A Dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, for the Degree of Master of Science (MED). JOHANNESBURG, 1986 / The Literature Review covers the immunosuppressive and immunopotentiating properties of antibiotics on the immune system and the effects these could have on the resolution of an infection. The possible pathogenic mechanisms of C. albicans are also reviewed in this section. The experimental section shows that pre-treatment of mice with erythromycin increases the mean survival time following intraperitoneal inoculation of C. albicans. It was shown that erythromycin enhanced lymphocyte transformation and PMNL migration in both in-vivo and in-vitro situations. These enhanced immunological components probably caused improved survival times in the aforementioned animal experiments. To investigate the effects of oral administration of erythromycin on in-vivo PMNL migration in adult volunteers a new quantitative test which could only be applied to humans was developed and is described in detail. Using this method preliminary data were obtained which show that erythromycin increases PMNL migration in-vivo. / IT2018

A Thesis Submitted to the Faculty of Medicine University of the Witwatersrand, Johannesburg in fulfillment of the requirements for the Degree of Doctor of Science in Medicine Boston, U.S.A. 1983 / Vascular smooth muscle proliferation follows upon endothelial injury, and is thought to be an early component in the pathogenesis of atherosclerosis, and a possible noxious consequence of vascular surgery. We have shown that heparin suppresses vascular smooth muscle proliferation iri vivo and in vitro. The inhibitory effect is specific for heparin, and not other anions, and is not related to the antithrombin III binding activity of heparin. It is dependent on the size of the molecule, (hexasaccharidees or smaller being ineffective), and O-sulfation, but not N-sulfation / IT2018

IT2018

A Thesis presented for the degree of Doctor of Philosophy in the University of the Witwatersrand. Johannesburg, January, 1967. / Although reports of the medicinal use of iron date back to ancient times it was not until the present century that the many functions of iron in the body were studied. Once started, the investigation received impetus from the seriousness of iron deficiency anaemia, a major cause of ill health throughout the world. The introduction of radio-isotope tracer techniques in 1939 greatly facilitated investigation of absorption, excretion and the metabolic pathways of iron. The tremendous amount of work already carried out has led to a fairly comprehensive knowledge of the various aspects of iron metabolism. Nevertheless, there remain wide gaps in the overall picture. In / IT2018

A Thesis Submitted to the Faculty of Medicine, in Fulfilment of the Requirements for the Degree of • Doctor of Philosophy in the Department of Chemical Pathology, School of Pathology and the South African Institute for Medical Research, University of the Witwatersrand Medical School, Johannesburg, South Africa. December 1991. / Numerous studies have assessed the effects of single fatty acids on various aspects of lipid metabolism, particularly cancer. Established cell lines have largely been used for this purpose. The choice of control cells, however, has often been inappropriate. There is also a surprising lack of knowledge of the effects of fatty acids in the 'real world", in which normal cells in vivo are presented with mixtures of dietary fatty acids. Before transformed cells can be used as models of disease states, it is essential to fully understand fatty acid metabolism in normal (control) cells / IT2018

Tyrosine tRNA was isolated from bovine liver and its nucleotide sequence was determined using in vitro 32p_ labeling techniques. Several important structural features of the tRNA are: the presence of gal-Q in the first position of the anticodon, acp3U at position 20, and a pair of adjacent N,N-dimethylguanosines (residues 26 and 27). A human DNA fragment harbored in a lambda phage clone was isolated, and restriction enzyme analysis revealed the presence of three tRNA genes in a 6.0-kb BamHI subfragment. Portions of the 6.0-kb DNA fragment containing the tRNA genes were sequenced by the method of Maxam and Gilbert and analyzed for transcriptional activity in vitro using homologous cytoplasmic extracts. A threonine tRNAUGU gene exhibited high transcriptional activity dependent on its 5'- flanking sequence. The enhanced transcription is not completely inhibited by alpha-amanitin. The value of studying tRNA structure in concert with the cognate tRNA. genes is discussed.

A dissertation submitted in fulfilment of the requirements for the degree of Master of Science in Medicine Faculty of Health Sciences University of the Witwatersrand Johannesburg 2015 / Treatment of hormone-dependent breast tumours is typically conducted using hormone-therapy, with NK cell immunotherapy a novel modality. In this study, the effects of hormone-therapy and combined hormone-therapy with immunotherapy in MCF-7 breast cancer cells was investigated. A hormone pre-treatment of 17β-oestradiol and progesterone was performed to simulate the in vivo microenvironment. Subsequently cells were treated with the hormone-therapy drugs Anastrozole or RU486 alone, or with continued hormone simulation. Combined therapy was conducted with in vitro activated NK cells co-cultured with MCF-7 cells undergoing hormone-therapy. Biomarkers ERα, PR and MUC1 were immunolocalised and expression analysed qualitatively, and quantitatively using image analysis software. Hormone pre-treatment reduced biomarker expression, stressing the importance of hormone environment simulation for in vitro experimentation. Hormone-therapy increased cytoplasmic ERα and decreased PR expression. Anastrozole increased MUC1 and RU486 decreased nuclear MUC1. With continued hormone simulation, Anastrozole further decreased all biomarkers whereas RU486 decreased ERα, increased PR expression with variable effects on MUC1 expression. RU486 induced MUC1/PR and MUC1/ERα correlation, which, under continued hormone simulation, was maintained in the nucleus only. Anastrozole induced MUC1/PR correlation in the cytoplasm which was maintained under continued hormone simulation. Hormone-therapy also induced a decrease in apoptosis, with continued hormone simulation abrogating Anastrozole induced apoptosis. While hormone-therapy did not increase proliferation, the associated changes observed in biomarker expression are linked with tumour progression indicating that short-term treatment may be detrimental for overall survival. Combined NK cell immunotherapy resulted in decreased PR, while ERα and MUC1 expression increased in a hormone-dependent manner. Biomarker correlation was evident, albeit reduced with continued hormone simulation. Independently of hormone-therapy and hormone stimulation, immunotherapy reduced apoptosis, contrary to expectation. Proliferation was marginally reduced by immunotherapy. The results indicate that immune cell function is inhibited by interaction with tumour cells, an effect that hormone-therapy cannot abrogate. Furthermore, that this study shows treatment alters both nuclear and cytoplasmic expression of biomarkers, indicates that diagnostic procedures should consider both cellular compartments in tumour progression. It is further shown that qualitative analysis of biomarker expression is not always validated by quantitative analysis, with the latter proposed as a more objective and precise method to be used diagnostically.

O objetivo do estudo foi testar métodos de desenvolvimento de lesões artificiais de cárie não cavitadas em esmalte de dentes humanos, avaliando a capacidade da microrradiografia transversal (TMR) de diferenciar os efeitos de um dentifrício fluoretado e de um não fluoretado, a fim de selecionar modelos para estudos posteriores. A partir de dentes permanentes e decíduos, 20 blocos de esmalte de dentes permanentes e 15 de decíduos foram obtidos e selecionados por meio da microdureza de superfície. Na primeira etapa, amostras de dentes permanentes (n=5) foram submetidas ao modelo 1, que consistiu na indução de lesão pela imersão durante 96h em solução contendo 2,2mM de CaCl2, 2,2mM de KH2PO4, 0,05M de ácido acético, tendo o pH ajustado para 4,4 com 1M de KOH e, após, a ciclos de desmineralização e remineralização (des/re) por 10 dias. Os espécimes de dentes decíduos (n=5) foram imersos durante 96h em solução contendo 2,2 mM CaCl2, 2,2 mM NaH2PO4, 0,05M de ácido acético e 0,25ppmF, sendo o pH ajustado em 4,5 pela adição de 1M KOH e, após, durante 10 dias, a ciclos des/re (modelo 2). Em relação ao modelo 1, houve cavitação das lesões após os ciclos de 10 dias. Já com o modelo 2, no entanto, houve formação de lesões de subsuperfície observadas por microradiografia transversal (TMR), sem ocorrência de cavitação. Baseado nisso, o modelo 2 foi repetido em amostras de dentes permanentes (n = 5) e lesões de subsuperfície foram obtidas. Com base nesses resultados, na segunda etapa o modelo 2 foi utilizado em amostras de esmalte de dentes permanentes (n=10) e decíduos (n=10); neste momento, porém, metade das amostras foram submetidas a tratamento com dentifrício fluoretado e as demais com dentifrício sem flúor, para observar se o TMR seria capaz de detectar diferença entre tratamentos. O resultado obtido foi a formação de lesões de subsuperfície em dentes permanentes e decíduos e o método foi capaz de diferenciar ambos os tratamentos. / The aim of this study was to test methods of development of non-cavitated artificial caries lesions in human teeth enamel, analyzing the ability of transversal microrradiography to differentiate the effects of fluoride and non-fluoride dentifrices and select models to posterior experiments. From permanent and deciduous human teeth, 20 enamel blocks of permanent and 15 of deciduous teeth were obtained and selected by surface microhardness. In the first step, samples of permanent teeth (n = 5) were submitted to lesion induction by immersion during 96 hours in solution composed by 2.2mM CaCl2,2.2mM KH2PO4, 0.05M acetic acid, with pH 4.4 adjusted by 1M KOH, and, after this, to pH cycles of demineralization and remineralization (de/re) during 10 days (model 1). The specimens of deciduous teeth (n = 5) were immersed during 96 hours in solution composed by 2.2 mM CaCl2, 2.2 mM NaH2PO4, 0.05M acetic acid and 0.25ppmF, with pH 4.5 adjusted by 1M KOH and, posterior, during 10 days, to pH cycles (model 2). Concerning the model 1, occurred cavitation of the lesion after the 10 days cycles. Model 2, however, formed subsurface lesions observed by transversal microrradiography (TMR), without cavitation of the surface. Based on this result, this model was used to permanent enamel (n = 5), and was able to develop subsurface lesion. In the second step, the model 2 was applied to samples of permanent teeth enamel (n = 10) and deciduous teeth enamel (n = 10); in this moment, nevertheless, half of the samples were submitted to treatment with fluoridated dentifrice and the other with non-fluoridated dentifrice, to observe if the TMR would be able to detect difference between treatments. The result obtained was the induction of subsurface lesions in permanent and deciduous enamel, and the method was able to differentiate the treatments.

O objetivo do estudo foi testar métodos de desenvolvimento de lesões artificiais de cárie não cavitadas em esmalte de dentes humanos, avaliando a capacidade da microrradiografia transversal (TMR) de diferenciar os efeitos de um dentifrício fluoretado e de um não fluoretado, a fim de selecionar modelos para estudos posteriores. A partir de dentes permanentes e decíduos, 20 blocos de esmalte de dentes permanentes e 15 de decíduos foram obtidos e selecionados por meio da microdureza de superfície. Na primeira etapa, amostras de dentes permanentes (n=5) foram submetidas ao modelo 1, que consistiu na indução de lesão pela imersão durante 96h em solução contendo 2,2mM de CaCl2, 2,2mM de KH2PO4, 0,05M de ácido acético, tendo o pH ajustado para 4,4 com 1M de KOH e, após, a ciclos de desmineralização e remineralização (des/re) por 10 dias. Os espécimes de dentes decíduos (n=5) foram imersos durante 96h em solução contendo 2,2 mM CaCl2, 2,2 mM NaH2PO4, 0,05M de ácido acético e 0,25ppmF, sendo o pH ajustado em 4,5 pela adição de 1M KOH e, após, durante 10 dias, a ciclos des/re (modelo 2). Em relação ao modelo 1, houve cavitação das lesões após os ciclos de 10 dias. Já com o modelo 2, no entanto, houve formação de lesões de subsuperfície observadas por microradiografia transversal (TMR), sem ocorrência de cavitação. Baseado nisso, o modelo 2 foi repetido em amostras de dentes permanentes (n = 5) e lesões de subsuperfície foram obtidas. Com base nesses resultados, na segunda etapa o modelo 2 foi utilizado em amostras de esmalte de dentes permanentes (n=10) e decíduos (n=10); neste momento, porém, metade das amostras foram submetidas a tratamento com dentifrício fluoretado e as demais com dentifrício sem flúor, para observar se o TMR seria capaz de detectar diferença entre tratamentos. O resultado obtido foi a formação de lesões de subsuperfície em dentes permanentes e decíduos e o método foi capaz de diferenciar ambos os tratamentos. / The aim of this study was to test methods of development of non-cavitated artificial caries lesions in human teeth enamel, analyzing the ability of transversal microrradiography to differentiate the effects of fluoride and non-fluoride dentifrices and select models to posterior experiments. From permanent and deciduous human teeth, 20 enamel blocks of permanent and 15 of deciduous teeth were obtained and selected by surface microhardness. In the first step, samples of permanent teeth (n = 5) were submitted to lesion induction by immersion during 96 hours in solution composed by 2.2mM CaCl2,2.2mM KH2PO4, 0.05M acetic acid, with pH 4.4 adjusted by 1M KOH, and, after this, to pH cycles of demineralization and remineralization (de/re) during 10 days (model 1). The specimens of deciduous teeth (n = 5) were immersed during 96 hours in solution composed by 2.2 mM CaCl2, 2.2 mM NaH2PO4, 0.05M acetic acid and 0.25ppmF, with pH 4.5 adjusted by 1M KOH and, posterior, during 10 days, to pH cycles (model 2). Concerning the model 1, occurred cavitation of the lesion after the 10 days cycles. Model 2, however, formed subsurface lesions observed by transversal microrradiography (TMR), without cavitation of the surface. Based on this result, this model was used to permanent enamel (n = 5), and was able to develop subsurface lesion. In the second step, the model 2 was applied to samples of permanent teeth enamel (n = 10) and deciduous teeth enamel (n = 10); in this moment, nevertheless, half of the samples were submitted to treatment with fluoridated dentifrice and the other with non-fluoridated dentifrice, to observe if the TMR would be able to detect difference between treatments. The result obtained was the induction of subsurface lesions in permanent and deciduous enamel, and the method was able to differentiate the treatments.

Submitted by LEONARDO DE FREITAS SILVA null (leonardofreitas86@gmail.com) on 2016-10-20T13:26:49Z No. of bitstreams: 1 Dissertação de mestrado- reapresentação 1.pdf: 1472109 bytes, checksum: e157f95a9ba34bce0469c51f091af276 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-10-26T17:52:37Z (GMT) No. of bitstreams: 1 silva_lf_me_arafo.pdf: 1472109 bytes, checksum: e157f95a9ba34bce0469c51f091af276 (MD5) / Made available in DSpace on 2016-10-26T17:52:37Z (GMT). No. of bitstreams: 1 silva_lf_me_arafo.pdf: 1472109 bytes, checksum: e157f95a9ba34bce0469c51f091af276 (MD5) Previous issue date: 2016-10-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A estabilidade primária de implantes dentários corresponde a um fenômeno mecânico relativo à qualidade ou quantidade óssea, ao tipo de implante e a técnica de instalação. O objetivo deste trabalho foi avaliar o tempo de fresagem, aquecimento dos sítios fresados e a estabilidade dos implantes instalados em cavidades realizadas com ultrassom cirúrgico e instrumentos rotatórios. Foram realizadas 64 cavidades em 04 blocos de poliuretano simulando as densidades de ossos tipo I, II, III e IV. A temperatura da superfície do bloco nos leitos foi medida durante a fresagem. A estabilidade dos implantes foi mensurada por meio do torque de inserção, de remoção e frequência de ressonância. O implante cilíndrico TitaOss 3,75 x 11 mm foi instalado em todas as cavidades. Os resultados mostraram maior tempo e temperatura para o grupo em que foi usado o ultrassom. Quanto à estabilidade primária não houve diferença significante entre os grupos estudados. Pôde-se concluir que a estabilidade primária dos implantes não foi influenciada pelos métodos de fresagem utilizados e que o ultrassom cirúrgico necessitou de mais tempo e gerou mais calor do que o instrumento rotatório para o preparo das cavidades. / The primary stability of dental implants corresponds to a mechanical phenomenon related to bone quality or quantity, type of implant and installation technique. The objective of this study was to evaluate the time of drilling, heating drilled sites and stability of implants placed in cavities made with piezosurgery and rotary instruments. Polyurethane blocks were used simulating the densities of bone type I, II, III and IV. The surface temperature of the block was measured in the cavity during drilling, and recorded the highest temperature variation. The stability of the implants was measured with a torque insertion, torque of removal and resonance frequency. The cylindrical implant TitaOss 3.75 x 11 mm was used in all cavities. The results showed greater time and temperature for the group that was used piezosurgery. The primary stability was no significant difference between groups. It could be concluded that implant primary stability was not influenced by the used methods and piezosurgery took more time and generated more heat than the conventional rotatory instruments to prepare the cavities.