-01-01

Acne vulgaris is the most common disease of the skin affecting adolescents and young adults causing psychological distress. The combination of antibiotic resistance, adverse effects of topical and systemic anti acne medications and desire for high tech approaches have all led to new enthusiasm for light based acne treatment. Intense pulse light (IPL) therapy has three modes of action in acne vulgaris i.e., photochemical, photo thermal and photo immunological. (1) to study efficacy of IPL therapy in facial acne vulgaris. (2) To compare two fluences - one normal and other subnormal on right and left side of face respectively. (Including settings and design and statistical analysis used). Total 45 patients in age group 16 to 28 years with inflammatory facial acne vulgaris were included in prospective study. Baseline data for each patient was recorded. All patients were given 4 sittings of IPL at 2 weeks interval and were followed for 2 months every 2 weeks. Fluence used was 35J/cm(2) on right and 20J/cm(2) on left side. Percentage reduction in lesion count was calculated at each sitting and follow up and graded as mild (0-25%), moderate (26-50%), good (51-75%) and excellent (76-100%). Side effects were noted. The results were analysed using Mann-Whitney Test. On right side, excellent results were achieved in 10(22%), good in 22(49%) and moderate in 13(29%) patients. On left side excellent were results achieved in 7(15%), good in 19(42%) and moderate in 16(43%) patients. There was no statically significant difference noted in efficacy of two fluences used in treatment of facial acne vulgaris. IPL is a effective and safe option for inflammatory acne vulgaris with minimal reversible side effects. Subnormal fluence is as effective as normal fluence in Indian skin.

Susceptibility of Enterococcus faecalis and Propionibacterium acnes to antimicrobial photodynamic therapy.

PubMed

de Annunzio, Sarah Raquel; de Freitas, Laura Marise; Blanco, Ana Lígia; da Costa, Mardoqueu Martins; Carmona-Vargas, Christian C; de Oliveira, Kleber Thiago; Fontana, Carla Raquel

2018-01-01

Bacterial resistance to available antibiotics nowadays is a global threat leading researchers around the world to study new treatment modalities for infections. Antimicrobial photodynamic therapy (aPDT) has been considered an effective and promising therapeutic alternative in this scenario. Briefly, this therapy is based on the activation of a non-toxic photosensitizing agent, known as photosensitizer (PS), by light at a specific wavelength generating cytotoxic singlet oxygen and free radicals. Virtually all studies related to aPDT involve a huge screening to identify ideal PS concentration and light dose combinations, a laborious and time-consuming process that is hardly disclosed in the literature. Herein, we describe an antimicrobial Photodynamic Therapy (aPDT) study against Enterococcus faecalis and Propionibacterium acnes employing methylene blue, chlorin-e6 or curcumin as PS. Similarities and discrepancies between the two bacterial species were pointed out in an attempt to speed up and facilitate futures studies against those clinical relevant strains. Susceptibility tests were performed by the broth microdilution method. Our results demonstrate that aPDT mediated by the three above-mentioned PS was effective in eliminating both gram-positive bacteria, although P. acnes showed remarkably higher susceptibility to aPDT when compared to E. faecalis. PS uptake assays revealed that P. acnes is 80 times more efficient than E. faecalis in internalizing all three PS molecules. Our results evidence that the cell wall structure is not a limiting feature when predicting bacterial susceptibility to aPDT treatment. Copyright © 2017. Published by Elsevier B.V.

In silico modelling of apoptosis induced by photodynamic therapy.

PubMed

López-Marín, N; Mulet, R

2018-01-07

Photodynamic therapy (PDT) is an emergent technique used for the treatment of several diseases. After PDT, cells die by necrosis, apoptosis or autophagy. Necrosis is produced immediately during photodynamic therapy by high concentration of reactive oxygen species, apoptosis and autophagy are triggered by mild or low doses of light and photosensitizer. In this work we model the cell response to low doses of PDT assuming a bi-dimensional matrix of interacting cells. For each cell of the matrix we simulate in detail, with the help of the Gillespie's algorithm, the two main chemical pathways leading to apoptosis. We unveil the role of both pathways in the cell death rate of the tumor, as well as the relevance of several molecules in the process. Our model suggests values of concentrations for several species of molecules to enhance the effectiveness of PDT. Copyright © 2017 Elsevier Ltd. All rights reserved.

ALA-Butyrate prodrugs for Photo-Dynamic Therapy

NASA Astrophysics Data System (ADS)

Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

2010-05-01

The use of 5-aminolevulinic acid (ALA) administration has led to many applications of photodynamic therapy (PDT) in cancer. However, the hydrophilic nature of ALA limits its ability to penetrate the cells and tissues, and therefore the need for ALA derivatives became an urgent research target. In this study we investigated the activity of novel multifunctional acyloxyalkyl ester prodrugs of ALA that upon metabolic hydrolysis release active components such as, formaldehyde, and the histone deacetylase inhibitory moiety, butyric acid. Evaluation of these prodrugs under photo-irradiation conditions showed that butyryloxyethyl 5-amino-4-oxopentanoate (ALA-BAC) generated the most efficient photodynamic destruction compared to ALA. ALA-BAC stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells which resulted in generation of intracellular ROS, reduction of mitochondrial activity, leading to apoptotic and necrotic death of the cells. The apoptotic cell death induced by ALA / ALA-BAC followed by PDT equally activate intrinsic and extrinsic apoptotic signals and both pathways may occur simultaneously. The main advantage of ALA-BAC over ALA stems from its ability to induce photo-damage at a significantly lower dose than ALA.

Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia.

PubMed

Kawczyk-Krupka, Aleksandra; Waśkowska, Jadwiga; Raczkowska-Siostrzonek, Agnieszka; Kościarz-Grzesiok, Anna; Kwiatek, Sebastian; Straszak, Dariusz; Latos, Wojciech; Koszowski, Rafał; Sieroń, Aleksander

2012-06-01

Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic. Copyright © 2011 Elsevier B.V. All rights reserved.

New hybrid composites for photodynamic therapy: synthesis, characterization and biological study

NASA Astrophysics Data System (ADS)

Kutsevol, N.; Naumenko, A.; Harahuts, Yu.; Chumachenko, V.; Shton, I.; Shishko, E.; Lukianova, N.; Chekhun, V.

2018-04-01

Photodynamic therapy is a procedure that uses a photosensitizing drug to apply light therapy selectively to target cancer treatment. This study is focused on a synthesis and characterization of a new hybrid nanocomposites based on the branched copolymers dextran-polyacrylamide in nonionic, D-g-PAA and anionic D-g-PAA(PE) form, with incorporated gold nanoparticles (AuNPs) and photosensitizer chlorin e6 (Ce6) simultaneously. Double polymer/AuNPs and trial polymer/AuNPs/Ce6 were studied by TEM, UV-visible, SOSG fluorescence. It was found the drastic difference for absorbance for trial nanosystems synthesized in nonionic and anionic polymers matrices. It was established that for the nanocomposite synthesised in anionic polymer matrix with the Ce6:Au mass ratio 1:10 generation of singlet oxygen (1O2) was quite close to that for free Ce6. The study of ability of this nanosystem to sensitize MT-4 cells to photodynamic damage has shown that the nanocomposite, that contained AuNPs during the synthesis of which HAuCl4:NaBH4 mass ratio was 1:2 showed higher photodynamic activity, than Ce6 itself. Nanosystem D70-g-PAA(PE)/AuNPs/Ce6 can be recommended to experiment in vivo.

In vitro evaluation of photodynamic therapy using curcumin on Leishmania major and Leishmania braziliensis.

PubMed

Pinto, Juliana Guerra; Fontana, Letícia Correa; de Oliveira, Marco Antonio; Kurachi, Cristina; Raniero, Leandro José; Ferreira-Strixino, Juliana

2016-07-01

Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 μg/ml up to 7.8 μg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm(2) at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed.

Real-time quantitative reverse transcription-PCR analysis of expression stability of Aggregatibacter actinomycetemcomitans fimbria-associated gene in response to photodynamic therapy.

PubMed

Pourhajibagher, Maryam; Monzavi, Abbas; Chiniforush, Nasim; Monzavi, Mohammad Moein; Sobhani, Shaghayegh; Shahabi, Sima; Bahador, Abbas

2017-06-01

Aggregatibacter actinomycetemcomitans is an etiological agent of both chronic and aggressive periodontitis. Dissemination of A. actinomycetemcomitans from the oral cavity and initiation of systemic infections has led to new approaches for treatment being needed. In this study, a series of experiments presented investigated the effect of methylene blue (MB)-mediated antimicrobial photodynamic therapy (aPDT) on cell viability and expression of fimbria-associated gene (rcpA) in A. actinomycetemcomitans. To determine the dose-depended effects of aPDT, A. actinomycetemcomitans ATCC 33384 strain photosensitized with MB was irradiated with diode laser following bacterial viability measurements. Cell-surviving assay and expression ratio of rcpA were assessed by colony forming unit and real-time quantitative reverse transcription-PCR (qRT-PCR) assays, respectively. In the current study, MB-mediated aPDT using 100μg/mL showed significant reduction in A. actinomycetemcomitans growth when compared to the control (P<0.05). Sub-lethal dose of aPDT against A. actinomycetemcomitans was 25μg/mL MB at fluency of 93.75J/cm 2 . Sub-lethal dose of aPDT could lead to about four-fold suppression of expression of rcpA. High doses of MB-mediated aPDT could potentially exhibit antimicrobial activity, and the expression of rcpA as an important virulence factor of this strain is reduced in cells surviving aPDT with MB. So, aPDT can be a valuable tool for the treatment of A. actinomycetemcomitans infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Photodynamic inactivation of Candida albicans sensitized by tri- and tetra-cationic porphyrin derivatives.

PubMed

Cormick, M Paula; Alvarez, M Gabriela; Rovera, Marisa; Durantini, Edgardo N

2009-04-01

The photodynamic action of 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide (TFAP(3+)) and 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP(4+)) has been studied in vitro on Candida albicans. The results of these cationic porphyrins were compared with those of 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS(4-)), which characterizes an anionic sensitizer. In vitro investigations show that these cationic porphyrins are rapidly bound to C. albicans cells, reaching a value of approximately 1.4 nmol/10(6) cells, when the cellular suspensions were incubated with 5 microM sensitizer for 30 min. In contrast, TPPS(4-) is poorly uptaken by yeast cells. The fluorescence spectra of these sensitizers into the cells confirm this behaviour. The amount of porphyrin binds to cells is dependent on both sensitizer concentrations (1-5 microM) and cells densities (10(6)-10(8) cells/mL). Photosensitized inactivation of C. albicans cellular suspensions increases with sensitizer concentration, causing a approximately 5 log decrease of cell survival, when the cultures are treated with 5 microM of cationic porphyrin and irradiated for 30 min. However, the photocytotoxicity decreases with an increase in the cell density, according to its low binding to cells. Under these conditions, the photodynamic activity of TFAP(3+) is quite similar to that produced by TMAP(4+), whereas no important inactivation effect was found for TPPS(4)(-). The high photodynamic activity of cationic porphyrins was confirmed by growth delay experiments. Thus, C. albicans cell growth was not detected in the presence of 5 microM TFAP(3+). Photodynamic inactivation capacities of these sensitizers were also evaluated on C. albicans cells growing in colonies on agar surfaces. Cationic porphyrins produce a growth delay of C. albicans colonies and viability of cells was not observed after 3 h irradiation, indicating a complete inactivation of yeast cells

Neutron Fluence and Energy Reconstruction with the LNE-IRSN/MIMAC Recoil Detector MicroTPC at 27 keV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maire, D.; Lebreton, L.; Querre, Ph.

2015-07-01

The French Institute for Radiation protection and Nuclear Safety (IRSN), designated by the French Metrology Institute (LNE) for neutron metrology, is developing a time projection chamber using a Micromegas anode: microTPC. This work is carried out in collaboration with the Laboratory of Subatomic Physics and Cosmology (LPSC). The aim is to characterize the energy distribution of neutron fluence in the energy range 8 keV - 5 MeV with a primary procedure. The time projection chambers are gaseous detectors able to measure charged particles energy and to reconstruct their track if a pixelated anode is used. In our case, the gasmore » is used as a (n, p) converter in order to detect neutrons down to few keV. Coming from elastic collisions with neutrons, recoil protons lose a part of their kinetic energy by ionizing the gas. The ionization electrons are drifted toward a pixelated anode (2D projection), read at 50 MHz by a self-triggered electronic system to obtain the third track dimension. The neutron energy is reconstructed event by event thanks to proton scattering angle and proton energy measurements. The scattering angle is deduced from the 3D track. The proton energy is obtained by charge collection measurements, knowing the ionization quenching factor (i.e. the part of proton kinetic energy lost by ionizing the gas). The fluence is calculated thanks to the detected events number and the simulation of the detector response. The μTPC is a new reliable detector able to measure energy distribution of the neutron fluence without unfolding procedure or prior neutron calibration contrary to usual gaseous counters. The microTPC is still being developed and measurements have been carried out at the AMANDE facility, with neutrons energies going from 8 keV to 565 keV. After the context and the μ-TPC working principle presentation, measurements of the neutron energy and fluence at 27 keV and 144 keV are shown and compared to the complete detector response simulation. This

Involvement of Bim in Photofrin-mediated photodynamically induced apoptosis.

PubMed

Wang, Xianwang; He, Xiaobing; Hu, Shujuan; Sun, Anbang; Lu, Chengbiao

2015-01-01

Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2 family proteins play important roles in PDT-induced apoptosis. However, whether Bcl-2-interacting mediator of cell death (Bim) is involved in photodynamic treatment remains unknown. In this study, we attempt to determine the effect of Bim on Photofrin photodynamic treatment (PPT)-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells. The translocation of Bim/Bax of the cells were monitored by laser confocal scanning microscope. The levels of Bim protein and activated caspase-3 in cells were detected by western blot assay. Caspase-3 activities were measured by Caspase-3 Fluorogenic Substrate (Ac-DEVD-AFC) analysis. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. The effect of Bim on PPT-induced apoptosis was determined by RNAi. BimL translocated to mitochondria in response to PPT, similar to the downstream pro-apoptotic protein Bax activation. PPT increased the level of Bim and activated caspase-3 in cells and that knockdown of Bim by RNAi significantly protected against caspase-3 activity. PPT-induced apoptosis were suppressed in cells transfected with shRNA-Bim. We demonstrated the involvement of Bim in PPT-induced apoptosis in human ASTC-a-1 lung adenocarcinoma cells and suggested that enhancing Bim activity might be a potential strategy for treating human cancers. © 2015 S. Karger AG, Basel.

Clinical and microbiological effectiveness of photodynamic therapy on primary endodontic infections: a 6-month randomized clinical trial.

PubMed

de Miranda, Rachel Garcia; Colombo, Ana Paula Vieira

2018-05-01

This short-term randomized controlled trial evaluated the effectiveness of photodynamic therapy (PDT) on clinical success (periapical healing) and on the microbiota of primary endodontic infections. Thirty-two patients presenting mandibular molars with apical periodontitis (one tooth/patient) were selected and randomly allocated into two therapeutic groups: control (chemo-mechanical debridement [CMD]; n = 16) and PDT (CMD + PDT; n = 16). All teeth in both groups had intracanal medication with calcium hydroxide for 7 days before final obturation. Follow-up radiographs were made at 3 and 6 months. Periapical healing was evaluated by the periapical index (PAI). Samples were obtained at baseline, after CMD with or without PDT, and just before root filling to determine the frequency and levels of 37 taxa by checkerboard. Significant decreases in PAI scores were observed in both groups over time, although at 6 months, the PDT group presented a significantly better healing score than the control (p < 0.05). At baseline, the most prevalent species in all samples were Candida albicans (46.9%), Dialister pneumosintes (31.2%), Prevotella nigrescens (28.2%), Prevotella tannerae (28.1%), and Peptostreptococcus anaerobius (25%). Most species reduced over time in both groups, and no significant differences in frequency and levels of the tested species were observed between groups in any time point evaluated. C. albicans and D. pneumosintes were still detected in high frequency in both groups at 3 months post-therapy. Conventional endodontic therapy with or without PDT is effective in reducing microbial load, resulting in periapical healing. Nevertheless, adjunctive PDT provides better periapical healing at 6-month follow-up. Teeth with apical periodontitis treated with PDT adjunct to conventional treatment would demonstrate superior healing and reduction of microorganisms.

Enhanced Plasmonic Resonance Energy Transfer in Mesoporous Silica-Encased Gold Nanorod for Two-Photon-Activated Photodynamic Therapy

PubMed Central

Chen, Nai-Tzu; Tang, Kuo-Chun; Chung, Ming-Fang; Cheng, Shih-Hsun; Huang, Ching-Mao; Chu, Chia-Hui; Chou, Pi-Tai; Souris, Jeffrey S.; Chen, Chin-Tu; Mou, Chung-Yuan; Lo, Leu-Wei

2014-01-01

The unique optical properties of gold nanorods (GNRs) have recently drawn considerable interest from those working in in vivo biomolecular sensing and bioimaging. Especially appealing in these applications is the plasmon-enhanced photoluminescence of GNRs induced by two-photon excitation at infrared wavelengths, owing to the significant penetration depth of infrared light in tissue. Unfortunately, many studies have also shown that often the intensity of pulsed coherent irradiation of GNRs needed results in irreversible deformation of GNRs, greatly reducing their two-photon luminescence (TPL) emission intensity. In this work we report the design, synthesis, and evaluation of mesoporous silica-encased gold nanorods (MS-GNRs) that incorporate photosensitizers (PSs) for two-photon-activated photodynamic therapy (TPA-PDT). The PSs, doped into the nano-channels of the mesoporous silica shell, can be efficiently excited via intra-particle plasmonic resonance energy transfer from the encased two-photon excited gold nanorod and further generates cytotoxic singlet oxygen for cancer eradication. In addition, due to the mechanical support provided by encapsulating mesoporous silica matrix against thermal deformation, the two-photon luminescence stability of GNRs was significantly improved; after 100 seconds of 800 nm repetitive laser pulse with the 30 times higher than average power for imaging acquisition, MS-GNR luminescence intensity exhibited ~260% better resistance to deformation than that of the uncoated gold nanorods. These results strongly suggest that MS-GNRs with embedded PSs might provide a promising photodynamic therapy for the treatment of deeply situated cancers via plasmonic resonance energy transfer. PMID:24955141

Photodynamic Cell Killing Effects and Acute Skin Photosensitivity of Aluminum‐chloro‐tetrasulfonated Phthalocyanine and Hematoporphyrin Derivative

PubMed Central

Komatsu, Kazuto

1991-01-01

Aluminum‐chloro‐tetrasulfonated phthalocyanine (PC) showing an absorption peak at 678 nm was compared to hematoporphyrin derivative (MpD), a photosensitizer commonly used in the photodynamic therapy (PDT) of cancers. In vitro studies: KK‐47 cells were exposed to long‐wavelength ultraviolet (UVA) or red light (>600 nm, >640 nm and >660 nm) after drug sensitization. With UVA irradiation, a higher photodynamic cell killing effect was observed in the cells treated with HpD than with PC. However, with red light irradiation (both > 640 nm and >660 nm) PC resulted in greater cell damage. PC was less toxic to KK‐47 cells in the dark. In vivo studies: Using a gold vapor laser (GVL: 627.8 nm, 200 mW/cm2, 200 J/cm2), the photodynamic tumor response was determined in C3H/He mice bearing transplantable squamous cell carcinoma. No significant difference was observed in the tumor volume between the PC and HpD groups, except that the PC group (10.0 mg/kg body weight) showed a significantly higher remission rate (3/6) than the control group (0/10, P<0.05). Skin Photosensitivity test: Skin photosensitivity was estimated by measuring changes in back skin thickness due to photosensitization. With UVA irradiation, a stronger skin reaction was observed in the HpD group, while with visible light irradiation there was no significant difference between the HpD and PC groups. Based on the superior cell killing effect with red light, reduced toxicity to the cells in the dark and mild skin reaction with UVA, PC may be a more promising photosensitizer for PDT. PMID:1905706

Long-term results in low-fluence 1064-nm Q-Switched Nd:YAG laser for melasma: Is it effective?

PubMed

Gokalp, Hilal; Akkaya, Ayse Deniz; Oram, Yasemin

2016-12-01

This study assessed the safety and clinical efficacy of a low-fluence 1064-nm Q-switched neodymium-doped:yttrium aluminum garnet (QS-Nd:YAG) laser in the treatment of patients with melasma. The study evaluated 34 melasma patients treated at a single institution using a 1064-nm QS-Nd:YAG laser. The laser parameters were 6 mm spot size and 2.5 J/cm 2 fluence with multiple passes for 6-10 (median 8) sessions at 2-week intervals. Outcomes were evaluated using photography, the modified Melasma Area and Severity Index (mMASI) score, and patient satisfaction interviews after the last treatment and 1 year after the last treatment. After the low-fluence 1064-nm QS-Nd:YAG laser treatments, the mean mMASI score decreased from 6.7 ± 3.3 to 3.2 ± 1.6 (P < 0.01). After treatment completion, 20 of 34 patients (58.8%) rated themselves as having at least a 50% reduction in melasma severity. One year after the last treatment, recurrence was observed in 20 patients (58.8%) and the mean mMASI score increased from 3.2 ± 1.6 to 5.8 ± 1.9 in all patients. The recurrence of low-fluence 1064-nm QS-Nd:YAG laser rates in melasma was high when the long-term results were considered. This result may be attributed to certain patient and treatment-related factors. © 2016 Wiley Periodicals, Inc.

Ultralow-Power Near Infrared Lamp Light Operable Targeted Organic Nanoparticle Photodynamic Therapy.

PubMed

Huang, Ling; Li, Zhanjun; Zhao, Yang; Zhang, Yuanwei; Wu, Shuang; Zhao, Jianzhang; Han, Gang

2016-11-09

Tissue penetration depth is a major challenge in practical photodynamic therapy (PDT). A biocompatible and highly effective near infrared (NIR)-light-absorbing carbazole-substituted BODIPY (Car-BDP) molecule is reported as a class of imaging-guidable deep-tissue activatable photosensitizers for PDT. Car-BDP possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high singlet oxygen quantum yield (Φ Δ = 67%). After being encapsulated with biodegradable PLA-PEG-FA polymers, Car-BDP can form uniform and small organic nanoparticles that are water-soluble and tumor-targetable. Rather than using laser light, such nanoparticles offer an unprecedented deep-tissue, tumor targeting photodynamic therapeutic effect by using an exceptionally low-power-density and cost-effective lamp light (12 mW cm -2 ). In addition, these nanoparticles can be simultaneously traced in vivo due to their excellent NIR fluorescence. This study signals a major step forward in photodynamic therapy by developing a new class of NIR-absorbing biocompatible organic nanoparticles for effective targeting and treatment of deep-tissue tumors. This work also provides a potential new platform for precise tumor-targeting theranostics and novel opportunities for future affordable clinical cancer treatment.

Nodal weighting factor method for ex-core fast neutron fluence evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiang, R. T.

The nodal weighting factor method is developed for evaluating ex-core fast neutron flux in a nuclear reactor by utilizing adjoint neutron flux, a fictitious unit detector cross section for neutron energy above 1 or 0.1 MeV, the unit fission source, and relative assembly nodal powers. The method determines each nodal weighting factor for ex-core neutron fast flux evaluation by solving the steady-state adjoint neutron transport equation with a fictitious unit detector cross section for neutron energy above 1 or 0.1 MeV as the adjoint source, by integrating the unit fission source with a typical fission spectrum to the solved adjointmore » flux over all energies, all angles and given nodal volume, and by dividing it with the sum of all nodal weighting factors, which is a normalization factor. Then, the fast neutron flux can be obtained by summing the various relative nodal powers times the corresponding nodal weighting factors of the adjacent significantly contributed peripheral assembly nodes and times a proper fast neutron attenuation coefficient over an operating period. A generic set of nodal weighting factors can be used to evaluate neutron fluence at the same location for similar core design and fuel cycles, but the set of nodal weighting factors needs to be re-calibrated for a transition-fuel-cycle. This newly developed nodal weighting factor method should be a useful and simplified tool for evaluating fast neutron fluence at selected locations of interest in ex-core components of contemporary nuclear power reactors. (authors)« less

The fluence effects of low-level laser therapy on inflammation, fibroblast-like synoviocytes, and synovial apoptosis in rats with adjuvant-induced arthritis.

PubMed

Hsieh, Yueh-Ling; Cheng, Yu-Jung; Huang, Fang-Chuen; Yang, Chen-Chia

2014-12-01

The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA.

The Fluence Effects of Low-Level Laser Therapy on Inflammation, Fibroblast-Like Synoviocytes, and Synovial Apoptosis in Rats with Adjuvant-Induced Arthritis

PubMed Central

Hsieh, Yueh-Ling; Cheng, Yu-Jung; Huang, Fang-Chuen

2014-01-01

Abstract Objective: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. Background data: Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. Methods: Monoarthritis was induced in adult male Sprague–Dawley rats (250–300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Results: LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. Conclusions: LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA. PMID:25394331

The fast neutron fluence and the activation detector activity calculations using the effective source method and the adjoint function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hep, J.; Konecna, A.; Krysl, V.

2011-07-01

This paper describes the application of effective source in forward calculations and the adjoint method to the solution of fast neutron fluence and activation detector activities in the reactor pressure vessel (RPV) and RPV cavity of a VVER-440 reactor. Its objective is the demonstration of both methods on a practical task. The effective source method applies the Boltzmann transport operator to time integrated source data in order to obtain neutron fluence and detector activities. By weighting the source data by time dependent decay of the detector activity, the result of the calculation is the detector activity. Alternatively, if the weightingmore » is uniform with respect to time, the result is the fluence. The approach works because of the inherent linearity of radiation transport in non-multiplying time-invariant media. Integrated in this way, the source data are referred to as the effective source. The effective source in the forward calculations method thereby enables the analyst to replace numerous intensive transport calculations with a single transport calculation in which the time dependence and magnitude of the source are correctly represented. In this work, the effective source method has been expanded slightly in the following way: neutron source data were performed with few group method calculation using the active core calculation code MOBY-DICK. The follow-up neutron transport calculation was performed using the neutron transport code TORT to perform multigroup calculations. For comparison, an alternative method of calculation has been used based upon adjoint functions of the Boltzmann transport equation. Calculation of the three-dimensional (3-D) adjoint function for each required computational outcome has been obtained using the deterministic code TORT and the cross section library BGL440. Adjoint functions appropriate to the required fast neutron flux density and neutron reaction rates have been calculated for several significant points within

[The randomized study of efficiency of preoperative photodynamic].

PubMed

Akopov, A L; Rusanov, A A; Molodtsova, V P; Gerasin, A V; Kazakov, N V; Urtenova, M A; Chistiakov, I V

2013-01-01

The authors made a prospective randomized comparison of results of preoperative photodynamic therapy (PhT) with chemotherapy, preoperative chemotherapy in initial unresectable central non-small cell lung cancer in stage III. The efficiency and safety of preoperative therapy were estimated as well as the possibility of subsequent surgical treatment. The research included patients in stage IIIA and IIIB of central non-small cell lung cancer with lesions of primary bronchi and lower section of the trachea, which initially were unresectable, but potentially the patients could be operated on after preoperative treatment. The photodynamic therapy was performed using chlorine E6 and the light of wave length 662 nm. Since January 2008 till December 2011,42 patients were included in the research, 21 patients were randomized in the group for photodynamic therapy and 21--in group without PhT. These groups were compared according to their sex, age, stage of the disease and histological findings. After nonadjuvant treatment the remissions were reached in 19 (90%) patients of the group with PhT and in 16 (76%) patients without PhT and all the patients were operated on. The explorative operations were made on 3 patients out of 16 operated on in the group without PhT (19%). In the group PhT 14 pneumonectomies and 5 lobectomies were perfomed opposite 10 pneumonectomies and 3 lobectomies in group without PhT. The degree of radicalism of resection appears to be reliably higher in the group PhT (RO-89%, R1-11% as against RO-54%, R1-46% in group without PhT), p = 0.038. The preoperative endobronchial PhT conducted with chemotherapy was characterized by efficiency and safety, allowed the surgical treatment and elevated the degree of radicalism of this treatment in selected patients, initially assessed as unresectable.

SU-E-T-191: First Principle Calculation of Quantum Yield in Photodynamic Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abolfath, R; Guo, F; Chen, Z

Purpose: We present a first-principle method to calculate the spin transfer efficiency in oxygen induced by any photon fields especially in MeV energy range. The optical pumping is mediated through photosensitizers, e.g., porphyrin and/or ensemble of quantum dots. Methods: Under normal conditions, oxygen molecules are in the relatively non-reactive triplet state. In the presence of certain photosensitizer compounds such as porphyrins, electromagnetic radiation of specific wavelengths can excite oxygen to highly reactive singlet state. With selective uptake of photosensitizers by certain malignant cells, photon irradiation of phosensitized tumors can lead to selective killing of cancer cells. This is the basismore » of photodynamic therapy (PDT). Despite several attempts, PDT has not been clinically successful except in limited superficial cancers. Many parameters such as photon energy, conjugation with quantum dots etc. can be potentially combined with PDT in order to extend the role of PDT in cancer management. The key quantity for this optimization is the spin transfer efficiency in oxygen by any photon field. The first principle calculation model presented here, is an attempt to fill this need. We employ stochastic density matrix description of the quantum jumps and the rate equation methods in quantum optics based on Markov/Poisson processes and calculate time evolution of the population of the optically pumped singlet oxygen. Results: The results demonstrate the feasibility of our model in showing the dependence of the optical yield in generating spin-singlet oxygen on the experimental conditions. The adjustable variables can be tuned to maximize the population of the singlet oxygen hence the efficacy of the photodynamic therapy. Conclusion: The present model can be employed to fit and analyze the experimental data and possibly to assist researchers in optimizing the experimental conditions in photodynamic therapy.« less

Probing the Relationship Between Detected Ion Intensity, Laser Fluence, and Beam Profile in Thin Film and Tissue in MALDI MSI

NASA Astrophysics Data System (ADS)

Steven, Rory T.; Race, Alan M.; Bunch, Josephine

2016-08-01

Matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is increasingly widely used to provide information regarding molecular location within tissue samples. The nature of the photon distribution within the irradiated region, the laser beam profile, and fluence, will significantly affect the form and abundance of the detected ions. Previous studies into these phenomena have focused on circular-core optic fibers or Gaussian beam profiles irradiating dried droplet preparations, where peptides were employed as the analyte of interest. Within this work, we use both round and novel square core optic fibers of 100 and 50 μm diameter to deliver the laser photons to the sample. The laser beam profiles were recorded and analyzed to quantify aspects of the photon distributions and their relation to the spectral data obtained with each optic fiber. Beam profiles with a relatively small number of large beam profile features were found to give rise to the lowest threshold fluence. The detected ion intensity versus fluence relationship was investigated, for the first time, in both thin films of α-cyano-4-hydroxycinnamic acid (CHCA) with phosphatidylcholine (PC) 34:1 lipid standard and in CHCA coated murine tissue sections for both the square and round optic fibers in continuous raster imaging mode. The fluence threshold of ion detection was found to occur at between ~14 and ~64 J/m2 higher in tissue compared with thin film for the same lipid, depending upon the optic fiber employed. The image quality is also observed to depend upon the fluence employed during image acquisition.

Effectiveness of repeated photodynamic therapy in the elimination of intracanal Enterococcus faecalis biofilm: an in vitro study.

PubMed

Prażmo, Ewa Joanna; Godlewska, Renata Alicja; Mielczarek, Agnieszka Beata

2017-04-01

The study aimed to investigate the effectiveness of photodynamic therapy in the elimination of intracanal Enterococcus faecalis biofilm and to analyse how a repeated light irradiation, replenishment of oxygen and photosensitiser affect the results of the photodynamic disinfecting protocol. After chemomechanical preparation, 46 single-rooted human teeth were infected with a clinical strain of E. faecalis and incubated for a week in microaerobic conditions. The experimental procedures included groups of single application of photodynamic therapy, two cycles of PDT, irrigation with 5.25% NaOCl solution and negative and positive control. The number of residing bacterial colonies in the root canals was determined based on the CFU/ml method. In the group of preparations irrigated with NaOCl, bacterial colonies were not observed. A single PDT eliminated 45% of the initial CFU/ml. Repeated PDT eradicated 95% of the intracanal bacterial biofilm. Photodynamic therapy has a high potential for the elimination of E. faecalis biofilm. There is a safe therapeutic window where photoinduced disinfection can be used as an adjuvant to conventional endodontic treatment, which remains the most effective.

Three-dimensional in vitro cancer spheroid models for Photodynamic Therapy: Strengths and Opportunities

NASA Astrophysics Data System (ADS)

Evans, Conor

2015-03-01

Three dimensional, in vitro spheroid cultures offer considerable utility for the development and testing of anticancer photodynamic therapy regimens. More complex than monolayer cultures, three-dimensional spheroid systems replicate many of the important cell-cell and cell-matrix interactions that modulate treatment response in vivo. Simple enough to be grown by the thousands and small enough to be optically interrogated, spheroid cultures lend themselves to high-content and high-throughput imaging approaches. These advantages have enabled studies investigating photosensitizer uptake, spatiotemporal patterns of therapeutic response, alterations in oxygen diffusion and consumption during therapy, and the exploration of mechanisms that underlie therapeutic synergy. The use of quantitative imaging methods, in particular, has accelerated the pace of three-dimensional in vitro photodynamic therapy studies, enabling the rapid compilation of multiple treatment response parameters in a single experiment. Improvements in model cultures, the creation of new molecular probes of cell state and function, and innovations in imaging toolkits will be important for the advancement of spheroid culture systems for future photodynamic therapy studies.

Photodynamic toxicity and its prevention by antioxidative agents in Bufo arenarum embryos.

PubMed

Stockert, Juan C; Herkovits, Jorge

2003-11-05

In this work we describe an experimental model to evaluate the photodynamic toxicity on amphibian embryos, as well as the protective effect of antioxidants against the lethal oxidative stress induced by photosensitization. Bufo arenarum embryos were treated with 10 mg/l methylene blue (MB) in AMPHITOX solution for 72 h and then irradiated with a red laser or white light for variable times. Both light sources affected the survival of MB-treated animals and lethal effects occurred within the initial 12 h post-irradiation. For white light irradiation, the most effective phototoxic condition in our study, the LD10, 50 and 90 at 6 h post-irradiation corresponded to 13.57, 19.87 and 29.10 J/cm2, respectively. To explore the action of antioxidants against the photogenerated oxidative stress, MB-treated embryos were incubated with 1mM glutathione (GSH) or ascorbic acid (AA) during 48 h before irradiation. For GSH and 21.6 J/cm2 irradiation, the survival increased from 20 to 90%, whereas 100% survival was achieved with AA even after 43.2 J/cm2 irradiation. These results indicate that both the lethal photodynamic effect and its prevention by antioxidants can be evaluated by means of a simple toxicity test employing amphibian embryos.

Lutetium(III) acetate phthalocyanines for photodynamic therapy applications: Synthesis and photophysicochemical properties.

PubMed

Mantareva, Vanya; Durmuş, Mahmut; Aliosman, Meliha; Stoineva, Ivanka; Angelov, Ivan

2016-06-01

The development of new water-soluble photosensitizers for photodynamic therapy (PDT) applications is a very active research topic. Efforts have been made to obtain the far-red absorbing phthalocyanine complexes with molecular design that facilitates the uptake and selectivity for a high PDT efficiency. The monomolecular lutetium(III) acetate phthalocyanines (LuPcs) substituted with methylpyridyloxy groups at non-peripheral (5) and peripheral (6) positions were synthesized by following the modification of the well-known synthetical routes. The photo-physicochemical properties of the both quaternized LuPcs were evaluated by the steady-state and time-resolved spectroscopy. The photochemical technique was applied to study the generation of the singlet oxygen. Two water-soluble and cationic LuPcs were synthesized and chemically characterized. The photo-physicochemical properties of absorption (675 and 685nm) and the red shifted fluorescence (704 and 721nm) as well as the fluorescence lifetimes (2.24 and 3.27ns) were studied. The promising values of singlet oxygen quantum yields (0.32 for 5 and 0.35 for 6) were determined. Lutetium(III) acetate phthalocyanine complexes were synthesized and evaluated with physicochemical properties suitable for future photodynamic therapy applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Phthalocyanines And Their Sulfonated Derivatives As Photosensitizers In Photodynamic Therapy.

NASA Astrophysics Data System (ADS)

Riesz, Peter; Krishna, C. Murali

1988-02-01

Photodynamic therapy (PDT) of human tumors with hematoporphyrin derivative (HpD) has achieved encouraging results. However, HpD is a complex mixture whose composition varies in different preparations and with time of storage. The future promise of PDT for cancer treatment depends on the development of new chemically defined sensitizers which absorb more strongly than HpD in the 600-800 nm region. A shift to higher wavelengths is desirable since it allows increased light penetration in human tissues. In vivo, these sensitizers should be non-toxic, localize selectively in tumors and generate cytotoxic species upon illumination with a high quantum yield. These damaging species may be singlet oxygen (1O2) produced by the transfer of energy from the triplet state of the sensitizer to oxygen (Type II) or superoxide anion radicals formed by electron transfer to oxygen or substrate radicals generated by electron or hydrogen transfer directly from the sensitizer (Type I). The recent work of several groups indicating that phthalocyanines and their water soluble derivatives are promising candidates for PDT is reviewed. The photophysics, photochemistry, photosensitized killing of cultured mammalian cells and the use for in vivo photodynamic therapy of phthalocyanines is outlined. Our studies of the post-illumination photohemolysis of human red blood cells as a model system for membrane photomodification sensitized by phthalocyanine sulfonates are consistent with the predominant role of 1O2 as the damaging species.

Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection

NASA Astrophysics Data System (ADS)

Chen, Zhuo; Zhang, Yaxin; Wang, Dong; Li, Linsen; Zhou, Shanyong; Huang, Joy H.; Chen, Jincan; Hu, Ping; Huang, Mingdong

2016-01-01

Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-Lys). Compared with its anionic ZnPc counterpart, ZnPc-Lys showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-Lys was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.

SU-E-T-261: Plan Quality Assurance of VMAT Using Fluence Images Reconstituted From Log-Files

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsuta, Y; Shimizu, E; Matsunaga, K

2014-06-01

Purpose: A successful VMAT plan delivery includes precise modulations of dose rate, gantry rotational and multi-leaf collimator (MLC) shapes. One of the main problem in the plan quality assurance is dosimetric errors associated with leaf-positional errors are difficult to analyze because they vary with MU delivered and leaf number. In this study, we calculated integrated fluence error image (IFEI) from log-files and evaluated plan quality in the area of all and individual MLC leaves scanned. Methods: The log-file reported the expected and actual position for inner 20 MLC leaves and the dose fraction every 0.25 seconds during prostate VMAT onmore » Elekta Synergy. These data were imported to in-house software that developed to calculate expected and actual fluence images from the difference of opposing leaf trajectories and dose fraction at each time. The IFEI was obtained by adding all of the absolute value of the difference between expected and actual fluence images corresponding. Results: In the area all MLC leaves scanned in the IFEI, the average and root mean square (rms) were 2.5 and 3.6 MU, the area of errors below 10, 5 and 3 MU were 98.5, 86.7 and 68.1 %, the 95 % of area was covered with less than error of 7.1 MU. In the area individual MLC leaves scanned in the IFEI, the average and rms value were 2.1 – 3.0 and 3.1 – 4.0 MU, the area of errors below 10, 5 and 3 MU were 97.6 – 99.5, 81.7 – 89.5 and 51.2 – 72.8 %, the 95 % of area was covered with less than error of 6.6 – 8.2 MU. Conclusion: The analysis of the IFEI reconstituted from log-file was provided detailed information about the delivery in the area of all and individual MLC leaves scanned.« less

Two-photon excitation photodynamic therapy with Photofrin

NASA Astrophysics Data System (ADS)