Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

Paraoxonase 1 (PON1) is an enzyme synthesised in the liver that is associated with High Density Lipoprotein (HDL) and increasingly with a number of human diseases, including cardiovascular disease and cancer. PON1 is (i) a lactonase, hydrolysing aliphatic and aromatic lactones, (ii) a phosphotriesterase, acting on certain organophosphates and (iii) a peroxidase that combats lipid oxidation. The aim of this study was to investigate the extent to which PON1 might impact on the levels of lactone-induced and oxidative DNA damage. Initially, the plasmid DNA (pDNA) nicking assay was used to show that of the 12 lactones and homocysteine (HC) examined, only alpha angelica lactone (AAL), Furanone (FUR) and HC caused DNA single strand breaks (SSB) under physiological conditions. Further studies indicated that AP sites were not involved suggesting that DNA-phosphotriesters were responsible. AAL-reacted pDNA bound the damage sensing protein, Atl1, and AAL, HC and HC thiolactone (HCTL) -reacted calf thymus DNA inhibited the activity of the DNA repair protein, MGMT, both indicating the presence of O6-alkylguanines in DNA, although this could not be confirmed using MALDI-ToF MS analyses of tryptic digests of MGMT incubated with lactone-reacted DNA. The inhibition of rPON1 by these lactones and HC was determined using paraoxon as a substrate and two groups were identified comprising lactones that caused reductions in PON1 activity of (i) ˃15% (e.g. HCTL, and AAL) and (ii) ˂10% (e.g. FUR, and HC). The pDNA nicking assay then showed that only AAL and FUR induced DNA single strand breaks. PON1 itself nicked pDNA, and bound to group 1 lactone-reacted pDNA by an unknown mechanism, both effects not previously reported, but, with the possible exception of AAL, did not increase the extent of plasmid nicking. The MTT, cell viability assay, indicated that all of the lactones with the exception of γ-BL (IC50 >12 mM) were to some degree toxic in HepG2 cells with AAL being the most toxic (IC50 1.0 ±0.03 mM). It was not possible to quantify PON1 activity in HepG2 cells and agents that are reported to change the expression levels of PON1 had no detectable impact on the toxicity of AAL, γ-VL, FUR or MBL, so any possible effect of PON1 could not be determined. The neutral Comet assay showed that AAL and HCTL generated the highest levels of DNA double strand breaks and DNA fragmentation in HepG2 cells, and that this effect was greatly enhanced for most of the lactones by the addition of rPON1. The impact of PON1 on oxidative stress was investigated using serum samples collected as part of a previous case-control study of lung cancer. Initially, an in-house developed ELISA assay to quantify 8-hydroxydeoxyguanosine (8-OHdG) levels had insufficient sensitivity and poor reproducibility. Hence 8OHdG levels were measured using kits along with PON1 levels and other serum parameters including HDL-C, LDL-C, TG and apoAI in serum from 112 patients with lung cancer and 249 patients without. No correlation was found between serum level of PON1 activity and level of 8-OHdG in patients with lung cancer, however a negative non-significant correlation was found between PON1 and 8-OHdG in control. The level of 8-OHdG was significantly higher in lung cancer patients than in controls and in the controls, the OGG1 wild type genotype correlated with reduced levels of 8-OHdG in serum. These studies showed that certain lactones, are toxic and DNA damaging and this can be increased by PON1, suggesting that any association between PON1 and human disease will be substrate dependent and may be PON1 genotype-dependent.

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Orientador: Mary Luci de Souza Queiroz / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T18:05:13Z (GMT). No. of bitstreams: 1 Constantino_AndersonThiago_M.pdf: 315170 bytes, checksum: 7e3457066496dcfe611cc5e368b31aeb (MD5) Previous issue date: 2009 / Resumo: As propriedades imunomoduladoras do extrato seco da raiz de Angelica sinensis Diels (EAS) foram avaliadas em camundongos Balb-c machos utilizandose o modelo de infecção por Listeria monocytogenes. Administrou-se profilaticamente doses de 10, 25, 50 e 100mg/Kg de EAS durante 10 dias. As doses de 10, 25 e 50mg/Kg protegeram os camundongos contra uma dose letal de Listeria monocytogenes observando-se uma taxa de sobrevida de 10%, 20% e 30%, respectivamente. Essas doses também impediram a mielossupressão e a esplenomegalia frente a uma dose subletal de Listeria monocytogenes aumentando de forma significativa o número de progenitores de macrófagos e granulócitos (CFU-GM) na medula óssea. A investigação da atividade dos fatores estimuladores de colônia (CSF) demonstrou aumento na atividade estimuladora de colônia no soro (CSA) de animais pré-tratados com EAS. Curiosamente, não se observou efeitos com a dose 100 mg/kg, em comparação com controles infectados não tratados, sugerindo estimulação dose-dependente da mielopoiese e CSA, onde a dose biológica ativa ótima foi a de 50 mg / kg. Esta dose foi utilizada nos experimentos para investigar os níveis de INF-y e TNF-a. Observou-se aumento nos níveis de INF-y e TNF-a em culturas de macrófagos esplênicos de animais tratados com EAS, sugerindo aumento na atividade microbicida de macrófagos. Estes resultados sugerem que EAS modula a atividade imune de forma indireta e provavelmente inibe a atividade supressora da LM por induzir um aumento na reserva de progenitores mielóide da medula óssea em conseqüência de uma liberação ativa de citocinas (CFS, INF-y e TNF-a). / Abstract: The immunomodulatory properties of dry extract of the roots of Angelica sinensis Diels (ASE) were evaluated in Male BALB/c mice using the model of infection with Listeria monocytogenes. Prophylactic administration of ASE (10, 25, 50 and 100 mg/kg) stimulated marrow myelopoiesis in a dose-dependent manner and reduced spleen colony formation to control values. Evaluation of the colonystimulating factors (CSF) showed an increase in the colony-stimulating activity (CSA) in the serum of animals pre-treated with ASE. Interestingly, no effects were observed with the 100 mg/Kg dose, compared with infected non-treated controls, suggesting a stimulation of myelopoiesis and CSA occurred in a dose-dependent manner, with a peak being reached with dose of 50 mg/kg. This dose was used to investigate levels of INF-y and TNF-a. There was an increase in the levels of INF-y and TNF-a in culture of splenic macrophages from animals treated with ASE, and this result points to increased microbicide activity of macrophages. All together, the results suggest that the ASE indirectly modulates the immune activity and probably disengages LM-induced suppression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CFS, INF-y and TNF-a). / Mestrado / Farmacologia / Mestre em Farmacologia

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Master of Music / Department of Music, Theatre, and Dance / Patricia Thompson / The purpose of this graduate report is to explore the influential stories and historical aspects behind the composition of selected works from the soprano repertoire. This document is completed in partial fulfillment of the requirements for the Master of Music degree in vocal performance. The recital was held on Sunday, April 29, 2018, at seven-thirty o’clock in the evening at the First Presbyterian Church, located on 801 Leavenworth Street in Manhattan, KS. Works for this recital were chosen to create a contrasting and unique program to span the soprano repertoire from the Baroque era to late twentieth century, and to display the histories and influences of these compositions. The following works are examined in detail within this document: 1. “Komm in mein Herzenhaus” from Ein’ feste Burg ist unser Gott, BWV 80, by Johann Sebastian Bach 2. “On mighty pens” from The Creation by Franz Joseph Haydn 3. Fêtes galantes I (1882) by Claude Debussy 1. “En sourdine” 2. “Fantoches” 3. “Clair de lune” 4. “Senza mama” from Suor Angelica by Giacomo Puccini 5. As it fell upon a day by Aaron Copland 6. A Letter from Sullivan Ballou by John Kander 7. “What Good Would the Moon Be?” from Street Scene by Kurt Weill 8. Les filles de Cadix by Léo Delibes Each chapter of this document is dedicated to a specific work from the program, and contains the following: 1) biographical information on the composer, 2) historical information and influences on the composition as well as from its grander counterpart if the selection is from a larger work, and 3) a textual and musical analysis of the selection.

LEGIO ANGELICA - HISTORY AND INSPIRATION FOR EDUCATION OF ALTAR BOYS. Main focus of this master thesis is on altar boys education in Legio Angelica. This association was founded in 1929 by a Benedictine priest Method Klement (1889-1979). It existed until 1948 and gave a number of personalities to the Church in Czechoslovakia. First the thesis briefly describes liturgical and scout movement, which had a significant impact on the organization. Furthermore it presents: the history of Legio Angelica with regard to the life stories of its directors, the functioning of the association, the magazine Legio Angelica (which is the main source of the work) and other themes from the associations history. The principal part of the thesis are the third chapter which reflects the educational objectives in Legio Angelica and the fourth chapter that deals with the particular tools of this education. Eventually the author returns to the scouting which has turned into interesting enrichment of the association. Keywords Legio Angelica, Fr. Method Klement, altar boys, education, catholic scouting

[pt] Este trabalho realiza a tradução para o português de Esta breve tragedia de la carne, obra da dramaturga, atriz e diretora de teatro espanhola Angélica Liddell (n. 1966). Ao mesmo tempo, tomando como objeto da tradução um texto de performance teatral, procura contribuir com discussões recentes no campo dos Estudos da Tradução a respeito das relações entre tradução e performance, como as que se veem, com interesses variados, em trabalhos de Guilherme Gontijo Flores, Rodrigo Tadeu Gonçalves, Álvaro Faleiros e Helena Martins, entre outros. Posicionando-se diante dessas discussões, o trabalho assume para Esta breve tragedia de la carne três paradigmas básicos de leitura. O primeiro é o de que a identidade do texto é dada pela relação que se estabelece entre o texto e o tradutor; o segundo é o de que esse texto corresponde a um certo conjunto de performances dele mesmo, e não somente ao original tomado como fato estático, e que é esse conjunto, e não o original, o objeto da tradução, enquanto por outro lado a tradução também se apresenta como mais uma performance que participa do conjunto; o terceiro é o de que a leitura de Esta breve tragedia de la carne provoca ações, ou tarefas, e de que essas ações tornam possível observar no texto um modo específico de conflito entre corpo e palavra que estrutura a sua performatividade. A dissertação, então, acontece em três movimentos. O primeiro consiste em enunciar um conjunto de performances que compõem o texto de Esta breve tragedia de la carne. Nesse conjunto incluem-se apresentações da obra e da ética de Angélica Liddell, bem como um mapeamento de sua recepção no Brasil e uma descrição da encenação da própria Liddell para Esta breve tragedia de la carne, em 2015. O segundo movimento consiste na realização de três traduções de Esta breve tragedia de la carne para o português, cada qual orientada por um distinto programa performativo, procedimento composicional concebido por Eleonora Fabião. O terceiro e último movimento é um ensaio teórico que, traçando um diálogo entre dimensões performativas da tradução e a tradição tradutória legada por Haroldo e Augusto de Campos, oferece uma análise do experimento de tradução realizado no trabalho e procura articulá-lo a práticas mais amplas de tradução no Brasil. / [en] This study offers a translation into portuguese of Esta breve tragedia de la carne, a work by Spanish writer, actress, and theatre director Angélica Liddell (b. 1966). By taking a text which was given for theatrical performance as an object of translation, it seeks at the same time to contribute to recent debates on Translation Studies regarding relations between translation and performance, such as those put forward, with diverse interests, in works by Guilherme Gontijo Flores, Rodrigo Tadeu Gonçalves, Álvaro Faleiros, and Helena Martins, amongst others. In joining these debates, this study reads Esta breve tragedia de la carne in accordance with three basic paradigms. The first one is that the text s identity is given by the relation established between text and translator; the second is that this text is taken not as a static original but as a certain number of performances of itself, the object of translation being these performances, which include its translations; the third paradigm is that the reading of Esta breve tragedia de la carne basically prompts actions, or tasks, and that these actions show a specific conflict between word and body that structures the text s performance. This study, then, is set forth in three movements. The first consists in enunciating a set of performances that make up Esta breve tragedia de la carne s text. This set includes materializations of Angélica Liddell s work and ethics, as well as a mapping of her reception in Brazil and a description of her own staging of Esta breve tragedia de la carne, in 2015. The second movement consists in the execution of three distinct translations into portuguese of Esta breve tragedia de la carne, each oriented by a different performative program, a composing procedure devised by Brazilian performer Eleonora Fabião. The third and last movement is an essay which, while reflecting on performative dimensions of translation within the Brazilian tradition of translation studies established by Haroldo and Augusto de Campos, offers an analysis of this study s particular experiment and seeks to articulate it with broader translation practices in Brazil.

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