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published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Colorectal cancer is the second leading cause of cancer-related mortality in Hong Kong and lack of selectivity has limited the success of conventional chemotherapy. Given the recent interest in the anti-cancer effects of traditional Chinese medicine (TCM), there are two approaches to studying its bioactivity: as a mixture of ingredients or as single compounds. The objective of the present study is to examine the anti-tumor effects of Angelicae Sinensis Radix (DG) and Garcinia hanburyi resin (TH) using both approaches, respectively, as they are traditionally used to treat inflammation. In the present study, their anti-cancer effects and the mechanisms of actions were examined for the development of potential novel chemotherapeutic drugs for colon cancer since inflammation is a predisposing factor for colon cancer. / DG extract and its three main bioactive phtbalides: n-butylidenephthalide, senkyunolide A and z-ligustilide (LGT), were found to be cytotoxic to HT-29 cells with IC50 values (24 h) of 20.70 +/- 0.85, 72.51 +/- 8.65, 18.74 +/- 1.14 and 41.98 +/- 3.64 mug/ml, respectively. The results evidenced that LGT induced G0/G 1 arrest and apoptosis, triggering cleavage of PARP, pro-caspases-3, -8 and -9 and nuclear fragmentation. LGT and cisplatin synergistically reduced the viability of HT-29 cells. More interestingly, DG extract was more potent than individual phthalides, suggesting that there are other bioactive components and/or synergistic interactions. / Individual compounds purified from TH were investigated because gambogic acid isolated from this herb has been used clinically to treat cancer, 30-Epicambogin (EPC) and guttiferone K (GUTK) showed the highest cytotoxic selectivity and potency on HT-29 cells among 15 isolated compounds. IC50 values (24 h) for EPC and GUTK in HT-29 cells were 5.36+/-0.25 and 5.39+/-0.22 muM, respectively, and both induced G0/G1 arrest by down-regulation of cyclins D1, D3, CDK4 and CDK6, while up-regulation of p21Waf1/CiP1 and p27KiP1. Both compounds triggered the activation of caspases-3, -8 and -9 in apoptosis. The in vivo anti-tumor effects of GUTK were further investigated by using a subcutaneous Colon-26 mouse tumor model. GUTK (10 mg/kg i.p.) reduced tumor volume by 33.6% and potentiated the anti-tumor effects of 5-fluorouracil when administered concurrently. / Our findings revealed that DG rather than individual phthalides, is worthy for further study as a potential anti-cancer drug, due to the synergistic interactions among multi-components in the herb. On the other hand, EPC and GUTK, isolated from TH have potential to be developed as novel anti-tumor candidates for combination use with 5-fluorouracil. The results strongly support the use of different approaches to study TCM for chemotherapy, according to its traditional and empirical use. / Subsequently, the anti-proliferative effects of DG and Chuanxiong Rhizoma (CX) extracts and mixtures containing three phthalides in the proportions similar to their presence in both extracts were examined, since CX also contains the same phthalides, but in different proportions. DG extract was significantly more potent than its corresponding phthalide mixture to inhibit cancer cell proliferation and synergistic interaction was observed among the phthalides and other bioactive components, while the phthalides in CX extract interacted antagonistically with other components. / Kan, Lai Ting Winnie. / Adviser: Ge Lin. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 267-311). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

This thesis focuses on the Summa Angelica de casibus conscientie written by Angelo da Chivasso (d. 1495), first printed in 1486. Angelo belonged to the Observantine branch of the Franciscan Order and was its vicar general four times. Having documented Angelo's life and career, the thesis centres on the construction and purpose of his Summa. It assesses its originality within the tradition of confession manuals and the reasons for its popularity. It argues that the structure is very clear because Angelo intended it for the use of simplices confessores, by which he probably meant priests who did not have a university degree. He arranged his material alphabetically and in the longer sections, paragraphs were numbered, making cross-referencing easy. He included a list of authorities and explained the manner of quoting from them. Not all these features were original, but together they helped to make the Summa popular. There are several noteworthy features of Angelo's Summa. The procedures described had been laid down in earlier manuals, including the need for more rigorous questions - ad status – relating to the profession of each penitent and where this might lead to sin. Angelo however diverged from some earlier authorities by warning about excessive rigour. Circumstances were to be taken into account, and where possible penitents to be given the benefit of the doubt. The number of copies of Angelo's Summa printed throughout Western Christendom during his lifetime and following his death are a tribute to its importance. The period of fame however, was short. Martin Luther was a particularly virulent critic of the Summa, and the Catholic Church changed the method of hearing confessions, making much of it redundant, though it survived for some centuries more as a work of reference for confessors.

I have studied the genetic variation of single species using morphological variation and enzyme electrophoresis. I have striven to understand the interaction between the breeding structure and the ecology of the species in relation to the community, in which it lives. The work was done in the county of Västerbotten, northern Sweden. In the Skeppsvik archipelago I have studied the population structure of Silene dioica: ecotypic variation in other populations. I have also studied the genetic diversity of Angelica archangelica, Bistorta vivipara, Viscaria alpina and the earthworm Eiseniella tetraedra along the free-flowing Vindel and Sävar Rivers and the regulated Urne River. The island populations of S. dioica are subdivided into several breeding units and levels of differentiation among subpopulations within islands were about twice as high as among islands. Restricted seed and pollen dispersal creates patches made up of related individuals that may diverge as a result of drift. Frequent seed and pollen dispersal occurs among islands and they will receive the same alleles. This may explain the pattern of differentiation observed. In contrast, the patches within islands may be founded by only a few individuals. * S. dioica exhibits morphological differentiation in vegetative and floral characters between serpentine, cold spring, rich forest and coastal habitats. There was no association between  genetic and geographical distance or between genetic distance and habitat. Serpentine and cold spring, which represented the most extreme habitats were also most differentiated. Populations of S. dioica are subject to herbivory; predation may exert a selective pressure on vegetative characters. A number of selective forces such as pollinators and fungal parasites act on reproductive characters. Assuming that water dispersal is important I tested several hypotheses to explain patterns of genetic diversity expected to be exhibited by riparian organisms along free-flowing and regulated rivers. I show that dispersal, distribution and breeding structure are important determinants of the evolution of the riparian flora. Patterns of genetic diversity may be exhibited at many spatial scales, e.g. among entire rivers, and between types of riverbanks within a river reach. Populations must be sampled at a spatial scale relevant to the hypothesis to be tested. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 2002, härtill 5 uppsatser.</p> / digitalisering@umu

In the exploration into new therapeutic agents for human disease, medicinal herbs offer an enormous resource due to their wide range of biologically active components. However, because of these biologically active components, medicinal herbs can also have toxic side effects. The focus of this thesis is the effect of herbal therapies, both good and bad, on chronic kidney disease (CKD) and tubulointerstitial fibrosis. Tubulointerstitial fibrosis is considered one of the defining characteristics of CKD. In Chapter 1, the literature regarding the pathogenesis of tubulointerstitial fibrosis is reviewed, beginning with the mechanisms of its development, the main structural and functional features, and the molecular mediators. The structural features include activation of resident fibroblasts and transition of tubular epithelial cells into myofibroblasts, deposition of extracellular matrix proteins, increased apoptosis of normal cells of the renal nephron and development of tubular atrophy, increased renal oxidative stress, and hypoxia of renal tissues. Molecular mediators that are explored include angiotensin II, transforming growth factor-ß1 and numerous other cytokines and growth factors. Pharmacological manipulation of these features and their molecular mediators for regression of tubulointerstitial fibrosis is then discussed. Currently, the gold standard of therapy for people with CKD is blockade of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs). Because of the complexity of the pathogenesis of renal fibrosis and the multiple mechanisms by which ACEIs and ARBs work, this portion of the thesis focuses on the qualities that additional agents should have to complement their actions. These additional agents could work by decreasing oxidative damage, by decreasing fibroblast numbers through apoptosis, through the interruption of inflammatory, fibrotic mediators, by increasing anti-inflammatory mediators or through other mechanisms. The literature review therefore continues with a discussion of the historical use of medicinal herbs in genitourinary pathologies and the known contributions that medicinal herbs can make to the treatment or development of tubulointerstitial fibrosis and CKD. From this review, a large number of herbs were identified as having traditional use in renal disorders or as being of interest, currently, to researchers of renal pathologies. However, much information is lacking regarding the mechanisms by which the hypothesised benefits occur, making it impossible to assess which herb(s) may offer valuable additive support or alternative treatments to the therapies currently given to people with CKD. Furthermore, there is a lack of information regarding toxicity of these herbs; many herbs have never been assessed in cell culture or in animal toxicity studies. It was apparent that preliminary in vitro work was necessary before in vivo pharmacological work could be undertaken. This thesis, therefore, aimed to test the following hypotheses: (1) That medicinal herbs used currently for treatment of renal dysfunction have high anti-oxidant properties that can be further enhanced by specific extraction processes; (2) That the in vitro testing of selected extracts from medicinal herbs, identified in (1), will reveal some anti-oxidant benefits or indications of toxicity that need careful analysis in animal studies; (3) That careful in vivo testing of specific toxic medicinal herbs identified in these leadup studies will define specific pathological processes that predict an outcome of CKD; and (4) That careful in vivo testing of selected medicinal herbs, used in conjunction with more conventional medicines for CKD, will show an additive benefit when used to ameliorate development of CKD induced using an established animal model. The subsequent laboratory work was designed to test the validity of these hypotheses and the results are then presented in Chapters that each comprise a publication. The aim of Chapter 2 was to present a systematic analysis of the oxidant properties of 55 medicinal herbs that have been used traditionally to treat kidney and urinary disorders or have been of recent interest to researchers of renal disorders. Since different extraction processes yield different constituents, each of the herbs was sequentially extracted with three solvents of decreasing polarity. An assay was performed on each of the fractions to determine the oxygen radical absorbance capacity. The aim of Chapter 3 was to test the benefit or otherwise of each of the three extracts of the chosen herbs using an in vitro cell study. Each extract was tested for potential toxic, apoptotic, mutagenic and antioxidant activity on normal mammalian renal tubular epithelial cells (NRK-52E). The effect of the extracts on renal fibroblasts (NRK-49F) was also analysed. Several specific hypotheses arose from the combination of the systematic analyses and the literature review regarding benefits and toxicities of a number of the extracts. The subsequent in vivo work was designed to test the validity of two of these hypotheses. The aim of Chapter 4 was to test the hypotheses developed from the results of the previous Chapter. The herb Dioscorea villosa had demonstrated extreme cytotoxicity to mammalian renal epithelial cells and had caused transdifferentiation of epithelial cells into fibroblasts. An in vivo rodent model was used to test chronic dosage with this herb and its toxicity and predisposition for induction of CKD verified. The aim of Chapter 5 was to determine whether a herbal preparation (Angelica sinensis and Astragalus membranaceus) that had some support from the literature and the results from Chapters 2 and 3, could complement the actions of ACEIs in a rodent model of renal fibrosis (unilateral ureteral obstruction). The combination of herbal medicines and the ACEI was significantly more effective than the ACEI alone in ameliorating several characteristics of CKD development. To conclude the thesis, Chapter 6 provides an overview discussion of the results and a critical analysis of the methods used. Further, Chapter 6 looks towards future experiments that are planned to further resolve issues of concern about effects on renal health from use of medicinal herbs. .

abstract: The focus of this in-depth study is to look at the gestation, performance history, and reception of Giacomo Puccini's evening of three one-act operas called Il Trittico and differentiate the particular components, Il Tabarro, Suor Angelica, and Gianni Schicchi to analyze them for their individual stylistic elements of Italian Opera. These were the styles of verismo, pathos and sentimentality, and opera buffa. As substantiated by written criticism, the audience and the critics did not fully comprehend the hidden meaning behind the individual works of Il Trittico. Puccini, enigmatically, had chosen to present one last glimpse of outmoded Italian operatic traditions. In order to evaluate Il Trittico's importance in the history of Italian opera, this study will first review the musically changing landscape in Italy during the early to mid-nineteenth century, then the second part of the nineteenth and beginning of the twentieth-century when German, French, and eventually Russian music were starting to influence audience taste. Puccini who, over the course of his compositional life, absorbed and incorporated these different styles realized that long held Italian operatic tradition had reached a fork in the road. One path would ensure Italian composers a place in this new order and the other a stagnant dead end. Even though Puccini's triptych garnered primarily negative reviews, the basis for this negativity was the perception that Il Trittico had broken with the historically traditional Italian musical styles. Though the present study acknowledges that break to a degree, it will also present a historically based rationale for the deviation, one left largely unnoticed by Puccini's critics. In the end, this author plans to realize their symbolic importance as a farewell to three uniquely Italian styles and a departure point for a new operatic tradition. Looking forward to the centenary of the work, this author seeks to illuminate how Puccini reached the pinnacle of firmly rooted genres of Italian opera. Ultimately this might help to unravel the enigma of Il Trittico while it continues to secure its rightful place as one of the masterpieces of the Puccini canon. / Dissertation/Thesis / Masters Thesis Music 2015

[pt] Partindo da discussão sobre o que se entende por poesia contemporânea, passando pelos possíveis recortes geracionais da segunda metade do século passado até a atualidade, esta dissertação analisa a obra de duas jovens poetas contemporâneas, Angélica Freitas e Alice Sant Anna, cujos livros de estreia foram publicados no século XXI. / [en] On the basis of the discussion concerning what is meant by contemporary poetry and what counts as a generation in the period from the mid twentieth century to the present, this thesis examines the work of two contemporary young women poets, Angélica Freitas and Alice Sant Anna, who published their first books in the twenty-first century.

This dissertation examines the confluence of ideas about classicism, commerce, and authorship in Britain in the final decades of the eighteenth century, when the commercial potential of classical forms and, conversely, the artistic potential of ‘mechanical’ forms of production both seemed greater, and yet more vulnerable, than they had ever been. While classical antiquity was a crucial source of artistic authority in this period, the emergence of a model of individual, inwardly generated, original authorship provided a different opportunity for commercial classicists to distinguish themselves in a crowded and competitive marketplace. In successive chapters of the dissertation, I discuss four makers whose works were produced in the context of competing models of authorship and authority: the architect, Robert Adam; the potter and manufacturer, Josiah Wedgwood; the painter and printmaker, Angelica Kauffman; and the sculptor and designer, John Flaxman. Each of these authors straddled the worlds of the mechanical and liberal arts, using a self-consciously classical artistic vocabulary in conjunction with highly commercial production and marketing strategies. They increasingly shaped and presented their works and style as their own proprietary creations, capitalising on emerging concepts of original genius and individual authorship: the very concepts that seem to be at odds both with academic classicism and with reproductive practices. Adam, Wedgwood, Kauffman, and Flaxman demonstrate how classicism, the idea of genius, and commercial, industrial modernity were mutually constitutive, resulting in the creation of artistic styles that are still associated with their authors today.