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Sample records for showed enhanced pdt

  1. Enhancing protoporphyrin IX-induced PDT

    Science.gov (United States)

    Curnow, Alison; Pye, Andrew; Campbell, Sandra

    2009-06-01

    Photodynamic therapy (PDT) using porphyrin precursors is commonly used in dermatology. Evidence indicates that good clinical outcomes (associated with excellent cosmesis) can be achieved in superficial precancers and basal cell carcinoma (BCC), however, efficacy appears less favorable for thicker nodular BCC (nBCC) unless multiple PDT treatment cycles are performed. Enhancement is therefore required if nBCC lesions are to be treated effectively with a single PDT treatment. The most common technique currently being routinely employed clinically is the use of aminolevulinic acid (ALA) esters (usually methyl (MAL) or hexyl (HAL)). Standard dermatological PDT employing these porphyrin precursors already manipulates the normal heme biosynthesis pathway resulting in a temporary accumulation of the natural photosensitizer, protoporphyrin IX (PpIX). Further manipulation using iron chelating agents is possible however. In normal and malignant human cells in vitro, the novel iron chelating agent CP94 produced greater PPIX fluorescence when administered with ALA or MAL than either congener produced alone. CP94 was also significantly more effective than the clinically established iron chelating agent desferrioxamine (DFO). Topical application of ALA+CP94 to clinical nBCC lesions was a simple and safe treatment modification which produced a significant increase in clinical clearance when CP94 was included in the cream.

  2. ATX-S10(Na)-PDT shows more potent effect on collagen metabolism of human normal and scleroderma dermal fibroblasts than ALA-PDT.

    Science.gov (United States)

    Takahashi, Hidetoshi; Komatsu, Shigetsuna; Ibe, Masaki; Ishida-Yamamoto, Akemi; Nakajima, Susumu; Sakata, Isao; Iizuka, Hajime

    2006-11-01

    Recent study revealed that photodynamic therapy (PDT) with a novel photosensitizer (ATX-S10(Na)) shows more potent effects for various skin diseases than ALA-PDT. The effect of ATX-S10(Na)-PDT on dermal fibroblasts is still unknown. Using dermal fibroblasts derived from normal and scleroderma patients, and mouse skin in vivo, we compared the effects of ATX-S10(Na)-PDT and ALA-PDT. Fibroblasts from normal, scleroderma patients or mice skin were treated with ATX-S10(Na)-PDT or ALA-PDT. After the PDT treatments, the expression of matrix metalloproteinases (MMPs) Tissue inhibitors of metalloproteinases (TIMPs) and collagen synthesis was assayed using ELISA and reverse transcription-PCR (RT-PCR). The expression of MMP-1 and MMP-3 was slightly decreased and collagen I mRNA was significantly increased in scleroderma fibroblasts compared with normal fibroblasts. Both ATX-S10(Na)-PDT and ALA-PDT increased the expression of MMP-1 and MMP-3 in protein and mRNA levels in both normal and scleroderma fibroblasts with more potent effect by ATX-S10(N)-PDT. Collagen I synthesis was markedly decreased by ATX-S10(Na)-PDT and by ALA-PDT again with more potent effect by ATX-S10(Na)-PDT in both normal and scleroderma fibroblasts. In mice skin the effect of PDT for MMPs and collagen I was also detected and the effect was more potent in ATX-S10(Na)-PDT. In contrast, MMP-2, TIMP-1, TIMP-2, and collagen III expression was not affected by the ATX-S10(Na)-PDT or ALA-PDT treatment. ATX-S10(Na)-PDT is more potent modulator for dermal matrix components than ALA-PDT and might be useful for scleroderma patients.

  3. Hyperglycemia enhances the effectiveness of PDT

    Science.gov (United States)

    Fan, Keichun; Huang, Yingcai; Li, Junheng

    1995-05-01

    The effect of injection of 10 mg/g 50% glucose on photodynamic therapy of mouse transplantable S-180 sarcoma was studied. The concentration of hematoporphyrin monomethylether in plasma, skin, and tumor was measured by recording spectrofluorophotometer. tumor pathological section was made and necrosis area of tumor longitudinal section was measured by image processing after photoradiation of gold vapor laser. The results of this study suggested that the uptake of photosensitizer in tumor significantly increased while the uptake of photosensitizer in skin remained unchanged after glucose administration. Furthermore, glucose administration combined with PDT produced a greater tumor necrosis area than using PDT alone. The mechanisms and clinical significance were also discussed.

  4. Using iron chelating agents to enhance dermatological PDT

    Science.gov (United States)

    Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra

    2009-06-01

    Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.

  5. Resveratrol enhances the effects of ALA-PDT on skin squamous cells A431 through p38/ MAPK signaling pathway.

    Science.gov (United States)

    Zhang, Xin; Liu, Xia; Kang, Shuxia; Liu, Caiyun; Hao, Yuqin

    2017-12-23

    Squamous cell carcinoma (SCC) is one of the most common skin cancers. Photodynamic therapy (PDT) is a non-invasive treatment for SCC, but it is usually effective only on tumors just under the skin. Resveratrol (Res) is a polyphenolic compound, which is capable of promoting apoptosis of a variety of cancer cells. Res administration is non-invasive and effective on SCC, thus it may be used as an adjuvant for PDT. So far, there is no published study investigating the combination use of PDT with Res to improve clinical outcome of SCC. So in this study, we will examine the effectiveness of combined treatment of PDT and Res as well as its underlying mechanism. The human HaCaT keratinocytes and human A431 epidermoid carcinoma cells were treated with ALA-PDT or/and Res, and cell proliferation and apoptosis were evaluated by MTT and flow cytometry respectively afterwards. p-ERK, p38, p53 and caspase-3 protein expression was examined by western blot. Then a p38 inhibitor was added to test the involvement of p38 pathway in A431 cells responding to ALA-PDT and Res treatments. The results showed that Res could enhance the effect of ALA-PDT on cell proliferation and apoptosis in A431 cells. We also found that the expression of p-ERK, p-p38, p53 and caspase-3 was increased. However, inhibition of p38 pathway attenuated the effect of Res. Our study demonstrated that Res could enhance the effect of ALA-PDT against skin cancer cells through p38/ MAPK pathway.

  6. Assessment of in vivo experiments: The newly synthesized porphyrin with proper light source enhanced effectiveness of PDT comparing to 5-ALA-mediated PDT.

    Science.gov (United States)

    Jurczyszyn, Kamil; Woźniak, Marta; Symonowicz, Krzysztof; Sprutta, Natasza; Latos-Grażyński, Lechosław; Ziółkowski, Piotr; Ivonyak, Yurij; Tuchowski, Piotr; Trzeciakowski, Witold

    2017-06-01

    The search for new photosensitizers for application in photodynamic therapy has quite a long history. In the past, a large number of potent photosensitizers were used in both basic and clinical studies; however, only a few turned out to be effective and safe. In the present study, two compounds were used: 5-aminolevulinic acid in two formulations (free and liposomal), and the newly synthesized porphyrin, 5,10,15,20-tetra-p-tolyl-22,24-dithiadibenzocarbaporphyrin, termed DTDB. Two different light sources, a halogen lamp (wavelength 450+/-20nm) and a diode laser (wavelength 450nm), were used to sensitize the compounds. The entire experiment was performed on mice bearing mouse mammary carcinoma, 4T1. The results showed that the DTDB-PDT applied by means of a laser proved to be most effective and caused the 83.3% necrosis of treated tumors. The overall effect of laser PDT was more potent than that of the halogen lamp-mediated PDT. In the present study, we would like to show that modifications of porphyrins lead to an increase in the effectiveness of PDT and that this effect could also be potentiated by using a proper light source. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).

    Science.gov (United States)

    Kue, Chin Siang; Kamkaew, Anyanee; Lee, Hong Boon; Chung, Lip Yong; Kiew, Lik Voon; Burgess, Kevin

    2015-01-05

    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs.

  8. Fractionated PDT with 5-aminolevulinic acid: effective, cost effective, and patient friendly

    Science.gov (United States)

    de Vijlder, Hannah C.; Middelburg, Tom A.; de Bruijn, Henriette S.; Robinson, Dominic J.; Neumann, H. A. Martino; de Haas, Ellen R. M.

    2009-06-01

    PDT with ALA and MAL is established as a relatively effective treatment for non-melanoma skin cancer and premalignancies. PDT is often repeated, because a single treatment gives poor long term results. Preclinical studies showed that ALA-PDT applying a fractionated illumination scheme with a small first light fraction and a second larger light fraction separated by a dark interval of two hours resulted in a significant increase in efficacy. Whereas the efficacy was not enhanced by fractionating MAL-PDT, indicating that ALA-PDT mechanism is not the same as MAL-PDT mechanism. The increase in efficacy using fractionated PDT was confirmed clinically. A randomized comparative clinical study comparing fractionated ALA-PDT versus non-fractionated ALA-PDT in the treatment of superficial basal cell carcinoma showed a significant higher response rate in the lesions treated with fractionated ALA-PDT after a follow-up of one year ( ptreatment day, instead of two treatment days using the Metvix treatment protocol (two MAL-PDT treatments separated by one week), both reducing direct and indirect costs and the burden to the patient.

  9. Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy.

    Science.gov (United States)

    Zhang, Da; Wu, Ming; Zeng, Yongyi; Wu, Lingjie; Wang, Qingtang; Han, Xiao; Liu, Xiaolong; Liu, Jingfeng

    2015-04-22

    Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

  10. ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway.

    Science.gov (United States)

    Qiao, Li; Mei, Zhusong; Yang, Zhiyong; Li, Xinji; Cai, Hong; Liu, Wei

    2016-06-01

    Previous studies suggest that apoptosis of carcinoma cells led by photodynamics is mainly intrinsic apoptosis, but whether the extrinsic pathway is involved in the treatment of carcinoma by photodynamic therapy is not confirmed. This research investigated the effect of ALA-PDT on the proliferation and apoptosis of SCC cell A431 and COLO-16, and discussed the role played by JAK/STAT3 signal pathway in this process. Our data showed that the expression levels STAT3 and p-STAT3 protein in the cancer tissue are higher than the corresponding adjacent tissue to carcinoma. The expression level of p-STAT3 in cancerous tissue has a correlation with the tumor size and tissue histopathological differentiation. ALA-PDT could inhibit proliferation of A431 and COLO-16 cells, STAT3 knock down could enhance ALA-PDT's inhibition of cell proliferation, and promote apoptosis induced by ALA-PDT. On the other hand, overexpression of STAT3 has the opposite effect. In addition, ALA-PDT can weaken the protein expression of STAT3 and its target gene Bcl-2 mRNA, and ALA-PDT can strengthen the protein expression of STAT3's target gene Bax mRNA. Overexpression of STAT3 can offset the effect on Bcl-2 and Bax by ALA-PDT; on the other hand, STAT3 knocking down can strengthen ALA-PDT's effect on Bcl-2 and Bax. Copyright © 2016. Published by Elsevier B.V.

  11. Quantity language speakers show enhanced subcortical processing.

    Science.gov (United States)

    Dawson, Caitlin; Aalto, Daniel; Šimko, Juraj; Putkinen, Vesa; Tervaniemi, Mari; Vainio, Martti

    2016-07-01

    The complex auditory brainstem response (cABR) can reflect language-based plasticity in subcortical stages of auditory processing. It is sensitive to differences between language groups as well as stimulus properties, e.g. intensity or frequency. It is also sensitive to the synchronicity of the neural population stimulated by sound, which results in increased amplitude of wave V. Finnish is a full-fledged quantity language, in which word meaning is dependent upon duration of the vowels and consonants. Previous studies have shown that Finnish speakers have enhanced behavioural sound duration discrimination ability and larger cortical mismatch negativity (MMN) to duration change compared to German and French speakers. The next step is to find out whether these enhanced duration discrimination abilities of quantity language speakers originate at the brainstem level. Since German has a complementary quantity contrast which restricts the possible patterns of short and long vowels and consonants, the current experiment compared cABR between nonmusician Finnish and German native speakers using seven short complex stimuli. Finnish speakers had a larger cABR peak amplitude than German speakers, while the peak onset latency was only affected by stimulus intensity and spectral band. The results suggest that early cABR responses are better synchronised for Finns, which could underpin the enhanced duration sensitivity of quantity language speakers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells.

    Science.gov (United States)

    Wang, Xiaojie; Ji, Jie; Zhang, Haiyan; Fan, Zhixia; Zhang, Linglin; Shi, Lei; Zhou, Feifan; Chen, Wei R; Wang, Hongwei; Wang, Xiuli

    2015-12-29

    Photodynamic therapy (PDT) not only kills tumor cells directly but also rapidly recruits and activates immune cells favoring the development of antitumor adaptive immunity. It is believed that Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) can induce anti-tumor immune responses through dangerous signals damage-associated molecular patterns (DAMPs). In this study, we investigated the effect of ALA-PDT induced DAMPs on immune cells. We focused on the stimulation of dendritic cells by major DAMPs, enhanced the expression of calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), either individually or in combination. We evaluated in vitro and in vivo expressions of DAMPs induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important part in activating DCs by PDT-treated tumor cells, including phenotypic maturation (increase of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can increase DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.

  13. PDT: What's Past Is Prologue.

    Science.gov (United States)

    Cengel, Keith A; Simone, Charles B; Glatstein, Eli

    2016-05-01

    Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497-9. ©2016 AACRSee related article by Dougherty et al., Cancer Res 1978;38:2628-35Visit the Cancer Research 75(th) Anniversary timeline. ©2016 American Association for Cancer Research.

  14. PDT-based combinations in overcoming chemoresistance from stromal and heterotypic cellular communication (Conference Presentation)

    Science.gov (United States)

    Rizvi, Imran; Bulin, Anne-Laure; Anbil, Sriram R.; Briars, Emma A.; Vecchio, Daniela; Celli, Jonathan P.; Broekgaarden, Mans; Hasan, Tayyaba

    2017-02-01

    Targeting the molecular and cellular cues that influence treatment resistance in tumors is critical to effectively treating unresponsive populations of stubborn disease. The informed design of mechanism-based combinations is emerging as increasingly important to targeting resistance and improving the efficacy of conventional treatments, while minimizing toxicity. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Increasing evidence shows that PDT-based combinations cooperate mechanistically with, and improve the therapeutic index of, traditional chemotherapies. These and other findings emphasize the importance of including PDT as part of comprehensive treatment plans for cancer, particularly in complex disease sites. Identifying effective combinations requires a multi-faceted approach that includes the development of bioengineered cancer models and corresponding image analysis tools. The molecular and phenotypic basis of verteporfin-mediated PDT-based enhancement of chemotherapeutic efficacy and predictability in complex 3D models for ovarian cancer will be presented.

  15. Differential susceptibility of primary cultured human skin cells to hypericin PDT in an in vitro model.

    Science.gov (United States)

    Popovic, A; Wiggins, T; Davids, L M

    2015-08-01

    Skin cancer is the most common cancer worldwide, and its incidence rate in South Africa is increasing. Photodynamic therapy (PDT) has been shown to be an effective treatment modality, through topical administration, for treatment of non-melanoma skin cancers. Our group investigates hypericin-induced PDT (HYP-PDT) for the treatment of both non-melanoma and melanoma skin cancers. However, a prerequisite for effective cancer treatments is efficient and selective targeting of the tumoral cells with minimal collateral damage to the surrounding normal cells, as it is well established that cancer therapies have bystander effects on normal cells in the body, often causing undesirable side effects. The aim of this study was to investigate the cellular and molecular effects of HYP-PDT on normal primary human keratinocytes (Kc), melanocytes (Mc) and fibroblasts (Fb) in an in vitro tissue culture model which represented both the epidermal and dermal cellular compartments of human skin. Cell viability analysis revealed a differential cytotoxic response to a range of HYP-PDT doses in all the human skin cell types, showing that Fb (LD50=1.75μM) were the most susceptible to HYP-PDT, followed by Mc (LD50=3.5μM) and Kc (LD50>4μM HYP-PDT) These results correlated with the morphological analysis which displayed distinct morphological changes in Fb and Mc, 24h post treatment with non-lethal (1μM) and lethal (3μM) doses of HYP-PDT, but the highest HYP-PDT doses had no effect on Kc morphology. Fluorescent microscopy displayed cytoplasmic localization of HYP in all the 3 skin cell types and additionally, HYP was excluded from the nuclei in all the cell types. Intracellular ROS levels measured in Fb at 3μM HYP-PDT, displayed a significant 3.8 fold (pPDT. These results depict a differential response to HYP-PDT by different human skin cells thus highlighting the efficacy and indeed, the potential bystander effect of if administered in vivo. This study contributes toward our knowledge

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

    Science.gov (United States)

    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.

  17. Current methods for photodynamic therapy in the US: comparison of MAL/PDT and ALA/PDT.

    Science.gov (United States)

    Lee, Peter K; Kloser, Andrew

    2013-08-01

    There is some debate regarding the rate of progression of actinic keratosis (AK) into squamous cell carcinoma (SCC).1-4 However, it is clear that treatment for AK lesions is warranted. Results from numerous studies with aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) for the treatment of AKs, SCC, and Bowen's disease show high rates of clearance for these lesions. MAL/PDT provides similar efficacy to ALA/PDT with the benefits of shorter incubation times according to the approved FDA labeling, greater selectivity, reduced pain during and immediately following therapy, and fewer systemic side effects. Cosmetic outcomes are better with PDT than with cryosurgery or excisional surgery. A number of case reports show efficacy with ALA/PDT and MAL/PDT for acne, photorejuvenation, and other off-label indications. Side effects with PDT tend to be mild to moderate and transient in nature. Overall, ALA/PDT and MAL/PDT are effective for a variety of skin diseases and conditions. MAL/PDT provides some advantages over ALA/PDT.

  18. Direct imaging of macrophage activation during PDT treatment

    Science.gov (United States)

    Song, Sheng; Zhou, Feifan; Chen, Wei R.; Xing, Da

    2012-03-01

    Mounting evidence describes a more complex progress of macrophage activation during photodynamic therapy (PDT), which performing distinct immunological functions and different physiologies on surrounding cells and tissues. Macrophage-targeted PDT has been applied in the selective killing of cells involved in inflammation and tumor. We have previously shown that PDT-mediated tumor cells apoptosis can induce a higher level immune response than necrosis, and enhance the macrophage activation. However, the molecular mechanism of macrophage activation during PDT-induced apoptotic cells (AC) still unclear. Here, we use confocal microscopy to image the phagocytosis of tumor cells by macrophages. We also observed that PDT-treated AC can activate Toll-like receptors (TLRs) which are present on macrophages surface. Besides, the increase in nitric oxide (NO) formation in macrophages was detected in real time by a laser scanning microscopy. This study provided more details for understanding the molecular mechanism of the immune response induced by PDT-treated AC.

  19. PDT: What’s Past is Prologue*

    Science.gov (United States)

    Cengel, Keith A.; Simone, Charles B.; Glatstein, Eli

    2017-01-01

    Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900’s, the landmark paper in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has become increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale in order to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. PMID:27197260

  20. Photodynamic Therapy (PDT)

    Indian Academy of Sciences (India)

    In Part 1 of this series on photodynamic therapy (PDT)!, we discussed salient features of this new modality against cancer with special emphasis on the physical and biochemical prin- ciples involved. The subsequent article was devoted to the design and clinical applications of porphyrinic and non- porphyrinic ...

  1. Studying the effect of photodynamic therapy (PDT) to enhance healing of femur fractures using polarimetric second-harmonic generation microscopy

    Science.gov (United States)

    Golaraei, Ahmad; Raja, Vaishnavi; Akens, Margarete K.; Wilson, Brian C.; Barzda, Virginijus

    2017-07-01

    Linear polarization-in, polarization-out second-harmonic generation microscopy was used to study the effect of Photodynamic therapy treatment on enhancing the healing of femur fracture by investigating the ultrastructure of collagen as a major component of bone matrix.

  2. Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells.

    Science.gov (United States)

    Kim, Jisun; Lim, Haesoon; Kim, Sangwoo; Cho, Hyejung; Kim, Yong; Li, Xiaojie; Choi, Hongran; Kim, Okjoon

    2016-04-01

    We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm2. We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death.

  3. Development of resistance to photodynamic therapy (PDT) in human breast cancer cells is photosensitizer-dependent: Possible mechanisms and approaches for overcoming PDT-resistance.

    Science.gov (United States)

    Olsen, Cathrine Elisabeth; Weyergang, Anette; Edwards, Victoria Tudor; Berg, Kristian; Brech, Andreas; Weisheit, Sabine; Høgset, Anders; Selbo, Pål Kristian

    2017-11-15

    Here we report on the induction of resistance to photodynamic therapy (PDT) in the ABCG2-high human breast cancer cell line MA11 after repetitive PDT, using either Pheophorbide A (PhA) or di-sulphonated meso-tetraphenylchlorin (TPCS 2a ) as photosensitizer. Resistance to PhA-PDT was associated with enhanced expression of the efflux pump ABCG2. TPCS 2a -PDT-resistance was neither found to correspond with lower TPCS 2a -accumulation nor reduced generation of reactive oxygen species (ROS). Cross-resistance to chemotherapy (doxorubicin) or radiotherapy was not observed. TPCS 2a -PDT-resistant cells acquired a higher proliferation capacity and an enhanced expression of EGFR and ERK1/2. p38 MAPK was found to be a death-signalling pathway in the MA11 cells post TPCS 2a -PDT, contrasting the MA11/TR cells in which PDT generated a sustained phosphorylation of p38 that had lost its death-mediated signalling, and an abrogated activation of its downstream effector MAPKAPK2. No difference in apoptosis, necrosis or autophagy responses was found between the treated cell lines. Development of TPCS 2a -PDT resistance in the MDA-MB-231 cell line was also established, however, p38 MAPK did not play a role in the PDT-resistance. MCF-7 cells did not develop TPCS 2a -PDT-resistance. Photochemical internalisation (PCI) of 1 pM of EGF-saporin induced equal strong cytotoxicity in both MA11 and MA11/TR cells. In conclusion, loss of p38 MAPK-inducing death signalling is the main mechanism of resistance to TPCS 2a -PDT in the MA11/TR cell line. This work provides mechanistic knowledge of intrinsic and acquired PDT-resistance which is dependent on choice of photosensitizer, and suggests PCI as a rational therapeutic intervention for the elimination of PDT-resistant cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness.

    Science.gov (United States)

    Schmid, T E; Greubel, C; Hable, V; Zlobinskaya, O; Michalski, D; Girst, S; Siebenwirth, C; Schmid, E; Molls, M; Multhoff, G; Dollinger, G

    2012-10-07

    This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm(-1)) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBE(MN) = 1.48 ± 0.07) and dicentrics (RBE(D) = 1.92 ± 0.15), in human-hamster hybrid (A(L)) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm(2) matrix compared to quasi homogeneous in a 1 × 1 µm(2) matrix applied protons (RBE(MN) = 1.28 ± 0.07; RBE(D) = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a (12)C ion with 55 MeV total energy (4.48 MeV u(-1)). The enhancements are about half of that obtained for (12)C ions (RBE(MN) = 2.20 ± 0.06 and RBE(D) = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.

  5. Daylight PDT with MAL - current data and practical recommendations of an expert panel.

    Science.gov (United States)

    Philipp-Dormston, Wolfgang G; Karrer, Sigrid; Petering, Holger; Ulrich, Claas; Dirschka, Thomas; Berking, Carola; Lonsdorf, Anke S; Gerber, Peter Arne; Radakovic, Sonja; Hunger, Robert E; Szeimies, Rolf-Markus

    2015-12-01

    Photodynamic Therapy (PDT) is one of the standard treatment modalities for actinic keratoses (AKs). Daylight PDT (DL-PDT) with MAL cream is a rather recent development, which, instead of an artificial light source, uses daylight for the activation of the photosensitizer. The present review summarizes available data based on a selective literature search, highlights practical aspects, and reflects the authors' expert knowledge in using DL-PDT. With respect to efficacy, study data shows that DL-PDT is noninferior to conventional PDT (cPDT). However, given that DL-PDT is markedly less painful, it is significantly better tolerated than cPDT. In Europe, DL-PDT can be performed from March to October, on sunny as well as on cloudy days. UV protection of untreated areas of the body should be observed. Outside temperature should not fall below 10°C. On hot days, patients should be advised to stay in the shade if necessary. Representing a useful addition to current therapeutic options, DL-PDT with MAL cream is, among others, suitable for patients with field cancerization and/or those who have experienced severe pain associated with cPDT. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  6. Four-channel PDT dose dosimetry for pleural photodynamic therapy

    Science.gov (United States)

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

    2017-02-01

    We have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and sensitizer fluorescence data from four sites in the thoracic cavity during pleural photodynamic therapy (PDT). Photosensitizer fluorescence emitted during PDT is of interest for the monitoring of local concentration of the photosensitizer and its photobleaching. However, the variation in tissue optical properties will cause the photosensitizer fluorescence to alter. Optical properties correction to the measured fluorescence is required for absolute quantification of photosensitizer concentration. In this study, we determine an empirical optical properties correction function using Monte Carlo (MC) simulations of fluorescence for a range of physiologically relevant tissue optical properties. Optical properties correction factors for Photofrin fluorescence were determined experimentally using the same empirical function to recover the Photofrin concentration from measured fluorescence during PDT. The results showed no photobleaching of Photofrin during the course of PDT. PDT doses delivered to multiple sites in the thoracic cavity of 4 patients were presented and showed that PDT dose can be different by 4.4 times intra-patients and 9.1 times inter-patients.

  7. The role of reactive oxygen species in PDT efficacy

    Science.gov (United States)

    Price, Michael; Okan-Mensah, Nakaiya; Santiago, Ann Marie; Kessel, David

    2009-02-01

    While the first reactive oxygen species (ROS) formed during photodynamic therapy (PDT) is singlet molecular oxygen (1O2), other ROS are formed downstream including superoxide anion radical (•CO2 -), hydrogen peroxide (H2O2) and hydroxyl radical (•OH). In this study, we examined the role of H2O2 in the phototoxic response to PDT in murine leukemia L388 cells. Inhibition of catalase activity, a major pathway to H2O2 detoxification, led to enhanced apoptosis and cell death. Addition of exogenous catalase offered protection from phototoxicity as did chelation of Fe+2, a co-factor in •OH production from H2O2. These results indicate the H2O2 formed during PDT plays a role in PDT efficacy.

  8. A pilot split-face study comparing conventional methyl aminolevulinate-photodynamic therapy (PDT) with microneedling-assisted PDT on actinically damaged skin.

    Science.gov (United States)

    Torezan, Luís; Chaves, Yuri; Niwa, Ane; Sanches, José A; Festa-Neto, Cyro; Szeimies, Rolf-Markus

    2013-08-01

    Topical photodynamic therapy (PDT) is an approved treatment for superficial nonmelanoma skin cancers. To enhance photosensitizer penetration into the epidermis, microneedling (MN) devices or ablative carbon dioxide lasers are combined with PDT. To compare the efficacy and safety of MN-assisted PDT with that of conventional PDT in human skin field cancerization. Ten patients with multiple actinic keratoses (AKs) and photodamage were randomized to receive conventional methyl aminolevulinate (MAL) with previous gentle curettage on one side of the face and MAL-PDT combined with 1.5-mm-length MN on the other side after MAL application. After a 90-minute incubation, patients were illuminated with a red light-emitting diode and evaluated for improvement of photodamage, clearance of AKs, and side effects before and after 30 and 90 days. At day 30, global scores for photodamage, mottled pigmentation, roughness, and sallowness improved on both sides (p PDT side (p = .004). At day 90, facial erythema (p = .04) and coarse wrinkles (p = .002) also improved on the MN-PDT side, in addition to fine lines for conventional MAL-PDT (p = .01). Erythema (p = .009), edema (p = .01), crusting (p = .01), and pain (p = .004) were more common and intense on the MN-PDT side. One patient developed a secondary bacterial infection at day 7 on the MN-PDT side. Average AK clearance was 88.3%, with no difference between the sides. Microneedling-assisted PDT is a safe and effective method and can produce superior cosmetic results to conventional MAL-PDT for improving photodamaged skin. Further larger prospective studies are needed to determine whether the addition of MN decreases actinic keratosis. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  9. Psychopaths show enhanced amygdala activation during fear conditioning

    Directory of Open Access Journals (Sweden)

    Douglas eSchultz

    2016-03-01

    Full Text Available Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into primary and secondary psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional fearlessness, while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  10. Monitoring blood flow and photobleaching during topical ALA PDT treatment

    Science.gov (United States)

    Sands, Theresa L.; Sunar, Ulas; Foster, Thomas H.; Oseroff, Allan R.

    2009-02-01

    Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) is currently used as a clinical treatment for nonmelanoma skin cancers. In order to optimize PDT treatment, vascular shutdown early in treatment must be identified and prevented. This is especially important for topical ALA PDT where vascular shutdown is only temporary and is not a primary method of cell death. Shutdown in vasculature would limit the delivery of oxygen which is necessary for effective PDT treatment. Diffuse correlation spectroscopy (DCS) was used to monitor relative blood flow changes in Balb/C mice undergoing PDT at fluence rates of 10mW/cm2 and 75mW/cm2 for colon-26 tumors implanted intradermally. DCS is a preferable method to monitor the blood flow during PDT of lesions due to its ability to be used noninvasively throughout treatment, returning data from differing depths of tissue. Photobleaching of the photosensitizer was also monitored during treatment as an indirect manner of monitoring singlet oxygen production. In this paper, we show the conditions that cause vascular shutdown in our tumor model and its effects on the photobleaching rate.

  11. Photodynamic therapy for actinic keratosis: Is the European consensus protocol for daylight PDT superior to conventional protocol for Aktilite CL 128 PDT?

    Science.gov (United States)

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

    2017-09-01

    Topical photodynamic therapy (PDT) is an established treatment modality for various dermato-oncologic conditions. In Europe, initially requiring irradiation with red light, PDT of actinic keratosis (AK) can now also be carried out with exposure to daylight that has been clinically proven to be as effective as and less painful than red light. In this paper, we propose a comparison between the conventional protocol for Aktilite CL 128 (red light source) PDT and the European consensus protocol for daylight PDT - with the exposure is assumed to be performed during either a clear sunny day or an overcast day - in the treatment of AK with methyl aminolevulinate through a mathematical modeling. This already published modeling that is based on an iterative procedure alternating determination of the local fluence rate and updating of the local optical properties enables to estimate the local damage induced by the therapy. The European consensus protocol for daylight PDT during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times higher PDT local damages at the end of the treatment than those obtained using the conventional protocol for Aktilite CL 128 PDT, respectively. Results analysis shows that, even performed during an overcast day, the European consensus protocol for daylight PDT leads to higher PDT local damages than the efficient conventional protocol for Aktilite CL 128. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Tumor PDT-associated immune response: relevance of sphingolipids

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Separovic, Duska M.

    2010-02-01

    Sphingolipids have become recognized as essential effector molecules in signal transduction with involvement in various aspects of cell function and death, immune response and cancer treatment response. Major representatives of sphingolipids family, ceramide, sphingosine and sphingosine-1-phosphate (S1P), have attracted interest in their relevance to tumor response to photodynamic therapy (PDT) because of their roles as enhancers of apoptosis, mediators of cell growth and vasculogenesis, and regulators of immune response. Our recent in vivo studies with mouse tumor models have confirmed that PDT treatment has a pronounced impact on sphingolipid profile in the targeted tumor and that significant advances in therapeutic gain with PDT can be attained by combining this modality with adjuvant treatment with ceramide analog LCL29.

  13. Fluorescence Guided PDT for Optimization of Skin Cancer Treatment

    Science.gov (United States)

    Blanco, Kate; Moriyama, Lilian; Inada, Natalia; Kurachi, Cristina; Salvio, Ana; Leite, Everson; Menezes, Priscila; Bagnato, Vanderlei

    2015-04-01

    The photodynamic therapy (PDT) is an alternative technique that can be indicated for superficial basal cell carcinoma (sBCC), Bowen’s disease and actinic keratosis with high efficiency. The objective of this study is to present the importance of fluorescence imaging for PDT guidance and monitoring in real time. Confirming that the lesion is well prepared and the photosensitizer shows a homogenous distribution, the outcome after few PDT sessions will be positive and the recurrence should be lower. Our proposition in this study is use the widefield fluorescence imaging to evaluate the PDT protocol in situ and in real time for each lesion. This evaluation procedure is performed in two steps: first with the monitoring of the production of protoporphyrin IX (PpIX) induced by methyl aminolevulinate (MAL), an derivative of 5-aminolevulinic acid (ALA) and second with the detection of PpIX photobleaching after illumination. The fluorescence images provide information correlated with distinct clinical features and with the treatment outcome. Eight BCC lesions are presented and discussed in this study. Different fluorescence patterns of PpIX production and photobleaching could be correlated with the treatment response. The presented results show the potential of using widefield fluorescence imaging as a guidance tool to customized PDT.

  14. PDT-apoptotic tumor cells induce macrophage immune response

    Science.gov (United States)

    Zhou, Fei-fan; Xing, Da; Chen, Wei R.

    2008-02-01

    Photodynamic therapy (PDT) functions as a cancer therapy through two major cell death mechanisms: apoptosis and necrosis. Immunological responses induced by PDT has been mainly associated with necrosis while apoptosis associated immune responses have not fully investigated. Heat shock proteins (HSPs) play an important role in regulating immune responses. In present study, we studied whether apoptotic tumor cells could induce immune response and how the HSP70 regulates immune response. The endocytosis of tumor cells by the activated macrophages was observed at single cell level by LSM. The TNF-α release of macrophages induced by co-incubated with PDT-apoptotic tumor cells was detected by ELISA. We found that apoptotic tumor cells treated by PDT could activate the macrophages, and the immune effect decreased evidently when HSP70 was blocked. These findings not only show that apoptosis can induce immunological responses, but also show HSP70 may serves as a danger signal for immune cells and induce immune responses to regulate the efficacy of PDT.

  15. PDT in periodontal disease of HAART resistance patients

    Science.gov (United States)

    Giovani, Elcio M.; Noro-Filho, Gilberto A.; Caputo, Bruno V.; Casarin, Renato; Costa, Claudio; Salgado, Daniela; Santos, Camila C.

    2016-03-01

    HIV/Aids patients present a change of microbiota associated with host immunodeficiency. Photodynamic therapy (PDT) showed as a promising and viable alternative in reducing microbiota. Present study evaluate effectiveness of photodynamic therapy in periodontal disease of AIDS patients with highly activity antiretroviral therapy (HAART) failure, measuring the clinical periodontal parameters and periodontal microbiota. Twelve patients with HARRT resistance (R group) divided into two groups (control and PDT) and 12 patients with no HAART resistance (NR group) divided into two groups (control and PDT). The results show the difference in baseline of CD4 cells count, NR group 640.0 +/- 176.2 cells/mm3 R group and 333.3 +/- 205.8 cells / mm3 (pperiodontal parameters (PD and CAL), PDT was more effective than the control group only in the NR group (p periodontal parameters between the both R groups (p>0.05%). Microbiological evaluation in R group presents a general reduction in the Aa at 3 and 6 months. Furthermore, demonstrated a reduction of Pg in all groups at 6 months and in R group at 3 months. The impact assessment of photodynamic therapy in patients with different levels of immunosuppression determined that the combination of mechanical periodontal treatment with photodynamic therapy in patients with HAART failure did not cause additional benefits. Therefore, PDT in this study could not been indicated in HAART resistance patients.

  16. Early activation of fibroblasts during PDT treatment in leg ulcers.

    Science.gov (United States)

    Corsi, Alessandro; Lecci, Pier P; Bacci, Stefano; Cappugi, Pietro; Pimpinelli, Nicola

    2016-06-01

    This pilot study was aimed to assess the variations of some microscopical parameters in skin ulcers, caused by chronic venous insufficiency of the lower extremities (chronic leg ulcers), in 15 patients refractory to previous conventional treatments during photodynamic therapy (PDT). Samples of control, wounded and PDT treated skin were taken and analyzed by immunohistochemistry. The cellular infiltrate, as well as the thickness of epidermis, vascularization, mast cell and fibroblast numbers, were increased in chronic wounds as compared to healthy skin. After completion of PDT, fibroblasts appeared further increased in number. Mast cells, closely clustered with fibroblasts, also showed an increase in their numbers, degranulation index and expression of basic fibroblast growth factor. The present findings support a primary role of fibroblasts in the wound healing process upon PDT treatment, given their early and intense reaction to injury. Mast cells seem to play an accessory yet important role, on the basis of their number and degranulation index variations and expression of basic FGF. In addition, the clustering of mast cells with fibroblasts around blood vessels suggest that these cells may stimulate angiogenesis and, in parallel, fibroblasts to secrete extracellular matrix during PDT therapy.

  17. A heterogeneous algorithm for PDT dose optimization for prostate

    Science.gov (United States)

    Altschuler, Martin D.; Zhu, Timothy C.; Hu, Yida; Finlay, Jarod C.; Dimofte, Andreea; Wang, Ken; Li, Jun; Cengel, Keith; Malkowicz, S.B.; Hahn, Stephen M.

    2015-01-01

    The object of this study is to develop optimization procedures that account for both the optical heterogeneity as well as photosensitizer (PS) drug distribution of the patient prostate and thereby enable delivery of uniform photodynamic dose to that gland. We use the heterogeneous optical properties measured for a patient prostate to calculate a light fluence kernel (table). PS distribution is then multiplied with the light fluence kernel to form the PDT dose kernel. The Cimmino feasibility algorithm, which is fast, linear, and always converges reliably, is applied as a search tool to choose the weights of the light sources to optimize PDT dose. Maximum and minimum PDT dose limits chosen for sample points in the prostate constrain the solution for the source strengths of the cylindrical diffuser fibers (CDF). We tested the Cimmino optimization procedures using the light fluence kernel generated for heterogeneous optical properties, and compared the optimized treatment plans with those obtained using homogeneous optical properties. To study how different photosensitizer distributions in the prostate affect optimization, comparisons of light fluence rate and PDT dose distributions were made with three distributions of photosensitizer: uniform, linear spatial distribution, and the measured PS distribution. The study shows that optimization of individual light source positions and intensities are feasible for the heterogeneous prostate during PDT. PMID:25914793

  18. The role of photodynamic therapy (PDT) physics.

    Science.gov (United States)

    Zhu, Timothy C; Finlay, Jarod C

    2008-07-01

    Photodynamic therapy (PDT) is an emerging treatment modality that employs the photochemical interaction of three components: light, photosensitizer, and oxygen. Tremendous progress has been made in the last 2 decades in new technical development of all components as well as understanding of the biophysical mechanism of PDT. The authors will review the current state of art in PDT research, with an emphasis in PDT physics. They foresee a merge of current separate areas of research in light production and delivery, PDT dosimetry, multimodality imaging, new photosensitizer development, and PDT biology into interdisciplinary combination of two to three areas. Ultimately, they strongly believe that all these categories of research will be linked to develop an integrated model for real-time dosimetry and treatment planning based on biological response.

  19. PDT - PARTICLE DISPLACEMENT TRACKING SOFTWARE

    Science.gov (United States)

    Wernet, M. P.

    1994-01-01

    Particle Imaging Velocimetry (PIV) is a quantitative velocity measurement technique for measuring instantaneous planar cross sections of a flow field. The technique offers very high precision (1%) directionally resolved velocity vector estimates, but its use has been limited by high equipment costs and complexity of operation. Particle Displacement Tracking (PDT) is an all-electronic PIV data acquisition and reduction procedure which is simple, fast, and easily implemented. The procedure uses a low power, continuous wave laser and a Charged Coupled Device (CCD) camera to electronically record the particle images. A frame grabber board in a PC is used for data acquisition and reduction processing. PDT eliminates the need for photographic processing, system costs are moderately low, and reduced data are available within seconds of acquisition. The technique results in velocity estimate accuracies on the order of 5%. The software is fully menu-driven from the acquisition to the reduction and analysis of the data. Options are available to acquire a single image or 5- or 25-field series of images separated in time by multiples of 1/60 second. The user may process each image, specifying its boundaries to remove unwanted glare from the periphery and adjusting its background level to clearly resolve the particle images. Data reduction routines determine the particle image centroids and create time history files. PDT then identifies the velocity vectors which describe the particle movement in the flow field. Graphical data analysis routines are included which allow the user to graph the time history files and display the velocity vector maps, interpolated velocity vector grids, iso-velocity vector contours, and flow streamlines. The PDT data processing software is written in FORTRAN 77 and the data acquisition routine is written in C-Language for 80386-based IBM PC compatibles running MS-DOS v3.0 or higher. Machine requirements include 4 MB RAM (3 MB Extended), a single or

  20. An IR Navigation System for Pleural PDT.

    Science.gov (United States)

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

    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 fluence 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.

  1. An IR Navigation System for Pleural PDT

    Directory of Open Access Journals (Sweden)

    Timothy C Zhu

    2015-03-01

    Full Text Available 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.

  2. An IR Navigation System for Pleural PDT

    Science.gov (United States)

    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.

  3. Preclinical Study of Antineoplastic Sinoporphyrin Sodium-PDT via In Vitro and In Vivo Models.

    Science.gov (United States)

    Shi, Rui; Li, Chao; Jiang, Zhihuan; Li, Wanfang; Wang, Aiping; Wei, Jinfeng

    2017-01-11

    Photodynamic therapy (PDT) investigations have seen stable increases and the development of new photosensitizers is a heated topic. Sinoporphyrin sodium is a new photosensitizer isolated from Photofrin. This article evaluated its anticancer effects by clonogenic assays, MTT assays and xenograft experiments in comparison to Photofrin. The clonogenicity inhibition rates of sinoporphyrin sodium-PDT towards four human cancer cell lines ranged from 85.5% to 94.2% at 0.5 μg/mL under 630 nm irradiation of 30 mW/cm² for 180 s. For MTT assays, the IC 50 ranges of Photofrin-PDT and sinoporphyrin sodium-PDT towards human cancer cells were 0.3 μg/mL to 5.5 μg/mL and 0.1 μg/mL to 0.8 μg/mL under the same irradiation conditions, respectively. The IC 50 values of Photofrin-PDT and sinoporphyrin sodium-PDT towards human skin cells, HaCaT, were 10 μg/mL and 1.0 μg/mL, respectively. Esophagus carcinoma and hepatoma xenograft models were established to evaluate the in vivo antineoplastic efficacy. A control group, Photofrin-PDT group (20 mg/kg) and sinoporphyrin sodium group at three doses, 0.5 mg/kg, 1 mg/kg and 2 mg/kg, were set. Mice were injected with photosensitizers 24 h before 60 J 630 nm laser irradiation. The tumor weight inhibition ratio of 2 mg/kg sinoporphyrin sodium-PDT reached approximately 90%. Besides, the tumor growths were significantly slowed down by 2 mg/kg sinoporphyrin sodium-PDT, which was equivalent to 20 mg/kg Photofrin-PDT. In sum, sinoporphyrin sodium-PDT showed great anticancer efficacy and with a smaller dose compared with Photofrin. Further investigations are warranted.

  4. Comparative tumor imaging and PDT Efficacy of HPPH conjugated in the mono- and di-forms to various polymethine cyanine dyes: part - 2.

    Science.gov (United States)

    James, Nadine S; Ohulchanskyy, Tymish Y; Chen, Yihui; Joshi, Penny; Zheng, Xiang; Goswami, Lalit N; Pandey, Ravindra K

    2013-01-01

    Previous reports from our laboratory have shown that a bifunctional agent obtained by conjugating a photosensitizer (HPPH) to a cyanine dye (CD) can be used for fluorescence image-guided treatment of tumor by photodynamic therapy (PDT). However, the resulting HPPH-CD conjugate showed a significant difference between the tumor-imaging and therapeutic doses. It was demonstrated that the singlet oxygen ( (1) O 2 (*), a key cytotoxic agent in PDT) produced by the conjugate upon excitation of the HPPH moiety was partially quenched by the CD-moiety; this resulted in a reduced PDT response when compared to HPPH-PDT under similar treatment parameters. To improve the therapeutic potential of the conjugate, we synthesized a series of dual functional agents in which one or two HPPH moieties were separately conjugated to three different dyes (Cypate, modified IR820 or modified IR783). The newly synthesized conjugates were compared with our lead compound HPPH-CD in terms of photophysical properties, in vitro and in vivo PDT efficacy, tumor uptake and imaging potential. Among the analogs investigated, the conjugate, in which two HPPH moieties were linked to the modified IR820 produced enhanced tumor uptake and tumor contrast in both Colon 26 (a murine Colon carcinoma) and U87 (a human glioblastoma) cell lines. The long-term PDT efficacy (cure) of this conjugate in BALB/c mice, bearing Colon 26 tumors was also enhanced; however, its efficacy in Nude mice bearing U87 tumors was slightly reduced. It was also found that in all the conjugates the singlet oxygen generation and, consequently, PDT efficacy were compromised by a competing pathway, whereby an electronic excitation of HPPH, the energy donor, is deactivated through an electronic excitation energy transfer (Forster Resonance Energy Transfer, FRET) to the CD fluorophore, the energy acceptor, resulting in overall reduction of the singlet oxygen production. Conjugates with increased FRET showed reduced singlet oxygen production

  5. ALA-PDT mediated DC vaccine for skin squamous cell carcinoma

    Science.gov (United States)

    Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.

    2015-03-01

    Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.

  6. Improvement of DC vaccine with ALA-PDT induced immunogenic apoptotic cells for skin squamous cell carcinoma.

    Science.gov (United States)

    Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Chen, Wei R; Wang, Xiuli

    2015-07-10

    Dendritic cell (DC) based vaccines have emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have achieved only limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated using electron microscopy, FACS, and ELISA. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with a mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including morphology maturation (enlargement of dendrites and increase of lysosomes), phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secrete IFN-γ and IL-12, and to induce T cell proliferation). Most interestingly, PDT-induced apoptotic tumor cells are more capable of potentiating maturation of DCs than PDT-treated or freeze/thaw treated necrotic tumor cells. ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumors in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing a DC-based cancer vaccine, which could improve the clinical application of PDT-DC vaccines.

  7. Interstitial PDT using diffuser fiber-investigation in phantom and in vivo models.

    Science.gov (United States)

    Stringasci, Mirian D; Fortunato, Thereza C; Moriyama, Lilian T; Filho, José Dirceu Vollet; Bagnato, Vanderlei S; Kurachi, Cristina

    2017-07-01

    Photodynamic therapy (PDT) has been used for local treatment of several types of tumors. Light penetration of biological tissue is one limiting factor in PDT, decreasing the success rates of the treatment of invasive and solid tumors. In those cases, a possible solution is to use interstitial PDT, in which both diffuser optical fibers are inserted into the tumor. The uniformity of the diffuser emission plays a crucial role in planning the delivery of the appropriate light fluence and in ensuring treatment success. In this study, we characterized a diffuser optical fiber concerning its homogeneity. We showed that the diffuser emission can be inhomogeneous and that the necrosis generated by interstitial PDT using such a diffuser for illumination is asymmetrical in volume as a result. This observation has relevant consequences in achieving success in PDT and phototherapies in general, as the delivered light fluence depends on adequate previous knowledge of the irradiation profile.

  8. Can daylight-PDT be performed indoor?

    Science.gov (United States)

    Mordon, Serge; Vignion-Dewalle, Anne S; Thecua, Elise; Vicentini, Claire; Maire, Cyril; Deleporte, Pascal; Baert, Gregory; Lecomte, Fabienne; Mortier, Laurent

    2018-02-07

    Natural DayLight-mediated PhotoDynamic Therapy (NDL-PDT) is an efficacious treatment option for thin actinic keratosis that offers advantages over conventional PDT in terms of tolerability, treatment duration, and cost. It is now accepted that the minimum criteria required for effective NDL-PDT is a dose of 4 J/cm2 with a treatment time of 2 h and a minimum temperature of 10°C, corresponding to a minimum illuminance of 11 000 lux. This value is easily achievable: 20 000 lux can be obtained during a typical overcast day at midday. It can reach 110 000 lux with a bright sunlight However, it is limited to certain times of the year at our latitude. However rain and cold temperatures appear the main limitations of NDL-PDT. Greenhouses make possible to perform the illumination even in harsh weather conditions. Furthermore, it is difficult to install a greenhouse everywhere. Several solutions are now proposed to carry out indoor illumination so-called artificial white light or simulated daylight (SDL-PDT). Illumination sources installed at the ceiling of the treatment room is one option. Several lamp pairs can be combined to illuminate groups of patients simultaneously. A surgical theatre light can be used or dedicated systems using white LEDs can be used to deliver the required illumination dose. In conclusion, Indoor lightning (or simulated daylight: SDL-PDT or Artificial White Light: AWL) could offer an interesting alternative to NDL-PDT.

  9. Hepatic scar in a case of healed candidiasis showing prolonged enhancement on CT

    Energy Technology Data Exchange (ETDEWEB)

    Itai, Yuji; Yashiro, Naobumi

    1987-08-01

    A patient with acute myelocytic leukemia recovering from hepatic candidiasis after long-term administration of amphotericin B had large scar in the liver which showed prominent prolonged enhancement on postcontrast CT. Prolonged enhancement can occur in regions other than hepatic masses.

  10. Pathway-PDT: a flexible pathway analysis tool for nuclear families.

    Science.gov (United States)

    Park, Yo Son; Schmidt, Michael; Martin, Eden R; Pericak-Vance, Margaret A; Chung, Ren-Hua

    2013-09-04

    Pathway analysis based on Genome-Wide Association Studies (GWAS) data has become popular as a secondary analysis strategy. Although many pathway analysis tools have been developed for case-control studies, there is no tool that can use all information from raw genotypes in general nuclear families. We developed Pathway-PDT, which uses the framework of Pedigree Disequilibrium Test (PDT) for general family data, to perform pathway analysis based on raw genotypes in family-based GWAS. Simulation results showed that Pathway-PDT is more powerful than the p-value based method, ALIGATOR. Pathway-PDT also can be more powerful than the PLINK set-based test when analyzing general nuclear families with multiple siblings or missing parents. Additionally, Pathway-PDT has a flexible and convenient user interface, which allows users to modify their analysis parameters as well as to apply various types of gene and pathway definitions. The Pathway-PDT method is implemented in C++ with POSIX threads and is computationally feasible for pathway analysis with large scale family GWAS datasets. The Windows binary along with Makefile and source codes for the Linux are available at https://sourceforge.net/projects/pathway-pdt/.

  11. mTHPC mediated photodynamic therapy (PDT) of squamous cell carcinoma in the head and neck: a systematic review.

    Science.gov (United States)

    de Visscher, S A H J; Dijkstra, P U; Tan, I B; Roodenburg, J L N; Witjes, M J H

    2013-03-01

    Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC). To evaluate available evidence on the use of mTHPC (Foscan®) mediated PDT, we conducted a review of the literature. A systematic review was performed by searching seven bibliographic databases on database specific mesh terms and free text words in the categories; "head and neck neoplasms", "Photodynamic Therapy" and "Foscan". Papers identified were assessed on several criteria by two independent reviewers. The search identified 566 unique papers. Twelve studies were included for our review. Six studies reported PDT with curative intent and six studies reported PDT with palliative intent, of which three studies used interstitial PDT. The studies did not compare PDT to other treatments and none exceeded level 3 using the Oxford levels of evidence. Pooling of data (n=301) was possible for four of the six studies with curative intent. T1 tumors showed higher complete response rates compared to T2 (86% vs 63%). PDT with palliative intent was predominantly used in patients unsuitable for further conventional treatment. After PDT, substantial tumor response and increase in quality of life was observed. Complications of PDT were mostly related to non-compliance to light restriction guidelines. The studies on mTHPC mediated PDT for HNSCC are not sufficient for adequate assessment of the efficacy for curative intent. To assess efficacy of PDT with curative intent, high quality comparative, randomized studies are needed. Palliative treatment with PDT seems to increase the quality of life in otherwise untreatable patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells.

    Science.gov (United States)

    Qiao, Li; Xu, Chengshan; Li, Qiang; Mei, Zhusong; Li, Xinji; Cai, Hong; Liu, Wei

    2016-06-01

    5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC-Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (pPDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (pPDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. Copyright © 2016. Published by Elsevier B.V.

  13. The synergistic effect of PDT and oxacillin on clinical isolates of Staphylococcus aureus.

    Science.gov (United States)

    Iluz, Natanel; Maor, Yasmin; Keller, Natan; Malik, Zvi

    2018-01-15

    Staphylococcus aureus is a major pathogen in clinical microbiology. It is known to cause infections at various body sites and can be life-threatening. The development of resistance to many well-established antibiotic treatments and the prevalence of methicillin-resistant S. aureus (MRAS) among hospital patients and the general community pose challenges in treating the pathogen. The antimicrobial effect of photodynamic therapy (PDT) has been a subject of study for a long time and can offer new strategies for dealing with resistant strains. In our study, we searched for a positive synergistic relationship between PDT and the standard antibiotics used to treat S. aureus and MRSA infections. The phototoxic profile of deuteroporphyrin (DP) in both resistant and susceptible clinical strains of S. aureus was determined by plating of treated and untreated broth cultures. Electron microscopy imaging was done to explore possible sites of damage and free-radical accumulation in the cells during DP-PDT. Minimal inhibitory concentration (MIC) of oxacillin, gentamicin, vancomycin, rifampin, and fusidic acid was determined using the broth dilution method, and the checkerboard method was used to detect and evaluate the synergistic potential of DP-PDT and antibiotic combinations. A synergistic combination was further characterized using broth cultures and plating. DP-PDT using a light dose of 15 J/cm 2 showed a bactericidal effect even with a small concentration of 17 μM DP. Transmission electron microscopy indicated profound damage in the cell wall and cell membrane, and the appearance of mesosome-like structures. Free radicals tend to localize in the cell membrane and inside the mesosome. No synergistic effect was detected by combining PDT with gentamicin, vancomycin, rifampin, and fusidic acid treatments. A positive synergistic effect was observed only in DP-PDT-oxacillin combined treatment using the checkerboard method. The effect was observed in clinical antibiotic

  14. The effect of Radachlorin® PDT in advanced NSCLC: a pilot study.

    Science.gov (United States)

    Ji, Wonjun; Yoo, Jung-wan; Bae, Eun Kyung; Lee, Ji Hye; Choi, Chang-Min

    2013-05-01

    Palliative effect of PDT in advanced NSCLC has been proven. Radachlorin® is a second generation photosensitizer that has quicker pharmacokinetics than first generation photosensitizers. Although there are reports describing Radachlorin®, limited data are available regarding its advantages in PDT. Advanced NSCLC patients with central airway obstruction were enrolled. Patients who had comorbidity effects on drug metabolism were excluded. All patients received 1mg/kg of Radachlorin®, 4 h before light irradiation. 200 J/cm² of laser was irradiated during 11 min 6 s. Bronchial toileting was performed the following day. A PFT was performed before and after PDT. The primary treatment outcome was improvement of airway obstruction, which was evaluated according to bronchoscopic findings and improvement of FEV1. Secondary treatment outcomes included the rate of PDT-related complications, one year survival rate and progression free survival. Ten patients were enrolled between June 2010 and May 2011. Their median age was 58.5 years and their baseline cancer stage was more than IIIA. 20% of patients showed successful results, 70% showed partially successful results and 10% showed an unsuccessful result. All patients showed improvement in their obstructive symptoms. The mean FEV1 before PDT was 1.70±0.69 L, while the mean FEV1 after PDT was 1.99±0.60 L (P=0.029). No patients had major complications. Eight patients were undergoing additional treatment after resolving airway obstruction. The one year survival rate after PDT was 70%. Radachlorin®-based PDT is safe and effective treatment for relieving central airway obstruction in advanced NSCLC. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. PDT Dose Dosimeter for Pleural Photodynamic Therapy.

    Science.gov (United States)

    Kim, Michele M; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C; Zhu, Timothy C

    2016-03-17

    PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry.

  16. Deciphering PDT-induced inflammatory responses using real-time FDG-PET in a mouse tumour model.

    Science.gov (United States)

    Cauchon, Nicole; Hasséssian, Haroutioun M; Turcotte, Eric; Lecomte, Roger; van Lier, Johan E

    2014-10-01

    Dynamic positron emission tomography (PET), combined with constant infusion of 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG), enables real-time monitoring of transient metabolic changes in vivo, which can serve to understand the underlying physiology. Here we investigated characteristic changes in the tumour FDG-uptake profiles in relation to acute localized inflammatory responses induced by photodynamic therapy (PDT). Dynamic PET imaging with constant FDG infusion was used with EMT-6 tumour bearing mice. FDG time-activity uptake curves were measured simultaneously, in treated and reference tumours, for 3 hours, before, during and after PDT light treatment. Inflammation was studied when evoked, either by PDT using a trisulfonated porphyrazine photosensitizer, or lipopolysaccharide (LPS), and inhibited using indomethacin. The distinct transient patterns, characterized by drops and subsequent recovery of tumour FDG uptake rates, were also analysed using immunohistochemical markers for apoptosis, necrosis, and inflammation. Typical profiles for tumour FDG-uptake, consisted of a drop during PDT, followed by a gradual recovery period. Tumours treated with LPS, but not with light, showed a continuous increase in FDG-uptake during the 3 h experimental period. Treatment with indomethacin, inhibited the rise in FDG-uptake observed with either LPS or PDT. Tumour FDG-uptake profiles correlated with necrosis markers during PDT, and inflammatory response markers post-PDT, but not with an apoptosis marker at any time during or after PDT. Dynamic FDG-PET imaging combined with indomethacin reveals that, the drop in the tumour FDG-uptake rate during the PDT illumination phase reflects vascular collapse and necrosis, while the increased tumour FDG-uptake rate immediately post-illumination involves an acute localized inflammatory response. Dynamic FDG infusion and PET imaging, combined with the use of selective inhibitors, provides unique insight for deciphering the complex underlying

  17. The mechanism of PDT-induced apoptosis

    Science.gov (United States)

    Cai, Xiongwei; Liu, Timon C.; Ding, Xin-Min; Gu, Ying; Liu, Fan-Guang; Liu, Song-Hao

    2003-12-01

    Photodynamic therapy (PDT) can induce apoptosis in many cancer cells in vitro and in tumors in vivo. Cells become more oxidation with PDT, and maintain differentiation and proliferation, go apoptosis and necrosis with the increase of reactive oxygen species (ROS) concentration. ROS can induce apoptosis through mitochondria by inhibiting respiration chain or oxidative phosphorylation or damaging mitochondrial membrane. ROS can initiate apoptosis through endoplamic reticulum(ER) by opening Ca2+ channel or starting unfold protein response (UPR). ROS can also induce apoptosis through Golgi by producing ganglioside GD3 by use of ceramide, which induces apoptosis by activating caspase-3, JNK and p38 MAPK. It can also induce apoptosis by activating Bip (mitochondria-dependant) or preocaspase-12 (mitochondria- independent) or inhibiting protein synthesizing. There are so complicated cross-talking among different signal pathways or organnells that we think PDT-induced apoptosis is mediated by multiplex pathways and excessive levels in a refined network.

  18. The in Vitro Antimicrobial Efficacy of PDT against Periodontopathogenic Bacteria.

    Science.gov (United States)

    Haag, Philippe A; Steiger-Ronay, Valerie; Schmidlin, Patrick R

    2015-11-13

    Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT) as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. The focused question was: "Is it possible to decrease (at least 3 log steps or 99.9%) or even eliminate bacterial growth by photodynamic therapy in vitro when compared to untreated control groups or control groups treated by placebo?" In general, PDT resulted in a substantial reduction of surviving bacteria. However, not all studies showed the desired reduction or elimination. The ranges of log10-reduction were 0.38 (58%) to a complete eradication (100%) for P. gingivalis, 0.21 (39%) to 100% for A. actinomycetemcomitans and 0.3 (50%) to 100% for F. nucleatum. In conclusion, further and particularly more comparable studies are needed to evaluate if PDT can be clinically successful as an adjuvant in periodontal therapy.

  19. The in Vitro Antimicrobial Efficacy of PDT against Periodontopathogenic Bacteria

    Science.gov (United States)

    Haag, Philippe A.; Steiger-Ronay, Valerie; Schmidlin, Patrick R.

    2015-01-01

    Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT) as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. The focused question was: “Is it possible to decrease (at least 3 log steps or 99.9%) or even eliminate bacterial growth by photodynamic therapy in vitro when compared to untreated control groups or control groups treated by placebo?” In general, PDT resulted in a substantial reduction of surviving bacteria. However, not all studies showed the desired reduction or elimination. The ranges of log10-reduction were 0.38 (58%) to a complete eradication (100%) for P. gingivalis, 0.21 (39%) to 100% for A. actinomycetemcomitans and 0.3 (50%) to 100% for F. nucleatum. In conclusion, further and particularly more comparable studies are needed to evaluate if PDT can be clinically successful as an adjuvant in periodontal therapy. PMID:26580607

  20. The in Vitro Antimicrobial Efficacy of PDT against Periodontopathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Philippe A. Haag

    2015-11-01

    Full Text Available Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. The focused question was: “Is it possible to decrease (at least 3 log steps or 99.9% or even eliminate bacterial growth by photodynamic therapy in vitro when compared to untreated control groups or control groups treated by placebo?” In general, PDT resulted in a substantial reduction of surviving bacteria. However, not all studies showed the desired reduction or elimination. The ranges of log10-reduction were 0.38 (58% to a complete eradication (100% for P. gingivalis, 0.21 (39% to 100% for A. actinomycetemcomitans and 0.3 (50% to 100% for F. nucleatum. In conclusion, further and particularly more comparable studies are needed to evaluate if PDT can be clinically successful as an adjuvant in periodontal therapy.

  1. PDT (Product Data Technology), Production and Society

    DEFF Research Database (Denmark)

    Vesterager, Johan

    1997-01-01

    Information and communication technology (ICT) constitute a genuine technical revolution by enabling a dynamic and flexible support or automation of knowledge and information work. Bearing in mind that products are frozen knowledge, ICT as known will change the way we produce products dramatically....... The use of ICT in engineering of products constitutes product data technology (PDT).This paper presents a a basic platform for an understanding the ongoing revolution with focus on the PDT-area taking outset in the fundamental elements of knowledge and information work: creation, transformation...

  2. Photodynamic therapy (PDT) for malignant brain tumors--where do we stand?

    Science.gov (United States)

    Quirk, Brendan J; Brandal, Garth; Donlon, Steven; Vera, Juan Carlos; Mang, Thomas S; Foy, Andrew B; Lew, Sean M; Girotti, Albert W; Jogal, Sachin; LaViolette, Peter S; Connelly, Jennifer M; Whelan, Harry T

    2015-09-01

    What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve standard of care. The questions we wish to answer are: where are we clinically with PDT, why is it not standard of care, and what is being done in clinical trials to get us there. Rather than a meta-analysis or comprehensive review, our review focuses on who the major research groups are, what their approaches to the problem are, and how their results compare to standard of care. Secondary questions include what the effective depth of light penetration is, and how deep can we expect to kill tumor cells. A measurable degree of necrosis is seen to a depth of about 5mm. Cavitary PDT with hematoporphyrin derivative (HpD) results are encouraging, but need an adequate Phase III trial. Talaporfin with cavitary light application appears promising, although only a small case series has been reported. Foscan for fluorescence guided resection (FGR) plus intraoperative cavitary PDT results were improved over controls, but are poor compared to other groups. 5-Aminolevulinic acid-FGR plus postop cavitary HpD PDT show improvement over controls, but the comparison to standard of care is still poor. Continued research in PDT will determine whether the advances shown will mitigate morbidity and mortality, but certainly the potential for this modality to revolutionize the treatment of brain tumors remains. The various uses for PDT in clinical practice should be pursued. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

    2003-12-01

    Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

  4. Lifetime-resolved photoacoustic (LPA) spectroscopy for monitoring oxygen change and photodynamic therapy (PDT)

    Science.gov (United States)

    Jo, Janggun; Lee, Chang Heon; Kopelman, Raoul; Wang, Xueding

    2016-03-01

    The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.

  5. Lifetime-resolved Photoacoustic (LPA) Spectroscopy for monitoring Oxygen change and Photodynamic Therapy (PDT).

    Science.gov (United States)

    Jo, Janggun; Lee, Chang Heon; Kopelman, Raoul; Wang, Xueding

    2016-02-13

    The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.

  6. Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase.

    Science.gov (United States)

    Yang, Deng-Fu; Chen, Jia-Haur; Chiang, Chun-Pin; Huang, Zheng; Lee, Jeng-Woei; Liu, Chung-Ji; Chang, Junn-Liang; Hsu, Yih-Chih

    2014-09-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT could be further improved by calcipotriol (CAL). Precancerous lesions in the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA). Lesions were treated with multiple topical ALA-PDT with or without CAL pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX, and FECH) were examined in an in vitro model using human squamous cell carcinoma (SCC) cells (SCC4, SAS) using Western blots. Fluorescence spectroscopy revealed that PpIX reached its peak level in precancerous epithelial cells of buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both treatment regimens showed similar response rates, but the complete response was achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (pPDT in treating precancerous lesions, likely through the increase in CPOX level and in PpIX production. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Tumor-targeting nanogel that can function independently for both photodynamic and photothermal therapy and its synergy from the procedure of PDT followed by PTT.

    Science.gov (United States)

    Kim, Ja-Young; Choi, Won Il; Kim, Manse; Tae, Giyoong

    2013-10-28

    A dual-function nano-system for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) was constructed. Gold nanorods (GNRs) as a PTT agent and chlorin e6 (Ce6) as a photosensitizer (PS) for PDT were loaded into a chitosan-functionalized, Pluronic-based nanogel that was proven to be an efficient delivery vehicle to the tumor site in vivo. Previously reported combined therapy systems relied on quenching and de-quenching of PS for PDT upon thermo-impact of PTT, thus only PTT followed by PDT procedure was possible. In contrast, the present dual-acting system has no quenching between PS and GNRs by preventing direct contact and self-aggregation of photo-sensitizers, allowing independent PDT or PTT procedure. In both in vitro cell culture and in vivo tumor-bearing mice experiments, a remarkably enhanced tumor ablation compared to the treatment of PDT or PTT only was observed by the treatment of PDT followed by PTT, but not significantly by the treatment of PTT followed by PDT. Thus, the present study demonstrated the synergistic effect of PDT and PTT in a sequence-dependent manner, and our system is a promising dual function nano system to achieve the enhanced phototherapy in vivo. © 2013.

  8. Grapheme-color synesthetes show enhanced crossmodal processing between auditory and visual modalities.

    Science.gov (United States)

    Brang, David; Williams, Lisa E; Ramachandran, Vilayanur S

    2012-05-01

    Synesthesia is an involuntary experience in which stimulation of one sensory modality triggers additional, atypical sensory experiences. Strong multisensory processes are present in the general population, but the relationship between these 'normal' sensory interactions and synesthesia is currently unknown. Neuroimaging research suggests that some forms of synesthesia are caused by enhanced cross-activation between brain areas specialized for the processing of different sensory attributes, and finds evidence of increased white matter connections among regions known to be involved in typical crossmodal processes. Using two classic crossmodal integration tasks we show that grapheme-color synesthetes exhibit enhanced crossmodal interactions between auditory and visual modalities, suggesting that the experience of synesthesia in one modality generalizes to enhanced crossmodal processes with other modalities. This finding supports our conjecture that the atypical sensory experiences of synesthetes represent a selective expression of a more diffuse propensity toward 'typical' crossmodality interactions. Copyright © 2011 Elsevier Srl. All rights reserved.

  9. PDT-induced in vitro bystander effect

    Science.gov (United States)

    Olivier, David; Douilard, Samuel; Patrice, Thierry

    2009-06-01

    The mechanisms of Photodynamic therapy (PDT) include singlet oxygen and reactive oxygen species (ROS) production that damage tumor cells and vasculature. The resulting effect is a balance between photo-oxidations via primary or secondary ROS and scavenging activity. Sensitizers distribute in the extra-cellular space before and during cell sensitization, suggesting that PDT could act directly on cell structures and on extra-cellular compartments, including sera. In this paper we endeavored to determine whether the application of PDT to culture media could have an effect on cell survival. Culture media (RPMI supplemented with Fetal Calf Serum (FCS)) was incubated with Rose Bengal (RB) and irradiated before being added to cells for various times of contact, as a replacement for untreated media. Treatedmedia reduced cell survival by up to 40% after 30 min of contact for 10 μg/mL of RB and 20 J/cm2. This effect was RB or light dose-dependent. The survival reduction observed when adding treated-media was more pronounced when cell doubling time was shorter. Analysis of ROS or peroxide production in treated-media revealed a long-lasting oxidizing activity. Our findings support the hypothesis of a ROS or peroxide-mediated, PDT-induced, delayed cell toxicity

  10. Photodynamic Therapy (PDT)-Basic Principles

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 4. Photodynamic Therapy (PDT) - Basic Principles. Bhaskar G Maiya. Series Article Volume 5 Issue 4 April 2000 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/005/04/0006-0018 ...

  11. Gadofluorine M-enhanced MRI shows involvement of circumventricular organs in neuroinflammation

    Directory of Open Access Journals (Sweden)

    Glumm Robert

    2010-10-01

    Full Text Available Abstract Background Circumventricular organs (CVO are cerebral areas with incomplete endothelial blood-brain barrier (BBB and therefore regarded as "gates to the brain". During inflammation, they may exert an active role in determining immune cell recruitment into the brain. Methods In a longitudinal study we investigated in vivo alterations of CVO during neuroinflammation, applying Gadofluorine M- (Gf enhanced magnetic resonance imaging (MRI in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. SJL/J mice were monitored by Gadopentate dimeglumine- (Gd-DTPA and Gf-enhanced MRI after adoptive transfer of proteolipid-protein-specific T cells. Mean Gf intensity ratios were calculated individually for different CVO and correlated to the clinical disease course. Subsequently, the tissue distribution of fluorescence-labeled Gf as well as the extent of cellular inflammation was assessed in corresponding histological slices. Results We could show that the Gf signal intensity of the choroid plexus, the subfornicular organ and the area postrema increased significantly during experimental autoimmune encephalomyelitis, correlating with (1 disease severity and (2 the delay of disease onset after immunization. For the choroid plexus, the extent of Gf enhancement served as a diagnostic criterion to distinguish between diseased and healthy control mice with a sensitivity of 89% and a specificity of 80%. Furthermore, Gf improved the detection of lesions, being particularly sensitive to optic neuritis. In correlated histological slices, Gf initially accumulated in the extracellular matrix surrounding inflammatory foci and was subsequently incorporated by macrophages/microglia. Conclusion Gf-enhanced MRI provides a novel highly sensitive technique to study cerebral BBB alterations. We demonstrate for the first time in vivo the involvement of CVO during the development of neuroinflammation.

  12. Effects of ALA-PDT on HPV16-immortalized cervical epithelial cell.

    Science.gov (United States)

    Wu, S X; Ren, X Y; Pan, Y L; Guan, D D; Liu, S; Zou, X Y; Shi, C G; Li, Y Z; Zhang, Y Z

    2017-01-01

    Current treatments for high-grade cervical intraepithelial neoplasia (CIN) and persistent infection with high-risk human papillomavirus (HR-HPV) type are mainly surgical interventions. However, such treatments are associated with adverse side effects and pose risks for future pregnancies. In order to reduce the requirement for excisional procedures, an effective and noninvasive therapy is needed for women at reproductive age. ALA-PDT has proved to be effective in the treatment of HPV-associated disease in several clinical investigations. In this study, the anti-proliferative effect of ALA-PDT was investigated in HPV16-immortalized cervical epithelial H8 cells. CCK-8 assay was used to measure cytotoxicity in H8 cells. The IC50 of ALA-PDT on H8 cells was about 120.75 ± 1.18 µM. We have now evaluated the mechanism by which ALA-PDT induces cell death. Annexin V-FITC/PI staining showed a significant dose-dependent induction of apoptosis by ALA-PDT in H8 cells, associated with accumulation of the tumor suppressor protein p53 and the cyclin-dependent kinase inhibitor p21. Furthermore, ALA-PDT down-regulates expression of HPV E6/E7 oncogene as well as up-regulate tumor suppressor RbAp48 protein. Together, our data provides a basis for understanding and developing ALA-PDT as a cure for HPV infection-associated diseases and prevention of cervical cancer.

  13. Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity

    Science.gov (United States)

    Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

    2014-01-01

    In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed “biomimetic”. Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells. PMID:24648728

  14. Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity.

    Science.gov (United States)

    Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

    2014-01-01

    In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed "biomimetic". Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells.

  15. Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

    Science.gov (United States)

    Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

    2009-06-01

    Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

  16. Antimicrobial efficacy of the EndoVac system plus PDT against intracanal Candida albicans: an ex vivo study.

    Science.gov (United States)

    de Miranda, Rachel Garcia; Gusman, Heloisa Dell Santo; Colombo, Ana Paula Vieira

    2015-01-01

    This study evaluated the ex vivoantimicrobial efficacy of the EndoVac system and the photodynamic therapy (PDT) associated with chemomechanical debridement (CMD) and intracanal medication on Candida albicans. Seventy-eight sterile premolars were contaminated withC. albicans (ATCC 21433) for 30 days. The teeth were randomly assigned into four groups: Control (CMD with conventional irrigation); Endovac (CMD with EndoVac system); PDT (CMD with conventional irrigation and PDT); and Endovac + PDT (CMD with EndoVac and PDT). After the therapies, intracanal dressing (calcium hydroxide) was applied to all teeth for seven days. Samples were obtained before (T1) and after the therapeutic procedures (T2), and after intracanal medication (T3), plated onto BHI agar and incubated (37°C, 48 h) to determine the colony-forming units (CFU)/mL. The overall mean level ofC. albicans at baseline was relatively high (1.85 x 106 ± 2.7 x 106 CFU mL-1). A significant reduction of C. albicans(p PDT group had the highest counts of this microorganism (p PDT showed a very limited efficacy against this species.

  17. Histopathological and expression profiling studies of early tumor responses to near-infrared PDT treatment in SCID mice

    Science.gov (United States)

    Starkey, Jean R.; Rebane, Aleksander; Drobizhev, Mikhail A.; Meng, Fanqin; Gong, Aijun; Elliott, Aleisha; McInnerney, Kate; Pascucci, Elizabeth; Spangler, Charles W.

    2008-02-01

    A novel class of porphyrin-based near-infrared photodynamic therapy (PDT) sensitizers is studied. We achieve regressions of human small cell lung cancer (NCI-H69), non-small cell lung cancer (A 459) and breast cancer (MDAMB- 231) xenografts in SCID mice at significant tissue depth by irradiation with an amplified femtosecond pulsed laser at 800 nm wavelength. Significant tumor regressions were observed during the first 10-14 days post treatment. Tumor histopathology was consistent with known PDT effects, while no significant changes were noted in irradiated normal tissues. In vivo imaging studies using intravenous injections of fluorescent dextran demonstrated an early loss of tumor blood flow. RNA was isolated from NCI-H69 PDT treated SCID mouse xenografts and paired untreated xenografts at 4 hours post laser irradiation. Similarly RNA was isolated from PDT treated and untreated Lewis lung carcinomas growing in C57/Bl6 mice. Expression profiling was carried out using Affymetrix TM human and mouse GeneChips®. Cluster analysis of microarray expression profiling results demonstrated reproducible increases in transcripts associated with apoptosis, stress, oxygen transport and gene regulation in the PDT treated NCI-H69 samples. In addition, PDT treated Lewis lung carcinomas showed reproducible increases in transcripts associated with immune response and lipid biosynthesis. PDT treated C57/Bl6 mice developed cytotoxic T cell activity towards this tumor, while untreated tumor bearing mice failed to do so.

  18. The development of adaptive memory: Young children show enhanced retention of animacy-related information.

    Science.gov (United States)

    Aslan, Alp; John, Thomas

    2016-12-01

    Previous developmental work has indicated that animacy is a foundational ontogenetic category that is given priority already early in life. Here, we investigated whether such priority is also present in children's episodic memory, examining whether young children show enhanced retention of animacy-related information. Kindergartners and younger and older elementary school children were presented with fictitious (non)words (e.g., BULA, LAFE) paired with properties characteristic of humans (e.g., "likes music"), (nonhuman) animals (e.g., "builds nests"), and inanimate things (e.g., "has four edges") and were asked to rate the animacy status of each nonword. After a retention interval, a surprise recognition test for the nonwords was administered. We found enhanced recognition of nonwords paired with human and animal properties compared with (the same) nonwords paired with inanimate properties. The size of this animacy advantage was comparable across age groups, suggesting developmental invariance of the advantage over the age range examined (i.e., 4-11years). The results support a functional-evolutionary view on memory, suggesting that already young children's memory is "tuned" to process and retain animacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    Science.gov (United States)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  20. Comparison of pulsed dye laser (PDL) and photodynamic therapy (PDT) for treatment of facial port-wine stain (PWS) birthmarks in pediatric patients.

    Science.gov (United States)

    Zhang, Bin; Zhang, Tao-Hua; Huang, Zheng; Li, Qin; Yuan, Kai-Hua; Hu, Zhi-Qi

    2014-12-01

    Vascular-acting photodynamic therapy (PDT) might be an alternative approach for treating port wine stain (PWS) birthmarks, but the usefulness of PDT for pediatric patients has not been fully investigated. Medical records of pediatric patients (3-10 years old) with red and purple facial PWS were analyzed. Clinical outcomes after one session of PDL (585 nm, 4.8-6.5 J/cm(2)) and PDT (Hemoporfin - 3.5mg/kg, copper vapour laser - 120 J/cm(2)) were compared. The rate of excellent response in PDT group was significantly higher than that in PDL group (25.0% vs 10.9%). For red lesions there was no significant difference in overall response between PDL and PDT group, but for purple lesions the overall response rate of PDT group was significantly higher than that of PDL group (93.0% vs 75.6%). Lesions located at the forehead, cheek and jaw regions showed better responses to PDT. Incidences of pigmentation and scar formation in PDT group were significantly lower than PDL group (8.3% vs 21.1%). This study suggests that PDT is safe and effective for treating facial PWS of childhood patients. Copyright © 2014. Published by Elsevier B.V.

  1. The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

    Science.gov (United States)

    Carrera, E. T.; Dias, H. B.; Corbi, S. C. T.; Marcantonio, R. A. C.; Bernardi, A. C. A.; Bagnato, V. S.; Hamblin, M. R.; Rastelli, A. N. S.

    2016-12-01

    In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.

  2. The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

    Science.gov (United States)

    Carrera, E T; Dias, H B; Corbi, S C T; Marcantonio, R A C; Bernardi, A C A; Bagnato, V S; Hamblin, M R; Rastelli, A N S

    2017-01-01

    In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications. PMID:29151775

  3. Correlations between photoactivable porphyrins' fluorescence, erythema and the pain induced by PDT on normal skin using ALA-derivatives.

    Science.gov (United States)

    Barge, Jérôme; Glanzmann, Thomas; Zellweger, Matthieu; Salomon, Denis; van den Bergh, Hubert; Wagnières, Georges

    2013-12-01

    Photodynamic therapy (PDT) with precursors of photoactivable porphyrins is a well-established treatment modality for skin pathologies as well as hair removal. Pain is a major side effect thereof, and it affects the treatment compliance and acceptance. Five male subjects underwent a PDT procedure on normal skin, either with a diode laser (635 nm) or a lamp (405 nm), 3 or 6h after application of various precursors of photoactivable porphyrins (ALA 1M; Metvix(®) 1M; ALA-DGME 1M; ALA-DGME 3.66 M). Light doses ranged from 30 to 150 J/cm(2) and irradiances were 100 or 180 mW/cm(2). Fluorescence measurements were performed just before PDT, pain was quantified during PDT, and erythema was determined 24h afterwards. Because precursor ALA-DGME was very selective for the pilosebaceous apparatus vs. the epidermis, we solely carried out the PDTs using this precursor. In the absence of light, no pain was reported. An increase in pain was observed when increasing the irradiance. A correlation was observed between the follicular fluorescence and the maximal pain score during PDT. A correlation was observed between follicular fluorescence and skin erythema, and between pain score and skin erythema. With our well-controlled PDT parameters and homogenous subjects' conditions, we showed that pain could be reduced by reducing irradiance during PDT procedures. With the various correlations observed, we conclude that both pain and PaP fluorescence are useful tools to predict the post-PDT tissue effects (side effects and outcome). We suggest that A∂ nerve fibres would be the best candidate as first generators of PDT-induced pain. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Comparison of PDT parameters for RIF and H460 tumor models during HPPH-mediated PDT.

    Science.gov (United States)

    Liu, Baochang; Kim, Michele M; Gallagher-Colombo, Shannon M; Busch, Theresa M; Zhu, Timothy C

    2014-03-05

    Singlet oxygen ( 1 O 2 ) is the major cytotoxic species producing PDT effects, but it is difficult to monitor in vivo due to its short life time in real biological environments. Mathematical models are then useful to calculate 1 O 2 concentrations for PDT dosimetry. Our previously introduced macroscopic model has four PDT parameters: ξ , σ , β and g describing initial oxygen consumption rate, ratio of photobleaching to reaction between 1 O 2 and cellular targets, ratio of triplet state (T) phosphorescence to reaction between T and oxygen ( 3 O 2 ), and oxygen supply rate to tissue, respectively. In addition, the model calculates a fifth parameter, threshold 1 O 2 dose ([ 1 O 2 ] rx,sd ). These PDT parameters have been investigated for HPPH using radiation-induced fibrosarcoma (RIF) tumors in an in-vivo C3H mouse model. In recent studies, we additionally investigated these parameters in human non-small cell lung carcinoma (H460) tumor xenografts, also using HPPH-mediated PDT. In-vivo studies are performed with nude female mice with H460 tumors grown intradermally on their right shoulders. HPPH (0.25 mg/kg) is injected i.v. at 24 hours prior to light delivery. Initial in vivo HPPH concentration is quantified via interstitial HPPH fluorescence measurements after correction for tissue optical properties. Light is delivered by a linear source at various light doses (12-50 J/cm) with powers ranging from 12 to 150 mW per cm length. The necrosis radius is quantified using ScanScope after tumor sectioning and hematoxylin and eosin (H&E) staining. The macroscopic optimization model is used to fit the results and generate four PDT parameters. Initial results of the parameters for H460 tumors will be reported and compared with those for the RIF tumor.

  5. Montmorillonite enhanced ciprofloxacin transport in saturated porous media with sorbed ciprofloxacin showing antibiotic activity

    Science.gov (United States)

    Chen, Hao; Gao, Bin; Yang, Liu-Yan; Ma, Lena Q.

    2015-02-01

    Antibiotic ciprofloxacin (CIP) is immobile in the subsurface but it has been frequently detected in the aquatic system. Therefore it is important to investigate the factors impacting CIP's mobilization in aquifer. Laboratory columns packed with sand were used to test colloid-facilitated CIP transport by 1) using kaolinite or montmorillonite to mobilize presorbed-CIP in a column or 2) co-transporting with CIP by pre-mixing them before transport. The Langmuir model showed that CIP sorption by montmorillonite (23 g kg- 1) was 100 times more effective than sand or kaolinite. Even with strong CIP complexation ability to Fe/Al coating on sand surface, montmorillonite promoted CIP transport, but not kaolinite. All presorbed-CIP by sand was mobilized by montmorillonite after 3 pore volumes through co-transporting of CIP with montmorillonite. The majority of CIP was fixed onto the montmorillonite interlayer but still showed inhibition of bacteria growth. Our results suggested that montmorillonite with high CIP sorption ability can act as a carrier to enhance CIP's mobility in aquifer.

  6. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  7. Folic acid-polydopamine nanofibers show enhanced ordered-stacking via π-π interactions.

    Science.gov (United States)

    Fan, Hailong; Yu, Xiang; Liu, Yang; Shi, Zujin; Liu, Huihui; Nie, Zongxiu; Wu, Decheng; Jin, Zhaoxia

    2015-06-21

    Recent research has indicated that polydopamine and synthetic eumelanins are optoelectronic biomaterials in which one-dimensional aggregates composed of ordered-stacking oligomers have been proposed as unique organic semiconductors. However, improving the ordered-stacking of oligomers in polydopamine nanostructures is a big challenge. Herein, we first demonstrate how folic acid molecules influence the morphology and nanostructure of polydopamine via tuning the π-π interactions of oligomers. MALDI-TOF mass spectrometry reveals that porphyrin-like tetramers are characteristic of folic acid-polydopamine (FA-PDA) nanofibers. X-ray diffraction combined with simulation studies indicate that these oligomers favour aggregation into graphite-like ordered nanostructures via strong π-π interactions. High-resolution TEM characterization of carbonized FA-PDA hybrids show that in FA-PDA nanofibers the size of the graphite-like domains is over 100 nm. The addition of folic acid in polydopamine enhances the ordered stacking of oligomers in its nanostructure. Our study steps forward to discover the mystery of the structure-property relationship of FA-PDA hybrids. It paves a way to optimize the properties of PDA through the design and selection of oligomer structures.

  8. Self-Assembled Complexes of Horseradish Peroxidase with Magnetic Nanoparticles Showing Enhanced Peroxidase Activity

    KAUST Repository

    Corgié, Stéphane C.

    2012-02-15

    Bio-nanocatalysts (BNCs) consisting of horseradish peroxidase (HRP) self-assembled with magnetic nanoparticles (MNPs) enhance enzymatic activity due to the faster turnover and lower inhibition of the enzyme. The size and magnetization of the MNPs affect the formation of the BNCs, and ultimately control the activity of the bound enzymes. Smaller MNPs form small clusters with a low affinity for the HRP. While the turnover for the bound fraction is drastically increased, there is no difference in the H 2O 2 inhibitory concentration. Larger MNPs with a higher magnetization aggregate in larger clusters and have a higher affinity for the enzyme and a lower substrate inhibition. All of the BNCs are more active than the free enzyme or the MNPs (BNCs > HRP ≤laquo; MNPs). Since the BNCs show surprising resilience in various reaction conditions, they may pave the way towards new hybrid biocatalysts with increased activities and unique catalytic properties for magnetosensitive enzymatic reactions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. A real-time treatment guidance system for Pleural PDT

    Science.gov (United States)

    Zhu, Timothy C.; Liang, Xing; Sandell, Julia; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Cengel, Keith; Friedberg, Joseph; Hahn, Stephen M; Glatstein, Eli

    2015-01-01

    Intrapleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have reported previously the success of using IR camera to passively monitor the light fluence rate distribution. In this study, the real-time feedback has been implemented in the current system prototype, by transferring data from the IR camera to a computer at a rate of 20 Hz, and by calculation/displaying using Matlab. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings. Preliminary data from a phantom showed superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown using the correction method dose model. PMID:26005245

  10. A real-time treatment guidance system for pleural PDT

    Science.gov (United States)

    Zhu, Timothy C.; Liang, Xing; Sandell, Julia; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Cengel, Keith; Friedberg, Joseph; Hahn, Stephen M.; Glatstein, Eli

    2012-02-01

    Intrapleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have reported previously the success of using IR camera to passively monitor the light fluence rate distribution. In this study, the real-time feedback has been implemented in the current system prototype, by transferring data from the IR camera to a computer at a rate of 20 Hz, and by calculation/displaying using Matlab. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings. Preliminary data from a phantom showed superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown using the correction method dose model.

  11. PDT in non-surgical treatment of periodontitis in kidney transplanted patients: a split-mouth, randomized clinical trial

    Science.gov (United States)

    Marinho, Kelly C. T.; Giovani, Elcio M.

    2016-03-01

    This study was to evaluate clinical and microbiological effectiveness of photodynamic therapy (PDT) in the treatment of periodontal disease in kidney-transplanted patients. Eight kidney transplanted patients treated at Paulista University were arranged in two groups: SRP performed scaling and root planning by ultrasound; SRP+PDT- in the same patient, which was held to PDT in the opposite quadrant, with 0.01% methylene blue and red laser gallium aluminum arsenide, wavelength 660 nm, power 100 mW. There was reduction in probing pocket depth after 45 days and 3 months regardless the group examined; plaque and bleeding index showed improvement over time, regardless the technique used, and bleeding index in the SRP+PDT group was lower when compared with the baseline the other times. There was no difference in the frequency of pathogens. Photodynamic therapy may be an option for treatment of periodontal disease in renal-transplanted patients and its effectiveness is similar to conventional therapy.

  12. Photodynamic therapy (PDT) resistance by PARP1 regulation on PDT-induced apoptosis with autophagy in head and neck cancer cells.

    Science.gov (United States)

    Kim, Jisun; Lim, Wonbong; Kim, Sangwoo; Jeon, Sangmi; Hui, Zheng; Ni, Kou; Kim, Changsu; Im, Yeonggwan; Choi, Hongran; Kim, Okjoon

    2014-10-01

    Photodynamic therapy (PDT) is an anticancer treatment that generates excessive reactive oxygen species after photosensitizer treatments following specific wavelength irradiation. In another reports, PDT was regulated with autophagic cell death and apoptotic cell death. However, the mechanism of PDT resistance in PDT-stimulated cell death is unclear. In this study, we determined PDT resistance by autophagy and apoptosis in HP-PDT-treated oral cancer cells. Cells were treated hematoporphyrin and then irradiation with or without inhibitor. Cell lysates were checked protein expression with specific antibody. PDT resistance cells were generated with PDT repeated treatments. In HP-PDT, PDT induced autophagy through mTOR, ATG5, and LC3 in dose-dependent manners. Also, PDT at high dose induced apoptosis through caspase activation and PARP-1. Moreover, PARP-1 inhibitor protected cells against HP-PDT-induced cell death, but not by caspase inhibitor. At low dose of HP, autophagy inhibitor partially protected from HP-PDT-induced cell death. In autophagy phases, at low doses, HP-PDT regulated autophagic cell death through the inhibition of LC3II. Although autophagy inhibitor did not alter cell death directly, autophagy has associated with HP-PDT-induced apoptotic cell death by PARP-1 regulation. Taken together, HP-PDT induces apoptotic cell death with autophagy in oral cancer cells. PDT resistance is related to autophagy by PARP-1 regulation in oral cancer cells. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress.

    Science.gov (United States)

    Dickhaus, Britta; Mayer, Emeran A; Firooz, Nazanin; Stains, Jean; Conde, Francisco; Olivas, Teresa I; Fass, Ronnie; Chang, Lin; Mayer, Minou; Naliboff, Bruce D

    2003-01-01

    Symptoms in irritable bowel syndrome (IBS) patients are sensitive to psychological stressors. These effects may operate through an enhanced responsiveness of the emotional motor system, a network of brain circuits that modulate arousal, viscerosomatic perception, and autonomic responses associated with emotional responses, including anxiety and anger. The aim of this study was to test the primary hypothesis that IBS patients show altered perceptual responses to rectal balloon distention during experimentally induced psychological stress compared with healthy control subjects. A total of 15 IBS patients (nine women and six men) and 14 healthy controls (seven women and seven men) were studied during two laboratory sessions: 1) a mild stress condition (dichotomous listening to two conflicting types of music), and 2) a control condition (relaxing nature sounds). The stress and relaxation auditory stimuli were delivered over a 10-min listening period preceding rectal distentions and during the rectal distentions but not during the distention rating process. Ratings of intensity and unpleasantness of the visceral sensations, subjective emotional responses, heart rate, and neuroendocrine measures (norepinephrine, cortisol, adrenocorticotropic hormone [ACTH], and prolactin) were obtained during the study. IBS patients, but not healthy controls, rated the 45-mm Hg visceral stimulus significantly higher in terms of intensity and unpleasantness during the stress condition compared with the relaxation condition. IBS patients also reported higher ratings of stress, anger, and anxiety during the stress compared with the relaxing condition, whereas controls had smaller and nonsignificant subjective responses. Heart rate measurements, but not other neuroendocrine stress measures, were increased under the stress condition in both groups. These findings confirm the hypothesis of altered stress-induced modulation of visceral perception in IBS patients.

  14. The relevance of light diffusion profiles for interstitial PDT using light-diffusing optical fibers

    Science.gov (United States)

    Stringasci, Mirian D.; Fortunato, Thereza C.; Moriyama, Lilian T.; Vollet Filho, José Dirceu; Bagnato, Vanderlei S.; Kurachi, Cristina

    2017-02-01

    Photodynamic therapy (PDT) is a technique used for several tumor types treatment. Light penetration on biological tissue is one limiting factor for PDT applied to large tumors. An alternative is using interstitial PDT, in which optical fibers are inserted into tumors. Cylindrical diffusers have been used in interstitial PDT. Light emission of different diffusers depends on the manufacturing process, size and optical properties of fibers, which make difficult to establish an adequate light dosimetry, since usually light profile is not designed for direct tissue-fiber contact. This study discusses the relevance of light distribution by a cylindrical diffuser into a turbid lipid emulsion solution, and how parts of a single diffuser contribute to illumination. A 2 cm-long cylindrical diffuser optical fiber was connected to a diode laser (630 nm), and the light spatial distribution was measured by scanning the solution with a collection probe. From the light field profile generated by a 1 mm-long intermediary element of a 20 mm-long cylindrical diffuser, recovery of light distribution for the entire diffuser was obtained. PDT was performed in rat healthy liver for a real treatment outcome analysis. By using computational tools, a typical necrosis profile generated by the irradiation with such a diffuser fiber was reconstructed. The results showed that it was possible predicting theoretically the shape of a necrosis profile in a healthy, homogeneous tissue with reasonable accuracy. The ability to predict the necrosis profile obtained from an interstitial illumination by optical diffusers has the potential improve light dosimetry for interstitial PDT.

  15. 3D lung spheroid cultures for evaluation of photodynamic therapy (PDT) procedures in microfluidic Lab-on-a-Chip system.

    Science.gov (United States)

    Zuchowska, Agnieszka; Jastrzebska, Elzbieta; Chudy, Michal; Dybko, Artur; Brzozka, Zbigniew

    2017-10-16

    The purpose of this paper is to present a fully integrated microchip for the evaluation of PDT procedures efficiency on 3D lung spheroid cultures. Human lung carcinoma A549 and non-malignant MRC-5 spheroids were utilized as culture models. Spheroid viability was evaluated 24 h after PDT treatment, in which 5-aminolevulinic acid (ALA) had been used as a precursor of a photosensitizer (protoporphyrin IX - PpIX). Moreover, spheroid viability over a long-term (10-day) culture was also examined. We showed that the proposed PDT treatment was toxic only for cancer spheroids. This could be because of a much-favoured enzymatic conversion of ALA to PpIX in cancer as opposed normal cells. Moreover, we showed that to obtain high effectiveness of ALA-PDT on lung cancer spheroids additional time of spheroid after light exposure was required. It was found that PDT had been effective 5 days after PDT treatment with 3 mM ALA. To the best of our knowledge this has been the first presentation of such research performed on a 3D lung spheroids culture in a microfluidic system. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Topical application of ALA PDT for the treatment of moderate to severe acne vulgaris

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Zhang, Ling-Lin; Su, Lina; Guo, Ming-Xia; Huang, Zheng

    2009-06-01

    Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)- medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and after treatment up to 3 months. Results: All patents showed response to ALA PDT. Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients (37.5%). One case showed recurrence after complete clearance at 2 months and another two showed recurrence after complete clearance at 3 months. However, the number of new lesions were significantly reduced. Adverse effects were minimal. Conclusions: The results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and useful therapeutic option for the treatment of moderate to severe acne. Further studies to evaluate the treatment with a larger number of patients and for a longer period of follow-up are needed.

  17. A new optical intra-tissue fiber irradiation ALA-PDT in the treatment of acne vulgaris in rabbit model: improved safety and tolerability.

    Science.gov (United States)

    Wang, Qian; Jiang, Can; Liu, Wei; Chen, Jin; Lin, Xinyu; Huang, Xiangning; Duan, Xiling

    2017-01-01

    Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (PPDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (PPDT group was obviously lower than that of the ALA-PDT group (PPDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

  18. Adaptive Memory: Young Children Show Enhanced Retention of Fitness-Related Information

    Science.gov (United States)

    Aslan, Alp; Bauml, Karl-Heinz T.

    2012-01-01

    Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on…

  19. Photodynamic therapy combined with terbinafine against chromoblastomycosis and the effect of PDT on Fonsecaea monophora in vitro.

    Science.gov (United States)

    Hu, Yongxuan; Huang, Xiaowen; Lu, Sha; Hamblin, Michael R; Mylonakis, Eleftherios; Zhang, Junmin; Xi, Liyan

    2015-02-01

    Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue caused by dematiaceous fungi, is associated with low cure and high relapse rates. Among all factors affecting clinical outcome, etiological agents have an important position. In southern China, Fonsecaea pedrosoi and Fonsecaea monophora are main causative agents causing Chromoblastomycosis. We treated one case of chromoblastomycosis by photodynamic therapy (PDT) of 5-aminolevulinic acid (ALA) irradiation combined with terbinafine 250 mg a day. The lesions were improved after two sessions of ALA-PDT treatment, each including nine times, at an interval of 1 week, combined with terbinafine 250 mg/day oral, and clinical improvement could be observed. In the following study, based on the clinical treatment, the effect of PDT and antifungal drugs on this isolate was detected in vitro. It showed sensitivity to terbinafine, itraconazole or voriconazole, and PDT inhibited the growth. Both the clinic and experiments in vitro confirm the good outcome of ALA-PDT applied in the inhibition of F. monophora. It demonstrated that combination of antifungal drugs with ALA-PDT arises as a promising alternative method for the treatment of these refractory cases of chromoblastomycosis.

  20. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  1. Subterranean mammals show convergent regression in ocular genes and enhancers, along with adaptation to tunneling

    Science.gov (United States)

    Partha, Raghavendran; Chauhan, Bharesh K; Ferreira, Zelia; Robinson, Joseph D; Lathrop, Kira; Nischal, Ken K

    2017-01-01

    The underground environment imposes unique demands on life that have led subterranean species to evolve specialized traits, many of which evolved convergently. We studied convergence in evolutionary rate in subterranean mammals in order to associate phenotypic evolution with specific genetic regions. We identified a strong excess of vision- and skin-related genes that changed at accelerated rates in the subterranean environment due to relaxed constraint and adaptive evolution. We also demonstrate that ocular-specific transcriptional enhancers were convergently accelerated, whereas enhancers active outside the eye were not. Furthermore, several uncharacterized genes and regulatory sequences demonstrated convergence and thus constitute novel candidate sequences for congenital ocular disorders. The strong evidence of convergence in these species indicates that evolution in this environment is recurrent and predictable and can be used to gain insights into phenotype–genotype relationships. PMID:29035697

  2. BODIPY-doped silica nanoparticles with reduced dye leakage and enhanced singlet oxygen generation.

    Science.gov (United States)

    Wang, Zhuyuan; Hong, Xuehua; Zong, Shenfei; Tang, Changquan; Cui, Yiping; Zheng, Qingdong

    2015-07-27

    Photodynamic therapy (PDT) is a promising modality for cancer treatment. The essential element in PDT is the photosensitizer, which can be excited by light of a specific wavelength to generate cytotoxic oxygen species (ROS) capable of killing tumor cells. The effectiveness of PDT is limited in part by the low yield of ROS from existing photosensitizers and the unwanted side effects induced by the photosensitizers toward normal cells. Thus the design of nanoplatforms with enhanced PDT is highly desirable but remains challenging. Here, we developed a heavy atom (I) containing dipyrromethene boron difluoride (BODIPY) dye with a silylated functional group, which can be covalently incorporated into a silica matrix to form dye-doped nanoparticles. The incorporated heavy atoms can enhance the generation efficiency of ROS. Meanwhile, the covalently dye-encapsulated nanoparticles can significantly reduce dye leakage and subsequently reduce unwanted side effects. The nanoparticles were successfully taken up by various tumor cells and showed salient phototoxicity against these cells upon light irradiation, demonstrating promising applications in PDT. Moreover, the incorporated iodine atom can be replaced by a radiolabeled iodine atom (e.g., I-124, I-125). The resulting nanoparticles will be good contrast agents for positron emission tomography (PET) imaging with their PDT functionality retained.

  3. Nanotextured polymer substrates show enhanced cancer cell isolation and cell culture

    Science.gov (United States)

    Islam, Muhymin; Sajid, Adeel; Arif Iftakher Mahmood, M.; Motasim Bellah, Mohammad; Allen, Peter B.; Kim, Young-Tae; Iqbal, Samir M.

    2015-06-01

    Detection of circulating tumor cells (CTCs) in the early stages of cancer is a great challenge because of their exceedingly small concentration. There are only a few approaches sensitive enough to differentiate tumor cells from the plethora of other cells in a sample like blood. In order to detect CTCs, several antibodies and aptamers have already shown high affinity. Nanotexture can be used to mimic basement membrane to further enhance this affinity. This article reports an approach to fabricate nanotextured polydimethylsiloxane (PDMS) substrates using micro reactive ion etching (micro-RIE). Three recipes were used to prepare nanotextured PDMS using oxygen and carbon tetrafluoride. Micro-RIE provided better control on surface properties. Nanotexturing improved the affinity of PDMS surfaces to capture cancer cells using surface immobilized aptamers against cell membrane overexpressed with epidermal growth factor receptors. In all cases, nanotexture of PDMS increased the effective surface area by creating nanoscale roughness on the surface. Nanotexture also enhanced the growth rate of cultured cells compared to plain surfaces. A comparison among the three nanotextured surfaces demonstrated an almost linear relationship between the surface roughness and density of captured tumor cells. The nanotextured PDMS mimicked biophysical environments for cells to grow faster. This can have many implications in microfluidic platforms used for cell handling.

  4. Microneedling Prior to Levulan PDT for the Treatment of Actinic Keratoses: A Split-Face, Blinded Trial.

    Science.gov (United States)

    Spencer, James M; Freeman, Scott A

    2016-09-01

    Photodynamic Therapy (PDT) with topical Levulan is an approved and efficacious method for treating actinic keratoses. This therapy depends on the ability of the Levulan (delta amino levulinic acid) to penetrate the stratum corneum and enter the cells of the epidermis. Microneedling is an increasing popular cosmetic therapy in which an array of tiny needles is used to make holes in the epidermis and presumably induce a wound healing cascade that leads to cosmetic improvement of the skin. We were interested to know if prior microneedling would enhance the penetration of topical Levulan and thus enhance the PDT treatment, and if a cosmetic improvement beyond the PDT alone would be seen when it is used in conjunction with microneedling. 20 patients each with at least 4 non hyperkeratotic AKs on each side of their face were enrolled. All patients were randomized to receive multiple passes with a microneedling device to ½ of their face, left or right, followed by application of Levulan to the entire face. The Levulan was allowed to incubate 1 hour followed by exposure to blue light (Blu U) for 1000 seconds. 19 patients completed the study with 4-month follow up. The mean percentage reduction in AKs was 89.3% on the microneedling side versus 69.5% on the PDT alone side, a significant difference. A physician's global cosmetic assessment was performed based on Canfield Visia photographs: 15 of the 19 patients had a noticeable improved cosmetic appearance on one side of the face versus the other, and in 13 of these patients the improved side was the microneedled side. Prior microneedling significantly enhances the effect of Levulan PDT. It also seems to provide a cosmetic benefit above and beyond the PDT alone. It was safe and well tolerated in this study. J Drugs Dermatol. 2016;15(9):1072-1074.

  5. 5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

    Science.gov (United States)

    Nemes, Andrei; Fortmann, Thomas; Poeschke, Stephan; Greve, Burkhard; Prevedello, Daniel; Santacroce, Antonio; Stummer, Walter; Senner, Volker; Ewelt, Christian

    2016-01-01

    Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations.

  6. Larval antlions with more pronounced behavioural asymmetry show enhanced cognitive skills.

    Science.gov (United States)

    Miler, Krzysztof; Kuszewska, Karolina; Woyciechowski, Michał

    2017-02-01

    Brain lateralization is hypothesized to improve the efficiency of information processing. Here, we found that some Myrmeleon bore antlion larvae showed individual asymmetry in righting from a supine to normal position over one side of their body, which can be considered a reflection of greater brain lateralization. We demonstrated that these behaviourally asymmetrical individuals showed improved learning abilities, providing novel evidence that brain lateralization leads to beneficial effects on cognitive functions. © 2017 The Author(s).

  7. Design of porous silica supported tantalum oxide hollow spheres showing enhanced photocatalytic activity.

    Science.gov (United States)

    Sharma, Manu; Das, Debashree; Baruah, Arabinda; Jain, Archana; Ganguli, Ashok K

    2014-03-25

    Silica-supported tantalum oxide (ST) hollow spheres were designed for photocatalytic applications in the UV range of 4.1 to 4.8 eV. These nanostructures with a variable diameter of 100-250 nm and shell thickness of 24-58 nm were obtained by the hydrothermal treatment of tantalum isopropoxide and tetraethylorthosilicate at 120 °C for 48 h in the presence of cetyl trimethyl ammonium bromide, which was used as a capping agent. The maximum observed surface area was found to be 610 m(2)/g and pore size distribution of ST hollow spheres varied from 13.4 to 19.0 nm. Lewis acidity of silica and the contact area between SiO2 and Ta2O5 plays a crucial role in controlling the photocatalytic properties of the ST hollow spheres. We observe a remarkable 6× enhancement in the photoactivity of silica-supported tantalum oxide hollow spheres compared to pure Ta2O5.

  8. A novel solubility-enhanced curcumin formulation showing stability and maintenance of anticancer activity.

    Science.gov (United States)

    Zhang, Fang; Koh, Gar Yee; Jeansonne, Duane P; Hollingsworth, Javoris; Russo, Paul S; Vicente, Graca; Stout, Rhett W; Liu, Zhijun

    2011-07-01

    Curcumin (CUR) is an active food compound, but its insolubility and instability in water contributes to low bioavailability. In this study, the solubility of CUR was enhanced by utilizing the solubilizing properties of rubusoside (RUB). The solubility of CUR in water increased linearly from 61 μg/mL to 2.318 mg/mL in the presence of RUB ranging from 1% to 10% (w/v). Dynamic light scattering and transmission electron microscopy studies found that CUR and RUB formed CUR-RUB nanoparticle (∼8 nm) complexes. The RUB-solubilized CUR was stable in physiological conditions and did not precipitate when diluted or degrade when spray-dried to a completely reconstitutable powder. Furthermore, cell viability assays demonstrated the efficacy of RUB-solubilized CUR against human colon, breast, and pancreatic cancer cell lines. The development of this new solubilized, stable, and biologically active CUR formulation lays the foundation for future bioavailability improvement. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  9. Optimization of targeted two-photon PDT triads for the treatment of head and neck cancers

    Science.gov (United States)

    Spangler, Charles W.; Starkey, Jean R.; Dubinina, Galyna; Fahlstrom, Carl; Shepard, Joyce

    2012-02-01

    Synthesis of new PDT triads that incorporate a tumor-killing porphyrin with large two-photon cross-section for 150 fs laser pulses (2000 GM) in the Near-infrared (NIR) at 840 nm, a NIR imaging agent, and a small peptide that targets over-expressed EGF receptors on the tumor surface. This triad formulation has been optimized over the past year to treat FADU Head and Neck SCC xenograft tumors in SCID mice. Effective PDT triad dose (1-10 mg/Kg) and laser operating parameters (840 nm, 15-45 min, 900 mW) have been established. Light, dark and PDT treatment toxicities were determined, showing no adverse effects. Previous experiments in phantom and mouse models indicate that tumors can be treated directly through the skin to effective depths between 2 and 5 cm. Treated mice demonstrated rapid tumor regression with some complete cures in as little as 15-20 days. No adverse effects were observed in any healthy tissue through which the focused laser beam passed before reaching the tumor site, and excellent healing occurred post treatment including rapid hair re-growth. Not all irradiation protocols lead to complete cures. Since two-photon PDT is carried out by rastering focused irradiation throughout the tumor, there is the possibility that as the treatment depth increases, some parts of the tumor may escape irradiation due to increased scattering, thus raising the possibility that tumor re-growth could be triggered by small islands of untreated cells, especially at the rapidly growing tumor margins, a problem we hope to alleviate by using image-guided two-photon PDT.

  10. Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement

    Directory of Open Access Journals (Sweden)

    Shamsa Akbar

    Full Text Available ABSTRACT Background: Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Results: Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100 mg L-1 within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4 and Ochrobactrum sp. (FCp1. These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200 mg kg-1 within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76 mg-1 kg-1 d-1 with rate constants varying between 0.047 and 0.069 d-1. These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200 mg L-1 was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5

  11. Fluoride-tolerant mutants of Aspergillus niger show enhanced phosphate solubilization capacity.

    Directory of Open Access Journals (Sweden)

    Ubiana de Cássia Silva

    Full Text Available P-solubilizing microorganisms are a promising alternative for a sustainable use of P against a backdrop of depletion of high-grade rock phosphates (RPs. Nevertheless, toxic elements present in RPs, such as fluorine, can negatively affect microbial solubilization. Thus, this study aimed at selecting Aspergillus niger mutants efficient at P solubilization in the presence of fluoride (F-. The mutants were obtained by exposition of conidia to UV light followed by screening in a medium supplemented with Ca3(PO42 and F-. The mutant FS1-555 showed the highest solubilization in the presence of F-, releasing approximately 70% of the P contained in Ca3(PO42, a value 1.7 times higher than that obtained for the wild type (WT. The mutant FS1-331 showed improved ability of solubilizing fluorapatites, increasing the solubilization of Araxá, Catalão, and Patos RPs by 1.7, 1.6, and 2.5 times that of the WT, respectively. These mutants also grew better in the presence of F-, indicating that mutagenesis allowed the acquisition of F- tolerance. Higher production of oxalic acid by FS1-331 correlated with its improved capacity for RP solubilization. This mutant represents a significant improvement and possess a high potential for application in solubilization systems with fluoride-rich phosphate sources.

  12. Tolvaptan plus Pasireotide Shows Enhanced Efficacy in a PKD1 Model

    Science.gov (United States)

    Hopp, Katharina; Hommerding, Cynthia J.; Wang, Xiaofang; Ye, Hong; Harris, Peter C.

    2015-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of ESRD. A central defect associated with ADPKD pathology is elevated levels of 3′, 5′-cyclic AMP (cAMP). Compounds such as tolvaptan and pasireotide, which indirectly reduce adenylyl cyclase 6 (AC6) activity, have hence proven effective in slowing cyst progression. Here, we tested the efficacy of these compounds individually and in combination in a hypomorphic PKD1 model, Pkd1R3277C/R3277C (Pkd1RC/RC), in a 5-month preclinical trial. Initially, the Pkd1RC/RC model was inbred into the C57BL/6 background, minimizing disease variability, and the pathogenic effect of elevating cAMP was confirmed by treatment with the AC6 stimulant desmopressin. Treatment with tolvaptan or pasireotide alone markedly reduced cyst progression and in combination showed a clear additive effect. Furthermore, combination treatment significantly reduced cystic and fibrotic volume and decreased cAMP to wild-type levels. We also showed that Pkd1RC/RC mice experience hepatic hypertrophy that can be corrected by pasireotide. The observed additive effect reinforces the central role of AC6 and cAMP in ADPKD pathogenesis and highlights the likely benefit of combination therapy for patients with ADPKD. PMID:24994926

  13. Antimicrobial efficacy of the EndoVac system plus PDT against intracanal Candida albicans: an ex vivo study

    Directory of Open Access Journals (Sweden)

    Rachel Garcia de MIRANDA

    2015-01-01

    Full Text Available This study evaluated the ex vivoantimicrobial efficacy of the EndoVac system and the photodynamic therapy (PDT associated with chemomechanical debridement (CMD and intracanal medication on Candida albicans. Seventy-eight sterile premolars were contaminated withC. albicans (ATCC 21433 for 30 days. The teeth were randomly assigned into four groups: Control (CMD with conventional irrigation; Endovac (CMD with EndoVac system; PDT (CMD with conventional irrigation and PDT; and Endovac + PDT (CMD with EndoVac and PDT. After the therapies, intracanal dressing (calcium hydroxide was applied to all teeth for seven days. Samples were obtained before (T1 and after the therapeutic procedures (T2, and after intracanal medication (T3, plated onto BHI agar and incubated (37°C, 48 h to determine the colony-forming units (CFU/mL. The overall mean level ofC. albicans at baseline was relatively high (1.85 x 106 ± 2.7 x 106 CFU mL-1. A significant reduction of C. albicans(p < 0.05 was observed over time (T1 to T2 and T1 to T3 in all groups. An additional significant reduction from T2 to T3 was observed only in the Endovac group (p < 0.05. No differences in mean reduction of C. albicans were observed among groups. However, the Endovac group presented the lowest mean counts of C. albicans at T3, whereas the PDT group had the highest counts of this microorganism (p < 0.05. The EndoVac system of irrigation/aspiration associated with CMD was the most effective therapeutic protocol for reducing intracanal levels of C. albicans. PDT showed a very limited efficacy against this species.

  14. Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory

    Science.gov (United States)

    Koo, Ja Wook; Duman, Ronald S.

    2013-01-01

    IL-1β is a proinflammatory cytokine that contributes to psychological stress responses and has been implicated in various psychiatric disorders most notably depression. Preclinical studies also demonstrate that IL-1β modulates anxiety- and fear-related behaviors, although these findings are difficult to assess because IL-1β infusions influence locomotor activity and nociception. Here we demonstrate that IL-1RI null mice exhibit a behavioral phenotype consistent with a decrease in anxiety-related behaviors. This includes significant effects in the elevated plus maze, light–dark, and novelty-induced hypophagia tests compared to wild-type mice, with no differences in locomotor activity. With regard to fear conditioning, IL-1RI null mice showed more freezing in auditory and contextual fear conditioning tests, and there was no effect on pain sensitivity. Taken together, the results indicate that the IL-1β/IL-1RI signaling pathway induces anxiety-related behaviors and impairs fear memory. PMID:19429130

  15. Monitoring PDT by means of superficial reflectance spectroscopy

    NARCIS (Netherlands)

    Amelink, A.; van der Ploeg van den Heuvel, A.; de Wolf, W. J.; Robinson, D. J.; Sterenborg, H. J. C. M.

    2005-01-01

    Monitoring of relevant parameters during photodynamic therapy (PDT) and correlating these with treatment response is necessary to guarantee optimal and reproducible treatment outcome. In this paper we study the correlation between changes in the local tissue optical properties (absorption and

  16. Photodynamic Therapy (PDT)-New Approaches and Newer ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 8. Photodynamic Therapy (PDT) - New Approaches and Newer Applications. Bhaskar G Maiya G Hariprasad L Giribabu. Series Article Volume 5 Issue 8 August 2000 pp 13-21 ...

  17. Percutaneous dilatational tracheostomy (PDT) in trauma patients: a safe procedure.

    Science.gov (United States)

    Decker, S; Gottlieb, J; Cruz, D L; Müller, C W; Wilhelmi, M; Krettek, C; Wilhelmi, M

    2016-10-01

    Percutaneous dilatational tracheostomy (PDT) is a standard procedure routinely performed on intensive care units. While complication rates and long-term outcomes have been studied in different patient populations, there are few studies known to these authors involving PDT in trauma patients and the complications which may result. Between March 2007 and August 2013, all instances and peri-procedural complications during PDT occurring on the trauma intensive care unit, a unit specialized in the care of injured patients and especially polytrauma patients, were documented. PDTs were performed by a surgeon with the assistance and supervision of another, using bronchoscopic guidance performed by the respiratory medicine department. 289 patients were included in the study, 225 men and 64 women with a mean age of 49 ± 21 years. Complications occurred in 37.4 % of cases. The most common complication, bleeding, occurred in 26.3 % of patients ranging from little to severe bleeding. Fracture of tracheal cartilage occurred in 6 % of PDT cases. Additional complications such as dislocation of the guidewire, hypotension, and oxygen desaturation were observed. Most complications did not require treatment. The second tracheal intercartilaginous space was successfully intubated in 82 % of cases. PDT is a safe procedure in trauma patients. When considering the severity of complications such as major blood loss, pneumothorax, or death, this evidence suggests that PDT is safer in trauma patients compared to other patient cohorts.

  18. Full macular translocation (FMT) versus photodynamic therapy (PDT) with verteporfin in the treatment of neovascular age-related macular degeneration: 2-year results of a prospective, controlled, randomised pilot trial (FMT-PDT).

    Science.gov (United States)

    Lüke, Matthias; Ziemssen, Focke; Völker, Michael; Altpeter, Elke; Beutel, Julia; Besch, Dorothea; Bartz-Schmidt, Karl Ulrich; Gelisken, Faik

    2009-06-01

    To report the outcome of best-corrected visual acuity (BCVA), near visual acuity (NVA), contrast sensitivity (CS) and vision-related quality of life (VRQOL) in patients 2 years after undergoing photodynamic therapy (PDT) or full macular translocation (FMT) for the treatment of neovascular age-related macular degeneration (AMD). Fifty patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. BCVA was determined according a standardized protocol with ETDRS charts. NVA were calculated after testing with SNAB (Swiss National Association of and for the Blind) visual acuity cards. CS was measured with Pelli-Robson charts. The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25 plus supplement) was performed. Primary end points were the changes of BCVA, NVA, CS and VRQOL at 24-month examination. A stabilisation of BCVA (+0.3 letters) was found in the FMT group, whereas a decrease of more than 12 letters (-12.6 letters) was found in the PDT group (p = 0.052). Mean NVA improved by 7.0 letters in the FMT group and was superior to the PDT group (-9.6 letters, p = 0.036), while mean CS showed a time-dependent decrease in both treatment groups (FMT: -3.3 letters, PDT: -3.8 letters, p = 0.726). Considering the results of the VRQOL scores, the improvement of the subscales scores for general vision (p = 0.015), mental health (p = 0.028) and near activity (p = 0.020) were significantly higher in the FMT group. FMT can stabilise BCVA and improve NVA over a period of 2 years in patients with subfoveal classic CNV secondary to neovascular AMD, whereas a decrease of BCVA and NVA was found in the PDT group. CS did not differ between FMT and PDT. A significant increase of VRQOL scores was only found in the FMT group and not in the PDT group. FMT seems to be a therapeutic approach that can increase visual function resulting in an improvement of patient's VRQOL, but exhibits a higher number of

  19. On involvement of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells, activator protein-1 and signal transducer and activator of transcription-3 in photodynamic therapy-induced death of crayfish neurons and satellite glial cells

    Science.gov (United States)

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

    2015-07-01

    Photodynamic therapy (PDT) is currently used in the treatment of brain tumors. However, not only malignant cells but also neighboring normal neurons and glial cells are damaged during PDT. In order to study the potential role of transcription factors-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein (AP-1), and signal transducer and activator of transcription-3 (STAT-3)-in photodynamic injury of normal neurons and glia, we photosensitized the isolated crayfish mechanoreceptor consisting of a single sensory neuron enveloped by glial cells. Application of different inhibitors and activators showed that transcription factors NF-κB (inhibitors caffeic acid phenethyl ester and parthenolide, activator betulinic acid), AP-1 (inhibitor SR11302), and STAT-3 (inhibitors stattic and cucurbitacine) influenced PDT-induced death and survival of neurons and glial cells in different ways. These experiments indicated involvement of NF-κB in PDT-induced necrosis of neurons and apoptosis of glial cells. However, in glial cells, it played the antinecrotic role. AP-1 was not involved in PDT-induced necrosis of neurons and glia, but mediated glial apoptosis. STAT-3 was involved in PDT-induced apoptosis of glial cells and necrosis of neurons and glia. Therefore, signaling pathways that regulate cell death and survival in neurons and glial cells are different. Using various inhibitors or activators of transcription factors, one can differently influence the sensitivity and resistance of neurons and glial cells to PDT.

  20. Monitoring and assessment of tumor hemodynamics during pleural PDT

    Science.gov (United States)

    Ong, Yi Hong; Kim, Michele M.; Penjweini, Rozhin; Rodriguez, Carmen E.; Dimofte, Andrea; Finlay, Jarod C.; Busch, Theresa M.; Yodh, Arjun G.; Cengel, Keith A.; Singhal, Sunil; Zhu, Timothy C.

    2017-02-01

    Intrapleural photodynamic therapy (PDT) has been used in combination with lung sparing surgery to treat patients with malignant pleural mesothelioma. The light, photosensitizers and tissue oxygen are the three most important factors required by type II PDT to produce singlet oxygen, 1O2, which is the main photocytotoxic agent that damages the tumor vasculature and stimulates the body's anti-tumor immune response. Although light fluence rate and photosensitizer concentrations are routinely monitored during clinical PDT, there is so far a lack of a Food and Drug Administration (FDA)-approved non-invasive technique that can be employed clinically to monitor tissue oxygen in vivo. In this paper, we demonstrated that blood flow correlates well with tissue oxygen concentration during PDT and can be used in place of [3O2] to calculate reacted singlet oxygen concentration [1O2]rx using the macroscopic singlet oxygen model. Diffuse correlation spectroscopy (DCS) was used to monitor the change in tissue blood flow non-invasively during pleural PDT. A contact probe with three source and detectors separations, 0.4, 0.7 and 1.0-cm, was sutured to the pleural cavity wall of the patients after surgical resection of the pleural mesothelioma tumor to monitor the tissue blood flow during intraoperative PDT treatment. The changes of blood flow during PDT of 2 patients are found to be in good correlation with the treatment light fluence rate recorded by the isotropic detector placed adjacent to the DCS probe. [1O2]rx calculated based on light fluence, mean photosensitizer concentration, and relative blood flow was found to be 32% higher in patient #4 (0.50mM) than that for patient #3 (0.38mM).

  1. ALA-PDT suppressing the cell growth and reducing the lipogenesis in human SZ95 sebocytes by mTOR signaling pathway in vitro.

    Science.gov (United States)

    Tuo, Jiang; Wang, Qianqian; Zouboulis, Christos C; Liu, Ye; Ma, Ying; Ma, Li; Ying, Jiayi; Zhang, Chengfeng; Xiang, Leihong

    2017-06-01

    5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, the therapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate the effects and mechanisms of ALA-PDT on the cell growth and lipogenesis of human SZ95 sebocytes. Human SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6K/p70 S6K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells. ALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cells in suppressing the cell growth and reducing the secretion of lipids. ALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγ signaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Efficacy of 3.6% topical ALA-PDT for the treatment of severe acne vulgaris.

    Science.gov (United States)

    Tao, S-Q; Xia, R-S; Li, F; Cao, L; Fan, H; Fan, Y; Yang, L-J

    2016-01-01

    To evaluate the efficacy and safety of topical 5-aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) for the treatment of severe acne vulgaris. A total of 125 patients with Pillsbury III-IV severe facial acne were treated with 3 courses of ALA-PDT with an interval of 2 weeks. ALA gel (3.6%) was applied topically to acne lesions for 1.5 h. The lesions were irradiated by a LED light of 633 nm with a light intensity of 66 mW/cm² and a light dose of 126 J/cm². Patients were evaluated for efficacy and safety at weeks 2, 4, 6, 8, 12 after the initial treatment. The total effective rates were 1.6%, 24.8%, 68.8%, 89.6% and 88.8% at the 2- 4- 6- 8- and 12-week after the initial treatment respectively. The clinical outcomes were the best at 4 weeks after the final treatment. The best effective rate and cure rate were 89.6% and 44% respectively. 26 patients and 16 patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment respectively, but all of them showed good or excellent improvement after 3-course treatment. Adverse reactions were mild and transient. 3.6% ALA-PDT is a simple, safe and effective therapeutic option for the treatment of severe acne vulgaris.

  3. Mitochondrial pathway and endoplasmic reticulum stress participate in the photosensitizing effectiveness of AE-PDT in MG63 cells.

    Science.gov (United States)

    Li, Kai-Ting; Chen, Qing; Wang, Da-Wu; Duan, Qin-Qin; Tian, Si; He, Juan-Wen; Ou, Yun-Sheng; Bai, Ding-Qun

    2016-11-01

    Photodynamic therapy (PDT) is a promising treatment in cancer therapy, with a photosensitizer activated by visible light. Aloe-emodin (AE) is a promising photosensitive agent. In this study, the photosensitizing effects and possible mechanisms of AE-PDT in MG63 cells were evaluated. The efficiency of AE-PDT was analyzed by MTT assay. The mode of cell death was investigated by Hoechst 33,342 staining and flow cytometer. The intracellular distribution of AE was detected with confocal microscopy. The formation of reactive oxygen species (ROS) was detected by DCFH-DA. The mitochondrial membrane potential (MMP) was measured by Rhodamine 123. The expression of proteins including cytochrome c, caspase-3, -9, and -12, CHOP and GRP78 was detected by western blot. Apoptosis is the primary mode of cell death in our study, which occurs in a manner of depending on AE concentration and irradiation dose. Confocal microscopy showed that AE was primarily localized on the mitochondria and endoplasmic reticulum (ER) of MG63 cells. AE-PDT resulted in rapid increases of intracellular ROS production, which reached a peak at 2 h, followed by declining of mitochondrial membrane potential, releasing of cytochrome c from mitochondria into the cytoplasm, and up-regulation of caspase-3, -9, and -12, CHOP and GRP78. These results suggest that death of MG63 cells induced by AE-PDT is triggered by ROS. Meanwhile, Mitochondria and ER serve as the subcellular targets, which are responsible for AE-PDT-induced death of MG63 cells. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Comparison between mALA- and ALA-PDT in the treatment of basal cell carcinomas

    Science.gov (United States)

    Schleier, Peter; Zenk, Witold; Hyckel, Peter; Berndt, Alexander

    2006-02-01

    Introduction: The external application of aminoleavulinic acid (ALA), which is a substrate of physiologic cell metabolism, represents a possible treatment option in superficial basal cell carcinomas (BCC). The development of new ALA-esters (mALA) with potential for higher penetration depths promises higher therapeutic success. This research aimed to prove the following hypothesis: The cytotoxic effect of the mALA- photodynamic therapy (mALA-PDT), when compared to the ALA-PDT, leads to a higher clinical success rate. Material and Methods: 24 patients with multiple facial tumors, after having received several local surgical excisions with known histology, were treated with either ALA- or mALA-PDT, during the past two years. In total, 89 basal cell carcinoma, 45 actinic keratoses, 6 keratoacanthoma, and 2 squamous cell carcinomas were treated. ALA-PDT: A thermo gel with 40 % mALA or ALA was applied from a cooled syringe. Three to five hours after gel application the skin was cleaned from any gel residues. Irradiation was done with a diode laser and was performed in two sessions, each 10 min long. After intervals of 2, 4 and 12 weeks, the patients were recalled to assess therapeutic efficacy. This was followed by photographic documentation. Results: More than 80% of the tumors treated primarily were resolved successfully. A recurrence rate of approximately 15% was observed. Three per cent of the tumors showed no reaction to therapy. There were no statistically significant differences between the two therapeutic groups. Discussion: The advantage of the use of ALA lies foremost in the fast metabolic use of the body's own photosensitizer PpIX. There are no known side effects of this therapy. Moreover, external application is superior to systemic application with regard to patient management. The method can be combined with other therapies. Although the mALA should have a better penetration in tumor tissue, the therapeutic outcome is similar to the use of ALA.

  5. Combination of MPPa-PDT and HSV1-TK/GCV gene therapy on prostate cancer.

    Science.gov (United States)

    Liang, Liming; Bi, Wenxiang; Chen, Weiwen; Lin, Yani; Tian, Yuanyuan

    2018-02-01

    We combined pyropheophorbide-a methyl ester, photodynamic therapy (MPPa-PDT), 670 ± 10 nm, 4 mW/cm 2 , with herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV1-TK/GCV) to improve the therapeutic effect. We built HSV1-TK expression vector GV230-TK and we observed a bright green fluorescence under fluorescence microscope. It indicated the recombinant plasmid was transfected into PC-3M prostate cancer cells successfully. As the abundant glucose-regulated protein 78 (GRP78) promoter in PC-3M cells can cause active expression of HSV1-TK, cell protein was collected for western blot to determine the expression of HSV1-TK. In CCK-8 assay (n = 6), the cell survival rate of combined treatment group was about 10%, less than that of pure MPPa-PDT group (23%) and pure HSV1-TK/GCV group (35%) (t test, P PDT group (about 22%) and pure HSV1-TK/GCV group (about 19%). The results showed that the combination of the two treatments can effectively improve the cytocidal effect in PC-3M cells.

  6. An IR navigation system for real-time treatment guidance of Pleural PDT

    Science.gov (United States)

    Zhu, Timothy C.; Liang, Xing; Chang, Chang; Sandell, Julia; Finlay, Jarod C.; Dimofte, Andreea; Rodrigeus, Carmen; Cengel, Keith; Friedberg, Joseph; Glatstein, Eli; Hahn, Stephen M.

    2015-01-01

    Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcome. However, common practice uses a point source to deliver light to the pleural cavity with the light uniformity monitored by 7 detectors placed within the pleural cavity. To improve the uniformity of light fluence rate distribution, we have used a real-time infrared (IR) tracking camera to track the movement of the light point source. The same tracking device is used to determine the surface contour of the treatment area. This study examines the light fluence (rate) delivered between the measurement and calculation in phantom studies. Isotropic detectors were used for in-vivo light dosimetry. Light fluence rate in the pleural cavity is calculated and compared with the in-vivo calculation. Phantom studies show that the surface contour can be determined with an accuracy of 2 mm, with maximum deviation of 5 mm. We can successfully match the calculated light fluence rates with the in-vivo measurements. Preliminary results indicate that the light fluence rate can have up to 50% deviation compared to the prescription in phantom experiments. The IR camera has been used successfully in pleural PDT patient treatment to track the motion of light source in real-time. We concluded that it is feasible to develop an IR camera based system to guide the motion of the light source to improve the uniformity of light distribution. PMID:26005244

  7. An indica rice genotype showed a similar yield enhancement to that of hybrid rice under free air carbon dioxide enrichment

    Science.gov (United States)

    Zhu, Chunwu; Xu, Xi; Wang, Dan; Zhu, Jianguo; Liu, Gang

    2015-07-01

    Although the rice growth response to FACE (free-air CO2 enrichment) has been widely studied and is considered important within the scientific community, few studies have attempted to examine the effects of FACE on the yield of indica rice, which is typically the parent of indica hybrids in China. The effects of FACE on the yield, yield components, biomass, N uptake and leaf photosynthesis of Yangdao 6 Hao (an indica rice) in China were examined over 2 years. The grain yield increased over 30%, the panicle number increased 12.4% on average, and the spikelet number per panicle also showed an average increase of 8.2% at elevated CO2. FACE caused a significant enhancement in both the filled spikelet percentage (+5.9%) and the individual grain weight (+3.0%). Compared with three prior FACE studies on rice, a similar enhancement of yield in hybrid indica was shown under FACE, with much a higher value than for the japonica rice cultivar (approximately + 13%) because of indica’s stronger sink generation and N uptake capacity, which help coordinate the C/N balance to avoid photosynthetic acclimation. The high enhancement of the indica rice yield under FACE holds promise for improved cultivar selection for future food security.

  8. Appropriate nonwoven filters effectively capture human peripheral blood cells and mesenchymal stem cells, which show enhanced production of growth factors.

    Science.gov (United States)

    Hori, Hideo; Iwamoto, Ushio; Niimi, Gen; Shinzato, Masanori; Hiki, Yoshiyuki; Tokushima, Yasuo; Kawaguchi, Kazunori; Ohashi, Atsushi; Nakai, Shigeru; Yasutake, Mikitomo; Kitaguchi, Nobuya

    2015-03-01

    Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 μm fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 μm captured over 70% of leukocytes or 90% of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor β1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues.

  9. Effect of antioxidants on PDT treatment of cultured tumor cells

    Science.gov (United States)

    Melnikova, Vladislava; Bezdetnaya, Lina N.; Belitchenko, Irina; Potapenko, Alexander Y.; Merlin, Jean-Louis; Guillemin, Francois H.

    1998-05-01

    Lipid peroxidation (LP) is involved in cell damage induced by photodynamic treatment (PDT) sensitized by some lipophylic porphyrins. We investigated an effect of lipophylic antioxidant (alpha) -tocopherol and its water-soluble analog, trolox, on meta-tetra(hydroxyphenyl)chlorin (mTHPC) sensitized PDT (413 nm) of cultured human colon adenocarcinoma cells (HT29). Cell survival was measured by the 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide conversion to farmazan (MTT assay). Both antioxidants in concentrations lower than 0.1 mM did not affect photokilling of HT29 cells. These data might suggest that LP is not of crucial importance in cell damage photosensitized by mTHPC. One mM (alpha) -tocopherol or trolox decreased cell survival by ca. 15 and 13% respectively. Both antioxidants increased PDT- induced damage of HT29. Potentiation was evident as the decrease in the initial shoulder part of fluence dependence curve. We propose that antioxidants at height, pro-oxidant concentrations can potentiate PDT induced killing of tumor cells.

  10. Techport Input for Propulsive Descent Technologies (PDT) Project

    Science.gov (United States)

    Campbell, Charles H.

    2013-01-01

    The PDT project will investigate the use of retro propulsion during the supersonic phase of atmospheric entry for Mars missions. The project technical approach involves a combination of procurement and evaluation of commercially provided flight data, development of candidate vehicle configurations, and engineering calibration of computational fluid dynamics models to the available flight data.

  11. PDT: Photometric DeTrending Algorithm Using Machine Learning

    Science.gov (United States)

    Kim, Dae-Won

    2016-05-01

    PDT removes systematic trends in light curves. It finds clusters of light curves that are highly correlated using machine learning, constructs one master trend per cluster and detrends an individual light curve using the constructed master trends by minimizing residuals while constraining coefficients to be positive.

  12. mTHPC mediated, systemic photodynamic therapy (PDT) for nonmelanoma skin cancers: Case and literature review.

    Science.gov (United States)

    Horlings, Rudolf K; Terra, Jorrit B; Witjes, Max J H

    2015-12-01

    Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multiple NMSCs up to a depth of 10 mm in a single session. These unique properties offer an attractive alternative to regular therapies (e.g., surgery or radiation) to these patients. A systemic search was carried out that focused on the main clinical studies using mTHPC-PDT on NMSCs in humans. This review describes some of the basic principles of the treatment, the most effective treatment parameters as well as its possible adverse outcomes, which is illustrated with a short description of our own experiences using this treatment modality on four patients with multiple NMSCs. To date, only four clinical studies have been published. It was demonstrated that mTHPC-PDT could be highly effective. On illuminating 1-2 days after drug administration, plasma drug levels were high and the tumor clearance rates were high (up to 100%), with relative few side effects and excellent cosmetic and functional outcomes. These results were obtained with a relatively low, patient friendly photosensitizer dose (0.04-0.05 mg/kg) as skin photosensitivity was shorter after the procedure. Although the patients personally experienced consistently good cure rates, the healing times varied greatly between anatomical areas. The head and neck areas heal well with good cosmesis, while the lower leg and foot areas show delayed, at times compromised, healing with scarring. Although mTHPC-PDT is described in the literature as an interesting and promising therapeutic option, especially for multiple NMSCs, a randomized clinical trial is lacking and personal experiences warrant too much skepticism. With the recent introduction of the hedgehog pathway inhibitor vismodegib, mTHPC-PDT seems to be less suitable as a first line of

  13. Measured Deformation Enhancement in Western Greenland Shows the Importance of Viscosity Reduction for Elevated Melt Season Velocities

    Science.gov (United States)

    Maier, N. T.; Humphrey, N. F.; Harper, J. T.; Meierbachtol, T. W.

    2016-12-01

    There is increasing evidence that much of the bed on the Western Margin of the Greenland Ice Sheet (GrIS) is hydrologically isolated during the melt season, making it necessary to understand how ice dynamics regulates basal flow between active and inactive regions of the bed. We present measurements of englacial shear strain rates collected by tilt sensors embedded in a boreholes approximately 670 m deep during the 2015 melt season at a field site on the Western Margin of the GrIS. The measurements demonstrate that shear strain rates during the melt season can increase by a factor of three. The increase in shear strain rates and deformation velocity is well correlated to the surface and basal sliding velocity measured at the field site. Coincident with the enhanced deformation, the effective stress calculated from the surficial strain rate tensor increases from approximately 70-160 kPa. During this period each stress component shows a high degree of variability. The magnitude and range of the effective stress is in agreement with the change in the effective stress necessary to produce the elevated strain rates observed englacially. This result demonstrates that spatially variable flow at the onset of the melt season can result in a significant decrease in the effective ice viscosity. The decrease in the effective ice viscosity is sufficient to increase the deformation velocity from approximately 20 to 40 ma-1. The increase in the deformation velocity is well correlated to the observed increase in basal sliding suggesting that ice softening may be an important mechanism to enhance basal flow in isolated regions of the bed. For a glacier on a hard bed, the rate of basal sliding is controlled by the rate at which the basal ice can deform around bedrock obstacles. In this context, a reduction in the effective viscosity can enhance the basal sliding velocity without a basal friction reduction through local changes in basal water pressure or water storage.

  14. A basic study on hypericin-PDT in vitro.

    Science.gov (United States)

    Nakajima, Nobue; Kawashima, Norimichi

    2012-09-01

    The effect of photo dynamic therapy (PDT) using hypericin as a photosensitiser and the effect of PDT on intracellular ATP levels using different lamps in a human leukemic monocyte lymphoma cell line (U937) were studied. The time required for hypericin to penetrate into the cancer cells was 1h, and incubation for more than 3h post-irradiation with hypericin-PDT was required to observe effects. Thus, if cancer cell death does not occur immediately following irradiation, it is unnecessary to perform additional irradiation, as most of the cells die via apoptosis during the incubation period post-irradiation. When hypericin-PDT was performed using a Na-Li lamp as a light source, the cell viability decreased approximately 55% immediately following irradiation for 5 min; however, after a 5-h post-irradiation incubation, the cell viability approached 0%. Concurrently, intracellular ATP levels increased markedly; thus, irradiation (0.225 J/cm(2)) for 5 min provided the best results in terms of the highest degree of cancer cell apoptosis. Similar experiments were performed using three different LED lamps respectively. When cells were treated with the LED lamps, with maximum peaks of 599 nm and 595 nm, the cell viability approached 0% after incubation for 5h following 15 min of irradiation (0.04 J/cm(2) and 0.099 J/cm(2), respectively). We confirmed that incubating the cells for more than 3h in a 100 × diluted hypericin solution was the most effective for PDT and that a LED lamp of low light intensity led to the highest apoptosis rate in the U937 cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. The effects of PDT in primary malignant brain tumours could be improved by intraoperative radiotherapy.

    Science.gov (United States)

    Lyons, Matthew; Phang, Isaac; Eljamel, Sam

    2012-03-01

    GBM has a poor survival despite surgery and chemoradiotherapy. Cytoreduction and PDT have postulated to afford better local GBM-control. However, the interaction of PDT with newer novel therapies had not been fully investigated. This study reviewed the impact of PDT in conjunction with intraoperative radiotherapy. Case note review of prospectively collected data of GBMs treated surgically by the senior author (SE). Patients received standard therapy (ST), ST+PDT or ST+PDT+IORT. ST involved maximum safe resection, PDT involved intracavity 100 J/cm² 630 nm laser and IORT involved intracavity 10-15 Gys using the PRS400®. Patients were followed up clinically and radiologically till death. There were 73 patients included in this analysis (42 males). The average age was 59years. Thirty received PDT and 43 did not. The mean survival of PDT-patients was significantly longer than those had ST alone (62.9 weeks vs. 20.6 weeks) (p=0.001). Patients PDT+IORT was substantially higher than those who received PDT alone (79 weeks vs. 39.7 weeks). Using a Cox regression covariant analysis, demonstrated that PDT was the only therapy to make a statistically significant difference to survival (p=0.018). PDT in high grade glioma was statistically significant therapeutic modality and its effects were further improved by IORT. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. PHOTODYNAMIC THERAPY (PDT) USING HPPH FOR THE TREATMENT OF PRECANCEROUS LESIONS ASSOCIATED WITH BARRETT’S ESOPHAGUS

    Science.gov (United States)

    Nava, Hector R; Allamaneni, Shyam S; Dougherty, Thomas J; Cooper, Michele T; Tan, Wei; Wilding, Gregory; Henderson, Barbara W

    2011-01-01

    Background and Objectives Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett’s esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT. Study Design/Materials and Methods Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m2. At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175 or 200 J/cm of 665 nm light. Results Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced Grade 3 & 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 h), 3 and 4 mg/m2 of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m2 HPPH, light at 24 h), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m2 HPPH plus 175 J/cm and 4 mg/m2 HPPH plus 150 J/cm showing complete responses at 1 year. Conclusions HPPH-PDT for precancerous lesions in Barrett’s esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT. PMID:22057498

  17. 5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay; Wilson, Clara; Iyer, Karthik

    2011-02-01

    5-Fluorouracil (5-FU) was developed in the 1950s as an anticancer drug and is now widely used to treat many cancers, including colon and breast carcinoma. 5-FU causes fluoronucleotide misincorporation into RNA and DNA, inhibits thymidylate synthase, and leads to growth arrest and apoptosis. For skin precancers (actinic keratoses; AK), 5-FU is prescribed as a topical agent and was essentially the only option for treating widespread AK of the skin prior to FDA approval of photodynamic therapy (PDT) in 1999. PDT is now gradually replacing 5-FU as a preferred treatment for AK, but neither PDT nor 5-FU are effective for true skin cancers (basal or squamous cell), particularly for tumors >1 mm in depth. In our ongoing work to improve the efficacy of PDT for skin cancer, we previously showed that PDT efficacy can be significantly enhanced by preconditioning tumors with methotrexate (MTX), which leads to increased production of protoporphyrin IX (PpIX) in target cells. However, because MTX must be given orally or intravenously, it is considered unacceptable for widespread human use due to potential toxicity. MTX and 5-FU exert similar effects on the thymidylate synthesis pathway, so we reasoned that topical 5-FU could be a potential alternative to MTX. In this paper, exploratory studies that test 5-FU as a preconditioning agent for PDT are presented. In a cutaneous model of squamous cell carcinoma (chemically-induced papillomatous tumors in mice), 5-FU significantly enhances PpIX accumulation and therefore emerges as a new candidate agent for combination therapy with PDT.

  18. Topical ALA-PDT as alternative therapeutic option in treatment-recalcitrant dermatosis: Report of 4 cases.

    Science.gov (United States)

    Theresia, Calvina; Zheng, Jie; Chen, Xiao-Ying

    2017-12-01

    Topical Photodynamic therapy (PDT) is widely acknowledged for its safety and effectiveness in treating oncologic skin diseases such as basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its broad applications in dermatology, this method is a relatively new therapeutic option for treating inflammatory/infectious skin diseases. To determine whether topical PDT is a safe and effective treatment option in treating treatment-recalcitrant dermatosis. We presented one of each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment options were either ineffective or not feasible, then those patients underwent topical PDT and showed significant improvement with minimal side effects. Topical PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment has shown no or minimal improvement, or in whom ablative or invasive procedure is to be avoided or not well tolerated. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer.

    Science.gov (United States)

    Yoo, So Young; Bang, Seo Young; Jeong, Su-Nam; Kang, Dae Hwan; Heo, Jeong

    2016-03-29

    Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer.

  20. Transgenic alfalfa (Medicago sativa) with increased sucrose phosphate synthase activity shows enhanced growth when grown under N2-fixing conditions.

    Science.gov (United States)

    Gebril, Sayed; Seger, Mark; Villanueva, Fabiola Muro; Ortega, Jose Luis; Bagga, Suman; Sengupta-Gopalan, Champa

    2015-10-01

    Overexpression of SPS in alfalfa is accompanied by early flowering, increased plant growth and an increase in elemental N and protein content when grown under N2-fixing conditions. Sucrose phosphate synthase (SPS; EC 2.3.1.14) is the key enzyme in the synthesis of sucrose in plants. The outcome of overexpression of SPS in different plants using transgenic approaches has been quite varied, but the general consensus is that increased SPS activity is associated with the production of new sinks and increased sink strength. In legumes, the root nodule is a strong C sink and in this study our objective was to see how increasing SPS activity in a legume would affect nodule number and function. Here we have transformed alfalfa (Medicago sativa, cv. Regen SY), with a maize SPS gene driven by the constitutive CaMV35S promoter. Our results showed that overexpression of SPS in alfalfa, is accompanied by an increase in nodule number and mass and an overall increase in nitrogenase activity at the whole plant level. The nodules exhibited an increase in the level of key enzymes contributing to N assimilation including glutamine synthetase and asparagine synthetase. Moreover, the stems of the transformants showed higher level of the transport amino acids, Asx, indicating increased export of N from the nodules. The transformants exhibited a dramatic increase in growth both of the shoots and roots, and earlier flowering time, leading to increased yields. Moreover, the transformants showed an increase in elemental N and protein content. The overall conclusion is that increased SPS activity improves the N status and plant performance, suggesting that the availability of more C in the form of sucrose enhances N acquisition and assimilation in the nodules.

  1. Photos of Lansmont PDT 80 drop test machine at Los Alamos

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Murray E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-12-21

    The Los Alamos RP-SVS Radiation Protection Services group designed and constructed a drop tower facility for TA- 55 support work. The drop mechanism was supplied by the Lansmont company in Monterey CA. Los Alamos staffers Murray Moore and Yong Tao have noticed that the system is not dropping loads correctly, and they have photographed aspects of the PDT- 80 model system. The first 10 photos show the platen loaded with a cylindrical steel bar. The next 10 photos are of the roller-cam mechanism in the drop tower, and the last 2 photos indicate the amount of looseness in the platen when it is being pulled by a person.

  2. Topically Delivered Adipose Derived Stem Cells Show an Activated-Fibroblast Phenotype and Enhance Granulation Tissue Formation in Skin Wounds

    Science.gov (United States)

    Hong, Seok Jong; Xu, Wei; Leung, Kai P.; Mustoe, Thomas A.; Galiano, Robert D.

    2013-01-01

    Multipotent mesenchymal stem cells (MSCs) are found in various tissues and can proliferate extensively in vitro. MSCs have been used in preclinical animal studies and clinical trials in many fields. Adipose derived stem cells (ASCs) have several advantages compared to other MSCs for use in cell-based treatments because they are easy to isolate with relative abundance. However, quantitative approaches for wound repair using ASCs have been limited because of lack of animal models which allow for quantification. Here, we addressed the effect of topically delivered ASCs in wound repair by quantitative analysis using the rabbit ear model. We characterized rabbit ASCs, and analyzed their multipotency in comparison to bone marrow derived-MSCs (BM-MSCs) and dermal fibroblasts (DFs) in vitro. Topically delivered ASCs increased granulation tissue formation in wounds when compared to saline controls, whereas BM-MSCs or DFs did not. These studies suggest that ASCs and BM-MSCs are not identical, though they have similar surface markers. We found that topically delivered ASCs are engrafted and proliferate in the wounds. We showed that transplanted ASCs exhibited activated fibroblast phenotype, increased endothelial cell recruitment, and enhanced macrophage recruitment in vivo. PMID:23383253

  3. Combined expression of p20 and p23 proteins from Citrus tristeza virus show enhanced local silencing suppressor activity

    Directory of Open Access Journals (Sweden)

    Ângela A. COSTA

    2016-07-01

    Full Text Available Viruses developed a strategy to counter-defence the posttranscriptional gene silencing mechanism (PTGS based on the activity of silencing suppressor proteins. Citrus tristeza virus (CTV, a member of the genus Closterovirus, has two suppressor proteins (p20 and p23 that target the local RNA silencing response of the host. In GFP transient co-expression assays performed on Nicotiana benthamiana 16C plants, local suppressor activity of p23 and p20 was similar. Co-expression of both proteins from a mild or a stem pitting CTV isolate showed stronger local suppression activity than either suppressor alone, with an increased GFP transcript level six- (for Gp M to nine-fold (for Gp 3a higher than non-inoculated 16C plants, in parallel with low accumulation of siRNAs. Further, GFP brightness of leaves infiltrated with Agrobacterium cultures at an OD600 of 0.5 was comparable to those infiltrated with OD600 0.25. These findings indicate that combined action of p20 and p23 proteins results in enhanced suppressor activity.

  4. Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release of Damage-Associated Molecular Patterns (DAMPs) in human HeLa cells.

    Science.gov (United States)

    Panzarini, Elisa; Inguscio, Valentina; Fimia, Gian Maria; Dini, Luciana

    2014-01-01

    The new concept of Immunogenic Cell Death (ICD), associated with Damage Associated Molecular Patterns (DAMPs) exposure and/or release, is recently becoming very appealing in cancer treatment. In this context, PhotoDynamic Therapy (PDT) can give rise to ICD and to immune response upon dead cells removal. The list of PhotoSensitizers (PSs) able to induce ICD is still short and includes Photofrin, Hypericin, Foscan and 5-ALA. The goal of the present work was to investigate if Rose Bengal Acetate (RBAc), a powerful PS able to trigger apoptosis and autophagy, enables photosensitized HeLa cells to expose and/or release pivotal DAMPs, i.e. ATP, HSP70, HSP90, HMGB1, and calreticulin (CRT), that characterize ICD. We found that apoptotic HeLa cells after RBAc-PDT exposed and released, early after the treatment, high amount of ATP, HSP70, HSP90 and CRT; the latter was distributed on the cell surface as uneven patches and co-exposed with ERp57. Conversely, autophagic HeLa cells after RBAc-PDT exposed and released HSP70, HSP90 but not CRT and ATP. Exposure and release of HSP70 and HSP90 were always higher on apoptotic than on autophagic cells. HMGB1 was released concomitantly to secondary necrosis (24 h after RBAc-PDT). Phagocytosis assay suggests that CRT is involved in removal of RBAc-PDT generated apoptotic HeLa cells. Altogether, our data suggest that RBAc has all the prerequisites (i.e. exposure and/or release of ATP, CRT, HSP70 and HSP90), that must be verified in future vaccination experiments, to be considered a good PS candidate to ignite ICD. We also showed tha CRT is involved in the clearance of RBAc photokilled HeLa cells. Interestingly, RBAc-PDT is the first cancer PDT protocol able to induce the translocation of HSP90 and plasma membrane co-exposure of CRT with ERp57.

  5. Chemically primed bone-marrow derived mesenchymal stem cells show enhanced expression of chemokine receptors contributed to their migration capability

    Directory of Open Access Journals (Sweden)

    Hamid Reza Bidkhori

    2016-01-01

    Full Text Available Objective(s:The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC is the key obstacle in MSC-based therapy. It is believed that chemokines and chemokine receptor interactions play key roles in cellular processes associated with migration. Meanwhile, MSCs express a low level of distinct chemokine receptors and they even lose these receptors on their surface after a few passages which influence their therapeutic applications negatively. This study investigated whether treatment of BM-MSCs with hypoxia-mimicking agents would increase expression of some chemokine receptors and cell migration. Materials and Methods: BM-MSCs were treated at passage 2 for our gene expression profiling. All qPCR experiments were performed by SYBR Green method in CFX-96 Bio-Rad Real-Time PCR. The Boyden chamber assay was utilized to investigate BM-MSC homing. Results:Possible approaches to increasing the expression level of chemokine receptors by different hypoxia-mimicking agents such as valproic acid (VPA, CoCl2, and desferrioxamine (DFX are described. Results show DFX efficiently up-regulate the CXCR7 and CXCR4 gene expression while VPA increase only the CXCR7 gene expression and no significant change in expression level of CXCR4 and the CXCR7 gene was detectable by CoCl2 treatment. Chemotaxis assay results show that pre-treatment with DFX, VPA, and Cocl2 enhances significantly the migration ability of BM-MSCs compared with the untreated control group and DFX treatment accelerates MSCs homing significantly with a higher rate than VPA and Cocl2 treatments. Conclusion: Our data supports the notion that pretreatment of MSC with VPA and DFX improves the efficiency of MSC therapy by triggering homing regulatory signaling pathways.

  6. In planta Transformed Cumin (Cuminum cyminum L. Plants, Overexpressing the SbNHX1 Gene Showed Enhanced Salt Endurance.

    Directory of Open Access Journals (Sweden)

    Sonika Pandey

    Full Text Available Cumin is an annual, herbaceous, medicinal, aromatic, spice glycophyte that contains diverse applications as a food and flavoring additive, and therapeutic agents. An efficient, less time consuming, Agrobacterium-mediated, a tissue culture-independent in planta genetic transformation method was established for the first time using cumin seeds. The SbNHX1 gene, cloned from an extreme halophyte Salicornia brachiata was transformed in cumin using optimized in planta transformation method. The SbNHX1 gene encodes a vacuolar Na+/H+ antiporter and is involved in the compartmentalization of excess Na+ ions into the vacuole and maintenance of ion homeostasis Transgenic cumin plants were confirmed by PCR using gene (SbNHX1, uidA and hptII specific primers. The single gene integration event and overexpression of the gene were confirmed by Southern hybridization and competitive RT-PCR, respectively. Transgenic lines L3 and L13 showed high expression of the SbNHX1 gene compared to L6 whereas moderate expression was detected in L5 and L10 transgenic lines. Transgenic lines (L3, L5, L10 and L13, overexpressing the SbNHX1 gene, showed higher photosynthetic pigments (chlorophyll a, b and carotenoid, and lower electrolytic leakage, lipid peroxidation (MDA content and proline content as compared to wild type plants under salinity stress. Though transgenic lines were also affected by salinity stress but performed better compared to WT plants. The ectopic expression of the SbNHX1 gene confirmed enhanced salinity stress tolerance in cumin as compared to wild type plants under stress condition. The present study is the first report of engineering salt tolerance in cumin, so far and the plant may be utilized for the cultivation in saline areas.

  7. dhm1, an Arabidopsis mutant with increased sensitivity to alkamides shows tumorous shoot development and enhanced lateral root formation.

    Science.gov (United States)

    Pelagio-Flores, Ramón; Ortiz-Castro, Randy; López-Bucio, José

    2013-04-01

    The control of cell division by growth regulators is critical to proper shoot and root development. Alkamides belong to a class of small lipid amides involved in plant morphogenetic processes, from which N-isobutyl decanamide is one of the most active compounds identified. This work describes the isolation and characterization of an N-isobutyl decanamide-hypersensitive (dhm1) mutant of Arabidopsis (Arabidopsis thaliana). dhm1 seedlings grown in vitro develop disorganized tumorous tissue in petioles, leaves and stems. N-isobutyl decanamide treatment exacerbates the dhm1 phenotype resulting in widespread production of callus-like structures in the mutant. Together with these morphological alterations in shoot, dhm1 seedlings sustained increased lateral root formation and greater sensitivity to alkamides in the inhibition of primary root growth. The mutants also show reduced etiolation when grown in darkness. When grown in soil, adult dhm1 plants were characterized by reduced plant size, and decreased fertility. Genetic analysis indicated that the mutant phenotype segregates as a single recessive Mendelian trait. Developmental alterations in dhm1 were related to an enhanced expression of the cell division marker CycB1-uidA both in the shoot and root system, which correlated with altered expression of auxin and cytokinin responsive gene markers. Pharmacological inhibition of auxin transport decreased LR formation in WT and dhm1 seedlings in a similar manner, indicating that auxin transport is involved in the dhm1 root phenotype. These data show an important role of alkamide signaling in cell proliferation and plant architecture remodeling likely acting through the DHM1 protein.

  8. In planta Transformed Cumin (Cuminum cyminum L.) Plants, Overexpressing the SbNHX1 Gene Showed Enhanced Salt Endurance.

    Science.gov (United States)

    Pandey, Sonika; Patel, Manish Kumar; Mishra, Avinash; Jha, Bhavanath

    2016-01-01

    Cumin is an annual, herbaceous, medicinal, aromatic, spice glycophyte that contains diverse applications as a food and flavoring additive, and therapeutic agents. An efficient, less time consuming, Agrobacterium-mediated, a tissue culture-independent in planta genetic transformation method was established for the first time using cumin seeds. The SbNHX1 gene, cloned from an extreme halophyte Salicornia brachiata was transformed in cumin using optimized in planta transformation method. The SbNHX1 gene encodes a vacuolar Na+/H+ antiporter and is involved in the compartmentalization of excess Na+ ions into the vacuole and maintenance of ion homeostasis Transgenic cumin plants were confirmed by PCR using gene (SbNHX1, uidA and hptII) specific primers. The single gene integration event and overexpression of the gene were confirmed by Southern hybridization and competitive RT-PCR, respectively. Transgenic lines L3 and L13 showed high expression of the SbNHX1 gene compared to L6 whereas moderate expression was detected in L5 and L10 transgenic lines. Transgenic lines (L3, L5, L10 and L13), overexpressing the SbNHX1 gene, showed higher photosynthetic pigments (chlorophyll a, b and carotenoid), and lower electrolytic leakage, lipid peroxidation (MDA content) and proline content as compared to wild type plants under salinity stress. Though transgenic lines were also affected by salinity stress but performed better compared to WT plants. The ectopic expression of the SbNHX1 gene confirmed enhanced salinity stress tolerance in cumin as compared to wild type plants under stress condition. The present study is the first report of engineering salt tolerance in cumin, so far and the plant may be utilized for the cultivation in saline areas.

  9. Multimodal OCT for assessment of vasculature-targeted PDT success

    Science.gov (United States)

    Sirotkina, Marina A.; Gubarkova, Ekaterina V.; Kiseleva, Elena B.; Zaitsev, Vladimir Y.; Kirillin, Mikhail Y.; Sovetsky, Alexander A.; Matveyev, Alexander L.; Matveev, Lev A.; Kuznetsov, Sergey S.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

    2017-02-01

    The main goal of the study was a vasculature targeted PDT. A new approach named M-mode-like OCT (MML OCT) was applied to monitor early response to PDT. Due to the chosen filtering parameters (96 Hz filter threshold), this approach visualizes only vessels with flowing blood. Without flowing blood even filled vessels are not visualized because flow-less blood causes speckle variations with significantly lower frequencies (<50 Hz corresponding to speckle decorrelation time for stationary blood). This feature allows us to detect thrombosis of blood vessels, the results of MML OCT and histological examination being perfectly coinciding. The advantages of MML OCT such as a simple and fast process of obtaining microvasculature images and label-free nature of the visualization makes this method perspective in routine clinical monitoring of antitumor therapies.

  10. Immobilized silver nanoparticles enhance contact killing and show highest efficacy: elucidation of the mechanism of bactericidal action of silver

    Science.gov (United States)

    Agnihotri, Shekhar; Mukherji, Soumyo; Mukherji, Suparna

    2013-07-01

    Antimicrobial materials with immobilized/entrapped silver nanoparticles (AgNPs) are of considerable interest. There is significant debate on the mode of bactericidal action of AgNPs, and both contact killing and/or ion mediated killing have been proposed. In this study, AgNPs were immobilized on an amine-functionalized silica surface and their bactericidal activity was studied concurrently with the silver release profile over time. This was compared with similar studies performed using colloidal AgNPs and AgCl surfaces that released Ag ions. We conclude that contact killing is the predominant bactericidal mechanism and surface immobilized nanoparticles show greater efficacy than colloidal AgNPs, as well as a higher concentration of silver ions in solution. In addition, the AgNP immobilized substrate was used multiple times with good efficacy, indicating this immobilization protocol is effective for retaining AgNPs while maintaining their disinfection potential. The antibacterial surface was found to be extremely stable in aqueous medium and no significant leaching (~1.15% of total silver deposited) of the AgNPs was observed. Thus, immobilization of AgNPs on a surface may promote reuse, reduce environmental risks associated with leaching of AgNPs and enhance cost effectiveness.Antimicrobial materials with immobilized/entrapped silver nanoparticles (AgNPs) are of considerable interest. There is significant debate on the mode of bactericidal action of AgNPs, and both contact killing and/or ion mediated killing have been proposed. In this study, AgNPs were immobilized on an amine-functionalized silica surface and their bactericidal activity was studied concurrently with the silver release profile over time. This was compared with similar studies performed using colloidal AgNPs and AgCl surfaces that released Ag ions. We conclude that contact killing is the predominant bactericidal mechanism and surface immobilized nanoparticles show greater efficacy than colloidal Ag

  11. Mars Mission Scenario: Data Volume and PDT Notes

    Science.gov (United States)

    Hemmati, Hamid; Biswas, A.; Piazzolla, S.; Townes, S.

    2012-01-01

    Objectives of this work are: (1) Investigate methods for quantifying the value of interoperability for deep space missions: A network of optical receive stations Each one potentially owned by a different space agency. Reduces overall cost to any individual agency Provides geographically diverse locations to mitigate weather problems (clouds, wind, rain, dust, etc.) (2) Metrics: a. Total data volume returned over mission duration b. Percent data transferred (PDT) or something similar.

  12. Perspectives of Fullerene Derivatives in PDT and Radiotherapy of Cancers

    OpenAIRE

    Orlova, Marina A.; Trofimova, Tatiana P.; Orlov, Alexey P.; Oleg A. Shatalov

    2013-01-01

    Nanoparticles of fullerenes and their water-soluble derivatives have been firmly introduced into solution of medical problems. Although there are still debates about their toxicity and long-term consequences of their application in the clinic, the success of fullerenes application in some sections is undeniable, in particular, in photodynamic therapy (PDT) of cancer tumors. Besides there are interesting data on radiotherapy where fullerenes appear to be more transporters than drugs, but due t...

  13. The in Vitro Antimicrobial Efficacy of PDT against Periodontopathogenic Bacteria

    OpenAIRE

    Haag, Philippe A.; Steiger-Ronay, Valerie; Schmidlin, Patrick R.

    2015-01-01

    Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT) as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter act...

  14. PDT-treated apoptotic cells induce macrophage synthesis NO

    Science.gov (United States)

    Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

    2009-11-01

    Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

  15. Mice lacking thyroid hormone receptor Beta show enhanced apoptosis and delayed liver commitment for proliferation after partial hepatectomy.

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    Raquel López-Fontal

    Full Text Available BACKGROUND: The role of thyroid hormones and their receptors (TR during liver regeneration after partial hepatectomy (PH was studied using genetic and pharmacologic approaches. Roles in liver regeneration have been suggested for T3, but there is no clear evidence distinguishing the contribution of increased amounts of T3 from the modulation by unoccupied TRs. METHODOLOGY/PRINCIPAL FINDINGS: Mice lacking TRalpha1/TRbeta or TRbeta alone fully regenerated liver mass after PH, but showed delayed commitment to the initial round of hepatocyte proliferation and transient but intense apoptosis at 48h post-PH, affecting approximately 30% of the remaining hepatocytes. Pharmacologically induced hypothyroidism yielded similar results. Loss of TR activity was associated with enhanced nitrosative stress in the liver remnant, due to an increase in the activity of the nitric oxide synthase (NOS 2 and 3, caused by a transient decrease in the concentration of asymmetric dimethylarginine (ADMA, a potent NOS inhibitor. This decrease in the ADMA levels was due to the presence of a higher activity of dimethylarginineaminohydrolase-1 (DDAH-1 in the regenerating liver of animals lacking TRalpha1/TRbeta or TRbeta. DDAH-1 expression and activity was paralleled by the activity of FXR, a transcription factor involved in liver regeneration and up-regulated in the absence of TR. CONCLUSIONS/SIGNIFICANCE: We report that TRs are not required for liver regeneration; however, hypothyroid mice and TRbeta- or TRalpha1/TRbeta-deficient mice exhibit a delay in the restoration of liver mass, suggesting a specific role for TRbeta in liver regeneration. Altered regenerative responses are related with a delay in the expression of cyclins D1 and E, and the occurrence of liver apoptosis in the absence of activated TRbeta that can be prevented by administration of NOS inhibitors. Taken together, these results indicate that TRbeta contributes significantly to the rapid initial round of

  16. Modulation of telomerase and signal transduction proteins by hexyl-ALA-photodynamic therapy (PDT) in human doxorubicin resistant cancer cell models.

    Science.gov (United States)

    Chu, Ellie S M; Yow, Christine M N

    2012-09-01

    This study employed a doxorubicin resistant (MES-SA-Dx5) human uterine sarcoma cell line and its counterpart (MES-SA), to elucidate the efficacy of aminolevulinic acid-hexylester (hexyl-ALA) mediated PDT at molecular and transcriptional levels. Hexyl-ALA generated protoporphyrin IX in both cells were determined by molecular probes using Confocal Laser Scanning Microscopy. The hexyl-ALA-PDT induced signal transduction proteins and mode of cell death were quantitated by CASE ELISA assays and DAPI staining. The modulation of hTERT mRNA expression and telomerase activity were investigated by TaqMan real-time PCR and ELISA respectively. Hexyl-ALA-PDT mediated cell migratory effect was determined by wound-healing assay. The results demonstrated that mitochondria were the major target of hexyl-ALA. At LD(30), hexyl-ALA-PDT significantly provoked an up-regulation of phosphorylated p38MAPK and JNK proteins in both cells. Hexyl-ALA-PDT down-regulated hTERT (a catalytic subunit of telomerase) mRNA expression and showed a strong correlation with diminished telomerase activity in both cells (MES-SA: r(2) = 0.9932; MES-SA-Dx5: r(2) = 0.9775). The suppression of cell migratory effect in both cells was obtained after hexyl-ALA-PDT. Further, 50% and 30% of apoptotic cells were attained at LD(50), for wild-type and drug resistant cells respectively. Unlike the wild-type, a higher PDT dose was crucial to induce apoptosis in the drug resistant cells. Our study provides the first evidence that p38MAPK and JNK kinases played a vital role in triggering hexyl-ALA-PDT-induced apoptosis, down-regulated hTERT mRNA expression and telomerase activity in both proposed cells. In vivo studies are worth examining for the benefit of clinical applications in drug resistant cancers and PDT development. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Nontrivial Berry phase and type-II Dirac transport in the layered material PdT e2

    Science.gov (United States)

    Fei, Fucong; Bo, Xiangyan; Wang, Rui; Wu, Bin; Jiang, Juan; Fu, Dongzhi; Gao, Ming; Zheng, Hao; Chen, Yulin; Wang, Xuefeng; Bu, Haijun; Song, Fengqi; Wan, Xiangang; Wang, Baigeng; Wang, Guanghou

    2017-07-01

    We report on a systematic study of type-II Dirac fermions in a layered crystal of PdT e2 . De Haas-van Alphen oscillations show a small Fermi-surface pocket with a cross section of 0.077 n m-2 with a nontrivial Berry phase. First-principles calculation reveals that the nontrivial Berry phase originates from a hole pocket formed by the tilted Dirac cone. In addition, the band dispersion measured with angle-resolved photoemission spectroscopy is found to be consistent with that of a type-II Dirac cone dispersion. We propose that PdT e2 is an improved platform to host topological superconductors.

  18. Choroidal lymphoma shows calm, rippled, or undulating topography on enhanced depth imaging optical coherence tomography in 14 eyes.

    Science.gov (United States)

    Shields, Carol L; Arepalli, Sruthi; Pellegrini, Marco; Mashayekhi, Arman; Shields, Jerry A

    2014-07-01

    To describe the features of choroidal lymphoma on enhanced depth imaging optical coherence tomography. This retrospective observational case series included 14 eyes of 13 patients, with choroidal lymphoma, studied by enhanced depth imaging optical coherence tomography. The mean age at presentation was 63 years (median, 65 years; range, 32-87 years). Systemic lymphoproliferative disease was present in 2 cases as non-Hodgkin lymphoma (n = 1) or Waldenstrom macroglobulinemia (n = 1). On clinical examination, the choroidal infiltrate was classified as unifocal (n = 3), multifocal (n = 4), or diffuse (n = 7). Enhanced depth imaging optical coherence tomography scans through the tumor epicenter revealed infiltration of the choroid with apparent inward compression of choroidal vascular structures, creating an anterior tumor surface topography that appeared smooth (calm) (n = 7), mini-wavy (rippled) (n = 2), or maxi-wavy (undulating) (n = 5). Greater tumor thickness correlated with increasing tumor surface fluctuation as calm was mean 1.7mm, rippled was 2.8 mm, and undulating surface was 4.1 mm in ultrasonographic thickness. On enhanced depth imaging optical coherence tomography, the mean subfoveolar choroidal thickness, measurable in 9 eyes, was 484 μm (median, 423 μm; range, 156-1,002 μm) (81% greater) versus 267 μm (median, 276 μm; range, 142-501 μm) in the unaffected eye. The mean maximal tumor thickness, measurable in 8 eyes, was 117% greater at 602 μm (median, 538 μm; range, 241-966 μm) compared with the corresponding unaffected choroid in the contralateral eye at 278 μm (median, 245 μm; range, 189-511 μm) (P = 0.046). Inability to measure choroidal thickness was due to dense tumor-induced optical shadowing with inability to visualize the sclerochoroidal junction (P = 0.009). There was no visible infiltration into the overlying retina in any case. Enhanced depth imaging optical coherence tomography of choroidal lymphoma revealed 1 of 3 surface

  19. Biomedical, translational and clinical research on PDT of TMJ

    Science.gov (United States)

    Kamenoff, J.

    2017-02-01

    Electromagnetic energy of laser light has some typical properties which are found to be a premise for discussions on laser irradiation abilities to control the severe and chronic disorders in TMJ. In world literature PDT application is recommended when soft tissues in TMJ are damaged, in cases of degenerative diseases of discus articularis, medial and lateral distensions of joint ligaments, chronic inflammatory processes in TMJ, occlusion trauma, etc. The aim of our clinical study was to analyze the theoretical achievements up to now in depth and basing on our clinic al observations suggest new methods guaranteeing high therapeutic efficacy of Photodynamic therapy.

  20. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications.

    Science.gov (United States)

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-09-25

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects.

  1. In-vivo outcome study of HPPH mediated PDT using singlet oxygen explicit dosimetry (SOED).

    Science.gov (United States)

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

    2015-03-02

    Type II photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive singlet oxygen. However, the medical application of this technique has been limited due to inaccurate PDT dosimetric methods. The goal of this study is to examine the relationship between outcome (in terms of tumor growth rate) and calculated reacted singlet oxygen concentration ([ 1 O 2 ] rx ) after HPPH-mediated PDT to compare with other PDT dose metrics, such as PDT dose or total light fluence. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration and tissue optical properties via fluorescence and absorption measurement with a contact probe before and after PDT were taken to then quantify total light fluence, PDT dose, and [ 1 O 2 ] rx based on a macroscopic model of singlet oxygen. In addition, photobleaching of photosenitizer were measured during PDT as a second check of the model. Changes in tumor volume were tracked following treatment and compared to the three calculated dose metrics. The correlations between total light fluence, PDT dose, reacted [ 1 O 2 ] rx and tumor growth demonstrate that [ 1 O 2 ] rx serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor growth endpoint.

  2. Efficacy and safety of topical ALA-PDT in the treatment of EMPD.

    Science.gov (United States)

    Gao, Yang; Zhang, Xing-Cun; Wang, Wen-Sheng; Yang, Yang; Wang, Hai-Lin; Lu, Yuan-Gang; Fan, Dong-Li

    2015-03-01

    Photodynamic therapy (PDT) is a successful treatment for non-melanoma skin cancers in clinical practice. More and more doctors use PDT to cure the patients with skin cancer, especially in the elder. The purpose of this study was to evaluate the efficacy and safety of topical PDT using aminolevulinic acid (5-ALA) in the treatment of Extramammary Paget's disease (EMPD) and its role in surgical improvements. A total of 38 cases were included in this study. Lesions were located in the scrotum and the penis. Thirty-one cases had surgical resection of the lesions followed by ALA-PDT (combination of PDT and surgery group). Seven cases received ALA-PDT without receiving surgical resection because the surgery is extremely difficult or the patients refused surgery (simple PDT group). Each tumor lesion was irradiated with 120J/cm(2) using a 635-nm laser for 15min. A total of 3 times of assisted ALA-PDT was applied after surgery. In the combination group, there was no recurrence in 6 months after treatment. In another group, recurrence occurred in 1 case in 6 months. All patients were able to complete the treatment protocol, with well cosmetic results and no moderate adverse reactions. As an assistive therapy after tumor resection, ALA-PDT can reduce the excision range of the tumor lesions and will play more important role in the treatment of EMPD. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. In-vivo outcome study of HPPH mediated PDT using singlet oxygen explicit dosimetry (SOED)

    Science.gov (United States)

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

    2015-03-01

    Type II photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive singlet oxygen. However, the medical application of this technique has been limited due to inaccurate PDT dosimetric methods. The goal of this study is to examine the relationship between outcome (in terms of tumor growth rate) and calculated reacted singlet oxygen concentration [1O2]rx after HPPH-mediated PDT to compare with other PDT dose metrics, such as PDT dose or total light fluence. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration and tissue optical properties via fluorescence and absorption measurement with a contact probe before and after PDT were taken to then quantify total light fluence, PDT dose, and [1O2]rx based on a macroscopic model of singlet oxygen. In addition, photobleaching of photosenitizer were measured during PDT as a second check of the model. Changes in tumor volume were tracked following treatment and compared to the three calculated dose metrics. The correlations between total light fluence, PDT dose, reacted [1O2]rx and tumor growth demonstrate that [1O2]rx serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor growth endpoint.

  4. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications

    Directory of Open Access Journals (Sweden)

    Miri Kim

    2015-09-01

    Full Text Available Photodynamic therapy (PDT uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects.

  5. Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion.

    Science.gov (United States)

    Vecchio, Daniela; Dai, Tianhong; Huang, Liyi; Fantetti, Lia; Roncucci, Gabrio; Hamblin, Michael R

    2013-09-01

    Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Real-time treatment feedback guidance of Pleural PDT

    Science.gov (United States)

    Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Liu, Baochang; Meo, Julia L.; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles B.; Cengel, Keith; Friedberg, Joseph S.

    2015-01-01

    Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma with remarkable results. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have improved the GUI of the light dose calculation engine to provide real-time light fluence distribution suitable for guiding the surgery to delivery light more uniformly. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings using both direct and scatter light models. An improved measurement device is developed to automatically acquire laser position for the point source. Comparison of the effects of the guidance is presented in phantom study. PMID:25999647

  7. Noncoherent light for PDT of spontaneous animal tumors

    Science.gov (United States)

    Lucroy, Michael D.; Ridgway, Tisha D.; Higbee, Russell G.; Reeds, Kimberly

    2004-07-01

    Cultured 9L cells were incubated with graded doses of pheophorbide-a-hexyl ether (HPPH) and exposed to 665 nm red light from either a noncoherent light source or a KTP-pumped dye laser. Cell death was observed after irradiation using either light source, with the noncoherent light being most effective at the highest HPPH concentrations. To determing the practicality of using the noncoherent light source for clinical PDT, dogs and cats with spontaneous tumors were injected intravenously with 0.15 mg/kg HPPH one hour before their tumors were irradiated with 665 nm noncoherent light (50 mW cm-2, 100 J cm-2). Of the 9 tumors treated, 8 complete responses were observed, all of which occurred in animals with squamous cell carcinoma. After 68 weeks of follow up, the median initial disease free interval had not been reached. These data support the use of noncoherent light sources for PDT of spontaneous tumors in animals, representing a cost-effective alternative to medical lasers in both veterinary and human dermatology and oncology.

  8. Real-time treatment feedback guidance of Pleural PDT

    Science.gov (United States)

    Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Liu, Baochang; Meo, Julia L.; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Cengel, Keith; Friedberg, Joseph

    2013-03-01

    Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma with remarkable results. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have improved the GUI of the light dose calculation engine to provide real-time light fluence distribution suitable for guiding the surgery to delivery light more uniformly. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings using both direct and scatter light models. An improved measurement device is developed to automatically acquire laser position for the point source. Comparison of the effects of the guidance is presented in phantom study.

  9. Monte Carlo simulation of light fluence calculation during pleural PDT

    Science.gov (United States)

    Meo, Julia L.; Zhu, Timothy

    2013-03-01

    A thorough understanding of light distribution in the desired tissue is necessary for accurate light dosimetry in PDT. Solving the problem of light dose depends, in part, on the geometry of the tissue to be treated. When considering PDT in the thoracic cavity for treatment of malignant, localized tumors such as those observed in malignant pleural mesothelioma (MPM), changes in light dose caused by the cavity geometry should be accounted for in order to improve treatment efficacy. Cavity-like geometries demonstrate what is known as the "integrating sphere effect" where multiple light scattering off the cavity walls induces an overall increase in light dose in the cavity. We present a Monte Carlo simulation of light fluence based on a spherical and an elliptical cavity geometry with various dimensions. The tissue optical properties as well as the non-scattering medium (air and water) varies. We have also introduced small absorption inside the cavity to simulate the effect of blood absorption. We expand the MC simulation to track photons both within the cavity and in the surrounding cavity walls. Simulations are run for a variety of cavity optical properties determined using spectroscopic methods. We concluded from the MC simulation that the light fluence inside the cavity is inversely proportional to the surface area.

  10. Effect of PDT-treated apoptotic cells on macrophages

    Science.gov (United States)

    Song, Sheng; Xing, Da; Zhou, Fei-fan; Chen, Wei R.

    2009-02-01

    Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis. However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages, induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response induced by apoptotic cells in tumor cells growth.

  11. A General Framework for Formal Tests of Interaction after Exhaustive Search Methods with Applications to MDR and MDR-PDT

    Science.gov (United States)

    Edwards, Todd L.; Turner, Stephen D.; Torstenson, Eric S.; Dudek, Scott M.; Martin, Eden R.; Ritchie, Marylyn D.

    2010-01-01

    The initial presentation of multifactor dimensionality reduction (MDR) featured cross-validation to mitigate over-fitting, computationally efficient searches of the epistatic model space, and variable construction with constructive induction to alleviate the curse of dimensionality. However, the method was unable to differentiate association signals arising from true interactions from those due to independent main effects at individual loci. This issue leads to problems in inference and interpretability for the results from MDR and the family-based compliment the MDR-pedigree disequilibrium test (PDT). A suggestion from previous work was to fit regression models post hoc to specifically evaluate the null hypothesis of no interaction for MDR or MDR-PDT models. We demonstrate with simulation that fitting a regression model on the same data as that analyzed by MDR or MDR-PDT is not a valid test of interaction. This is likely to be true for any other procedure that searches for models, and then performs an uncorrected test for interaction. We also show with simulation that when strong main effects are present and the null hypothesis of no interaction is true, that MDR and MDR-PDT reject at far greater than the nominal rate. We also provide a valid regression-based permutation test procedure that specifically tests the null hypothesis of no interaction, and does not reject the null when only main effects are present. The regression-based permutation test implemented here conducts a valid test of interaction after a search for multilocus models, and can be applied to any method that conducts a search to find a multilocus model representing an interaction. PMID:20186329

  12. The utilization of a non-invasive fluorescence imaging system to follow clinical dermatological MAL-PDT

    Science.gov (United States)

    Tyrrell, Jessica; Campbell, Sandra; Curnow, Alison

    2009-06-01

    This study employed a commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany), to measure protoporphyrin IX (PpIX) concentration at several different stages during clinical dermatological methyl aminolevulinate photodynamic therapy (MAL-PDT). We validated the system prior to use to ensure that the PpIX changes witnessed were accurate and not due to environmental or user induced artifacts. The system was then employed to acquire color (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. Clinical data was collected from a range of licensed dermatological conditions (actinic keratosis, Bowen's disease and superficial basal cell carcinoma) during initial and subsequent PDT treatment cycles. The initial clinical data indicated that each type of licensed lesion considered responded in a similar manner following the application of Metvix (Galderma, U.K.) and the subsequent light irradiation (Aktilite, Galderma, U.K.). Images acquired three hours after Metvix application showed a significant increase in PpIX concentration within the lesion (P treatment cycles accumulated significantly less PpIX (P < 0.05) prior to irradiation.

  13. Migration of mesenchymal stem cells towards glioblastoma cells depends on hepatocyte-growth factor and is enhanced by aminolaevulinic acid-mediated photodynamic treatment.

    Science.gov (United States)

    Vogel, Sebastian; Peters, Corinna; Etminan, Nima; Börger, Verena; Schimanski, Adrian; Sabel, Michael C; Sorg, Rüdiger V

    2013-02-15

    Hepatocyte-growth factor (HGF) is expressed by glioblastomas and contributes to their growth, migration and invasion. HGF also mediates migration of mesenchymal stem cells (MSC) to sites of apoptotic cell death. Moreover, MSC show tropism for glioblastomas, which is exploited in gene therapy to deliver the therapeutics to the tumor cells. Here, we have studied whether HGF contributes to the recruitment of MSC by glioblastoma cells and whether aminolaevulinic acid-mediated photodynamic therapy (ALA/PDT), a novel therapeutic approach that induces apoptosis in glioblastoma cells, affects HGF release and this migratory response. MSC expressed the HGF receptor MET and migrated towards U87 and U251 glioblastoma spheroids. Migration increased significantly when spheroids were subjected to ALA/PDT, which was associated with induction of apoptosis and up-regulation of HGF. Neutralizing HGF resulted in significant inhibition of MSC migration towards untreated as well as ALA/PDT-treated spheroids. Thus, glioblastoma cells express HGF, which contributes to the attraction of MSC. ALA/PDT induces apoptosis and augments HGF release causing enhanced MSC migration towards the tumor cells. ALA/PDT may therefore be exploited to improve targeting of MSC delivered gene therapy, but it may also constitute a risk in terms of beneficial effects for the tumor. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Extremophile extracts and enhancement techniques show promise for the development of a live vaccine against Flavobacterium columnare

    Science.gov (United States)

    Powell, D.B.; Palm, R.C.; MacKenzie, A.P.; Winton, J.R.

    2009-01-01

    The effects of temperature, ionic strength, and new cryopreservatives derived from polar ice bacteria were investigated to help accelerate the development of economical, live attenuated vaccines for aquaculture. Extracts of the extremophile Gelidibacter algens functioned very well as part of a lyophilization cryoprotectant formulation in a 15-week storage trial. The bacterial extract and trehalose additives resulted in significantly higher colony counts of columnaris bacteria (Flavobacterium columnare) compared to nonfat milk or physiological saline at all time points measured. The bacterial extract combined with trehalose appeared to enhance the relative efficiency of recovery and growth potential of columnaris in flask culture compared to saline, nonfat milk, or trehalose-only controls. Pre-lyophilization temperature treatments significantly affected F. columnare survival following rehydration. A 30-min exposure at 0 ??C resulted in a 10-fold increase in bacterial survival following rehydration compared to mid-range temperature treatments. The brief 30 and 35 ??C pre-lyophilization exposures appeared to be detrimental to the rehydration survival of the bacteria. The survival of F. columnare through the lyophilization process was also strongly affected by changes in ionic strength of the bacterial suspension. Changes in rehydration constituents were also found to be important in promoting increased survival and growth. As the sodium chloride concentration increased, the viability of rehydrated F. columnare decreased. ?? 2009 Elsevier Inc.

  15. Musicians show general enhancement of complex sound encoding and better inhibition of irrelevant auditory change in music: an ERP study.

    Science.gov (United States)

    Kaganovich, Natalya; Kim, Jihyun; Herring, Caryn; Schumaker, Jennifer; Macpherson, Megan; Weber-Fox, Christine

    2013-04-01

    Using electrophysiology, we have examined two questions in relation to musical training - namely, whether it enhances sensory encoding of the human voice and whether it improves the ability to ignore irrelevant auditory change. Participants performed an auditory distraction task, in which they identified each sound as either short (350 ms) or long (550 ms) and ignored a change in timbre of the sounds. Sounds consisted of a male and a female voice saying a neutral sound [a], and of a cello and a French Horn playing an F3 note. In some blocks, musical sounds occurred on 80% of trials, while voice sounds on 20% of trials. In other blocks, the reverse was true. Participants heard naturally recorded sounds in half of experimental blocks and their spectrally-rotated versions in the other half. Regarding voice perception, we found that musicians had a larger N1 event-related potential component not only to vocal sounds but also to their never before heard spectrally-rotated versions. We therefore conclude that musical training is associated with a general improvement in the early neural encoding of complex sounds. Regarding the ability to ignore irrelevant auditory change, musicians' accuracy tended to suffer less from the change in timbre of the sounds, especially when deviants were musical notes. This behavioral finding was accompanied by a marginally larger re-orienting negativity in musicians, suggesting that their advantage may lie in a more efficient disengagement of attention from the distracting auditory dimension. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. Multimodal Imaging and Choroidal Volumetric Changes After Half-fluence PDT in Central Serous Chorioretinopathy.

    Science.gov (United States)

    Munk, Marion R; Shah, Ronil; Pappas, Frankie; Baddar, Dina; Wong, Brandon; Jampol, Lee M; Fawzi, Amani A

    2016-01-01

    The purpose of this study was to identify SD-OCT changes that correspond to leakage on fluorescein (FA) and indocyanine angiography (ICGA) and evaluate effect of half-fluence photodynamic therapy (PDT) on choroidal volume in chronic central serous choroidoretinopathy (CSC). Retrospective analysis of patients with chronic CSC who had undergone PDT. Baseline FA and ICGA images were overlaid on SD-OCT to identify OCT correlates of FA or ICGA hyperfluorescence. Choroidal volume was evaluated in a subgroup of eyes before and after PDT. Twenty eyes were evaluated at baseline, of which seven eyes had choroidal volume evaluations at baseline and 3 months following PDT. SD-OCT changes corresponding to FA hyperfluorescence were subretinal fluid (73%), RPE microrip (50%), RPE double-layer sign (31%), RPE detachment (15%), and RPE thickening (8%). ICGA hyperfluoresence was correlated in 93% with hyperreflective spots in the superficial choroid. Choroidal volume decreased from 9.35 ± 1.99 to 8.52 ± 1.92 and 8.04 ± 1.7 mm(3) (at 1 and 3 months post PDT, respectively, p ≤ 0.001). We identified specific OCT findings that correlate with FA and ICGA leakage sites. SD-OCT is a valuable tool to localize CSC lesions and may be useful to guide PDT treatment. Generalized choroidal volume decrease occurs following PDT and extends beyond PDT treatment site.

  17. Monitoring Interstitial m-THPC-PDT In Vivo Using Fluorescence and Reflectance Spectroscopy

    NARCIS (Netherlands)

    Kruijt, Bastiaan; van der Ploeg-van den Heuvel, Angelique; de Bruijn, Henriette S.; Sterenborg, Henricus J. C. M.; Amelink, Arjen; Robinson, Dominic J.

    2009-01-01

    Background and Objective: In order to understand the mechanisms of photodynamic therapy (PDT) it is important to monitor parameters during illumination that yield information on deposited PDT dose. The aim of this study is to investigate the possibility of monitoring implicit parameters, such as

  18. Characterization of fetal keratinocytes, showing enhanced stem cell-like properties: a potential source of cells for skin reconstruction.

    Science.gov (United States)

    Tan, Kenneth K B; Salgado, Giorgiana; Connolly, John E; Chan, Jerry K Y; Lane, E Birgitte

    2014-08-12

    Epidermal stem cells have been in clinical application as a source of culture-generated grafts. Although applications for such cells are increasing due to aging populations and the greater incidence of diabetes, current keratinocyte grafting technology is limited by immunological barriers and the time needed for culture amplification. We studied the feasibility of using human fetal skin cells for allogeneic transplantation and showed that fetal keratinocytes have faster expansion times, longer telomeres, lower immunogenicity indicators, and greater clonogenicity with more stem cell indicators than adult keratinocytes. The fetal cells did not induce proliferation of T cells in coculture and were able to suppress the proliferation of stimulated T cells. Nevertheless, fetal keratinocytes could stratify normally in vitro. Experimental transplantation of fetal keratinocytes in vivo seeded on an engineered plasma scaffold yielded a well-stratified epidermal architecture and showed stable skin regeneration. These results support the possibility of using fetal skin cells for cell-based therapeutic grafting. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. G-Protein-Gated Inwardly Rectifying Potassium (GIRK) Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward

    Science.gov (United States)

    Tipps, Megan E.; Raybuck, Jonathan D.; Kozell, Laura B.; Lattal, K. Matthew; Buck, Kari J.

    2016-01-01

    Background G protein-coupled inwardly rectifying potassium (GIRK) channels contribute to the effects of a number of drugs of abuse, including ethanol. However, the roles of individual subunits in the rewarding effects of ethanol are poorly understood. Methods We compare conditioned place preference (CPP) in GIRK3 subunit knock-out (GIRK3−/−), heterozygote (GIRK3+/−), and wild-type (WT) mice. In addition, the development of locomotor tolerance/sensitization and the effects of ethanol intoxication on associative learning (fear conditioning) are also assessed. Results Our data show significant ethanol CPP in GIRK3−/− and GIRK3+/− mice, but not in the WT littermates. In addition, we demonstrate that these effects are not due to differences in ethanol metabolism, the development of ethanol tolerance/sensitivity, or associative learning abilities. While there were no consistent genotype differences in the fear conditioning assay, our data do show a selective sensitization of the impairing effects of ethanol intoxication on contextual learning, but no effect on cued learning. Conclusions These findings suggest that GIRK3 plays a role in ethanol reward. Further, the selectivity of this effect suggests that GIRK channels could be an effective therapeutic target for the prevention and/or treatment of alcoholism. PMID:27012303

  20. Sensitive detection of PDT-induced cell damages with luminescent oxygen nanosensors.

    Science.gov (United States)

    Ma, Hong-Ru; Peng, Hong-Shang; You, Fang-Tian; Ping, Jian-Tao; Zhou, Chao; Guo, Lan-Ying

    2016-07-28

    In this work luminescent nanosensors specifically created for intracellular oxygen (ic-O 2 ) were utilized to assess photodynamic therapy (PDT) -induced cell damages. Firstly, ic-O 2 was demonstrated to be consumed much faster than extracellular O 2 with respective O 2 nanosensors. Using the ic-O 2 nanosensors, PDT-treated cells with different degree of impairment were then resolved according to the oxygen consumption rate (OCR). The evolving trend of cytotoxicity derived from OCRs was in agreement with cell viability obtained from 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the direct damage of PDT on cell mitochondria was successfully detected by monitoring respiration instantly after PDT treatment, which is actually beyond the scope of MTT assay. These results suggest that fluorescence sensing of ic-O 2 -associated cell respiration is promising and even may become a standardized method, complementary to MTT assay, to evaluate PDT-induced cytotoxicity.

  1. Sensitive detection of PDT-induced cell damages with luminescent oxygen nanosensors

    Science.gov (United States)

    Ma, Hong-Ru; Peng, Hong-shang; You, Fang-tian; Ping, Jian-tao; Zhou, Chao; Guo, Lan-ying

    2016-09-01

    In this work luminescent nanosensors specifically created for intracellular oxygen (ic-O2) were utilized to assess photodynamic therapy (PDT) -induced cell damages. Firstly, ic-O2 was demonstrated to be consumed much faster than extracellular O2 with respective O2 nanosensors. Using the ic-O2 nanosensors, PDT-treated cells with different degree of impairment were then resolved according to the oxygen consumption rate (OCR). The evolving trend of cytotoxicity derived from OCRs was in agreement with cell viability obtained from 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the direct damage of PDT on cell mitochondria was successfully detected by monitoring respiration instantly after PDT treatment, which is actually beyond the scope of MTT assay. These results suggest that fluorescence sensing of ic-O2-associated cell respiration is promising and even may become a standardized method, complementary to MTT assay, to evaluate PDT-induced cytotoxicity.

  2. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers.

    Directory of Open Access Journals (Sweden)

    David Gonzalez

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα, Tcf4 and α-smooth muscle actin (α-SMA levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs, which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases.

  3. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers

    Science.gov (United States)

    Gonzalez, David; Contreras, Osvaldo; Rebolledo, Daniela L.; Espinoza, Juan Pablo; van Zundert, Brigitte

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM) components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα), Tcf4 and α-smooth muscle actin (α-SMA) levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs), which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF) signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases. PMID:28520806

  4. Eurasian jays do not copy the choices of conspecifics, but they do show evidence of stimulus enhancement

    Directory of Open Access Journals (Sweden)

    Rachael Miller

    2016-12-01

    Full Text Available Corvids (birds in the crow family are hypothesised to have a general cognitive tool-kit because they show a wide range of transferrable skills across social, physical and temporal tasks, despite differences in socioecology. However, it is unknown whether relatively asocial corvids differ from social corvids in their use of social information in the context of copying the choices of others, because only one such test has been conducted in a relatively asocial corvid. We investigated whether relatively asocial Eurasian jays (Garrulus glandarius use social information (i.e., information made available by others. Previous studies have indicated that jays attend to social context in their caching and mate provisioning behaviour; however, it is unknown whether jays copy the choices of others. We tested the jays in two different tasks varying in difficulty, where social corvid species have demonstrated social information use in both tasks. Firstly, an object-dropping task was conducted requiring objects to be dropped down a tube to release a food reward from a collapsible platform, which corvids can learn through explicit training. Only one rook and one New Caledonian crow have learned the task using social information from a demonstrator. Secondly, we tested the birds on a simple colour discrimination task, which should be easy to solve, because it has been shown that corvids can make colour discriminations. Using the same colour discrimination task in a previous study, all common ravens and carrion crows copied the demonstrator. After observing a conspecific demonstrator, none of the jays solved the object-dropping task, though all jays were subsequently able to learn to solve the task in a non-social situation through explicit training, and jays chose the demonstrated colour at chance levels. Our results suggest that social and relatively asocial corvids differ in social information use, indicating that relatively asocial species may have

  5. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

    Science.gov (United States)

    Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

    2018-01-02

    Cannabinoid CB1 receptors (CB1R) and serotonergic 2A receptors (5HT2AR) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB1R-5HT2AR heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na+ currents in patch clamp recordings. Interestingly, CB1R-5HT2AR heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB1R-5HT2AR heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

  6. Antimicrobial photodynamic therapy (aPDT) induction of biofilm matrix architectural and bioadhesive modifications.

    Science.gov (United States)

    Mang, Thomas; Rogers, Stephen; Keinan, David; Honma, Kiyonobu; Baier, Robert

    2016-03-01

    Dental implants are commonly used today for the treatment of partially and fully edentulous patients. Despite the high success rate they are not resistant to complications and failure due to a variety of problems including peri-implantitis or peri-mucositis due to bacterial biofilm formation on the implant surface. The use of non-surgical and surgical treatment procedure to promote healing in cases with peri-implantitis have limited efficacy. Here we studied the ability of photodynamic therapy to destroy a known bacterial pathogen and the extracellular matrix architecture of biofilm attached to titanium plates and germanium prisms. Titanium plates or germanium prisms were incubated for 24h with Fusobacterium nucleatum a fusiform, gram-negative bacterium was used to enable biofilm formation. Photodynamic therapy was carried out by incubating the biofilm samples on each substrata with porfimer sodium. Treatment was carried out using a diode laser at 630nm, 150mW/cm(2) for light doses ranging from 25-100J/cm(2). Evaluation of killing efficacy was done by counting colony forming units compared to controls. Multiple attenuated internal reflection-infrared spectroscopy (MAIR-IR) and SEM were used to analyze the samples pre and post PDT for validation. F. nucleatum was significantly reduced in a dose dependent manner by treatment with PDT. Changes in biofilm components and strength of bioadhesion were examined with MAIR-IR following jet impingement using calibrated water jets. SEM demonstrates significant morphological alterations in the bacteria, consistent with damage associated with exposure to reactive oxygen species. The results are indicative that aPDT is a method that can be used to eradicate micro-organisms associated with biofilm in peri-implantitis on relevant substrata. Data shows that the slime layer of the biofilm is removed and that further methods need to be employed to completely remove weakened or destroyed biofilm matrix components. Reactive oxygen

  7. Characterization of Pure Ductal Carcinoma In Situ on Dynamic Contrast-Enhanced MR Imaging: Do Nonhigh Grade and High Grade Show Different Imaging Features?

    Directory of Open Access Journals (Sweden)

    Siwa Chan

    2010-01-01

    Full Text Available To characterize imaging features of pure DCIS on dynamic contrast-enhanced MR imaging (DCE-MRI, 31 consecutive patients (37-81 years old, mean 56, including 2 Grade I, 16 Grade II, and 13 Grade III, were studied. MR images were reviewed retrospectively and the morphological appearances and kinetic features of breast lesions were categorized according to the ACR BI-RADS breast MRI lexicon. DCE-MRI was a sensitive imaging modality in detecting pure DCIS. MR imaging showed enhancing lesions in 29/31 (94% cases. Pure DCIS appeared as mass type or non-mass lesions on MRI with nearly equal frequency. The 29 MR detected lesions include 15 mass lesions (52%, and 14 lesions showing non-mass-like lesions (48%. For the mass lesions, the most frequent presentations were irregular shape (50%, irregular margin (50% and heterogeneous enhancement (67%. For the non-mass-like lesions, the clumped internal enhancement pattern was the dominate feature, seen in 9/14 cases (64%. Regarding enhancement kinetic curve, 21/29 (78% lesions showed suspicious malignant type kinetics. No significant difference was found in morphology (>.05, tumor size (P = 0.21, and kinetic characteristics (=.38 between non-high grade (I+II and high-grade (III pure DCIS.

  8. Fractionated aminolevulinic acid-photodynamic therapy provides additional evidence for the use of PDT for non-melanoma skin cancer

    NARCIS (Netherlands)

    de Haas, E. R. M.; de Vijlder, H. C.; Sterenborg, H. J. C. M.; Neumann, H. A. M.; Robinson, D. J.

    2008-01-01

    ?Background Photodynamic therapy (PDT) is an accepted treatment for superficial basal cel carcinoma (sBCC) and Bowens disease. In Rotterdam, extensive preclinical research has lead to an optimized twofold illumination scheme for aminolevulinic acid-PDT (ALA-PDT). Objective To provide additional

  9. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

    Science.gov (United States)

    Shirmanova, Marina; Yuzhakova, Diana; Snopova, Ludmila; Perelman, Gregory; Serebrovskaya, Ekaterina; Lukyanov, Konstantin; Turchin, Ilya; Subochev, Pavel; Lukyanov, Sergey; Kamensky, Vladislav; Zagaynova, Elena

    2015-01-01

    The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.

  10. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

    Directory of Open Access Journals (Sweden)

    Marina Shirmanova

    Full Text Available The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm and pulsed laser (584 nm, 10 Hz, 18 ns modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.

  11. Apoptotic effects of Photofrin-Diomed 630-PDT on SHEEC human esophageal squamous cancer cells.

    Science.gov (United States)

    Gao, Shegan; Zhang, Mengxi; Zhu, Xiaojuan; Qu, Zhifeng; Shan, Tanyou; Xie, Xuanhu; Wang, Ying; Feng, Xiaoshan

    2015-01-01

    Photodynamic therapy (PDT) using photofrin-II is a clinically effective treatment for both non-neoplastic and neoplastic diseases. Herein, we performed an in vitro experiment to study the anti-tumor effect and mechanisms of photofrin-II mediated PDT for esophageal squamous cell carcinoma (ESCC) cell line, SHEEC. In this study, human ESCC cell line SHEEC and parental normal cell line SHEE were used. The anti-tumor effect of PDT was determined by evaluating cell viability using CCK-8 assay, apoptosis and generation of reactive oxygen species (ROS). PDT induced significant apoptosis in SHEEC and SHEE cells in a time- and photofrin-II dose-dependent manner. Furthermore, PDT treatment induced significant death of SHEEC, instead of SHEE cells. The apoptotic outcome was accompanied by concurrent generation of ROS. In summary, PDT shed light on therapy of ESCC, functioning as a useful tool for ESCC clinical treatment, providing a better understanding of Photofrin-Diomed 630-PDT in SHEEC cells.

  12. SU-D-16A-07: Photobleaching Predicts Necrosis in Interstitial PDT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, M; Finlay, J; Liu, B; Zhu, T [University of Pennsylvania, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Dosimetry for PDT has proven to be a challenge thus far, and for prediction of PDT outcome, a singlet oxygen model based on fundamental photophysical parameters has been developed. Previously, the photobleaching effect of photosensitizers was taken into account in the singlet oxygen explicit dosimetry model; here we report of direct measurements of photobleaching in the same model to assess the conditions under which implicit dosimetry using photobleaching can serve as an intermediate surrogate for PDT damage. Methods: Fluorescence spectra were measured interstitially in sensitized mouse tumors prior to after irradiation via a cylindrical diffuser. Photobleaching was determined by the relative decrease in fluorescence amplitude from the initial pre-treatment measurement. Spectra were analyzed by singular value decomposition to determine the photosensitizer concentration. Different photosensitizers were used to see the effect of photobleaching on PDT outcome and the impact of fluence on photobleaching. The drugs used were BPD (at two drug-light intervals), HPPH, and Photofrin. PDT outcome was determined by tumor necrosis radii measured upon sectioning and staining of treated tumors. Results: Post-PDT photosentizer concentrations were compared to initial pre-PDT photosensitizer concentrations, and the decrease was greater with a higher fluence measured during treatment. Furthermore, photobleaching and necrosis radius were found to be positively correlated. The relationship between photobleaching and necrosis radius is sensitizer-dependent, however the differences among sensitizers can be understood in terms of their respective photophysical parameters. Conclusions: Photobleaching is predictive of PDT outcome, but a comprehensive singlet oxygen model, has the potential to further improve the prediction of PDT outcome and the understanding of implicit dosimetry.

  13. A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy

    Science.gov (United States)

    Mou, Juan; Lin, Tianquan; Huang, Fuqiang; Shi, Jianlin; Chen, Hangrong

    2017-01-01

    A new kind of green titania (G-TiO2-x) with obvious green color was facilely synthesized from black titania (B-TiO2-x) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth. Furthermore, since mitochondria are preferred subcellular organelles for PDT/PTT, G-TiO2-x was further designed to conjugate with triphenylphosphonium (TPP) ligand for mitochondria-targeted PDT/PTT to obtain precise cancer treatment. Attributing to the high mitochondria-targeting efficiency and simultaneously synergistic PDT/PTT, high phototherapeutic efficacy and safety with a much lower laser power density (980 nm, 0.72 W cm-2) and low materials dosage were achieved both in vitro and in vivo. In addition, negligible toxicity was found, indicating high biocompatibility. This novel G-TiO2-x could provide new strategies for future precise minimal/non-invasive tumor treatment. PMID:28529636

  14. Single treatment of low-risk basal cell carcinomas with pulsed dye laser-mediated photodynamic therapy (PDL-PDT) compared with photodynamic therapy (PDT): A controlled, investigator-blinded, intra-individual prospective study.

    Science.gov (United States)

    Čarija, Antoanela; Puizina-Ivić, Neira; Vuković, Dubravka; Mirić Kovačević, Lina; Čapkun, Vesna

    2016-12-01

    To compare a single treatment of PDL-PDT with PDT for BCCs in terms of efficacy, aesthetic outcome, and pain in patients with multiple BCCs. A prospective, controlled, intra-individual, investigator-blinded study was conducted on 15 patients with 62 BCCs. The BCCs on an individual patient were divided into two similarly-sized groups, and treated with PDT (630nm LED light source, fluence rate=30mW/cm 2 , total dose of 150J/cm 2 ) and 585 nm-PDL-PDT (spot size=7mm, fluence=10J/cm 2 , pulse duration=10ms, 10% overlap, three passes, and cooling). Primary outcomes were complete BCC regression at months 3 and 12. Secondary outcomes were pain immediately after treatment, and aesthetic outcome evaluated by a blinded investigator. No significant difference was found in the therapeutic effect between the two treatments (P=0.285). Complete regression of BCCs at 3-months follow-up occurred in 79% of the PDT treated area and 74% of the PDL-PDT area. At month 12, complete regression using PDT was 75% (95% confidence interval (CI) 0.55-0.89) compared to 59% (95% CI 0.41-0.75) for the PDL-PDT treated areas. Both treatments had low mean pain scores: 1.7 for PDT and 2.6 for PDL-PDT (P=0.049) and the aesthetic appearance was similar (P=0.763). A single treatment with three passes of PDL-PDT is effective in clearing BCCs, but the recurrence rate is higher than in case of conventional PDT. PDL-PDT is associated with low treatment related pain, has similar cosmetic advantages as PDT but it requires less treatment time. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy

    DEFF Research Database (Denmark)

    Bay, Christiane; Lerche, Catharina Margrethe; Ferrick, Bradford

    2017-01-01

    Importance: Skin pretreatment is recommended for adequate penetration of topical photosensitizing agents and subsequent protoporphyrin IX (PPIX) accumulation in photodynamic therapy (PDT). Objective: To compare the relative potential of different physical pretreatments to enhance PPIX fluorescence...... indicate relatively enhanced PDT response by AFXL pretreatment in diseased skin. Trial Registration: clinicaltrials.gov Identifier: NCT02372370....

  16. Acute myocardial infarction: serial cardiac MR imaging shows a decrease in delayed enhancement of the myocardium during the 1st week after reperfusion.

    Science.gov (United States)

    Ibrahim, Tareq; Hackl, Thomas; Nekolla, Stephan G; Breuer, Martin; Feldmair, Michael; Schömig, Albert; Schwaiger, Markus

    2010-01-01

    To evaluate the time course of delayed gadolinium enhancement of infarcted myocardium by using serial contrast agent-enhanced (CE) cardiac magnetic resonance (MR) images obtained during the acute, subacute, and chronic stages of infarction. The study protocol was reviewed and approved by the local ethics committee, and written informed consent was obtained. Seventeen patients with reperfused acute myocardial infarction (AMI) underwent cine and CE cardiac MR a median of 1, 7, 35, and 180 days after reperfusion. Infarct size determined on the basis of delayed enhancement MR imaging at different times was compared by using nonparametric tests and Bland-Altman analysis. Extent of myocardial enhancement was compared with single photon emission computed tomographic (SPECT) measures of infarct size with Spearman correlation. Regional myocardial enhancement extent and contractility were analyzed with nonparametric tests. Infarct size was 18.3% of total myocardial LV volume on day 1 after AMI and decreased to 12.9% on day 7, 11.3% on day 35, and 11.6% on day 180 (all P infarct size on day 7, as compared with day 1 enhancement size, declined by 57.1% within the epicardium and by 6.3% within the endocardium (both P Infarct size on day 7 showed only minor changes at subsequent imaging and yielded a high correlation with SPECT measurements of infarct size (r = 0.84). Infarct size on day 7 inversely correlated with long-term wall thickening (P infarction. Thus, timing of CE cardiac MR imaging is crucial for accurate measurement of myocardial infarct size early after AMI.

  17. mTHPC Mediated, Systemic Photodynamic Therapy (PDT) for Nonmelanoma Skin Cancers : Case and Literature Review

    NARCIS (Netherlands)

    Horlings, Rudolf K.; Terra, Jorrit B.; Witjes, Max J. H.

    2015-01-01

    Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat

  18. Preparation and Protonation of Fe2(pdt)(CNR)6, Electron-Rich Analogues of Fe2(pdt)(CO)6.

    Science.gov (United States)

    Zhou, Xiaoyuan; Barton, Bryan E; Chambers, Geoffrey M; Rauchfuss, Thomas B; Arrigoni, Federica; Zampella, Giuseppe

    2016-04-04

    The complexes Fe2(pdt)(CNR)6 (pdt(2-) = CH2(CH2S(-))2) were prepared by thermal substitution of the hexacarbonyl complex with the isocyanides RNC for R = C6H4-4-OMe (1), C6H4-4-Cl (2), Me (3). These complexes represent electron-rich analogues of the parent Fe2(pdt)(CO)6. Unlike most substituted derivatives of Fe2(pdt)(CO)6, these isocyanide complexes are sterically unencumbered and have the same idealized symmetry as the parent hexacarbonyl derivatives. Like the hexacarbonyls, the stereodynamics of 1-3 involve both turnstile rotation of the Fe(CNR)3 as well as the inversion of the chair conformation of the pdt ligand. Structural studies indicate that the basal isocyanide has nonlinear CNC bonds and short Fe-C distances, indicating that they engage in stronger Fe-C π-backbonding than the apical ligands. Cyclic voltammetry reveals that these new complexes are far more reducing than the hexacarbonyls, although the redox behavior is complex. Estimated reduction potentials are E1/2 ≈ -0.6 ([2](+/0)), -0.7 ([1](+/0)), and -1.25 ([3](+/0)). According to DFT calculations, the rotated isomer of 3 is only 2.2 kcal/mol higher in energy than the crystallographically observed unrotated structure. The effects of rotated versus unrotated structure and of solvent coordination (THF, MeCN) on redox potentials were assessed computationally. These factors shift the redox couple by as much as 0.25 V, usually less. Compounds 1 and 2 protonate with strong acids to give the expected μ-hydrides [H1](+) and [H2](+). In contrast, 3 protonates with [HNEt3]BAr(F)4 (pKa(MeCN) = 18.7) to give the aminocarbyne [Fe2(pdt)(CNMe)5(μ-CN(H)Me)](+) ([3H](+)). According to NMR measurements and DFT calculations, this species adopts an unsymmetrical, rotated structure. DFT calculations further indicate that the previously described carbyne complex [Fe2(SMe)2(CO)3(PMe3)2(CCF3)](+) also adopts a rotated structure with a bridging carbyne ligand. Complex [3H](+) reversibly adds MeNC to give [Fe2(pdt

  19. Treatment of lip florid papillomatosis with topical ALA-PDT combined with curettage: Outcome and safety.

    Science.gov (United States)

    Gao, Yang; Wang, Hai-Lin; Wang, Wen-Sheng; Liu, Jia; Lu, Yuan-Gang

    2016-09-01

    Photodynamic therapy (PDT) is a successful treatment in clinical practice. PDT is increasingly used to cure the patients with skin cancer, especially in the elder. The purpose of this study was to evaluate the treatment outcome and safety of PDT with aminolevulinic acid (5-ALA) combined with surgical curettage for lip florid papillomatosis. In this study, 4 cases of lip florid papillomatosis were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the warts were removed with the patient under local anesthesia. The depth of the ablation and curettage reached the dermal layer. Then, the first session of PDT was performed after 2days. Ten percent 5-ALA cream was applied to lesional skin with occlusive dressing for a 3-h incubation period and the lesions of warts were irradiated for 10min by using a 635-nm laser beam of 177mW/cm2 intensity. The ALA-PDT was repeated after 1 and 3 weeks and two other treatments applied if necessary. Follow-up evaluation was performed at our outpatient clinic at 3 and 6 months after completion of therapy. After three PDT sessions following surgical curettage, 3 patients were cured at 3 months off treatment, one cases relapsed, corresponding to a recurrent rate of 25%. There was no other recurrence at 6 months off treatment. The satisfaction rate of patients was 95% at 3 month and 100% at 6 months after treatment. The combined treatment of topical ALA-PDT and curettage was proven to be safe and effective in lip florid papillomatosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Efficacy of topical ALA-PDT combined with excision in the treatment of skin malignant tumor.

    Science.gov (United States)

    Lu, Yuan-gang; Wang, Yuan-yuan; Yang, Ya-dong; Zhang, Xing-cun; Gao, Yang; Yang, Yang; Zhang, Jun-bo; Li, Guo-ling

    2014-06-01

    Photodynamic therapy (PDT) is a successful treatment for non-melanoma skin cancers in clinical practice. In China, more and more doctors use PDT to cure the patients with skin cancer, especially in the elder. The purpose of this study was to evaluate the efficacy of topical PDT using aminolevulinic acid (5-ALA) combined with excision in the treatment of skin malignant tumor and its role in surgical improvements. A total of 58 cases including 32 cases of BCC, 13 cases of Bowen's disease, 8 cases of Paget's disease and 5 cases of SCC were included in this study. All cases were treated with topical ALA-PDT after surgery. Each tumor region was irradiated with 120 J/cm(2) using a 635-nm laser for 15 min. A total of 3 times of assisted ALA-PDT was applied after surgery. There was no recurrence in 6 months after treatment. Only 5 cases of Paget's disease and 2 cases of SCC experienced disease recurrence in 1 year. All patients were able to complete the treatment protocol, with well cosmetic results and no moderate adverse reactions. As an assistive therapy after tumor resection, ALA-PDT can reduce the excision range of the tumor lesions. However, its role in the reduction of recurrence rate remains to be further investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Nuclear medicine for photodynamic therapy in cancer: Planning, monitoring and nuclear PDT.

    Science.gov (United States)

    Kharroubi Lakouas, Dris; Huglo, Damien; Mordon, Serge; Vermandel, Maximilien

    2017-06-01

    Photodynamic therapy (PDT) is a modality with promising results for the treatment of various cancers. PDT is increasingly included in the standard of care for different pathologies. This therapy relies on the effects of light delivered to photosensitized cells. At different stages of delivery, PDT requires imaging to plan, evaluate and monitor treatment. The contribution of molecular imaging in this context is important and continues to increase. In this article, we review the contribution of nuclear medicine imaging in oncology to PDT for planning and therapeutic monitoring purposes. Several solutions have been proposed to plan PDT from nuclear medicine imaging. For instance, photosensitizer biodistribution has been evaluated with a radiolabeled photosensitizer or with conventional radiopharmaceuticals on positron emission tomography. The effects of PDT delivery have also been explored with specific SPECT or PET radiopharmaceuticals to evaluate the effects on cells (apoptosis, necrosis, proliferation, metabolism) or vascular damage. Finally, the synergy between photosensitizers and radiopharmaceuticals has been studied considering the Cerenkov effect to activate photosensitized cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. EGF targeted fluorescence molecular tomography as a predictor of PDT outcomes in pancreas cancer models

    Science.gov (United States)

    Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; Isabelle, Martin E.; O'Hara, Julia; Hasan, Tayyaba; Pogue, Brian W.

    2010-02-01

    Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm3 and both tumor volume and EGF binding were followed with MR-guided FMT.

  3. Transformation of Lettuce with rol ABC Genes: Extracts Show Enhanced Antioxidant, Analgesic, Anti-Inflammatory, Antidepressant, and Anticoagulant Activities in Rats.

    Science.gov (United States)

    Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Mirza, Bushra

    2017-03-01

    Lettuce is an edible crop that is well known for dietary and antioxidant benefits. The present study was conducted to investigate the effects of rol ABC genes on antioxidant and medicinal potential of lettuce by Agrobacterium-mediated transformation. Transgene integration and expression was confirmed through PCR and real-time RT-PCR, respectively. The transformed plants showed 91-102 % increase in total phenolic contents and 53-65 % increase in total flavonoid contents compared to untransformed plants. Total antioxidant capacity and total reducing power increased up to 112 and 133 % in transformed plants, respectively. Results of DPPH assay showed maximum 51 % increase, and lipid peroxidation assay exhibited 20 % increase in antioxidant activity of transformed plants compared to controls. Different in vivo assays were carried out in rats. The transgenic plants showed up to 80 % inhibition in both hot plate analgesic assay and carrageenan-induced hind paw edema test, while untransformed plants showed only 45 % inhibition. Antidepressant and anticoagulant potential of transformed plants was also significantly enhanced compared to untransformed plants. Taken together, the present work highlights the use of rol genes to enhance the secondary metabolite production in lettuce and improve its analgesic, anti-inflammatory, antidepressant, and anticoagulatory properties.

  4. PET/PDT theranostics: synthesis and biological evaluation of a peptide-targeted gallium porphyrin.

    Science.gov (United States)

    Bryden, Francesca; Savoie, Huguette; Rosca, Elena V; Boyle, Ross W

    2015-03-21

    The development of novel theranostic agents is an important step in the pathway towards personalised medicine, with the combination of diagnostic and therapeutic modalities into a single treatment agent naturally lending itself to the optimisation and personalisation of treatment. In pursuit of the goal of a molecular theranostic suitable for use as a PET radiotracer and a photosensitiser for PDT, a novel radiolabelled peptide-porphyrin conjugate targeting the α6β1-integrin has been developed. (69/71)Ga and (68)Ga labelling of an azide-functionalised porphyrin has been carried out in excellent yields, with subsequent bioconjugation to an alkyne-functionalised peptide demonstrated. α6β1-integrin expression of two cell lines has been evaluated by flow cytometry, and therapeutic potential of the conjugate demonstrated. Evaluation of the phototoxicity of the porphyrin-peptide theranostic conjugate in comparison to an untargeted control porphyrin in vitro, demonstrated significantly enhanced activity for a cell line with higher α6β1-integrin expression when compared with a cell line exhibiting lower α6β1-integrin expression.

  5. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    Science.gov (United States)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2011-03-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  6. The use of a novel intense pulsed light and heat source and ALA-PDT in the treatment of moderate to severe inflammatory acne vulgaris.

    Science.gov (United States)

    Gold, Michael H; Bradshaw, Virginia L; Boring, Molly M; Bridges, Tancy M; Biron, Julie A; Carter, Leitha N

    2004-01-01

    The use of lasers and noncoherent light sources is becoming more commonplace in the treatment of inflammatory acne vulgaris. Topical 5-aminolevulinic acid (ALA) is finding its niche as an enhancer to these laser and light sources. Twenty patients with moderate to severe inflammatory acne vulgaris were enrolled in a clinical trial to evaluate the efficacy of ALA-PDT with activation by a SkinStation LHE (Radiancy, Inc., Orangeburg, NY), a novel intense pulsed light (IPL) and heat source that emits 430-nm to 1100-nm radiation at 3 to 9 J/cm2 fluences. Patients were given topical ALA (Levulan Kerastick, Dusa Pharmaceuticals, Inc., Wilmington, MA) photosensitizing agent that remained in contact with skin for one hour before irradiation. Fifteen patients completed the trial and 12 responded to the treatment. Among respondents, reduction in active inflammatory acne lesions was, on average, 50.1% at the end of the 4-week treatment period, 68.5% 4 weeks after the final treatment, and 71.8% 12 weeks after the final treatment. ALA-PDT with IPL activation was well-tolerated by all patients. No treated lesion recurred at the end of the follow-up period. ALA-PDT with IPL activation is a treatment option for patients with moderate to severe inflammatory acne vulgaris.

  7. Effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilm in experimental primary and secondary endodontic infections.

    Science.gov (United States)

    Tennert, Christian; Feldmann, Katharina; Haamann, Edwina; Al-Ahmad, Ali; Follo, Marie; Wrbas, Karl-Thomas; Hellwig, Elmar; Altenburger, Markus J

    2014-11-04

    To determine the antibacterial effect of photodynamic Therapy on Enterococcus faecalis (E. faecalis) biofilms in experimentally infected human root canals in primary infections and endodontic retreatments. One hundred and sixty single-rooted extracted teeth with one root canal were prepared using ProTaper instruments. Seventy specimens were left without root canal filling and autoclaved. The root canals of another 70 specimens were filled with Thermafil and AH Plus and the root canal fillings were removed after 24 hours using ProTaper D files and plasma sterilized. The specimens were infected with a clinical isolate of E. faecalis for 72 hours. Samples were taken using sterile paper points to determine the presence of E. faecalis in the root canals. The specimens were randomly divided into groups according to their treatment with 20 teeth each and a control. In the PDT group the teeth were treated using PDT, consisting of the photosensitizer toluidine blue and the PDT light source at 635 nm. In the NaOCl (sodium hypochlorite) group the root canals were rinsed with 10 mL of 3% NaOCl. In the NaOCl-PDT group the root canals were rinsed with 10 mL of 3% of sodium hypochlorite and then treated with PDT. Samples were taken after treatments using sterile paper points. Additionally, remaining root canal filling material was recovered from the root canal walls. Survival fractions of the samples were calculated by counting colony-forming units. A one-way analysis of variance (ANOVA) was applied to the data to assess the effect of different treatment techniques. Antimicrobial treatment of root canals caused a significant reduction of bacterial load in all groups. NaOCl irrigation eliminated E. faecalis most effectively. PDT alone was less effective compared to NaOCl irrigation and the combination of NaOCl irrigation and PDT. CFU levels recovered from the filling material after NaOCl irrigation of the root canals were 10fold higher compared to PDT and the combination of Na

  8. Effect of hematoporphyrin monomethyl ether-mediated PDT on the mitochondria of canine breast cancer cells.

    Science.gov (United States)

    Li, H T; Song, X Y; Yang, C; Li, Q; Tang, Damu; Tian, W R; Liu, Y

    2013-12-01

    Hematoporphyrin monomethyl ether (HMME) is a promising porphyrin-related photosensitize for photodynamic therapy (PDT). There still remains unknown changes regarding the mitochondrial in canine breast cancer cells treated with HMME-PDT. The aim of this study is to investigate the effect of HMME-PDT on structure and dysfunction of mitochondrial in cancer cells. The experimental approach included an initial study on the uptake of HMME using microscopic observation of the HMME-treated cells, optimization of the PDT-induced cell death by the MTT assay. These cells were then treated with HMME and a He-Ne laser at the wavelength of 632.8 nm following our optimized condition. Examination of mitochondrial changes by observing the stained cells under light microscope, mitochjondrial membrane potential flow cytometry, measuring the Ca(2+), SOD/GSH activity, ATPase and MDA contents for the mitochondria functions. The kinetics of HMME uptake in CHMm cells was determined and its cytocolic instead of nuclear distribution was demonstrated. The dose of 16mM HMME-PDT combined with 2.8 J/cm(2) laser irradiation was had the maximal impact on cell viability. This treatment resulted in structural changes in mitochondria that were accompanied with the loss of mitochjondrial membrane potential. As a result, HMME-PDT increased mitochondrial ROS, inhibited the enzymatic activities of mitochondrial SOD and GSH-Px, abolished mitochondrial ability in the uptake and release of calcium, and decreased mitochondrial ATPase activity. The combination of these abnormalities led to accumulation of ROS in mitochondrial to high levels, which in turn contributed to HMME-PDT-induced damages of mitochondrial structure and mitochondrial dysfunction. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Liposomal delivery of ferrous chlorophyllin: A novel third generation photosensitizer for in vitro PDT of melanoma.

    Science.gov (United States)

    Gomaa, Iman; Sebak, Aya; Afifi, Nagia; Abdel-Kader, Mahmoud

    2017-06-01

    Cutaneous melanoma (CM) has substantially increased among Caucasian populations in the past few decades. This increased the number of CM deaths throughout the world. Pigmentation of melanoma reduces the efficacy of photodynamic therapy (PDT). Third generation photosensitizers (PSs) are characterized by improved targeting to the diseased tissue and reduced systemic side effects. This study is directed towards synthesis and characterization of liposomes encapsulating sodium ferrous chlorophyllin (Fe-CHL) and assessing its efficacy as a PS in PDT of melanoma. Phenylthiourea (PTU) was used as a melanin synthesis inhibitor. PDT has been applied on de-pigmented melanoma cells using liposomes-encapsulated Fe-CHL. Cell death mechanisms after PDT were evaluated. Treatment of melanoma cells with 200μM of PTU for 48h provided 49.9% melanin inhibition without significant cytotoxicity. Transmission electron microscope (TEM) results proved an increase in the cellular uptake of liposomes by increasing incubation period from 6 to 24h via endocytosis with preferential accumulation in the mitochondria and the nucleus. Following de-pigmentation, PDT was applied resulting in LC 50 of 18.20 and 1.77μM after 24 and 48h incubation with liposomes-encapsulated Fe-CHL respectively and exposure to 56.2J/cm 2 monochromatic red laser of wavelength of 652nm. Mechanism of cell death of Fe-CHL mediated PDT was found to be a combination of both apoptosis and necrosis. Liposomes could be efficiently employed as a potential sustained release delivery system in the Fe-CHL-mediated PDT of de-pigmented melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Enhancement of photodynamic therapy effect by temporally inhibiting infarction with anticoagulant heparin

    Science.gov (United States)

    Yang, Liyong; Zhao, Hongyou

    2008-12-01

    Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.

  11. Switchable PDT for reducing skin photosensitization by a NIR dye inducing self-assembled and photo-disassembled nanoparticles.

    Science.gov (United States)

    Zhang, Yifan; He, Lingyi; Wu, Jie; Wang, Kaikai; Wang, Juan; Dai, Weimin; Yuan, Ahu; Wu, Jinhui; Hu, Yiqiao

    2016-11-01

    Photodynamic therapy (PDT) is the combination of light and photosensitizer (PS) to kill tumor cells, which has the potential to meet many currently unmet medical needs. However, the whole body distribution and activatability by sunlight of photosensitizers to induce skin photosensitivity have limited the extensive clinic application of PDT. Herein, a novel strategy is presented to overcome these limitations by using a hydrophobic Near-infared (NIR) dye IR-780 iodide (IR780) to induce the self-assembly of albumin-PS conjugates, as a switchable PDT (Switch-PDT) agent. The PDT effect of PS is effectively inhibited by IR780 and recovered by NIR light irradiation in vitro. This quench/recovery strategy dose not sacrifice the anti-tumor ability in vivo, and the combined PDT and PTT (photothermal) effect contributes a very effective tumor inhibition rate of 100%. More importantly, the PDT effect is significantly suppressed after intravenous administration in mice or subcutaneous administration in rabbits as exhibited by the negligible skin response, while traditional PDT agent arouses severe skin erythema and edema. To the best of our knowledge, the switchable PDT is the first time to be used to eradicate the skin photosensitization of PS in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model.

    Science.gov (United States)

    Rizvi, Imran; Anbil, Sriram; Alagic, Nermina; Celli, Jonathan; Celli, Jonathan P; Zheng, Lei Zak; Palanisami, Akilan; Glidden, Michael D; Pogue, Brian W; Hasan, Tayyaba

    2013-01-01

    The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J cm(-2)). Three endpoints were used to evaluate treatment response: (1) Viability evaluated every 24 h for 5 days post-PDT; (2) Photobleaching assessed immediately post-PDT; and (3) Caspase-3 activation determined 24 h post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 and 1 μM BPD a reduction in irradiance from 150 to 0.5 mW cm(-2) is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning. © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.

  13. PDT Dose Parameters Impact Tumoricidal Durability and Cell Death Pathways in a 3D Ovarian Cancer Model

    Science.gov (United States)

    Rizvi, Imran; Anbil, Sriram; Alagic, Nermina; Celli, Jonathan P.; Zheng, Lei Zak; Palanisami, Akilan; Glidden, Michael D.; Pogue, Brian W.; Hasan, Tayyaba

    2013-01-01

    The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J/cm2). Three endpoints were used to evaluate treatment response: 1.) Viability evaluated every 24 hours for 5 days post-PDT; 2.) Photobleaching assessed immediately post-PDT; and 3.) Caspase-3 activation determined 24-hours post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 μM and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 μM and 1 μM BPD a reduction in irradiance from 150 mW/cm2 to 0.5 mW/cm2 is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning. PMID:23442192

  14. Our experience of PDT of cancer with two Russian-produced photosensitizers

    Science.gov (United States)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.

    1995-05-01

    Analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder, rectum,and other locations has been made. During 1992-1994 432 tumoral foci in 108 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect or they were not treated due to contraindications either because of sever accompanying diseases or because of old age. A number of the patients had PDT because of recurrences or intradermal metastases within one to two years after surgical, radial, or combined treatment. Two homemade preparations were used as photosensitizers: Photohem (hematoporphyrin derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were an American dye laser with argon laser pumping and homemade laser devices including a copper vapor laser-pumped dye laser, gas discharge unit, gold vapor laser for the Photohem sessions, wile for the Photosense sessions were used solid state lasers on yttrium aluminate. Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 90.7% of patients including complete regression of tumors in 52% and partial in 38.7%. Currently this new technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.

  15. Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

    Directory of Open Access Journals (Sweden)

    David J Marcus

    Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

  16. Fusion proteins of flagellin and the major birch pollen allergen Bet v 1 show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity.

    Science.gov (United States)

    Kitzmüller, Claudia; Kalser, Julia; Mutschlechner, Sonja; Hauser, Michael; Zlabinger, Gerhard J; Ferreira, Fatima; Bohle, Barbara

    2018-01-01

    Recombinant fusion proteins of flagellin and antigens have been demonstrated to induce strong innate and adaptive immune responses. Such fusion proteins can enhance the efficacy of allergen-specific immunotherapy. We sought to characterize different fusion proteins of flagellin and the major birch pollen allergen Bet v 1 for suitability as allergy vaccines. A truncated version of flagellin (NtCFlg) was genetically fused to the N- or C-terminus of Bet v 1. Toll-like receptor (TLR) 5 binding was assessed with HEK293 cells expressing TLR5. Upregulation of CD40, CD80, CD83, and CD86 on monocyte-derived dendritic cells from allergic patients was analyzed by using flow cytometry. The T cell-stimulatory capacity of the fusion proteins was assessed with naive and Bet v 1-specific T cells. IgE binding was tested in inhibition ELISAs and basophil activation tests. Mice were immunized with the fusion proteins in the absence and presence of aluminum hydroxide. Cellular and antibody responses were monitored. Murine antibodies were tested for blocking capacity in basophil activation tests. Both fusion proteins matured monocyte-derived dendritic cells through TLR5. Compared with Bet v 1, the fusion proteins showed stronger T cell-stimulatory and reduced IgE-binding capacity and induced murine Bet v 1-specific antibodies in the absence of aluminum hydroxide. However, only antibodies induced by means of immunization with NtCFlg fused to the C-terminus of Bet v 1 inhibited binding of patients' IgE antibodies to Bet v 1. Bet v 1-flagellin fusion proteins show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity and thus represent promising vaccines for birch pollen allergen-specific immunotherapy. However, the sequential order of allergen and adjuvant within a fusion protein determines its immunologic characteristics. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Threshold effects of PDT in the normal rat colon with ALA photosensitization

    Science.gov (United States)

    Messmann, Helmut; Mlkvy, Peter; Davies, Claire; MacRobert, Alexander J.; Bown, Stephen G.

    1995-03-01

    Early clinical results of PDT on colon tumors using up to 60 mg/kg ALA given orally (comparable to 30 mg/kg if given i.v.) with light doses of 50 J showed only superficial necrosis. We investigated whether this could be due to subthreshold tissue concentrations of Protoporphyrin IX (PP IX) or suboptimal light treatment schedules. Normal Wistar rats were sensitized with 25 - 400 mg/kg ALA given i.v. and irradiated with 100 mW red light at 630 nm (copper vapor pumped dye laser) 10 - 200 J delivered via a fiber placed touching the colon mucosa at laparotomy at the time of peak PP IX concentration (1 - 4 hours depending on the dose used). Animals were killed 3 days later and the diameter of mucosal necrosis measured. No lesion was seen with 25 mg/kg. Increasing the ALA dose from 50 - 400 mg/kg, the lowest light dose to produce a lesion of > 5 mm fell from 100 J to 25 J. If ALA doses for rats and humans are comparable (which is likely) these results suggest that the drug and light doses used clinically are close to the thresholds levels, so better clinical results may be achieved by increasing the value of one or both.

  18. Combination ALA-PDT and Ablative Fractional Er:YAG Laser (2,940 nm) on the Treatment of Severe Acne

    Science.gov (United States)

    Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei; Hamblin, Michael R.

    2014-01-01

    Background Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. Objective To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. Methods A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Results Significant reductions in acne score (P<0.01) were obtained at follow-up visits after 1, 3, 6, and 12 months. After 6 month, the lesions showed overall improvement in all of subjects (good to excellent in acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. Conclusions PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. PMID:24391075

  19. Ultrasound guided ablative-laser assisted photodynamic therapy of basal cell carcinoma (US-aL-PDT).

    Science.gov (United States)

    Smucler, Roman; Kriz, Martin; Lippert, Jan; Vlk, Marek

    2012-04-01

    With proper noninvasive ultrasound measurement of tumor depth, case selection for laser pre-ablation followed by PDT is possible. This combination of methods provides a less invasive approach to the treatment of BCC. Basal cell carcinoma (BCC) primarily affects the face, and, therefore, radical excision is problematic because of the possibility of poor aesthetic outcomes. Photodynamic therapy (PDT) offers an advantage in aesthetic outcomes, but topical PDT is only effective for tumors with a depth up to 2 mm. Seventy-five histologically verified BCCs from 67 patients were selected and divided into three therapeutic groups based on the tumor depth, which was determined by 20 MHz skin ultrasound. The three groups were: A/PDT), B/ 2-3 mm (Er:YAG laser ablation+PDT), and C/>3 mm (diode laser ablation+PDT). The treatment consisted of laser ablation (or no ablation) followed by the application of methyl-aminolevulinate (MAL) and a 3-h treatment period using an occlusive bandage. Subsequently, illumination with 630 nm (MAL-PDT) was performed. MAL-PDT was repeated 1-3 weeks after the first treatment. A clinical evaluation was performed after 6 months. A 100% clearance rate (CR) in the group with the deepest tumors was observed. In addition, a 94.7% CR occurred in the group with tumors 2-3 mm in depth, and an 81.2% CR was observed in the group with superficial tumors. With proper ultrasound case selection and laser ablation before MAL-PDT, the depth of a BCC lesion is not a limiting factor for PDT, and aesthetic outcomes are very good. Therefore, ultrasound-guided ablative laser-assisted PDT of BCC can be the method of choice, particularly in aesthetically challenging cases.

  20. Contribution of the nos-pdt operon to virulence phenotypes in methicillin-sensitive Staphylococcus aureus.

    Science.gov (United States)

    Sapp, April M; Mogen, Austin B; Almand, Erin A; Rivera, Frances E; Shaw, Lindsey N; Richardson, Anthony R; Rice, Kelly C

    2014-01-01

    Nitric oxide (NO) is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS) enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT) enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS) were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and potential

  1. Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin).

    Science.gov (United States)

    Tanaka, Mamoru; Kataoka, Hiromi; Yano, Shigenobu; Sawada, Takuya; Akashi, Haruo; Inoue, Masahiro; Suzuki, Shugo; Inagaki, Yusuke; Hayashi, Noriyuki; Nishie, Hirotada; Shimura, Takaya; Mizoshita, Tsutomu; Mori, Yoshinori; Kubota, Eiji; Tanida, Satoshi; Takahashi, Satoru; Joh, Takashi

    2016-07-26

    Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release.

  2. Novel carbohydrate-substituted metallo-porphyrazine comparison for cancer tissue-type specificity during PDT.

    Science.gov (United States)

    Horne, Tamarisk K; Cronjé, Marianne J

    2017-08-01

    A longstanding obstacle to cancer eradication centers on the heterogeneous nature of the tissue that manifests it. Variations between cancer cell resistance profiles often result in a survival percentage following classic therapeutics. As an alternative, photodynamic therapys' (PDT) unique non-specific cell damage mechanism and high degree of application control enables it to potentially deliver an efficient treatment regime to a broad range of heterogeneous tissue types thereby overcoming individual resistance profiles. This study follows on from previous design, characterization and solubility analyses of three novel carbohydrate-ligated zinc-porphyrazine (Zn(II)Pz) derivatives. Here we report on their PDT application potential in the treatment of five common cancer tissue types in vitro. Following analyses of metabolic homeostasis, toxicity and cell death induction, overall Zn(II)Pz-PDT proved comparably efficient between all cancer tissue populations. Differential localization patterns of Zn(II)Pz derivatives between cell types did not appear to influence the overall PDT effect. All cell types exhibited significant disruptions to mitochondrial activity and associated ATP production levels. Toxicity and chromatin structure profiles revealed indiscernible patterns of damage between Zn(II)Pz derivatives and cell type. The subtle differences observed between individual Zn(II)Pz derivatives is most likely due to a combination of carbohydrate moiety characteristics on energy transfer processes and associated dosage optimization requirements per tissue type. Collectively, this indicates that resistance profiles are negated to a significant extent by Zn(II)Pz-PDT making these derivatives attractive candidates for PDT applications across multiple tissue types and subtypes. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Contribution of the nos-pdt operon to virulence phenotypes in methicillin-sensitive Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    April M Sapp

    Full Text Available Nitric oxide (NO is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and

  4. Treatment of perianal condyloma acuminate with topical ALA-PDT combined with curettage: outcome and safety.

    Science.gov (United States)

    Lu, Yuan-gang; Yang, Ya-dong; Wu, Jin-jin; Lei, Xia; Cheng, Qiong-hui; He, Yang; Yang, Wen

    2012-03-01

    The purpose of this study was to evaluate the treatment outcome and safety of topical photodynamic therapy (PDT) with aminolevulinic acid (5-ALA) combined with surgical curettage for perianal condyloma acuminata. Condyloma acuminata is the most common sexually transmitted disease, with a high relapse rate, especially in the perianal area. The outcomes of many treatment methods for perianal genital warts are not satisfactory. In this study, 40 cases of perianal condyloma acuminata were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the warts were removed with the patient under local anesthesia. The depth of the ablation and curettage reached the dermal layer. Then, the first session of PDT was performed after 2 days. Ten percent 5-ALA cream was applied to lesional skin with occlusive dressing for a 3-h incubation period and the lesions of warts were irradiated for 10 min by using a 635-nm laser beam of 177 mW/cm(2) intensity. The ALA-PDT was repeated after 1 and 3 weeks. Follow-up evaluation was performed at our outpatient clinic at 1 and 3 months after completion of therapy. Before treatment and at each follow-up visit, the lesions were photographed; the treatment outcome was evaluated as recurrence rate, and patient satisfaction was surveyed. After three PDT sessions following surgical curettage, all 40 patients were cured and there was no recurrence at 1 month off treatment. At 3 months off treatment, six cases relapsed, corresponding to a recurrent rate of 15%. The satisfaction rate of patients was 100% at 1 month and 95% at 3 months after treatment. Combination of surgical curettage and topical PDT has been proven to be a safe and effective procedure, and may offer a wide clinical application for the treatment of perianal condyloma acuminata.

  5. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    Directory of Open Access Journals (Sweden)

    James E Norton

    Full Text Available We have previously shown that live-attenuated rabies virus (RABV-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1 to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1, on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1. We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV, rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3 focus forming units (ffu/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a

  6. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    Science.gov (United States)

    Norton, James E; Lytle, Andrew G; Shen, Shixue; Tzvetkov, Evgeni P; Dorfmeier, Corin L; McGettigan, James P

    2014-01-01

    We have previously shown that live-attenuated rabies virus (RABV)-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1) to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1), on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1). We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV), rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3) focus forming units (ffu)/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a single-dose RABV

  7. Magnetic nanoemulsions as drug delivery system for Foscan ®: Skin permeation and retention in vitro assays for topical application in photodynamic therapy (PDT) of skin cancer

    Science.gov (United States)

    Primo, Fernando L.; Michieleto, Leandro; Rodrigues, Marcilene A. M.; Macaroff, Patrícia P.; Morais, Paulo C.; Lacava, Zulmira G. M.; Bentley, Maria Vitória L. B.; Tedesco, Antonio C.

    2007-04-01

    In this work, we performed the synthesis and in vitro characterization of a new class of drug delivery system (DDS) denominated magnetic nanoemulsion (MNE). The association of colloidal nanoparticles with biocompatible magnetic fluids results in a new DDS for application in photodynamic therapy (PDT) and magnetic hyperthermia treatment. It works in a synergic manner with an expected enhancement in tumor damage after minimum drug doses, based on heat dissipation and/or light photosensitization. For this purpose, we investigated the permeation and retention in vitro model using Foscan ® as a photosensitizer incorporated in MNE using a Franz diffusion cell and a biological skin model in biomimetic conditions.

  8. Magnetic nanoemulsions as drug delivery system for Foscan[reg]: Skin permeation and retention in vitro assays for topical application in photodynamic therapy (PDT) of skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Primo, Fernando L. [Depto. de Quimica, Universidade de Sao Paulo, FFCLRP-USP, 14040-901, Ribeirao Preto-SP (Brazil); Michieleto, Leandro [Depto. de Quimica, Universidade de Sao Paulo, FFCLRP-USP, 14040-901, Ribeirao Preto-SP (Brazil); Rodrigues, Marcilene A.M. [Depto. de Quimica, Universidade de Sao Paulo, FFCLRP-USP, 14040-901, Ribeirao Preto-SP (Brazil); Macaroff, Patricia P. [Depto. de Quimica, Universidade de Sao Paulo, FFCLRP-USP, 14040-901, Ribeirao Preto-SP (Brazil); Morais, Paulo C. [Instituto de Fisica, Universidade de Brasilia, Nucleo de Fisica Aplicada, 70919-970 Brasilia-DF (Brazil); Lacava, Zulmira G.M. [Instituto de Ciencias Biologicas, Universidade de Brasilia, 70910-900 Brasilia -DF (Brazil); Bentley, Maria Vitoria L.B. [Depto. de Ciencias Farmaceuticas, Universidade de Sao Paulo, FCFRP, 14040-901 Ribeirao Preto-SP (Brazil); Tedesco, Antonio C. [Depto. de Quimica, Universidade de Sao Paulo, FFCLRP-USP, 14040-901, Ribeirao Preto-SP (Brazil)]. E-mail: atedesco@usp.br

    2007-04-15

    In this work, we performed the synthesis and in vitro characterization of a new class of drug delivery system (DDS) denominated magnetic nanoemulsion (MNE). The association of colloidal nanoparticles with biocompatible magnetic fluids results in a new DDS for application in photodynamic therapy (PDT) and magnetic hyperthermia treatment. It works in a synergic manner with an expected enhancement in tumor damage after minimum drug doses, based on heat dissipation and/or light photosensitization. For this purpose, we investigated the permeation and retention in vitro model using Foscan[reg] as a photosensitizer incorporated in MNE using a Franz diffusion cell and a biological skin model in biomimetic conditions.

  9. Safety evaluation of repeated intravenous infusion of sinoporphyrin with and without PDT in rats.

    Science.gov (United States)

    Shi, Rui; Lin, Xiaoqi; Zhang, Jingxuan; Jin, Hongtao; Wang, Aiping; Wei, Jinfeng

    2016-11-02

    Photodynamic therapy (PDT) is a promising antineoplastic modality in the oncology field. We assessed the safety of repeated intravenous administrations of sinoporphyrin, a porphyrin derivative, with and without illumination in rats. Toxicokinetic studies of single and multiple administrations of sinoporphyrin were also carried out. Sprague-Dawley rats were randomly assigned to the dark-toxicity and PDT groups. Animals in the dark toxicity group received an i.v. infusion of sinoporphyrin at 3 doses: 2 mg kg -1 , 6 mg kg -1 , and 18 mg kg -1 . The PDT group included 2 doses of sinoporphyrin (2 mg kg -1 and 18 mg kg -1 ), and the rats received 60 J of 630 nm laser illumination 24 h after photosensitizer infusion. The treatments were repeated every 7 days for 5 cycles and were followed by a 14-day recovery period. Systematic analyses were conducted at the end of treatment and recovery periods. Blood samples were obtained 5 min, 30 min, 2 h, 8 h, 24 h, 48 h, 72 h, and 96 h after the first and fifth treatments for toxicokinetic studies. Sinoporphyrin-PDT led to the death of one out of 270 rats; the dead animal had been treated with 18 mg kg -1 sinoporphyrin and died at the end of the fifth PDT treatment. Liver injury, the primary toxicity observed in the study, was identified using biochemical tests, necropsy, and histopathology. Elevated white blood cell and neutrophil counts were found in the rats in both the dark toxicity and PDT groups. Skin lesions at the illumination site were obvious in the PDT group. Pigment deposits were detected in multiple organs such as the liver, spleen, lymph nodes, and ovaries in the 6 mg kg -1 and 18 mg kg -1 groups. No other abnormalities were observed. The toxicokinetic parameters of single and multiple sinoporphyrin administrations were calculated and compared. Repeated sinoporphyrin administrations both alone and in combination with laser illumination were tolerable, and all toxicities were transient. The no observed adverse effect

  10. A Review of Three Commonly Used Herbs Which Enhance Memory and New Evidences Which Show Their Combination Could Improve Memory in Young Animals.

    Science.gov (United States)

    Hong, Fei; Wang, Liju; Wu, Sharon L; Tang, H C; Sha, Ou; Wai, Maria S M; Yew, David T

    2017-01-01

    This review looks into the herbs Gingko biloba, Polygala tenuifolia, and Lycii fructus for their widely studied neuroprotective properties. In particular, we investigated memory enhancing effect of these herbs, and their potential synergetic effect on memory with new data. Sixmonth treated mice demonstrated shorter escape latency in water maze and shorter arrival time in a consolidated memory task. Immunochemistry showed evident increase in superoxide dismutase activities in the prefrontal cortex, implying protection against free radicals during aging. Discrete increase of catecholaminergic neurons was found in the prefrontal cortex, hippocampus, corpus striatum, and midbrain, suggesting better memory and better control on mood and behavior. Necrotic cells in the brain decreased as indicated by immunocytochemistry of lactic dehydrogenase. Terminal deoxynucleotidyl transferase dUTP nick end labeling showed no apoptotic cells in most brain areas in high dose group. Biochemistry revealed increase of dopaminergic cells in treatment groups at prefrontal cortex, and in the hippocampus and cerebellum of the high dose group. Most 6-month groups showed increase of serotonin in all three areas. For the high dose group, GABA increased in the hippocampus but not prefrontal cortex, which would help induce sleep at night. Protein kinase C increased in most groups at prefrontal cortex, hippocampus and cerebellum, signifying increase of possible signal transduction pathways for memory or other nervous activations. Our results intimate that the interaction of the three herbs exerts beneficial effects on memory, associated cognitive function, and necrosis. Future investigations based on the present data shall aid development of clinically relevant medication. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin, Electroporation enhances antimicrobial photodynamic inactivation

    OpenAIRE

    de Melo, Wanessa de Cássia Martins Antunes; Lee, Alexander N; Perussi, Janice Rodrigues; Hamblin, Michael R.

    2013-01-01

    The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this...

  12. mTHPC mediated photodynamic therapy (PDT) of squamous cell carcinoma in the head and neck : A systematic review

    NARCIS (Netherlands)

    de Visscher, S. A. H. J.; Dijkstra, P. U.; Tan, I. B.; Roodenburg, J. L. N.; Witjes, M. J. H.

    Objective: Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC). To evaluate available evidence on the use of mTHPC (Foscan (R)) mediated PDT, we conducted a review of the literature. Materials and methods: A systematic review was

  13. Report on the National Survey of Photodynamic Therapy (PDT) for Gastric Cancer in Japan (a secondary publication).

    Science.gov (United States)

    Oinuma, Takeshi; Nakamura, Tetsuya; Nishiwaki, Yoshiro

    2016-06-29

    Background and Aims: A national survey of photodynamic therapy (PDT) was carried out in order to understand the present situation in Japan and the efficacy of PDT for gastric cancer. Materials and Methods: A questionnaire concerning with PDT was sent to all hospitals performing or previously performed PDT. The answers were collected and analyzed. An additional investigation about efficacy of PDT for gastric cancer was conducted for the main 3 hospitals. Results: In 18 of 19 responded hospitals, PDT was performed for 386 cases of superficial early gastric cancer and for 27 cases of advanced gastric cancer. In the 3 main hospitals, a complete response was achieved in 42 of 57 patients (73.7%) of superficial early gastric cancer not indicated for surgery or other endoscopic treatments such as endoscopic submucosal dissection. No serious complication occurred. Conclusions: PDT has been shown to be a safe and effective treatment for early gastric cancer, not only for the intramucosal type, but also for the submucosal invasion. PDT will be one of the important endoscopic treatments for gastric cancer especially in a super ageing society like Japan.

  14. Genome-wide analysis of AP2/ERF family genes from Lotus corniculatus shows LcERF054 enhances salt tolerance.

    Science.gov (United States)

    Sun, Zhan-Min; Zhou, Mei-Liang; Xiao, Xing-Guo; Tang, Yi-Xiong; Wu, Yan-Min

    2014-09-01

    Lotus corniculatus is used in agriculture as a main forage plant. Members of the Apetala2/ethylene response factor (AP2/ERF) family play important roles in regulating gene expression in response to many forms of stress, including drought and salt. Here, starting from database of the L. corniculatus var. japonicus genome, we identified 127 AP2/ERF genes by insilico cloning method. The phylogeny, gene structures, and putative conserved motifs in L. corniculatus var. japonicus ERF proteins were analyzed. Based on the number of AP2/ERF domains and the function of the genes, 127 AP2/ERF genes from L. corniculatus var. japonicus were classified into five subfamilies named the AP2, dehydration-responsive element binding factor (DREB), ERF, RAV, and a soloist. Outside the AP2/ERF domain, many L. corniculatus var. japonicus-specific conserved motifs were detected. Expression profile analysis of AP2/ERF genes by quantitative real-time PCR revealed that 19 LcERF genes, including LcERF054 (KJ004728), were significantly induced by salt stress. The results showed that the LcERF054 gene encodes a nuclear transcription activator. Overexpression of LcERF054 in Arabidopsis enhanced the tolerances to salt stress, showed higher germination ratio of seeds, and had elevated levels of relative moisture contents, soluble sugars, proline, and lower levels of malondialdehyde under stress conditions compared to wild-type plants. The expression of hyperosmotic salinity response genes COR15A, LEA4-5, P5CS1, and RD29A was found to be elevated in the LcERF054-overexpressing Arabidopsis plants compared to wild type. These results revealed that the LcERF genes play important roles in L. corniculatus cv Leo under salt stress and that LcERFs are attractive engineering targets in applied efforts to improve abiotic stress tolerances in L. corniculatus cv Leo or other crops.

  15. Hydrogen bonding motifs, spectral characterization, theoretical computations and anticancer studies on chloride salt of 6-mercaptopurine: An assembly of corrugated lamina shows enhanced solubility

    Science.gov (United States)

    Suresh Kumar, S.; Athimoolam, S.; Sridhar, B.

    2015-10-01

    6-Mercaptopurine (an anti cancer drug), is coming under the class II Biopharmaceutics Classification System (BCS). In order to enhance the solubility with retained physiochemical/pharmaceutical properties, the present work was attempted with its salt form. The single crystals of 6-mercaptopurinium chloride (6MPCl) were successfully grown by slow evaporation technique under ambient temperature. The X-ray diffraction study shows that the crystal packing is dominated by N-H⋯Cl classical hydrogen bonds leading to corrugated laminar network. The hydrogen bonds present in the lamina can be dismantled as three chain C21(6), C21(7) and C21(8) motifs running along ab-diagonal of the unit cell. These primary chain motifs are interlinked to each other forming ring R63(21) motifs. These chain and ring motifs are aggregated like a dendrimer structure leading to the above said corrugated lamina. This low dimensional molecular architecture differs from the ladder like arrays in pure drug though it possess lattice water molecule in lieu of the chloride anion in the present compound. Geometrical optimizations of 6MPCl were done by Density Functional Theory (DFT) using B3LYP function with two different basis sets. The optimized molecular geometries and computed vibrational spectra are compared with their experimental counterparts. The Natural Bond Orbital (NBO) analysis was carried out to interpret hyperconjugative interaction and Intramolecular Charge Transfer (ICT). The chemical hardness, electronegativity, chemical potential and electrophilicity index of 6MPCl were found along with the HOMO-LUMO plot. The lower band gap value obtained from the Frontier Molecular Orbital (FMO) analysis reiterates the pharmaceutical activity of the compound. The anticancer studies show that 6MPCl retains its activity against human cervical cancer cell line (HeLa). Hence, this anticancer efficacy and improved solubility demands 6MPCl towards the further pharmaceutical applications.

  16. The Peripheral Detection Task (PDT) : On-line measurement of driver cognitive workload and selective attention

    NARCIS (Netherlands)

    Horst, A.R.A. van der; Martens, M.H.

    2010-01-01

    Peaks in workload while driving might have immediate safety implications. The Peripheral Detection Task (PDT) has shown to be a sensitive objective workload measure. Drivers have to respond to the onset of a peripherally presented simple visual stimulus (red square or LED) by pressing a finger

  17. In-vitro singlet oxygen threshold dose at PDT with Radachlorin photosensitizer

    Science.gov (United States)

    Klimenko, V. V.; Shmakov, S. V.; Kaydanov, N. E.; Knyazev, N. A.; Kazakov, N. V.; Rusanov, A. A.; Bogdanov, A. A.; Dubina, M. V.

    2017-07-01

    In this present study we investigate the Radachlorin photosensitizer accumulation in K562 cells and Hela cells and determined the cell viability after PDT. Using the macroscopic singlet oxygen modeling and cellular photosensitizer concentration the singlet oxygen threshold doses for K562 cells and Hela cells were calculated.

  18. Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an (18)F-Radiolabeled Water-Soluble Porphyrin.

    Science.gov (United States)

    Entract, Guy M; Bryden, Francesca; Domarkas, Juozas; Savoie, Huguette; Allott, Louis; Archibald, Stephen J; Cawthorne, Chris; Boyle, Ross W

    2015-12-07

    Synthesis of the first water-soluble porphyrin radiolabeled with fluorine-18 is described: a new molecular theranostic agent which integrates the therapeutic selectivity of photodynamic therapy (PDT) with the imaging efficacy of positron emission tomography (PET). Generation of the theranostic was carried out through the conjugation of a cationic water-soluble porphyrin bearing an azide functionality to a fluorine-18 radiolabeled prosthetic bearing an alkyne functionality through click conjugation, with excellent yields obtained in both cold and hot synthesis. Biological evaluation of the synthesized structures shows the first example of an (18)F-radiolabeled porphyrin retaining photocytotoxicity following radiolabeling and demonstrable conjugate uptake and potential application as a radiotracer in vivo. The promising results gained from biological evaluation demonstrate the potential of this structure as a clinically relevant theranostic agent, offering exciting possibilities for the simultaneous imaging and photodynamic treatment of tumors.

  19. Human Wharton's jelly-derived mesenchymal stromal cells engineered to secrete Epstein-Barr virus interleukin-10 show enhanced immunosuppressive properties.

    Science.gov (United States)

    Quaranta, Paola; Focosi, Daniele; Di Iesu, Marilena; Cursi, Chiara; Zucca, Alessandra; Curcio, Michele; Lapi, Simone; Boldrini, Linda; Stampacchia, Giulia; Paolicchi, Aldo; Scatena, Fabrizio; Freer, Giulia; Pistello, Mauro

    2016-02-01

    Mesenchymal stromal cells (MSCs) modulate the immune response and represent a potential treatment for inflammatory and autoimmune diseases. We hypothesized that this feature could be potentiated by co-administering anti-inflammatory cytokines. In this article, we asked whether engineering of Wharton Jelly-derived human MSCs (WJ-hMSCs) to express an anti-inflammatory cytokine increases cell immunomodulatory properties without altering their native features. We used Epstein-Barr virus-derived interleukin-10 (vIL-10), which shares some immunosuppressive properties with human IL-10 but lacks immunostimulatory activity. Engineering was accomplished by transducing WJ-hMSCs with a self-inactivating feline immunodeficiency virus-derived vector co-expressing vIL-10 and herpes simplex virus type-1 thymidine kinase (TK). TK was added to allow future tracking of WJ-hMSC in vivo by positron electron tomography (PET). The results show that (i) expression of TK and/or vIL-10 does not change WJ-hMSC phenotypic and functional properties; (ii) vIL-10 is secreted, biologically active and enhances the immunosuppressing functions of WJ-hMSCs; (iii) v-IL10 and TK can be produced simultaneously by the same cells and do not interfere with each other. WJ-hMSCs engineered to secrete vIL-10 could be a powerful tool for adoptive cell therapy of immune-mediated diseases, and therefore, additional studies are warranted to confirm their efficacy in suitable animal disease models. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. PDT-induced epigenetic changes in the mouse cerebral cortex: a protein microarray study.

    Science.gov (United States)

    Demyanenko, S V; Uzdensky, A B; Sharifulina, S A; Lapteva, T O; Polyakova, L P

    2014-01-01

    Photodynamic therapy (PDT) is used for cancer treatment including brain tumors. But the role of epigenetic processes in photodynamic injury of normal brain tissue is unknown. 5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), was used to photosensitize mouse cerebral cortex. PpIX accumulation in cortical tissue was measured spectrofluorometrically. Hematoxylin/eosin, gallocyanin-chromalum and immunohistochemical staining were used to study morphological changes in PDT-treated cerebral cortex. Proteomic antibody microarrays were used to evaluate expression of 112 proteins involved in epigenetic regulation. ALA administration induced 2.5-fold increase in the PpIX accumulation in the mouse brain cortex compared to untreated mice. Histological study demonstrated PDT-induced injury of some neurons and cortical vessels. ALA-PDT induced dimethylation of histone H3, upregulation of histone deacetylases HDAC-1 and HDAC-11, and DNA methylation-dependent protein Kaiso that suppressed transcriptional activity. Upregulation of HDAC-1 and H3K9me2 was confirmed immunohistochemically. Down-regulation of transcription factor FOXC2, PABP, and hBrm/hsnf2a negatively regulated transcription. Overexpression of phosphorylated histone H2AX indicated activation of DNA repair, but down-regulation of MTA1/MTA1L1 and PML - impairment of DNA repair. Overexpression of arginine methyltransferase PRMT5 correlated with up-regulation of transcription factor E2F4 and importin α5/7. ALA-PDT injures and kills some but not all neurons and caused limited microvascular alterations in the mouse cerebral cortex. It alters expression of some proteins involved in epigenetic regulation of transcription, histone modification, DNA repair, nuclear protein import, and proliferation. These data indicate epigenetic markers of photo-oxidative injury of normal brain tissue. © 2013.

  1. A review of photodynamic therapy (PDT) for the treatment of acne vulgaris.

    Science.gov (United States)

    Riddle, Christy C; Terrell, Shaundre N; Menser, Molly B; Aires, Daniel J; Schweiger, Eric S

    2009-11-01

    Photodynamic therapy (PDT) is increasing in dermatology. Antibiotic resistance and the challenges of isotretinoin therapy have led to investigation of PDT in the treatment of acne vulgaris. To review the results of clinical trials and case series with respect to light source, topical photosensitizing agent, adverse events, efficacy and skin type. A non-critical review is presented of a PubMed search for studies examining PDT in the treatment of acne vulgaris. The authors found 21 clinical trials and case series of various designs. Eight studies employed a split-face design comparing photosensitizer to placebo, no treatment or another photosensitizer. Two trials used three test spots and one control spot per patient. Three studies utilized control subjects receiving no photosensitizer with or without light therapy. All 21 studies reported a reduction in inflammatory lesions and/or a significant improvement in acne. The light sources utilized included blue light, pulsed-dye laser (PDL), intense pulsed light (IPL) and red light. Studies comparing the use of PDT to light therapy alone demonstrated greater improvement in treatment groups pretreated with a photosensitizer. All studies reported reduction in inflammatory lesions or significant improvement in acne. Several studies confirm a light source combined with photosensitizer is superior to light alone. Adverse reactions including photosensitivity, pustular eruptions, and crusting varied among photosensitizers and light sources. PDT appears to be a useful therapeutic option for acne patients who are recalcitrant to standard treatments and poor candidates for systemic retinoids. Further studies are still needed before a consensus protocol can be established. Additional investigations are needed to establish optimal incubation time, activating light source and frequency of treatment.

  2. Metronomic photodynamic therapy (mPDT) for intracranial neoplasm: physiological, biological, and dosimetry considerations

    Science.gov (United States)

    Bisland, Stuart L.; Lilge, Lothar; Lin, Annie; Wilson, Brian C.

    2003-10-01

    Metronomic photodynamic therapy (mPDT), a procedure in which both the photosensitizer and light are delivered continuously so that the individual doses overlap pharmacologically is introduced. The fundamental hypothesis in mPDT is that by providing therapy at low fluence over extended periods of time, there is potential for improved selectivity in tumor cell kill through non necrotic pathways. This is especially important in the treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PiIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue nor apoptosis in the latter. However, in order to achieve tumor control, multiple PDT treatments, such as hyper fractionation or metronomic delivery, are required, where the frequency and duration of the treatment are determined by the levels of apoptosis achieved in relationship to tumor cell doubling times, mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery at a sufficiently high enough density to achieve low fluence exposure to the brain adjacent to tumor or the entire hemisphere. In a rat model we evaluated the feasibility of delivering sustained ALA administration via the drinking water for up to 10 days without loss of PPIX selectivity. Post mortem quantitative spectrofluorimetry of tumor, normal brain and other tissues demonstrates a 4 times higher PPIX concentration in the 9L gliosarcoma model without noticeable toxicity. Light sources and delivery devices based either on laser diode or light emitting diode (LED) coupled to an implanted optical fiber were shown to be feasible. The maximum permissible spacing of cylindrical isotropic emitters is determined using known apoptotic indices and the necrosis

  3. Metronomic photodynamic therapy (mPDT): concepts and technical feasibility in brain tumor

    Science.gov (United States)

    Wilson, Brian C.; Bisland, Stuart K.; Bogaards, Arjen; Lin, Annie; Moriyama, Eduardo H.; Zhang, Kai; Lilge, Lothar D.

    2003-06-01

    The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are delivered continuously at low rates over extended periods in order to increase selective tumor cell kill through apoptosis. The focus of the present work is on mPDT treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue or apoptosis in the latter. In order to produce enough tumor cell kill to be an effective therapy, multiple PDT treatments, such as hyperfractionation or metronomic delivery, are likely requried, based on the levels of apoptosis achieved and model calculations of tumor growth rates. mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery while allowing free movement. In rat models ALA administration via the drinking water has been accomplished at significant doses for up to 10 days, and ex vivo spectrofluorimetry of tumore, normal brain and other tissues post mortem demonstrates a 3-4 increase in the tumor-to-brain concentration of PpIX, without toxicity. Prototype light sources and delivery devices are also shown to be practical, either using a laser diode or light emitting diode (LED) coupled to an implanted optical fiber in the case of the rat model or a directly-implanted LED in rabbits. The combined delivery of both drug and light over an extended period, with survival of the animals, is demonstrated. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.

  4. Exploiting biosynthetic gold nanoparticles for improving the aqueous solubility of metal-free phthalocyanine as biocompatible PDT agent.

    Science.gov (United States)

    Alexeree, Shaimaa M I; Sliem, Mahmoud A; El-Balshy, Ragaa M; Amin, Rehab M; Harith, M A

    2017-07-01

    Increasing the limit of dispersion of metal-free phthalocyanine (H2Pc) in an aqueous medium using biosynthetic gold nanoparticles for photodynamic therapy (PDT) is investigated. Gold nanoparticles (Au NPs) are biosynthesized in one step using Potatoes (Solanum tuberosum) extract and are characterized by UV/VIS spectrophotometry, Fourier transformer infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). The metal-free phthalocyanine is conjugated to the surface of the gold nanoparticles in a side to side regime through the secondary amine groups of H2Pc. The clear violet solution of phthalocyanine-gold (Pc-Au) nanoconjugates is investigated by UV-VIS, FTIR and TEM techniques. Disappearance of the absorption band of the secondary amine in the Pc-Au nanoconjugates compared to that of the parent H2Pc, and detection of the absorption band of H2Pc in the aqueous medium confirmed the dispersion of H2Pc and consequently the loading of H2Pc on the surface of Au NPs. The cytotoxic effect of biosynthetic gold nanoparticles and Pc-Au nanoconjugates compared to chemically synthesized gold nanoparticles on buffalo epithelial cells has been studied in vitro. Interestingly, the results showed that the biosynthetic Au NPs as well as Pc-Au nanoconjugates have no effect on buffalo epithelial cells viability, which indicating their biocompatibility contrary to the chemically synthesized Au NPs. This work will open the door, for the first time, for using H2Pc suspended in water for PDT and other phototherapeutic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer.

    Science.gov (United States)

    Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M; Busch, Theresa M; Cengel, Keith A

    2012-12-01

    Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT-mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT-mediated activation of EGFR were also observed in response to BPD-mediated PDT in multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and was observed to occur in response to porfimer sodium-mediated PDT. In addition, we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR association and that inhibiting STAT3 signaling prior to PDT leads to increased PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to increased PDT cytotoxicity through a mechanism that involves increased apoptotic cell death. Taken together, these results demonstrate that PDT stimulates the nuclear accumulation of both EGFR and STAT3 and that targeting these survival pathways is a potentially promising strategy that could be adapted for clinical trials of PDT for patients with serosal spread of malignancy.

  6. Full macular translocation versus photodynamic therapy with verteporfin in the treatment of neovascular age-related macular degeneration: 1-year results of a prospective, controlled, randomised pilot trial (FMT-PDT).

    Science.gov (United States)

    Gelisken, Faik; Voelker, Michael; Schwabe, Rainer; Besch, Dorothea; Aisenbrey, Sabine; Szurman, Peter; Grisanti, Salvatore; Herzau, Volker; Bartz-Schmidt, Karl U

    2007-08-01

    The purpose of this study was to compare full macular translocation (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related macular degeneration (AMD). In a prospective, randomised, non-masked, mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or PDT. Baseline and control examinations in 3-monthly intervals over a 12-month period included standardized protocol refraction, visual acuity testing and fluorescein angiography. Primary outcome measurements were made to establish the change in distant visual acuity from the baseline to the 12-month examination. The statistical analyses were carried out on the intent-to-treat principle. The improvement of one or more ETDRS lines was 56% (14/25) of the eyes in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five patients) were recorded in the FMT group. None of the eyes treated in the FMT group had phtysis. This pilot study showed that no statistically significant difference existed between the FMT and PDT in terms of the vision loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of vision improvement was significantly higher for the patients in the FMT group. However, in the era of promising therapy with anti-vascular endothelial growth factor for neovascular AMD, FMT should not be offered as a standard primary procedure for neovascular AMD.

  7. Real-time treatment light dose guidance of Pleural PDT: an update

    Science.gov (United States)

    Zhu, Timothy C.; Kim, Michele M.; Jacques, Steve L.; Penjweini, Rozhin; Dimofte, Andreea; Finlay, Jarod C.; Simone, Charles B.; Cengel, Keith A.; Friedberg, Joseph

    2015-01-01

    The goal of this study was to develop and improve an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, several detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. Monte-Carlo simulation is used to improve the calculation algorithm for the effect of light that undergoes multiple scattering along the surface in addition to an improvement of the direct light calculation using an improved model that accounts for the anisotropy of the light from the light source. PMID:25999654

  8. Quantitative optical diagnostics in pathology recognition and monitoring of tissue reaction to PDT

    Science.gov (United States)

    Kirillin, Mikhail; Shakhova, Maria; Meller, Alina; Sapunov, Dmitry; Agrba, Pavel; Khilov, Alexander; Pasukhin, Mikhail; Kondratieva, Olga; Chikalova, Ksenia; Motovilova, Tatiana; Sergeeva, Ekaterina; Turchin, Ilya; Shakhova, Natalia

    2017-07-01

    Optical coherence tomography (OCT) is currently actively introduced into clinical practice. Besides diagnostics, it can be efficiently employed for treatment monitoring allowing for timely correction of the treatment procedure. In monitoring of photodynamic therapy (PDT) traditionally employed fluorescence imaging (FI) can benefit from complementary use of OCT. Additional diagnostic efficiency can be derived from numerical processing of optical diagnostics data providing more information compared to visual evaluation. In this paper we report on application of OCT together with numerical processing for clinical diagnostic in gynecology and otolaryngology, for monitoring of PDT in otolaryngology and on OCT and FI applications in clinical and aesthetic dermatology. Image numerical processing and quantification provides increase in diagnostic accuracy. Keywords: optical coherence tomography, fluorescence imaging, photod

  9. Overview of computational simulations for PDT treatments based on optimal choice of singlet oxygen

    Science.gov (United States)

    Beeson, Karl; Parilov, Evgueni; Potasek, Mary

    2017-02-01

    Effective photodynamic therapy (PDT) treatment planning and treatment monitoring requires computer simulations of both light transport in tissue and photosensitizer (PS) photophysics to accurately estimate singlet oxygen. Simply using fixed prescribed values of light dose (fluence) or PDT dose (the time integral of `PS concentration' times the `fluence rate') - one value for all patients - does not account for differences in the amount of singlet oxygen formed when fluence rates change or patient tissue parameters change. We will focus on singlet oxygen dose which is calculated by solving the photokinetics rate equations and which determines the effectiveness of the subsequent reactions of singlet oxygen with the cancer target and the negative effect of PS photobleaching.

  10. On the in vivo photochemical rate parameters for PDT reactive oxygen species modeling

    Science.gov (United States)

    Kim, Michele M.; Ghogare, Ashwini A.; Greer, Alexander; Zhu, Timothy C.

    2017-03-01

    Photosensitizer photochemical parameters are crucial data in accurate dosimetry for photodynamic therapy (PDT) based on photochemical modeling. Progress has been made in the last few decades in determining the photochemical properties of commonly used photosensitizers (PS), but mostly in solution or in vitro. Recent developments allow for the estimation of some of these photochemical parameters in vivo. This review will cover the currently available in vivo photochemical properties of photosensitizers as well as the techniques for measuring those parameters. Furthermore, photochemical parameters that are independent of environmental factors or are universal for different photosensitizers will be examined. Most photosensitizers discussed in this review are of the type II (singlet oxygen) photooxidation category, although type I photosensitizers that involve other reactive oxygen species (ROS) will be discussed as well. The compilation of these parameters will be essential for ROS modeling of PDT.

  11. The potential of photodynamic therapy (PDT)-Experimental investigations and clinical use.

    Science.gov (United States)

    Oniszczuk, Anna; Wojtunik-Kulesza, Karolina A; Oniszczuk, Tomasz; Kasprzak, Kamila

    2016-10-01

    Photodynamic therapy (PDT) is an intensively studied part of medicine based on free radicals. These reactive species, extremely harmful for whole human organism, are used for eradication numerous diseases. Specific structure of ill tissues causes accumulation free radicals inside them without attack remaining healthy tissues. A rapid development of medicine and scientific research has led to extension of PDT towards treatment many diseases such as cancer, herpes, acne and based on antimicrobials. The presented review article is focused on the aforementioned disorders with accurate analysis of the newest available scientific achievements. The discussed cases explicitly indicate on high efficacy of the therapy. In most cases, free radicals turned out to be solution of many afflictions. Photodynamic therapy can be considered as promising treatment with comparable effectiveness but without side effects characteristic for chemotherapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. An update on the regulatory status of PDT photosensitizers in China.

    Science.gov (United States)

    Huang, Zheng

    2008-12-01

    Numerous photosensitizers have been developed and evaluated in China. HiPorfin, a hematoporphyrin derivative (HpD) received the first regulatory approval in the early 2000s. Aila, a topical formulation containing predrug 5-aminolevulinic acid, received the regulatory approval in 2007. Recently, new drug applications have been filed for several hematoporphyrin derivatives and a zinc phthalocyanine (ZnPc) derivative. This short report will summarize the current regulatory status of Chinese photosensitizers developed for photodynamic therapy (PDT).

  13. Coblation plus photodynamic therapy (PDT) for the treatment of juvenile onset laryngeal papillomatosis: case reports.

    Science.gov (United States)

    Zhou, Chengyong; Sun, Baochun; Wang, Feng; Dai, Zhiyao; Han, Zeli; Han, Jiahong; Chen, Maomao; Shen, Yao

    2014-08-29

    In treating juvenile-onset laryngeal papillomatosis, the most difficult aspect is preventing recurrence. After a single treatment, recurrence can begin after as soon as 20 days and the recurrent rate can be higher than 90%. The causes of recurrence include the presence of mucosal cells infected with papilloma virus, which are undetectable with the naked eyes, and surgery-induced infection. Photodynamic therapy (PDT) could effectively solve this problem. Virus-infected cells have a very high metabolic energy for capturing and internalizing the photosensitizer, which, after light stimulation, subsequently induces active oxygen species inside the nucleus, which kill infected cells. The second generation of photosensitizer agents (PA) are locally applied to avoid the intravenous systemic damage caused by first-generation PAs, and this method is widely used for the treatment of genital warts to very good effect. We used the photodynamic method to treat laryngeal papillomatosis in children and obtained significant efficacy. We followed three juvenile subjects with recurrent laryngeal papillomatosis through a course of treatment (each course includes three PDT sessions), with a follow-up after 6 months. The characteristic procedures involve exposing the larynx with a laryngoscope and using low-temperature plasma technology to visualize the tumor resection, as the effects of plasma technology can reduce postoperative laryngeal edema and reduce intraoperative metastasis. PDT was performed during the first surgery, 20 days after and 30 days after surgery. At the 6-month follow-ups, there was no recurrence. This was the world's first successful reported case of the use of PDT treatment for juvenile laryngeal papillomatosis.

  14. [Five-year visual outcomes of typical age-related macular degeneration and/or polypoidal choroidal vasculopathy patients who received photodynamic therapy (PDT) as initial treatment in comparison with patients prior to the PDT era].

    Science.gov (United States)

    Hata, Masayuki; Mandai, Michiko; Kojima, Hiroshi; Kameda, Takanori; Miyamoto, Noriko; Kurimoto, Yasuo

    2012-10-01

    To evaluate five-year visual outcomes of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in patients who received photodynamic therapy (PDT) as initial treatment compared with the outcomes of patients prior to the PDT era. Twenty-three eyes observed for 5 years before PDT was available (group A: typical AMD/PCV 16 eyes/7 eyes) and 61 eyes which had been observed for 5 years after PDT with additional treatment as needed (group B: typical AMD/PCV 25 eyes/36 eyes). The visual changes in these groups were retrospectively compared. In group A of typical AMD patients, the mean visual acuity (VA, logMAR) was significantly worse at the 3-year visit and later. In group B of typical AMD patients, the VA was stabilized after 2 years and no significant mean VA deterioration was observed for 5 years. More patients in group B retained a logMAR of less than 1.0 (43% vs. 25%) than in group A. Those patients in group B with PCV, maintained the VA for one year, but it gradually worsened thereafter. The PDT shortened the duration of VA deterioration in typical AMD patients from 5 to 2 years with no significant VA decrease for 5 years. The positive effect of PDT on PCV eyes was temporary.

  15. Evaluation of polymeric PLGA nanoparticles conjugated to curcumin for use in aPDT

    Directory of Open Access Journals (Sweden)

    Renata Celi Carvalho de Souza Pietra

    2017-07-01

    Full Text Available ABSTRACT Antimicrobial photodynamic therapy (aPDT involves the association of a photosensitizing agent with a light source with the goal of causing apoptosis or microbial lysing. The use of compounds with natural active principles is gaining prominence throughout the world. Several studies from groups that are linked to the development of innovations in the pharmaceutical market have used natural dyes, such as curcumin, the efficacy of which has been demonstrated in aPDT trials. Difficulties related to physicochemical stability, solubility and cell penetration are some of the challenges associated with this field. The present work aimed to prepare, investigate the characteristics and improve the photodynamic activity of PLGA-based nanoparticles loaded with curcumin for use in aPDT therapy. Using the simple technique of emulsion during the evaporation of a solvent, the particles were built, characterized and tested against microorganisms with importance for medicine and dentistry. The results revealed that the particles were able to protect the curcumin against degradation and eliminate some microorganism species at nanomolar concentrations.

  16. Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus.

    Science.gov (United States)

    Gray, J; Fullarton, G M

    2013-12-01

    Barrett's high grade dysplasia (HGD) is a pre-malignant condition which requires treatment with either oesophagectomy or ablative endoscopic therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded PDT due to improved efficacy and safety profile there remains a significant cohort of patients previously treated by PDT where the long term outcome is unclear. This study's aim was to assess the long term efficacy of PDT in patients with Barrett's HGD. Between June 2002 and 2007 21 patients (16 male, median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior to endoscopic light activation by laser light at 630 nm. The patients returned at 6-12 weekly intervals for repeat endoscopy and biopsy. Sixteen patients remained free of HGD at median 62 (range 36-114) months. Three patients developed adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated endoscopically with RFA and YAG laser, while one patient had surgical resection. Four patients developed recurrent HGD treated with repeat PDT. There was a significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients developed photosensitivity reactions. PDT successfully ablated HGD in 84% of patients and could therefore still be considered an effective salvage treatment for this condition in patients with co-morbidities precluding them for surgical resection. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. First-principles study on surface properties of t-LiFeSO4F: Showing a potential way to enhance electronic conductivity

    Science.gov (United States)

    Xie, Weina; Yang, Xiaoling; Lin, Yanyun; Zhuang, Weiling; Luo, Qiong

    2017-09-01

    Systematic theoretical investigation on the surface properties of t-LiFeSO4F based on the stoichiometric (1 0 0), (0 1 0), and (0 0 1) surfaces at the lowest energy termination has been performed within the GGA+U framework. The surface energies of (1 0 0), (0 1 0), and (0 0 1) surfaces are 1.10, 1.64 and 1.04 J/m2 respectively. The (1 0 0) and (0 1 0) surfaces are charge transfer insulators with band gaps of 2.92 and 1.95 eV, respectively. The predicted (0 0 1) surface exhibits metallic-like character. This study suggests that increasing the percentage of (0 0 1) surface on t-LiFeSO4F crystals is an effective solution to enhance its electronic conductivity.

  18. Next-generation bis-locked nucleic acids with stacking linker and 2'-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes

    DEFF Research Database (Denmark)

    Geny, Sylvain; Moreno, Pedro M D; Krzywkowski, Tomasz

    2016-01-01

    nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen-arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further...... improvements were obtained by substituting LNA with 2'-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14-nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting...... of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context....

  19. The use of pH-sensitive functional selenium nanoparticles shows enhanced in vivo VEGF-siRNA silencing and fluorescence imaging

    Science.gov (United States)

    Yu, Qianqian; Liu, Yanan; Cao, Chengwen; Le, Fangling; Qin, Xiuying; Sun, Dongdong; Liu, Jie

    2014-07-01

    The utility of small interfering RNAs (siRNAs) has shown great promise in treating a variety of diseases including many types of cancer. While their ability to silence a wide range of target genes underlies their effectiveness, the application of therapies remains hindered by a lack of an effective delivery system. In this study, we sought to develop an siRNA-delivery system for VEGF, a known signaling molecule involved in cancer, that consists of two selenium nanoparticles SeNPs and G2/PAH-Cit/SeNPs. A G2/PAH-Cit/SeNP is a pH-sensitive delivery system that is capable of enhancing siRNA loading, thus increasing siRNA release efficiency and subsequent target gene silencing both in vitro and in vivo. In vivo experiments using G2/PAH-Cit/SeNPs@siRNA led to significantly higher accumulation of siRNA within the tumor itself, VEGF gene silencing, and reduced angiogenesis in the tumor. Furthermore, the G2/PAH-Cit/SeNP delivery system not only enhanced anti-tumor effects on tumor-bearing nude mice as compared to SeNPs@siRNA, but also resulted in weak occurrence of lesions in major target organs. In sum, this study provides a new class of siRNA delivery system, thereby providing an alternative therapeutic route for cancer treatment.The utility of small interfering RNAs (siRNAs) has shown great promise in treating a variety of diseases including many types of cancer. While their ability to silence a wide range of target genes underlies their effectiveness, the application of therapies remains hindered by a lack of an effective delivery system. In this study, we sought to develop an siRNA-delivery system for VEGF, a known signaling molecule involved in cancer, that consists of two selenium nanoparticles SeNPs and G2/PAH-Cit/SeNPs. A G2/PAH-Cit/SeNP is a pH-sensitive delivery system that is capable of enhancing siRNA loading, thus increasing siRNA release efficiency and subsequent target gene silencing both in vitro and in vivo. In vivo experiments using G2/PAH

  20. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  1. PDT in the thoracic cavity: Spectroscopic methods and fluence modeling for treatment planning

    Science.gov (United States)

    Meo, Julia Lauren

    PDT for the thoracic cavity provides a promising cancer treatment modality, but improvements in treatment planning, particularly in PDT dosimetry, can be made to improve uniformity of light delivery. When a cavity of arbitrary geometry is illuminated, the fluence increases due to multiple-scattered photons, referred to as the Integrating Sphere Effect (ISE). Current pleural PDT treatment protocol at the University of Pennsylvania monitors light fluence (hereafter simply fluence, measured in W/cm2) via seven isotropic detectors sutured at different locations in thoracic cavity of a patient. This protocol monitors light at discrete locations, but does not provide a measurement of fluence for the thoracic cavity as a whole. Current calculation of light fluence includes direct light only and thus does not account for the unique optical properties of each tissue type present, which in turn affects the accuracy of the calculated light distribution in the surrounding tissue and, in turn, the overall cell death and treatment efficacy. Treatment planning for pleural PDT can be improved, in part, by considering the contribution of scattered light, which is affected by the two factors of geometry and in vivo optical properties. We expanded the work by Willem Star in regards to the ISE in a spherical cavity. A series of Monte Carlo (MC) simulations were run for semi-infinite planar, spherical, and ellipsoidal geometries for a range of optical properties. The results of these simulations are compared to theory and numerical solutions for fluence in the cavity and at the cavity-medium boundary. The development via MC simulations offers a general method of calculating the required light fluence specialized to each patient, based on the treatment surface area. The scattered fluence calculation is dependent on in vivo optical properties (μa and μs') of the tissues treated. Diffuse reflectance and fluorescence spectroscopy methods are used to determine the optical properties and

  2. Synthesis of decacationic [60]fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation.

    Science.gov (United States)

    Wang, Min; Maragani, Satyanarayana; Huang, Liyi; Jeon, Seaho; Canteenwala, Taizoon; Hamblin, Michael R; Chiang, Long Y

    2013-05-01

    We report a novel class of highly water-soluble decacationic methano[60]fullerene decaiodides C60[>M(C3N6(+)C3)2]-(I(-))10 [1-(I(-))10] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths. The O2(-)·-production efficiency of 1-(I(-))10 was confirmed by using an O2(-)·-reactive bis(2,4-dinitrobenzenesulfonyl)tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to (3)C60*[>M(C3N6(+)C3)2] leading to C60(-)·[>M(C3N6(+)C3)2]. Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells. We used the well-characterized malonato[60]fullerene diester monoadduct C60[>M(t-Bu)2] as the starting fullerene derivative to provide a better synthetic route to C60[>M(C3N6(+)C3)2] via transesterification reaction under trifluoroacetic acid catalyzed conditions. These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.

    Science.gov (United States)

    Tudor, Diana; Nenu, Iuliana; Filip, Gabriela Adriana; Olteanu, Diana; Cenariu, Mihai; Tabaran, Flaviu; Ion, Rodica Mariana; Gligor, Lucian; Baldea, Ioana

    2017-01-01

    Melanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT) might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine-Gallium phthalocyanine chloride (GaPc) and Metformin was used against melanoma. The study aimed to: (1) find the anti-melanoma efficacy of GaPc-PDT, (2) assess possible beneficial effects of Metformin addition to PDT, (3) uncover some of the mechanisms underlining cell killing and anti-angiogenic effects. Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting. GaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF)-κB activation and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT. Metformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects. Combination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

  4. Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.

    Directory of Open Access Journals (Sweden)

    Diana Tudor

    Full Text Available Melanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine-Gallium phthalocyanine chloride (GaPc and Metformin was used against melanoma. The study aimed to: (1 find the anti-melanoma efficacy of GaPc-PDT, (2 assess possible beneficial effects of Metformin addition to PDT, (3 uncover some of the mechanisms underlining cell killing and anti-angiogenic effects.Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting.GaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF-κB activation and tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT.Metformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects.Combination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

  5. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  6. Treatment of facial actinic keratoses with aminolevulinic acid photodynamic therapy (ALA-PDT) or ingenol mebutate 0.015% gel with and without prior treatment with ALA-PDT.

    Science.gov (United States)

    Berman, Brian; Nestor, Mark S; Newburger, Jessica; Park, Huynhee; Swenson, Nicole

    2014-11-01

    This randomized, 3-group study compared the efficacy and tolerability of 3 treatment modalities for facial actinic keratoses. Twenty-four healthy adult male and female subjects who had 4 to 8 clinically visible and discrete actinic keratoses on the face in a contiguous 25cm2 treatment area. Subjects were randomized into one of three treatment groups: 2 treatments with 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT), 1 ALA-PDT treatment and 1 course of ingenol mebutate (ingenol mebutate) 0.015% gel daily for 3 consecutive days, or 1 course of ingenol mebutate gel alone. Actinic keratoses in the treatment field were counted at the baseline visit, and at the completion of the study (day 57 or day 71). At the site of application, local site reactions were graded at each visit. Subjects in the two ALA-PDT treatment group had a 97.5% mean reduction (PPDT plus ingenol mebutate gel group had an 86.7% mean reduction (PPDT group, 10.375 for the ALA-PDT followed by ingenol mebutate gel group, and 12.625 for the ingenol mebutate gel alone group (P=0.0004 and 0.001, respectively). ALA-PDT, ingenol mebutate gel, and a combination of the two treatment modalities are successful topical therapies for the reduction of actinic keratoses on the face. The group of subjects receiving 2 consecutive treatments with ALA-PDT, compared to treatment with ingenol mebutate gel alone or sequentially after one course of ALA-PDT had a significantly lower mean composite LSR score and a non-significant trend for greater efficacy.

  7. Models of the iron-only hydrogenase: a comparison of chelate and bridge isomers of Fe2(CO)4{Ph2PN(R)PPh2}(μ-pdt) as proton-reduction catalysts.

    Science.gov (United States)

    Ghosh, Shishir; Hogarth, Graeme; Hollingsworth, Nathan; Holt, Katherine B; Richards, Idris; Richmond, Michael G; Sanchez, Ben E; Unwin, David

    2013-05-21

    Reactions of Fe2(CO)6(μ-pdt) (pdt = SCH2CH2CH2S) with aminodiphosphines Ph2PN(R)PPh2 (R = allyl, (i)Pr, (i)Bu, p-tolyl, H) have been carried out under different conditions. At room temperature in MeCN with added Me3NO·2H2O, dibasal chelate complexes Fe2(CO)4{κ(2)-Ph2PN(R)PPh2}(μ-pdt) are formed, while in refluxing toluene bridge isomers Fe2(CO)4{μ-Ph2PN(R)PPh2}(μ-pdt) are the major products. Separate studies have shown that chelate complexes convert to the bridge isomers at higher temperatures. Two pairs of bridge and chelate isomers (R = allyl, (i)Pr) have been crystallographically characterised together with Fe2(CO)4{μ-Ph2PN(H)PPh2}(μ-pdt). Chelate complexes adopt the dibasal diphosphine arrangement in the solid state and exhibit very small P-Fe-P bite-angles, while the bridge complexes adopt the expected cisoid dibasal geometry. Density functional calculations have been carried out on the chelate and bridge isomers of the model compound Fe2(CO)4{Ph2PN(Me)PPh2}(μ-pdt) and reveal that the bridge isomer is thermodynamically favourable relative to the chelate isomers that are isoenergetic. The HOMO in each of the three isomers exhibits significant metal-metal bonding character, supporting a site-specific protonation of the iron-iron bond upon treatment with acid. Addition of HBF4·Et2O to the Fe2(CO)4{κ(2)-Ph2PN(allyl)PPh2}(μ-pdt) results in the clean formation of the corresponding dibasal hydride complex [Fe2(CO)4{κ(2)-Ph2PN(allyl)PPh2}(μ-H)(μ-pdt)][BF4], with spectroscopic measurements revealing the intermediate formation of a basal-apical isomer. A crystallographic study reveals that there are only very small metric changes upon protonation. In contrast, the bridge isomers react more slowly to form unstable species that cannot be isolated. Electrochemical and electrocatalysis studies have been carried out on the isomers of Fe2(CO)4{Ph2PN(allyl)PPh2}(μ-pdt). Electron accession is predicted to occur at an orbital that is anti-bonding with respect to

  8. Au Nanoclusters Sensitized Black TiO2-x Nanotubes for Enhanced Photodynamic Therapy Driven by Near-Infrared Light.

    Science.gov (United States)

    Yang, Dan; Gulzar, Arif; Yang, Guixin; Gai, Shili; He, Fei; Dai, Yunlu; Zhong, Chongna; Yang, Piaoping

    2017-12-01

    The low reactive oxygen species production capability and the shallow tissue penetration of excited light (UV) are still two barriers in photodynamic therapy (PDT). Here, Au cluster anchored black anatase TiO2-x nanotubes (abbreviated as Au25 /B-TiO2-x NTs) are synthesized by gaseous reduction of anatase TiO2 NTs and subsequent deposition of noble metal. The Au25 /B-TiO2-x NTs with thickness of about 2 nm exhibit excellent PDT performance. The reduction process increased the density of Ti3+ on the surface of TiO2 , which effectively depresses the recombination of electron and hole. Furthermore, after modification of Au25 nanoclusters, the PDT efficiency is further enhanced owing to the changed electrical distribution in the composite, which forms a shallow potential well on the metal-TiO2 interface to further hamper the recombination of electron and hole. Especially, the reduction of anatase TiO2 can expend the light response range (UV) of TiO2 to the visible and even near infrared (NIR) light region with high tissue penetration depth. When excited by NIR light, the nanoplatform shows markedly improved therapeutic efficacy attributed to the photocatalytic synergistic effect, and promotes separation or restrained recombination of electron and hole, which is verified by experimental results in vitro and in vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Mixed culture biofilms of Salmonella Typhimurium and cultivable indigenous microorganisms on lettuce show enhanced resistance of their sessile cells to cold oxygen plasma.

    Science.gov (United States)

    Jahid, Iqbal Kabir; Han, Noori; Zhang, Cheng-Yi; Ha, Sang-Do

    2015-04-01

    Control of foodborne pathogens in fresh produce is crucial for food safety, and numerous Salmonella Typhimurium (ST) outbreaks have been reported already. The present study was done to assess effectiveness of cold oxygen plasma (COP) against biofilms of ST mixed with cultivable indigenous microorganisms (CIM). ST and CIM were grown at 15 °C as monocultures and mixed cultures for planktonic state, biofilm on stainless steel, and lettuce leaves. Thereafter, the samples were treated with COP and surviving populations were counted using plate counting methods. Biofilms and stomatal colonization were examined using field emission scanning electron microscopy (FESEM) and food quality was assessed after treatment. Mixed cultures of ST and CIM showed an antagonistic interaction on lettuce but not on SS or in planktonic state. Mixed cultures showed significantly (p lettuce but not on SS or planktonic state. Shift from smooth to rugose colony type was found for planktonic and for biofilms on SS but not on lettuce for ST. Mixed culture biofilms colonized stomata on the inside as demonstrated by FESEM. Although, lettuce quality was not affected by COP, this technology has to be optimized for further development of the successful inactivation of complex multispecies biofilm structures presented by real food environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Development of a safe ultraviolet camera system to enhance awareness by showing effects of UV radiation and UV protection of the skin (Conference Presentation)

    Science.gov (United States)

    Verdaasdonk, Rudolf M.; Wedzinga, Rosaline; van Montfrans, Bibi; Stok, Mirte; Klaessens, John; van der Veen, Albert

    2016-03-01

    The significant increase of skin cancer occurring in the western world is attributed to longer sun expose during leisure time. For prevention, people should become aware of the risks of UV light exposure by showing skin damage and the protective effect of sunscreen with an UV camera. An UV awareness imaging system optimized for 365 nm (UV-A) was develop using consumer components being interactive, safe and mobile. A Sony NEX5t camera was adapted to full spectral range. In addition, UV transparent lenses and filters were selected based on spectral characteristics measured (Schott S8612 and Hoya U-340 filters) to obtain the highest contrast for e.g. melanin spots and wrinkles on the skin. For uniform UV illumination, 2 facial tanner units were adapted with UV 365 nm black light fluorescent tubes. Safety of the UV illumination was determined relative to the sun and with absolute irradiance measurements at the working distance. A maximum exposure time over 15 minutes was calculate according the international safety standards. The UV camera was successfully demonstrated during the Dutch National Skin Cancer day and was well received by dermatologists and participating public. Especially, the 'black paint' effect putting sun screen on the face was dramatic and contributed to the awareness of regions on the face what are likely to be missed applying sunscreen. The UV imaging system shows to be promising for diagnostics and clinical studies in dermatology and potentially in other areas (dentistry and ophthalmology)

  11. Sustained ERK [corrected] inhibition by EGFR targeting therapies is a predictive factor for synergistic cytotoxicity with PDT as neoadjuvant therapy.

    Science.gov (United States)

    Weyergang, Anette; Selbo, Pål K; Berg, Kristian

    2013-03-01

    Tyrosin kinase inhibitors (TKIs) and monoclonal antibodies aimed to target epidermal growth factor receptor (EGFR) have shown limited effect as monotherapies and drug resistance is a major limitation for therapeutic success. Adjuvant therapies to EGFR targeting therapeutics are therefore of high clinical relevance. Three EGFR targeting drugs, Cetuximab, Erlotinib and Tyrphostin AG1478 were used in combination with photodynamic therapy (PDT) in two EGFR positive cell lines, A-431 epidermoid skin carcinoma and WiDr colorectal adenocarcinoma cells. The amphiphilic meso-tetraphenylporphine with 2 sulphonate groups on adjacent phenyl rings (TPPS(2a)) was utilized as a photosensitizer for PDT. The cytotoxic outcome of the combined treatments was evaluated by cell counting and MTT. Cellular signalling was explored by Western blotting. PDT as neoadjuvant to Tyrphostin in A-431 cells as well as to Tyrphostin or Erlotinib in WiDr cells revealed synergistic cytotoxicity. In contrast, Erlotinib or Cetuximab combined with neoadjuvant PDT induced an antagonistic effect on cell survival of A-431 cells. Neoadjuvant PDT and EGFR targeting therapies induced a synergistic inhibition of ERK as well as synergistic cytotoxicity only when the EGFR targeting monotherapies caused a prolonged ERK inhibition. There were no correlation between EGFR inhibition by the EGFR targeting monotherapies or the combined therapies and the cytotoxic outcome combination-therapies. The results suggest that sustained ERK inhibition by EGFR targeting monotherapies is a predictive factor for synergistic cytotoxicity when combined with neoadjuvant PDT. The present study provides a rationale for selecting anticancer drugs which may benefit from PDT as adjuvant therapy.

  12. Low dose Photofrin PDT for recurrent in-situ squamous cell tumors of the head and neck

    Science.gov (United States)

    Allison, R. R.; Austerlitz, C.; Sheng, C.; Mota, H.; Brodish, B.; Camnitz, P.; Sibata, C. H.

    2009-06-01

    Multifocal recurrence of in-situ squamous cell cancer of the oral cavity, pharynx and vocal cord following surgical failure can be a therapeutic dilemma. Salvage surgery or radiation may be an option but morbidity can be significant. We evaluated the potential role of low dose Photofrin (1.2mg/Kg) Photodynamic Therapy for this cohort of patients. A total of 25 patients with multifocal recurrent in-situ squamous cell cancer of the oral cavity, pharynx and vocal cord who had failed local resection, and where additional surgery or radiation therapy would likely result in permanent morbidity, were offered Photodynamic Therapy. PDT consisted of off label infusion of Photofrin (1.2mg/kg) followed 48 hours later by illumination at 630nm employing a light diffuser (300J) and/or microlens (150Jcm2). All patients completed their prescribed PDT and no patient has been lost to follow up (minimum 1 year). No photosensitivity reactions were noted. No significant morbidity was seen. All patients were able to maintain oral nutrition. Procedure related pain was well controlled by one week of oral narcotics. At one month post PDT all patients were biopsy negative in the treatment region and no failures within the treatment region have been noted. No fibrosis or permanent PDT morbidity has been seen with follow up to three years. Vocal cord and voice function were excellent. Three patients developed new regions of in-situ disease outside the PDT fields, two underwent additional PDT and one had laser resection. Low dose Photofrin PDT offers excellent palliation and durable local control of recurrent in-situ squamous cell cancers of the oral cavity, pharynx and true cords. This is a well tolerated therapy. Low dose Photofrin appears to improve selectivity and minimize normal tissue injury. It should be tested in a larger patient population.

  13. The cataract-associated V41M mutant of human γS-crystallin shows specific structural changes that directly enhance local surface hydrophobicity

    Energy Technology Data Exchange (ETDEWEB)

    Bharat, Somireddy Venkata; Shekhtman, Alexander; Pande, Jayanti, E-mail: jpande@albany.edu

    2014-01-03

    Highlights: •We present NMR analysis of V41M, a cataract-causing mutant of human γS-crystallin. •Mutation alters strand–strand interactions throughout the N-terminal domain. •Mutation directly affects Trp46 due to key Met41-S–Trp46-pi interactions. •We identify the basis of the surface hydrophobicity increase and residues involved. -- Abstract: The major crystallins expressed in the human lens are γS-, γC- and γD-crystallins. Several mutations in γS-crystallin are associated with hereditary cataracts, one of which involves the substitution of a highly conserved Valine at position 41 to Methionine. According to a recent report, the mutant protein, V41M, shows lower stability and increased surface hydrophobicity compared to the wild-type, and a propensity for self-aggregation. Here we address the structural differences between the two proteins, with residue-level specificity using NMR spectroscopy. Based on the structural model of the mutant protein, our results clearly show that the mutation creates a major local perturbation almost at the junction of the first and second “Greek-key” motifs in the N-terminal domain. A larger section of the second motif (residues 44–86) appears to be mainly affected. Based on the sizeable chemical shift of the imino proton of the indole side-chain of Trp46 in V41M, we suggest that the sulphur atom of Met41 is involved in an S–π interaction with Trp46. This interaction would bring the last β-strand of the first “Greek-key” motif closer to the first β-strand of the second motif. This appears to lead to a domino effect, towards both the N- and C-terminal ends, even as it decays off substantially beyond the domain interface. During this process discreet hydrophobic surface patches are created, as revealed by ANS-binding. Such changes would not affect the secondary structure or cause a major change in the tertiary structure, but can lead to self-aggregation or aberrant binding interactions of the mutant

  14. Transgenic rice plants expressing the antifungal AFP protein from Aspergillus giganteus show enhanced resistance to the rice blast fungus Magnaporthe grisea.

    Science.gov (United States)

    Coca, María; Bortolotti, Cristina; Rufat, Mar; Peñas, Gisela; Eritja, Ramón; Tharreau, Didier; del Pozo, Alvaro Martinez; Messeguer, Joaquima; San Segundo, Blanca

    2004-01-01

    The Aspergillus giganteus antifungal protein (AFP), encoded by the afp gene, has been reported to possess in vitro antifungal activity against various economically important fungal pathogens, including the rice blast fungus Magnaporthe grisea. In this study, transgenic rice ( Oryza sativa ) constitutively expressing the afp gene was generated by Agrobacterium -mediated transformation. Two different DNA constructs containing either the afp cDNA sequence from Aspergillus or a chemically synthesized codon-optimized afp gene were introduced into rice plants. In both cases, the DNA region encoding the signal sequence from the tobacco AP24 gene was N-terminally fused to the coding sequence of the mature AFP protein. Transgenic rice plants showed stable integration and inheritance of the transgene. No effect on plant morphology was observed in the afp -expressing rice lines. The inhibitory activity of protein extracts prepared from leaves of afp plants on the in vitro growth of M. grisea indicated that the AFP protein produced by the trangenic rice plants was biologically active. Several of the T(2) homozygous afp lines were challenged with M. grisea in a detached leaf infection assay. Transformants exhibited resistance to rice blast at various levels. Altogether, the results presented here indicate that AFP can be functionally expressed in rice plants for protection against the rice blast fungus M. grisea.

  15. Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer

    OpenAIRE

    Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M.; Busch, Theresa M.; Cengel, Keith A.

    2012-01-01

    Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicit...

  16. Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for age-related macular degeneration patients with large lesions.

    Science.gov (United States)

    Otsuji, Tsuyoshi; Sho, Kenichiro; Tsumura, Akiko; Koike, Naoko; Nishimura, Tetsuya; Takahashi, Kanji

    2016-01-01

    To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat. The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named "Ironing PDT." This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University. No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes. Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy.

  17. A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT.

    Science.gov (United States)

    Zhu, Timothy C; Kim, Michele M; Ong, Yi-Hong; Penjweini, Rozhin; Dimofte, Andreea; Finlay, Jarod C; Rodriguez, Carmen; Cengel, Keith A

    2017-01-28

    Uniform delivery of light fluence is an important goal for photodynamic therapy. We present summary results for an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. A MATLAB-based GUI program is developed to display the light dose in real-time during PDT to guide the PDT treatment delivery to improve the uniformity of the light dose. A dualcorrection algorithm is used to improve the agreement between calculations and in-situ measurements. A comprehensive analysis of the distribution of light fluence during PDT is presented in both phantom conditions and in clinical cases.

  18. Specific light exposure of galactosylated Zn(II) phthalocyanines for selective PDT effects on breast cancer cells

    Science.gov (United States)

    Mantareva, V. N.; Kril, A.; Angelov, I.; Avramov, L.

    2013-03-01

    Photodynamic therapy (PDT) is a clinically approved non-invasive and curative procedure for different oncological and non-oncological applications. PDT is still under development due to several limitations which lead to partially successful photodynamic response. The crucial steps in PDT procedure are binding of the photosensitizer to outer cell membrane, its penetration and subcellular localization which envisage the target sites of reactive oxygen species generated during irradiation. Since the surrounding normal cells are also exposed to the photosensitizer and the ambient daylight can be harmful for healthy tissues after therapeutic light application, the challenging task in PDT research is to optimize the procedure in a way to reach tumor cell selectivity. The present study outlines the influence of a light exposure pre-treatment (prior therapeutic light) with specific wavelengths (365 nm and 635 nm) on the uptake, the localization and further re-localization of galactose-substituted Zn(II) phthalocyanines into MDA-MB-231 breast cancer cells. The in vitro photodynamic effect towards tumor cells was studied in comparison to the normal cell line Balb/c 3T3 (clone 31) after pre-irradiation with UV light (365 nm) and red LED (635 nm). The results suggest that the galactose functional groups of Zn(II) phthalocyanine and the harmless UV light at 365 nm favor the selective PDT response.

  19. Effect of HMME-PDT with different parameters in rabbit ear model: a possible way for hypertrophic scarring

    Science.gov (United States)

    Cai, Hong; Gu, Ying; Zeng, Jing; Li, Shao-ran; Sun, Qiang; Wang, Ying; Shi, Dong-wen; Zhang, Lu-yong

    2007-11-01

    Background and Objective: Hypertrophic scar is a pathological scar that grows aberrantly by excessive deposition of collagens in the dermis. It is known that photodynamic therapy (PDT) contributes to a variety of diseases, however, the use of inhibiting scar formation has not been fully explored. The purpose of this study is to investigate the effect of HMME-PDT (Photodynamic therapy induced by Hematoporphyrin Monomethyl Ether) with different parameters on hypertrophic scar in rabbit ear. Materials and Methods: After the placement of 7-mm diameter dermal wounds on each ear, the acute model of dermal hypertrophic scar in the New Zealand white rabbits was established. Scar wounds were randomly separated into 2 groups: the experimental group received HMME-PDT with different parameters, and the control group received no special treatment. Specimens were harvested from scar wounds on postoperative day 28. Scar and hypertrophic index (HI) were observed by haematoxylin-eosin staining. Results: Compared with the control group, scar formation was inhibited by HMME-PDT in the experimental group with parameters as follows: photosensitizer dose 10mg/kg, power density 20mw/cm2, fluence 5J/cm2, meanwhile, HI was decreased significantly. Conclusion: HMME-PDT may play a role in inhibiting hypertrophic scarring in rabbit ear. The biological effect is determined by the dose of photosensitizer, interval between the injection of photosensitizer and irradiation, power density and energy fluence.

  20. A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT

    Science.gov (United States)

    Zhu, Timothy C.; Kim, Michele M.; Ong, Yi-Hong; Penjweini, Rozhin; Dimofte, Andreea; Finlay, Jarod C.; Rodriguez, Carmen; Cengel, Keith A.

    2017-02-01

    Uniform delivery of light fluence is an important goal for photodynamic therapy. We present summary results for an infrared (IR) navigation system to deliver light dose uniformly during intracavitory PDT by tracking the movement of the light source and providing real-time feedback on the light fluence rate on the entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors placed in selected locations in the pleural cavity monitor the light doses. To improve the delivery of light dose uniformity, an IR camera system is used to track the motion of the light source as well as the surface contour of the pleural cavity. A MATLAB-based GUI program is developed to display the light dose in real-time during PDT to guide the PDT treatment delivery to improve the uniformity of the light dose. A dualcorrection algorithm is used to improve the agreement between calculations and in-situ measurements. A comprehensive analysis of the distribution of light fluence during PDT is presented in both phantom conditions and in clinical cases.

  1. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

    Science.gov (United States)

    Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

    2014-09-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

  2. Determination of tissue optical properties in PDT treated Head & Neck patients

    Science.gov (United States)

    Dimofte, Andreea; Finlay, Jarod C.; Sharikova, Anna V.; Cengel, Keith A.; Ahn, Peter; Busch, Theresa M.; Zhu, Timothy C.

    2015-01-01

    Determination of optical properties (absorption (μa) and scattering (μs′) coefficients) in human tissue is important when it comes to accurate calculation of fluence rate in and around tissue area. ALA application to the tissue induces production of protoporphyrin IX when activated by red light. Changes in the tissue optical properties can send information such as treatment outcome and tissue drug concentration. Patients in this study were treated with PDT for head and neck mucosal dysplasia. They were enrolled in a phase I study of escalating light doses and oral ALA with 60mg/kg. Red light at 630nm was administered to the tumor from a laser. The light dose was escalated from 50–200J/cm2 with a measured fluence rate at tissue surface of 100mW/cm2. We developed a light detection device for the purpose of determining optical properties in vivo using the semi-infinite method. The light detection device consists of two parallel, placed 5mm apart. In one of the catheters a 2 mm long linear diffusing light source is placed while in the second catheter, a calibrated isotropic detector is placed. The detector is scanned along the length of the light source containing catheter. Scans are done with the device placed on the treatment area (tumor) and on the normal tissue. Optical properties were measured in-vivo before and after PDT delivery for both normal tissue and tumor. PMID:25999648

  3. Verteporfin PDT for subfoveal occult CNV in AMD: two-year results of a randomized trial.

    Science.gov (United States)

    Kaiser, Peter K

    2009-08-01

    To determine whether verteporfin photodynamic therapy (PDT) can safely reduce the risk of vision loss in patients with subfoveal occult with no classic choroidal neovascularization (CNV) due to age-related macular degeneration. Eligible patients were > or =50 years of age with lesion size or =15 and > or =30 letters of visual acuity (VA) from baseline at 12 and 24 months. This study was registered with ClinicalTrials.gov on 20 July 2005. ClinicalTrials.gov identifier: NCT00121407. A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost > or =15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost > or =30 letters at month 12 and month 24, respectively. These differences were not statistically significant. Four (1.6%) verteporfin-treated patients and one placebo patient (who received verteporfin in error) experienced an acute severe VA decrease; all five patients recovered some degree of vision. No unexpected ocular or systemic adverse events were identified. Verteporfin PDT in the treatment of occult with no classic CNV was safe and well-tolerated. The differences between the two groups in the primary efficacy variables were not significant. Baseline characteristics and patient selection methods may have contributed to the small treatment effect.

  4. Phenomenon of PDT-induced post-irradiation apoptosis in biological liquids cancer cells using sulphonated phthalocyanine aluminum photosensitizer

    Science.gov (United States)

    Douplik, Alexandre Y.; Loschenov, Victor B.; Vorozhtsov, Georgy N.; Kogan, Eugenia A.; Kusin, Michael; Ablitsov, Y.; Ilyina, O. S.

    1997-12-01

    Discovered during last year's phenomenon of PDT-induced apoptosis (programmed cell destruction) in cell culture immediately after light irradiation using phthalocyanine photosensitizers can be used for treatment of cancer. Experiments were carried out on mice with ascites. Ascitic liquid with the added photosensitizer was irradiated by light source with wavelength 660 - 680 nm and used according to ex vivo procedure. Actuation and development of apoptosis process in ascitic liquid were estimated by cytomorphological tests. It has been observed the phenomenon of growth of relative fraction of cells damage level expressed mainly as apoptosis after PDT procedure ex vivo. We suggest to call this phenomenon as PDT-induced post-irradiation apoptosis (PIP- apoptosis). Dependence between level of expressing of PIP- apoptosis and sulphonated phthalocyanine aluminum photosensitizer (Photosense) concentration at used photosensitizer concentrations has not been found out.

  5. Imbalance of Ca2+ and K+ fluxes in C6 glioma cells after PDT measured with scanning ion-selective electrode technique.

    Science.gov (United States)

    Hu, Sheng-Li; Du, Peng; Hu, Rong; Li, Fei; Feng, Hua

    2014-05-01

    Photodynamic therapy (PDT) possesses the capacity to lead to death of C6 glioma in vitro and in vivo. The purpose of this study was to investigate whether Ca(2+) and K(+) homeostasis of C6 glioma cells were affected by PDT. C6 glioma cells were randomly divided into five groups: control group, Hematoporphyrin derivative (HpD) group (10 mg/l, without irradiation), PDT group (HpD 10 mg/l + irradiation), PDT&6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) group (HpD 10 mg/l + CNQX 50 mol/l + irradiation), and HpD&CNQX group (HpD 10 mg/l + CNQX 50 mol/l, without irradiation). Glioma cells in PDT and PDT&CNQX group were subjected to PDT. Cells in PDT&CNQX group were administered α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist CNQX prior to PDT on C6 glioma cells. The changes of Ca(2+) and K(+) fluxes were studied by using a non-invasive scanning ion-selective electrode technique (SIET). Morphology of C6 cells was observed with optical microscopy. PDT induced Ca(2+) influx and K(+) efflux significantly, which resulted in death of C6 cells. When AMPA glutamate receptor antagonist CNQX was applied, Ca(2+) influx and K(+) efflux were partly blocked up and viability of C6 cells increased. These results indicate that Ca(2+) influx and K(+) efflux may correlate with the treatment effects of PDT on C6 glioma cells.

  6. Squamous cell carcinoma of dogs and cats: an ideal test system for human head and neck PDT protocols

    Science.gov (United States)

    Lucroy, Michael D.

    2006-02-01

    Photodynamic therapy (PDT) is ideally suited for the treatment of head and neck cancer (HNC) in humans. Developing useful PDT protocols for HNC is challenging due to the expense of Phase I and II clinical trials. Moreover, the often-poor predictive value of murine models means that photosensitizers may proceed far into development before problems are noted. Dogs and cats with spontaneous oral squamous cell carcinoma (SCC) share striking similarities with humans affected with oral SCC. These similarities include viral and environmental tobacco smoke as risk factors, location-dependent prognoses, and relative resistance to chemotherapy. The relatively large oral cancers encountered in veterinary patients allow for light and drug dosimetry that are directly applicable to humans. The irregular shape of oral SCC allows a rigorous evaluation of novel photodynamic therapy protocols under field conditions. Because spontaneous tumors in dogs and cats arise in an outbred animal population it is possible to observe an intact host response to PDT. The shorter lifespan of dogs and cats allows rapid accrual of endpoint data. External beam radiation therapy and chemotherapy are commonplace in veterinary medicine, making dogs and cats with spontaneous SCC a useful resource to study the interactions with PDT and other cancer treatment modalities. Our preliminary results demonstrate that PDT is well-tolerated by dogs with oral cancer, and a Phase II clinical trial of zinc-phthalocyanine-based photodynamic therapy is underway in dogs with oral SCC. The usefulness of 5-aminolevulinic acid methyl ester-based PDT is being investigated in cats with oral SCC.

  7. ALA-PDT combined with antibiotics for the treatment of atypical mycobacterial skin infections: Outcomes and safety.

    Science.gov (United States)

    Sun, Kedai; Yang, Hang; Huang, Xianqiong; Gong, Nanpeng; Qin, Qin; Lu, Weiping; Lei, Xia

    2017-09-01

    Photodynamic therapy (PDT) has been shown to be a very successful therapy in clinical practice, and its usefulness as a treatment for bacterial infections has been gradually recognized by researchers, who believe it has very good clinical prospects. Atypical mycobacterial skin infections are a type of rare refractory infection. The aim of this study was to evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics for the treatment of atypical mycobacterial skin infections. In this study, 4 patients with atypical mycobacterial skin infections were treated with ALA-PDT combined with antibiotic therapy. These patients were diagnosed with atypical mycobacterial skin infections by bacterial culture and microarray analysis, tests that were also useful for identifying the strains responsible for the infections. In addition to being treated with antibiotics, the skin was also treated locally with ALA-PDT (20% ALA was applied to the lesion and incubated in the dark, then, the lesion was irradiated with a red light with an energy density of 100J/cm 2 ) every 10days for a total of 3-5 sessions. All four patients enrolled in the study were cured with 100% efficiency after receiving combination therapy with ALA-PDT and antibiotics for three months. All patients experienced redness and pain during treatment but did not experience any other forms of severe discomfort and were satisfied with the results of their treatments. Local ALA-PDT combined with antibiotics is a safe and effective method of treating atypical mycobacterial skin infections. Copyright © 2017. Published by Elsevier B.V.

  8. Combination of PDT and a DNA demethylating agent produces anti-tumor immune response in a mouse tumor model

    Science.gov (United States)

    Mroz, Pawel; Hamblin, Michael R.

    2009-06-01

    Epigenetic mechanisms, which involve DNA methylation and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. However, these changes must be actively maintained after each cell division rendering them a promising target for pharmacologic inhibition. DNA methyltransferase inhibitors like 5-aza-deoxycytidine (5-aza-dC) induce and/or up-regulate the expression of MAGE-type antigens in human and mice cancer cells. Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of stimulating tumor-directed immune response. We studied the effects of a new therapy that combined the demethylating agent 5-aza-dC with PDT in the breast cancer model 4T1 syngenic to immunocompetent BALB/c mice. PDT was used as a locally ablating tumor treatment that is capable of eliciting strong and tumor directed immune response while 5-aza-dC pretreatment was used promote de novo induction of the expression of P1A.protein. This is the mouse homolog of human MAGE family antigens and is reported to function as a tumor rejection antigen in certain mouse tumors. This strategy led to an increase in PDT-mediated immune response and better treatment outcome. These results strongly suggest that the MAGE family antigens are important target for PDT mediated immune response but that their expression can be silenced by epigenetic mechanisms. Therefore the possibility that PDT can be combined with epigenetic strategies to elicit anti-tumor immunity in MAGE-positive tumor models is highly clinically significant and should be studied in detail.

  9. In-vivo monitoring of oxygen saturation in murine carcinoma during PDT by diode laser light diffuse reflectance

    Science.gov (United States)

    Kholin, Vladimir V.; Chepurna, Oksana M.; Shton, Irina O.; Voytsehovich, Valerii S.; Pavlov, Sergii V.; Zabolotna, Natalia I.; Romaniuk, Ryszard; Wójcik, Waldemar; Amirgaliyev, Yedilkhan; Kovalev, Vladimir

    2017-08-01

    In the paper we explored the possibility of monitoring oxygenation of the tumor tissue through the registration of light diffuse reflectance. This method can also be helpful for assessment the effectiveness of PDT, defining the level of vascular damage and the degree of the tumor oxygenation. We also propose the modification of PDT procedure by using a modulated laser that enables to better maintain the necessary parameters for the PS activation and oxygen generation in irradiated tissues simultaneously allowing to reduce the light dose required for tumor treatment.

  10. Children and guns: The detection of recent contact with firearms on children's hands by the PDT reagent.

    Science.gov (United States)

    Bar-Or, Karni L; Almog, Joseph

    2015-08-01

    Throughout the world, young children are worryingly found to be involved in both unintentional and intentional gun violence, rendering the forensic investigation of gun handling by children a highly important matter. The effectiveness of the PDT reaction for mapping iron traces on hands of children has been tested and compared to its application on adults. Counter-intuitively, children were found to produce considerably more intense PDT impressions than adults. A plausible explanation which is based on physiological differences between children and adolescents is suggested. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Added value of OCT in evaluating the presence of leakage in patients with age-related macular degeneration treated with PDT

    NARCIS (Netherlands)

    van Velthoven, M. E. J.; de Smet, M. D.; Schlingemann, R. O.; Magnani, M.; Verbraak, F. D.

    2006-01-01

    BACKGROUND: Evaluating the presence of leakage on fluorescein angiography (FA) in patients with age-related macular degeneration (AMD) retreated with photodynamic therapy (PDT) can be difficult. New diagnostic tools such as optical coherence tomography (OCT) might help to optimize PDT management.

  12. Efficiency of autofluorescence diagnosis and photodynamic therapy (PDT) of bladder tumors: our own experience

    Science.gov (United States)

    Szygula, Michal; Wojciechowski, Boguslaw; Sieron, Aleksander; Adamek, Mariusz; Cebula, Wojciech; Biniszkiewicz, Tomasz; Zieleznik, Witold; Kawczyk-Krupka, Aleksandra

    2001-01-01

    The efficiency of autofluorescence diagnosis within urinary bladder was analyzed in the study. We examined two groups of patients: the first one consisting of 22 patients suspected to have bladder cancer and the second one consisting of 45 patients who have undergone transurethral electro resection due to urinary bladder neoplasms. Our goal was to detect cancerous tissue invisible in white-light examination. In the first group sensitivity was 100 percent and specificity was 69.23 percent. In the second group sensitivity was 96 percent and specificity was 80 percent. We also report in the study treatment efficiency of PDT in 12 patients with superficial bladder cancer. In our procedure two hours after the instillation of bladder with ALA solution, the lesion was irradiated by laser light. In 9 out of 12 treated patients regression of bladder tumor was obtained, while in 3 cases a progression of neoplasmatic process was observed.

  13. MEDIASI DALAM PENYELESAIAN SENGKETA WARIS: Studi Putusan No. 181/Pdt. G/2013/PA.Yk

    Directory of Open Access Journals (Sweden)

    Rini Fahriyani Ilham

    2017-03-01

    [Dalam kehidupan bermasyarakat sering kali terjadi persengketaan yang berkaitan dengan hak dan kewajiban dengan berbagai alasan. Pada umumnya sengketa dapat diselesaikan melalui mediasi. Mediasi dapat diterapkan di luar pengadilan (nonlitigasi ataupun di pengadilan (litigasi, seperti dalam sengketa kewarisan bagi orang Islam. Sengketa kewarisan termasuk salah satu kewenangan absolut Pengadilan Agama dengan objek sengketa berupa harta benda. Sengketa waris yang diajukan ke Pengadilan Agama dan diselesaikan melalui mediasi salah satunya adalah Putusan No. 181/Pdt. G/2013/PA.Yk yang diputus oleh Pengadilan Agama Yogyakarta. Tulisan ini mendeskripsikan proses mediasi serta tinjauan hukum Islam terhadap proses mediasi dalam penyelesaian sengketa waris terhadap putusan tersebut. Sengketa waris dalam putusan tersebut terjadi karena sebagian ahli waris telah menjual harta warisan dan masih ada ahli waris lain yang belum mendapat bagian.

  14. Low-irradiance red LED traffic lamps as light source in PDT for actinic keratoses.

    Science.gov (United States)

    Enk, Claes D; Levi, Assi

    2012-12-01

    LED light sources for photodynamic therapy have become increasingly popular due to their narrow emission spectra that accurately match the absorption spectrum of porphyrins. Photodynamic therapy at low fluence rates has been shown to be as effective as high output irradiation for treatment of non-melanoma skin cancers. Fifteen patients with multiple non-hypertrophic actinic keratoses covering the scalp and the face were treated with aminolaevulinic acid photodynamic therapy using ordinary red LED traffic lamps as light source. All 15 patients improved clinically after one photodynamic therapy session. Only two patients required a second session to obtain satisfactory remission. Pain was minimal during these sessions. Red LED traffic lights constitute a simple alternative to far more complicated and expensive PDT light sources. © 2012 John Wiley & Sons A/S.

  15. The involvement of NF-κB in PDT-induced death of crayfish glial and nerve cells

    Science.gov (United States)

    Berezhnaya, E. V.; Neginskaya, M. A.; Kovaleva, V. D.; Rudkovskii, M. V.; Uzdensky, A. B.

    2015-03-01

    Photodynamic therapy (PDT) is used for selective destruction of cells, in particular, for treatment of brain tumors. However, photodynamic treatment damages not only tumor cells, but also healthy neurons and glial cells. To study the possible role of NF-κB in photodynamic injury of neurons and glial cells, we investigated the combined effect of photodynamic treatment and NF-κB modulators: activator betulinic acid, or inhibitors parthenolide and CAPE on an isolated crayfish stretch receptor consisting of a single neuron surrounded by glial cells. A laser diode (670 nm, 0.4 W/cm2) was used as a light source. The inhibition of NF-κB during PDT increased the duration of neuron firing and glial necrosis and decreased neuron necrosis and glial apoptosis. The activation of NF-κB during PDT increased neuron necrosis and glial apoptosis and decreased glial necrosis. The difference between the effects of NF-κB modulators on photosensitized neurons and glial cells indicates the difference in NF-κB-mediated signaling pathways in these cell types. Thus, NF-κB is involved in PDT-induced shortening of neuron firing, neuronal and glial necrosis, and apoptosis of glial cells.

  16. Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

    Science.gov (United States)

    Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

    2014-02-01

    Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ΔT up to 80°C was measured.

  17. Metronomic photodynamic therapy (mPDT) -- headlights to lead the way forward: technical feasibility and rationale in brain tumor

    Science.gov (United States)

    Bisland, Stuart L.; Lilge, Lothar D.; Lin, Annie; Bogaards, Arjen; Wilson, Brian C.

    2003-12-01

    The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are deliverd continuously at low rates over extended periods in order to increase selective tumor cell kill through apoptosis. The focus of the present work is on mPDT treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown taht low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells within causing nectrosis in either tumor or normal brain tissue or apoptosis in teh latter. In order to produce enough tumor cell kill to be an effective therapy, multiple PDT treatments, such as hyperfractionation or metronomic delivery, are likely required, based on the levels of apoptosis achieved and model calculations of tumor growth rates. mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery while allowing free movement. In rat models ALAL administration via the drinking water has been accomplished at significant doesse (up to 10 times therapeutic dose) for up to 10 days, and ex vivo spectrofluorimetry of tumor, normal brain and other tissues post mortem demonstrates a 3-4 increase in the tumor-to-brain concentration of PpIX, without toxicity. Prototype light sources and delivery devices are also shown to be practical, either using laser diode or light emitting diode (LED) coupled to an implanted optical fiber in the case of the rat model or a directly-implanted LED in rabbits. The combined delivery of both drug and light over an extended period, with survival of the animls, is demonstrated. Preliminary evidence of selective aopotosis of tumor under these conditions is presented.

  18. Preclinical dosimetric estimation of [{sup 111}In] 5, 10, 15, 20-tetra phenyl porphyrin complex as a possible imaging/PDT agent

    Energy Technology Data Exchange (ETDEWEB)

    Fazaeli, Yousef; Shanehsazzadeh, Saeed; Feizi, Shahzad; Jalilian, Amirreza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Lahooti, Afsaneh [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Medical Physics and Biomedical Engineering

    2016-08-01

    Recent studies show that porphyrin derivatives have interesting pharmacological and photodynamic properties and wide range of usage in photodynamic therapy treatment. This study describes the preparation, biodistribution and absorbed dose prediction of [{sup 111}In] labeled 5, 10, 15, 20-tetra phenyl porphyrin (TPP) in human organs, based on rats' biodistribution data. Five rats were sacrificed at each exact time intervals (2, 4 and 24 h post injection) and the percentage of injected dose per gram of each organ was measured by direct counting from rats data from 12 harvested organs. The Medical Internal Radiation Dose (MIRD) formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. From rat data we estimated that injection of [{sup 111}In] TPP into the humans would result in an estimated effective absorbed dose of 0.09 mSv/MBq in the whole body. While the highest effective absorbed dose for {sup 111}In-TPP was in the heart wall (0.22 mSv), the organs that received the next highest doses were the Kidneys (0.06 mSv), thymus (0.04 mSv) and lungs (0.03 mSv). The skin dose will four times higher compare to the other {sup 111}In compounds, which was due to magnificent skin uptakes. According to the fast wash-out, tumor avidity and the short half-life, [{sup 111}In] can be a suitable candidate for labeling of photo dynamic therapy (PDT) agents as a tracer for accurate biological evaluation of other PDT agents such as Photofrin and its homologs.

  19. Optimization and therapeutic effects of PDT mediated by ALA and MAL in the treatment of cutaneous malignant lesions: A comparative study.

    Science.gov (United States)

    Lima, Cassio Aparecido; Goulart, Viviane Pereira; Bechara, Etelvino Jose Henriques; Correa, Luciana; Zezell, Denise Maria

    2016-12-01

    5-aminolevulinic acid (ALA) and its methylated ester (MAL) are the most common topical agents used in photodynamic therapy (PDT) as precursors of the photosensitizer protoporphyrin IX (PpIX). The induction of newly PpIX depends on incubation time of each photosensitizer in the tissue and the presence of high intralesional porphyrin levels is an important parameter for the PDT effectiveness. This study used laser-induced fluorescence (LIF) spectroscopy to evaluate the optimum time to light exposure of PDT mediated by ALA (20% w/w) and MAL (10% w/w) to treat malignant lesions precursors of cutaneous squamous cell carcinoma induced in mice. The therapeutic effects obtained by optimized ALA- and MAL-PDT were assessed 10 and 20 days after treatments. Higher PpIX levels were evidenced in the lesions photosensitized by ALA than MAL and according to LIF measurements the PDT irradiation was performed, respectively, at 300 and 330 minutes after ALA and MAL incubation. Histopathological analysis evidenced necrosis and epithelial atrophy after 10 days of PDT using both prodrugs, as well as reepitelization and collagen deposition at 20 days. Thus, despite the distinct concentration of ALA and MAL used in the formulation of each photosensitizing cream, PDT mediated by both photosensitizing agents obtained similar therapeutic outcomes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress.

    Science.gov (United States)

    Li, Donghong; Li, Lei; Li, Pengxi; Li, Yi; Chen, Xiangyun

    2015-01-01

    Photodynamic therapy (PDT) is emerging as a viable treatment for many cancers. To decrease the cutaneous photosensitivity induced by PDT, many attempts have been made to search for a targeting photosensitizer; however, few reports describe the molecular mechanism of PDT mediated by this type of targeting photosensitizer. The present study aimed to investigate the molecular mechanism of PDT induced by a new targeting photosensitizer (PS I), reported previously by us, on HeLa cells. Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug-light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER) of HeLa cells. PS I PDT resulted in rapid increases in intracellular reactive oxygen species (ROS) production and Ca(2+) concentration, both of which reached a peak nearly simultaneously at 15 minutes, followed by the loss of mitochondrial membrane potential at 30 minutes, release of cytochrome c from mitochondria into the cytoplasm, downregulation of Bcl-2 expression, and upregulation of Bax expression. Meanwhile, activation of caspase-3, -9, and -12, as well as induction of C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP78), in HeLa cells after PS I PDT was also detected. These results suggest that apoptosis of HeLa cells induced by PS I PDT is not only triggered by ROS but is also regulated by Ca(2+) overload. Mitochondria and the ER serve as the subcellular targets of PS I PDT, the effective activation of which is responsible for PS I PDT-induced apoptosis in HeLa cells.

  1. Vascular targeting to the SST2 receptor improves the therapeutic response to near-IR two-photon activated PDT for deep-tissue cancer treatment.

    Science.gov (United States)

    Starkey, Jean R; Pascucci, Elizabeth M; Drobizhev, Mikhail A; Elliott, Aleisha; Rebane, Aleksander K

    2013-10-01

    Broader clinical acceptance of photodynamic therapy is currently hindered by (a) poor depth efficacy, and (b) predisposition towards establishment of an angiogenic environment during the treatment. Improved depth efficacy is being sought by exploiting the NIR tissue transparency window and by photo-activation using two-photon absorption (2PA). Here, we use two-photon activation of PDT sensitizers, untargeted and targeted to SST2 receptors or EGF receptors, to achieve deep tissue treatment. Human tumor lines, positive or negative for SST2r expression were used, as well as murine 3LL cells and bovine aortic endothelial cells. Expression of SST2 receptors on cancer cells and tumor vasculature was evaluated in vitro and frozen xenograft sections. PDT effects on tumor blood flow were followed using in vivo scanning after intravenous injection of FITC conjugated dextran 150K. Dependence of the PDT efficacy on the laser pulse duration was evaluated. Effectiveness of targeting to vascular SST2 receptors was compared to that of EGF receptors, or no targeting. Tumor vasculature stained for SST2 receptors even in tumors from SST2 receptor negative cell lines, and SST2r targeted PDT led to tumor vascular shutdown. Stretching the pulse from ~120fs to ~3ps led to loss of the PDT efficacy especially at greater depth. PDT targeted to SST2 receptors was much more effective than untargeted PDT or PDT targeted to EGF receptors. The use of octreotate to target SST2 receptors expressed on tumor vessels is an excellent approach to PDT with few recurrences and some long term cures. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Noninvasive imaging of absolute PpIX concentration distribution in nonmelanoma skin tumors at pre-PDT

    Science.gov (United States)

    Sunar, Ulas; Rohrbach, Daniel; Morgan, Janet; Zeitouni, Natalie

    2013-03-01

    Photodynamic Therapy (PDT) has proven to be an effective treatment option for nonmelanoma skin cancers. The ability to quantify the concentration of drug in the treated area is crucial for effective treatment planning as well as predicting outcomes. We utilized spatial frequency domain imaging for quantifying the accurate concentration of protoporphyrin IX (PpIX) in phantoms and in vivo. We correct fluorescence against the effects of native tissue absorption and scattering parameters. First we quantified the absorption and scattering of the tissue non-invasively. Then, we corrected raw fluorescence signal by compensating for optical properties to get the absolute drug concentration. After phantom experiments, we used basal cell carcinoma (BCC) model in Gli mice to determine optical properties and drug concentration in vivo at pre-PDT.

  3. Calculation of singlet oxygen formation from one photon absorbing photosensitizers used in PDT

    Science.gov (United States)

    Potasek, M.; Parilov, Evgueni; Beeson, K.

    2013-03-01

    Advances in biophotonic medicine require new information on photodynamic mechanisms. In photodynamic therapy (PDT), a photosensitizer (PS) is injected into the body and accumulates at higher concentrations in diseased tissue compared to normal tissue. The PS absorbs light from a light source and generates excited-state triplet states of the PS. The excited triplet states of the PS can then react with ground state molecular oxygen to form excited singlet - state oxygen or form other highly reactive species. The reactive species react with living cells, resulting in cel l death. This treatment is used in many forms of cancer including those in the prostrate, head and neck, lungs, bladder, esophagus and certain skin cancers. We developed a novel numerical method to model the photophysical and photochemical processes in the PS and the subsequent energy transfer to O2, improving the understanding of these processes at a molecular level. Our numerical method simulates light propagation and photo-physics in PS using methods that build on techniques previously developed for optical communications and nonlinear optics applications.

  4. Report on MPACT Deliverable M3FT-16LA040106035 (High Dose Evaluation of Improved PDT Detector Pod)

    Energy Technology Data Exchange (ETDEWEB)

    Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-18

    This report provides the results for the initial high gamma dose tests for the boron-10 plate detector that was fabricated by PDT, Inc. under contract to LANL The specifications for the detector were developed using MCNP code simulations and prior experimental tests at LANL. The goal in the development was to provide high neutron detection efficiency together with gamma-ray resistance at very high gamma dose levels that are characteristic of the electrochemical fuel processing activity.

  5. ALA-PDT elicits oxidative damage and apoptosis in UVB-induced premature senescence of human skin fibroblasts.

    Science.gov (United States)

    Zhou, Bing-Rong; Zhang, Li-Chao; Permatasari, Felicia; Liu, Juan; Xu, Yang; Luo, Dan

    2016-06-01

    5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been used for the treatment of skin photoaging. It can significantly improve the appearance of fine lines, dotted pigmentation, and roughness of photoaged skin. However, the mechanisms by which ALA-PDT yields rejuvenating effects on photoaged skin have not been well elucidated. Thus, in this study we explored the effects of ALA-PDT in photoaged fibroblasts. We established a stress-induced premature senescence (SIPS) model by repeated exposures of human dermal fibroblasts (HDFs) to ultraviolet B (UVB) irradiation. Cells were irradiated by red light laser at 635nm wavelength (50mW/cm(2)). Intracellular protoporphyrin IX (PpIX) was detected by confocal microscopy. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) change were detected by fluorescence microscopy and flow cytometry. Morphological changes were observed by optical microscopy. Proliferative activity was measured by a cell counting kit-8 (CCK-8). Cell apoptosis was detected by fluorescence microscopy using Hoechst staining and flow cytometry using annexin V/propidium Iodide double staining. Intracellular PpIX fluorescence in UVB-induced premature senescent HDFs (UVB-SIPS-HDFs) reached the highest intensity after incubation with 1.00mmol/L ALA for 6h (PPDT, which were positively correlated to ALA incubation time and red light laser dose. Our study demonstrated that ALA-PDT elicits oxidative damage and apoptosis in photoaged fibroblasts in vitro, which may be the basis for the rejuvenating effects on photoaged skin. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Evaluation of resistance development and viability recovery by a non-enveloped virus after repeated cycles of aPDT.

    Science.gov (United States)

    Costa, Liliana; Tomé, João P C; Neves, Maria G P M S; Tomé, Augusto C; Cavaleiro, José A S; Faustino, Maria A F; Cunha, Ângela; Gomes, Newton C M; Almeida, Adelaide

    2011-09-01

    Nowadays, the emergence of drug resistant microorganisms is a public health concern. The antimicrobial photodynamic therapy (aPDT) has an efficient action against a wide range of microorganisms and can be viewed as an alternative approach for treating microbial infections. The aim of this study was to determine if a model target virus (T4-like bacteriophage), in the presence of the tricationic porphyrin 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin tri-iodide (Tri-Py(+)-Me-PF), can develop resistance to aPDT and recover its viability after photodynamic treatments. To assess the development of aPDT resistance after repeated treatments, a suspension of T4-like bacteriophage was irradiated with white light (40 Wm(-2)) for 120 min in the presence of 5.0 μM of Tri-Py(+)-Me-PF (99.99% of inactivation) and new phage suspensions were produced from the surviving phages, after each cycle of light exposure. The procedure was repeated ten times. To evaluate the recovery of viral viability after photoinactivation, a suspension of T4-like bacteriophage was irradiated with white light for 120 min in the presence of 5.0 μM of Tri-Py(+)-Me-PF on five consecutive days. In each day, an aliquot of the irradiated suspension was plated and the number of lysis plaques was counted after 24, 48, 72, 96 and 120 h of dark incubation at 37 °C. The profile of bacteriophage photoinactivation did not change after ten consecutive cycles and no recovery of viability was detected after five accumulated cycles of photodynamic treatment. The results suggest that aPDT represents a valuable and promising alternative therapy to treat viral infections, overcoming the problem of microbial resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Development of image-guided targeted two-photon PDT for the treatment of head and neck cancers

    Science.gov (United States)

    Spangler, Charles W.; Starkey, Jean R.; Liang, Bo; Fedorka, Sara; Yang, Hao; Jiang, Huabei

    2014-03-01

    There has been significant effort over the past two decades in the treatment of malignancies of epithelial origin, including some of the most devastating of cancers, such as colorectal cancer (CRC), squamous call carcinoma of the head and neck (HNSCC), and carcinomas of the pancreas, lungs, (both Small Cell and Non-Small Cell), renal cell, prostate, bladder and breast. Recurring, refractory HNSCC is a particularly difficult cancer to treat once the tumors recur due to mutations that are resistant to repeat chemotherapy and radiation. In addition, repeat surgery is often difficult due to the requirement of significant surgical margins that may not be possible due to the attending potential functional deficits (e.g., salivary glands, nerves and major blood vessels in confined areas). In this study FaDu HNSCC xenograft tumors in SCID mice were imaged, and "optical", as opposed to "surgical" margins defined for the tumor being treated. The subsequent two-photon treatment irradiation was computer-controlled to carry out the tumor treatment by rastering the laser beam throughout the tumor volume plus the defined optical margins simultaneously. In our initial studies, up to 85% regression in tumor volume was observed in 5 days post PDT, with complete tumor regression in 18 days. No re-growth was observed up to 41 days post-PDT, with little or no scarring and complete hair re-growth. However, competition between imaging and PDT moieties was also observed in some mouse models, possibly favoring tumor re-growth. Strategies to selectively optimize the PDT effect will be discussed.

  8. Systemic ALA-PDT effectively blocks the development of psoriasis-like lesions and alleviates leucocyte infiltration in the K14-VEGF transgenic mouse.

    Science.gov (United States)

    Chen, T; Zhang, L-W; Fu, L-X; Wu, Y-B; Liu, X-Y; Guo, Z-P

    2017-12-01

    Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders. In spite of significant advances in the treatment of psoriasis, more effective and safer therapeutic strategies are still needed. Photodynamic therapy (PDT) is a method of light treatment that is being used increasingly in the treatment of dermatological diseases. To evaluate the therapeutic effects of systemic 5-aminolaevulinic acid (ALA)-PDT on psoriasis and to explore its potential mechanism of action. We investigated the therapeutic effects of systemic ALA-PDT in K14-vascular endothelial growth factor (VEGF) transgenic homozygous mice, an animal model of psoriasis, which has many clinical and histopathological characteristics similar to those of human psoriasis. Using haematoxylin and eosin staining, immunohistochemistry and real-time quantitative PCR respectively, we assessed the changes in psoriasis-like lesions, cellular infiltration of T cells, dendritic cells (DCs) and neutrophils, and the mRNA expression of the inflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in the lesions. Systemic ALA-PDT blocked the development of psoriasis-like lesions and moderately attenuated the histopathological changes in K14-VEGF transgenic mice. Furthermore, systemic ALA-PDT produced an obvious reduction in infiltration of T cells, CD11c+ DCs and neutrophils in psoriasis-like lesions. In addition, systemic ALA-PDT also significantly decreased the mRNA expression of IL-17 and IFN-γ. We suggest that the mechanism of systemic ALA-PDT in this psoriasis-like model might be associated with selective damage to abnormal T helper (Th)1 and Th17 cells, and reduction of the inflammatory cytokines IL-17 and IFN-γ. These observations partly explain the potential mechanism of systemic ALA-PDT in psoriasis and other inflammatory skin diseases. © 2017 British Association of Dermatologists.

  9. Cellular density, a major factor involved in PDT cytotoxic responses: Study on three different lines of human retinoblastoma grafted on nude mice.

    Science.gov (United States)

    Thomas, Carole D; Poyer, Florent; Maillard, Philippe; Chauvin, Benoit; Lupu, Mihaela; Mispelter, Joël

    2015-06-01

    PDT represents a very localized and non-mutagen antitumoral treatment using a photosensitive molecule (porphyrin family) light activated. The first way of cell damage is a direct one, active on the very site where ROSs have been produced. The second one is indirect by activating and transmitting the processes of cellular death signaling. In order to seek for a better characterization of the photo-biology involved in in vivo PDT and to better understand the differences on the treatment outcome, we have used three different human retinoblastomas xenografted on mice. Mice were treated according to the double targeting protocol exposed in a previous paper. One i.v. dose (0.6 mg/kg) of PS was followed by a second dose, separated by a 3 h interval (double targeting PDT). As a consequence both cancer cells and blood vessels were targeted. The treatment was repeated two times, at 4 days interval. First of all, sodium MRI revealed qualitative differences in the sodium average content of the three retinoblastoma lines before treatment. After the PDT treatments the tumor responses were different between the lines as revealed by sodium MRI and later on by histology. We have put into evidence that PDT is accompanied by a bystander effect that may propagate the cellular death triggered by the initial photoreaction. This effect is highly dependent on the cellular density of the tissue; therefore this factor is to be taken into account in clinical PDT protocols. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin

    Directory of Open Access Journals (Sweden)

    Li-Wen Zhang

    2011-03-01

    Full Text Available Photodynamic therapy (PDT is a popular technique for skin cancer treatment. Protoporphyrin IX, which is a photosensitizing agent, converted enzymatically from the prodrug 5-aminolevulinic acid (ALA, is used as a photosensitizer in PDT for cancer. However, ALA penetrates with difficulty through intact skin; therefore, improving delivery systems for ALA in the skin will play an important role in ALA-PDT. Enhancement of ALA skin penetration can be achieved by physical methods, such as iontophoresis, laser, microneedles, ultrasound, and by adding chemical penetration enhancers, such as, dimethyl sulfoxide, oleic acid, and others, whereas some researches used lipophilic ALA derivatives and different vehicles to improve the transdermal delivery of ALA. This review introduces several enhancement techniques for increasing ALA permeation through the skin.

  11. Effectiveness in total reduction of Candida albicans promoted by PDT with hypocrellin B:lanthanum

    Science.gov (United States)

    Tofolli, Daniel J.; Prates, Renato A.; Ribeiro, Martha S.; Vieira, Nilson D., Jr.; Hashimoto, M. C. E.; Courrol, Lilia C.

    2009-06-01

    In this work we described the potentiality of the Hypocrellin B (HB) modified with the presence of lanthanum (La3+) ions, in eliminate Candida albicans in suspension. The results showed that the presence of lanthanum ions promotes a red shift of the HB absorption band and an enhancement in singlet oxygen quantum yield in 32%. Also in this work we obtained that the best molar ration between HB and La concentrations was 1:2. No photobleaching was observed in our experimental conditions. Antimicrobial activity was studied exciting C. albicans suspension with a 460 nm LED and a 660 nm laser both with 330 mW/cm2 irradiance. Best irradiation time, PS concentration and ROS production profile were determined showing that using 460 nm LED with 10 μM of PS, only 30 s of irradiation time was sufficient to reduce 100 % C. albicans colonies.

  12. Polymer-bound meso-chlorin e6 for PDT (Invited Paper)

    Science.gov (United States)

    Krinick, Nancy L.; Sun, Ying; Joyner, D. A.; Reed, R.; Spikes, John D.; Straight, Richard C.; Kopecek, Jindrich

    1992-06-01

    characteristics of current PDT treatment such as light ultrasensitivity in skin may be reduced by improving localization selectivity.

  13. Persamaan Unsur Pokok Pada Suatu Merek Terkenal (Analisis Putusan MA Nomor 162 K/Pdt.Sus-HKI/2014

    Directory of Open Access Journals (Sweden)

    Dandi Pahusa

    2016-04-01

    Full Text Available Abstract: Equation Basic Element In A Famous Brand (Analysis of the Decision of the Supreme Court Number 162 K / Pdt.Sus-IPR / 2014. Criteria for determining the equation of the constituents in a well-known brand that is the similarity of images, sounds, names, words, letters, numbers, color composition or a combination of these elements, either for goods or services that are similar or dissimilar based on general knowledge of the public, the brand earned a reputation as a massive campaign, and with evidence of the trademark registration in several countries. The impact of the decision of the Supreme Court Number 162 K / Pdt.Sus-IPR / 2014 for brand owners who have registered and well-known to always protect its brand, namely by taking into account the bad faith of the owner of the other brands. If there are other brands that have been registered in the Directorate General of Intellectual Property and published in General News Brands, the owner of the mark that has been registered in advance immediately appealed and the cancellation of the trademark. Abstrak: Persamaan Unsur Pokok Pada Suatu Merek Terkenal (Analisis atas Putusan MA Nomor 162 K/Pdt.Sus-HKI/2014. Kriteria penentuan persamaan unsur pokok pada suatu merek terkenal yaitu adanya kemiripan gambar, bunyi, nama, kata, huruf-huruf, angka-angka, susunan warna atau kombinasi dari unsur-unsur tersebut, baik terhadap barang atau jasa yang sejenis maupun tidak sejenis yang didasarkan pada pengetahuan umum masyarakat, reputasi merek yang diperoleh karena promosi besar-besaran, dan disertai bukti pendaftaran merek tersebut di beberapa negara. Dampak dari putusan Mahkamah Agung Nomor 162 K/Pdt.Sus-HKI/2014 bagi pemilik merek yang telah terdaftar dan terkenal agar selalu melindungi mereknya yaitu dengan memperhatikan adanya itikad tidak baik dari pemilik merek lain. Apabila terdapat merek lain yang telah terdaftar di Dirjen HKI dan diumumkan dalam Berita Umum Merek, maka pemilik merek yang telah

  14. FosPeg® PDT alters the EBV miRNAs and LMP1 protein expression in EBV positive nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Wu, Ricky W K; Chu, Ellie S M; Huang, Zheng; Xu, C S; Ip, C W; Yow, Christine M N

    2013-10-05

    Nasopharyngeal carcinoma (NPC) is one of the top ten cancers highly prevalent in Hong Kong and South China. Epstein-Barr virus (EBV) infection contributes to the tumorigenesis of NPC through the expression of different viral proteins. Among these, Latent Membrane Protein 1(LMP1) is the major oncoprotein expressed by EBV. Foscan® (Biolitec AG), m-tetrahydroxyphenylchlorin (mTHPC)-based photosensitizing drug, has been used in the photodynamic therapy (PDT) for head and neck cancers. FosPeg® (Biolitec AG) is a new formulation of mTHPC contained in PEGylated liposomes with optimized distribution properties. In this in vitro study, the potential of FosPeg®-PDT on human EBV positive NPC cell (c666-1) and EBV negative cells (HK1 and CNE2) were investigated. Effects of FosPeg®-PDT on the expression of EBV BART miRNAs (EBV miRNA BART 1-5p, BART 16, and BART 17-5p), LMP1 mRNA and proteins on c666-1 cells were also elucidated. The killing efficacy of FosPeg®-PDT on NPC cells were determined by MTT assay after LED activation. Effects of FosPeg®-PDT on the expression of LMP1 mRNA and protein were examined by real time PCR and western blot analysis. FosPeg®-PDT demonstrated its antitumor effect on c666-1 cells in a drug and light dose dependent manner. LD30, LD50 and LD70 were achieved by applying LED activation (3J/cm(2)) at 4h post incubated cells with 0.05μg/ml, 0.07μg/ml and 0.3μg/ml FosPeg®, respectively. Up-regulation of both LMP1 mRNA and protein were observed after FosPeg®-PDT in a dose dependent manner. FosPeg®-PDT exerted antitumor effect on c666-1 cells through up-regulation of LMP1 protein. Understanding the mechanism of FosPeg®-PDT may help to develop better strategies for the treatment of NPC. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress

    Directory of Open Access Journals (Sweden)

    Li D

    2015-04-01

    Full Text Available Donghong Li,1 Lei Li,2 Pengxi Li,1 Yi Li,3 Xiangyun Chen1 1State Key Laboratory of Trauma, Burn and Combined Injury, The Second Department of Research Institute of Surgery, 2The First Department of Research Institute of Surgery, 3Cancer Center, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Photodynamic therapy (PDT is emerging as a viable treatment for many cancers. To decrease the cutaneous photosensitivity induced by PDT, many attempts have been made to search for a targeting photosensitizer; however, few reports describe the molecular mechanism of PDT mediated by this type of targeting photosensitizer. The present study aimed to investigate the molecular mechanism of PDT induced by a new targeting photosensitizer (PS I, reported previously by us, on HeLa cells. Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug–light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER of HeLa cells. PS I PDT resulted in rapid increases in intracellular reactive oxygen species (ROS production and Ca2+ concentration, both of which reached a peak nearly simultaneously at 15 minutes, followed by the loss of mitochondrial membrane potential at 30 minutes, release of cytochrome c from mitochondria into the cytoplasm, downregulation of Bcl-2 expression, and upregulation of Bax expression. Meanwhile, activation of caspase-3, -9, and -12, as well as induction of C/EBP homologous protein (CHOP and glucose-regulated protein (GRP78, in HeLa cells after PS I PDT was also detected. These results suggest that apoptosis of HeLa cells induced by PS I PDT is not only triggered by ROS but is also regulated by Ca2+ overload. Mitochondria and the ER serve as the subcellular targets of PS I PDT, the effective activation of which

  16. Show-Bix &

    DEFF Research Database (Denmark)

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies...... are made from digital scans of the original dias slides located in the collection of the Museum of Contemporary Art in Roskilde. In front of the audience entering the space and placed on it’s own stand, is an original 60s style telephone with turning dial. Action begins when the audience lift the phone...... and dial a number. Any number will make the Dias change. All numbers are also assigned to specific sound documents: clips form rare interviews and the complete sound-re-enactment of the Show-Bix piece ‘Omringning’ (‘Surrounding’) in five channels (a quintophonie). This was originally produced...

  17. Show and Tell

    DEFF Research Database (Denmark)

    2013-01-01

    Fredag d. 1 november blev Kunsthal Charlottenborg indtaget af performanceprogrammet Show & Tell med et bredspektret program af danske og internationale kunstnere indenfor performance-, lyd- og installationskunst. Programmet præsenterer værker, der undersøger kroppens stadig mere symbiotiske forhold...... og studienævnet på Performance-design. Show & Tell - Performance program: kl. 16.30-19 Adresse: Kunsthal Charlottenborg, Nyhavn 2, 1051 København K...

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

    Science.gov (United States)

    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.

  19. SnWO4-based nanohybrids with full energy transfer for largely enhanced photodynamic therapy and radiotherapy.

    Science.gov (United States)

    Zhang, Meng; Cui, Zhaowen; Song, Ruixue; Lv, Bin; Tang, Zhongmin; Meng, Xianfu; Chen, Xiaoyan; Zheng, Xiangpeng; Zhang, Jiawen; Yao, Zhenwei; Bu, Wenbo

    2018-02-01

    The "partial matching" between upconversion nanoparticle (UCNP) emission and absorption by photosensitizers (PSs) often leads to a theoretically reduced therapeutic efficiency in UC-based photodynamic therapy (PDT) strategies in which the chosen PSs have limited capabilities and are unable to utilize all the near-infrared-upconverted light. In this study, needle-like SnWO 4 nanocrystals (SWs) with a broad UV-vis absorption region were synthesized to solve the problem. After covalent conjugation with UCNPs, all the UCNP-emitted light was effectively absorbed by SWs, triggering the type-I PDT process to activate ROS maxima. The unique nanostructure of the as-formed UCNP-SnWO 4 nanohybrids (USWs) also enhanced the receiving light intensities of SW, which further boosted the antitumor efficacy. Meanwhile, the strong X-ray attenuation capacity of both tungsten and tin elements qualified the USWs as excellent radio-sensitizers for radiotherapy (RT) enhancement, which played a complementary role with PDT treatment because PDT-mediated induction arrested the cells in the G0-G1 cell cycle phase, and RT was more damaging toward cells in the G2/M phase. The remarkably enhanced UC-PDT/RT efficiency of USWs was next validated in vitro and in vivo, and the combined NIR light and ionizing irradiation treatment completely suppressed tumor growth, revealing its great potential as an efficient anticancer therapeutic agent against solid tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Assessment of Photodynamic Therapy (PDT) in Disinfection of Deeper Dentinal Tubules in a Root Canal System: An In Vitro Study.

    Science.gov (United States)

    Bumb, Swapnil Sunil; Bhaskar, Dara John; Agali, Chandan R; Punia, Himanshu; Gupta, Vipul; Singh, Vikas; Kadtane, Safalya; Chandra, Sneha

    2014-11-01

    The success of endodontic treatment therapy depends on how well we eliminate pathogenic microflora from the root canal system as micro organism as the major cause of root canal infection. Conventional root canal treatment can fail if microorganisms cannot be removed sufficiently by thorough cleaning, shaping of root canal. Newer modalities such as photodynamic therapy are being tried now a days for disinfection of root canals. Aim & Objectives: The basic aim of this study was assessment of the antimicrobial efficacy of Photodynamic Therapy in deeper dentinal tubules for effective disinfection of root canals using microbiological and scanning electron microscopic examination in vitro. The study was conducted at Teerthanker Mahaveer Dental College & Research Centre. The teeth required for study was collected from Department of Oral and Maxillofacial Surgery. Only freshly extracted 20 intact, non carious single rooted teeth which were indicated for orthodontic treatment were taken for this study. Statistical analysis was done using Student's Unpaired t-test were at (pPDT group as compared to control group. The results of the present study indicate that PDT can be effectively used during antimicrobial procedures along with conventional disinfection procedure for sterilization of root canals.

  1. Short and long term stability of the Diomed 630PDT laser evaluated with integrating sphere, power meter, and calorimeter

    Science.gov (United States)

    Austerlitz, C.; Campos, D.; Allison, R.; Sheng, C.; Bonnerup, C.; Sibata, C.

    2009-06-01

    The short and long term stability of the Diomed 630 PDT laser with attached fiberoptic microlens was evaluated by means of integrating sphere, power meter and a calorimetric system. The calorimeter system was designed as a thermal mug with absorbing media (dye and water). Both the tip of the irradiation fiber and the detection probe of a thermocouple thermometer were positioned inside the dye solution and stirred during the measurements. The calorimetric system yielded measurement results consistent with the other two methods, and similar long term variations were observed by all methods. With an indicated laser power of 1 W, the detectors' readings ranged from 0.66 to 1.29 W. For short term stability study, the deviation of laser output assessed by integrating sphere, power meter and calorimetric system were 0.3%, 0.1% and 2.8% with long term deviations of 13%, 7% and 9% respectively. This wide variation in the laser output implies the needs to establish quality control procedures involving measurements pre and post PDT procedures. The calorimetric system has been demonstrated to be a powerful tool for clinical laser QA and maintenance of the calibration factor of the detectors used in this work.

  2. Effectiveness of antimicrobial photodynamic therapy (AmPDT) on Staphylococcus aureus using phenothiazine compound with red laser.

    Science.gov (United States)

    Monteiro, Juliana S C; de Oliveira, Susana C P S; Pires Santos, Gustavo M; Pires Sampaio, Fernando José; Pinheiro Soares, Luiz Guilherme; Pinheiro, Antônio L B

    2017-01-01

    The aim of this study was to evaluate, in vitro, the bactericidal effect of antimicrobial photodynamic therapy (AmPDT) using phenothiazinium dyes (Toluidine Blue O and methylene blue, 1:1) using different concentrations (100, 50, 25, 12.5, and 6.25 μg/mL) associated to red laser with different energy densities (2.4, 4.8, 7.2, 9.6, and 12 J/cm 2 ) on a strain of Staphylococcus aureus (ATCC 23529). On this study, tests were performed in triplicate and the samples were distributed into 36 test groups: Control and bacterial suspensions were irradiated with the different energy densities, respectively, in the absence of photosensitizer, bacterial suspensions were irradiated with the laser in the different concentrations of the photosensitizer, and finally bacterial suspensions only in the presence of phenothiazinium dye. The pre-irradiation time was 5 min. Therefore, we analyzed the potential of the AmPDT by counting colony-forming units. The logarithm of CFU/mL (log10 CFU/mL) was calculated and the data was analyzed statistically (ANOVA, Tukey's test, p antimicrobial effect of phenothiazines and both concentration of the compound and energy density are important factors for greater effectiveness of therapy.

  3. Talking with TV shows

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Laursen, Ditte

    2014-01-01

    User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication....... More specifically, the article demonstrates how online comments posted on the day of Voice’s 2012 season finale can be grouped into four basic action types: (1) Invitation to consume content, (2) Request for participation, (3) Request for collaboration and (4) Online commenting. These action types...

  4. Um show de cacau

    OpenAIRE

    Rezende, José Francisco; UNIGRANRIO / PPGA; Mello, Simone; UNIGRANRIO

    2016-01-01

    O caso de ensino apresenta a trajetória de Alexandre Tadeu da Costa e da chocolateria Cacau Show. Seu objetivo é levar os estudantes a identificar alternativas e tomar decisões sobre posicionamento para continuidade do desenvolvimento de vantagens competitivas, sustentação de competência logística e possíveis abordagens ao mercado externo. 

  5. Taking in a Show.

    Science.gov (United States)

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments.

  6. Showing Value (Editorial

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2009-06-01

    Full Text Available When Su Cleyle and I first decided to start Evidence Based Library and Information Practice, one of the things we agreed upon immediately was that the journal be open access. We knew that a major obstacle to librarians using the research literature was that they did not have access to the research literature. Although Su and I are both academic librarians who can access a wide variety of library and information literature from our institutions, we belong to a profession where not everyone has equal access to the research in our field. Without such access to our own body of literature, how can we ever hope for practitioners to use research evidence in their decision making? It would have been contradictory to the principles of evidence based library and information practice to do otherwise.One of the specific groups we thought could use such an open access venue for discovering research literature was school librarians. School librarians are often isolated and lacking access to the research literature that may help them prove to stakeholders the importance of their libraries and their role within schools. Certainly, school libraries have been in decline and the use of evidence to show value is needed. As Ken Haycock noted in his 2003 report, The Crisis in Canada’s School Libraries: The Case for Reform and Reinvestment, “Across the country, teacher-librarians are losing their jobs or being reassigned. Collections are becoming depleted owing to budget cuts. Some principals believe that in the age of the Internet and the classroom workstation, the school library is an artifact” (9. Within this context, school librarians are looking to our research literature for evidence of the impact that school library programs have on learning outcomes and student success. They are integrating that evidence into their practice, and reflecting upon what can be improved locally. They are focusing on students and showing the impact of school libraries and

  7. Efficiency enhancement of flexible Cu(In,Ga)Se2 solar cells deposited on polyimide-coated soda lime glass substrate by alkali treatment

    Science.gov (United States)

    Sadono, Adiyudha; Ogihara, Tomohiro; Hino, Masashi; Yamamoto, Kenji; Nakada, Kazuyoshi; Yamada, Akira

    2017-08-01

    Alkali treatment effects on Cu(In,Ga)Se2 (CIGS) solar cells deposited on polyimide-coated soda lime glass (PI-coated SLG) were investigated. CIGS on PI-coated SLG shows Na diffusion from the substrate, which should be controlled to obtain high efficiencies. Further incorporation of Na was achieved by enhancing diffusion from the substrate or by external incorporation using post-deposition treatment (PDT) methods. Both methods lead to a high efficiency of approximately 15%. Moreover, aside from Na, K was also incorporated by KF-PDT, resulting in efficiency improvement from 12% for an untreated CIGS to more than 18% at the maximum substrate temperature of 450 °C, which is comparable to CIGS deposited at higher temperatures using the same equipment. It was also found that the alkali concentration of CIGS deposited on PI-coated SLG shows almost the same behavior as that of a film deposited on a rigid glass, suggesting that the deposition technique for CIGS on the rigid glass can be applied to flexible substrates.

  8. EKSEPSI PLURIUM LITIS CONSORTIUM (Studi Terhadap Putusan Pengadilan Tinggi Semarang No. 401/Pdt/2002/PT. Smg jo. Putusan Pengadilan Negeri Purwokerto No.41/Pdt.G/2000/PN.Pwt

    Directory of Open Access Journals (Sweden)

    Siti Muflichah

    2008-05-01

    Full Text Available In the civil jurisdiction, truth searched is the formal truth. This matter of course different from the criminal justice, where truth searched is material truth. Searching the formal truth, meaning that judge may not be abysmal of boundary that raised by the parties. This matter contain the congeniality, that verification process is not see at wight or content, but to wide of case scope or dispute that raised by the parties. In this case judge have the passive character. in civil jurisdiction, truth searched is a truth that relying on formal verification. The Judge decision shall contain the rule of law element, justice and benefit. For the reason judge have to careful, goodness in making draft of decision and also decision intake later. In Case No. 401/ Pdt / 2002 / PT. Smg, The Judge of High Court of middle of Java made the decision by strengthening decision of District Court of Purwokerto in case No. 41/Pdt.G/2000/PN Pwt. This Judge Decision represent an example of careless of the judge in make decision. exception of the lack of party had refused. Therefore, judge have to consider this matter in its decision. Therefore, judge have to consider this matter in its decision. This matter of course relative harm the plaintiff, because if suing is not accepted, plaintiff can improve/ repair its suing or make a lawsuit to the court newly again. But refusedly of suing make the plaintiff cannot improve/ repair its suing or make the new suing again. finally, the decision which is not careful will not fulfill the rule of law elements, justice and benefit.

  9. Novel Use of PRF and PDT in the Management of Trauma Induced Root Resorption and Infrabony Defect.

    Science.gov (United States)

    Pruthi, Preeti Jain; Yadav, Neha; Nawal, Ruchika Roongta; Talwar, Sangeeta; Lamba, Arundeep Kaur

    2015-05-01

    Root resorption is a common squeal of traumatic injury to the dentition. Its progression can be minimized by early diagnosis and appropriate treatment. This case report presents the diagnosis and management of a case of trauma induced trio of apical root resorption, intraradicular root resorption and infrabony defect in maxillary central incisor. The main aim in treating such cases of resorption is to limit the inflammatory response at the periapical region so as to halt the resorptive process. To allow faster regeneration of the periodontal tissues, Platelet rich fibrin (PRF), a second generation platelet concentrate was used as an apical matrix over which MTA plug was given. The periodontal defect was managed with the help of localized antimicrobial photodynamic therapy (aPDT).

  10. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

    Science.gov (United States)

    Castano, Ana P.; Hamblin, Michael R.

    2006-02-01

    , chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.

  11. Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti-Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT.

    Directory of Open Access Journals (Sweden)

    Luke Rogers

    Full Text Available Due to the ongoing development of clinical photodynamic therapy (PDT, the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensitizer that could overcome one or both of these drawbacks would be highly attractive to those engaged in clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs when used in combination with PDT have shown to increase the cytotoxicity of the treatment modality by targeting the tumor microenvironment. Temoporfin (m-THPC, the gold standard chlorin-based photosensitizer (PS since its discovery in the 1980's, has successfully been conjugated to non-steroidal anti-inflammatory compounds, in an attempt to address the issue of post-treatment tumor regrowth. Using a modified Steglich esterification reaction, a library of "iPorphyrins" was successfully synthesized and evaluated for their PDT efficacy.

  12. One-session root canal treatment with antimicrobial photodynamic therapy (aPDT): an in vivo study.

    Science.gov (United States)

    Borsatto, M C; Correa-Afonso, A M; Lucisano, M P; Bezerra da Silva, R A; Paula-Silva, F W G; Nelson-Filho, P; Bezerra da Silva, L A

    2016-06-01

    To evaluate the response of the apical and periapical tissues of dog teeth with apical periodontitis after one-session root canal treatment with and without antimicrobial photodynamic therapy (aPDT) compared with the use of an intracanal dressing. Sixty root canals with an induced periapical lesion were instrumented and assigned to three groups: I, two-session root canal treatment using antibacterial dressing with calcium hydroxide-based paste; II, one-session root canal treatment using aPDT; and III, one-session root canal treatment in which the root canals were filled immediately after biomechanical preparation. The animals were euthanized after a 90-day experimental period. The maxillas and mandibles with teeth were submitted to histotechnical processing and haematoxylin-eosin staining. Descriptive microscopic analysis of the apical and periapical region characteristics was performed, as well as morphometric assessment of the periapical lesion areas in fluorescence microscopy. Quantitative data were analysed statistically by the nonparametric Kruskal-Wallis test and Dunn's post-test (α = 0.05). Group I was characterized by progressive repair, with the presence of fibres, cells and blood vessels. Group II had periodontal ligaments with the presence of collagen fibres and residual inflammatory cells. Group III had a dense inflammatory infiltrate with extensive oedematous areas and fibrillar dissociation, suggesting a persistent inflammatory and resorptive condition. Regarding periapical lesion size, group I had significantly smaller lesions (P < 0.05) than groups II and III, which did not differ significantly from each other. Two-session root canal treatment using a calcium hydroxide-based dressing was associated with significantly smaller periapical lesions at 90 days and characterized by progressive repair. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  13. Tetrahydroporphyrin-tetratosylat (THPTS): A near-infrared photosensitizer for targeted and efficient photodynamic therapy (PDT) of human bladder carcinoma. An in vitro study.

    Science.gov (United States)

    Berndt-Paetz, Mandy; Weimann, Annett; Sieger, Nadine; Schastak, Stanislaw; Riyad, Yasser M; Griebel, Jan; Arthanareeswaran, Vinodh K A; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

    2017-06-01

    Efficacy of PDT in muscle-invasive bladder cancer is hampered by low tissue penetration of most photosensitizers by short excitation wavelength. THPTS is excitable at near-infrared (760nm) allowing tissue penetration up to 15mm. We examined the cellular effects of THPTS-PDT in human bladder cancer cells. We used four human transitional carcinoma cell lines, epithelial bladder progenitors (HBLAK) and bladder smooth muscle cells (HBSMC). We used flow cytometry to examine pharmacokinetics of THPTS, confocal laser scanning microscopy to analyze subcellular localization and production of reactive oxidative species (ROS), examined cytotoxicity and cell death pathways (qRT-PCR). Total uptake varied between cell lines and was significantly high in HBLAK and HBSMC. Lysosomal localization was mainly seen in cancer cells and HBLAK, while THPTS was distributed throughout the cytoplasm in HBSMC. Significant ROS production was detected 30min after THPTS-PDT. Growth arrest occurred within 4h and resulted in apoptotic and necrotic cytotoxicity after 24h. Cytotoxicity was dose-dependent and specifically high in cancer cells and HBLAK and significantly low in HBSMC. THPTS-PDT induces cellular mechanisms leading to cellular growth arrest, apoptosis and necrosis in human bladder cancer cells. These effects are only partly dependent on the total amount of THPTS uptake and rather dependent on its subcellular compartmentalization. HBSMC are hardly affected by THPTS-PDT confirming tumor specificity and safety. THPTS is a promising new photosensitizer with the unique advantage of deep tissue penetration allowing the treatment of solid tumors and warranting further animal studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Minimally toxic approach for treatment of cutaneous breast cancer metastases: capecitabine-enhanced photodynamic therapy

    Science.gov (United States)

    Anand, Sanjay; Bullock, Taylor; Maytin, Edward V.

    2017-02-01

    Cutaneous metastasis (CM) occurs in 20% of patients with breast carcinoma (BCA), and is extremely difficult to treat. These CM are relatively resistant to chemotherapy, generally responding only to ionizing radiation (IR). Multiple rounds of IR, however, lead to debilitating fibrosis and radiation dermatitis. An alternative to IR is needed for better management of BCA/CM. In our laboratory, we have developed differentiation-enhanced combination PDT (cPDT), a concept in which a pro-differentiating agent (methotrexate; vitamin D; or 5-fluorouracil, 5FU) is used as a neoadjuvant prior to PDT. After using these neoadjuvants, levels of protoporphyrin IX (PpIX) were elevated in animal tumor models of skin, prostate, and BCA, leading to better PDT efficacy. However, all the agents have toxicity issues. Here, we use a nontoxic 5FU precursor called Capecitabine (CPBN) for cPDT. CBPN is a standard chemotherapeutic for metastatic BCA, and is metabolized to 5FU specifically within tumor tissue. Murine (4T1) and human (MCF-7) BCA cell lines were injected into breast fat pads of nude mice. After tumor nodules appeared, CPBN (400-600 mg/kg/day) was administered by oral gavage for five days followed by intraperitoneal ALA administration on day 6. Mice were sacrificed and tumors harvested. CPBN pretreatment led to a 4-fold elevation of PpIX levels in tumors, relative to vehicle control. Not only did PpIX levels increase, but also PpIX distribution became more homogeneous after CPBN pretreatment. In summary, the use of non-toxic CPBN as a neoadjuvant prior to PDT is a combination approach with significant potential for translation into the clinic.

  15. Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate mediated photodynamic therapy in normal mouse skin.

    NARCIS (Netherlands)

    Bruijn, H.S. de; Haas, E.R. de; Hebeda, K.M.; Ploeg-van den Heuvel, A. van der; Sterenborg, H.J.C.M.; Neumann, H.A.; Robinson, D.J.

    2007-01-01

    Previous work demonstrated that fractionated illumination using two fractions separated by a dark interval of 2 h, significantly enhanced the clinical efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). Considering the increasing clinical use of methyl 5-aminolevulinate (MAL)

  16. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan [Department of Pharmaceutics, Qingdao University of Science and Technology, 53 Zhengzhou Road, P.O. Box 70, Qingdao 266042 (China); Liu, Junhong, E-mail: liujh@qust.edu.cn [Department of Pharmaceutics, Qingdao University of Science and Technology, 53 Zhengzhou Road, P.O. Box 70, Qingdao 266042 (China)

    2011-05-15

    Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants.

  17. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants.

    Science.gov (United States)

    Zhang, Yuanyuan; Liu, Junhong

    2011-05-15

    Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules.

    Science.gov (United States)

    Datta, Sanchita; Roy, Syamal; Manna, Madhumita

    2015-01-01

    Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model. The T-cell proliferation level, the mRNA expression level of inducible nitric oxide synthase (iNOS) and tumor growth factor-beta (TGF-β) genes and finally the phosphorylation levels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) and p38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c mice model immunized with radio-attenuated Leishmania donovani parasites through I.M. route. Higher T-cell proliferation, increased iNOS level, and suppressed TGF-β level were found in treated infected animal groups (100 and 150Gy) in relation to untreated infected animals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groups were increased when compared to untreated infected controls. The clearance of the parasites from treated infected groups of animals may be mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovani parasites. The killing of parasites was mediated by increase in nitric oxide release through PDK1, PI3K and p38MAPK signaling pathways. A lower TGF-β expression has augmented the restored Th1 ambience in the 100 and 150Gy treated animal groups proving further the efficacy of the candidate vaccine. Copyright © 2015. Published by Elsevier Editora Ltda.

  19. Antimicrobial photodynamic therapy (aPDT) and photobiomodulation (PBM - 660nm) in a dog with chronic gingivostomatitis.

    Science.gov (United States)

    Abreu Villela, Paula; Souza, Naiá de Carvalho de; Baia, Juliana Durigan; Gioso, Marco Antonio; Aranha, Ana Cecília Corrêa; de Freitas, Patrícia Moreira

    2017-12-01

    Chronic gingivostomatitis in dogs is an inflammatory syndrome of the oral cavity, which treatment and control of concomitant periodontitis allow healing in most of the cases. In the presence of recurrent lesions, invasive methods are necessary to treat lesions and pain. As a conservative adjuvant method, photobiomodulation (PBM) with low power laser is able to promote reduction of tissue pain and tissue inflammation besides increasing vascularization and healing, restoring the normal function of the irradiated organ in a shorter time. In veterinary medicine, there is no standardization of technique for its use in oral tissue for treating gingivostomatitis in dogs. In the present case, a dog was submitted to aPDT (7.2J/point, 3min/point, 180J/cm2) and PBM (1.6J/point, 40s/point, 25J/cm2), using a semiconductor diode laser, with wavelength of 660nm, spot size of ​​0.04cm2 and output power of 40mW. The established protocol proved to be effective as coadjutant treatment for chronic gingivostomatitis, restoring the integrity of dog's affected mucosa and gingiva. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Lead structures for applications in photodynamic therapy. 6. Temoporfin anti-inflammatory conjugates to target the tumor microenvironment for in vitro PDT

    OpenAIRE

    Rogers, L.; Sergeeva, NN; Paszko, E; Vaz, GMF; Senge, MO

    2015-01-01

    PUBLISHED Export Date: 22 August 2015 Due to the ongoing development of clinical photodynamic therapy (PDT), the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensit...

  1. Combination ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) on the treatment of severe acne.

    Science.gov (United States)

    Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei; Hamblin, Michael R

    2014-03-01

    Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Significant reductions in acne score (P acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. © 2014 Wiley Periodicals, Inc.

  2. Research of ALA combined with HpD-PDT which induced s180 ascitic tumor cells, death or apoptosis on cytology

    Science.gov (United States)

    Zhu, Jing; Yan, Min; Zhang, Hui-Guo; Li, Enling; Luo, Hongyu

    2005-07-01

    To ascertain the adequate dosage of ALA combined with HpD-PDT which induced tumor cell death or apoptosis on cytology. And to study the different effect of ALA-PDT and HPD-PDT used only. Rat ascitic tumor cells(S180) were randomly divided into several groups and incubated with ALA(20μg/ml 、40μg/ml、80μg/ml 、160μg/ml)、HPD(2.5μg/ml、5μg/ml、10μg/ml)and their combination dosages. 630nm light (total output 2W) was delivered to tumor cells at a constant fluence rate: 200mw/cm2 and a constant irradiated time period: 20 minutes. We set 3 groups (no photosensitizers or no irradiation or neither) to be the control groups. We used inversion microscopy to observe the morphological change of tumor cells and flow cytometry technology to detect the death or apoptosis of tumor cells during the experiment. ..

  3. Comparison of the efficacy of anti-VEGF monotherapy versus PDT and intravitreal anti-VEGF combination treatment in AMD: a Meta-analysis and systematic review.

    Science.gov (United States)

    Tong, Yao; Zhao, Ke-Ke; Feng, Dong; Biswal, Manas; Zhao, Pei-Quan; Wang, Zhao-Yang; Zhang, Yun

    2016-01-01

    To compare the effect of anti-vascular endothelial growth factor (VEGF) monotherapy versus photodynamic therapy (PDT) and anti-VEGF combination treatment in age-related macular degeneration (AMD). A computerized online search was performed using PubMed, Web of Science and the Cochrane Library. Studies that compared anti-VEGF monotherapy with PDT and anti-VEGF combination treatment of AMD and were designed as randomized controlled trials were included. The means and standard deviations of the best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of treatments and proportions of patients who gained BCVA ≥15, 10, 5, or 0 letters at 12(th) month were extracted. A systematic review and Meta-analysis of the comparison of the two approaches was conducted using Review Manager 5.2. Subgroup. A sensitivity analysis was also performed. Eight studies were included. When the subgroup and sensitivity analysis was conducted, the results indicated that in the findings that included the monotherapy group and PDT (standard fluence, SF) group of Kaiser's study, the patients in the monotherapy group had a better BCVA compared with the combination group at 12(th) month in the PDT (SF) subgroup [weighted mean difference (WMD): 3.54; 95%CI: 0.36 to 6.73; P=0.03], and there were more patients who gained ≥15 letters of BCVA in the monotherapy group compared with the combination group in the total result [odds ratio (OR): 1.41; 95%CI: 1.02 to 1.95; P=0.04]. The same conclusion was obtained in the total result that included the monotherapy group and PDT (reduced fluence, RF) group of Kaiser's study (OR: 1.56; 95%CI: 1.13 to 2.15; P=0.007). However, there were no significant differences in the other indexes between the two therapies. We found that anti-VEGF monotherapy is more effective on the recovery of visual acuity than combination therapy and more researches with lager sample size should be performed to study on the effect of the two therapy approaches on CRT

  4. In vivo demonstration of enhanced radiotherapy using rare earth doped titania nanoparticles

    Science.gov (United States)

    Townley, Helen E.; Kim, Jeewon; Dobson, Peter J.

    2012-07-01

    Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal structure. Specific activation of the nanoparticles by X-ray can result in generation of ROS leading to cell death in a tumour-localized manner. We show here that intratumoural injection of RE doped titania nanoparticles can enhance the efficacy of radiotherapy in vivo.Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal

  5. Towards automatic segmentation of MS lesions in PD/T2 MR images

    Science.gov (United States)

    Atkins, M. Stella; Drew, Mark S.; Tauber, Zinovi

    2000-06-01

    Recognizing that conspicuous multiple sclerosis (MS) lesions have high intensities in both dual-echo T2 and PD-weighted MR brain images, we show that it is possible to automatically determine a thresholding mechanism to locate conspicuous lesion pixels and also to identify pixels that suffer from reduced intensity due to partial volume effects. To do so, we first transform a T2-PD feature space via a log(T2)- log(T2+PD) remapping. In the feature space, we note that each MR slice, and in fact the whole brain, is approximately transformed into a line structure. Pixels high in both T2 and PD, corresponding to candidate conspicuous lesion pixels, also fall near this line. Therefore we first preprocess images to achieve RF-correction, isolation of the brain, and rescaling of image pixels into the range 0 - 255. Then, following remapping to log space, we find the main linear structure in feature space using a robust estimator that discounts outliers. We first extract the larger conspicuous lesions which do not show partial volume effects by performing a second robust regression for 1D distances along the line. The robust estimator concomitantly produces a threshold for outliers, which we identify with conspicuous lesion pixels in the high region. Finally, we perform a third regression on the conspicuous lesion pixels alone, producing a 2D conspicuous lesion line and confidence interval band. This band can be projected back into the adjacent, non-conspicuous, region to identify tissue pixels which have been subjected to the partial volume effect.

  6. Anthrax surrogate spores are destroyed by PDT mediated by phenothiazinium dyes

    Science.gov (United States)

    Demidova, Tatiana N.; Hamblin, Michael R.

    2005-04-01

    Some Gram-positive bacteria (including the causative agent of anthrax - Bacillus anthracis) survive conditions of stress and starvation by producing dormant stage spores. The spore"s multilayered capsule consists of inner and outer membranes, cortex, proteinaceous spore coat, and in some species an exosporium. These outer layers enclose dehydrated and condensed DNA, saturated with small, acid-soluble proteins. These protective structures make spores highly resistant to damage by heat, radiation, and commonly employed anti-bacterial agents. Previously Bacillus spores have been shown to be resistant to photodynamic inactivation (PDI) using dyes and light that easily destroy the corresponding vegetative bacteria, but recently we have discovered that they are susceptible to PDI. Photoinactivation, however, is only possible if phenothiazinium dyes are used. Dimethylmethylene blue, methylene blue, new methylene blue and toluidine blue O are all effective photosensitizers. Alternative photosensitizers such as Rose Bengal, polylysine chlorin(e6) conjugate, a tricationic porphyrin and benzoporphyrin derivative are ineffective against spores even though they can easily kill vegetative cells. Spores of B. cereus and B. thuringiensis are most susceptible, B. subtilis and B. atrophaeus are also killed, while B. megaterium is resistant. Photoinactivation is most effective when excess dye is washed from the spores showing that the dye binds to the spores and that excess dye in solution can quench light delivery. The relatively mild conditions needed for spore killing could have applications for treating wounds contaminated by anthrax spores and for which conventional sporicides would have unacceptable tissue toxicity.

  7. A randomized, multi-national, non-inferiority, phase III trial to evaluate the safety and efficacy of BF-200 ALA gel versus MAL cream in the treatment of non-aggressive basal cell carcinoma with photodynamic therapy (PDT).

    Science.gov (United States)

    Morton, C A; Dominicus, R; Radny, P; Dirschka, T; Hauschild, A; Reinhold, U; Aschoff, R; Ulrich, M; Keohane, S; Ekanayake-Bohlig, S; Ibbotson, S; Ostendorf, R; Berking, C; Gröne, D; Schulze, H J; Ockenfels, H M; Jasnoch, V; Kurzen, H; Sebastian, M; Stege, H; Staubach-Renz, P; Gupta, G; Hübinger, F; Ziabreva, I; Schmitz, B; Gertzmann, A; Lübbert, H; Szeimies, R-M

    2018-02-12

    Basal cell carcinoma (BCC) represents the most common non-melanoma skin cancer worldwide affecting mainly adult, fair-skinned individuals. The WHO distinguishes aggressive and non-aggressive forms of which prototypical variants of the latter are primary nodular and superficial BCC. To demonstrate non-inferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared to MAL (a cream containing methyl-aminolevulinate) in the treatment of non-aggressive BCC with photodynamic therapy (PDT). Non-inferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%. The study was a randomized, phase III trial performed in Germany and the UK with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA, 143 with MAL. Patients received two PDT sessions one week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J/cm 2 ). Results shown include clinical endpoints as well as patients' reassessment 12 months after the last PDT. Of the BF-200 ALA-treated patients, 93.4% were complete responders compared to 91.8% in the MAL group. The difference of means was 1.6 with a one-sided 97.5% CI of -6.5, establishing non-inferiority (pPDT is highly effective and well tolerated with proven non-inferiority to MAL-PDT and demonstrates low recurrence rates after 1-year follow-up. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, M; Penjweini, R; Zhu, T [University Pennsylvania, Philadelphia, PA (United States)

    2016-06-15

    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. Software 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.

  9. Photodynamic Therapy (PDT)

    Indian Academy of Sciences (India)

    reactions of 102 include: lipid peroxidation; oxidation of unsat- urated fatty acids, proteins with oxidizable amino acid units and bases in DNA. The biological membranes, and in particular mitochondrial membranes are considered as the critical targets for cell killing by photosensitization. For example, Hp photo- sensitization ...

  10. Photodynamic Therapy (PDT)

    Indian Academy of Sciences (India)

    als using a mixture of sulfonated aluminum phthalocyanine against malignancies such as skin, breast, lung and gastrointes- tinal cancer are also under way. The addition of sulfonate groups to the periphery of the phthalocyanine greatly increases the solubility of these compounds, removing the need for liposo- mal delivery ...

  11. Multiorganelle Localization of Metallated Phthalocyanine Photosensitizer in Colorectal Cancer Cells (DLD-1 and CaCo-2 Enhances Efficacy of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Palesa Rose Sekhejane

    2014-01-01

    Full Text Available Colorectal cancer is the third most commonly diagnosed cancer. Amongst treatments that have been explored, photodynamic therapy (PDT is a treatment that is of interest as it poses ideal advantages such as affinity for cancer cells. This study aimed to determine the correlation between the localization site of a sulfonated zinc phthalocyanine (ZnPcSmix photosensitizer (PS and its associated cell death pathway in vitro in colorectal cancer cell lines (DLD-1 and CaCo-2. Visible morphological changes were observed in PDT treated cells after 24 h. Reactive oxygen species (ROS were detected and visualized 1 h after PDT. ZnPcSmix was predominantly localized in lysosomes and partially in the mitochondria. FITC Annexin V staining showed a significant decrease in the percentage of viable DLD-1 and CaCo-2 cells 24 h after PDT, with an increase in apoptotic cell population. Moreover, there was a significant increase in both cathepsin D and cytochrome C at 1 and 24 h. In conclusion, ZnPcSmix showed the ability of inducing apoptotic cell death features in PDT treated cells.

  12. 5:30 pm PDT Photographer : JPL Range : 1,550,000 km ( 961,000 miles ) These high resolution pictures

    Science.gov (United States)

    1979-01-01

    5:30 pm PDT Photographer : JPL Range : 1,550,000 km ( 961,000 miles ) These high resolution pictures of Jupiter's ring were obtained by Voyager 2 some 26 hrs. past the planet, 2 degrees below the ring plane. The forward scattering of sunlight reveals a radial distribution and density gradient of very small particles extending inward from the ring toward Jupiter. There is an indication of structure within the ring, but unfortunatly the spacecrafts motion during these long exposures blurred out the highest resolution detail, particularly in the frame at right.

  13. A dynamic model for ALA-PDT of skin: simulation of temporal and spatial distributions of ground-state oxygen, photosensitizer and singlet oxygen

    Science.gov (United States)

    Liu, Baochang; Farrell, Thomas J.; Patterson, Michael S.

    2010-10-01

    Singlet oxygen (\\rm {^{1}O_{2}}) direct dosimetry and photosensitizer fluorescence photobleaching are being investigated and applied as dosimetric tools during 5-aminolevulinic acid (ALA)-induced protophorphyrin IX (PpIX) photodynamic therapy (PDT) of normal skin and skin cancers. The correlations of photosensitizer fluorescence and singlet oxygen luminescence (SOL) emission signals to \\rm {^{1}O_{2}} distribution and cumulative \\rm {^{1}O_{2}} dose are difficult to interpret because of the temporal and spatial variations of three essential components (light fluence rate, photosensitizer concentration and oxygen concentration) in PDT. A one-dimensional model is proposed in this paper to simulate the dynamic process of ALA-PDT of normal human skin in order to investigate the time-resolved evolution of PpIX, ground-state oxygen (\\rm {^{3}O_{2}}) and \\rm {^{1}O_{2}} distributions. The model incorporates a simplified three-layer semi-infinite skin tissue, Monte Carlo simulations of excitation light fluence and both PpIX fluorescence and SOL emission signals reaching the skin surface, \\rm {^{1}O_{2}} -mediated photobleaching mechanism for updating PpIX, \\rm {^{3}O_{2}} and \\rm {^{1}O_{2}} distributions after the delivery of each light dose increment, ground-state oxygen supply by diffusion from the atmosphere and perfusion from blood vessels, a cumulative \\rm {^{1}O_{2}} -dependent threshold vascular response, and the initial non-uniform distribution of PpIX. The PpIX fluorescence simulated using this model is compared with clinical data reported by Cottrell et al (2008 Clin. Cancer Res. 14 4475-83) for a range of irradiances (10-150 mW cm-2). Except for the vascular response, one set of parameters is used to fit data at all irradiances. The time-resolved depth-dependent distributions of PpIX, \\rm {^{3}O_{2}} and \\rm {^{1}O_{2}} at representative irradiances are presented and discussed in this paper, as well as the PDT-induced vascular response at different

  14. Hey Teacher, Your Personality's Showing!

    Science.gov (United States)

    Paulsen, James R.

    1977-01-01

    A study of 30 fourth, fifth, and sixth grade teachers and 300 of their students showed that a teacher's age, sex, and years of experience did not relate to students' mathematics achievement, but that more effective teachers showed greater "freedom from defensive behavior" than did less effective teachers. (DT)

  15. Planning a Successful Tech Show

    Science.gov (United States)

    Nikirk, Martin

    2011-01-01

    Tech shows are a great way to introduce prospective students, parents, and local business and industry to a technology and engineering or career and technical education program. In addition to showcasing instructional programs, a tech show allows students to demonstrate their professionalism and skills, practice public presentations, and interact…

  16. Cave Cyanobacteria showing antibacterial activity

    Directory of Open Access Journals (Sweden)

    Vasiliki Lamprinou

    2015-09-01

    Full Text Available Cave Cyanobacteria - thriving in an ‘extreme’ environment with interesting species biodiversity - are supposed to be a potential source of bioactive compounds. Lipid extracts from pure cultures of two recently established Cyanobacteria from Greek caves, Toxopsis calypsus and Phormidium melanochroun, were used for antibacterial screening against human pathogenic bacteria (reference and clinical isolates. Antimicrobial Susceptibility testing for both taxa was carried out using the disc-diffusion (Kirby Bauer method, while preliminary data applying the standard broth microdilution method for the determination of the Minimal Inhibitory Concentration (MIC are given only for T. calypsus. Antibacterial activity was demonstrated against the Gram-positive clinical and reference bacteria, mostly pronounced in enterococci; no activity was observed against the Gram-negative bacteria. The above screening is the first record of antibacterial activity from lipid extracts of cave Cyanobacteria enhancing the importance of cave microbiota and the necessity for cave conservation.

  17. Risk Aversion in Game Shows

    DEFF Research Database (Denmark)

    Andersen, Steffen; Harrison, Glenn W.; Lau, Morten I.

    2008-01-01

    We review the use of behavior from television game shows to infer risk attitudes. These shows provide evidence when contestants are making decisions over very large stakes, and in a replicated, structured way. Inferences are generally confounded by the subjective assessment of skill in some games......, and the dynamic nature of the task in most games. We consider the game shows Card Sharks, Jeopardy!, Lingo, and finally Deal Or No Deal. We provide a detailed case study of the analyses of Deal Or No Deal, since it is suitable for inference about risk attitudes and has attracted considerable attention....

  18. Measuring performance at trade shows

    DEFF Research Database (Denmark)

    Hansen, Kåre

    2004-01-01

    Trade shows is an increasingly important marketing activity to many companies, but current measures of trade show performance do not adequately capture dimensions important to exhibitors. Based on the marketing literature's outcome and behavior-based control system taxonomy, a model is built...... that captures a outcome-based sales dimension and four behavior-based dimensions (i.e. information-gathering, relationship building, image building, and motivation activities). A 16-item instrument is developed for assessing exhibitors perceptions of their trade show performance. The paper presents evidence...... of the scale's reliability, factor structure, and validity on the basis of analyzing data from independent samples of exhibitors at the international trade shows SIAL (Paris) and ANUGA (Cologne); and it concludes with a discussion of potential managerial applications and implications for future research. New...

  19. In vivo demonstration of enhanced radiotherapy using rare earth doped titania nanoparticles†

    Science.gov (United States)

    Townley, Helen E.; Kim, Jeewon; Dobson, Peter J.

    2017-01-01

    Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal structure. Specific activation of the nanoparticles by X-ray can result in generation of ROS leading to cell death in a tumour-localized manner. We show here that intratumoural injection of RE doped titania nanoparticles can enhance the efficacy of radiotherapy in vivo. PMID:22767269

  20. In vivo demonstration of enhanced radiotherapy using rare earth doped titania nanoparticles.

    Science.gov (United States)

    Townley, Helen E; Kim, Jeewon; Dobson, Peter J

    2012-08-21

    Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal structure. Specific activation of the nanoparticles by X-ray can result in generation of ROS leading to cell death in a tumour-localized manner. We show here that intratumoural injection of RE doped titania nanoparticles can enhance the efficacy of radiotherapy in vivo.

  1. Tokyo Motor Show 2003; Tokyo Motor Show 2003

    Energy Technology Data Exchange (ETDEWEB)

    Joly, E.

    2004-01-01

    The text which follows present the different techniques exposed during the 37. Tokyo Motor Show. The report points out the great tendencies of developments of the Japanese automobile industry. The hybrid electric-powered vehicles or those equipped with fuel cells have been highlighted by the Japanese manufacturers which allow considerable budgets in the research of less polluting vehicles. The exposed models, although being all different according to the manufacturer, use always a hybrid system: fuel cell/battery. The manufacturers have stressed too on the intelligent systems for navigation and safety as well as on the design and comfort. (O.M.)

  2. Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay

    2016-03-01

    In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

  3. Reality show: um paradoxo nietzschiano

    Directory of Open Access Journals (Sweden)

    Ilana Feldman

    2011-01-01

    Full Text Available

    O fenômeno dos reality shows - e a subseqüente relação entre imagem e verdade - assenta-se sobre uma série de paradoxos. Tais paradoxos podem ser compreendidos à luz do pensamento do filósofo alemão Friedrich Nietzsche, que, através dos usos de formulações paradoxais, concebia a realidade como um mundo de pura aparência e a verdade como um acréscimo ficcional, como um efeito. A ficção é então tomada, na filosofia de Nietzsche, não em seu aspecto falsificante e desrealizador - como sempre pleiteou nossa tradição metafísica -, mas como condição necessária para que certa espécie de invenção possa operar como verdade. Sendo assim, a própria expressão reality show, através de sua formulação paradoxal, engendra explicitamente um mundo de pura aparência, em que a verdade, a parte reality da proposição, é da ordem do suplemento, daquilo que se acrescenta ficcionalmente - como um adjetivo - a show. O ornamento, nesse caso, passa a ocupar o lugar central, apontando para o efeito produzido: o efeito-de-verdade. Seguindo, então, o pensamento nietzschiano e sua atualização na contemporaneidade, investigaremos de que forma os televisivos “shows de realidade” operam paradoxalmente, em consonância com nossas paradoxais práticas culturais.

  4. Antibacterial photodynamic treatment of periodontopathogenic bacteria with indocyanine green and near-infrared laser light enhanced by Trolox(TM).

    Science.gov (United States)

    Kranz, Stefan; Huebsch, Marie; Guellmar, Andre; Voelpel, Andrea; Tonndorf-Martini, Silke; Sigusch, Bernd W

    2015-04-01

    It has been shown that certain vitamins can significantly enhance the effect of photodynamic anti-tumor therapy. Unfortunately, there is no sufficient information available about the impact of those antioxidants on antimicrobial Photodynamic Therapy (aPDT). The present study is aimed at investigating the antimicrobial effect of the dye indocyanine green (ICG) in the presence of Trolox(TM) , a vitamin E analogue, upon irradiation with near-infrared (NIR) laser light (808 nm) on the gramnegative periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.) and Fusobacterium nucleatum (F.n.). Bacteria solved in PBS were incubated with ICG (50-500 μg/ml) in the presence and absence of Trolox(TM) (2 mM). Irradiation was performed after 10 minutes of dark-incubation with NIR-laser-light (25-100 J/cm(2) , 810 nm). During treatment, temperature was also recorded inside the bacterial solutions. The treated suspensions were serial diluted and plated onto blood agar plates. After anaerobe cultivation for 5 days the colony-forming units (CFU/ml) were determined. The antibacterial effect was ICG-concentration and exposure dependent. It was found that high ICG-concentrations and light fluence rates caused bacterial reduction due to hyperthermia. Where low ICG-concentrations (Trolox(TM) -administration significantly enhanced the photodynamic effect. While treatment of A.a. (250 μg/ml ICG, 100 J/cm(2) ) without Trolox(TM) caused no bacterial reduction, additional administration led to total eradication. In the presence of Trolox(TM) reduction to one-fifth of the original ICG-concentration (50 μg/ml) still induced total suppression of P.g. and F.n. at identical fluence (100 J/cm(2) ). Treatment with ICG, NIR-light or Trolox(TM) alone showed no remarkable bactericidal effect. Application of high ICG-concentrations (500 μg/ml) and exposure values (100 J/cm(2) ) caused peak temperatures of 64.53°C. The results

  5. Show Me My Health Plans

    Directory of Open Access Journals (Sweden)

    Mary C. Politi PhD

    2016-11-01

    Full Text Available Introduction: Since the Affordable Care Act was passed, more than 12 million individuals have enrolled in the health insurance marketplace. Without support, many struggle to make an informed plan choice that meets their health and financial needs. Methods: We designed and evaluated a decision aid, Show Me My Health Plans (SMHP, that provides education, preference assessment, and an annual out-of-pocket cost calculator with plan recommendations produced by a tailored, risk-adjusted algorithm incorporating age, gender, and health status. We evaluated whether SMHP compared to HealthCare.gov improved health insurance decision quality and the match between plan choice, needs, and preferences among 328 Missourians enrolling in the marketplace. Results: Participants who used SMHP had higher health insurance knowledge (LS-Mean = 78 vs. 62; P < 0.001, decision self-efficacy (LS-Mean = 83 vs. 75; P < 0.002, confidence in their choice (LS-Mean = 3.5 vs. 2.9; P < 0.001, and improved health insurance literacy (odds ratio = 2.52, P < 0.001 compared to participants using HealthCare.gov . Those using SMHP were 10.3 times more likely to select a silver- or gold-tier plan (P < 0.0001. Discussion: SMHP can improve health insurance decision quality and the odds that consumers select an insurance plan with coverage likely needed to meet their health needs. This study represents a unique context through which to apply principles of decision support to improve health insurance choices.

  6. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

    Directory of Open Access Journals (Sweden)

    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  7. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Photodynamic Therapy (PDT) using intratumoral injection of the 5- aminolevulinic acid (5-ALA) for the treatment of eye cancer in cattle

    Science.gov (United States)

    Hage, Raduan; Mancilha, Geraldo; Zângaro, Renato A.; Munin, Egberto; Plapler, Hélio

    2007-02-01

    A six-year old Holstein cow with an eye cancer (ocular squamous cell carcinoma) involving the third eyelid and conjunctiva was submitted to photodynamic therapy using intratumoral 20% aminolevulinic acid (5-ALA - Aldrich Chemical Company, Milwaukee, USA) and a light emitting diode (LED - VET LED - MMOptics (R)) with wavelength between 600 and 700 nm, 2 cm diameter circular light beam, power of 150 mW, light dose of 50 J/cm2 as a source of irradiation. Fifteen days after the experimental procedure we observed about 50% tumor reduction and complete remission after 3 months. Relapse was not observed up to 12 months after the treatment. Although the study only includes one animal not allowing definite conclusions, it indicates that PDT represents a safe and technically feasible approach in the treatment of eye cancer in cattle.

  9. Application of an octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl]porphyrin (H2OCP) as dual sensitizer for BNCT and PDT

    Science.gov (United States)

    The applications of the octa-anionic 5,10,15,20-tetra[3,5-(nidocarboranylmethyl) phenyl]porphyrin (H2OCP) as a boron delivery agent in boron neutron capture therapy (BNCT) and a photosensitizer in photodynamic therapy (PDT) have been investigated. Using F98 Rat glioma cells, we evaluated the cytotox...

  10. Plasmonic enhancement of cyanine dyes for near-infrared light-triggered photodynamic/photothermal therapy and fluorescent imaging

    Science.gov (United States)

    Lu, Mindan; Kang, Ning; Chen, Chuan; Yang, Liuqing; Li, Yang; Hong, Minghui; Luo, Xiangang; Ren, Lei; Wang, Xiumin

    2017-11-01

    Near-infrared (NIR) triggered cyanine dyes have attracted considerable attention in multimodal tumor theranostics. However, NIR cyanine dyes used in tumor treatment often suffer from low fluorescence intensity and weak singlet oxygen generation efficiency, resulting in inadequate diagnostic and therapy efficacy for tumors. It is still a great challenge to improve both the photodynamic therapy (PDT) and fluorescent imaging (FLI) efficacy of cyanine dyes in tumor applications. Herein, a novel multifunctional nanoagent AuNRs@SiO2-IR795 was developed to realize the integrated photothermal/photodynamic therapy (PTT/PDT) and FLI at a very low dosage of IR795 (0.4 μM) based on metal-enhanced fluorescence (MEF) effects. In our design, both the fluorescence intensity and reactive oxygen species of AuNRs@SiO2-IR795 nanocomposites were significantly enhanced up to 51.7 and 6.3 folds compared with free IR795, owing to the localized surface plasmon resonance band of AuNRs overlapping with the absorption or fluorescence emission band of the IR795 dye. Under NIR laser irradiation, the cancer cell inhibition efficiency in vitro with synergetic PDT/PTT was up to 82.3%, compared with 10.3% for free IR795. Moreover, the enhanced fluorescence intensity of our designed nanocomposites was helpful to track their behavior in tumor cells. Therefore, our designed nanoagents highlight the applications of multimodal diagnostics and therapy in tumors based on MEF.

  11. Nissan at 33rd Tokyo Motor Show; Dai 33 kai Tokyo Motor show

    Energy Technology Data Exchange (ETDEWEB)

    Sekiguchi, M. [Nissan Motor Co. Ltd., Tokyo (Japan)

    2000-01-01

    The Tokyo Motor Show is one of the leading exhibition opportunities for automobile companies world wide in terms of both scale and features, including the number of visitors as well as the devotion of each participant. For many years, we have worked hard to excell at each session of this show, (through the display of concept cars and Nissan Motor's technological developments), the show has played an increasing role in enhancing Nissan's brand image. At the 33rd Tokyo Motor Show in October 1999 was held at a time when Nissan had drawn the attention of the market because of its tic-up with Renault. Nissan demonstrated a revolutionary change through the introduction of concept cars, environmental technology, safety technology, new models, and so on. (author)

  12. Synergistic enhancement of antitumor effect of β-Lapachone by photodynamic induction of quinone oxidoreductase (NQO1).

    Science.gov (United States)

    Lamberti, María Julia; Vittar, Natalia Belén Rumie; da Silva, Fernando de Carvalho; Ferreira, Vitor Francisco; Rivarola, Viviana Alicia

    2013-08-15

    β-Lapachone is a phytochemotherapeutic originally isolated from Lapacho tree whose extract has been used medicinally for centuries. It is well known that NAD(P)H:quinone oxidoreductase (NQO1) activity is the principal determinant of β-Lapachone cytotoxicity. As NQO1 is overexpressed in most common carcinomas, recent investigations suggest its potential application against cancer. Photodynamic therapy (PDT) is a clinically approved and rapidly developing cancer treatment. PDT involves the administration of photosensitizer (PS) followed by local illumination with visible light of specific wavelength. In the presence of oxygen molecules, the light illumination of PS can lead to a series of photochemical reactions and consequently the generation of cytotoxic reactive oxygen species (ROS). It has been reported that β-Lapachone synergistically interacts with ionizing radiation, hyperthermia and cisplatin and that the sensitivity of cells to β-Lapachone is closely related to the activity of NQO1. So, the present study aimed to investigate the feasibility of PDT to increase the anticancer effect of β-Lapachone by up-regulating NQO1 expression on breast cancer MCF-7c3 cells. NQO1 expression was evaluated by Western blot analysis at different times after PDT using ME-ALA as PS. The cytotoxicity of the photodynamic treatment and β-Lapachone alone or in combination was determined by MTT assay and the combination index (CI)-isobologram method and the dose reduction index (DRI) analysis were used to assess the effect of drug combinations. Our studies for the first time demonstrated that the expression of NQO1 is induced 24h after photodynamic treatment. The sensitivity of cancer cells to β-Lapachone treatment increased 24h after PDT and a synergistic inhibitory effect on MCF-7c3 cells was showed. Taken together, these results lead us to conclude that the synergistic interaction between β-Lapachone and PDT in killing cells was consistent with the up-regulation of NQO1

  13. Visual perception enhancement for detection of cancerous oral tissue by multi-spectral imaging

    Science.gov (United States)

    Wang, Hsiang-Chen; Tsai, Meng-Tsan; Chiang, Chun-Ping

    2013-05-01

    Color reproduction systems based on the multi-spectral imaging technique (MSI) for both directly estimating reflection spectra and direct visualization of oral tissues using various light sources are proposed. Images from three oral cancer patients were taken as the experimental samples, and spectral differences between pre-cancerous and normal oral mucosal tissues were calculated at three time points during 5-aminolevulinic acid photodynamic therapy (ALA-PDT) to analyze whether they were consistent with disease processes. To check the successful treatment of oral cancer with ALA-PDT, oral cavity images by swept source optical coherence tomography (SS-OCT) are demonstrated. This system can also reproduce images under different light sources. For pre-cancerous detection, the oral images after the second ALA-PDT are assigned as the target samples. By using RGB LEDs with various correlated color temperatures (CCTs) for color difference comparison, the light source with a CCT of about 4500 K was found to have the best ability to enhance the color difference between pre-cancerous and normal oral mucosal tissues in the oral cavity. Compared with the fluorescent lighting commonly used today, the color difference can be improved by 39.2% from 16.5270 to 23.0023. Hence, this light source and spectral analysis increase the efficiency of the medical diagnosis of oral cancer and aid patients in receiving early treatment.

  14. AXIOLOGY ARBITRATION VALUE RULING IN THE CASE SETTLEMENT TRADE (Case Study Decision Of Supreme Court Number : 199 K / Pdt.Sus / 2012

    Directory of Open Access Journals (Sweden)

    Safrin Salam

    2016-12-01

    Full Text Available The existence of the Indonesian National Arbitration Board (BANI in Indonesia that still exist to this day is one manifestation of diakomodasinya patterns of dispute resolution outside the court. Legal Considerations Application Reasons Cancellation Arbitral Article 70 of Law No. 30 of 1999 on Arbitration and Alternative Dispute Resolution in Supreme Court Decision No. 199 K / Pdt.Sus / 2012 Relation Ensure Legal Certainty In the disputing parties are legal considerations of the cancellation decision was not all acceptance or rejection of the cancellation request arbitration decision based on legal grounds contained in Article 70 of Law No. 30 of 1999. Act No. 30 of 1999 on the ADR needs to be improved, especially the explanation of article 60 and article 70 which could lead to legal uncertainty for justice seekers among businesses in the dispute and the opportunity loss of trust businesses to resolve the dispute out of court through arbitration institution (the Arbitration Tribunal Ad-Hoc, BANI, etc.

  15. Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2

    Directory of Open Access Journals (Sweden)

    Cheng-Cheng Wang

    2017-05-01

    Full Text Available Brazilian green propolis (BGP is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo.

  16. Designing molecules for PDT: red light-induced DNA cleavage on disulfide bond activation in a dicopper(II) complex.

    Science.gov (United States)

    Dhar, Shanta; Nethaji, Munirathinam; Chakravarty, Akhil R

    2005-01-21

    The binuclear copper(II) complex [Cu)(RSSR)2](1), where RSSR is a dianionic Schiff base derived from 2-(thioethyl)salicylaldimine having a disulfide bond is prepared, structurally characterized by X-ray crystallography and its photo-induced DNA cleavage activity studied. The Schiff base ligand H2RSSR is also structurally characterized. The crystal structure of shows the discrete dimeric nature of the complex with each metal showing square-planar geometry with a CuN2O2 coordination (Cu...Cu, 5.011(1)A). The tetradentate Schiff base RSSR acts as a linker of two copper centers. The sulfur atoms in the disulfide unit do not show any apparent interaction with the metal ion. Complex 1, which is cleavage inactive in the dark in the presence of reducing agents, shows significant cleavage of supercoiled pUC19 DNA on exposure to UV light of 312 nm or visible light of different wavelengths under aerobic conditions, in the absence of any additives. DNA cleavage data from control experiments reveal involvement of the disulfide unit as a photosensitizer undergoing photo-induced S-S bond cleavage on exposure to UV light and the resulting species activates molecular oxygen to form singlet oxygen (1O2) that causes DNA cleavage following a type-II process. Photo-induced DNA cleavage by 1 on red-light exposure using a CW laser of 632.8 nm or a pulsed ruby laser of 694 nm is proposed to involve sulfide radicals in a type-I process and hydroxyl radicals as the reactive species.

  17. PERLINDUNGAN HUKUM PEMEGANG HAK ATAS TANAH BERDASARKAN JUAL BELI DI BAWAH TANGAN (Kajian Terhadap Putusan Nomor: 1860K/Pdt/2005

    Directory of Open Access Journals (Sweden)

    Ketut Dezy Ari Utami

    2015-06-01

    Full Text Available Abstract This thesis behind this is the norm of any conflict between the sale and purchase agreement made by the Plaintiff husband (deceased Suwadi with Sri Lestari sealed with receipt in Decision No. 1860 K/Pdt/2005 with the principle of legal certainty. The problems studied in this thesis are: 1 Is the sale of land under the hand without the presence of witnesses can be justified by the law. 2 What are the forms of legal protection of land rights holders in the sale and purchase under the hand without the presence of witnesses? To answer the problem studied, the authors use the method of normative approach. Based on the results of the study, the authors obtained answers to existing problems, namely the purchase agreement sealed on top of the basic elements of the agreement have met or commonly referred to the "essentialia". The first is preventative protection of land registration. Second, legislation, legal protection represeif: First, do a lawsuit to district court, the Second, compensation sanctions.   Key words: protection law, land rights, sale   Abstrak Tujuan dari penulisan jurnal ini adalah untuk mengetahui dan menganalisis apakah jual beli tanah dibawah tangan tanpa dihadiri oleh saksi dapat dibenarkan oleh hukum dan bagaimana bentuk perlindungan hukum pemegang hak atas tanah dalam jual beli  dibawah tangan tanpa dihadiri oleh saksi. Metode penelitian yang digunakan dalam penulisan jurnal ini adalah penelitian normatif yang menggunakan pendekatan perundang-undangan (statue approach dan pendekatan konsep (conseptual approach. Berdasarkan hasil penelitian, penulis memperoleh jawaban atas permasalahan yang ada, yaitu perjanjian jual beli bersegel di atas telah memenuhi unsur pokok perjanjian atau biasa disebut dengan unsur “essentialia”. Menyikapi hal-hal tersebut di atas,Perjanjan jual beli haruslah memperhatikan asas itikad baik dan juga asas-asas perjanjian lainnya yang harus menjadi dasar pijakan para pihak dalam membuat suatu

  18. Evaluation of the efficacy of AmPDT of oral microorganisms with Photogem associated to red LED (λ640ηm+/-5ηm): in vitro

    Science.gov (United States)

    Pires Santos, Gustavo M.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. d. C.; Marques, Aparecida Maria C.; Bagnato, Vanderlei S.; Pinheiro, Antônio L. B.

    2017-02-01

    The aim of this study is to evaluate the Antimicrobial Photodynamic Therapy (AmPDT) of microorganisms mediated by red LED (λ640 +/- 5 ηm, 120 mW, spot of 0.785 cm2) associated with Photogem. Microorganisms of the posterior dorsal region of the tongue and oral mucosa were collected and inoculated in 8 mL of TSB medium overnight followed by inverse homogenization. Culture plates with 24 wells were used for the irradiated and non-irradiated species. Each well received 400 μL of the suspension containing the microorganisms. In eight wells no Photogem was used and they were the irradiated and non-irradiated controls. The remain of the wells had Photogem applied with a pre-irradiation time of 5 min in concentrations of 40, 20, 10, 5 e 2.5 μg/mL. LED was applied for 5 min and 45 sec (50 J/cm2). After agitation, 200 μL were withdrawn from each well and colorimetric measurements were immediately taken. Other 200 μL were withdrawn from the wells after 1 hour in bacteriological incubator for a second measurement. The best results found were for 40 μg/mL of Photogem associated with LED irradiation and immediate (36.7%) and for 5 μg/mL with LED irradiation with measurements one hour after incubation (42.8%). This study suggests that antimicrobial photodynamic therapy with Photogem associated to red LED can be a potential mechanism of control of oral microorganisms.

  19. Enhancing photodynamic therapy of refractory solid cancers

    NARCIS (Netherlands)

    Weijer, R.

    2017-01-01

    Photodynamic therapy (PDT) is based on the activation of a photosensitizer by (laser) light to locally produce highly destructive reactive oxygen species. When employed for cancer treatment, PDT is able to induce tumor cell death, microvascular damage, and an anti-tumor immune response. All these

  20. Synthesis, DNA interactions and antibacterial PDT of Cu(II) complexes of phenanthroline based photosensitizers via singlet oxygen generation

    Science.gov (United States)

    Sudhamani, C. N.; Bhojya Naik, H. S.; Sangeetha Gowda, K. R.; Giridhar, M.; Girija, D.; Prashanth Kumar, P. N.

    2015-03-01

    Cu(II) complexes [Cu(mqt)(B)H2O]ClO4(1-3) of 2-thiol 4-methylquinoline and phenanthroline bases (B), viz 1,10-phenanthroline (phen in 1), Dipyrido[3,2-d:2‧,3‧-f]quinoxaline (dpq in 2) and Dipyrido[3,2-a:2‧,3‧-c]phenazine (dppz in 3) have been prepared and characterized by elemental analysis, IR, UV-Vis, magnetic moment values, EPR spectra and conductivity measurements. The spectral data reveal that all the complexes exhibit square-pyramidal geometry. The DNA-binding behaviors of the three complexes were investigated by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes (1), (2) and (3) were determined to 2.2 × 103, 1.3 × 104 and 8.6 × 104 M-1 respectively. The experimental results suggest that these complexes interact with DNA through groove-binding mode. The photo induced cleavage studies shows that the complexes possess photonuclease property against pUC19 DNA under UV-Visible irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against Escherichiacoli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.

  1. Autopsied case of tuberculous meningitis showing interesting CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Abiko, Takashi; Higuchi, Hiroshi; Imada, Ryuichi; Nagai, Kenichi (Iwate Prefectural Central Hospital (Japan))

    1983-11-01

    A 61-year-old female patient died of a neurological disorder of unknown origin one month after the first visit and was found to have had tuberculous meningitis at autopsy. CT revealed a low density area showing an enlargement of the cerebral ventricle but did not reveal contrast enhancement in the basal cistern peculiar to tuberculous meningitis.

  2. Synthesis and photophysical properties of the photoactivatable cationic porphyrin 5-(4-N-dodecylpyridyl)-10,15,20-tri(4-N-methylpyridyl)-21H,23H-porphyrin tetraiodide for anti-malaria PDT.

    Science.gov (United States)

    Stallivieri, Aurélie; Le Guern, Florent; Vanderesse, Régis; Meledje, Esme; Jori, Giulio; Frochot, Céline; Acherar, Samir

    2015-07-01

    This article describes a new synthetic method for obtaining three water soluble porphyrins. The more sophisticated porphyrin [5-(4-N-dodecylpyridyl)-10,15,20-tri(4-N-methylpyridyl)-21H,23H-porphyrin tetraiodide], also named C12 porphyrin, was obtained through a three step methodology. The improvements, compared to syntheses described in the literature, mostly concern the purification procedures. The photophysical properties of the three porphyrins are described and the C12 porphyrin presents a very good (1)O2 yield compared to its chemical intermediates. This porphyrin seems to be a very promising candidate for PDT applications.

  3. Doxorubicin-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for NIR-triggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancers.

    Science.gov (United States)

    Zeng, Leyong; Pan, Yuanwei; Tian, Ying; Wang, Xin; Ren, Wenzhi; Wang, Shouju; Lu, Guangming; Wu, Aiguo

    2015-07-01

    The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment

    DEFF Research Database (Denmark)

    Haedersdal, M; Katsnelson, J; Sakamoto, F H

    2011-01-01

    Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT-response in deep skin layers. The purpose of this study was to evaluate whether pre......-treating the skin with AFR before topically applied methyl aminolevulinate (MAL) could enable a deep PDT-response....

  5. Zenith Movie showing Phoenix's Lidar Beam (Animation)

    Science.gov (United States)

    2008-01-01

    [figure removed for brevity, see original site] Click on image for animation A laser beam from the Canadian-built lidar instrument on NASA's Phoenix Mars Lander can be seen in this contrast-enhanced sequence of 10 images taken by Phoenix's Surface Stereo Imager on July 26, 2008, during early Martian morning hours of the mission's 61st Martian day after landing. The view is almost straight up and includes about 1.5 kilometer (about 1 mile) of the length of the beam. The camera, from its position close to the lidar on the lander deck, took the images through a green filter centered on light with wavelength 532 nanometers, the same wavelength of the laser beam. The movie has been artificially colored to to approximately match the color that would be seen looking through this filter on Mars. Contrast is enhanced to make the beam more visible. The lidar beam can be seen extending from the lower right to the upper right, near the zenith, as it reflects off particles suspended in the atmosphere. Particles that scatter the beam directly into the camera can be seen to produce brief sparkles of light. In the background, dust can be seen drifting across the sky pushed by winds aloft. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  6. Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment

    DEFF Research Database (Denmark)

    Haedersdal, M; Katsnelson, J; Sakamoto, F H

    2011-01-01

    Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT-response in deep skin layers. The purpose of this study was to evaluate whether pre...

  7. The Physics of Equestrian Show Jumping

    Science.gov (United States)

    Stinner, Art

    2014-01-01

    This article discusses the kinematics and dynamics of equestrian show jumping. For some time I have attended a series of show jumping events at Spruce Meadows, an international equestrian center near Calgary, Alberta, often referred to as the "Wimbledon of equestrian jumping." I have always had a desire to write an article such as this…

  8. Voyeurismo Televisivo, Reality Shows e Brasilidade Televisiva

    Directory of Open Access Journals (Sweden)

    Suzana Kilpp

    2008-12-01

    Full Text Available In the last years we watched a boom of reality shows in the media and also in the academic production specialized in this subject. It remains, however, a epistemological gap related to the aesthetic and techniques (which are related to the televisions grammars that TV uses in these programs to enunciate ethics directions to its own voyeurism, that goes far beyond reality shows, having repercussions on social imaginary of transparency and surveillance, and the redesign of public and private spaces. In this gap, the article points out the debate of Brazilian reality shows in the perspective of the televisions grammars.

  9. Diabetes Drug Shows Promise Against Parkinson's

    Science.gov (United States)

    ... fullstory_167612.html Diabetes Drug Shows Promise Against Parkinson's Byetta improved symptoms of motor disease in small, ... may do double duty as a treatment for Parkinson's disease, a new study suggests. "This is a ...

  10. UV Photography Shows Hidden Sun Damage

    Science.gov (United States)

    ... mcat1=de12", ]; for (var c = 0; c UV photography shows hidden sun damage A UV photograph gives ... developing skin cancer and prematurely aged skin. Normal photography UV photography 18 months of age: This boy's ...

  11. Career development at London Vet Show.

    Science.gov (United States)

    2016-09-03

    Are you considering a career change? Perhaps you want help to develop within your current role? Either way, you will find a relevant session in the BVA Career Development stream at the London Vet Show in November. British Veterinary Association.

  12. Laser Therapy Shows Promise Against Eye 'Floaters'

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_167324.html Laser Therapy Shows Promise Against Eye 'Floaters' These spots ... 2017 THURSDAY, July 20, 2017 (HealthDay News) -- A laser treatment can reduce spots in people's vision known ...

  13. Online Italian fandoms of American TV shows

    Directory of Open Access Journals (Sweden)

    Eleonora Benecchi

    2015-06-01

    Full Text Available The Internet has changed media fandom in two main ways: it helps fans connect with each other despite physical distance, leading to the formation of international fan communities; and it helps fans connect with the creators of the TV show, deepening the relationship between TV producers and international fandoms. To assess whether Italian fan communities active online are indeed part of transnational online communities and whether the Internet has actually altered their relationship with the creators of the original text they are devoted to, qualitative analysis and narrative interviews of 26 Italian fans of American TV shows were conducted to explore the fan-producer relationship. Results indicated that the online Italian fans surveyed preferred to stay local, rather than using geography-leveling online tools. Further, the sampled Italian fans' relationships with the show runners were mediated or even absent.

  14. 2008 LHC Open Days Physics: the show

    CERN Document Server

    2008-01-01

    A host of events and activities await visitors to the LHC Open Days on 5 and 6 April. A highlight will be the physics shows funded by the European Physical Society (EPS), which are set to surprise and challenge children and adults alike! School children use their experience of riding a bicycle to understand how planets move around the sun (Copyright : Circus Naturally) Participating in the Circus Naturally show could leave a strange taste in your mouth! (Copyright : Circus Naturally) The Rino Foundation’s experiments with liquid nitrogen can be pretty exciting! (Copyright: The Rino Foundation)What does a bicycle have in common with the solar system? Have you ever tried to weigh air or visualise sound? Ever heard of a vacuum bazooka? If you want to discover the answers to these questions and more then come to the Physics Shows taking place at the CERN O...

  15. Satire og diskurs i The Daily Show

    OpenAIRE

    Rygaard, Alexander Leicht; Dall, Christoffer; Jakobsen, Sebastian Rasch; Duvander, Søren; Knøster, Morten; Kirkegaard, Elissa Valles; Wallin, Dea

    2014-01-01

    This project examines how The Daily Show and its host Jon Stewart takes part in the American political debate. Furthermore, the term satire is explained by linguist Paul Simpson who reckons that satire is not as much a genre as it is a practice of discourse. By the use of detailed statistics by Gallup and Pew Research Center, a picture of the American media and its consumers is provided to explain why The Daily Show has gained more viewership through the years. Throughout a critical discourse...

  16. TV-Show Retrieval and Classification

    NARCIS (Netherlands)

    Musto, C.; Narducci, F.; Lops, P.; Semeraro G.; Gemmis, M. de; Barbieri, M.; Korst, J.H.M.; Pronk, S.P.P.; Clout, R.A.W.

    2012-01-01

    Recommender systems are becoming popular tools to aid users in finding interesting and relevant TV-shows and other digital video assets,based on implicitly learned user preferences. In this context, a common assumption is that user preferences can be specified by program types (movie, sports, ...)

  17. The Last Great American Picture Show

    NARCIS (Netherlands)

    Elsaesser, Thomas; King, Noel; Horwath, Alexander

    2004-01-01

    The Last Great American Picture Show brings together essays by scholars and writers who chart the changing evaluations of the American cinema of the 1970s, sometimes referred to as the decade of the lost generation, but now more and more recognized as the first New Hollywood, without which the

  18. Mike Pentz showing visitors around CESAR

    CERN Multimedia

    CERN PhotoLab

    1964-01-01

    Mike Pentz, leader of the CESAR Group, shows visitors around the 2 MeV electron storage ring. Here they are in the vault of the injector (a 2 MV van de Graaff generator), next to the 2 beam lines, one leading to the ring, the other to the spectrometer.

  19. Show Them You Really Want the Job

    Science.gov (United States)

    Perlmutter, David D.

    2012-01-01

    Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

  20. Laser entertainment and light shows in education

    Science.gov (United States)

    Sabaratnam, Andrew T.; Symons, Charles

    2002-05-01

    Laser shows and beam effects have been a source of entertainment since its first public performance May 9, 1969, at Mills College in Oakland, California. Since 1997, the Photonics Center, NgeeAnn Polytechnic, Singapore, has been using laser shows as a teaching tool. Students are able to exhibit their creative skills and learn at the same time how lasers are used in the entertainment industry. Students will acquire a number of skills including handling three- phase power supply, operation of cooling system, and laser alignment. Students also acquire an appreciation of the arts, learning about shapes and contours as they develop graphics for the shows. After holography, laser show animation provides a combination of the arts and technology. This paper aims to briefly describe how a krypton-argon laser, galvanometer scanners, a polychromatic acousto-optic modulator and related electronics are put together to develop a laser projector. The paper also describes how students are trained to make their own laser animation and beam effects with music, and at the same time have an appreciation of the operation of a Class IV laser and the handling of optical components.

  1. See you at London Vet Show.

    Science.gov (United States)

    2016-11-05

    London Vet Show is fast approaching: it takes place from November 17 to 18 and is being held at ExCeL London for the first time. Zoe Davies, marketing manager, highlights some of what BVA is offering at the event. British Veterinary Association.

  2. UV Photography Shows Hidden Sun Damage

    Science.gov (United States)

    ... var c = 0; c UV photography shows hidden sun damage A UV photograph gives us a safe way to see how the sun damages our skin. In the UV photos that ... on the right, you can see what hidden sun damage looks like. Compare these UV photos with ...

  3. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    Suppression subtractive hybridization was used to identify genes showing differential expression profile associated withgrowth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus-culus longissimus muscle tissues of selected pigs with extreme expected ...

  4. Electrostriction enhancement in metamaterials

    CERN Document Server

    Smith, M J A; de Sterke, C Martijn; Wolff, C; Lapine, M; Poulton, C G

    2015-01-01

    We demonstrate a controllable enhancement in the electrostrictive properties of a medium using dilute composite artificial materials. Analytical expressions for the composite electrostriction are derived and used to show that enhancement, tunability and suppression can be achieved through a careful choice of constituent materials. Numerical examples with Ag, As$_2$S$_3$, Si and SiO$_2$ demonstrate that even in a non-resonant regime, artificial materials can bring more than a threefold enhancement in the electrostriction.

  5. Project Listen Compute Show (LCS) - Marine

    Science.gov (United States)

    2004-02-01

    TECHNICAL REPORT NATICK/TR-04/010 APA ^QO^U PROJECT LISTEN, COMPUTE, SHOW (LCS) - MARINE by Victor Zue* John Wroclawski* and Michael Bolotski...Voice Communication Strategy 37 6.3 Adaptive Channel Multiplexing 38 6.4 Web Performance and the Cache Information Protocol 41 7. Handheld Device...view of the BB-4 stack. The digital board is at the top. Most of the area is the large FPGA and the two frame buffer memories 61 Figure 14

  6. Trematode Hemoglobins Show Exceptionally High Oxygen Affinity

    OpenAIRE

    Kiger, Laurent; Rashid, Aftab K.; Griffon, Nathalie; Haque, Masoodul; Moens, Luc; Gibson, Quentin H.; Poyart, Claude; Marden, Michael C.

    1998-01-01

    Ligand binding studies were made with hemoglobin (Hb) isolated from trematode species Gastrothylax crumenifer (Gc), Paramphistomum epiclitum (Pe), Explanatum explanatum (Ee), parasitic worms of water buffalo Bubalus bubalis, and Isoparorchis hypselobagri (Ih) parasitic in the catfish Wallago attu. The kinetics of oxygen and carbon monoxide binding show very fast association rates. Whereas oxygen can be displaced on a millisecond time scale from human Hb at 25 degrees C, the dissociation of ox...

  7. Reality, ficción o show

    Directory of Open Access Journals (Sweden)

    Sandra Ruíz Moreno

    2002-01-01

    Full Text Available Para tener un punto de vista claro y objetivo frente a la polémica establecida en torno al programa “Protagonistas de novela” y la tendiente proliferación de los reality show en las parrillas de programación de la televisión colombiana, se realizó un análisis de texto y contenido de dicho programa, intentando definirlo desde sus posibilidades de realidad, ficción y show. Las unidades de análisis y el estudio de su tratamiento arrojaron un alto contenido que gira en torno a las emociones del ser humano relacionadas con la convivencia, tratadas a manera de show y con algunos aportes textuales de ficción, pero sin su elemento mediador básico, el actor, quitándole toda la posibilidad de tener un tratamiento con la profundidad, distancia y ética que requieren los temas de esta índole. El resultado es un formato que sólo busca altos índices de sintonía y que pertenece más a la denominada televisión “trash”, que a una búsqueda de realidad del hombre y mucho menos de sociedad.

  8. Software for portable laser light show system

    Science.gov (United States)

    Buruchin, Dmitrey J.; Leonov, Alexander F.

    1995-04-01

    Portable laser light show system LS-3500-10M is connected to the parallel port of IBM PC/AT compatible computer. Computer performs output of digital control data describing images. Specially designed control device is used to convert digital data coming from parallel port to the analog signal driving scanner. Capabilities of even cost nothing 286 computer are quite enough for laser graphics control. Technology of scanning used in laser graphics system LS-3500-10M essentially differs from widely spread systems based on galvanometers with mobile core or with mobile magnet. Such devices are based on the same principle of work as electrically driven servo-mechanism. As scanner we use elastic system with hydraulic dampen oscillations and opened loop. For most of applications of laser graphics such system provides satisfactory precision and speed of scanning. LS-3500-10M software gives user ability to create on PC and play his own laser graphics demonstrations. It is possible to render recognizable text and pictures using different styles, 3D and abstract animation. All types of demonstrations can be mixed in slide-show. Time synchronization is supported. Software has the following features: (1) Different types of text output. Built-in text editor for typing and editing of textural information. Different fonts can be used to display text. User can create his own fonts using specially developed font editor. (2) Editor of 3D animation with library of predefined shapes. (3) Abstract animation provided by software routines. (4) Support of different graphics files formats (PCX or DXF). Original algorithm of raster image tracing was implemented. (5) Built-in slide-show editor.

  9. Asteroid Ida - 6 Views Showing Rotation

    Science.gov (United States)

    1994-01-01

    This composite image shows the asteroid 243 Ida as seen from the Galileo spacecraft during its approach on August 28, 1993. The six views were shuttered through the camera's green filter and show Ida's rotation over a period of about 3 hours 18 minutes. The asteroid makes a complete rotation every 4 hours 38 minutes; therefore, this set of images spans about 3/4 of Ida's rotation period and shows most of Ida's surface. By combining the information in these views with that from the highest resolution images returned from the spacecraft in September 1993, the size and shape of this irregular body can now be determined accurately The asteroid appears to be about 58 kilometers (36 miles) long and about 23 kilometers wide, with a very irregular shape and volume of some 16,000 cubic kilometers. The images are arranged in chronological order from a time 3 hours 51 minutes before closest approach (upper left), through upper right, middle left, middle right lower left and lower right (33 minutes before closest approach). The six images show Ida at the same scale throughout. Ida's rotation axis is roughly vertical in these images, and the rotation causes the right-hand end of Ida to move toward the viewer as time progresses. The first image was taken from a range of about 171,000 km (106,000 miles) and provides an image resolution of about 1,700 meters per pixel (the highest resolution achieved for Ida is about 25 meters per pixel). The second, taken 70 minutes later, is from 119,000 kilometers, followed by 102,000 kilometers, 85,000 kilometers, 50,000 kilometers, and 25,000 kilometers. The features on Ida are less sharp in the earlier views because of the greater distances. Prominent in the middle three views is a deep depression across the short axis of the Asteroid. This feature tends to support the idea that Ida may have originally been formed from two or more separate large objects that collided softly and stuck together. Also visible in the lower left view is an

  10. Trematode hemoglobins show exceptionally high oxygen affinity.

    Science.gov (United States)

    Kiger, L; Rashid, A K; Griffon, N; Haque, M; Moens, L; Gibson, Q H; Poyart, C; Marden, M C

    1998-08-01

    Ligand binding studies were made with hemoglobin (Hb) isolated from trematode species Gastrothylax crumenifer (Gc), Paramphistomum epiclitum (Pe), Explanatum explanatum (Ee), parasitic worms of water buffalo Bubalus bubalis, and Isoparorchis hypselobagri (Ih) parasitic in the catfish Wallago attu. The kinetics of oxygen and carbon monoxide binding show very fast association rates. Whereas oxygen can be displaced on a millisecond time scale from human Hb at 25 degrees C, the dissociation of oxygen from trematode Hb may require a few seconds to over 20 s (for Hb Pe). Carbon monoxide dissociation is faster, however, than for other monomeric hemoglobins or myoglobins. Trematode hemoglobins also show a reduced rate of autoxidation; the oxy form is not readily oxidized by potassium ferricyanide, indicating that only the deoxy form reacts rapidly with this oxidizing agent. Unlike most vertebrate Hbs, the trematodes have a tyrosine residue at position E7 instead of the usual distal histidine. As for Hb Ascaris, which also displays a high oxygen affinity, the trematodes have a tyrosine in position B10; two H-bonds to the oxygen molecule are thought to be responsible for the very high oxygen affinity. The trematode hemoglobins display a combination of high association rates and very low dissociation rates, resulting in some of the highest oxygen affinities ever observed.

  11. Fully protected glycosylated zinc (II) phthalocyanine shows high uptake and photodynamic cytotoxicity in MCF-7 cancer cells.

    Science.gov (United States)

    Kimani, Stanley G; Shmigol, Tatiana A; Hammond, Samantha; Phillips, James B; Bruce, James I; MacRobert, Alexander J; Malakhov, Mikhail V; Golding, Jon P

    2013-01-01

    Phthalocyanine photosensitizers are effective in anticancer photodynamic therapy (PDT) but suffer from limited solubility, limited cellular uptake and limited selectivity for cancer cells. To improve these characteristics, we synthesized isopropylidene-protected and partially deprotected tetra β-glycosylated zinc (II) phthalocyanines and compared their uptake and accumulation kinetics, subcellular localization, in vitro photocytotoxicity and reactive oxygen species generation with those of disulfonated aluminum phthalocyanine. In MCF-7 cancer cells, one of the compounds, zinc phthalocyanine {4}, demonstrated 10-fold higher uptake, 5-fold greater PDT-induced cellular reactive oxygen species concentration and 2-fold greater phototoxicity than equimolar (9 μm) disulfonated aluminum phthalocyanine. Thus, isopropylidene-protected β-glycosylation of phthalocyanines provides a simple method of improving the efficacy of PDT. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  12. Microbiological and environmental issues in show caves.

    Science.gov (United States)

    Saiz-Jimenez, Cesareo

    2012-07-01

    Cultural tourism expanded in the last half of the twentieth century, and the interest of visitors has come to include caves containing archaeological remains. Some show caves attracted mass tourism, and economical interests prevailed over conservation, which led to a deterioration of the subterranean environment and the rock art. The presence and the role of microorganisms in caves is a topic that is often ignored in cave management. Knowledge of the colonisation patterns, the dispersion mechanisms, and the effect on human health and, when present, over rock art paintings of these microorganisms is of the utmost importance. In this review the most recent advances in the study of microorganisms in caves are presented, together with the environmental implications of the findings.

  13. Genotypically defined lissencephalies show distinct pathologies.

    Science.gov (United States)

    Forman, Mark S; Squier, Waney; Dobyns, William B; Golden, Jeffrey A

    2005-10-01

    Lissencephaly is traditionally divided into 2 distinct pathologic forms: classic (type I) and cobblestone (type II). To date, mutations in 4 genes, LIS1, DCX, RELN, and ARX, have been associated with distinct type I lissencephaly syndromes. Each of these genes has been shown to play a role in normal cell migration, consistent with the presumed pathogenesis of type I lissencephaly. Based on these data, we hypothesized that all forms of radiographically defined type I lissencephaly independent of genotype would be pathologically similar. To test this hypothesis, we examined brains from 16 patients, including 15 lissencephalic patients and one patient with subcortical band heterotopia. Of these 16 patients, 6 had LIS1 deletions, 2 had DCX mutations, and 2 had ARX mutations. In addition, 6 patients had no defined genetic defect, although the patient with subcortical band heterotopia exhibited the same pattern of malformation expected with an XLIS mutation. In all cases, the cortex was thickened; however, the topographic distribution of the cortical pathology varied, ranging from frontal- to occipital-biased pathology to diffuse involvement of the neocortex. Although brains with LIS1 deletions exhibited the classic 4-layer lissencephalic architecture, patients with DCX and ARX mutations each had unique cytoarchitectural findings distinct from LIS1. Furthermore, 2 of the 5 patients with no known genetic defect showed a fourth type of histopathology characterized by a 2-layered cortex. Interestingly, the 2 brains with the fourth type of lissencephaly showed profound brainstem and cerebellar abnormalities. In summary, we identified at least 4 distinct histopathologic subtypes of lissencephaly that stratify with the underlying genetic defect. Based on these data, a new classification for lissencephaly is proposed that incorporates both pathologic and genetic findings.

  14. Evaluation of the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally infected root canals.

    Science.gov (United States)

    Cheng, Xiaogang; Guan, Sumin; Lu, Hong; Zhao, Chunmiao; Chen, Xingxing; Li, Na; Bai, Qian; Tian, Yu; Yu, Qing

    2012-12-01

    In recent years, various laser systems have been introduced into the field of laser-assisted endodontic therapy. The aim of this study was to evaluate the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally infected root canals compared with standard endodontic treatment of 5.25% sodium hypochlorite (NaClO) irrigation. Two hundred and twenty infected root canals from extracted human teeth (contaminated with Enterococcus faecalis ATCC 4083 for 4 weeks) were randomly divided into five experimental groups (Nd:YAG, Er:YAG + 5.25% NaClO + 0.9% normal saline + distilled water (Er:YAG/NaClO/NS/DW), Er:YAG + 0.9% normal saline + distilled water (Er:YAG/NS/DW), Er,Cr:YSGG, and aPDT) and two control groups (5.25% NaClO as positive control and 0.9% normal saline (NS) as negative control). The numbers of bacteria on the surface of root canal walls and at different depths inside dentinal tubules before and after treatment were analyzed by means of one-way analysis of variance (one-way ANOVA). The morphology of bacterial cells before and after treatment was examined by scanning electron microscopy (SEM). After treatment, the bacterial reductions in the experimental groups and the positive control group were significantly greater than that of the negative control group (P therapy. Copyright © 2012 Wiley Periodicals, Inc.

  15. Individual ant workers show self-control.

    Science.gov (United States)

    Wendt, Stephanie; Czaczkes, Tomer J

    2017-10-01

    Often, the first option is not the best. Self-control can allow humans and animals to improve resource intake under such conditions. Self-control in animals is often investigated using intertemporal choice tasks-choosing a smaller reward immediately or a larger reward after a delay. However, intertemporal choice tasks may underestimate self-control, as test subjects may not fully understand the task. Vertebrates show much greater apparent self-control in more natural foraging contexts and spatial discounting tasks than in intertemporal choice tasks. However, little is still known about self-control in invertebrates. Here, we investigate self-control in the black garden ant Lasius niger We confront individual workers with a spatial discounting task, offering a high-quality reward far from the nest and a poor-quality reward closer to the nest. Most ants (69%) successfully ignored the closer, poorer reward in favour of the further, better one. However, when both the far and the close rewards were of the same quality, most ants (83%) chose the closer feeder, indicating that the ants were indeed exercising self-control, as opposed to a fixation on an already known food source. © 2017 The Author(s).

  16. Offshore technology stresses substance over show

    Energy Technology Data Exchange (ETDEWEB)

    Wright, T.R. Jr.; Abraham, K.S.

    1988-07-01

    Emphasis these days continues to be on practical, cost-effective solutions to real problems. With a couple of exceptions, gone are the glitz and glamour of big-ticket items developed on speculation for projects and situations that don't yet exist. Manufacturers are cautiously spending money on R and D for more down-to-earth items. There seems to be a motto that ''less can be more,'' if researchers focus their limited resources on developing items that are more efficient, easier to install and operate, and save money. Items reviewed on this and other pages by WORLD OIL this year are certainly reflective of such attitudes. Short on show, but long on substance, they provide practical answers to everyday, routine problems encountered by offshore operators. They range from a subsea wireline lubricator developed by BP and Schlumberger, to a new ''armoring'' system that coats platform risers and saves them from the ravages of Mother Nature. There are also an electric safety valve and assorted other goodies. In addition, engineers have completed a fascinating study, which determined why some drilling vessels really sank during blowouts. It is incorrect to assume that large-sized innovations have disappeared completely. For instance, Conoco and others have designed a single-leg, tension-leg platform for Gulf of Mexico duty, which is featured below. Keep in mind, however, the primary motivation for this design was to improve logistics, shorten the timeframe, and save money.

  17. Pregnant rats show enhanced spatial memory, decreased anxiety, and altered levels of monoaminergic neurotransmitters

    Science.gov (United States)

    Macbeth, A.H.; Gautreaux, C.; Luine, V.N.

    2008-01-01

    Spatial memory, anxiety and central monoaminergic activities were measured in non-pregnant (NP) and pregnant females during two time periods of pregnancy: gestational day 7–9 (GD7, GD9) & gestation day 16–18 (GD16, GD18). Pregnant females discriminated between object locations on both test days on an object placement task, whereas NP females were unable to discriminate between locations. Pregnant females displayed decreased anxiety on the elevated plus maze on GD9 compared to NP females, followed by increased anxiety-like behavior on the elevated plus maze on GD18. Monoamine levels and activity (as indexed by turnover ratio) were measured in prefrontal cortex (PFC), CA1 and CA3 regions of the hippocampus (areas important for memory), and medial preoptic area (mPOA, an area important in display of maternal behaviors). In the PFC, NP females generally had higher monoamine levels and turnover ratios; however, norepinephrine (NE) turnover was higher in pregnant females at GD18. In the CA1 and CA3 regions of the hippocampus, monoamine levels and turnover ratios were generally higher during pregnancy, particularly on GD9. In the mPOA, pregnancy was associated with increases in NE activity, a previously unreported finding. The present study expands upon existing research indicating that pregnancy is beneficial to spatial memory and may decrease anxiety. Changes in monoamine levels and activity in specific brain regions indicate that the dopamine, norepinephrine and serotonin systems may contribute to the observed behavioral differences. PMID:18823955

  18. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis.

    NARCIS (Netherlands)

    Zwijnenburg, P.J.G.; Poll, van der T.; Florquin, S; Akira, S; Takeda, K; Roord, J.J.; Furth, van A.M.

    2003-01-01

    To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of

  19. Enhanced Semantic TV-Show Representation for Personalized Electronic Program Guides

    NARCIS (Netherlands)

    Musto, C.; Narducci, F.; Lops, P.; Semeraro, G.; Gemmis, M. de; Barbieri, M.; Korst, J.H.M.; Pronk, S.P.P.; Clout, R.A.W.

    2012-01-01

    Personalized electronic program guides help users overcome information overload in the TV and video domain by exploiting recommender systems that automatically compile lists of novel and diverse video assets, based on implicitly or explicitly defined user preferences. Inthis context, we assume that

  20. Carbogen breathing significantly enhances the penetration of red light in murine tumours in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Mitra, Soumya [Department of Biochemistry and Biophysics, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY 14642 (United States); Foster, Thomas H [Department of Radiology, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY 14642 (United States)

    2004-05-21

    We report results of experiments that evaluated the influence of oxygenation on the penetration of red light in tissue, with particular emphasis on 630 and 650 nm laser wavelengths commonly used in photodynamic therapy (PDT) of solid tumours. Direct measurements in tissue-simulating phantoms comprised of intact human erythrocytes suspended in a scattering emulsion demonstrated significant enhancements in fluence rate at depths of 0.5-2 cm from the irradiated surface when the cells were fully oxygenated versus fully deoxygenated. The 630 and 650 nm fluence rates at depth in the homogeneous phantoms continued to increase when examined over a continuous range of oxygen partial pressures from 0 to 160 Torr. When considered as a function of haemoglobin oxygen saturation, the largest increases in fluence rate were observed as the saturation increased beyond 70%. Dramatic increases in optical fluence rate were measured at the base of 1-cm-thick subcutaneous EMT6 mammary carcinomas in vivo when the tumour-bearing mouse was subjected to carbogen through a nose cone. These results indicate that improved tumour oxygenation is important in PDT not only for the maintenance of the oxygen-dependent photochemistry but, through the effects reported here, may also enable more efficient treatment of thicker lesions.

  1. Pretreatment with 5-Fluorouracil Cream Enhances the Efficacy of Daylight-mediated Photodynamic Therapy for Actinic Keratosis

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Heerfordt, Ida Marie; Wiegell, Stine R

    2017-01-01

    The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized int...

  2. Photoinduced Electron-Transfer Mechanisms for Radical-Enhanced Photodynamic Therapy Mediated by Water-Soluble Decacationic C70 and C84O2 Fullerene Derivatives

    Science.gov (United States)

    Sperandio, Felipe F.; Sharma, Sulbha K.; Wang, Min; Jeon, Seaho; Huang, Ying-Ying; Dai, Tianhong; Nayka, Suhasini; de Sousa, Suzana C.O.M.; Chiang, Long Y.; Hamblin, Michael R.

    2012-01-01

    Fullerenes are promising candidates for photodynamic therapy (PDT). Thus, C70 and novel C84O2 fullerenes were functionalized with and without an additional deca-tertiary ethyleneamino-chain as an electron source, giving rise to two distinct pairs of photosensitizers, the monoadducts LC-17, LC-19 and the bisadducts LC18 and LC-20 to perform PDT in HeLa cells with UVA, blue, green, white and red light. Shorter wavelengths gave more phototoxicity with LC-20 while LC-19 was better at longer wavelengths; the ratio between killing obtained with LC-19 and LC-20 showed an almost perfect linear correlation (R = 0.975) with wavelength. The incorporation of a deca-tertiary amine chain in the C84O2 fullerene gave more PDT killing when excited with shorter wavelengths or in presence of low ascorbate concentration through higher generation of hydroxyl radicals. Photoactivated C84O2 fullerenes induced apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage demonstrated by acridine orange and rhodamine 123 fluorescent probes. PMID:23117043

  3. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

    Full Text Available Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA-mediated photodynamic therapy (PDT to treat oral precancers including oral leukoplakia (OL, oral erythroleukoplakia (OEL, and oral verrucous hyperplasia (OVH as well as oral cancers including oral verrucous carcinoma (OVC and oral squamous cell carcinoma (OSCC. Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2 was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2 on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for

  4. The Comparison Between Chinese Puppet Show and Chinese-Javanese Blend Puppet Show in Indonesia

    Directory of Open Access Journals (Sweden)

    Agustinus Sufianto

    2011-04-01

    Full Text Available Since some centuries ago, Indonesia has been one of the destinations for immigrating Chinese. When the Chinese came to Indonesia, they also brought their cultures and customs. Some of them have a cultural-cross marriage with local Indonesian and brought their cultures to be introduced to local Indonesian. When the relationship between Chinese and Indonesian became stronger in some fields such as trade, education and politic, some of Chinese cultures has been adapted by local Indonesian or has been assimilated with local cultures. This adaption process was hindered when the New Order of Soeharto government had banned all Chinese culture, including anything closely related. So, the Chinese-Javanese blend puppet show that also brings Chinese culture couldn’t get any supports and its development faces difficulties. The writer using a qualitative methodology interviewed some of Chinese-Javanese puppet show artist and observation of the puppet show performance to make a comparison between Chinese puppet show and Chinese-Javanese blend puppet show in Indonesia. Chinese-Javanese puppet show or usually can be determined as Indonesian potehi puppet Show has some differences from Chinese puppet show. The differences can be found in the making of puppet, puppet profiles, performance way and stories. 

  5. Tip enhancement

    CERN Document Server

    Kawata, Satoshi

    2007-01-01

    This book discusses the recent advances in the area of near-field Raman scattering, mainly focusing on tip-enhanced and surface-enhanced Raman scattering. Some of the key features covered here are the optical structuring and manipulations, single molecule sensitivity, analysis of single-walled carbon nanotubes, and analytic applications in chemistry, biology and material sciences. This book also discusses the plasmonic materials for better enhancement, and optical antennas. Further, near-field microscopy based on second harmonic generation is also discussed. Chapters have been written by some of the leading scientists in this field, who present some of their recent work in this field.·Near-field Raman scattering·Tip-enhanced Raman spectroscopy·Surface-enhanced Raman spectroscopy·Nano-photonics·Nanoanalysis of Physical, chemical and biological materials beyond the diffraction limits·Single molecule detection

  6. A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz(®) ) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED(®) lamp.

    Science.gov (United States)

    Reinhold, U; Dirschka, T; Ostendorf, R; Aschoff, R; Berking, C; Philipp-Dormston, W G; Hahn, S; Lau, K; Jäger, A; Schmitz, B; Lübbert, H; Szeimies, R-M

    2016-10-01

    Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun-damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial. To evaluate the efficacy, safety and cosmetic outcome of BF-200 ALA (a nanoemulsion formulation containing 10% aminolaevulinic acid hydrochloride) combined with the BF-RhodoLED(®) lamp for the field-directed treatment of mild-to-moderate AK with PDT. The study was performed as a randomized, multicentre, double-blind, placebo-controlled, parallel-group, phase III trial with BF-200 ALA and placebo in seven centres in Germany. A total of 94 patients were enrolled in this study; 87 were randomized (55 patients received BF-200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF-RhodoLED (635 nm ± 9 nm) until a total light dose of 37 J cm(-2) was achieved. BF-200 ALA was superior to placebo with respect to patient complete clearance rate (91% vs. 22%, P < 0·0001) and lesion complete clearance rate (94·3% vs. 32·9%, P < 0·0001) after a maximum of two PDTs. The confirmatory analysis of all key secondary variables supported this superiority" should not be skipped since this is an important result. Treatment-emergent adverse events (TEAEs) were experienced by 100% of the BF-200 ALA group and 69% of the placebo group. The most commonly reported TEAEs were TEAEs of the application site. The cosmetic outcome was improved in the BF-200 ALA group compared with placebo. Field-directed therapy with BF-200 ALA and BF-RhodoLED lamp is highly effective and well tolerated for multiple mild-to-moderate AK lesions, providing greatly improved skin quality. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on

  7. How the timing and location of video shows influence learning among rice farmers in Uganda

    National Research Council Canada - National Science Library

    Karubanga, Gabriel; Kibwika, Paul; Okry, Florent; Sseguya, Haroon

    Videos have the potential of enhancing learning among smallholder farmers. The study intended to establish whether timing and location of video shows influence learning among rice farmers in Kamwenge district, Uganda...

  8. Best in show but not best shape: a photographic assessment of show dog body condition.

    Science.gov (United States)

    Such, Z R; German, A J

    2015-08-01

    Previous studies suggest that owners often wrongly perceive overweight dogs to be in normal condition. The body shape of dogs attending shows might influence owners' perceptions, with online images of overweight show winners having a negative effect. This was an observational in silico study of canine body condition. 14 obese-prone breeds and 14 matched non-obese-probe breeds were first selected, and one operator then used an online search engine to identify 40 images, per breed, of dogs that had appeared at a major national UK show (Crufts). After images were anonymised and coded, a second observer subjectively assessed body condition, in a single sitting, using a previously validated method. Of 1120 photographs initially identified, 960 were suitable for assessing body condition, with all unsuitable images being from longhaired breeds. None of the dogs (0 per cent) were underweight, 708 (74 per cent) were in ideal condition and 252 (26 per cent) were overweight. Pugs, basset hounds and Labrador retrievers were most likely to be overweight, while standard poodles, Rhodesian ridgebacks, Hungarian vizslas and Dobermanns were least likely to be overweight. Given the proportion of show dogs from some breeds that are overweight, breed standards should be redefined to be consistent with a dog in optimal body condition. British Veterinary Association.

  9. Learning from a dive show in an aquarium setting

    Science.gov (United States)

    Walsh, Lori M.

    A study was conducted at an aquarium next to a theme park to understand information recalled from two versions of shows viewed at the largest display. The goal of this research was to determine if learning was enhanced by having a diver in water as the treatment group. This project focused on the knowledge recalled about shark and ray feeding adaptations, the information recalled about the mentioned conservation message about sustainable seafood and the potential of the two shows to make memorable experiences. During the project, 30 adult participants from each group were given a survey with five open-ended questions. Results suggest that the diver might distract from biological content information, or that the diver is such a novel element that it interferes with recall. While guests seemed to recall information about rays and sharks, the amount of information was not substantial. It appears that the diver does not affect content messaging but does impact whether guests attend to Seafood Watch messaging. The diver may have been so novel that the treatment group could not attend to the conservation message that was delivered, regardless of topic, or the control group recalled the message because the guests were not distracted by the diver or feeding. The absence of a diver seems to allow the guests to better attend to what is happening outside of the tank. While adding a diver increases photo opportunities and may bring guests to a show, the results seem to indicate that it does not significantly increase recall. The results of this study show that guests in a theme park setting can recall information from an educational program. Guests may not enter this hybrid aquarium with the intention of learning, but recall, one of the components in learning, does occur.

  10. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  11. Characterization of a GM7 glioblastoma cell line showing CD133 positivity and both cytoplasmic and nuclear localization of nestin.

    Science.gov (United States)

    Loja, Tomas; Chlapek, Petr; Kuglik, Petr; Pesakova, Martina; Oltova, Alexandra; Cejpek, Pavel; Veselska, Renata

    2009-01-01

    A newly established GM7 cell line was derived from the tumor tissue of a 65-year-old man surgically treated for a relapse of glioblastoma multiforme that occurred 10 months after first surgery following radiotherapy. GM7 cells exhibit spindle or glia-like morphology, and multinucleated giant cells are also present in the culture. The cells proliferate rapidly (PDT is about 18 h) and tend to grow in multilayer without contact inhibition. Using G-banding and SKY, the GM7 cell line was identified as near-triploid with a large number of structural and numerical abnormalities. Repeated karyotyping during long-term cultivation confirmed a chromosome number of 70+/-3 chromosomes per cell. Special attention was paid to the immunocytochemical analysis of protein markers in this cell line; GM7 cells showed strong positivity for CD133, vimentin, nestin, NF-160 and S-100 protein and weak positivity for GFAP and NSE, but were negative for synaptophysin. The most important features of the GM7 cell line are its stable phenotype CD133+/nestin+, which are accepted as stem cell markers in neural stem/progenitor cells, and especially unusual intracellular localization of the IF protein nestin, which was detected and repeatedly confirmed both in the cytoplasm and cell nucleus. For this reason, the new GM7 glioblastoma cell line represents an important model suitable not only for further studies on glioblastoma biology and cancer stem cells, but particularly for the detailed investigation of the role of nestin in transformed cells.

  12. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    Science.gov (United States)

    Bouwense, Stefan AW; Olesen, Søren S; Drewes, Asbjørn M; van Goor, Harry; Wilder-Smith, Oliver HG

    2015-01-01

    Background Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders) to placebo or pregabalin treatment. Methods This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15) or placebo (n=12; n=17) treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT) in dermatomes C5 (generalized effects) and Ventral T10 (segmental effects). Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM) paradigm. Results Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA) vs placebo responders (−0.1 mA; P=0.015). This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9%) vs placebo responders (−17%; P<0.001). CPM changed significantly vs baseline only for pregabalin responders (P=0.006). Conclusion This hypothesis-generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study. PMID:26203273

  13. Pulse photodynamic therapy reduces inflammation without compromising efficacy in the treatment of multiple mild actinic keratoses of the face and scalp

    DEFF Research Database (Denmark)

    Wiegell, S R; Petersen, Bibi Øager; Wulf, H C

    2016-01-01

    BACKGROUND: The main side-effects of photodynamic therapy (PDT) for actinic keratoses (AKs) are post-treatment erythema and oedema, and pain during illumination. Severe erythema after PDT enhances the down time associated with the treatment. OBJECTIVES: To evaluate in a randomized intraindividual...... study whether pulse-PDT and corticosteroid pulse-PDT would reduce treatment-induced erythema compared with conventional PDT. METHODS: Twenty-two patients with multiple mild AKs on the face and scalp were treated with methyl aminolaevulinate (MAL)-PDT in three similar areas. Two areas were incubated...... with MAL for 30 min (pulse-PDT) and one area was incubated with MAL for 3 h (conventional PDT). All areas were illuminated with red light after 3 h. In one of the pulse-PDT areas a superpotent corticosteroid was applied before and just after PDT (S-pulse-PDT). RESULTS: Pulse-PDT significantly reduced PDT...

  14. A possible relationship between the anti-cancer potency of photodynamic therapy using the novel photosensitizer ATX-s10-Na(II) and expression of the vascular endothelial growth factor in vivo.

    Science.gov (United States)

    Okunaka, T; Usuda, J; Ichinose, S; Hirata, H; Ohtani, K; Maehara, S; Inoue, T; Imai, K; Kubota, M; Tsunoda, Y; Kuroiwa, Y; Tsutsui, H; Furukawa, K; Nishio, K; Kato, H

    2007-09-01

    ATX-s10-Na(II) is a novel second-generation photo-sensitizer for photodynamic therapy (PDT). PDT using ATX-s10 and diode laser (670 nm) induces an apoptotic response, inflammatory reaction, immune reaction and damage to the microvasculature. In particular, the vascular shut-down effect plays an important role in the anti-tumor activity of ATX-s10-PDT. It has been reported that PDT induces hypoxia and expression of the vascular endothelial growth factor (VEGF) via the hypoxia-inducible factor 1 (HIF1)-alpha pathway. We hypothesized that the expression of VEGF may cause tumor recurrence after PDT and exert unfavorable effect against the anti-tumor activity of ATX-s10-PDT. In this study, we showed by DNA microarray analysis in vitro that VEGF mRNA expression was induced 3 h after laser irradiation in ATX-s10-PDT. We compared the anti-tumor activity of ATX-s10-PDT against lung cancer cell lines SBC-3 and SBC-3/VEGF, the latter overexpressing VEGF; there was no significant difference in the sensitivity to the PDT between the two cell lines as assessed by clonogenic assay. Furthermore, no statistically significant difference in the anti-tumor effect of PDT, as measured by tumor cures, was found between SBC-3 and SBC-3/VEGF tumors in female Balb/c-nu/nu nude mice in vivo. In conclusion, ATX-s10-PDT may prevent tumor recurrence despite induction of VEGF and promotion of tumor angiogenesis, which are known to enhance tumor proliferation and survival.

  15. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.

    Directory of Open Access Journals (Sweden)

    Vijee Mohan

    Full Text Available Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS, carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1 involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.

  16. PARK2 patient neuroprogenitors show increased mitochondrial sensitivity to copper.

    Science.gov (United States)

    Aboud, Asad A; Tidball, Andrew M; Kumar, Kevin K; Neely, M Diana; Han, Bingying; Ess, Kevin C; Hong, Charles C; Erikson, Keith M; Hedera, Peter; Bowman, Aaron B

    2015-01-01

    Poorly-defined interactions between environmental and genetic risk factors underlie Parkinson's disease (PD) etiology. Here we tested the hypothesis that human stem cell derived forebrain neuroprogenitors from patients with known familial risk for early onset PD will exhibit enhanced sensitivity to PD environmental risk factors compared to healthy control subjects without a family history of PD. Two male siblings (SM and PM) with biallelic loss-of-function mutations in PARK2 were identified. Human induced pluripotent stem cells (hiPSCs) from SM, PM, and four control subjects with no known family histories of PD or related neurodegenerative diseases were utilized. We tested the hypothesis that hiPSC-derived neuroprogenitors from patients with PARK2 mutations would show heightened cell death, mitochondrial dysfunction, and reactive oxygen species generation compared to control cells as a result of exposure to heavy metals (PD environmental risk factors). We report that PARK2 mutant neuroprogenitors showed increased cytotoxicity with copper (Cu) and cadmium (Cd) exposure but not manganese (Mn) or methyl mercury (MeHg) relative to control neuroprogenitors. PARK2 mutant neuroprogenitors also showed a substantial increase in mitochondrial fragmentation, initial ROS generation, and loss of mitochondrial membrane potential following Cu exposure. Our data substantiate Cu exposure as an environmental risk factor for PD. Furthermore, we report a shift in the lowest observable effect level (LOEL) for greater sensitivity to Cu-dependent mitochondrial dysfunction in patients SM and PM relative to controls, correlating with their increased genetic risk for PD. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Speech enhancement

    CERN Document Server

    Benesty, Jacob; Chen, Jingdong

    2006-01-01

    We live in a noisy world! In all applications (telecommunications, hands-free communications, recording, human-machine interfaces, etc.) that require at least one microphone, the signal of interest is usually contaminated by noise and reverberation. As a result, the microphone signal has to be ""cleaned"" with digital signal processing tools before it is played out, transmitted, or stored.This book is about speech enhancement. Different well-known and state-of-the-art methods for noise reduction, with one or multiple microphones, are discussed. By speech enhancement, we mean not only noise red

  18. Cholesterol Domains Enhance Transfection

    Science.gov (United States)

    Betker, Jamie L.; Kullberg, Max; Gomez, Joe; Anchordoquy, Thomas J.

    2014-01-01

    The formation of cholesterol domains in lipoplexes has been associated with enhanced serum stability and transfection rates both in cell culture and in vivo. This study utilizes the ability of saturated phosphatidylcholines to promote the formation of cholesterol domains at much lower cholesterol contents than have been utilized in previous work. The results show that lipoplexes with identical cholesterol and cationic lipid contents exhibit significantly improved transfection efficiencies when a domain is present, consistent with previous work. In addition, studies assessing transfection rates in the absence of serum demonstrate that the ability of domains to enhance transfection is not dependent on interactions with serum proteins. Consistent with this hypothesis, characterization of the adsorbed proteins composing the corona of these lipoplex formulations did not reveal a correlation between transfection and the adsorption of a specific protein. Finally, we show that the interaction with serum proteins can promote domain formation in some formulations, and thereby result in enhanced transfection only after serum exposure. PMID:23557286

  19. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

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    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  20. Enhanced aggressiveness of bystander cells in an anti-tumor photodynamic therapy model: Role of nitric oxide produced by targeted cells.

    Science.gov (United States)

    Bazak, Jerzy; Fahey, Jonathan M; Wawak, Katarzyna; Korytowski, Witold; Girotti, Albert W

    2017-01-01

    The bystander effects of anti-cancer ionizing radiation have been widely studied, but far less is known about such effects in the case of non-ionizing photodynamic therapy (PDT). In the present study, we tested the hypothesis that photodynamically-stressed prostate cancer PC3 cells can elicit nitric oxide (NO)-mediated pro-growth/migration responses in non-stressed bystander cells. A novel approach was used whereby both cell populations existed on a culture dish, but made no physical contact with one other. Visible light irradiation of target cells sensitized with 5-aminolevulinic acid-induced protoporphyrin IX resulted in a striking upregulation of inducible nitric oxide synthase (iNOS) along with NO, the level of which increased after irradiation. Slower and less pronounced iNOS/NO upregulation was also observed in bystander cells. Activation of transcription factor NF-κB was implicated in iNOS induction in both targeted and bystander cells. Like surviving targeted cells, bystanders exhibited a significant increase in growth and migration rate, both responses being strongly attenuated by an iNOS inhibitor (1400W), a NO scavenger (cPTIO), or iNOS knockdown. Incubating bystander cells with conditioned medium from targeted cells failed to stimulate growth/migration, ruling out involvement of relatively long-lived stimulants. The following post-irradiation changes in pro-survival/pro-growth proteins were observed in bystander cells: upregulation of COX-2 and activation of protein kinases Akt and ERK1/2, NO again playing a key role. This is the first reported evidence for NO-enhanced bystander aggressiveness in the context of PDT. In the clinical setting, such effects could be averted through pharmacologic use of iNOS inhibitors as PDT adjuvants. Copyright © 2016. Published by Elsevier Inc.

  1. Show that it works, lessons learned from facilitating building with nature experiments

    NARCIS (Netherlands)

    Lulofs, Kristiaan R.D.; Smit, M.R.H.

    2012-01-01

    In multi-actor governance systems, experimenting is believed to be essential to enhance the adaptive capacity by learning about alternatives. ‘Show that it works’ is an essential step en route to ‘make it happen’. The key challenge for innovators then becomes finding opportunities to show that it

  2. Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

    Science.gov (United States)

    2010-01-01

    Background The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia. Methods Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. Results We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. Conclusions We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad

  3. Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

    Directory of Open Access Journals (Sweden)

    Rao Benqiang

    2010-05-01

    Full Text Available Abstract Background The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT by conjugating factor VII (fVII protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT for cancer. fVII is a natural ligand for receptor tissue factor (TF with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC and many types of tumour cells, including solid tumours and leukaemia. Methods Murine factor VII protein (mfVII containing a mutation (Lys341Ala was covalently conjugated via a cross linker EDC with Veterporfin (VP that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. Results We showed that: (i fVII protein could be conjugated with VP without affecting its binding activity; (ii fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii fVII targeting enhanced the effect of VP PDT by three to four fold; (iii fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. Conclusions We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have

  4. Terapia fotodinámica (PDT en piel y estética: procedimiento, materiales y método en base a nuestra experiencia Photodinamic therapy in skin and aesthetics: procedure, matherials and method based on our experience

    Directory of Open Access Journals (Sweden)

    S. Mordon

    2012-09-01

    Full Text Available La terapia fotodinámica (PTD es un procedimiento cada vez más utilizado para tratar diversas afecciones dermatológicas y dermatoestéticas. Su aplicación obtiene buenos resultados en casos de carcinoma basocelular, enfermedad de Bowen, queratosis actínica, acné, rosácea y fotoenvejecimiento cutáneo. Los fotosensibilizantes y las fuentes de luz que se pueden utilizar son cada vez más variados, pero aún existe poco consenso en su metodología de aplicación, sistemas de irradiación y dosificaciones. En este artículo describimos los materiales y métodos disponibles en la actualidad y discutimos algunos detalles que, en base a nuestra experiencia, permiten mejorar los resultados. Presentamos también 5 casos clínicos ilustrativos de diferentes patologías.Photo Dynamic Therapy (PTD is an increasingly used technique in Dermatology and Dermocosmetics. PDT has a wide range of medical applications for the treatment of extended cutaneous cancer, offering also very good results in the treatment of basal cell carcinoma, Bowen's disease, actinic keratosis, acne, rosacea and in cutaneous rejuvenation. The sensitizers and light sources used for photoactivation are also more and more varied but there is still no consensus regarding methods and energy dosage. This study describes material and methods which are currently available and discusses a few details, that based on our own experience, can improve results. Five illustrative cases of different conditions are presented.

  5. Human-directed social behaviour in dogs shows significant heritability.

    Science.gov (United States)

    Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P

    2015-04-01

    Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  6. A novel nucleic acid analogue shows strong angiogenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Ikuko, E-mail: tukamoto@med.kagawa-u.ac.jp [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Sakakibara, Norikazu; Maruyama, Tokumi [Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193 (Japan); Igarashi, Junsuke; Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Kubota, Yasuo [Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Ashino, Hiromi [The Tokyo Metropolitan Institute of Medical Science, 1-6 Kamikitazawa2-chome, Setagaya-ku, Tokyo 156-8506 (Japan); Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro [Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Higashikagawa, Kagawa 769-2695 (Japan); Konishi, Ryoji [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan)

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  7. Orographic enhancement of snowfall.

    Science.gov (United States)

    Dore, A J; Choularton, T W; Fowler, D; Crossley, A

    1992-01-01

    Field studies have been conducted at a hill site in Scotland to measure the variation with altitude of wet deposition by snowfall. The results showed that, due to wind drift effects, snowflakes were captured very inefficiently by snow collectors. It was therefore not possible to measure an increase in precipitation with altitude. The average concentrations of principal ions dissolved in the snow water were calculated over a two-month period. The results showed that the concentrations increased by factors of between 1.4 and 1.9 with an altitude rise of 400 m. A model of the orographic enhancement of snowfall by the seeder-feeder effect showed that the orographic enhancements of precipitation and pollutant deposition were significantly greater for snowfall than for rainfall. The wind drift of snow crystals and the evaporation of precipitation in dry valley air were important in determining the patterns of deposition.

  8. Human freedom and enhancement.

    Science.gov (United States)

    Heilinger, Jan-Christoph; Crone, Katja

    2014-02-01

    Ideas about freedom and related concepts like autonomy and self-determination play a prominent role in the moral debate about human enhancement interventions. However, there is not a single understanding of freedom available, and arguments referring to freedom are simultaneously used to argue both for and against enhancement interventions. This gives rise to misunderstandings and polemical arguments. The paper attempts to disentangle the different distinguishable concepts, classifies them and shows how they relate to one another in order to allow for a more structured and clearer debate. It concludes in identifying the individual underpinnings and the social conditions of choice and decision-making as particularly salient dimensions of freedom in the ethical debate about human enhancement.

  9. Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

    Science.gov (United States)

    Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

    2009-02-01

    This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

  10. EDITORIAL: Enhancing nanolithography Enhancing nanolithography

    Science.gov (United States)

    Demming, Anna

    2012-01-01

    Lithography was invented in late 18th century Bavaria by an ambitious young playwright named Alois Senefelder. Senefelder experimented with stone, wax, water and ink in the hope of finding a way of reproducing text so that he might financially gain from a wider distribution of his already successful scripts. His discovery not only facilitated the profitability of his plays, but also provided the world with an affordable printing press that would ultimately democratize the dissemination of art, knowledge and literature. Since Senefelder, experiments in lithography have continued with a range of innovations including the use of electron beams and UV that allow increasingly higher-resolution features [1, 2]. Applications for this have now breached the limits of paper printing into the realms of semiconductor and microelectronic mechanical systems technology. In this issue, researchers demonstrate a technique for fabricating periodic features in poly(3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) [3]. Their method combines field enhancements from silica nanospheres with laser-interference lithography to provide a means of patterning a polymer that has the potential to open the market of low-end, high-volume microelectronics. Laser-interference lithography has already been used successfully in patterning. Researchers in Korea used laser-interference lithography to generate stamps for imprinting a two-dimensional photonic crystal structure into green light emitting diodes (LEDs) [4]. The imprinted patterns comprised depressions 100 nm deep and 180 nm wide with a periodicity of 295 nm. In comparison with unpatterned LEDs, the intensity of photoluminescence was enhanced by a factor of seven in the LEDs that had the photonic crystal structures imprinted in them. The potential of exploiting field enhancements around nanostructures for new technologies has also attracted a great deal of attention. Researchers in the USA and Australia have used the field

  11. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    Directory of Open Access Journals (Sweden)

    Bouwense SA

    2015-07-01

    Full Text Available Stefan AW Bouwense,1 Søren S Olesen,2 Asbjørn M Drewes,2 Harry van Goor,1 Oliver HG Wilder-Smith31Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands; 2Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 3Pain and Nociception Neuroscience Research Group, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud university medical center, Nijmegen, The NetherlandsBackground: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders to placebo or pregabalin treatment. Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15 or placebo (n=12; n=17 treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT in dermatomes C5 (generalized effects and Ventral T10 (segmental effects. Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM paradigm. Results: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA vs placebo responders (−0.1 mA; P=0.015. This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9% vs placebo responders (−17%; P<0.001. CPM changed significantly vs baseline only for pregabalin responders (P=0.006. Conclusion: This hypothesis

  12. MR findings of nasal cavity lesions showing the infundibular widening on

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Eun Kyung; Lee, Young Uk; Lee, Young Rae [Kangbuk Samsung Hospital, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-03-01

    Several kinds of nasal cavity lesions located in the region of the infundibulum on CT. At such time, the visualization of these lesions is very similar. The purpose of this study was to differentially diagnose these nasal cavity lesions through evaluation of the MR findings. In 51 cases of pathologically proven nasal cavity masses which on CT showed infundibular widening, we retrospectively evaluated the MR findings. The cases involved prolapsed antral mucosa from sinusitis(n=15), inverted papilloma(n=10), antrochoanal polyp(n=10), aspergillosis(n=9), and nasal polyp(n=7). All patients underwent both CT and MR. imaging. In all cases, CT findings were similar ; soft tissue masses filling the maxillary sinus and nasal cavity were associated with infundibular widening caused by pressure on the uncinate process, leading to erosion. Differential diagnosis by CT was very difficult ; MR T2 weighted imaging was most effective for differential diagnosis of these nasal cavity masses. Prolapsed antral mucosa showed central inhomogeneous mixed signal intensity, with a peripheral rim of hyperintensity along the sinus wall and nasal component. Antrochoanal polyps showed homogeneous bright signal intensity of the antral and nasal component. Aspergillosis showed central dark signal foci. Inverted papillomas showed mixed intermediate and high intensity mixed with high signal intensity. Nasal polyps showed striation mixed of intermediate and high signal intensity, while nasal polyp showed striation of intermediate and high intensity. On Gd-enhanced T1 weighted images, prolapsed antral mucosa and antrochoanal polyp showed peripheral rim enhancement of the antral and nasal component. In contrast, inverted papilloma and nasal polyp showed intense enhancement of the mass and can be separate from the sinus inflammatory disease. Various nasal cavity masses showing infundibular widening on CT can be differentiated on MR images, especially of these are T2 weighted or contrast enhanced T1

  13. Enhanced Visible-Light Photocatalytic Performance of Nanosized Anatase TiO2 Doped with CdS Quantum Dots for Cancer-Cell Treatment

    Directory of Open Access Journals (Sweden)

    Kangqiang Huang

    2012-01-01

    Full Text Available CdS quantum-dots-(QDs-doped TiO2 nanocomposites were successfully synthesized using the sol-gel technique and characterized by SEM, TEM, XRD, EDS, UV-Vis, and FS. They were then used as a new “photosensitizer” based on photodynamic therapy (PDT for cancer-cell treatment. The photocatalytic activities of CdS-TiO2 on leukemia tumors were investigated by using Cell Counting Kit-8 (CCK-8 assay. The ultrastructural morphology of treated cells was also studied by AFM. The experimental results indicated that an obvious inhibition of tumor growth would be observed in groups treated with CdS-TiO2 nanocomposites, and the PDT efficiency in the presence of CdS-doped TiO2 was significantly higher than that of TiO2, revealing that the photocatalytic activities of TiO2 could be effectively enhanced by the modification of CdS QDs. Additionally, CdS- TiO2 can exhibit a very high photodynamic efficiency of 80.5% at a final concentration of 200 μg/mL under visible-light irradiation. CdS-TiO2 nanocomposites in this case were regarded as a promising application for cancer-cell treatment.

  14. Altruistic people show no self-reference effect in memory.

    Science.gov (United States)

    Nakao, Takashi; Tokunaga, Satoko; Takamura, Masahiro; Nashiwa, Hitomi; Hayashi, Shunsuke; Miyatani, Makoto

    2012-01-01

    The self-reference effect (SRE), by which encoding of information is done in a self-referential manner (e.g., "Does the word describe you?"), enhances subsequent memory performance. It is thought to reflect that self-reference is a highly practiced task in everyday life. Accordingly, it is expected that the types of tasks that produce memory enhancement vary according to individual differences of past experiences. On the basis of neuroimaging studies, we hypothesized that social desirability reference ("Is this word socially desirable?") produces memory enhancement as with SRE in people who have chosen altruistic behavior frequently. Participants processed trait adjectives in relation to themselves, social desirability, and meaning. Then they performed a free recall task. The self-report altruism scale was used to assess the frequency of past altruistic behavior. Consistent with our prediction, the social desirability reference yielded the best retention in the high-altruism group. SRE was observed only in the low-altruism group.

  15. Propulsive Descent Technologies (PDT): Original Content Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Future missions to Mars require landed mass that exceeds the capability of current entry, descent, and landing technology.  New technology and techniques are...

  16. Speech Enhancement

    DEFF Research Database (Denmark)

    Benesty, Jacob; Jensen, Jesper Rindom; Christensen, Mads Græsbøll

    and their performance bounded and assessed in terms of noise reduction and speech distortion. The book shows how various filter designs can be obtained in this framework, including the maximum SNR, Wiener, LCMV, and MVDR filters, and how these can be applied in various contexts, like in single-channel and multichannel...

  17. Placebo can enhance creativity.

    Science.gov (United States)

    Rozenkrantz, Liron; Mayo, Avraham E; Ilan, Tomer; Hart, Yuval; Noy, Lior; Alon, Uri

    2017-01-01

    The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition. Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency. The placebo group showed higher originality than the control group both in the CFG (pcreativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity.

  18. Gd-enhanced MR imaging of the herniated lumbar disc: patterns of enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Kwag, Hyon Joo; Choi, Hye Young; Kim, Hyae Young; Kim, Yoo Kyung; Kim, Ah Young; Chung, Eun Chul [College of Medicine, Ewah Womans University, Seoul (Korea, Republic of)

    1995-07-15

    The purpose of this study is to describe the patterns of enhancement of the herniated lumbar disc with Gd-DTPA enhanced MR imaging. Out of 65 patients, 103 lumbar discs diagnosed to be herniated by MR image were retrospectively analyzed. The MR imaging was performed with 1.5 T MR unit, using T1-and T2-weighted sagittal and axial spin echo techniques. Contrast-enhanced T1 weighted sagittal and axial images were performed after intravenous injection of Gadopentetate-dimeglumine(Magnevist, Shering) (0.1 mmol/kg). Contrast enhancement was seen in 66 cases(64%). Thirteen cases of bulging disc were not enhanced. Twenty-eight cases of protruded disc showed intraannular enchantment in 23 cases, peripheral linear and irregular enhancement in each of one case, and nonenhancement in three cases. Fifty-seven cases of extruded disc showed irregular enhancement in 14 cases, peripheral linear enhancement in 12 cases, peripheral ring enhancement in five cases and intraannular enhancement in five cases. All five cases of sequestered disc showed peripheral ring enhancement. Protruded discs show intraannular enhancement frequently and sequestered discs usually show peripheral ring enhancement. Enhanced MR imaging may be helpful to evaluate the type of herniated lumbar disc and relationship among disc material, nerve root and thecal sac.

  19. Enhancing solidarity

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2012-01-01

    on solidarity are framed with reference to their respective national policies and debates. Therefore, different approaches exist between the two countries, albeit that all the NGOs aim to show new dimensions of integration in order to promote empathy towards immigrants. The goal of the NGOs is to contribute...... be able to solve contradictions related to the scope of human rights, politics of asylum and inclusion of irregular immigrants is still missing....

  20. If You Show Up, They'll Surprise You

    Science.gov (United States)

    Snow, Carrie C.

    2017-01-01

    One essential way to support students with autism is to "show up" for them. Showing up means connecting and building relationships with learners and trusting students to show us what they most need to boost their learning and social growth. Snow shares scenarios from her years as a special educator that showcase ways educators can…

  1. Proton magnetic resonance spectroscopy shows lower intramyocellular lipid accumulation in middle-aged subjects predisposed to familial longevity

    NARCIS (Netherlands)

    Wijsman, C. A.; van Opstal, A. M.; Kan, H. E.; Maier, A. B.; Westendorp, R. G.J.; Slagboom, P. E.; Webb, A. G.; Mooijaart, S. P.; van Heemst, D.

    Families predisposed to longevity show enhanced glucose tolerance and skeletal muscle insulin sensitivity compared with controls, independent of body composition and physical activity. Intramyocellular lipid (IMCL) accumulation in skeletal muscle has been associated with insulin resistance. Here, we

  2. Effects of TV Crime Shows on Behavioural Development of Children

    OpenAIRE

    Abdullah Mudassar; Abd Rahman Nik Adzrieman B.

    2017-01-01

    Television crime dramas and shows are very popular all over the world. This popularity is not bound to a certain age group, rather all the TV viewers like these shows very much. Like other countries, dozens of TV channels are telecasting these crime shows in Pakistan. Furthermore, few of the channels telecast crime shows at prime time which attests the popularity of such genre. Some of the media contents behave in morally disputed ways. The crime depictions as re-enactments of TV crime shows ...

  3. Bose enhancement and the ridge

    Energy Technology Data Exchange (ETDEWEB)

    Altinoluk, Tolga [Departamento de Física de Partículas and IGFAE, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Galicia (Spain); Armesto, Néstor, E-mail: nestor.armesto@usc.es [Departamento de Física de Partículas and IGFAE, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Galicia (Spain); Beuf, Guillaume [Department of Physics, Ben-Gurion University of the Negev, Beer Sheva 84105 (Israel); Kovner, Alex [Physics Department, University of Connecticut, 2152 Hillside Road, Storrs, CT 06269-3046 (United States); Lublinsky, Michael [Department of Physics, Ben-Gurion University of the Negev, Beer Sheva 84105 (Israel)

    2015-12-17

    We point out that Bose enhancement in a hadronic wave function generically leads to correlations between produced particles. We show explicitly, by calculating the projectile density matrix in the Color Glass Condensate approach to high-energy hadronic collisions, that the Bose enhancement of gluons in the projectile leads to azimuthal collimation of long range rapidity correlations of the produced particles, the so-called ridge correlations.

  4. Bose enhancement and the ridge

    Directory of Open Access Journals (Sweden)

    Tolga Altinoluk

    2015-12-01

    Full Text Available We point out that Bose enhancement in a hadronic wave function generically leads to correlations between produced particles. We show explicitly, by calculating the projectile density matrix in the Color Glass Condensate approach to high-energy hadronic collisions, that the Bose enhancement of gluons in the projectile leads to azimuthal collimation of long range rapidity correlations of the produced particles, the so-called ridge correlations.

  5. Ultrasonic activation and chemical modification of photosensitizers enhances the effects of photodynamic therapy against Enterococcus faecalis root-canal isolates.

    Science.gov (United States)

    Tennert, C; Drews, A M; Walther, V; Altenburger, M J; Karygianni, L; Wrbas, K T; Hellwig, E; Al-Ahmad, A

    2015-06-01

    The aim of this study was to evaluate the effect of photodynamic therapy (PDT) on Enterococcus faecalis biofilms in artificially infected root canals using modified photosensitizers and passive ultrasonic activation. Two hundred and seventy extracted human teeth with one root canal were instrumented utilizing ProTaper files, autoclaved, infected with E. faecalis T9 for 72 h and divided into different groups: irrigation with 3% sodium hypochlorite (NaOCl), 20% ethylenediaminetetraacetic acid (EDTA), or 20% citric acid, PDT without irrigation, PDT accompanied by irrigation with NaOCl, EDTA, or citric acid, PDT using an EDTA-based photosensitizer or a citric-acid-based photosensitizer and PDT with ultrasonic activation of the photosensitizer. A 15 mg/ml toluidine blue served as the photosensitizer, activated by a 100 mW LED light source. Sterile paper points were used for sampling the root canals and dentin chips were collected to assess the remaining contamination after treatment. Samples were cultured on blood agar plates and colony forming units were quantified. PDT alone achieved a reduction in E. faecalis counts by 92.7%, NaOCl irrigation alone and combined with PDT by 99.9%. The antibacterial effects increased by the combination of irrigation using EDTA or citric acid and PDT compared to irrigation alone. More than 99% of E. faecalis were killed using PDT with the modified photosensitizers and ultrasonic activation. NaOCl based disinfection achieved the highest antimicrobial effect. Using PDT with an EDTA-based or citric-acid-based phozosensitizer or activating the photosensitizer with ultrasound resulted in a significantly higher reduction in E. faecalis counts compared to conventional PDT. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Uudised : Otsman taas Riias show'l. Rokkstaarist ministriks

    Index Scriptorium Estoniae

    2007-01-01

    Drag-kabareeartist Erkki Otsman esineb detsembris Riias "Sapnu Fabrikas" toimuval jõulu-show'l. Austraalia rokkansambli Midnight Oil endine laulja Peter Garrett nimetati valitsuse keskkonnaministriks

  7. 47 CFR 73.24 - Broadcast facilities; showing required.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Broadcast facilities; showing required. 73.24 Section 73.24 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES AM Broadcast Stations § 73.24 Broadcast facilities; showing required. An...

  8. "The Daily Show with Jon Stewart": Part 1

    Science.gov (United States)

    Trier, James

    2008-01-01

    Comedy Central's popular program "The Daily Show With Jon Stewart" is the best critical media literacy program on television, and it can be used in valuable ways in the classroom as part of a media literacy pedagogy. This Media Literacy column provides an overview of the show and its accompanying website and considers ways it might be used in the…

  9. Effects of TV Crime Shows on Behavioural Development of Children

    Directory of Open Access Journals (Sweden)

    Abdullah Mudassar

    2017-01-01

    Full Text Available Television crime dramas and shows are very popular all over the world. This popularity is not bound to a certain age group, rather all the TV viewers like these shows very much. Like other countries, dozens of TV channels are telecasting these crime shows in Pakistan. Furthermore, few of the channels telecast crime shows at prime time which attests the popularity of such genre. Some of the media contents behave in morally disputed ways. The crime depictions as re-enactments of TV crime shows are questionable in the field of research signifying diverse cultural contexts. A large number of people are habitual to watch these shows, which may probably come out with negative behavioural outcomes. Especially the children who are at their behavioural developmental phase; are more susceptible to adopt negative behavioural leanings. In this research effort, introduction and detail of TV crime shows in Pakistan are provided, the literature concerning “media as risk factor“ in children development is discussed, and relevant theories inferences are deliberated.it was found that media has powerful role in behaviour formulating of children and violence media portrayal (TV crime shows may appear with grave concerns. Previous scientific literature was reviewed to find and discuss the problem in hand. In the research effort, the literature review provides research propositions to explore further dimensions to TV crime shows’ effects and possible negative or positive behavioural outcomes in children behaviour.

  10. TV shows on Light Pollution Education for the Public

    Science.gov (United States)

    Grigore, Valentin

    2015-03-01

    TV shows have the biggest impact for the public, so we can use them to inform and educate the public about light pollution and the importance of the dark sky for humanity and for the contemporary society. Some examples used in the TV show Us and the Sky at Columna TV, Romania, are presented.

  11. Pedagogical Techniques Employed by the Television Show "MythBusters"

    Science.gov (United States)

    Zavrel, Erik

    2016-01-01

    "MythBusters," the long-running though recently discontinued Discovery Channel science entertainment television program, has proven itself to be far more than just a highly rated show. While its focus is on entertainment, the show employs an array of pedagogical techniques to communicate scientific concepts to its audience. These…

  12. 36 CFR 14.24 - Showing as to citizenship required.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Showing as to citizenship... INTERIOR RIGHTS-OF-WAY Procedures § 14.24 Showing as to citizenship required. (a) Individuals. An... citizenship is claimed by virtue of naturalization of the father, evidence of his naturalization, and that the...

  13. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants.

    Science.gov (United States)

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-02-21

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DNA transfer. In this study, we examined the effect of GABA on T-DNA transfer using a tomato line with a low GABA content. Compared with the control, the T-DNA transfer frequency was increased in the low-GABA tomato line, indicating that GABA inhibits T-DNA transfer. Therefore, we bred a new A. tumefaciens strain with GABA transaminase activity and the ability to degrade GABA. The A. tumefaciens strain exhibited increased T-DNA transfer in two tomato cultivars and Erianthus arundinacues and an increased frequency of stable transformation in tomato.

  14. Some Attenuated Variants of Vesicular Stomatitis Virus Show Enhanced Oncolytic Activity against Human Glioblastoma Cells relative to Normal Brain Cells▿

    OpenAIRE

    Wollmann, Guido; Rogulin, Vitaliy; Simon, Ian; Rose, John K.; van den Pol, Anthony N.

    2009-01-01

    Vesicular stomatitis virus (VSV) has been shown in laboratory studies to be effective against a variety of tumors, including malignant brain tumors. However, attenuation of VSV may be necessary to balance the potential toxicity toward normal cells, particularly when targeting brain tumors. Here we compared 10 recombinant VSV variants resulting from different attenuation strategies. Attenuations included gene shifting (VSV-p1-GFP/RFP), M protein mutation (VSV-M51), G protein cytoplasmic tail t...

  15. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    Directory of Open Access Journals (Sweden)

    Hutzen Brian

    2012-11-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for the treatment of medulloblastoma.

  16. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants

    Science.gov (United States)

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-01-01

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DNA transfer. In this study, we examined the effect of GABA on T-DNA transfer using a tomato line with a low GABA content. Compared with the control, the T-DNA transfer frequency was increased in the low-GABA tomato line, indicating that GABA inhibits T-DNA transfer. Therefore, we bred a new A. tumefaciens strain with GABA transaminase activity and the ability to degrade GABA. The A. tumefaciens strain exhibited increased T-DNA transfer in two tomato cultivars and Erianthus arundinacues and an increased frequency of stable transformation in tomato. PMID:28220841

  17. Surface Plasmon Resonance sensor showing enhanced sensitivity for CO2 detection in the mid-infrared range.

    Science.gov (United States)

    Herminjard, Sylvain; Sirigu, Lorenzo; Herzig, Hans Peter; Studemann, Eric; Crottini, Andrea; Pellaux, Jean-Paul; Gresch, Tobias; Fischer, Milan; Faist, Jérôme

    2009-01-05

    We present the first optical sensor based on Surface Plasmon Resonance (SPR) operating in the mid-infrared range. The experimental setup is based on a Kretschmann geometry with Ti/Au layers deposited on a CaF(2) prism where light excitation is provided by a Quantum Cascade Laser (QCL) source. Evidence of SPR is presented and the sensing capability of the system is demonstrated by using CO(2) and N(2) mixtures as test samples. Due to the absorption of CO(2) at this wavelength, it is shown that the sensitivity of this configuration is five times higher than a similar SPR sensor operating in the visible range of the spectrum.

  18. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants

    OpenAIRE

    Satoko Nonaka; Tatsuhiko Someya; Sha Zhou; Mariko Takayama; Kouji Nakamura; Hiroshi Ezura

    2017-01-01

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DN...

  19. Mixed species biofilms of Listeria monocytogenes and Lactobacillus plantarum show enhanced resistance to benzalkonium chloride and peracetic acid

    NARCIS (Netherlands)

    Veen, van der S.; Abee, T.

    2011-01-01

    We investigated the formation of single and mixed species biofilms of Listeria monocytogenes strains EGD-e and LR-991, with Lactobacillus plantarum WCFS1 as secondary species, and their resistance to the disinfectants benzalkonium chloride and peracetic acid. Modulation of growth, biofilm formation,

  20. Topically Delivered Adipose Derived Stem Cells Show an Activated-Fibroblast Phenotype and Enhance Granulation Tissue Formation in Skin Wounds

    Science.gov (United States)

    2013-01-31

    Illinois, United States of America, 2 Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, Fort Sam Houston...were used as primary antibodies. Alexa Fluor 488 or 555 conjugated secondary antibodies were used to detect the primary antibody (Invitrogen). Nuclei

  1. Transgenic plants expressing ω-ACTX-Hv1a and snowdrop lectin (GNA) fusion protein show enhanced resistance to aphids.

    Science.gov (United States)

    Nakasu, Erich Y T; Edwards, Martin G; Fitches, Elaine; Gatehouse, John A; Gatehouse, Angharad M R

    2014-01-01

    Recombinant fusion proteins containing arthropod toxins have been developed as a new class of biopesticides. The recombinant fusion protein Hv1a/GNA, containing the spider venom toxin ω-ACTX-Hv1a linked to snowdrop lectin (GNA) was shown to reduce survival of the peach-potato aphid Myzus persicae when delivered in artificial diet, with survival plants contained intact fusion protein in leaf tissues at an estimated level of 25.6 ± 4.1 ng/mg FW. Transgenic Arabidopsis expressing Hv1a/GNA induced up to 40% mortality of M. persicae after 7 days exposure in detached leaf bioassays, demonstrating that transgenic plants can deliver fusion proteins to aphids. Grain aphids (Sitobion avenae) were more susceptible than M. persicae to the Hv1a/GNA fusion protein i