Dissertations / Theses: 'Photodynamic treatment'

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Hopper, Colin. "Photodynamic therapy for the treatment of oral cancer." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444444/.

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Photodynamic therapy (PDT) describes an interaction of a drug, light and oxygen that results in cell killing. The aim of this thesis is to describe the potential clinical applications of the three most commonly used drugs in PDT - aminolaevulinic acid (ALA), Photofrin and Foscan . Before it was considered safe to use this therapy on patients, a series of preclinical studies were undertaken to establish the safety of the treatment and to try to understand the likely clinical effects on normal tissues. Following this, a series of studies was undertaken to look at the biological effect of PDT on normal and neoplastic tissue. These studies showed the treatment to be safe and effective in destroying tissue while allowing healing with preservation of sufficient tissue structure to maintain tissue contour and function. Next, clinical studies were undertaken on dysplasia, early oral cancer and field change disease using the 3 sensitisers. ALA was found to be useful in the treatment of dysplasia, but has a very superficial effect so is not indicated for treatment of invasive disease. Photofrin and Foscan have a much deeper effect and can be used to treat early cancer and superficial field change disease. Both drugs have problems of prolonged sensitivity to light varying from 2 weeks (Foscan ) to 3 months (Photofrin ). Treatment times also vary from 200s (Foscan ) to 1000s (Photofrin ). The depth of effect limits the use of surface illumination to a maximum of 1cm, however, the use of interstitial therapy, where the light is delivered directly into a neoplastic tissue target allows more advanced cancers to be treated. Currently, Foscan is the only drug licensed for head and neck cancer and then only in the advanced or palliative setting where all other options have been exhausted or are not appropriate. While there is no single drug or technique for the treatment of all stages of oral cancer, PDT is now beginning to be used alongside surgery, radiotherapy and chemotherapy.

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Alsaif, Aysha S. Y. A. S. "Treatment of dental plaque biofilms using photodynamic therapy." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/18523/.

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BACKGROUND: Photodynamic therapy (PDT) is a treatment modality involving a dye that is activated by exposure to light of a specific wavelength in the presence of oxygen to form oxygen species causing localised damage to microorganisms. AIM: To determine the most effective bactericidal incubation and irradiation times of erythrosine-based PDT, using a tungsten filament lamp, on in vivo- formed dental plaque biofilms. MATERIALS AND METHODS: The study was a two-phase randomised controlled study consisting of in-vitro and in-situ phases. Phase-1 aimed to determine the most appropriate incubation-time using erythrosine(220μM) based-PDT on lactobacillus species grown in-vitro. Phase-2 was conducted on 18-healthy adult participants wearing intraoral appliances with human enamel slabs to collect dental plaque samples in two separate periods for use in arm-1 and arm-2. For phase-2, accumulated dental plaque samples were tested under different experimental conditions; a) Control-1 (No erythrosine, no light); b) Control-2 (+Erythrosine, no light); c) Treatment-1 (+Erythrosine, +15min continuous light); d) Treatment-2 (+Erythrosine, +30sec light pulses for 5- times separated by 1min dark periods). Incubation-times of 15min and 2min were used in arm-1 and arm-2, respectively; as adapted from the previous pilot study and phase-1. Following treatment, percentage reduction of total bacterial counts were compared between the different groups. Additionally, Confocal Laser Scanning Microscopy(CLSM) was used to investigate the effect of PDT on in vivo-formed plaque biofilms. RESULTS: Significant reductions in the percentage of total bacterial counts (~93-95%) of in vivo-formed biofilms were found when using either 2min or 15min incubation-times and applying 15min continuous light. Whereas, when applying fractionated light, there was more cell death when 15min incubation-time was used (~91%) compared with the 2min incubation-time (~64%). CLSM results supported these findings. CONCLUSION: Improving the clinical usefulness of PDT by reducing its overall treatment time seems to be promising and effective in killing in vivo- formed dental plaque biofilms.

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Dronyk, I. I. "Photodynamic therapy in complex treatment of generalized periodontitis." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19118.

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Stritt, Andrea Christina. "Photodynamic therapy in the treatment of actinic keratosis /." Bern : [s.n.], 2008. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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Millson, Charles Edward. "Photodynamic therapy for the treatment of helicobacter pylori infection." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281686.

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Pereira, José Carlos Ribeiro Ferreira. "Cytoskeleton regulation in bladder cancer cells after photodynamic treatment." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/21089.

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Mestrado em Biologia Molecular e Celular
A terapia fotodinâmica (PDT) é uma modalidade promissora para o tratamento do cancro. Esta terapia baseia-se na interação entre um composto químico (fotossensibilizador, PS), luz com um determinado comprimento de onda e oxigénio molecular para originar a produção de espécies reativas de oxigénio (ROS). Devido à sua elevada reatividade, estas espécies tóxicas podem causar danos severos conduzindo à morte celular. Atualmente, os PS disponíveis na clínica para o tratamento de tumores apresentam baixa seletividade para as células tumorais. Estudos anteriores do nosso grupo descreveram uma porfirina conjugada com unidades dendríticas de galactose (PorGal8) como um novo PS solúvel em solução aquosa, capaz de gerar ROS após fotoativação e com reconhecimento por parte de proteínas (galectina-1) que se encontram sobreexpressas nas células do cancro da bexiga. Vários estudos têm descrito alterações no citoesqueleto em resposta ao tratamento fotodinâmico. No entanto, a contribuição da desorganização do citoesqueleto na morte celular induzida por PDT encontra-se pouco esclarecida. Neste trabalho, avaliámos de que forma alterações nos constituintes do citoesqueleto – filamentos de actina, filamentos intermédios e microtúbulos – estão relacionadas com morte celular induzida por PDT com PorGal8. O uptake de PorGal8 em duas linhas celulares do cancro da bexiga derivadas de carcinoma de células transicionais (UM-UC-3 e HT-1376), foi dependente da concentração. O uptake celular de PorGal8 foi superior nas células UM-UC-3, que exibem níveis superiores da proteína galectina-1, comparativamente com as células HT-1376. PorGal8 mostrou não ser tóxico no escuro. A fotoativação da PorGal8 resultou numa fototoxicidade significativamente superior nas células UM-UC-3 relativamente às células HT-1376. A PorGal8 não induziu alterações significativas nos níveis de proteína α-tubulina nas células UM-UC-3. No entanto, observou-se uma redução significativa nos níveis de α-tubulina nas células HT-1376 vinte e quatro horas após tratamento com irradiação. Apesar de se ter observado uma recuperação na organização dos microtúbulos em algumas células, a intensidade da fluorescência diminuiu consideravelmente na maior parte das células HT-1376. Uma redução significativa nos níveis de proteína dos filamentos intermédios (vimentina) foi observada em ambas as linhas celulares vinte e quatro horas após irradiação. Trinta minutos após a irradiação, as células UM-UC-3 e HT-1376 apresentaram uma clara retração nos filamentos de actina com perda de fibras de stress. Ao contrário das células UM-UC-3 em que não se verificaram sinais de recuperação, em algumas células HT-1376 verificou-se uma certa reorganização dos filamentos de actina, com curtas fibras de stress, longas extensões, grandes filopodia, o que parece sugerir uma possível recuperação das células HT-1376. A RhoA, uma proteína da família de pequenas proteínas GTPases, descrita como estando relacionada com a expressão da galectina-1, foi adicionalmente avaliada. Resultados preliminares indicaram que a PorGal8 induziu uma tendência para aumentar os níveis de RhoA nas células HT-1376 vinte e quatro horas após tratamento com irradiação. Concluindo, os nossos resultados contribuem para o esclarecimento dos mecanismos subjacentes dos efeitos fototóxicos da PorGal8. Uma melhor compreensão dos intervenientes e das alterações induzidas imediatamente após PDT nas estruturas do citoesqueleto em cancros resistentes à terapia, poderão contribuir para o desenvolvimento de novos agentes terapêuticos adjuvantes à PDT.
Photodynamic therapy (PDT) is a promising modality for the treatment of cancer that involves light of an appropriate wavelength and a photosensitizing drug (photosensitizer, PS), used in conjunction with molecular oxygen, leading to the production of reactive oxygen species (ROS). In a biological environment, these toxic species can interact with the cellular constituents eliciting cell death. Currently, the PS available show poor tumor specificity. Previous work from our research group reported a porphyrin conjugated with dendritic units of galactose (PorGal8) as a new water soluble PS, able to generate ROS after photoactivation and exhibiting increased selectivity to bladder cancer cells overexpressing galectin-1. Several studies reported cytoskeleton alterations derived from photodynamic treatments. However, the role of cytoskeleton disorganization in cell death induced by PDT remains unclear. In this work we evaluated whether changes in the cytoskeletal constituents - actin filaments, intermediate filaments and microtubules - are correlated with cell death triggered by PDT with PorGal8. The uptake of PorGal8 in two bladder cancer lines derived from transitional cell carcinoma (UM-UC-3 and HT-1376 cells), was concentration dependent. Cellular uptake of PorGal8 was higher in UM-UC-3 cells that express higher levels of galectin-1 protein than HT-1376 cells. PorGal8 was nontoxic in dark. Photoactivation of PorGal8 resulted in a significantly higher phototoxicity in UM-UC-3 cells than HT-1376 cells. PorGal8 did not change the α-tubulin protein levels in UM-UC-3 cells but reduced α-tubulin twenty-four hours after photodynamic activation in HT-1376 cells. Although a few cells showed a recovery in microtubules organization, the fluorescence intensity decreased noticeably in most of the HT-1376 cells. A significant decrease in intermediate filaments (vimentin) protein levels was exhibited in both cell lines twenty-hours after irradiation. Thirty minutes post-irradiation, UM-UC-3 and HT-1376 cells showed a clear retraction of actin filaments with loss of stress fibers. Although no recovery was observed in UM-UC-3 cells, some cells present some reorganization in actin filaments, presenting short stress fibers, long extensions, like large filopodia, suggesting a possible recovery in HT-1376 cells. A small GTPases family protein, RhoA, referred to be involved with galectin-1 expression, was also evaluated, with preliminary results indicating a tendency towards an increase in HT-1376 cells twenty-four hours after therapy. Overall, our results give new insights into the mechanisms underlying the phototoxic effects of PorGal8. Better understanding the intrinsic web of events and alterations on cytoskeleton structures induced immediately after photodynamic treatment in resistant cancers may contribute to envisage new potential therapeutic adjuvants for PDT.

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Mitzel, Frieder. "Synthesis of acetylenic phthalocyanine analogues as sensitisers for photodynamic therapy." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249357.

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Rogowska, Agnieska Zofia. "Photodynamic therapy for the treatment of cancer of the pancreas." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394933.

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Thissen, Monique Rosalie Thérèse Mathieu. "Treatment of basal cell carcinoma in the light of photodynamic therapy." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 2000. http://arno.unimaas.nl/show.cgi?fid=5962.

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Fielding, David Ivor Keith. "Effects of interstitial laser photoagulation and photodynamic therapy on lung parenchyma." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264699.

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Macpherson, Alisdair N. "New sensitisers for photodynamic therapy : a photophysical study in model and biological systems." Thesis, Keele University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305882.

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Connell, Rowan James. "Photodynamic therapy to the endometrium as a primary treatment modality for menorrhagia." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445480/.

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Menorrhagia is a condition which affects a considerable number of women. The traditional treatment is hysterectomy, which has significant morbidity associated with it. Over recent years more minimally invasive techniques have been developed to treat menorrhagia without resorting to hysterectomy. Photodynamic therapy (PDT) is a non-thermal technique which can be used to cause tissue damage. It requires the activation of a photosensitiser with light, which in the presence of oxygen produces cytotoxic oxygen species. 5-aminolaevulinic acid (ALA) is a photosensitising agent which has been used as a pre-cursor for the photoactive protoporphyrin IX (PPIX) in the past to successfully destroy the endometrium in the rat and rabbit model. When the technique has been used in humans, the effect has been unsatisfactory and has not been reproducible. This thesis demonstrates that by the addition of an iron chelator CP94 there is a significantly increased level of PPIX in the endometrium, as measured with fluorescence microscopy after both chemicals are instilled into the uterine cavity of the rabbit. We show that pH has little effect on these data. The optimum time for PDT was shown to be seven hours after instillation. We show a dramatically increased PDT effect when using a combination of ALA and CP94 in the rabbit endometrium. In addition this PDT effect remains at 28 days. These studies showed that it may be possible to improve on the previously reported disappointing clinical results using ALA-PDT by the addition of the iron chelating agent, CP94. We performed preclinical trials of light distribution within the human uterine cavity using different light delivery systems. This showed that an effective light dose could be applied to the irregular shaped endometrial cavity, in order to maximise the PDT effect in humans. The technique is now ready to take into pilot clinical studies.

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Walther, Jan, Stanislas Schastak, Sladjana Dukic-Stefanovic, Peter Wiedemann, Jochen Neuhaus, and Thomas Claudepierre. "Efficient photodynamic therapy on human retinoblastoma cell lines." Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-148182.

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Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma.

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Fok, Wanyiu. "Theranostic porphyrin-cyclen gadolinium complex for photodynamic therapy and magnetic resonance imaging." HKBU Institutional Repository, 2019. https://repository.hkbu.edu.hk/etd_oa/706.

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Photodynamic therapy (PDT) and Magnetic resonance imaging (MRI) are two techniques used in therapeutic and diagnostic purpose respectively. PDT can selectively kill the cancer cells by utilizing light and photosensitizer, while MRI provides invasive imaging on our interior bodies. If these two techniques combine, the probe can act as both PDT and MRI agent at the same time. This theranostic agents can bring great efficiency in the cancer treatment. In this project, a porphyrin-cyclen gadolinium based dual functions bio-probe, PZnGdL, is designed for diagnostic and photodynamic therapeutic functions. PZnGdL demonstrated a great T1 signal enhancement for MRI, in which its T1 relaxivity is 15.06 mM-1s-1 (at 1.4T, 37oC). The T1 relaxivity is five-fold higher than the clinically approved MRI contrasting agent Gd-DOTA, (2.92 at 1.4T, 37oC). Furthermore, PZnGdL exhibits low dark toxicity and high photocytotoxicity. Therefore, its photodynamic therapeutic index (PDI) in HeLa cells is as high as 1348 upon 1 J/cm2 light irradiation. Results from the present study show that PZnGdL is an effective photodynamic therapy agent as well as a safe and promising MRI contrasting agent.

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Wang, Yuzhi. "Development of red light-activated porphycene-based photosensitizers for hypoxic anti-tumor photodynamic therapy." HKBU Institutional Repository, 2017. https://repository.hkbu.edu.hk/etd_oa/420.

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This work focuses on the development of red light-activated porphycene-based photosensitizers for anti-tumor photodynamic therapy (PDT) under both normoxic and hypoxic conditions. A total of seven water-soluble porphycenes have been designed, synthesized and evaluated as potential PDT agents in terms of their photophysical and photobiological properties using principally the human nasopharyngeal carcinoma (HK-1) cells. Among the porphycenes synthesized, two were neutral amphiphilic aryl porphycenes, TDEGPPo and Zn(II) TDEGPPo, with relatively weak photo-cytotoxic activities even under normoxic condition. Two cationic porphycenes, TPyBPo and TriPyPPo, exhibited strong photo-cytotoxic activities, with LD50 of 0.3 mM at a light dose of 3 J/cm2, under normoxic condition. However, much lower photo-cytotoxicity was observed under hypoxic condition for TPyBPo and TriPyPPo, with LD50 of 3 mM and 3.5 mM, respectively, obtained at high light doses (>10 J/cm2). Two alkyl porphycenes with one and two sulfonoamide diglycol functionalities, TBPoS-OH and TBPoS-2OH, were synthesized and shown to exhibit very potent photo-cytotoxic activities, with respective LD50 of 53 nM and 20 nM (light dose 8 J/cm2) under normoxic conditions. Most importantly, comparably potent photo-cytotoxicity was also observed for these porphycenes under hypoxic conditions, with respective LD50 of 65 nM and 50 nM (light dose 8 J/cm2). In addition, these porphycenes were taken up by the HK-1 cells very rapidly, with >90% accumulated inside the cells after only 1 h of incubation. Confocal microscopy revealed that these porphycenes were localized at the lysosomes, mitochondria as well as endoplasmic reticulum. Furthermore, the predominant mode of cell death caused by the PDT action of these porphycenes was shown to be apoptosis. In an attempt to effect mitochondria localization to enhance apoptotic cell death for these porphycenes, TBPoS-OH was conjugated with rhodamine B to produce the TBPoS-Rh B conjugate. This porphycene-Rh B conjugate also displayed very potent photo-cytotoxicity under both normoxic and hypoxic conditions, with LD50 of 52 nM and 85 nM, respectively, at a light dose of 8 J/cm2. However, confocal microscopy revealed its principal subcellular localization was at the lysosomes, not the mitochondria. The PDT activities of these porphycenes were compared to a well-known patented PDT agent, EtNBS, which is active under both normoxic and hypoxic conditions, with LD50 of 58 nM and large than 1000 nM, respectively, towards the HK-1 cells. This comparison clearly shows that our sulfonoamido-porphycenes, TBPoS-OH, TBPoS-2OH and TBPoS-Rh B conjugate, display a 15- to 25-fold stronger hypoxic PDT activity relative to EtNBS, thus making these porphycenes excellent candidates for hypoxic anti-tumor photodynamic therapy.

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Allen, Vincent. "Remote measurement of the effective attenuation coefficient of light in tissue." Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287328.

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Zawislak, A. A. "A study of clinical and pathological response to photodynamic therapy in the treatment of vulval lesions." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446131.

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Zhang, Jingxiang. "Series of porphyrin-ru conjugates as two-photon induced bifunctional therapeutic vectors : synthese, characterization, photophysis, cell imaging and photodynamic therapy." HKBU Institutional Repository, 2012. https://repository.hkbu.edu.hk/etd_ra/1447.

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Nour, El Din Suzanne [Verfasser]. "Azurin (P28) fusion protein mediated photodynamic therapy in the treatment of malignant tumors / Suzanne Nour El Din." Ulm : Universität Ulm, 2017. http://d-nb.info/1140118137/34.

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Issawi, Mohammad. "Plant photodynamic stress : study of molecular and cellular mechanisms in plant and plant cells upon porphyrin treatment." Thesis, Limoges, 2018. http://www.theses.fr/2018LIMO0081/document.

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Le traitement photodynamique antimicrobien (acronyme anglais APDT) est apparu comme une solution alternative pour lutter contre les microorganismes multi-résistants. Cette méthode basée sur l'utilisation de photosensibilisateurs dont les porphyrines, fonctionne aussi contre les agents pathogènes des plantes ce qui nous a conduit à proposer une approche de type APDT dans le domaine de l’agriculture. Au cours de ce travail de thèse, nous nous sommes intéressés au côté « vert » de la mise en place de cette approche en réalisant une étude approfondie sur des plantules de deux espèces végétales: Arabidopsis thaliana et Lycopersicum esculentum (tomate) et sur une suspension cellulaire de tabac (TBY-2). Des porphyrines anioniques et cationiques hydrosolubles ont été testées. Nous avons montré qu’aucune de ces porphyrines testées à forte concentration (⩾ 80 μM) n’était cytotoxique à l’obscurité sur les plantules ou la suspension. Par contre sous photopériode (16h), les porphyrines cationiques testées à faible concentration (3,5 μM) se sont révélées létales pour les plantules d’Arabidopsis alors qu’elles n’ont fait que ralentir la croissance des plantules de tomate. Etonnamment, les porphyrines anioniques même testées à forte concentration n’ont pas (ou très peu) induit d’altérations de croissance des plantules. Cette situation se trouve inversée dans les cellules TBY-2 qui sont beaucoup plus sensibles aux porphyrines anioniques photoactivées qui induisent leur mort par apoptose. Ce modèle cellulaire nous a permis de comprendre i) les mécanismes d'interaction porphyrines anioniques avec la paroi cellulaire et ii) quels mécanismes étaient mis en place dans les cellules en réponse au stress photodynamique. En conclusion, ces études préliminaires sur le végétal laissent sérieusement entrevoir la possibilité de développer l’APDT en agriculture ciblée aux pathogènes de plantes et sans effet notable sur les plantes d’intérêt agronomique et les microorganismes du sol
Antimicrobial photodynamic treatment (APDT) has emerged as an alternative modality to strive against multidrug-resistant microorganisms. This method, based on the use of photosensitizers including porphyrins, has also shown substantial efficiency to kill plant pathogens. This led us to propose an APDT approach in the field of agriculture. During this thesis work, we were interested in the "green" side of this approach. Thus, we performed an in-depth study on two plant species: Arabidopsis thaliana and Lycopersicum esculentum (tomato) and on Tobacco Bright Yellow-2 suspension culture (TBY-2 cells) using anionic and cationic water-soluble porphyrins. We have shown that none of these porphyrins tested at high concentration (⩾ 80 μM) was cytotoxic on plantlets or suspension cells under dark conditions. On the other hand, the cationic porphyrins tested at low concentration (3.5 μM) were lethal for Arabidopsis while they only slowed the growth of tomato plantlets under 16 h photoperiod. Surprisingly, the same anionic porphyrins tested at high concentrations did not induce growth alterations of both plantlets. This situation is reversed in TBY-2 cells, which are much more sensitive to photoactivated anionic porphyrins that induce apoptosis-like cell death. TBY-2 cells allowed to understand i) the interactions of anionic porphyrins with the cell wall and ii) the induced cellular and molecular mechanisms in response to photodynamic stress. In conclusion, these preliminary studies on the plants and plant cells suggest the possibility of developing APDT in agriculture. It will be targeted to plant pathogens without any side effects on plants of agronomic interest and soil microorganisms

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Bispo, Mafalda Alves Fernandes. "Galacto-silicon phthalocyanines for bladder cancer treatment." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/19029.

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Mestrado em Bioquímica - Bioquímica Clínica
A terapia fotodinâmica (PhotodynamicTherapy, PDT) é uma metodologia emergente no tratamento de diversas doenças oncológicas e tem por base o uso de oxigénio molecular, luz e um fotossensibilizador (FS) para seletivamente destruir as células tumorais. Em oncologia, a PDT leva à indução de espécies reativas de oxigénio (reactive oxygen species, ROS) no tecido tumoral, no qual ocorreu previamente o uptake preferencial e/ou a retenção de um FS. As ftalocianinas têm-se vindo a revelar FSs promissores na PDT devido às suas propriedades foto-físicas. Contudo, estes compostos para além de pouco solúveis em água, têm problemas de agregação e de especificidade para os tecidos tumorais. Assim, o trabalho apresentado nesta tese teve como objetivo principal conjugar co-axialmente ftalocianinas de silício (silicon phthalocyanines, SiPcs) com duas moléculas de galactose (SiPcGal2) e com duas unidades dendríticas de galactose (SiPcGal4) para que estes FSs fossem reconhecidos por galectinas (e.g. galectina-1) sobrexpressas em células tumorais. Contudo, os compostos desejados finais não foram obtidos, uma vez que a remoção dos grupos isopropilideno, protetores dos grupos hidroxilo das unidades de galactose, não foi conseguida. Assim, foram avaliadas as propriedades foto-físicas e foto-químicas das SiPcs com as galactoses protegidas, comparando com a SiPc dihidróxido (SiPc(OH)2), de forma a estudar a influência da conjugação co-axial de biomoléculas no core destes tipo de FSs. Infelizmente, a solubilidade das SiPcs em solventes aquosos não foi conseguida, contudo o seu espectro de absorção UV-visível evidenciou elevada absorção a altos comprimentos de onda (650-700 nm), janela espectrofotométrica onde ocorre uma penetração mais profunda da luz nos tecidos. Para além disso, estes FSs demonstraram-se excelentes marcadores fluorescentes, estáveis após irradiação e bons geradores de 1O2. Foram ainda realizados estudos in vitro com o objetivo de validar o seu potencial fotodinâmico no tratamento do cancro da bexiga, sendo que a SiPcGal4 e a SiPcGal2 agregaram nas células, tendo assim um baixo uptake, baixa toxicidade após foto-ativação e baixa produção de ROS. No geral, as SiPcs demonstraram um grande potencial como futuros FSs para a PDT, dado as suas excelentes propriedades foto-físicas, o que nos incentiva na descoberta de novas técnicas que diminuam a sua agregação nas células, como a utilização de bio-formulações estáveis e a desproteção das moléculas de galactose, que também irá aumentar a sua especificidade para células tumorais.
Photodynamic Therapy (PDT) relies on the combination of a photosensitizer (PS), light and molecular oxygen (O2) to generate reactive oxygen species (ROS), which can trigger cell death pathways. In oncology, the PS needs to be preferentially accumulated in cancer cells and a good generator of ROS (especially singlet oxygen, 1O2). Phthalocyanines (Pcs) are promising PSs in PDT due to their photochemical and photophysical properties. However, Pcs present solubility and aggregation problems, as well as low selectivity to the cancer tissue. Therefore, it will be conjugated a silicon phthalocyanine (SiPc) with two galactose molecules (SiPcGal2) and another with two galacto-dendritic units (SiPcGal4), both in axial positions. The aim of that conjugation is to promote the binding of the PS with galactose-binding proteins such as galectins (e.g. galectin-1) which are found to be overexpressed in cancer cells. Nevertheless, the desired compound were not obtained, once the hydrolysis of the isopropylidene galactose-protective groups didn’t work. Thereby, the photophysical and photochemical properties of those two SiPcs with the galactose-protective groups were studied in comparison with the SiPc dihydroxide (SiPc(OH)2), in order to study the SiPc core properties as well as the influence of an axial conjugation of biomolecules. The PSs solubility was compromised in an aqueous solution, however their absorption UV-Visible spectra showed high absorption peaks at a high wavelengths range (650–700 nm), which is the ideal therapeutical window where there is a higher penetration of light into the tissues. Furthermore, these SiPcs demonstrated to be good fluorescence labels, photostable and good 1O2 generators. In vitro studies were performed with the aim of validating them as photodynamic therapeutic agents against bladder cancer cells, however SiPcGal4 and SiPcGal2 aggregated on cells, having a low uptake, phototoxicity and ROS production. Overall, SiPcs have demonstrated a great potential as future PSs for PDT, thanks to their excellent photophysical properties, which prompt us in the discovery of different approaches that diminished their aggregation on cells, such as the incorporation of PSs into bio-stable formulations and the deprotection of the galactose molecules, which will also increase their specificity to tumoral cells.

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Song, Xuefei [Verfasser], and Carola [Akademischer Betreuer] Meier. "Impact of Hormone Treatment and Photodynamic Therapy (PDT) on Human Keratoconus Keratocytes in Vitro / Xuefei Song. Betreuer: Carola Meier." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2015. http://d-nb.info/1069104248/34.

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Grebinyk, Anna [Verfasser], Thomas [Gutachter] Dandekar, and Marcus [Gutachter] Frohme. "Synergistic Chemo- and Photodynamic Treatment of Cancer Cells with C_60 Fullerene Nanocomplexes / Anna Grebinyk ; Gutachter: Thomas Dandekar, Marcus Frohme." Würzburg : Universität Würzburg, 2021. http://d-nb.info/1226094066/34.

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Filho, Supercilio Barros. "Endodontic treatment of teeth with periapical lesion in one session with photodynamic therapy as an adjuvant: study "in vivo"." Universidade de Taubaté, 2012. http://www.bdtd.unitau.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=409.

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Hypothesis of the study: It is assumed that the use of photodynamic therapy (PDT) as an adjuvant in root canal therapy can promote the repair of teeth with periapical lesions treated in one session. Objectives: This in vivo study was to evaluate the effects of photodynamic therapy as an adjuvant in root canal therapy in one session for the repair of periapical lesions. Method: Fourteen human teeth with mortification pulp and periapical lesions were randomly divided into two groups (n=7): G1- endodontic treatment was performed in one session and G2 underwent endodontic therapy in one session associated with photodynamic therapy. The photodynamic therapy used methylene blue dye (100μ/mL) for five minutes and diode laser low power (685nm, 100mW) for three minutes. The follow-ups were performed by periapical radiographs. The images were evaluated by the computer program Adobe Photoshop CS 5.1, using the system K values. By which we assessed the area of periapical bone healing. Radiographs were taken prior to execution, immediately after treatment, and six months following the treatment. Results: There were statistically significant differences between the G2- endodontic therapy in one session associated with photodynamic therapy and G1- endodontic therapy in one session (p<0.05) without PDT. Conclusion: The endodontic treatment in one session associated with photodynamic therapy was more effective in repair of the periapical lesion.
Hipótese do estudo: O emprego da terapia fotodinâmica (PDT) como coadjuvante do tratamento endodôntico possa favorecer a reparação de dentes portadores de lesão periapical, tratados em sessão única. Objetivos: Este estudo in vivo, teve por objetivo avaliar, os efeitos da terapia fotodinâmica como coadjuvante do tratamento endodôntico em sessão única, na reparação de lesões periapicais. Método: Quatorze dentes humanos portadores de mortificação pulpar e lesão periapical, foram aleatoriamente divididos em dois grupos (n=7): G1- foi realizado tratamento endodôntico em sessão única, G2- foi submetido à terapia endodôntica em sessão única, associado à terapia fotodinâmica. Para a terapia fotodinâmica utilizou-se como corante o azul de metileno (100μ/mL) por cinco minutos e o laser de diodo de baixa potência (685nm, 100mW) por três minutos. A proservação foi realizada por meio de radiografias periapicais. As imagens foram avaliadas por um programa de computador Adobe Photoshop CS 5.1, valendo-se dos valores médios de K. Pelo qual foi avaliado a área de cicatrização óssea periapical. As radiografias foram tomadas antes da execução do tratamento endodôntico, imediatamente após e proservado com cento e oitenta dias após o tratamento. Resultados: Houve diferença estatísticamente significante entre o grupo G2- terapia endodôntica em sessão única associado à terapia fotodinâmica e G1- terapia endodôntica em sessão única (p< 0,05). Conclusão: O tratamento endodôntico em sessão única associado à terapia fotodinâmica mostrou-se mais eficaz na reparação da lesão periapical.

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Yano, Tomonori. "A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer." Kyoto University, 2017. http://hdl.handle.net/2433/228216.

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Shamali, Nedaa. "Development of a new approach (“Myc-PDI”) for the treatment of onychomycosis." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/20837.

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Die Onychomykose ist eine sehr häufige Erkrankung, deren Auftreten weltweit zunimmt und mit einer Pilzinfektion der Nägel einhergeht. Die Ineffizienz der verabreichte Antimykotika motiviert Bemühungen, nach alternativen Behandlungsmethoden zu suchen. Diese Dissertation untersucht die Auswirkungen der photodynamischen Inaktivierung (PDI) auf Dermatophyten und Schimmelpilze. Als Modellorganismen werden drei der Onychomykose auslösenden Pathogene untersucht: Trichophyton rubrum, Trichophyton interdigitale und der Schimmelpilz Scopulariopsis brevicaulis. Um das Potenzial der PDI gegen Onychomykose verursachende Pathogene, abzuschätzen, wurden Phototoxizitätstests mit drei Photosensibilisatoren (PS) durchgeführt: 5,10,15,20-Tetrakis(1-methylpyridinium-4-yl) porphyrintetra(p-toluenesulfonate) (TMPyP) und and 5,10,15-tris-(1-methylpyridinium-2-yl) corrolato-(trans-dihydroxo) phosphorus(V) (PCor+) sowie 4',5',7'-tetrabromo-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene] -1-one (Eosin G). Neben den Phototoxizitätstests wurden zeitaufgelöste Singulettsauerstoff-Lumineszenz Scans aufgenommen, die zur Verifizierung der PDI Effizienz genutzt wurden. Alle drei PS zeigen in vitro eine hohe phototoxische Wirkung. Diese konnte mit Singulettsauerstoff-Lumineszenzmessungen korreliert werden, bei denen ein hohes Singulettsauerstoff-Lumineszenzsignal erfasst wurde. An infizierten menschlichen Nägeln konnten die PS keinen phototoxischen Effekt induzieren. Singulettsauerstoff-Scans, die für einen Einblick in die zugrundeliegenden Ursachen durchgeführt wurden, zeigten fast kein Singulettsauerstoff-Lumineszenzsignal an menschlichen Nägeln. Könnten die verschiedenen bekannten Herausforderungen im Zusammenhang mit PDI an infizierten menschlichen Nägeln bewältigt werden, hätte die PDI das Potenzial, eine schnellwirkende Behandlung dieser Pilzinfektion im Zehennagel zu werden. Diese Studie zeigt erstmals den Zusammenhang zwischen der PDI-Behandlung von Onychomykose und Singulettsauerstoff.
Onychomycosis is a very common illness that befalls an increasing number of individuals worldwide and involves a fungal infection of the nails. The inefficiency of current treatments justifies the efforts to look for alternative treatment modalities. This dissertation investigates the impact of photodynamic inactivation (PDI) against dermatophytes and molds. Three of the causing pathogens of onychomycosis are under investigation: Trichophyton rubrum (T. rubrum), Trichophyton interdigitale (T. interdigitale) and the mold Scopulariopsis brevicaulis (S. brevicaulis). To assess the potential of PDI against onychomycosis causing pathogens, phototoxicity tests were performed using three photosensitizers (PSs): the cationic 5,10,15,20-Tetrakis(1-methylpyridinium-4-yl) porphyrintetra(p-toluenesulfonate) (TMPyP) and 5,10,15-tris-(1-methylpyridinium-2-yl) corrolato-(trans-dihydroxo) phosphorus(V) (PCor+) as well as the anionic 4',5',7'-tetrabromo-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one (Eosin Y). Alongside the phototoxicity tests, time resolved singlet oxygen luminescence scans were conducted to serve as a control method of PDI. All three PSs proved to have a high phototoxic effect against the three fungi species in vitro. Those could be correlated with singlet oxygen measurements, where a high singlet oxygen luminescence signal was acquired. Contrary to the expectations from the in vitro experiments were the results obtained ex vivo: On infected human nails, the PSs were not able to induce a phototoxic effect. Singlet oxygen scans conducted to get insight into the reasons behind these results showed nearly no singlet oxygen luminescence signal on human nails. Addressing the various known challenges associated with PDI on infected human nails PDI would have a great impact within short time on treating the toenail fungal infection. This study, for the first time, shows the correlation between PDI treatment of onychomycosis and singlet oxygen.

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Kulyk, Olena. "Light-tissue interactions for developing portable and wearable optoelectronic devices for sensing of tissue condition, diagnostics and treatment in photodynamic therapy (PDT)." Thesis, University of St Andrews, 2016. http://hdl.handle.net/10023/13199.

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This thesis presents the development and in-vivo applications of wearable and portable devices for the investigation of light interaction with tissue involved in Photodynamic therapy (PDT) and during contraction of muscles. A hand-held device and a clinical method were developed for time course in-vivo imaging of the fluorescence of the photosensitizer Protoporphyrin IX (PpIX) in healthy and diseased skin with the aim to guide improvement of PDT protocols. The device was used in a small clinical study on 11 healthy volunteers and 13 patients diagnosed with non-melanoma skin cancer (NMSC). Two types of PpIX precursors were administered: Ameluz gel and Metvix® cream. The fluorescence was imaged with a 10 minute time step over three hours which was the recommended metabolism time before commencing PDT treatment at Ninewells Hospital, Dundee. The fluorescence time course was calculated by integrating the areas with the highest intensity. The fluorescence continued to grow in all subjects during the three hours. The time course varied between individuals. There was no statistical significance between either healthy volunteers or patients in Ameluz vs Metvix® groups; nor was there statistical difference between the three lesions groups (Actinic keratosis (AK) Ameluz vs AK Metvix® vs Basal cell carcinoma (BCC) Metvix®). The p-value was larger than 0.05 in a two sample t-test with unequal variances for all the groups. However, there was strong body site dependence between the head & neck compared to the lower leg & feet, or the trunk & hands body site groups (p-value < 0.01). One of the possible explanations for this was temperature and vasculature variation in skin at different body sites: the temperature is higher and the vasculature structure is denser at the head and the neck compared to the lower leg or the trunk. The temperature was not measured during the study. So in order to support this hypothesis, typical skin temperatures at the lesion sites were taken from the IR thermal images of healthy skin available in literature. PpIX fluorescence had a positive correlation to temperature. If this hypothesis is true, it will be highly important to PDT treatment. Increasing the temperature could speed up the metabolism and reduce the waiting time before starting the treatment; ambient temperature should be taken into account for daylight PDT; cooling air as pain management should be administered with caution. Potential improvements for wearable PDT light sources were investigated by modelling light transport in skin for the current LED-based Ambulight PDT device, a commercial OLED for future devices and a directional OLED developed in the group. The optical models were implemented in commercial optical software (with intrinsic Monte Carlo ray tracing and Henyey-Greenstein scattering approximation) which was validated on diffuse reflectance and transmittance measurements using in-house made tissue phantoms. The modelling was applied to investigate the benefits from diffusive and forward scattering properties of skin on light transmission in treatment light sources. 1 mm thick skin can only compensate approximately 10% of non-uniform irradiance. It means that uniform illumination is crucial for the treatment light sources. Forward scattering in skin showed a 10% improved light transmission from a collimated emission compared to a wide angle Lambertian emission. However, depth-dependent transmission measurements of directional vs Lambertian emission from organic light emitting films (a nano-imprinted grating was fabricated to provide directional emission in one of the films), collimated vs diffused HeNe laser light through fresh porcine skin did not show the expected improvement. This could be explained by skin roughness which was previously found to change the optical properties and may also affect light coupling. The modelling was applied to guide an optical design of another wearable device – a muscle contraction sensor. Muscle is fibrous and because of that scatters light differently in different directions. The sensor detects the change in backscattered light in parallel and perpendicular directions with respect to muscle fibres. The sensor was implemented on a wearable bandage on fully flexible substrate with flexible OLED and organic photodiodes. The major advantages of organic optoelectronic sensing compared to conventional electromyography (EMG) sensors are the ability to distinguish two types of contractions (isotonic and isometric), insensitivity to electromagnetic interference and the absence of an immune response due to non-invasive electrode-free sensing. Optical modelling was performed to understand the operation of the sensor. A 3D anisotropic optical model of scattering in muscle was created by geometrical manipulations with the standard Henyey-Greenstein scattering volumes. The penetration depth from the Super Yellow OLED was found to be 20-25 mm; the optimal separation between the source and the detector was found to be 20 mm. This distance provided a still detectable signal along with the best discrimination between the two backscatterings. When a 2 mm thick layer of skin and a 2 mm thick layer of adipose tissue were added to the model, the signal was hugely diffused. The discrimination between the two backscatterings decreased by three orders of magnitude, the penetration depth in muscle was reduced, and the intensity of the signal dropped down but was still detectable. With 5 mm thick adipose tissue and 2 mm thick skin the signal was too diffused and interacted with very shallow layers of muscle which approached the limits of the optical sensing of muscle activity.

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Carrilho, Ana Margarida Mateus. "O papel do laser em endodontia." Master's thesis, [sn.n.], 2012. http://hdl.handle.net/10284/3791.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
Nas últimas duas décadas temos vindo a observar um crescente desenvolvimento da tecnologia Laser nas diversas áreas da saúde, inclusive na Medicina Dentária. Dentro destas aplicações, a associação das novas tecnologias às terapêuticas tradicionais na área da Endodontia tem sido alvo de interesse por parte dos investigadores. Sabemos atualmente que um dos principais objectivos da Endodontia é o de devolver ao sistema de canais radiculares as condições ideais de assepsia, eliminando os microrganismos patogénicos, e restabelecendo a função do dente. Deste modo, o insucesso do tratamento Endodôntico atribui-se hoje em dia à permanência dos microrganismos no SCR, não só devido à possibilidade de ocorrer uma desinfeção deficitária, mas também devido à possível re-contaminação, durante o tratamento ou devido a um selamento coronário insuficiente. Uma das principais utilizações dos Lasers na Endodontia prende-se com a eficácia comprovada dos Lasers como auxiliar na desinfeção dos canais radiculares, sendo que estudos científicos também revelam o seu desempenho noutras aplicações como os recobrimentos pulpares, obturação retrógrada, apicectomias e na obtenção do diagnóstico de vitalidade pulpar. Pareceu-nos pertinente a realização deste trabalho tendo como objectivo avaliar a situação atual da aplicação dos Lasers em Endodontia, de forma a melhor conhecer o seu funcionamento, as suas principais aplicações e indicações bem como os benefícios e desvantagens da sua utilização. A pesquisa bibliográfica deste trabalho foi realizada nas bibliotecas da Universidade Fernando Pessoa e Faculdade de Medicina Dentária da Universidade do Porto e nos motores de internet Pubmed, Science Direct e Scielo. Encontraram-se 732 artigos dos quais utilizamos 54. Como critérios de inclusão consideramos artigos escritos entre 2000 e 2012, em língua Portuguesa e Inglesa, que se encontrassem disponíveis publicamente. As palavras chave utilizadas foram “Laser”, “Endodontics”, “Root Canal Treatment”, “Desinfection”, “Apicectomy” e “Photodynamic Therapy”, “Laser em Endodontia”, que foram associadas de múltiplas formas. Como principais conclusões deste trabalho podemos afirmar que a tecnologia Laser pode ser eficazmente utilizada em diversos tratamentos desta área como coadjuvante às técnicas convencionais. In the past two decades there has been an increasing development of Laser technology in a several fields of healthcare, including Dentistry. Within these applications, combining new technologies with traditional therapies in Endodontics has been a matter of interest for many researchers. It is now known that a major goal of Endodontic therapy is to return to the root canal system the ideal condition of asepsis, eliminating pathogenic microorganisms, and restoring the tooth function. Therefore, Endodontic treatment failure is nowadays attributed to microorganisms persisting in the RCS, not only because of the possibility of an inefficient disinfection, but also due to the possible re-contamination during treatment or due to an insufficient coronal sealing. One of the highest uses of Lasers in Endodontics deals with the proven effectiveness of lasers to aid in the disinfection of root canals, and scientific studies also show its performance in other applications such as pulp coating, retrograde filling, apicoectomy and diagnosis. It seemed appropriate to conduct this study to assess the current situation of Laser applications in the Endodontic field, in order to comprehend its operation, its main applications and indications as well as the benefits and disadvantages of its use. A literature research was performed in the libraries of Universidade Fernando Pessoa e Faculdade de Medicina Dentária da Universidade do Porto and we used Pubmed, Science Direct and Scielo. There were found 732 articles of which 54 were chosen. Inclusion criteria considered articles written between 2000 and 2012 in Portuguese and English, which were publicly available. The key words were "Laser", "Endodontics," "Root Canal Treatment", "Desinfection", "Apicectomy" and "Photodynamic Therapy", "Laser em Endodontia", which have been linked in numerous ways. As a main conclusion of this work it can be stated that the use of Laser technology is effective in several Endodontic treatments when used as an adjuvant to conventional techniques.

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Pires, Layla. "Optical strategies for diagnosis and treatment of melanoma." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-01122017-154608/.

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Melanoma is a pigmented tumor that originates from the melanocytes; pigmented cells present throughout the body, including skin and iris. The cutaneous form is the most common type, and it represents about 5% of the skin tumors diagnosed in Brazil. Although it does not have a high incidence, it represents about 80% to 85% of all skin tumor deaths. The second most frequent type of melanoma is ocular. It represents 5% of all melanoma cases and is a potentially lethal disease, especially when it causes metastasis. The main therapeutic approach for melanomas, in general, is surgery, with resection of the cutaneous lesion or enucleation in the case of ocular melanoma. Other techniques such as adjuvant immunotherapy, palliative chemotherapy, and radiotherapy are also used. However, they have low efficacy and several side effects. Photodynamic therapy is a therapeutic modality based on the interaction of light at specific wavelength and photosensitizer, in the presence of molecular oxygen, leading the cell to death. As melanoma is a pigmented cancer, it usually does not respond well to photodynamic therapy due to the high absorption of light on the surface of the tumor, making volumetric eradication impossible. This project investigated optical strategies for the diagnosis and treatment of melanoma. For the diagnosis, it was evaluated the fluorescence lifetime technique to differentiate melanoma and normal skin. A sensitivity of 99.4%, specificity of 97.4% and accuracy of 98.4% were achieved using linear discrimination analysis. For the cutaneous melanoma treatment, PDT combined to optical clearing agents (OCAs) was investigated. Vascular and cell-target photosensitizers were evaluated combined or not to OCAs. OCA improved PDT response in all pigmented tumors treated, but the best results were achieved when a dual-photosensitizer treatment combined to OCA was performed. The treatment of conjunctival melanoma was conducted using 2-photon excitation photodynamic therapy. The advantage of this technique is the use of infrared light, in a wavelength that melanin has a low absorption, improving the light penetration into the tumor. The tumor histology shows that apoptosis was induced only at the treatment site, with no damage to the surrounding tissue. Additionally, a single TPE-PDT session could treat the entire tumor.
O melanoma é um tumor pigmentado que surge dos melanócitos, células pigmentadas presentes em todo o corpo, incluindo a pele e a íris. A forma cutânea é a mais comum e representa cerca de 5% dos tumores cutâneos diagnosticados no Brasil. Embora não tenha uma alta incidência, representa cerca de 80% a 85% de todas as mortes por tumor de pele. O segundo tipo de melanoma mais frequente é o ocular. Representa 5% de todos os casos de melanoma e é uma doença potencialmente letal, especialmente em casos de metástase. A principal abordagem terapêutica para melanomas, em geral, é a cirurgia, com ressecção da lesão cutânea ou enucleação no caso do melanoma ocular. Outras técnicas, como imunoterapia adjuvante, quimioterapia paliativa e radioterapia também são usadas, porém, apresentam baixa eficiência e muitos efeitos colaterais. A terapia fotodinâmica é uma modalidade terapêutica baseada na interação da luz em um comprimento de onda específico e um fotossensibilizador, na presença de oxigênio molecular, levando a célula à morte. Como o melanoma é um câncer pigmentado, geralmente não responde bem à terapia fotodinâmica devido à alta absorção de luz na superfície do tumor, impossibilitando a erradicação volumétrica. Este projeto investigou estratégias ópticas para o diagnóstico e tratamento do melanoma. Para o diagnóstico, foi avaliada a técnica de tempo de vida de fluorescência para distinguir melanoma de pele normal. Utilizando análise de discriminação linear, obteve-se uma sensibilidade de 99,4%, especificidade de 97,4% e precisão de 98,4%. Para o tratamento de melanoma cutâneo, a PDT combinada com clareadores ópticos (OCAs) foi investigada. Um fotossensibilizador que tem como alvo vaso sanguíneo e um fotossensibilizador de alvo celular foram avaliados combinados ou não com OCAs. OCAs são soluções hiperosmóticas que desidratam o tecido, diminuindo o espalhamento da luz e melhorando a penetração de luz em profundidade. OCA melhorou a resposta de PDT em todos os tumores melanóticos tratados, mas os melhores resultados foram obtidos quando a PDT foi realizada com a combinação dos fotossensibilizadores e clareador óptico em uma única sessão. O tratamento do melanoma conjuntival foi realizado utilizando a terapia fotodinâmica por excitação de 2 fótons (TPE-PDT). A vantagem desta técnica é o uso de luz na região do infravermelho, em um comprimento de onda que melanina tem baixa absorção, melhorando a penetração de luz no tumor. A histologia do tumor mostrou que a apoptose foi induzida apenas no local do tratamento, sem danos no tecido adjacente. Além disso, uma única sessão de TPE-PDT foi capaz de tratar todo o tumor.

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Buinauskaitė, Evelina. "AKTININĖS KERATOZĖS FOTODINAMINIO GYDYMO SKIRTINGOMIS RAUDONOSIOS ŠVIESOS DOZĖMIS VEIKSMINGUMAS." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140618_233345-93532.

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Šio tyrimo tikslas buvo įvertinti aktininės keratozės klinikinius ypatumus ir fotodinaminio gydymo skirtingomis raudonosios šviesos dozėmis veiks-mingumą. Aktininė keratozė – tai ikinavikinė odos liga, pasireiškianti ilgalaikio saulės poveikio srityse, o jos diagnozė nustatoma remiantis klinikiniu vaizdu. Histologinis tyrimas atliekamas tik neaiškiais atvejais. Vis tik pasitaiko diagnozavimo klaidų ir nesuta¬pimo atvejų tarp tyrėjų dermatologų bei dermatopatologų. Šiame darbe įvertinome ir nustatėme AK klinikinės raiškos ypatumus bei jų sąsajas su histologiniais požymiais, o taip pat AK klinikinio tyrimo jautrumą ir specifiškumą, remiantis histologinio tyrimo duomenimis. Nuo 0,025 iki 20 proc. atvejų AK transfor¬muojasi į plokščiųjų ląstelių karcinomą. Aktininę keratozę rekomenduojama gydyti, nes prognozuoti, kuri AK plis iš epidermio į gilesnius odos sluoksnius ir taps plokščiųjų ląstelių karcinoma, neįmanoma. Veiksmingas bei saugus būdas gydyti AK yra vietinio poveikio foto¬dinaminis gydymas, tačiau jo trūkumas – skausmas procedūros metu. Atlikę perspektyvųjį tyrimą, įvertinome aktininės keratozės klinikinės raiškos ypatumus po fotodinaminio gydymo su 5-aminolevulino rūgštimi. Nustatėme skausmą procedūros metu įtakojančius veiksnius. Nustatėme šio gydymo dviejomis raudonosios šviesos dozėmis veiksmingumą po dvejų metų stebėjimo bei AK atkrytį prognozuojančius veiksnius. Pateikėme praktines šio AK gydymo rekomendacijas.
The aim of this study was to evaluate clinical characteristics of actinic keratosis and the efficacy of photodynamic treatment with different red light doses. The diagnosis of AK is based upon its typical clinical aspects. However, there are data stating that diagnosing single AKs clinically is not precise and that there are even interobserver disagreements between dermatologists and dermatopathologists. In this study we assessed the clinical peculiarities of AK and its correlation with histological characteristics. We assessed the sensitivity and specificity of AK clinical diagnosis based on histopathological analysis. In 0.025% to 20% cases AK transforms into squamous cell carcinoma. It is impossible to predict which AK will spread from the epithelium into the deeper layers of the skin. Therefore, treatment of actinic keratosis is recommended in all cases. Topical photodynamic treatment is safe and effective therapy for AK but pain is the limitation of the procedure. We performed a prospective within-patient study and evaluated the clinical pecularities of actinic keratosis after photodynamic treatment. We assessed the factors that influence pain during the treatment. We assessed the efficacy of photodynamic treatment with different red light doses for actinic keratosis after two-years follow-up. Factors that influence the recurrence of AK were evaluated. Follow-up data for two years was used to formulate the practical recommendations of the study.

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Silva, Celso Monteiro da. "Efeito da associação da terapia fotodinâmica no tratamento endodôntico de dentes decíduos com polpa necrosada." Universidade de Taubaté, 2013. http://www.bdtd.unitau.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=637.

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avaliar a efetividade da terapia fotodinâmica (PDT) com fibra óptica ou peça de mão em canais radiculares de dentes decíduos com polpa morta, depois do preparo químico-cirúrgico, pela quantificação de microrganismos viáveis. Método: foram selecionados trinta dentes decíduos, de crianças na faixa etária entre quatro e sete anos com boa saúde geral que apresentavam um ou mais dentes com polpa morta e fístula visível clinicamente. Os dentes foram divididos em três grupos: G1- (n=10) que recebeu instrumentação com creme Endo-PTC e líquido de Dakin, G2- (n=10) que recebeu instrumentação com creme Endo-PTC e líquido de Dakin acrescida do PDT com fibra óptica e G3- (n=10) que recebeu instrumentação com creme Endo-PTC e líquido de Dakin acrescida do PDT com peça de mão. Após a obturação do canal e restauração do dente foi realizada uma tomada radiográfica. O material do interior do canal foi coletado com cones de papel esterilizados, imediatamente após a cirurgia de acesso aos canais, depois do preparo químico-cirúrgico e depois do PDT, e foram colocados em flaconetes com solução salina tamponada com fosfato (PBS) e levado ao laboratório para processamento Cada amostra foi agitada, diluída, semeada, incubada e as unidades formadoras de colônia (UFC) contadas e calculado o número de UFC/mL. Resultados: em todos os grupos experimentais houve redução do número de UFC/mL de forma significativa no interior do canal radicular. Houve redução significativa do G1 para G2 e de G1 para G3 quando comparado o log de UFC/mL da última coleta (coleta após instrumentação para G1 e após tratamento com PDT para G2 e G3), mas não houve diferença quando comparadas as últimas coletas de G2 e G3. Conclusão: a incorporação da terapia fotodinâmica, ao final do preparo químico-cirúrgico no tratamento endodôntico de dentes decíduos com polpa necrosada, potencializou a redução microbiana no interior dos canais radiculares.
to evaluate the effectiveness of photodynamic therapy (PDT) with optical fiber or handpiece in root canals of deciduous teeth with necrotic pulp, after chemical-surgical preparation, by the quantification of viable microorganisms. Method: thirty deciduous teeth were selected, of children aged between four and seven years in good general health who had one or more teeth with necrotic pulp and clinically visible fistulae. The teeth were divided into three groups: G1 (n=10) instrumentation with Endo-PTC cream and 0,5% sodium hypochlorite, G2 (n=10) instrumentation with Endo-PTC cream and 0,5% sodium hypochlorite added PDT by optical fiber, and G3 (n=10) instrumentation with Endo-PTC cream and 0,5% sodium hypochlorite added PDT with handpiece. After filling the canal and tooth restoration was performed radiography The samples were taken with sterile paper points immediately after the surgery to access the canals, after the chemical-surgical preparation, and after the PDT, and were placed in vials with saline solution buffered with phosphate (PBS) and taken to the laboratory for processing. Each sample was agitated, diluted, plated, and incubated, and the colony-forming units (CFU) were counted and the number of CFU/mL was calculated. Results: all the experimental groups showed a significant reduction in the number of CFU/mL in the root canal. There was a significant reduction from G1 to G2 and from G1 to G3, when comparing the logarithm of CFU/mL from the last sample (after instrumentation for G1 and after treatment with PDT for G2 and G3), but there was no difference when comparing the final samples of G2 and G3. Conclusion: the incorporation of photodynamic therapy at the end of the chemical-surgical preparation in the endodontic treatment of deciduous teeth with necrotic pulp increased the microbial reduction of root canals.

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Lambert, Christine [Verfasser]. "Role of reactive oxygen species in anti-cancer treatment: Investigations in 2-methoxyestradiol chemotherapy and 5-aminolevulinic acid based photodynamic therapy combined with hyperthermia : Investigations in 2-methoxyestradiol chemotherapy and 5-aminolevulinic acid based photodynamic therapy combined with hyperthermia / Christine Lambert." Aachen : Shaker, 2003. http://nbn-resolving.de/urn:nbn:de:101:1-2019022406152202951795.

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Lambert, Christine. "Role of reactive oxygen species in anti-cancer treatment investigations in 2-methoxyestradiol chemotherapy and 5-aminolevulinic acid based photodynamic therapy combined with hyperthermia /." [S.l. : s.n.], 2003. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10519019.

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Gonçalves, Leonardo. ""Efeito de fotoativadores utilizados na irradiação laser intracanal"." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/23/23145/tde-07062005-092622/.

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Este estudo teve como objetivo avaliar o grau de manchamento dental, ap¨®s o tratamento endodôntico, quando aplicada a terapia fotodinâmica, utilizando-se os corantes azuis de metileno e de orto toluidina como fotossensibilizadores, atrav¨¦s do sistema RGB e K de cores do programa Adobe Photoshop. Vinte dentes humanos unirradiculares tiveram seus canais preparados pela t¨¦cnica seriada com instrumentos endodônticos, Endo-PTC e liquido de Dakin. Constitu¨ªram-se tr¨ºs grupos experimentais, Grupo C: Corante em sua forma liquida, Grupo E: Substância qu¨ªmica Endo PTC associada ao corante em sua formulação e Grupo C+E: Corante em sua forma liquida com irrigação final de liquido de Dakin em conjunto com Endo PTC por 15 min. A leitura de cor foi executada antes (L0), imediatamente ap¨®s o preparo qu¨ªmico-cirurgico (L1) e dez dias depois da irradiação (L2). Analise estat¨ªstica pelo teste de Wilcoxon comprovou que os resultados dos esp¨¦cimes do Grupo E nas interações L1-L2 e L0-L2 não acarretaram diferenças significativas. Pelos resultados obtidos foi poss¨ªvel concluir que: com base no projeto experimental que executou a t¨¦cnica endodôntica tradicional, todos os corantes ativadores testados, alteraram os valores de K. Na an¨¢lise comprobat¨®ria dos resultados de alteração crom¨¢tica pelos valores de K os melhores resultados foram observados nos esp¨¦cimes dos grupos Metileno E e Toluidina E que na interação L0-L1 não apresentaram diferenças estatisticamente significantes a 5%.
The present study had as objective to evaluate the dental staining after the root canal treatment when it¡¯s used the photodynamic therapy, using the dies methylene blue and orto toluidina blue as photosensitizers, through the RGB and K color system from the software Adobe Photoshop. Twenty human single root teeth had its roots canals prepared by the seriated technique using the endodontic instruments plus Endo-PTC and Dakin. Three experimental groups were formed: Group C: dye in its liquid form; Group E: dye associated to the Endo-PTC cream and Group CE: dye in its liquid form with final irrigation of the Dakin plus Endo¨CPTC for 15 minutes. The color measure was taken before (L0), immediately after (L1) and ten days after the laser irradiation. The statistical analysis performed using the Wilcoxon text proves that the results of the specimens of the E Group on the interactions L1-L2 and L0-L2 didn¡¯t have any significant differences. Based on the results obtained it was possible to conclude that: based on the experimental design that performed the traditional endodontic technique, all the activating dyes tested altered the values of K. After carrying out an analysis of the chromatic alteration results according to K values, the best results were observed in specimens of group methylene E and group toluidine E, both of which presented no statistically significant difference for the interaction L0-L1 (p ¡Ü 5%).

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Lambert, Christine [Verfasser]. "Role of reactive oxygen species in anti-cancer treatment : investigations in 2-methoxyestradiol chemotherapy and 5-aminolevulinic acid based photodynamic therapy combined with hyperthermia / vorgelegt von Christine Lambert." Aachen : Shaker, 2003. http://d-nb.info/117902236X/34.

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Costa, Mardoqueu Martins da. "Estudo de viabilidade de um protótipo integrado para o diagnóstico e tratamento da acne por técnicas ópticas." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/18/18152/tde-13052015-165447/.

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A acne é a mais comum doença de pele encontrada pelos dermatologistas, representando cerca de 30% das consultas, onde esta é considerada crônica, pois apresenta alto grau de recidiva podendo acometer 50% da população na vida adulta. Diversos estudos evidenciam bons resultados para tratamento da acne através de fototerapias, entretanto, alguns trabalhos enfatizam que esta modalidade terapêutica é ainda recente e que estudos adicionais e mais detalhados devam ser realizados. Nesse contexto, o objetivo deste trabalho é o estudo da viabilidade de um protótipo integrado para o diagnóstico e tratamento da acne por técnicas ópticas, visando o desenvolvimento de um equipamento para diagnóstico por imagens de fluorescência e um sistema de tratamento por fototerapia para a eliminação das bactérias causadoras da acne, assim, propondo novas soluções para o diagnóstico e tratamento da acne. Para isso foi realizado o desenvolvimento do protótipo-v1 que é constituído pelo sistema de diagnóstico por imagens de fluorescência composto por 01 LED violeta em 405 nm para excitação das amostras (80 mW/cm2), um sistema de filtros e lentes para formação das imagens de fluorescência e uma câmera para a captura das imagens. O sistema de tratamento é composto por 01 LED UV em 405 nm que proporciona uma intensidade de irradiação de 150 mW/cm2 com um diâmetro de 40 mm. Para validação do protótipo-v1 foram realizados seis experimentos distintos, sendo: 1 – Avaliou-se as configurações iniciais do protótipo eram adequadas para a visualização de bactérias presentes no rosto, foram adquiridas imagens de fluorescência na região do nariz; 2 – Avaliou-se a detecção de bactérias presentes em quatro diferentes regiões da face; 3 – Avaliou-se somente com uma lavagem simples é possível fazer a remoção e eliminação das bactérias presentes no rosto; 4 – Avaliou-se a detecção da presença de bactérias no couro cabeludo que são possíveis causadoras de caspa e se ocorre uma maior formação de bactérias no couro cabeludo ao longo do tempo. 5 – Avaliou-se in vivo, em um voluntário, o sistema de diagnóstico e tratamento da acne do protótipo-v1; 6 – Avaliou-se in vitro e in vivo, 40 voluntários, o sistema de diagnóstico e tratamento da acne do protótipo-v1. Como resultado foi possível realizar a detecção da bactéria P. acnes e fazer uma análise de sua presença, formação e declínio em seis experimentos, através de processamento de imagens e análises comparativas. Sendo que no experimento 1 a 4 avaliou-se a qualidade e as configurações do equipamento de diagnóstico por fluorescência e os experimento 5 e 6 avaliaram tanto o sistema de diagnóstico como o sistema de tratamento. Assim, através destes experimentos realizados foi possível demostrar uma viabilidade da utilização do protótipo-v1 como sistema de diagnóstico e tratamento da acne, demonstrando que é possível se realizar o monitoramento das bactérias causadoras da acne através das imagens de fluorescência e o tratamento da acne utilizando técnicas ópticas.
Acne is the most common skin disease found by dermatologists, representing about 30% of the consultations, where it is considered chronic, because has a high degree of recurrence and can affect 50% of the population in adult life. Several studies have shown good results for treatment of acne via phototherapy, however, some studies emphasize that this type of treatment is still new and additional and more detailed studies should be conducted.In this context, the aim of this work is the viability study of an integrated prototype for acne diagnosis and treatment by optical techniques, aiming at the development of a system for diagnosis by fluorescence imaging and phototherapy for treatment and elimination of bacteria that cause the acne, therefore offering new solutions for the acne diagnosis and treatment. For this, the prototype v1 was developed, which is constituted for diagnostic system by fluorescence image composed of one violet LED at 405 nm for excitation of the samples (80 mW / cm2), a system of filters and lenses for the formation images of fluorescence and a CCD camera to capture the images. The treatment system is composed of one violet LED at 405 nm which provides an irradiation intensity of 150 mW/cm2 with a diameter of 40 mm. For validation of prototype v1 were conducted six different experiments, as follows: 1 - Were evaluated initial prototype settings for the visualization of bacteria in the face for that, were acquired fluorescence images in the nose; 2 - Were evaluated detection of bacteria in four different regions of the face; 3 - Was evaluated only with simple washing can make removal and elimination of bacteria from the face; 4 - Was evaluated detecting the presence of bacteria on the scalp which are possible cause of dandruff and there is a greater formation of bacteria in the scalp along of the time; 5 - Was evaluated in vivo, in a voluntary, the prototype of the system of diagnosis and treatment of acne; 6 - Was evaluated in vitro and in vivo, 40 volunteers, the prototype of the system of diagnosis and treatment of acne. As a result, was possible to detect the P. acnes bacteria and do an analysis of their presence, formation and decline in six experiments, through image processing and comparative analysis. Where in experiment 1 to 4 was evaluated the quality and configurations of diagnostic fluorescence prototype and 5 to 6 experiments evaluating both the diagnostic and treatment system. Thus, through these experiments it was possible to demonstrate the viability of using one prototype v1 as diagnostic system and acne treatment, demonstrating that it is possible to perform the monitoring of acne causing bacteria via fluorescence imaging and treatment of acne using optical techniques.

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Grande, Murilo Penteado Del. "Terapia fotodinâmica no tratamento do tumor de Ehrlich inoculado em camundongos: avaliação da eficácia e da resposta imunológica sistêmica." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-27112013-142927/.

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A terapia fotodinâmica (Photodynamic Therapy - PDT) é um método de tratar neoplasias baseado na interação entre luz, oxigênio molecular e um agente fotossensibilizador. Após a administração do agente, o tumor é iluminado com luz visível, ativando-o e produzindo espécies reativas de oxigênio, altamente citotóxicas, que provocam morte celular e destruição tecidual. Com a destruição do tumor há ativação do sistema imune inato e o subsequente processo inflamatório determina a apresentação de antígenos tumorais aos linfócitos, promovendo uma resposta imunológica adaptativa contra o tecido tumoral. O presente trabalho visou estudar a PDT associando um laser de diodo como fonte de luz e o fotossensibilizante Azul de Metileno (AM) a 1%, avaliando a sua efetividade no tratamento do Tumor de Ehrlich (TE) em sua forma sólida e a resposta imunológica nos animais tratados. Em um primeiro estudo, avaliou-se macro e microscopicamente tumores tratados, determinando a capacidade do protocolo em induzir inflamação e destruição do tecido tumoral. No segundo estudo, a resposta imune foi estudada em camundongos desafiados com um segundo implante de células do tumor de Ehrlich. O primeiro implante tumoral foi tratado com a PDT ou a excisão cirúrgica, comparando-se com um grupo controle sem tratamento. Os parâmetros avaliados após 17 dias foram o crescimento tumoral (p>0,05), peso relativo dos órgãos linfóides [Baço (p<0,05) e Linfonodo poplíteo (p>0,05)], tamanho relativo do linfonodo (p<0,05), presença de metástase em linfonodo poplíteo (p>0,05), contagem de leucócitos sanguíneos (p>0,05) e análise morfométrica quantitativa do tumor secundário [determinação da fração volumétrica de células tumorais (p<0,05), infiltrado inflamatório (p<0,05), necrose (p>0,06) e porcentagem da área tumoral em necrose (p<0,05)]. A PDT com o AM foi capaz de induzir necrose do TE e inflamação, havendo diferenças da resposta imune sistêmica quando comparado aos animais tratados por meio de excisão cirúrgica do tumor de Ehrlich.
Photodynamic therapy (PDT) is a method of treating neoplasms based on the interaction between light, molecular oxygen and a photosensitizing agent. After administration of the photosensitizer, the tumor is illuminated with visible light, activating the agent and producing reactive oxygen species (ROS). This highly cytotoxic ROS cause cell death and tissue destruction. The activation of the innate immune system and the subsequent inflammation induces tumor antigen presentation to lymphocytes, promoting an adaptive immune response against the tumor cells. This work aimed to study the PDT using a diode laser as light source and Methylene Blue (MB) 1% as photosensitizer. It was accessed its effectiveness in treating Ehrlich Solid tumor (ET) and the immune response produced in treated animals. First the treated tumors were evaluated macroscopically and microscopically, determining the ability of the protocol to induce inflammation and tumor tissue destruction. In a second study, the immune response was studied in mice challenged with a second tumor cell implant. The primary tumor was treated with PDT or surgical excision, comparing with a control group without treatment. The parameters evaluated after 17 days were tumor growth (p> 0.05), relative weight of lymphoid organs [spleen (p <0.05) and popliteal lymph node (p> 0.05)], the relative size of the lymph node (p <0, 05), metastasis at lymph node (p>0,05), blood leukocyte count (p> 0.05) and quantitative morphometric analysis of secondary tumor [determining the volume fraction of tumor cells (p <0.05), inflammatory infiltrate (p <0.05), necrosis (p> 0.06) and tumor necrosis area (p <0.05)]. PDT with MB was able to induce necrosis of the ET and inflammation, with differences in the immune response when compared to animals treated surgically to remove the Ehrlich tumor in its solid form.

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Ambrosini, Veronica. "Antimicrobial Photodynamic treatment as pest management. A study of the effects of photoactivated TPPS and Chlorophyllin on the fungus pathogen Botrytis cinerea, and on two plant models : Grapevine (Vitis vinifera) and Potato (Solanum tuberosum)." Thesis, Limoges, 2020. http://aurore.unilim.fr/theses/nxfile/default/990008db-1196-4108-9048-ba6f3d9a56c4/blobholder:0/2020LIMO0073.pdf.

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Un des problèmes majeurs de l'agriculture reste la lutte contre les agents pathogènes, en particulier les champignons. Depuis les années 60, l'utilisation de quantités phénoménales de pesticides, pour garantir les rendements des cultures, a provoqué́ une pollution désastreuse de l'environnement, une perte de la biodiversité et le développement de pathogènes multi-résistants. Les pratiques agricoles doivent donc devenir plus respectueuses de l'environnement tout en restant optimales. Le traitement photodynamique antimicrobien (APDT) est un traitement alternatif envisagé dans la lutte contre les microorganismes pathogènes, sans effet sur les plantes de culture et sur l'environnement voir la santé humaine. Dans l’intention de développer cette approche, deux photosensibilisateurs (PS) : une porphyrine anionique (TPPS) et une chlorine (la Chlorophylline) ont été testés sur un champignon pathogène (Botrytis cinerea) et deux de ses cibles : la vigne (Vitis vinifera) et la pomme de terre (Solanum tuberosum). Nous avons montré que TPPS même à très faible concentration inhibait la croissance du mycélium de B. cinerea sans pour autant altérer le développement des jeunes plants de vigne cultivés in vitro. Des résultats très similaires ont aussi été obtenus avec la Chlorophylline (Chl), molécule naturelle. TPPS et Chl semblent donc de très bons candidats pour une approche APDT. Cependant, dans le but d’une approche éco-responsable, nous privilégions plutôt Chl molécule naturelle contre TPPS, molécule de synthèse. En conclusion, les résultats obtenus tout au long de ces travaux de thèse sont réellement encourageants et nous permettent de défendre l’APDT comme stratégie agricole d’avenir et surtout éco-friendly
Nowadays, one of the major problems in agriculture remains the struggle against pathogens, especially fungi. In the last 60 years, the use of large amounts of pesticides to increase crop yield caused environmental pollution, loss of biodiversity, and the development of multi-resistant plant pathogens. Now, more than ever, agriculture practises must become environmentally friendly and thus, new strategies to improve agriculture, without side effects for the environment and human health, need to be developed. Antimicrobial photodynamic treatment (APDT) has emerged as an alternative treatment that can be envisaged in agronomic practices to fight against microorganisms, without harming plants. To develop this approach on complex living systems such as grapevine and potato, hosts of the fungus pathogen Botrytis cinerea and two photosensitizers were taken into consideration: an anionic porphyrin (TPPS) and a natural chlorin Chlorophyllin (Chl). More specifically, an extensive work was conducted using photoactivated TPPS. TPPS was very effectively inhibit Botrytis cinerea development and it did not cause any phenotypical or biochemical alterations of the grapevine varieties (Merlot, Chardonnay and Sauvignon). In the potato varieties, while there were alterations in its growth and development, the plants were able to defend themselves. Furthermore, in order to find a new eco-friendly solution that is more suitable for a large range of plants we tested a natural PS: the chlorophyllin (Chl). Surprisingly, Chl was able to inhibit Botrytis cinerea mycelium growth without disturbing neither potato nor grapevine plantlet growth. In conclusion, these preliminary studies based on the use of Chl suggest that the development of a safe but efficient APDT approach in agriculture may no longer be a dream

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39

Fracarolli, Letícia. "Isolamento, caracterização e avaliação da atividade fotossensibilizadora de cumarinas e furanocumarinas extraídas de espécies de Citrus." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-28102015-154212/.

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O crescente aumento da tolerância aos fungicidas atualmente utilizados é um dos principais problemas tanto na área clínica quanto na agrícola e tem estimulado o desenvolvimento de estratégias alternativas para o controle de fungos patogênicos, tais como o tratamento fotodinâmico antimicrobiano (TFA), que pode utilizar fotossensibilizadores (FS) de origem natural ou sintética. Alguns FS, como as cumarinas e furanocumarinas, são produzidos por espécies de Citrus como limão Tahiti (Citrus latifolia) e toranjas (Citrus paradisi). O presente estudo investigou o TFA in vitro de conídios do fungo fitopatogênico Colletotrichum acutatum com: (1) o corante fenotiazínico azul de metileno (MB), (2) uma furanocumarina comercial, 8-metoxipsoraleno (8-MOP), (3) uma cumarina comercial, (2H-chromen-2-one), (4) a cumarina 5,7-dimetoxicumarina extraída no presente trabalho a partir de óleo da casca do limão Tahiti, (5) a cumarina 7-hidroxicumarina extraída no presente trabalho a partir de óleo essencial de toranja rubi, (6) duas frações extraídas por De Menezes e colaboradores (2014a) a partir de um resíduo da indústria citrícola, uma delas constituída pela furanocumarina isopimpinelina e outra constituída por uma mistura das cumarinas 7-metoxicumarina e 5,7-dimetoxicumarina (3:1), (7) cinco extratos brutos obtidos a partir de óleos da casca e essencial de limão Tahiti e óleos essenciais de toranjas rubi e branca. Com exceção do extrato bruto obtido do óleo essencial de toranja branca, todos os demais extratos apresentaram cumarinas e/ou furanocumarinas em sua composição. As suspensões de conídios foram tratadas com os diferentes compostos (50 ?M para os compostos comerciais e as frações puras e 12,5 mg L-1 para os extratos e a mistura) e expostas à radiação solar por 1 h. O MB foi exposto à radiação solar por 30 min, 1 e 2 h. Determinou-se o efeito do tratamento fotodinâmico em folhas de mudas de laranja Valencia (Citrus sinensis) com (1) 8-MOP, (2) mistura de cumarinas, (3) 5,7-dimetoxicumarina e (4) o extrato bruto de limão Tahiti. Adicionalmente, experimentos para avaliar a estabilidade do 8-MOP exposto à radiação solar por até 12 h foram realizados. Nesses experimentos, soluções de 8-MOP (50 ?M) foram expostas à radiação solar e alíquotas foram retiradas após os diferentes tempos de exposição. Após as exposições, estudos de espectroscopia de absorção no UV e emissão de fluorescência foram realizados, além da realização de experimentos para avaliar a eficácia do TFA com os FS previamente expostos à radiação solar por 6 e 12 h. Os TFA mais eficazes foram com o MB, 8-MOP (ambos 50 ?M), a mistura de cumarinas e um dos extratos brutos obtidos de limão Tahiti (ambos 12,5 mg L-1), que mataram 99,998%, 99,378%, 99,336% e 65,049% dos conídios, respectivamente, após 1 h de exposição à radiação solar. Nenhum dano nas folhas de laranja foi observado após o TFA com os compostos. Os espectros de absorção e emissão de fluorescência das soluções de 8-MOP expostas à radiação solar mostraram fotodegradação do composto após 12 h de exposição. Entretanto, as soluções de 8-MOP expostas por 6 e por 12 h ainda foram capazes de matar 99,978% e 95,591% dos conídios de C. acutatum, respectivamente
Increasing tolerance to currently used fungicides is a major problem both in clinical and agricultural areas and has stimulated the development of alternative strategies to control pathogenic fungi such as the antimicrobial photodynamic treatment (APDT), that can use natural or synthetic photosensitizers (PS). Some PS, such as coumarins and furocoumarins are produced by Citrus species such Tahiti acid lime (Citrus latifolia) and grapefruit (Citrus paradisi). This study investigated the in vitro APDT of conidia of the plant-pathogenic fungi C. acutatum with: (1) the phenothiazinium dye methylene blue (MB), (2) commercial furocoumarin, 8-methoxypsoralen (8-MOP), (3) commercial coumarin (2H-chromen-2-one), (4) coumarin 5,7-dimethoxycoumarin, extracted in this study from Tahiti lime peel oil, (5) coumarin 7-hidroxycoumarina, extracted in this study from ruby grapefruit essential oil, (6) two fractions extracted by De Menezes et al (2014a) from a Citrus industry residue, one of them constituted by the furocoumarin isopimpinellin, and the other constituted by the mixture of coumarins 7-methoxycoumarin and 5,7-dimethoxycoumarin (3:1), (7) five crude extracts obtained from Tahiti lime peel or essential oil and ruby and white grapefruit essential oil. Except the extract from the white grapefruit, all the others presented coumarins and/or furocoumarins in their composition. Conidial suspentions were treated with the different PS (50 ?M for commercial and pure compounds and 12.5 mg L-1 for the extracts and the mixture) and exposed to solar radiation for 1 h. The MB was exposed to solar radiation for 30 min, 1 and 2 h. The APDT effect on the leaves of Valencia orange trees (Citrus sinensis) with (1) 8-MOP, (2) the mixture of coumarins, (3) 5,7-dimethoxycoumarin, and (4) the most efective extract from Tahiti lime were determined. Additionally, experiments to assess the 8-MOP stability after exposure to solar radiation for 12 h were realized. 8-MOP solutions (50 ?M) were exposed under solar radiation and rates were removed after different times of exposition. After the expositions, absorption spectroscopic studies in UV and fluorescence emission were realized, as well as holding the realization of experiments of APDT efficacy evaluation after 6 and 12 h to exposure under solar radiation. The more effective treatments were with MB, 8-MOP (both 50 ?M), the coumarins mixture and one of the extracts from Tahiti lime (both 12.5 mg L-1), killing at least 99,998%, 99,378%, 99,336% and 65,049% of the conidia, respectively after 1 h under solar radiation. No damage to orange tree leaves was observed after APDT with any of the compounds. The absorption and fluorescence intensity spectra showed the 8-MOP photodegradation after 12 h of exposition, although the 8-MOP solutions exposed under solar radiation for 6 and 12 h still killed at least 99,978% and 95,591% of the C. acutatum conidia, respectively

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Menezes, Henrique Dantas de. "Efeito da inativação fotodinâmica com fotossensibilizadores fenotiazínicos em microconídios não germinados e germinados dos fungos Fusarium oxysporum, Fusarium moniliforme e Fusarium solani." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-03072017-073451/.

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Fusarium é um grande gênero de fungos filamentosos amplamente distribuídos que são importantes patógenos de plantas, animais e humanos. As doenças causadas por Fusarium spp. geram grandes perdas econômicas na produção de frutas, legumes, cereais e de celulose. Em humanos, o controle da fusariose com apenas um antifúngico é ineficaz, apresentando uma elevada taxa de mortalidade, especialmente em pacientes imunocomprometidos. A maior resistência aos fungicidas utilizados atualmente tem estimulado o desenvolvimento de novas tecnologias mais eficazes para o controle de fungos patogênicos. Assim, é necessária a busca de alternativas para o controle de microrganismos em ambas as áreas, clínica e agrícola. A inativação fotodinâmica antimicrobiano (IFA) é uma promissora plataforma antifúngica alternativa que pode ser utilizada para controlar o inóculo de fungos em mamíferos e no meio ambiente. A IFA baseia-se na utilização de um fotossensibilizador (FS) que se acumula na célula fúngica alvo. A exposição do FS à luz com um comprimento de onda apropriado, inicia um processo fotoquímico que produz espécies reativas de oxigênio (EROs), principalmente o oxigênio singleto, causando um dano oxidativo não especifico levando a morte da célula fúngica, sem dano significativo às células do hospedeiro. Em comparação com os fungicidas utilizados atualmente, a multiplicidade dos danos causados pelas EROs, reduzem a chance de selecionar microrganismos tolerantes. No presente trabalho, avaliamos o efeito da IFA com a combinação de luz vermelhas com fluências de 10 e 15 J cm-2 e cinco FS fenotiazínicos, azul de metileno (MB), azul de toluidina O (TBO), novo azul de metileno N fórmula sem zinco (NMBN), novo azul de metileno N formula com zinco (NMBN Zn) e um novo fenotiazínico pentacíclico S137, em microconídios não germinados e 4 h-germinados de Fusarium oxysporum, F. moniliforme e F. solani. A IFA com NMBN Zn resultou em uma redução de aproximadamente 5-logs na sobrevivência dos microconídios não germinados (quiescentes) e 4 h-germinados (metabolicamente ativos) das três espécies de Fusarium quando expostas a luz na fluência de 15 J cm-2. A lavagem dos microconídios não germinados e 4 h-germinados para retirar o excesso de FS antes da exposição à luz reduziu, porém não impediu a morte provocada pela IFA. A IFA com todos os FS e fluência aumentou a permeabilidade da membrana celular dos microconídios nas três espécies de Fusarium. O dano oxidativo causado pelas EROs produzidos durante o processo fotoquímico da IFA foi avaliado nos lipídios, proteínas e DNA dos microconídios das espécies de Fusarium. Foi observado um aumento da peroxidação lipídica em microconídios das três espécies de Fusarium após a IFA com NMBN Zn e S137. Observamos o aumento na carbonilação de proteínas em microconídios de F. oxysporum após IFA subletal com todos os FS. O aumento no dano do DNA em microconídios não germinados e 4 h-germinados foi observado apenas para o S137 na fluência de 0, 10 e 15 J cm-2. Nossos estudos expandem a compreensão da inativação fotodinâmica de fungos filamentosos
Fusarium is a large genus of filamentous fungi widely distributed wich are important pathogens of plants, animals and humans. Crop diseases caused by Fusarium generate great economic losses in the production of fruit, vegetables, cereals, and cellulose. In humans the control of progression of fusariosis by single-agent antifungal therapy is problematic, leading to a high mortality rate, especially with immunocompromised patients. The increased tolerance to currently used fungicides has stimulated the development of novel and effective technologies to control pathogenic fungi. Thus, the search for alternatives to control microorganisms is necessary in both, clinical and agricultural areas. Antimicrobial photodynamic treatment (APDT) is a promising alternative antifungal platform that can be used to control fungi both in mammalian hosts and in the environment. APDT is based on the use of a photosensitizer (PS) that accumulates in the target fungal cell. The exposure of the PS to light of an appropriate wavelength starts a photochemical process that produces reactive oxygen species (ROS), especially singlet oxygen, leading to non-specific oxidative damage causing the death of the fungal cell without significant harm to the host cells. In comparison with currently used fungicides, the multiple and variable targets of ROS reduce the chance of selecting tolerant microorganisms. In the present study, we evaluated the effect of APDT with the combination of red light with fluence of 10 and 15 J cm-2, and five phenotiazinium photosensitizer, methylene blue (MB), toluidine blue O (TBO), new methylene blue N zinc free form (NMBN), new methylene blue N zinc chloride double salt (NMBN Zn) and a novel pentacyclic phenothiazinium S137, on ungerminated and germinated microconidia of Fusarium oxysporum, F. moniliforme and F. solani. APDT with NMBN Zn resulted in a reduction of approximately 5 logs in the survival of the quiescent ungerminated microconidia and metabolically active germinated microconidia of the three Fusarium species when the light fluence of 15 J cm-2 was applied. Washing out the PS from both ungerminated and germinated microconidia before light exposure reduced but did not prevent the killing effect of APDT. APDT with all the PS and fluences increased cell membrane permeability for the three Fusarium species. The oxidative damage caused by ROS produced during the photochemical process of APDT, was evaluated in the lipids, proteins and DNA present in the microconidia. Increases in lipid peroxidation in microconidia of the three Fusarium species were observed only after APDT with NMBN Zn and S137. Proteins oxidative damage was observed by the increase in protein carbonylation in microconidia of the F. oxysporum after APDT with all PS. The increases in DNA damage from both ungerminated and germinated microconidia was observed only for S137 at fluence of 0, 10 and 15 J cm-2. Our study expands the understanding of photodynamic inactivation in filamentous fungi

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Menezes, Henrique Dantas de. "Inativação fotodinâmica de conídios dos fungos Aspergillus nidulans, Colletotrichum acutatum e Colletotrichum gloeosporioides com fotossensibilizadores fenotiazínicos e cumarínicos." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-26102012-154056/.

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O tratamento fotodinâmico antifúngico (APDT) é um método promissor que combina um fotossensibilizador não tóxico (FS), oxigênio e luz visível para provocar a morte seletiva das células microbianas. O desenvolvimento do APDT depende da identificação de FS que sejam eficazes para as diferentes espécies de patógenos. No presente estudo, as suscetibilidades, in vitro, de conídios de Colletotrichum acutatum, C. gloeosporioides (ambas são espécies fitopatogênicas) e Aspergillus nidulans ao APDT com quatro FS fenotiazínicos [azul de metileno (MB), novo azul de metileno N (NMBN), azul de toluidina O (TBO) e o novo fenotiazínico pentacíclico S137 (S137)] em combinação com a luz vermelha, foram investigadas. Nós também avaliamos a suscetibilidade dos conídios de C. acutatum e A. nidulans ao APDT com o psoraleno 8-metóxipsoraleno (8-MOP), com duas cumarinas (7- metoxicumarina e 5,7-dimetóxicumarina) e com uma furanocumarina (isopimpinelina) em combinação com a radiação solar. Ambas as cumarinas e a furanocumarinas foram extraídas, no presente trabalho, do limão Tahiti (Citrus latifolia). Os efeitos dos tratamentos com os diferentes FS nas folhas de laranja-pera (Citrus sinensis) também foram avaliados. O NMBN e o S137 foram os fenotiazínicos mais eficazes. Os APDT com o NMBN (50 ?M) e S137 (10 ?M) e dose de luz de 25 J cm-2 resultaram na redução de aproximadamente 5 logs na sobrevivência dos conídios das três espécies. O APDT com o 8-MOP e com as cumarinas resultaram em uma redução de aproximadamente 4 logs na sobrevivência dos conídios de C. acutatum e A. nidulans. O APDT com a furanocumarina foi menos efetivo e resultou em uma redução na sobrevivência dos conídios de aproximadamente dois logs para C. acutatum e de três logs para A. nidulans. Nenhum dano nas folhas foi observado quando os FS foram colocados na superfície adaxial das folhas. Os estudos histológicos mostraram que nenhum dos FS fenotiazínicos atravessou a cutícula das folhas.
Antifungal photodynamic treatment (APDT) is a promising method that combines a nontoxic photosensitizer (PS), oxygen and visible light to cause selective killing of microbial cells. The development of APDT depends on identifying effective PS for the different pathogenic species. In the present study, the in vitro susceptibilities of Colletotrichum acutatum, C. gloeosporioides (both are phytophatogenic species) and Aspergillus nidulans conidia to APDT with four phenothiazinium PS [methylene blue (MB), new methylene blue N (NMBN), toluidine blue O (TBO) and the novel pentacicyclic phenothiazinium S137 (S137)] in combination with red light were investigated. We also evaluated the susceptibilities of C. acutatum and A. nidulans conidia to APDT with the psoralen 8-methoxypsoralen (8-MOP), with two coumarins (7-methoxicoumarin and 5,7-dimethoxycoumarin) and one furanocoumarin (isopimpinelin) in combination with solar radiation. Both the coumarins and the furanocoumarin were extracted, in the present work, from Tahiti lemon (Citrus latifolia). The effects of the treatments with all the PS on Citrus sinensis leaves were also evaluated. NMBN and S137 were the more effective phenothiazinium PS. APDT with NMBN (50 ?M) and S137 (10 ?M) and light dose of 25 J cm-2 resulted in a reduction of approximately 5 logs in the survival of the conidia of the three species. APDT with 8-MOP and with the coumarins resulted in a reduction of approximately 4 logs in the survival of C. acutatum and A. nidulans conidia. APDT with the furanocumarin was less effective and resulted in the reduction of approximately 2 logs for C. acutatum and 3 logs for A. nidulans. No damages to the leaves were observed when the PS were spotted on the adaxial surface of the leaves and the plants were exposed to solar radiation. Histological studies showed that the phenothiazinium PS did not cross the leave cuticle.

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PIRANI, VITTORIO. "Terapia combinata nella gestione delle complicanze in dome-shaped macula: esperienza della clinica oculistica di Ancona." Doctoral thesis, Università Politecnica delle Marche, 2020. http://hdl.handle.net/11566/273673.

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Obiettivo: valutare la variazione di spessore retinico maculare dopo trattamento combinato: fotodinamica (pdt) e laser giallo sotto soglia micropulsato nei pazienti con distacco sieroso del neuroepitelio (DNE) secondario a “dome shaped “refrattari a light fotodinamica(PDT), sicurezza ed efficacia di tali trattamenti. materiali e metodi: pazienti con diagnosi di DNE secondaria a dome shaped macula trattati presso la Clinica Oculistica di Ancona. Tutti i pazienti sono stati sottoposti a visita oculistica ,retinografia , autofluorescenza retinica,fluorangiografia (fag), esame al verde indocianina(icga),sd-oct,EDI-oct. 11 occhi miopi di 11 pazienti 8 di sesso femminile e 3 maschile con un’età media di 48 anni già sottoposti, almeno nei 3 mesi antecedenti, a light PDT e scarsamente responsivi a tale terapia sono stati oggetto di studio. Tutti i pazienti sono stati sottoposti a light PDT ICGA-guidata e dopo 2 settimane ad una seduta di laser giallo micropulsato sottosoglia 577. Risultati: alll’ultimo follow-up si mostravano uno spessore coroideale medio pari a 183.3μm (SD 75 .41μm) e uno spessore retinico foveale pari a 271.8μm (SD 64.19μm). Sono stati considerati responders i pazienti che mostravano una riduzione del DSNF > 30% rispetto al baseline. I responders al follow-up dei 6 mesi risultavano essere 5 occhi di 5 pazienti, con risoluzione del distacco sieroso in 2 occhi già rilevabile all’OCT eseguito alla visita di follow-up dei 3 mesi. Per quanto concerne l’acuità visiva in 6 occhi si è riscontrato un aumento di almeno 2 linee della BCVA, nessun peggioramento della BCVA né un aumento dello spessore retinico foveale è stato osservato Conclusioni:. Nel nostro studio abbiamo utilizzato la “combo therapy” ,PDT con effetto angio- occlusivo coroideale e laser giallo 577 micropulsato sottosoglia volto a stimolare l’attività di pompa dell’EPR i quali sembrano avere un effetto sinergico su due vie eziopatogenetiche alla base del distacco sieroso in dome shaped macula. Tale approccio si è rivelato sicuro nei pazienti presi in esame in quanto nessun paziente ha mostrato un peggioramento della BCVA né un aumento del DSNF né comparsa di neovascolarizzazione coroideale.
Purpose: the aim of the present study is to report on the results obtained in a pilot study with a combined treatment of half-fluence half-dose photodynamic therapy (PDT) and subthreshold 577 nm micropulse laser treatment (STLT) for SRD(sub retinal detachment) related to DSM(dome shaped macula) poorly responsive to previous LIGHT-PDT: Efficacy and Safety. Methods : 11 Patients (8 females and 3 males) referred to the Department of Ophthalmology of University Politecnica delle Marche with the diagnosis of symptomatic DSM were prospectively enrolled in the study. Inclusion criteria included the diagnosis of symptomatic DSM, associated with SRD; DSM was regarded as symptomatic whenever associated with visual acuity deterioration and distortion. DSM definition was based on the OCT identification of an inward bulge inside the chorioretinal posterior concavity of the macular area, according to Gaucher’s description. Patients who had undergone any previous treatment in the last 3 months or were affected by any other ocular disease were excluded from the study.Each patient underwent a complete ophthalmologic examination, including best-corrected visual acuity(BCVA) on standard Early Treatment Diabetic Retinopathy Study (ETDRS) charts, blue-light fundus autofluorescence, fluorescein angiography ( FA), indocyanine green angiography (ICGA), OCT and OCT Angiography (OCTA). The patients were regularly scheduled. Each patient was first treated with half-fluence half-dose photodynamic therapy; after two weeks subthreshold 577 nm micropulse laser treatment was performed. Results :Overall, 11 eyes of 11 patients were included in the study. Subfoveal choroidal thickness was 183μm(SD 75.41μm ) and mean Central foveal thickness was 271.8μm (SD 64.19μm) to the last follow-up.Half-fluence half-dose photodynamic therapy and subthreshold micropulse laser treatment were uneventfully performed in all the cases, and were addressed to the ICGA- detected hyperfluorescent area. Serous retinal detachment diminished in all cases, and 5 eyes registered complete resolution at the end of the 6 month follow-up. No case showed enlargement of atrophic alterations, as assessed on blue-light fundus autofluorescence, or development of choroidal neovascularization at the end of the follow-up.Conclusions :a multimodal imaging evaluation is mandatory in order to better evaluate the patient with dome-shaped macula and its complications and to choose the best treatment in each case. To date, there is no validated therapy leading to DSM-related SRD resolution. Many different therapeutic approaches to SRD secondary to DSM have been attempted, with variable results.A combined treatment PDT and subthreshold 577 nm micropulse laser, with different therapeutic targets, has not been evaluated yet. In our experience, “combo therapy” can be considered an effective and safe therapy in the treatment of SRD secondary to DSM.

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Tsao, Max. "Synthesis and Characterization of Novel Ru(II) Dipyrrin Complexes for Use as Photodynamic Therapy Agents in Cancer Treatments." University of Dayton / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=dayton156155545171778.

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N'diaye, Marline. "Formulation de liponanoparticules pour le traitement du rétinoblastome par bithérapie chimio/photodynamique." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS572.

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Le rétinoblastome est une tumeur maligne de la rétine qui touche essentiellement les nourrissons et jeunes enfants. Sa prise en charge est associée à la survenue d’effets secondaires sévères, certains traitements induisant le développement de tumeurs secondaires. Dans ce contexte, la thérapie photodynamique (PDT) apparaît comme une alternative prometteuse, car elle est non mutagène et génère des effets secondaires moins importants. Elle consiste à injecter un agent photosensibilisateur (PS) - une porphyrine par exemple – puis à illuminer la zone tumorale avec un laser. L'efficacité de la PDT nécessite l'accumulation de PS dans la tumeur. Cependant, la plupart des porphyrines sont hydrophobes et s'agrègent en milieu aqueux. Leur incorporation dans un nano-vecteur peut améliorer leur distribution au cytoplasme. Malheureusement, lorsqu'elles sont encapsulées dans le cœur des nanoparticules, les molécules de PS perdent leur phototoxicité en raison de leur auto-extinction. Dans ce travail, nous avons conçu des lipo-nanoparticules biodégradables (LNP) constituées d'une nanoparticule (NP) de poly (D,L)-lactide (PLA) recouverte d'une bicouche de phospholipides (POPC-DOTAP). Un principe actif anticancéreux, la bêta-lapachone et un agent photosensibilisateur ont ensuite été co-encapsulés dans notre système en vue de favoriser un effet synergique sur le rétinoblastome. Nous avons démontré la formation effective des LNPs et leur internalisation dans les cellules de rétinoblastome en quelques heures.Enfin, nous avons démontré une amélioration de l'activité antitumorale en combinant les deux traitement dans notre système par rapport au traitement simple par PDT ou chimiothérapie
Retinoblastoma is a malignant tumor of the retina in infants. Conventional therapies are associated to severe side effects and some of them induce secondary tumors. Therefore, photodynamic therapy (PDT) appears as a promising alternative as it is non-mutagenic and generates minimal side effects. It consists in injection of a photosensitizer (PS) like a porphyrin, and then illumination of the tumor area with a laser. The effectiveness of PDT requires the accumulation of the PS in the tumor. However, most porphyrins are hydrophobic and aggregate in aqueous medium. Their incorporation into a nanocarrier may improve their delivery to the cytoplasm. Unfortunately, when incorporated into a nanoparticle core, PS molecules lose their phototoxicity due to self-quenching. In this work, we have designed biodegradable liponanoparticles (LNPs) consisting of a poly(D,L)-lactide (PLA) nanoparticle (NP) coated with a phospholipid (POPC/DOTAP) bilayer. An anticancer drug, beta-lapachone (β-Lap), and a photosensitizer were then co-encapsulated in these LNPs for achieving synergistic effect on retinoblastoma. We have first demonstrated the effective formation of the LNPs and their internalization in retinoblastoma cells within few hours. Then we studied the cyto/phototoxicity of the system.The hybrid nanoparticles showed an improved antitumor activity when the PS and β-Lap were combined, compared to the single treatment by PDT or chemotherapy

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Carvalho, Filipa Baptista Neto Viegas de. "A terapêutica fotodinâmica nos tratamentos das lesões potencialmente malignas e cancro da cavidade oral." Master's thesis, [s.n.], 2015. http://hdl.handle.net/10284/5239.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
A terapia fotodinâmica (PDT, do inglês, photodynamic therapy) é uma opção terapêutica recente e valiosa, dirigida para a destruição das células tumorais, com potencial para ser incluída no tratamento principal de combate ao cancro, bem como adjuvante de outras terapêuticas. Atualmente é considerada uma estratégia terapêutica de sucesso, clinicamente, aprovada para o tratamento de lesões potencialmente malignas (LPM) e malignas da cavidade oral. A PDT envolve a administração de um fotossensibilizador (PS, do inglês, photosensitizer) que, por si só, não possui efeito farmacológico. Contudo, este é, posteriormente ativado por irradiação, com luz visível de comprimento de onda (λ) adequado ao local a tratar. Com a foto-ativação do PS ocorre a produção de espécies reativas de oxigénio (ROS, do inglês, reactive oxygen species) que dão inicio à morte celular. O processo está associado com a indução de uma forte reação inflamatória local, potenciando a resposta imunitária e conduzindo à destruição efetiva das células tumorais. O efeito citotóxico ocorre, apenas, no local de ativação da luz e o PS acumula-se preferencialmente nas células malignas, pelo que esta terapêutica apresenta elevada seletividade e um baixo número de efeitos secundários. No contexto clínico, a PDT é utilizada em diversas áreas da medicina como a oftalmologia, a dermatologia e a oncologia, entre outras. No entanto, a sua utilização no tratamento do cancro ainda é limitada.
Photodynamic therapy (PDT) is a new and valuable therapeutic option, directed to the destruction of tumor cells, with the potential to be included in the primary treatment to combat cancer, as well as an adjunct to other therapies. A successful therapeutic strategy, clinically approved for the treatment of premalignant lesions (LPM) and malignant oral cavity is considered currently. PDT involves the administration of a photosensitizer (PS) which, by itself, does not possess pharmacological effect. However, this is subsequently activated by irradiation with visible light of wavelength (λ) appropriate to the site to be treated. With the photo-activation of the PS occurs the production of reactive oxygen species (ROS, English, reactive oxygen species) that give beginning to cell death. The process is associated with the induction of a strong local inflammatory response, enhancing the immune response and leading to the effective destruction of tumor cells. The cytotoxic effect occurs only in the light activation site and the PS accumulates preferentially in malignant cells, whereby this treatment has high selectivity and a low number of side effects. In the clinical context, PDT is used in many areas of medicine such as ophthalmology, dermatology and oncology, among others. However, their use in cancer treatment is still limited.

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Gomes, Marisa Conceição Lima. "Susceptibility of Candida biofilms to photodynamic treatment." Master's thesis, 2015. http://hdl.handle.net/1822/41676.

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Dissertação de mestrado em Bioengenharia
In recent decades, the incidence of fungal infections caused by Candida spp. has significantly increased. C. albicans is the most important pathogen within this genus, since it is the most commonly isolated. However, other Candida species have gained importance over the last years, namely C. glabrata and C. parapsilosis. The rise of strains highly resistant to conventional antifungal treatments has increased the research for development of new effective antifungal therapies. Antimicrobial Photodynamic Therapy (APDT) has been proposed as a therapy for a large variety of localized infections. The aim of this work was to study the antifungal photodynamic effect of a new benzophenoxazine compound – FSc – on C. glabrata, C. parapsilosis and C. albicans biofilms. Biofilms were treated with different FSc concentrations (50 μM – 500 μM) for 18 h and irradiated with a xenon arc lamp (600 ± 2 nm) at various light doses (8 J cm-2 – 50 J cm-2). The efficiency of photodynamic treatment mediated by two widely used dyes – Nile blue chloride and Protoporphyrin IX – on C. albicans biofilms was also evaluated. Biofilms were incubated with 300 μM of each dye for 18 h and irradiated with a light dose of 36 J cm-2. In order to understand the oxidative stress response of Candida species to APDT, suspensions of C. albicans, C. glabrata and C. parapsilosis were incubated with 2 mM and 20 mM of two oxidant agents, hydrogen peroxide and paraquat, for 3 h. The effect of these oxidants on both cell viability and induction of antioxidant enzymes was evaluated. The photoinactivation of Candida biofilms with either FSc or PpIX as a photosensitizer was able to reduce the cell viability. On the other hand, Nile blue-mediated APDT assays showed no effect on cell viability. In general, photoinactivation of Candida cells was dependent on the dye concentration and light dose delivered. Nevertheless, irradiation with increasing light doses only resulted in a slight decrease of biofilm viability. Although the results of this study are encouraging, further investigations are needed to optimize protocols for maximal cell inactivation. Candida species showed high levels of resistance to the two oxidant agents, with the exception of C. glabrata that presented a greater sensitivity to paraquat. Generally, all Candida strains responded to hydrogen peroxide and paraquat exposure by increasing their content of catalase and superoxide dismutase, respectively. In summary, the data suggest that Candida species have different levels of resistance to oxidant agents and they use different defense mechanisms against these substances, showing differences in the induction of antioxidant enzymes.
Nas últimas décadas, a incidência de infeções fúngicas provocadas por espécies do género Candida tem aumentado significativamente. C. albicans é considerada a espécie mais patogénica dentro deste género, uma vez que é a mais comummente isolada. No entanto, nos últimos anos, outras espécies de Candida têm ganho importância, nomeadamente C. glabrata e C. parapsilosis. O aumento de estirpes altamente resistentes aos tratamentos antifúngicos convencionais tem aumentado a necessidade de desenvolvimento de novas terapias antifúngicas eficazes. A Terapia Fotodinâmica Antimicrobiana (TFDA) tem sido proposta como um tratamento para uma grande variedade de infeções localizadas. Este trabalho teve como objetivo estudar o efeito fotodinâmico de um corante pertencente ao grupo das benzofenoxazinas – FSc – em biofilmes de C. glabrata, C. parapsilosis e C. albicans. Os biofilmes foram incubados com diferentes concentrações de FSc (50 μM – 500 μM), durante 18 h, e irradiados com várias doses de luz (8 J cm-2 – 50 J cm-2), usando uma lâmpada de arco de xénon (600 ± 2 nm). Foi ainda avaliada a eficiência da TFDA com dois corantes amplamente utilizados – Azul do nilo e Protoporfirina IX – em biofilmes de C. albicans. Estes foram incubados com 300 μM de cada corante, durante 18 h, e irradiados com uma dose de luz de 36 J cm-2. De forma a compreender a resposta das espécies de Candida ao stresse oxidativo induzido pela TFDA, suspensões de C. albicans, C. glabrata e C. parapsilosis foram incubadas com 2 mM e 20 mM de dois agentes oxidantes, peróxido de hidrogénio e paraquato, durante 3 h. Determinou-se o efeito destes oxidantes na viabilidade celular e na indução de enzimas antioxidantes. Ao contrário da TFDA com Azul do nilo, a fotoinativação de biofilmes de Candida com os compostos FSc ou PpIX foi capaz de reduzir a viabilidade celular. De um modo geral, a inativação das células de Candida foi dependente da concentração de corante e da dose de luz aplicada. No entanto, a irradiação com doses crescentes de luz resultou apenas numa ligeira diminuição da viabilidade celular. Embora os resultados deste estudo sejam encorajadores, investigações posteriores são necessárias para otimizar os protocolos de modo a induzir uma maior inativação celular. As espécies de Candida apresentaram uma grande resistência aos dois agentes oxidantes, à exceção de C. glabrata que mostrou ser mais sensível ao paraquato. De um modo geral, as espécies de Candida responderam à exposição ao peróxido de hidrogénio e ao paraquato com a indução de catalase e de superóxido dismutase, respetivamente. Em suma, os resultados indicam que as espécies de Candida possuem distintos níveis de resistência aos agentes oxidantes, utilizando diferentes mecanismos de defesa contra esses mesmos compostos.

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Jamieson, Catriona Helen Macleod. "Benzoporphyrin derivative and the photodynamic extracorporeal treatment of leukemia." Thesis, 1992. http://hdl.handle.net/2429/2993.

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The main question that was addressed in this thesis was whether benzoporphyrin derivative (BPD), a potent photosensitizer, could be used to photodynamically purge residual leukemic cells from bone marrow prior to autologous bone marrow transplantation (ABMT). The ultimate aim was to design a new purging regimen that would selectively eliminate leukemic stem cells while sparing normal stem cells and thereby, provide for better engraftment and a greater log reduction in leukemic cells resulting in prolonged disease free survival or cure. Five systems were used to test this hypothesis. 1) Fluorescence activated cell sorting (FACS) analysis was used to analyze and sort normal and leukemic cells incubated with BPD, which emitted a characteristic red fluorescent signal (Chapter 2). These studies showed that BPD-uptake by leulcemic cells was significantly greater than by normal cells. Differences in BPD fluorescence between normal and leukemic cells facilitated sorting of leukemic from normal cells via FACS thus, providing a novel diagnostic method for assessing leukemic cell burden within bone marrow and possibly a new adjunct to purging regimens based on the use of small volumes of CD34+ cells that could be further purged of leukemic cells via FACS based on BPD fluorescence differences between normal and leukemic cells. 2) Clonogenic and hemopoietic progenitor cell (HPC) assays were used to assess normal or leukemic peripheral blood (PBL) or bone marrow progenitor cell survival subsequent to treatment with BPD and light (Chapters 3 and 4). Clonogenic assays revealed that approximately four logs of leukemic cells derived from the leukemic cell lines EM-2 and K562 could be eliminated at concentrations that eliminated less than one log of normal peripheral blood (PBL) progenitors. Similarly, chronic myelogenous leukemic (CML) PBL progenitors were markedly inhibited by treatment with 10 ng BPD/ml and light while, more than 70% of normal PBL progenitors survived treatment with this dose. Hence, photodynamic purging may be an effective means of eliminating leukemic progenitors from peripheral blood stem cell autogralts while maintaining the capacity of normal PBL stem cells to support engraftment in patients (Chapter 3). Similarly, a therapeutic window existed at 10 ng BPD/ml and 10.8 J/cm 2 of light between normal bone marrow (NBM) and CML bone marrow (CML BM) progenitors. 3) A primary long term marrow culture (LTMC) system demonstrated that CML primitive progenitors were substantially reduced at 10 ng BPD/ml while the majority of normal primitive bone marrow progenitors survived and normal stromal layer development was not impeded (Chapter 5). Two stage LTMC studies revealed that normal hemopoiesis persisted for 8 weeks subsequent to BPD and light treatment of model remission marrows. 4) A reverse polymerase chain reaction (PCR) system was used to detect surviving Philadelphia chromosome positive (Ph’+) cells in the supernatant of LTMCs and in plucked colonies derived from LTMC’s and HPC assays, respectively (Chapters 5). PCR analysis of model remission marrows composed of NBM and 1 % EM-2 leukemic cells revealed that all leukemic cells (four logs) were eliminated by 25 ng BPD/ml and light. Mixing experiments with NBM and 10% CML BM revealed that no Ph+ colonies persisted in 10 ng BPD/ml and light treated samples (Chapter 4). Also, two stage LTMC’s established from NBM and 10% CML BM, treated with 10 ng BPD/ml and light, and PCR analysis revealed that no Ph’ + cells survived this dose (Chapter 5). 5) A murine hemopoietic reconstitution model was established and demonstrated a four log reduction in murine leukemic (L12l0) cells at concentrations of BPD and light that spared normal marrow reconstituting stem cells in 50:50 mixtures of splenocytes and L12l0 cells (Chapter 6).

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48

Davies-Shawhyde, Nick. "Metronomic photodynamic therapy as a treatment for malignant brain tumours." 2006. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=450535&T=F.

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Lin, Chun-Wei, and 林君威. "Applicability Of Photodynamic Treatment To Inactivate White Spot Syndrome Virus." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/04178525906923928178.

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碩士
輔仁大學
生命科學系碩士班
102
White Spot Syndrome Virus (WSSV) is a serious viral disease to the shrimp culture industry. This study aims to create a powerful and energy-efficient method to inactive WSSV: Photodynamic treatment (PDT), to control the spread out of WSSV in shrimp’s culture pond. The WSSV was produced by Procambarus clarkii after muscle injection for 7 days .The energy-efficient LED and photosensitizing dyes were used in PDT for WSSV inactive. One hundred folds LD50 of WSSV were treated with PDT and injected into Litopenaeus vannamei’ muscle. The data showed the mortality rate were down from 100 to 33 % if the PDT is carry out with 160 mW /cm2 power consumed, 80 sec irradiation and 0.1 mM photosensitizing dyes. Excitingly, the mortality rate will down to zero only with the irradiate duration were increased to 100 sec. If the power consumed up to 225 mW /cm2, the mortality rate were down from 100 to 3 % with 20 sec irradiation. And the mortality rate also down to zero only if the irradiation time were up to 40 sec. Ten days after infection, the analysis of PCR for shrimp’s blood show that all of survival organisms don’t have any WSSV. On the other hands, if we take the healthy L. vannamei to carry out the PDT which could fully inactive WSSV (WPDT), results showed that the WPDT has not effect on the survival of shrimp during experiments. Under these results, we confirmed that the PDT has highly application potential to control the spread out of WSSV.

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Chen, Chao-Yu, and 陳朝煜. "Breaking the Artemia salina mediate WSSV transmission by photodynamic treatment." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/30972047581230584847.

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碩士
輔仁大學
生命科學系碩士班
104
White spot syndrome virus (WSSV) is a serious pathogen that can infect almost all crustaceans, like penaeid shrimp, lobsters, and crabs. After infection, the mortality typically reaches 100% within 3 to 10 days and caused great economic losses. The horizontal infection of WSSV may be between the penaeid shrimp by contacting or eating with the infected shrimp or ingesting some crustacea organism which carry WSSV. It was confirmed that the crustacean copepods can serve as a vector in WSSV transmission and the Marsupenaeus japonicas juvenile were infected by WSSV-positive copepods. More serious is the commercial feeding organism “Artemia cysts”, had the positive signal of WSSV with the analysis of polymerase chain reaction. The aim of this study is to develop the sterile process for removing the WSSV which was adhered by Artemia, at the same time, the mortality of artemia must be maintained. Photodynamic treatment (PDT) is the selected sterile technique, it need a specific light source for exciting the photosensitizer and produce the reactive oxygen species (ROS) to inhibit the growth of microorganisms. In the preparatory experiment, cysts of Artemia were cultured for 14 days, then incubated with crude extract of WSSV for 6 hours to confirm the WSSV carried by Artemia, after analysis by PCR. Eighty six percent of Artemia adult has positive signals. The WSSV carried percent would down to 27.78% if infected Artemia were immersed with 0.1mM photosensitizer for 1 hour. Under the irradiation with 320mW/cm2 LED (660 nm) for 60 seconds, all of positive signals of WSSV were cleared. At the same time, the survival rate of experimental artemia still above 80%. These results showed that we had created the aquacultural PDT process which can fully remove the adhered WSSV on living Artemia.

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