published_or_final_version / Dentistry / Master / Master of Dental Surgery

University of Macau / Institute of Chinese Medical Sciences

No description available.

The most promising therapy for cytomegalovirus (CMV) disease focuses on enhancing the patient’s immunity to viral pathogens. In this investigation, the therapeutic efficacy of bulk-cultured cytotoxic T lymphocytes was examined in primary murine cytomegalovirus infection. Virus-specific cytotoxic T cells (CTL( were generasted using immune spleen cells stimulated with irradiated murine CMV-infected cells. These CTL demonstrated significant cytolytic activity in a chromium-release assay. They were administered to mice infected with a lethal dose of murine CMV. The group receiving 107 CTL had a 50% reduction of mortality and lost 10% less weight. Virus titer of mice who received 107 CTL decreased 10 fold in the lungs and spleen and decreased 100 fold in the salivary gland. However, the therapy failed to decrease serum aminotransferase levels or restore lymphocyte blastogenic responsiveness. Although the mechanism is unclear, this therapy was effective in reducing mortality, morbidity, and virus titer in select organs. / Center for Medical Education

Submitted in fulfilment of the Master’s Degree in Clinical Technology, Durban University of Technology, 2012. / The sirolimus-eluting stent (Cypher) was the first approved drug- eluting stent by the Food and Drug Administration in April 2003. This is a stent that is based on a bare-metal stent and is coated with a layer of polymer incorporating sirolimus and releasing it by diffusion. Drug-eluting stents reduced risk of restenosis and repeat revascularization as compared with bare-metal stents. Clinical data has raised concerns that drug-eluting stents are associated with late untoward events. Objectives: The objective of this study was to test the hypothesis that stenting is safe and effective treatment for coronary artery disease. Methods and Results: Sirolimus-eluting stenting was performed in 30 patients with 34 coronary lesions. Detailed clinical follow-up data was collected by personal interview or telephone contact at 1, 6, 12 and 24 months. Patients were followed for 2 years for the occurrence of angina and cardiovascular events namely death, myocardial infarction, stent thrombosis and target lesion revascularization. The mean age of the cohort was 62.33±10.99 years; 83 percent were male, 6 percent were diabetic, 53 percent had hypertension. In spite of the overall patient and lesion complexity there were no incidences of major adverse cardiac events and all patients remained angina free out to two years. Dual antiplatelet therapy with aspirin and plavix varied from at least four weeks to one year. One patient had a bleeding event. Conclusions: Treatment of lesions with sirolimus-eluting stents is associated with a sustained clinical benefit two years after device implantation.

University of Macau / Institute of Chinese Medical Sciences

M.Sc. / Background: The continuous emergence of drug resistant strains of HIV as a result of errors made by reverse transcriptase coupled with undesirable side effects of available drugs, latency problems, cost etc, warrants the continuous search for new drug candidates. Chrysotherapy which is the use of gold compounds for the treatment of various ailments has been practiced since 2500 BC. The use of gold compounds such as auranofin for the treatment of rheumatoid arthritis has lead to remission of this disease. Gold compounds such as auranofin not only prevented the progression of arthritis but also increased the CD4+ count of an HIV positive patient who was not on antiretrovirals. These compounds have been implicated in the treatment of cancers, autoimmune diseases and microorganism infections. Objectives: In this work, novel gold compounds were evaluated with the aim of identifying lead compound(s) that can eventually serve as anti-HIV agents. Materials and Methods: Eleven gold (I) phosphine complexes, four of their corresponding ligands (compound without gold atom), and a gold (III) complex were tested for the ability to inhibit reverse transcriptase (RT) and protease (PR) in direct enzyme assays. Uptake of the compounds by host cells was evaluated with inductively coupled plasma atomic emission spectrometry (ICP-AES). Potential toxicity of the gold compounds was screened for by viability dyes and flow cytometry assays. To determine inhibition of whole virus by other mechanisms in addition to RT or PR, p24 production by infected cells was evaluated. Prior to all these analysis, stability of compounds in solution was determined by 31P nuclear magnetic resonance (NMR) and UV-visible spectroscopy. Results: The compounds were shown to be stable in solution over a one week period and were taken up by both continuous cell lines and primary cells. Eight of the gold compounds significantly inhibited HIV-1 reverse transcriptase at concentrations of 25 and 250 μM while four compounds and the four ligands did not. In a fluorogenic assay against HIV-1 PR, four of the gold compounds demonstrated inhibitory activity. The gold compounds were toxic to cells lines but not to primary cells. One of the complexes (EK231) significantly reduced p24 (p=0.0042) production at a concentration of 25 μM. Conclusion: Data provided here suggests that the therapeutic benefits of these gold containing compounds as potential HIV-1 reverse transcriptase and protease inhibitors should be considered.

D.Phil. / This enquiry represents an attempt to understand the ways in which the ecology of ideas surrounding HIV and Aids in post-apartheid South Africa functions discursively to silence people living with the dis-ease. In this regard, it seeks to understand how the range of subject positions available to people with HIV and Aids influences their opportunities for treatment and disclosure. The meanings emerging from this enquiry have implications for interventions aimed at people living with HIV and Aids, in that they challenge the liberal humanism underpinning a Western individualist paradigm which constructs people as ‘rational’ and ‘responsible’ on the basis that such constructions tend to attribute guilt or moral culpability to people living with HIV and Aids. The conversations and narratives elicited in the process of this enquiry suggest that such discourses constitute a form of disciplinary power in a Foucauldian sense, positioning people living with HIV and Aids defensively and limiting their options for ‘positive’ self-definition by foreclosing available subject positions, thereby contributing to the spread of HIV and Aids. Hence, this enquiry focuses on social constructions of morality and the impact of these on participants’ attempts to maintain key relationships that afford them a ‘positive’ sense of them-selves. Thus, it looks at experiences of connection and dis-connection and explores the ways in which efforts to retain ‘relatedness’ in order to maximise possibilities for the co-construction of a ‘moral self’ mediate opportunities for disclosure and treatment options. The enquiry aimed to assist participants in deconstructing dominant social constructions of HIV and Aids implicit in cultural and political discourse by applying a critical, poststructuralist and discourse-analytic lens in order that they might resist moral attributions based on liberal humanism and access their own voices in narrating the experience of living with HIV and Aids in keeping with their lived experience. My aim in this regard was to resurrect alternative or previously silenced accounts and to open up spaces for a multiplicity of meanings associated with HIV and Aids to emerge and be heard, toward the end of breaking the silence and creating a conversational space in which people’s meanings could simultaneously be heard and challenged through dialogue.Ultimately, this enquiry highlights the importance of attempting to understand the local and idiosyncratic nature of people’s constructions of HIV and Aids, which are often a hybrid mix of ideas and meanings circulating within social, cultural and political discourse. It also underscores the salience of considering people’s lives in context and particularly their need to maintain relationships that afford a positive sense of self. This is reflected in the tendency for participants to construct their identities in relation to significant others and for these relationships to mediate decision making in relation to HIV and Aids by availing or foreclosing certain subject positions, depending on the discourses within which they are situated.

Alzheimer's disease has become one of the most common diseases jeopardizing the health of the human being. The main pathological feature of AD is the accumulation of Aβ in the brain to form senile plaques. Therefore, it is of great significance to develop new and efficient drugs targeting at amyloid-β for the detection, diagnosis and therapeutics for Alzheimer's disease. Xanthohumol (Xn) naturally presents in hops (Humulus lupulus L). Studies have shown that it has anti-lipoperoxidative, anti-inflammatory, anti-proliferative activities, antiangiogenic and antioxidant effects, which further illustrates its potential therapeutic for AD. However, the bio-incompatibility and blood-brain barrier impermeability of Xanthohumol hindered it in vivo efficacy potential for treating Alzheimer's disease. Thus, we designed and prepared a series of Xanthohumol derivatives, namely, Xn-n, (n = 1-9) and its chalcone derivatives C-n, (n = 1-10) to enhance the desirable physical, biological and pharmacological properties, especially the blood-brain barrier permeability for intervention of AD. As an effective technique for in vivo visualization, Near-infrared fluorescence imaging based on organic small molecule probes has a promising application in the diagnosis of Alzheimer's disease. However, most of the reported imaging probes can only visualize Aβ-plaques but do not have therapeutic potential such as neuroprotection against Aβ induced toxicity. Herein, we designed and synthesized a series of oligomeric Aβ targeted near infrared (NIR) fluorescent probes for the diagnosis and therapeutics of Alzheimer's disease, namely DBAN-SLM, DBAN-SLOH, DBAN-OSLM which showed remarkably effective inhibitory effect on Aβ aggregation, significant neuroprotection effect against the Aβ-induced toxicities, and suppression on Aβ-induced ROS generation. indicating its great promise as a useful theragnostic agent for the early diagnosis and therapy of AD. Dual-modal imaging is an important approach to overcome the limitations of single imaging technology in the diagnosis of AD disease. Therefore, based on the dual-modal, we designed and synthesized the NIR/MR dual-modal detection and theragnostic probes namely Dyad-1, Dyad-2, Dyad-3 and NP@SiO2@F-SLOH. More surprising is that the two NIR/MR dual-modal probes show excellent biological properties, including the ability to inhibit Aβ aggregation to a certain extent, neuroprotective effects on cytotoxicity caused by different forms of Aβ species, blood-brain barrier (BBB) permeability, and high stability. All of these newly designed and synthesized molecules were characterized with 1H NMR, 13C NMR, and HRMS and found to show good agreement with the desired structures. The photophysical properties and biological properties of these novel designed and synthesized fluorescent probe such as UV-vis absorption, fluorescence emission, dissociation constant determined by fluorescence titration, cytotoxicity assay, neuroprotection, and inhibition of Aβ aggregation were investigated

Twenty-five gay men, 20 with Acquired Immune Deficiency Syndrome (AIDS) and 5 with either AIDS Related Complex (ARC) or who tested positive for the AIDS virus, were asked in semi-structured interviews whether they felt supported or isolated. Areas covered included society in general, employment, housing, health care, insurance, religion, families of origin, ex-wives, children, friends and lovers. Subjects indicated that fear of AIDS, homophobia, and death anxiety were all present in certain circumstances, but there was no attempt to differentiate between these three possible causes of social isolation in this exploratory study. / Master of Science