The unlubricated sliding wear behaviour of gas nitrided, plasma nitrided, and ferritic nitrocarburized BS970,905M39 (EN41B) steels was investigated systematically from an engineering point of view. Commercial nitriding processes were employed, and the wear studies were carried out using a pin-on-disc machine over a wide range of sliding speeds and applied loads. The worn specimens and wear debris were examined by several techniques; including optical and electron microscopy and X-ray analysis. A sharp wear rate transition between mild and severe regimes was identified by varying the load for both untreated and gas nitrided steels. The wear rate was reduced by gas nitriding by up to two orders of magnitude, depending on the sliding condition. Moreover, gas nitriding expanded the mild wear region toward higher loads and sliding speeds. In the mild regime an oxidative wear mechanism operated, contrasting with the metallic wear in the severe regime. Wear maps for untreated and gas nitrided steels have been constructed, which show the dominant regimes of the wear mechanisms. A "wear-face-limited" gas nitrided pin test showed that the benefit of the treatment was lost once the effective surface layer was completely worn away. It is suggested that hardness has a crucial role in determining the wear rate through nitrided diffusion layers. A thick and porous compound layer produced by gas nitriding showed a poor wear behaviour owing to its brittleness, while a thin nitrocarburized E-Fe3N compound layer exhibited a low wear rate. There was no significant difference between the nitride steels in terms of transition load and wear rate. However, the wear lives of the nitrided layers were dependent on their case depth. Severe wear should be avoided in engineering component design, and operating conditions should ensure that only mild wear occurs. Both the hardness profiles and the cost performance of nitriding processes should be considered in the selection of nitriding treatments.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Technikon Natal, 1999. / The purpose of this placebo-controlled study was to evaluate the efficacy of the homoeopathic simillimum treatment in halitosis in terms of the volatile sulphur compounds being measured objectively by the portable sulphide monitor and subjectively by organoleptic measurement\x87 / M

A dissertation presented to in partial fulfilment of the requirements for the Masters Degree in Technology: Chiropractic, Technikon Natal, 1996. / The aim of this study was to determine the effectiveness of adjustments versus mobilisation in the treatment of mechanical neck pain. It was hypothesized that treatment with adjustments over a three week period, with a further three week follow-up period, would be more effective than mobilisation in terms of improving the patients' cervical ranges of motion and their perceptions of pain and disability. / M

Masters of Art / High rates of substance use and its associated problems afflict Cape Town, underscoring the need for easily accessible substance abuse treatment. Despite the substantial benefits for both individuals and society at large that substance abuse treatment confers, substance abusers often first have to negotiate considerable challenges in order to access treatment and accumulate these gains. That is, experiencing barriers to accessing treatment, together with the presence of socio-demographic features, rather than “need for treatment”, decides who accesses treatment. Referrals are the gateway to inpatient substance abuse treatment in the Western Cape. While several barriers to accessing treatment have been identified by prior studies, none examine these phenomena from the point of view of the agents responsible for referring substance users for treatment. Moreover, access barriers to inpatient substance abuse services are a neglected area in extant literature. To address this gap, this study explored the perceptions of referring agents‟ of the barriers to accessing state-funded inpatient substance abuse treatment centres in the Western Cape. This enabled the researcher to compare existing access barriers to treatment as identified by prior research, to those elucidated in the study. Bronfenbrenner‟s Process-Person-Context-Time model was employed as the basis for understanding identified barriers. In accordance with the exploratory qualitative methodological framework of the study, six semi-structured individual in-depth interviews were conducted with referring agents‟ of differing professional titles who were purposefully selected and expressed a willingness to participate in the study. Interviews were audio-recorded, and transcripts were analysed and interpreted by means of Thematic Analysis. Two broad thematic categories of access barriers were identified: Person-related barriers (denial, motivation for treatment, gender considerations, disability, active TB disease, homelessness, psychiatric co-morbidity) and Context-related barriers to treatment (cultural and linguistic barriers, stigma, community beliefs about addiction and treatment, awareness of substance abuse treatment, affordability/ financial barriers, geographic locations of treatment facilities, waiting time, lack of collaboration within the treatment system, beliefs of service providers‟, lack of facilities/ resources within the treatment system, practices at inpatient facilities, referral protocol and uninformed staff). Results suggest that by targeting the aforementioned barriers, access to inpatient and outpatient treatment services can be improved, and recommendations for interventions are offered in this regard. Ethical principles such as obtaining informed consent and ensuring confidentiality were abided by throughout the study and thereafter.

No description available.

The 16α-alkylation was achieved via treatment of 3-methoxyestra-1,3,5(10)-trien-17-one-N,N-dimethylhydrazone (118) with n-butyllithium and the appropriate haloalkane to afford exclusive 16α-substitution (119). Subsequent, cupric ion-catalysed hydrolysis, 17-ketone reduction and removal of the 3-hydroxyl protecting group, furnished 16α-methylestra-1,3,5(10)-trien-3,17β-diol (122a) and 16α-ethylestra-1,3,5(10)-trien-3,17β-diol (122b). An alternative sequence to the 16α-ligands, by direct alkylation of the 17-keto-estrone enolate, was also investigated. In this manner 16α-allylestra-1,3,5(10)-trien-3,17β-diol (122c) and 16α-benzylestra-1,3,5,(10)-trien-3,17β-diol (122d) were obtained.

Childhood nocturnal enuresis (bedwetting) is a prevalent, clinically demanding condition affecting approximately 500,000 children in the United Kingdom. At the age of 5 years, around 15-20% of all children wet the bed at least twice weekly, this figure falling to 5% at age 10 years. The disorder can have far-reaching social and emotional consequences for both the child and their family if left untreated. The most successful treatments for childhood functional (non-organic) nocturnal enuresis are of behavioural origin, namely urine alarm training and dry-bed training. The former is widely adopted in the treatment of bedwetting; however, it has a high relapse rate. In contrast, the latter tends to have a better long-term remission rate. However, due to the intricate nature of dry-bed training and costs relating to its implementation, it is rarely utilised by healthcare practitioners. Two studies reported in this thesis (the first a pilot investigation, and the second a main investigation) examined the relative efficacy of urine alarm training and a modified version of drybed training in the treatment of childhood functional nocturnal enuresis when both were delivered by identical minimal intervention methods (i.e., biblio-cumvideo therapy combined with telephone and intermittent clinic supervision) at the primary care level of service delivery. The findings demonstrated that modified drybed training was significantly superior to urine alarm training in terms of its long term remission rate. Moreover, families of bedwetting children found the modified dry-bed training programme simple to understand and implement. As a result of these findings, and as an extension into the evaluation of minimal intervention service delivery, a study was conducted to investigate the relative efficacy of modified dry-bed training delivered via video-mediated consultation and face-to-face consultation in the treatment of childhood functional nocturnal enuresis. A further objective was to evaluate patient, parent, and therapist satisfaction with video mediated consultation as compared to face-to-face consultation. The findings revealed that modified dry-bed training was equally efficacious across both consultation modes in terms of its long-term remission rate. Patients and their parents were generally satisfied with both modes of consultation, with few significant differences between the 2 consultation groups on any variable as assessed by a post-treatment patient and parent satisfaction scale. However, the therapist was more satisfied with face-to-face consultation than video-mediated consultation. Results are discussed in terms of their relevance to future research and clinical practice.

This work focuses on the development of red light-activated porphycene-based photosensitizers for anti-tumor photodynamic therapy (PDT) under both normoxic and hypoxic conditions. A total of seven water-soluble porphycenes have been designed, synthesized and evaluated as potential PDT agents in terms of their photophysical and photobiological properties using principally the human nasopharyngeal carcinoma (HK-1) cells. Among the porphycenes synthesized, two were neutral amphiphilic aryl porphycenes, TDEGPPo and Zn(II) TDEGPPo, with relatively weak photo-cytotoxic activities even under normoxic condition. Two cationic porphycenes, TPyBPo and TriPyPPo, exhibited strong photo-cytotoxic activities, with LD50 of 0.3 mM at a light dose of 3 J/cm2, under normoxic condition. However, much lower photo-cytotoxicity was observed under hypoxic condition for TPyBPo and TriPyPPo, with LD50 of 3 mM and 3.5 mM, respectively, obtained at high light doses (>10 J/cm2). Two alkyl porphycenes with one and two sulfonoamide diglycol functionalities, TBPoS-OH and TBPoS-2OH, were synthesized and shown to exhibit very potent photo-cytotoxic activities, with respective LD50 of 53 nM and 20 nM (light dose 8 J/cm2) under normoxic conditions. Most importantly, comparably potent photo-cytotoxicity was also observed for these porphycenes under hypoxic conditions, with respective LD50 of 65 nM and 50 nM (light dose 8 J/cm2). In addition, these porphycenes were taken up by the HK-1 cells very rapidly, with >90% accumulated inside the cells after only 1 h of incubation. Confocal microscopy revealed that these porphycenes were localized at the lysosomes, mitochondria as well as endoplasmic reticulum. Furthermore, the predominant mode of cell death caused by the PDT action of these porphycenes was shown to be apoptosis. In an attempt to effect mitochondria localization to enhance apoptotic cell death for these porphycenes, TBPoS-OH was conjugated with rhodamine B to produce the TBPoS-Rh B conjugate. This porphycene-Rh B conjugate also displayed very potent photo-cytotoxicity under both normoxic and hypoxic conditions, with LD50 of 52 nM and 85 nM, respectively, at a light dose of 8 J/cm2. However, confocal microscopy revealed its principal subcellular localization was at the lysosomes, not the mitochondria. The PDT activities of these porphycenes were compared to a well-known patented PDT agent, EtNBS, which is active under both normoxic and hypoxic conditions, with LD50 of 58 nM and large than 1000 nM, respectively, towards the HK-1 cells. This comparison clearly shows that our sulfonoamido-porphycenes, TBPoS-OH, TBPoS-2OH and TBPoS-Rh B conjugate, display a 15- to 25-fold stronger hypoxic PDT activity relative to EtNBS, thus making these porphycenes excellent candidates for hypoxic anti-tumor photodynamic therapy.

Lung cancer accounted for 28% of all cancer related deaths in Hong Kong and has been the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the most common lung cancer (85%) and has been linked to poor prognosis with 5-year survival rates of only 15%. Low accumulation and lack of efficient penetration of therapeutic agents in the tumor site, and severe adverse effects are the main obstacles in efficient lung cancer chemotherapy.. Triptolide (TPL), a diterpenoid triepoxide, was first isolated from the Chinese medicinal plant Tripterygium wilfordii Hook F. It had attracted extensive attention for its anti-tumor effect. However, its therapeutic potential has been limited by the poor water solubility (0.017 mg/mL) and strong toxicity with LD50 of 0.8 mg/kg. To improve the therapeutic effects and facilitate the application of TPL in lung cancer therapy, we developed different ligands-modified TPL-loaded liposomal formulations for lung cancer specific delivery.. Antibody-decorated liposomes can facilitate the precise delivery of chemotherapeutic drugs to the lung by targeting a recognition factor present on the surface of lung tumor cells. Carbonic anhydrase IX (CA IX), an enzyme overexpressed on the surface of lung cancer cells with a restricted expression in normal lungs, is used as the target for NSCLC therapy. In the present study, anti-CA IX antibody-modified TPL-loaded liposomes was developed. CA IX-directed liposomes exhibited 1.7-fold enhancement in internalization effects and 2-fold higher cytotoxicity in CA IX-positive human non-small cell lung cancer cell line A549. In vivo, CA IX-directed liposomes confined the delivery specifically to the lung and resided up to 96 h, which further showed enhanced therapeutic efficiency in orthotopic lung tumor bearing mice.. CPP33 is a tumor lineage-homing cell-penetrating peptide reported to be highly permeable into human lung cancer cell. Here, we utilized CPP33 for translocation of TPL-liposomal formulation into lung tumor cells. In vitro, CPP33-TPL-lip significantly improved apoptotic feature on A549 cells than non-modified liposomes. CPP33-lip specifically promoted the penetration ability of liposomes on A549 rather than human lung fibroblast cells (MRC-5), showing prominent cell selectivity. Furthermore, CPP33-lip showed superior penetrating ability on 3D tumor spheroids compared to non-modified liposomes.. A dual-ligand TPL-loaded liposomes (dl-TPL-lip) via conjugation of anti-CA IX antibody (targeting module) and CPP33 (trans-membrane module) was further developed to improve the therapeutic efficacy of NSCLC. The dl-TPL-lip showed superior penetrating ability and inhibiting effect on 3D tumor spheroids and significantly enhanced TPL anti-cancer efficacy following pulmonary administration in orthotopic lung cancer nude mice. The encapsulation of TPL in liposomes reduced the exposure of TPL in systemic circulation, which is demonstrated by pharmacokinetic study in rat plasma by endotracheal administration. Further anti-cancer effect study showed that dl-TPL-lip exhibited the greatest efficacy compared to TPL solution, non-modified TPL-loaded liposomes, anti-CA IX Ab or CPP33 single ligand-modified liposomes.. In summary, the findings of this study establish promising TPL delivery systems for targeted therapy of lung cancer. Current research focusing on drug delivery systems provides an insight into targeted and safe delivery of TPL in preclinical setting.

University of Macau / Institute of Chinese Medical Sciences