Aim. The aim of this study was to synthesize and characterize novel analogues of [DACH-Pt-DMC] by using different stereoisomers of DACH; and to investigate any differences in in vitro activity of these complexes in human hepatocellular carcinoma (HCC), colorectal carcinoma (CRC) cell lines and acquired cisplatin or oxaliplatin resistant sub-lines, and to compare that of oxaliplatin and other established Pt-based anticancer agents. Mechanistic roles of DACH-Pt- and DMC components of the TCM-Pt complexes on affecting HCT 116 human CRC cell line were investigated by flow cytometry, COMET assay and cDNA microarray analysis. / Background. Demethylcantharidin (DMC), a modified component of the traditional Chinese medicine (TCM), integrated with a platinum (Pt) moiety created a series of TCM-Pt complexes [Pt(C8H8O 5)(NH2R)2] 1-5 which demonstrated superior antitumor activity and circumvention of cisplatin resistance in vitro. Compound 5, derived from the 1,2-diaminocyclohexane (DACH) ligand (where R=trans-C6H10) had the most potent antitumor activity and closest structural resemblance to oxaliplatin (R,R-DACH-Pt complex) which is the first Pt-based anticancer drug to demonstrate convincing clinical activity against colorectal cancer and has a mechanism of action and resistance that is clearly different from that of cisplatin and carboplatin. / Conclusion. This study is the first to examine the mechanism of anticancer activity of new complexes that integrate DMC with different isomers of DACH. It has shown that both DACH-Pt- and DMC components contribute significantly to the compounds' potent anticancer activity, but likely with different mechanisms of action. The DACH-Pt- component appears to dictate the cell cycle distribution, whereas the DMC component appears to enhance cytotoxicity by inducing more DNA damage in HCT 116 colorectal cancer cells. / Methods. DMC was reacted with appropriate DACH-Pt-(NO3) 2 intermediates, which were prepared from treatment of K2PtCl 4 with stereoisomeric DACH (RR-, SS- & cis-), followed by reaction with silver nitrate. Proton NMR, high-resolution MS, polarimetry and circular dichroism (CD) spectroscopy were used to characterize their chemical structures and optical activities. In vitro antitumor activity (IC50 of 72hr drug exposure time) were assessed by a standard MTT assay. Cell cycle analysis by flow cytometry was determined at 0, 6, 12, 18, 24, 48 and 72 h after drug treatment (cisplatin, carboplatin, oxaliplatin, DMC, compound 1 or trans-DACH-Pt-DMC analogues) at IC50 and 5 x IC50 concentrations with three to four replicates. Comet assay was performed with a fluorescent microscope and used to examine DNA damage after drug treatments (50muM of cisplatin, carboplatin, oxaliplatin, DMC, compound 1 or R,R-DACH-Pt-DMC) for 3hr. cDNA microarray was performed on Affymetrix Human Genome U133A Set and used to analyze gene expression profiles in HCT 116 exposed to trans-(+/-)-DACH-Pt-DMC or oxaliplatin at their IC50 for 72hr. / Results. The in vitro results showed that the trans-analogues were consistently the most potent amongst all the compounds tested in both HCC and CRC cell lines: the trans-(+)(1R,2R)-DACH-Pt-DMC complex, in particular, was the most effective stereoisomer. All of the stereoisomeric DACH-Pt-DMC complexes and oxaliplatin were apparently able to circumvent cisplatin resistance in Huh-7 and SK-Hep1 sub-lines, but cross resistant with oxaliplatin in HCT 116 oxaliplatin resistant sub-line. Flow cytometric analysis revealed the novel trans-DACH-Pt-DMC analogues and oxaliplatin behaved similarly: that is, the compounds at 5 x IC50 concentrations all caused a significant decrease in the S-phase population within 18h and at the same time induced G2/M arrest, and without obvious sub-G 1 phase accumulation, but distinct from that of cisplatin, carboplatin or DMC. Comet assay showed that trans-(+)-(1R,2 R)-DACH-Pt-DMC caused the most significant DNA damage at an equivalent molar concentration. Microarray analysis suggested that the mechanistic role of the DMC ligand can induce the cell cycle to accelerate from the G 1 to S-phase and cause M-phase arrest. / Yu Chun Wing. / "July 2006." / Advisers: Yee-ping Ho; Chik Fun Steve Au-Yeung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1586. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 191-232). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (M.A.)--University of South Africa, 1994.

This study propagates a move away from the dominant practices of psychodrama with its emphasis on catharsis and insight as the main components of a therapeutic experience. It proposes a systemic orientation to psychodrama where protagonists may encounter the circularity of the systems in which they are embedded and through this process encounter new meaning. Case studies are presented which exemplify an evolutionary process of creating what the author refers to as "ecosystemic psychodrama". This ecosystemic psychodrama is based on second-order cybernetics and what is aimed for is that as a therapy it should present something of the balance between the aesthetic and pragmatic views of therapy that Keeney (1983a) describes as complementary. / Psychology / M.A. (Clinical Psychology)

published_or_final_version / Biochemistry / Master / Master of Science

published_or_final_version / Anaesthesiology / Master / Master of Philosophy

published_or_final_version / Chinese Medicine / Master / Master of Philosophy

Within the last 15 years a large number of empirical investigations have explored the psychotherapeutic applications of meditative techniques. This research expands upon previous efforts in this area by comparing Kundalini Yoga with Progressive Muscle Relaxation, an attention-placebo control, and a no-treatment control on measures of anxiety (STAI Trait Form), personality development (Locus of Control Scale), and drug consumption. A total of 47 undergraduate student volunteers were randomly assigned to the four treatment conditions. Following a 2-week baseline phase to determine pretreatment drug consumption, subjects began a 6-week treatment phase during which time they attended two classes each week. Throughout the treatment phase subjects maintained detailed drug consumption diaries. Following this treatment phase, all subjects were readministered the aforementioned tests and questionnaires. Without exception, the research failed to find any significant treatment effects attributable to the practice of Kundalini Yoga. Moreover, none of the experimental treatment groups studied here displayed treatment gains over and above a no-treatment control group. There are at least two ways to account for this lack of significant differences. On the one hand, one could assert that the treatment groups were somehow impotent and incapable of effecting change any better than the nonspecific treatment factors working for the no-treatment group; or on the other hand, one could assert that the treatment groups were indeed therapeutic, but not significantly due to too brief of an intervention phase, and/or due to the highly variable treatment response of a nonpredisposed subject pool.

Thesis (M.A.)--University of South Africa, 1994.

Heart failure is a devastating disease which despite significant advances in therapy over the past two decades still results in a poor prognosis. Metabolic dysregulation is associated with heart failure; however, it remains unclear whether isoproterenol exerts deleterious effects through altered metabolic regulation. Whether metformin, a metabolic modulator, prevents isoproterenol-induced heart failure is unknown. The aim of this study was to determine whether metformin prevents functional and metabolic changes seen in the isoproterenol model of heart failure. Male Sprague-Dawley rats were administered isoproterenol and metformin for seven months. Thereafter, cardiac dimensions, metabolic gene expression and myocardial structural changes were assessed. Chronic administration of isoproterenol induced left ventricular dilatation and pump dysfunction and mitochondrial structural derangement. No changes were seen in metabolic gene expression. However, co-administration of metformin prevented isoproterenol-induced heart failure and retained mitochondrial structural arrangement. Therefore, cardiac dilatation and pump dysfunction induced by chronic administration of isoproterenol can be prevented by co-administering metformin.

A research report submitted to the Faculty of Humanities, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Arts (Drama Therapy) November 2017 / The research consists of a practical arts-based research component and a research report that surveys the practice. This document serves as the written element of the research and investigates the key theoretical standpoints, methodologies applied and creative outcomes. The research aimed to explore the dynamics of adults and play within Drama Therapy by investigating the relationship between six adult women and their personal play histories. It questioned what play meant to the individual and invited her to share her most memorable playful moments through various forms of expression in a number of individual interview-discussions. Through a practical arts-based research approach, an ethnographic narrative inquiry unfolded about women, play, childhood memory and present adulthood. The research took these shared narratives and presented them back to the six participants through various playful methods. With the use of methodologies such as inter-subjectivity, playful listening, narrative enquiry and Playback Theatre, the research offered a series of representational reflections of the shared stories. The creative outcomes were presented in a storybook representation which used imagery and poetic rhyme to document each narrative, a stop-motion film that used moving image and voice, and an presentation-installation that invited each woman to engage with her playful inner-self reflected back to her. The report is written with these playful elements which attempt to mirror the creative representational outcomes, inviting the reader to access his or her playful self. Thematically, three key factors presented themselves throughout the five-stage research process. These include the emotional experience associated with play, the notion of an inner-child or childhood and play within context. All three elements are discussed in the research report, with the use of the contextual factor symbolised by road signs to represent the intersectionality of play and its relationship to the individual. The research presents a number of key contributing factors to the discussion of adults and play in Drama Therapy. It attempts to explore alternative ways of delving into therapeutic process while respecting individual perspectives and personal narratives. It highlights the fundamental value of play within a drama therapeutic paradigm and how the notion of play and play memories contribute to the adult self. It also affirms the role of arts-based practice as a powerful tool for validation and witnessing of clients. / XL2018