Orientador: Juliana Campos Junqueira / Banca: Aguinaldo Silva Garcez Segundo / Banca: Antonio Olavo Cardoso Jorge / Resumo: A terapia fotodinâmica (TFD) tem demonstrado ação antimicrobiana sobre as leveduras do gênero Candida, sendo considerada uma técnica promissora para o tratamento de candidose. Recentemente foi relatado que a aplicação de TFD também pode resultar em ativação do sistema imunológico, contribuindo para a melhora da infecção. Assim, o objetivo desse estudo foi avaliar a ação da TFD e da terapia laser sobre a resposta imunológica à candidose experimental utilizando Galleria mellonella como modelo hospedeiro de infecção. Larvas de G. mellonella foram infectadas com diferentes cepas de Candida albicans e, após 30 min, foram tratadas com TFD mediada por azul de metileno e laser diodo emitido em 660 nm. A seguir, as larvas foram incubadas a 37°C por sete dias e analisadas diariamente para determinação da curva de sobrevivência. Para o estudo da resposta imunológica, após os tempos de 3, 6, 18 h da TFD foram realizados testes de determinação da densidade de hemócitos na hemolinfa de G. mellonella. Os dados obtidos na curva de sobrevivência foram avaliados pelo teste de Log-rank (Mantel Cox) e os resultados da análise imunológica por análise de variância ANOVA e teste de Tukey, com significância de 5%. Os resultados obtidos demonstraram que tanto para a cepa ATCC 18804 como para a cepa clínica 17 de C. albicans, a TFD prolongou a sobrevivência das larvas de G. mellonella infectadas por uma dose fúngica letal. Entretanto, houve diferença estatisticamente significante e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Photodynamic therapy (PDT) has demonstrated antimicrobial activity on the yeast of the genus Candida and is considered a promising technique for the treatment of candidiasis. Recently it was reported that the application of PDT may also result in activation of the immune system, contributing to the improvement of the infection. The objective of this study is to evaluate the action of PDT and laser therapy on the immune response to experimental candidiasis using Galleria mellonella as host of the infection. G. mellonella larvae were infected with different Candida albicans strains and, after 30 min were treated with methylene blue-mediated PDT and laser diode emitted at 660 nm. Then, the larvae were incubated at 37° C for seven days and analyzed daily in order to determine the survival curve. For the study of the immunological response, after intervals of 3, 6, 18 h of the PDT, tests were performed to determine the density of hemocytes in the hemolymph of G. mellonella. The data obtained in the survival curve were evaluated by the Log-rank test (Mantel Cox) and the results of the immunological analysis by analysis of variance ANOVA and Tukey test, with significance of 5%. The results demonstrated that for both the ATCC 18804 strain and the C. albicans clinical strain 17, PDT prolonged the survival of the infected G. mellonella larvae by a lethal fungal dose. However, there was a statistically significant difference between the PDT and the control groups only... (Complete abstract click electronic access below) / Mestre

Orientador: Luiz Antônio Salata / Banca: Osvaldo Magro Filho / Banca: Sérgio Luiz Scombatti Souza / Banca: Wilson Roberto Poi / Banca: Andreza Ribeiro Simioni / Resumo: A combinação de um fármaco fotossensível (FS) ativado por luz (vermelha, infravermelho ou ambas) forma uma das vertentes de aplicação da Terapia Fotodinâmica (TFD), que consiste na administração de um FS que posteriormente é ativado pela irradiação do LED ou Laser junto ao tecido, sendo que o FS ou a luz sozinhas, não apresentam citotoxicidade. O presente estudo teve por objetivos estabelecer o potencial regenerador do tecido ósseo para o reparo em calvária de coelho, utilizando três sistemas de liberação de drogas (DDS) de FS, estimulado pela combinação da fotobiomodulação de sistemas LED operando na faixa do visível e infravermelho. Foram utilizados 48 coelhos New Zealand White divididos em 3 grupos: Grupo LED 24/48 (dezoito coelhos) com aplicações de LED 24/48 horas após a cirurgia, Grupo LED 72/96 (dezoito coelhos) com aplicações de LED 72/96 horas após a cirurgia e Controle (doze coelhos) onde não houve aplicação de LED. Nos grupos experimentais foram realizadas 4 perfurações nas calvárias com preenchimento aleatoriamente de 1) Base em gel, 2) nanoemulsão carregada com FS, 3) lipossoma em gel com FS e 4) nanopartículas de albumina (BSA) carregada com FS. No grupo controle foram feitas duas perfurações, uma preenchida por osso autógeno e outra com coágulo. Dezesseis animais foram submetidos à eutanásia em cada tempo experimental: 5 dias, 10 dias e 20 dias. Lâminas histológicas foram feitas a partir dos defeitos e o osso neoformado foi mensurado. O uso de FS nos DDS não foi efetivo para abreviar o tempo de reparo ósseo em calvária de coelhos nos inervalos de tempo deste estudo / Abstract: The combination between photosensitizer substances with laser or LED (light emitting diode) form the photodynamic therapy (PDT) basis that consists of photosensitivity drug activated by low frequency light. This mechanism is used in soft tissue healing process to improve the oxygen tension leading to a fast revascularization. The objective of this study was to evaluate the effects of photosensitivity drugs activated through LED on bone healing process. Fourty eight New Zealand White rabbits were underwent to four bicortical calvaria defects made by 6.0 mm trephine drill. The defects were randomly filled up with (1) Gel, (2) Nanoemulsion + photosensitizer drug, (3) Liposome + photosensitizer drug, (4) NPS (nanostructure polymeric system) + photosensitizer drug. After 24/48 hours or 72/96 hours a LED were applied on all the rabbits. Sixteen animals were sacrificed, respectively, at 5, 10 and 20 days after surgery. Histological slides were prepared from each experimental site for histomorphometry and histological analysis. Bone graft was significant higher bone level in all experimental time points.. At 10 days liposome showed higher bone level than Gel (p=0,0161). However on 20 days, no difference was detected between the materials. The use of photosensitizer drugs activated by LED demonstrated do not achieve the stimulate bone formation on later time points on thsi presente study / Doutor

Orientador: Ana Claudia Pavarina / Resumo: O objetivo do estudo foi avaliar a eficácia da terapia fotodinâmica antimicrobiana (aPDT) associada a Nistatina (NYS) no tratamento de candidose oral induzida em camundongos infectados com Candida albicans resistente a fluconazol. Foram utilizados 174 camundongos Swiss fêmeas com aproximadamente 5 semanas de vida. Os animais foram imunossuprimidos com predinisolona 100 mg/kg no 1º, 5º e 13 º dias de experimento. No 2º dia, os animais foram sedados com 0,1 mL de cloridrato de clorpromazina e uma suspensão de C. albicans 107 UFC/mL foi inoculada na língua dos mesmos. Do dia 7 ao 11 os tratamentos foram realizados. No grupo aPDT foi utilizado 200 mg/L de Photodithazine (PDZ) associado à luz LED de 50 J/cm2 (grupo P+L+); no grupo (P+L-) foi utilizado apenas com PDZ; o grupo (P-L+) recebeu só luz LED e nos animais do grupo NYS o medicamento foi aplicado uma vez ao dia. Além disso, foi avaliada a combinação de duas terapias: P+L+NYS e NYS+P+L+. Um grupo recebeu apenas inoculação de C. albicans (grupo P-L-) e outro grupo de animais saudáveis (grupo CNI). Após os tratamentos, foi realizada a recuperação de C. albicans por meio de swabs estéreis. Então diluições seriadas foram realizadas e plaqueadas em placas de Petri com SDA. Após 48 horas de incubação a 37o C as colônias foram quantificadas e o número de UFC/mL foi determinado. Os camundongos foram sacrificados 24 horas e 7 dias após os tratamentos. Os resultados demonstraram que a combinação das terapias promoveu redução de 2,6 lo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of the present study was to evaluate of PDZ-mediated aPDT, as well as the association of this approach with antifungal nystatin, would be effective to treat oral candidosis in mice infected with fluconazole resistant C. albicans. Were used 174 female Swiss mice of 5 weeks-old-age approximately. The animals were immunosuppressed with predinisolone 100 mg/kg on the 1st, 5th and 13th days of the experiment. On day 2, the animals were sedated with 0.1 mL of chlorpromazine hydrochloride and a suspension of C. albicans 107 CFU/mL was inoculated into the tongue. From 7 to 11 the treatments were performed. In the aPDT group, was used 200 mg/L of Photodithazine (PDZ) associated with 50 J /cm2 LED light (P+L+ group). In the (P+L-) group was used only with PDZ; the group (P-L+) received only LED light and in the animals of the NYS group the drug was applied once a day. In addition, we evaluated the combination of two therapies: P+L+NYS and NYS+P+L+. One group received only inoculation of C. albicans (P-L- group) and another group of healthy animals (CNI group). After the treatments, recovery of C. albicans was performed by sterile swabs, then serial dilutions were performed and plated on Petri dishes with SDA. After 48 hours incubation at 37 °C the colonies were quantified, and the number of CFU/mL was determined. Mice were sacrificed 24 hours and 7 days after the treatments. The results showed that the combination of the therapies promoted reduction of 2.6 log10 and 2.1 log10 f... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:31:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T19:20:06Z : No. of bitstreams: 1 faria_pep_dr_araca.pdf: 1244848 bytes, checksum: 1c3d78205883be40533349acdfc5ffde (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A combinação de um fármaco fotossensível (FS) ativado por luz (vermelha, infravermelho ou ambas) forma uma das vertentes de aplicação da Terapia Fotodinâmica (TFD), que consiste na administração de um FS que posteriormente é ativado pela irradiação do LED ou Laser junto ao tecido, sendo que o FS ou a luz sozinhas, não apresentam citotoxicidade. O presente estudo teve por objetivos estabelecer o potencial regenerador do tecido ósseo para o reparo em calvária de coelho, utilizando três sistemas de liberação de drogas (DDS) de FS, estimulado pela combinação da fotobiomodulação de sistemas LED operando na faixa do visível e infravermelho. Foram utilizados 48 coelhos New Zealand White divididos em 3 grupos: Grupo LED 24/48 (dezoito coelhos) com aplicações de LED 24/48 horas após a cirurgia, Grupo LED 72/96 (dezoito coelhos) com aplicações de LED 72/96 horas após a cirurgia e Controle (doze coelhos) onde não houve aplicação de LED. Nos grupos experimentais foram realizadas 4 perfurações nas calvárias com preenchimento aleatoriamente de 1) Base em gel, 2) nanoemulsão carregada com FS, 3) lipossoma em gel com FS e 4) nanopartículas de albumina (BSA) carregada com FS. No grupo controle foram feitas duas perfurações, uma preenchida por osso autógeno e outra com coágulo. Dezesseis animais foram submetidos à eutanásia em cada tempo experimental: 5 dias, 10 dias e 20 dias. Lâminas histológicas foram feitas a partir dos defeitos e o osso neoformado foi mensurado. O uso de FS nos DDS não foi efetivo para abreviar o tempo de reparo ósseo em calvária de coelhos nos inervalos de tempo deste estudo / The combination between photosensitizer substances with laser or LED (light emitting diode) form the photodynamic therapy (PDT) basis that consists of photosensitivity drug activated by low frequency light. This mechanism is used in soft tissue healing process to improve the oxygen tension leading to a fast revascularization. The objective of this study was to evaluate the effects of photosensitivity drugs activated through LED on bone healing process. Fourty eight New Zealand White rabbits were underwent to four bicortical calvaria defects made by 6.0 mm trephine drill. The defects were randomly filled up with (1) Gel, (2) Nanoemulsion + photosensitizer drug, (3) Liposome + photosensitizer drug, (4) NPS (nanostructure polymeric system) + photosensitizer drug. After 24/48 hours or 72/96 hours a LED were applied on all the rabbits. Sixteen animals were sacrificed, respectively, at 5, 10 and 20 days after surgery. Histological slides were prepared from each experimental site for histomorphometry and histological analysis. Bone graft was significant higher bone level in all experimental time points.. At 10 days liposome showed higher bone level than Gel (p=0,0161). However on 20 days, no difference was detected between the materials. The use of photosensitizer drugs activated by LED demonstrated do not achieve the stimulate bone formation on later time points on thsi presente study

At the end of this thesis, 1H and 13C{ 1H} NMR spectra for all the new compounds and the crystallographic details for the X-ray structure are given as Appendices. / Chapter 1 presents an overview of photodynamic therapy, including its historical development, photophysial and biological mechanisms, and current clinical situation. A brief review of second-generation photosensitizers and the different approaches for targeted photodynamic therapy are also given. / Chapter 2 reports the synthesis and characterization of a silicon(IV) phthalocyanine which is substituted axially with two diamino moieties, together with its di- and tetramethylated derivatives. The non-methylated analogue shows a high photocytotoxicity toward HT29 human colorectal adenocarcinoma and HepG2 human hepatocarcinoma cells with IC50 values down to 0.01 muM. Interestingly, this compound also exhibits a pH-dependent behavior. The fluorescence quantum yield increases by four folds and the singlet oxygen quantum yield increases by three folds in water when the pH decreases from 7.0 to 5.0. The preliminary results suggest that this compound is a promising photosensitizer of which the photodynamic activity can be modulated by changing the pH of the environment. Furthermore, this compound can be used as a near-infrared fluorescence probe for optical imaging of intracellular acidic level. / Chapter 3 reports a novel series of aminophenyl-substituted silicon(IV) phthalocyanines. The aminophenyl moieties in these conjugates can also modulate the photophysical and photosensitizing properties of the phthalocyanine core through changing the pH of the environment. These phthalocyanines exhibit a low photocytotoxicity under physiological conditions (pH 7.4). It is likely that the amino groups, in the free amine form, can quench the singlet excited state of phthalocyanine by a photoinduced electron transfer (PET) mechanism, and reduce the chance of intersystem crossing and the efficiency in generating singlet oxygen. The strong aggregation tendency of these compounds in this pH environment is another major reason for the low photocytotoxicity. When the pH is lower to 6.4-6.9, the amino groups are protonated so that they are no longer electron donors, and the compounds become less aggregated. These changes lead to an increase in photocytotoxicity. The results of this study are reported in this Chapter. / Chapter 4 describes a new series of silicon(IV) phthalocyanines conjugated axially with various polyamine derivatives. Polyamines are naturally occurring compounds which are involved in a number of cell processes including cell proliferation and differentiation. Their biosynthetic activity and polyamine levels in some tumor cells are significantly higher than those in normal cells. Conjugation of polyamine analogues is therefore one of the promising approaches to improve the tumor-targeting property of photosensitizers. This Chapter describes the synthesis, spectroscopic characterization, and photophysical properties of these compounds. Their photodynamic activities toward HT29 and Chinese hamster ovary (CHO) cells have also been studied in detail. Their cellular uptake, subcellular localization, cell death mechanism, and in vivo photocytotoxicity have also been studied. / In Chapter 5, we report a series of silicon(IV) phthalocyanines containing one or two cholesterol unit(s) at the axial position(s), including their synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities. These cholesterol-containing photosensitizers can form stable conjugates with low-density lipoprotein (LDL), which is the major lipoprotein carrier for cholesterol in human plasma. On the basis that cancer cells generally express significantly more LDL receptors than normal cells, these cholesterol-conjugated phthalocyanines are designed with a view to enhancing their selectivity toward tumor. Unfortunately, conjugation of cholesterol reduces the photodynamic activity of the silicon(IV) phthalocyanines as a result of their higher aggregation tendency. / This thesis reports the synthesis, spectroscopic characterization, and photophysical and biological properties of several series of novel silicon(IV) phthalocyanines which are specially designed as efficient and selective photosensitizers for photodynamic therapy. / Jiang, Xiongjie. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references and index. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Lau, Ting Fong Janet. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references. / Abstracts in English and Chinese. / Abstract --- p.iii / Abstract (in Chinese) --- p.v / Acknowledgment --- p.vii / Table of Contents --- p.ix / List of Figures --- p.xiii / List of Tables --- p.xix / List of Schemes --- p.xxi / Abbreviations --- p.xxiii / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- General --- p.1 / Chapter 1.1.1 --- History of Phthalocyanines --- p.1 / Chapter 1.1.2 --- General Synthesis --- p.2 / Chapter 1.1.3 --- Properties and Usage of Phthalocyanines --- p.8 / Chapter 1.2 --- Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy --- p.9 / Chapter 1.2.1 --- Photophysical and Biological Mechanisms of Photodynamic Therapy --- p.10 / Chapter 1.2.2 --- Photosensitizers in Photodynamic Therapy --- p.13 / Chapter 1.2.2.1 --- First-Generation Photosensitizers --- p.13 / Chapter 1.2.2.2 --- Second-Generation Photosensitizers --- p.16 / Chapter 1.2.2.3 --- Phthalocyanine-Based Photosensitizers --- p.20 / Chapter 1.3 --- An Introduction on Supramolecular Chemistry --- p.27 / Chapter 1.3.1 --- Phthalocyanine-Based Supramolecular Systems --- p.28 / Chapter 1.3.2 --- Mixed Porphyrin-Phthalocyanine Supramolecular Assemblies --- p.31 / Chapter 1.4 --- Cyclodextrins as Building Blocks for Supramolecular Structures --- p.38 / Chapter 1.4.1 --- Background of Cyclodextrins --- p.38 / Chapter 1.4.2 --- Phthalocyanine-Cyclodextrin Supramolecular Systems --- p.41 / Chapter 1.5 --- Objectives of This Study --- p.47 / Chapter 1.6 --- References --- p.47 / Chapter Chapter 2 --- Permethylated β-Cyclodextrin Disubstituted Silicon(IV) Phthalocyanines / Chapter 2.1 --- Introduction --- p.55 / Chapter 2.2 --- Results and Discussion --- p.57 / Chapter 2.2.1 --- Preparation and Characterization --- p.57 / Chapter 2.2.2 --- Electronic Absorption and Photophysical Properties --- p.62 / Chapter 2.2.3 --- In vitro Photodynamic Activities --- p.66 / Chapter 2.3 --- Conclusion --- p.73 / Chapter 2.4 --- Experimental Section --- p.73 / Chapter 2.4.1 --- General --- p.73 / Chapter 2.4.2 --- Photophysical Measurements --- p.74 / Chapter 2.4.3 --- Synthesis --- p.75 / Chapter 2.4.4 --- Cell Lines and Culture Conditions --- p.83 / Chapter 2.4.5 --- Photocytotoxicity Assay --- p.83 / Chapter 2.4.6 --- ROS Measurements --- p.84 / Chapter 2.4.7 --- Microscopic Studies --- p.85 / Chapter 2.4.8 --- Subcellular Localization Studies --- p.85 / Chapter 2.5 --- References --- p.86 / Chapter Chapter 3 --- Unsymmetrically Substituted β-Cyclodextrin-Appended Silicon(IV) Phthalocyanines / Chapter 3.1 --- Introduction --- p.89 / Chapter 3.2 --- Results and Discussion --- p.90 / Chapter 3.2.1 --- Preparation and Characterization --- p.90 / Chapter 3.2.2 --- Electronic Absorption and Photophysical Properties --- p.94 / Chapter 3.2.3 --- In vitro Photodynamic Activities --- p.98 / Chapter 3.3 --- Conclusion --- p.107 / Chapter 3.4 --- Future Work --- p.108 / Chapter 3.5 --- Experimental Section --- p.108 / Chapter 3.5.1 --- General --- p.108 / Chapter 3.5.2 --- Synthesis --- p.109 / Chapter 3.6 --- References --- p.114 / Chapter Chapter 4 --- Construction of Mixed Phthalocyanine-Porphyrin Systems through Host-Guest Interactions in Aqueous Media / Chapter 4.1 --- Introduction --- p.117 / Chapter 4.2 --- Results and Discussion --- p.119 / Chapter 4.3 --- Conclusion --- p.132 / Chapter 4.4 --- Experimental Section --- p.132 / Chapter 4.5 --- References --- p.133 / Appendix A Determination of Binding Constants --- p.135 / Appendix B 1H and 13C{1H} NMR Spectra --- p.137 / Appendix C Mass Spectra --- p.151

Thesis (Ph.D.) OGI School of Science & Engineering at OHSU, March 2008. / Includes bibliographical references (leaves 105 - 114).

Thesis (M.S.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 57-62).

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xviii, 160 p.; also includes graphics Includes bibliographical references (p. 117-120). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 164-182).