Made available in DSpace on 2014-10-09T12:40:58Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:39Z (GMT). No. of bitstreams: 1 03973.pdf: 4389182 bytes, checksum: b10987cb9b3ec2a2bd2d1083fded1bfc (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Orientadores: Lourenço Correr Sobrinho, Manoel D. Sousa Neto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-06T21:00:51Z (GMT). No. of bitstreams: 1 CarvalhoJunior_JacyRibeirode_D.pdf: 2755756 bytes, checksum: 59923c36198814e2215e893514dcc76d (MD5) Previous issue date: 2006 / Resumo: No presente estudo, dois experimentos, com base na Especificação n° 57 para materiais obturadores de canais radiculares da American National Standardl American Dental Association (ANSI/ADA), foram realizados. No primeiro experimento, foi avaliada a radiopacidade dos cimentos AR PlusTM, Endofill@, EndoREZTM e EpiphanyTM, e de cones de guta-percha Dentsply-Maillefer@ e ResilonTM, por meio da digitalização direta de imagens (sistema de imagem digital Digora). Placas de acrílico, contendo 6 orificios (5 mm de diâmetro x 1 mm de espessura), foram preenchidas com os materiais, posicionadas juntamente com um penetrômetro de alumínio, padronizada pela Especificação n° 57 da ANSI/ADA, e radiografadas a uma distância foco-objeto de 30 em, com tempo de exposição de 0,2 s. As médias- das densidades radiográficas de cada material foram obtidas em escala de cinza. Os valores decrescentes de densidade radiográfica dos materiais estudados foram: ResilonTM (214,28), AR PlusTM (206,42), gutta-percha (199,04), EpiphanyTM (188,04), Endofill@ (180,34) e EndoREZTM (178,18). No segundo experimento, foi avaliado se a redução do volume de material obturador de canal radicular necessário para a confecção de corpos-de-prova para os testes de solubilidade e alteração dimensional pós-presa possibilitaria a execução dos testes e-atenderia as exigências da Especificação n° 57 da ANSI/ADA. Inicialmente, determinou-se a densidade dos corpos-de-prova padronizados (ANSI/ADA), para o teste de solubilidade e para o teste de alteração dimensional pós-presa, utilizando-se o cimento EndofiU@. Após a determinação da densidade, moldes, de menores dimensões, foram confeccionados e divididos em 6 grupos para cada um dos testes. Os moldes originais, padronizados pela Especificação n° 57 da ANSI/ADA, foram utilizados como grupo controle. Para a confecção dos corpos-de-prova, foram utilizados os cimentos AR PlusTM e Endofill@. Para solubilidade, os corpos-de-prova foram divididos em grupos, sendo estes imersos em volumes de água destilada e deionizada diferenciados, de acordo com a massa do corpo-de-prova: GSl (20 x 1,5 mm, imerso em 50 ml de água destilada, estabelecido pela ANSI/ADA); GS2 (14,14 x 1,5 mm, 25 ml); GS3 (10 x 1,5 mm, 12,5 ml); GS4 (8,94 x 1,5 nurí, 10 ml); GS5 (7,75 x 1,5 mm, 7,5 ml); GS6 (6,32 xl,5 mm, 5 rnl); GS7 (4,47 x 1,5 mm, 2,5 rnl). Dois corpos-de-prova, de cada grupo, foram pesados, em conjunto, antes. de serem imersos em água destilada e deionizada, e armazenados a 37°C, por 24 h. Após esse período, foram secos e pesados novamente. A solubilidade foi calculada pela perda de massa do conjunto (em %) e a água destilada utilizada foi submetida à espectrofotometria de absorção atômica, para análise da presença dos íons Zn e Ca. Para alteração dimensional pós-presa, os seguintes grupos foram formados: GADl (12 x 6 mm, imerso em 30 ml de água destilada, estabelecido pela ANSI/ADA); GAD2 (6,09 x 6 mm, 15,22 rnl); GAD3 (4,48 x 6 mm, 11,19 ml); GAD4 (3,58 x 6 mm, 8,96 ml); GAD5 (6,04 x 4 mm, 6,72 rnl); GAD6 (4,03 x 4mm, 4,48 ml); GAD7 (3,58 x 3 mm, 2,24 ml). Após a mensuração do comprimento, com micrômetro, as amostras foram imersas em água destilada a 37°C, por 30 dias, removidas, secas e mensuradas novamente. Com os comprimentos iniciais e finais, determinou-se a variação percentual para cada grupo. Para o teste de solubilidade, houve correlação entre a massa inicial e a diferença entre massas inicial e final para os diferentes grupos. O cimento . Endofill@ apresentou valor médio de solubilidade estatisticamente superior ao AR PlusTM é (1,55% e 0,06%, respectivamente). Para alteração dimensional pós-presa, houve correlação entre o comprimento inicial e a diferença entre comprimentos inicial e final para os diferentes grupos. O cimento Endofill@ apresentou contração (0,56%) e o AR PlusTM, expansão (0,62%). Concluiu-se que os cimentos AR PlusTM, Endofill@, EndoREZTM e EpiphanyTM, e de cones de guta-percha Dentsply-Maillefer@ e ResilonTM, apresent~ram radiopacidade superior aos 3 mm de alumínio, determinados pela Especificação n° 57 da ANSI/ADA e que a redução do volume de material obturador de canal radicular necessário para a confecção de corpos-de-prova para os testes de solubilidade e alteração dimensional pós-presa, possibilitou a execução dos testes, atendendo as exigências da Especificação n° 57 da ANSI/ADA / Abstract: In the present study, two experiments, according to American National Standardl American Dental Association (ANSI/ ADA) Specification No. 57 for endodontic sealing materiaIs, were performed. In the first experiment, the radiopacity of AR PlusTM, Endofilf~, EndoREZTM, and EpiphanyTM sealers, and gutta-percha (Dentsply-Maillefer) and ResilonTM cones were evaluated using direct digital image processing (digital image DigoraTM system). Acrylic plates, containing 6 wells (1 mm in depth and 5 mm in diameter), were filled with the materiaIs, positioned together with an aluminum stepwedge, according to ANSI/ADA Specification 57, and radiographed on an object-to-focus distance of 30 cm, with exposure time of 0.2 s. The averages of radiographic densities for each material were obtained using gray scale values. The decreasing values of radiographic density of the studied materiaIs were: ResilonTM (214.28), AR PlusTM (206.42), guttapercha (199.04), EpiphanyTM (188.04), Endofill@ (180.34), and EndoREZTM (178.18). In the second experiment, it was evaluated the possibility of decreasing the volume of material necessary for the production of test samples for solubility and dimensional change following setting tests, which comply with ANSI/ADA Specification No. 57, without committing the accuracy of the results of these methods. Initially, it was obtained the density of the standard test samples (ANSI/ADA), for solubility, and dimensional ch~nge following setting tests, using Endofill@ sealer. Once original density was determined, moulds, with smaller dimensions, were prepared and divided into 6 groups, ITom each <me of the test. The moulds standardized to ANSI/ ADA Specification 57 were used as control group. To preparing of test samples, it was used AR PlusTM and Endofill@ sealers. For solubility test, the test samples were divided into groups, being the samples immersed into volumes of distilIed and deionized water, according to the mass ofthe test sample: GS1 (20 mm x 1.5 mm, immersed into 50 rnL distilled water, according to ANSI/ADA); GS2 (14.14 mm x 1.5 mm, 25 rnL); GS3 (10 mm x 1.5 mm, 12.5 rnL); GS4 (8.94 mm x 1.5 mm, 10 mL); GS5 (7.75 mm x 1.5 mm, 7.5 rnL); GS6 (6.32 mm x 1.5 mm, 5 rnL); GS7 (4.47 mm x 1.5 mm, 2.5 rnL). Two test samples of eaclí group, were weighted, in set, before being immersed in distilled and deionized water, and stored at 37°C, for 24 h. After this time, they were dried and weighted again. The solubility was calculated using the weight loss (%) and the distilled water was evaluated through atomic absorption spectrometry analysis, to verify the presence ofZn, and Ca ions. For dimensional change following setting test, the following groups were performed: GDC1 (12 x 6 mm, immersed into 30 rnL distilled water, according to ANSI/ADA); GDC2 (6.09 x 6 mm, 15.22 rnL); GDC3 (4.48 x 6 mm, 11.19 rnL); GDC4 (3.58 x 6 mm, 8.96 rnL); GDC5 (6.04 x 4 mm, 6.72 rnL); GDC6 (4.03 x 4mm, 4.48 rnL); GDC7 (3.58 x 3 mm, 2.24 rnL). After height measurement using amicrometer, the test samples were immersed into distilled water, and stored at 37°C, for 30 days, removed, dried and measured again. With initial and final heights, it was established the percentage variation for each group. For solubility test, there was correlation between the initial mass and the difference among initial and final masses for the different groups. The Endofilfi) sealer present~d mean value significant1y higher than AR PlusTM sealer (1.55% and 0.06%, respectively). For dimensional change following setting, there was . correlation between the initial height and the difference among initial and final heights for the different groups. The Endofill@ sealer presented 'shrinkage (0.56%) and AR PlusTM sealer, expansion (0.62%). It can be conc1uded that AR PlusTM, Endofill@, EndoREZTM, and EpiphanyTM sealers, and gutta-percha (Dentsply-Maillefer) and ResilonTM cones showed radiopacity above the 3 mm of aluminum reco.mmended by ANSI/ADA Specification 57. In addition, the volume reduction of root canal filling material necessary for the production of test samples for solubility and dimensional change following setting tests made possible the execution ofthe tests, following the recommendations of ANSI/ADA Specification 57 / Doutorado / Materiais Dentarios / Doutor em Materiais Dentários

Made available in DSpace on 2014-10-09T12:40:58Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:39Z (GMT). No. of bitstreams: 1 03973.pdf: 4389182 bytes, checksum: b10987cb9b3ec2a2bd2d1083fded1bfc (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Orientador: Marcela Rocha de Oliveira Carrilho / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-13T10:43:41Z (GMT). No. of bitstreams: 1 Malacarne-Zanon_Juliana_D.pdf: 9128347 bytes, checksum: 0fea8a055f819faabf3edb9b08ea04de (MD5) Previous issue date: 2009 / Resumo: Este estudo, composto por três trabalhos, avaliou o efeito de diferentes tipos e concentrações de solventes orgânicos no grau de conversão (DC) e na permeabilidade de diferentes sistemas adesivos. No primeiro estudo, o DC de cinco adesivos experimentais de composição hidrófila/hidrófoba conhecida (R1<R2<R3<R4<R5), contendo 5%p/p ou 15%p/p etanol, assim como a sorção (WS), a solubilidade (SL) e a cinética de difusão da água (D) nos polímeros obtidos foram mensurados. No segundo estudo, a WS, a SL e a nanoinfiltração de prata (NN) em adesivos experimentais (R2, R3 e R5), polimerizados na presença de 15%p/p etanol ou 15%p/p acetona, foram avaliados após 7 dias (7d) e 6 meses (6m) de armazenamento. No terceiro estudo, foi avaliada a NN em sete adesivos comerciais, formulados com diferentes tipos e concentrações de solventes, para serem aplicados ao substrato dental com diferente número de passos clínicos. Todos os espécimes foram confeccionados em matriz metálica (0,8mm x 5,8mm), aplicando-se 80s de fotoativação a 650mW/cm2. O DC foi determinado por espectroscopia de infra-vermelho. Para o cálculo de WS, SL e D, os espécimes foram tratados de acordo com as normas da ISO 4049, exceto para os tempos de aferição das massas úmidas, que foram obtidos sequencialmente durante os 7 primeiros dias de armazenagem em água e após 6 meses. Para avaliação da nanoinfiltração, os espécimes foram infiltrados com nitrato de prata amoniacal, conforme protocolo de nanoinfiltração (Tay et al., 2002), exceto pelo tempo que os espécimes permaneceram na solução de nitrato de prata (48 h). Em seguida, os mesmos foram preparados para observação em microscópio eletrônico de varredura. Os valores obtidos de DC, WS, SL e D foram submetidos à análise de variância e, em seguida, ao teste de Tukey (a=0,05). A presença de etanol aumentou o DC de todas as resinas avaliadas, especialmente as mais hidrófobas R1 e R2 (p<0,05). A WS, a SL e o D dos adesivos experimentais aumentaram com a hidrofilia. Em geral, as resinas contendo 15% de solvente exibiram maior WS, SL e D que suas correspondentes não-solvatadas ou contendo 5% de solvente (p<0,05). Não foram encontradas diferenças significativas entre os tipos de solventes presentes (p>0,05). Diferenças significativas entre os tempos de avaliação de WS, de SL e de NN, em geral, foram encontradas para os espécimes mais hidrófilos (p<0,05). Os componentes menos hidrófilos dos sistemas adesivos indicados para serem aplicados utilizando-se maior número de etapas clínicas mostraram menor NN que os sistemas adesivos "simplificados". Adesivos hidrófilos apresentaram diferentes permeabilidades em solução aquosa. Os mais hidrófilos, contendo maiores concentrações de solventes orgânicos, são mais permeáveis e, consequentemente, mais susceptíveis à degradação ao longo do tempo. / Abstract: This study evaluated the effect of different solvent types and concentrations on the degree of conversion (DC) and permeability of different adhesive systems. In the first study, the DC of five experimental adhesives of known hydrophilicity based on their solubility parameters (R1<R2<R3<R4<R5), added with 5 wt% or 15 wt% ethanol, were evaluated. Additionally, water sorption (WS), solubility (SL) and diffusion coefficient of water (D) through the polymerized materials were also assessed. In the second work, the WS, SL and nanoleakage (NN) in model adhesives (R2, R3 e R5), polymerized in the presence of 15 wt% ethanol or 15 wt% acetone, were evaluated after 7 days (7d) and 6 months (6m) of water storage. In the third work, it was assessed the NN in seven commercial adhesive systems, formulated with different solvent types and concentrations, to be applied on dentin under different clinical approaches. All specimens were produced on teflon molds (0.8mm X 5.8mm), with 80 s of photoactivation, under 650 mmW/cm2. The DC was determined by infra-red spectroscopy. For WS, SL and D evaluations, specimens were treated according to ISO 4049, except for the times of m2 measurements, which were collected successively during the first 7 days of storage in water, and, then, after 6 months. For NN, specimens were stored in silver nitrate solution, according to the protocol reported by Tay et al. (2002), and then prepared for scanning electron microscopy evaluation. Values of DC, WS, SL and D were analyzed by ANOVA and Tukey's test (a=0,05). Ethanol addition increased the DC of all tested resins, but specially of the most hydrophobic ones, R1 and R2 (p<0.05). Permeability increased with the hydrophilicity of resin blends. In general, solvated resins exhibited significantly higher permeability than their correspondent neat versions (p<0.05). The only exceptions were R1 and R5, the least and the most hydrophilic adhesives respectively. Both exhibited similar WS values for neat and solvated versions (p>0.05). There were no significant differences when compared both solvents (p>0.05). Differences in WS, SL and NN, attributable to different times of water storage, were found for neat and solvated versions of R5. NN in the less hydrophilic components of commercial adhesive systems, indicated to be applied on dentin under multiple steps, were less evident than that observed in "simplified" adhesives. Based on the limitation of this study, it was concluded that more hydrophilic and solvated adhesives are more permeable to fluids diffusion and more vulnerable to water degradation effects over time. / Doutorado / Doutor em Materiais Dentários

Orientador: Marcela Rocha de Oliveira Carrilho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T03:11:48Z (GMT). No. of bitstreams: 1 Malacarne-Zanon_Juliana_M.pdf: 636484 bytes, checksum: 6d6f6fb65dab84312134d942c458dc89 (MD5) Previous issue date: 2005 / Resumo: Este estudo avaliou o comportamento em água de sistemas adesivos com caráter hidrófilo diferentes. No primeiro estudo, a cinética de difusão da água foi avaliada a partir da mensuração da sorção, da solubilidade e do coeficiente de difusão da água em cada adesivo selecionado. Os materiais empregados foram: as resinas adesivas dos sistemas Clearfil SE (SE) e Scotchbond Multiuso (MP), e os adesivos simplificados Single Bond (SB) e Excite (EX). Cinco resinas experimentais com caráter hidrófilo estabelecido em função de seus respectivos parâmetros de solubilidade foram também avaliadas de modo que servissem como referência de materiais mais ou menos hidrófilos. Os materiais foram dispensados em matriz metálica e fotoativados por 40s (650mW/cm2). Para cada material, foram obtidos quinze espécimes em forma de disco (0,8mm x 5,8mm). Estes foram armazenados em câmara dessecante a 37°C até que não houvesse variação de sua massa seca (m1), aferida em balança analítica. Em seguida, dez destes foram armazenados em água destilada, e tiveram suas massas (m2), mensuradas após 1,2,3,4,5,6,7,14 e 28 dias, para avaliação da variação de massa ao longo do tempo. Ao final dos 28 dias, os espécimes foram novamente submetidos ao ciclo de dessecamento, para determinação da massa seca final (m3), e dos valores de sorção e solubilidade. Os cinco espécimes restantes foram também armazenados em água destilada, mas tiveram suas massas ¿úmidas¿ mensuradas em intervalos mais curtos para o cálculo do coeficiente de difusão da água em cada material. A composição e o caráter hidrófilo dos materiais influenciaram o trânsito de fluidos através dos mesmos. Dentre os adesivos comerciais, os sistemas mais hidrófilos (SB e EX) apresentaram valores de sorção, de solubilidade e de coeficiente de difusão da água significativamente maiores que dos adesivos menos hidrófilos (MP e SE) (p<0.05). Comportamento semelhante foi observado com a resina experimental mais hidrófila, R5. Com exceção da R1, todos os adesivos (comerciais e experimentais) apresentaram o maior aumento de massa no primeiro dia de armazenamento em água. Num segundo estudo, foi avaliado o efeito da armazenagem em água na resistência máxima à tração (RMT) dos adesivos comerciais referenciados. Para cada adesivo, foram obtidos 60 (±2) espécimes com área de secção transversal retangular de aproximadamente 1mm2. Estes foram armazenados em câmara dessecante a 37°C por 24 horas. Doze a treze espécimes de cada material foram submetidos ao ensaio de tração a 0,5mm/min tão logo foram removidos da câmara dessecante. Os demais foram armazenados em água destilada a 37°C e testados após 24h, 7 dias, 30 dias ou 180 dias. O armazenamento em água por 24h determinou a redução significativa da RMT de todos os adesivos (p<0,05). A armazenagem prolongada em água promoveu a queda dos valores de RMT apenas para o adesivo EX, após 180 dias (p<0,05). Com base nos resultados, é possível concluir que adesivos mais hidrófilos absorvem mais água num período mais curto de avaliação. A queda mais significativa nos valores de RMT ocorreu após as primeiras 24 horas de armazenamento em água, coincidindo com o período de maior absorção de água / Abstract: This study evaluated the effect of water storage on the kinetics of moieties diffusion and on the ultimate tensile strength of dental adhesives with different degree of hydrophilicity. In the first study, kinetics of moieties diffusion in commercial and experimental adhesives were evaluated using parameters as itswater sorption, solubility and water diffusion coefficient after ageing in distilled water. Four current dental adhesives were employed: the bonding resins of Clearfil SE Bond (SE) and Scotchbond Multi-Purpose (MP) systems, and the simplified ¿one-bottle¿ systems, Single Bond (SB) and Excite (EX). Five experimental resins with hidrophilicity recognizably different were used as reference. Specimen discs were prepared from each material by dispensing the uncured resin into a mould (5.8mm x 0.8mm). The specimens were placed in a desiccator at 37°C until a constant mass was obtained. After desiccation, the cured specimens were stored in distilled water and the kinetic of moieties diffusion was evaluated during the following times: 1,2,3,4,5,6,7,14 and 28 days. Shorter time intervals were used to calculate diffusion coefficient. After the 28 days, water sorption and solubility related to the entire period of storage were determined. Resin composition and hydrophilicity influenced water sorption, solubility and kinetics of moieties diffusion of both the commercial and experimental resins. Between commercial adhesives, the most hydrophilic systems (SB and EX) showed water sorption, solubility and diffusion coefficient values significantly greater than the least hydrophilic materials (SE and MP). The most hydrophilic experimental resin, R5, showed the highest values of water sorption, solubility and diffusion coefficient. Except for resin R1, all materials (commercial and experimental) presented the greatest mass gain at the first day of water storage. In a second study, the effect of water storage on the ultimate tensile strength (TS) of the same commercial was evaluated. I-shaped specimens were prepared by pouring the adhesives mentioned above into a brass mould. The adhesives were light-cured, removed from the mould and stored in a desiccator at 37°C for 24 hours. Afterwards, twelve to thirteen specimens of each adhesive were tested under tension at 0.05 mm/min, while the remaining specimens were stored in distilled water for 24 hours, 7, 30 and 180 days, before testing. In contrast to dry storage, water immersion produced significantly lower values of UTS for all materials (p<0.05), within the first 24 hours of storage. For the adhesives SE, MP and SB no significant changes in the UTS were observed along the whole period of ageing in water. However, a significant reduction in the UTS was detected after 180 days of water storage for the EX system (p<0.05). Based on the results brought about with these two studies, it can be concluded that more hydrophilic dental adhesives absorb more water within a short period of storage. The greatest decrease in UTS occurred after 24 hours of water storage; period in which was also observed the greatest amount of water uptake. Prolonged water storage had a detrimental effect on the UTS of the EX system, one of the most hydrophilic adhesives employed in the study / Mestrado / Materiais Dentarios / Mestre em Materiais Dentários

Although Malaria rates are on the decline due to the efforts of the World Health Organization and other organizations dedicated to the eradication of this disease, a relaxed attitude towards the development of new antimalarial entities would be flawed. Due to the emergence of resistance in the parasite, the almost 50% world-wide reduction in malarial death rates that have been produced over the past 15 years are threatening to be lost New drugs are urgently needed and our approach focuses on the re-evaluation and optimization of the historic antimalarial ICI 56,780. Due to its causal prophylactic activity, along with its ability to prevent transmission and potent blood schizonticidal activities, it was revisited with the hopes of first understanding which functionalities were responsible to the compound's activity. Secondly, we wanted to optimize the substituents in the 3, 6 and 7-positions. Finally and most importantly, we wanted to address the cross-resistance problem of the ICI 56,780 scaffold. Initial, analogues showed the importance of the ester in facilitating the convergence of the RI towards 1. Although those analogues lost activity in W2, TM90-C2B, and Pb, they were our first glimpse at this important trend that was later exploited in our 3-halo-6-butyl-7-(2-phenoxyethoxy)quinolin-4(1H)-one and 3-halo-6-butyl-2-methyl-7-(2-phenoxyethoxy)quinolin-4(1H)-ones which showed RI values of < 5 for our best analogues. Although our lead compound 3-bromo-6-butyl-2-methyl7-(2phenoxyethoxy)quinolin-4(1H) one possessed decreased activities as compared to ICI 56,780 at 2.60 nM for W2, 12.2 nM for TM90-C2B and 2.12 nM for Pb, it had 100% inhibition of parasite development on day 6 PE in our scouting assay and 61% inhibition on day 6in our Thompson model, increased from the < 2% value given by the ICI 56,780. Solubility and unfavorable in vivo stability were still major issues for this scaffold. Therefore, a series of piperazinyl 4(1H)-quinolones with greatly enhanced solubility were designed and tested in detailed structure activity relationships and structure property relationship studies. Initial results showed that 7-piperazinyl-4(1H)-quinolones possessed greatly increased solubilities when compared to ICI 56,780 analogues. Primarily, the linker length and the piperazine core was probed. This showed that compounds with a single carbon spacer were most active. Further testing of the 6-position gave methyl 6-methyl-4-oxo-7-((4-phenylpiperazin-1-yl)methyl)-1,4-dihydroquinoline-3-carboxylate with W2 and TM90-C2B values of 0.435 nM and 147 nM respectively. Substitution on the piperazinyl phenyl gave the most active compounds however the RI of >1500 was unacceptable. Because of this, 3-halo substituents were added to these quinolones with promising results. With RIs of < 3, the compounds were promising, however they were not active in vivo. However, methyl 6-methoxy-4-oxo-7-((4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)-1,4-dihydroquinoline-3-carboxylate and methyl 6-methyl-4-oxo-7-((4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)-1,4-dihydroquinoline-3-carboxylate both gave cures in our in vivo Thomson model. These studies highlight the potential in using detailed structural activity and structural property studies to re-evaluate and optimize historic antimalarials. These studies have introduced a new generation of soluble 4(1H)-quinolones with high potency against P. falciparum.

Master of Science / Food Science Institute / Jayendra K. Amamcharla / Fouling and biofilm formation on stainless-steel (SS) surfaces can be sources for cross-contamination and pose a great threat to the public health and food quality. The dairy industry needs an intervention strategy focusing on technologies discouraging the biofilm attachment and developing a sustainable eco-friendly approach for biofilm removal from the dairy processing surfaces. Since fouling encourages the attachment of bacteria to the SS surfaces, it becomes important to study the ways of reducing the fouling. The bacterial attachment to the fouled SS surfaces can be prevented by modifying the SS surface properties by chemical (using coatings) or mechanical methods. On the other hand, the degree of fouling can also be reduced by using good quality raw materials. The objective-1 of the study was focused on understanding the relationship between effect of milk protein concentrate (MPC80) solubility characteristics and fouling on SS surfaces during thermal processing. The powders were stored at different temperatures (25 ºC and 40 ºC) for 2 weeks to generate powders with different dissolution characteristics. Fouling characteristics of reconstituted MPC80 powder were studied using a custom-built benchtop plate heat exchanger. Exposing the MPC80 powder to a higher temperature during storage (40 ºC) significantly decreased the solubility and increased the amount of foulant on SS coupons (P < 0.05). Microscopic investigations (scanning electron microscopy and laser scanning confocal microscopy) of resulting fouled layers revealed heterogeneous fouling layers of varying tomographies, consisting of lipids, proteins, and calcium. In the second study, the efficacy of Micro- and Nano-bubble aqueous ozone (MNAO) as a disinfectant was studied in removal of Bacillus cereus and Bacillus licheniformis biofilm from the SS surface. For the Bacillus cereus biofilm removal, a log reduction of only 0.68 cfu/cm2 was observed after the de-ionized water wash. Whereas both MNAO and cleaning-in-place (CIP) treatments significantly reduced the bacterial counts by 2.43 and 2.88 log10 cfu/cm2, respectively. On the other hand, for the Bacillus licheniformis biofilm removal from SS surfaces, a significant log reduction observed was 1.45, 3.03, 2.92 log10 cfu/cm2, respectively after de-ionzed water, MNAO, and CIP treatments. Thus, it was observed that MNAO has great potential for removal of Bacillus cereus and Bacillus licheniformis biofilms from the SS surface, and can be used in the dairy industry as an effective sanitizer/disinfectant

Aqueous solubilities of twelve chlorinated benzenes were determined by two methods. In one method, the solutions in water were prepared by a vigorous stirring method followed by n-hexane extraction and GC-ECD analysis. In the second method, HPLC was used to prepare the saturated solutions. Experimental results were compared with the predictive values, the relative standard deviations are around 10%. Most of the chlorinated benzenes exhibit water induced transformations. The transformation products were either isomeric or with higher and lower numbers of chlorine substituents. The transformation phenomena can be explained by polarity, symmetry, reactivity of the chlorine atoms, and hydrophobic interactions. The mechanism of the transformation is governed by the radical mechanism.

Barium sulphate is a widely used analytical precipitate and for this reason its properties have been extensively studied. The variety of results encountered with barium sulphate samples prepared by different methods is an indication of the complex nature of this interesting substance. Intro., p. 8.

African horsesickness virus (AHSV) belongs to the Orbivirus genus in the family Reoviridae. This non-enveloped virus consists of an outer capsid formed by two structural proteins, VP2 and VP5, and an inner core formed by structural proteins VP7 and VP3. Three additional structural proteins associated with viral replication, as well as ten dsRNA molecules responsible for replication, are found inside the core. VP7 is the smallest of the structural proteins and each monomer consist of two domains, a hydrophilic top and hydrophobic bottom domain. Upon expression of VP7, the protein spontaneously assembles into trimers. Recombinant expression of the core protein VP7 results in large hexagonal structures formed by a double layer of these VP7 trimers with the hydrophobic bottom domains on the inside and hydrophilic top domains on the outside. The use of these crystal structures as a general display system for the display of foreign peptides/epitopes is being investigated in our group. In this regard, sites for the insertion of foreign peptides/epitopes were constructed at amino acid positions 177, 144 and 200 of the top domain of the VP7 protein and the resultant proteins named vectors AHSV-9 VP7-177, AHSV-9 VP7-144 and AHSV-9 VP7-200. Various inserts ranging from the HIV-1 ELDKWA epitope and FMDV VP1 epitopes to the eGFP peptide were inserted and subsequently analysed for immunogenicity. Results showed that a significant immune response was only elicited if the soluble trimer component of a chimeric VP7 protein was used for inoculation purposes. The crystal particles initially investigated as a display system did not result in any immune response. These results emphasized the importance of protein solubility for eliciting a significant immune response. The importance of solubility prompted an investigation into the use of the Bluetongue virus (BTV) VP7 protein as a vaccine display system. This protein is inherently more soluble than AHSV VP7 and does not result in crystal hexagonal structures if recombinantly expressed. An insertion site analogous to that of the AHSV-9 VP7-177 vector, located at amino acid 177 within an RGD loop in the top domain of VP7 was constructed. This new BTV VP7 vector, BTV-10 VP7-169, was characterised with regard to solubility and the ability to form trimers. In order to investigate the effect on solubility and trimerisation, FMDV VP1 epitope and eGFP were inserted into the BTV-10 VP7-169 vector. Results showed that following the construction of the insertion site, the vector was largely insoluble compared to the AHSV VP7 vectors and that insertion of the abovementioned peptides/epitopes did not have a significant effect on solubility. Although trimers were present, the yield was low compared to that of the AHSV chimeric VP7 proteins. Methods of improving the solubility of the chimeric VP7 proteins were investigated by treatment with solubilisation agents, sarkosyl and L-arginine. The results indicated that a strong denaturant such as sarkosyl can solubilise the particulate component of all chimeric VP7 proteins whereas Larginine had limited effect. The effect of these agents on the folding of the proteins were evaluated using fluorescence, since the ability to fluoresce is regarded as an indicator of correct folding. A comparison of the different VP7-eGFP proteins treated with these solubilisation agents showed that the sarkosyl solubilised proteins were not necessarily correctly folded. These results combined with the previously performed solubility assays indicated that a large proportion of correctly folded chimeric VP7 proteins associate with the particulate fraction. Investigation showed that expression of a large amount of correctly folded chimeric proteins results in the aggregation of these proteins within the expressing host cell. Once harvested these proteins remain associated with the insoluble fraction but can be solubilised by arginine treatment, or in some cases mere resuspension in a low-salt buffer, and used for vaccination purposes. In conclusion, the comparative analyses of solubility and trimerisation for the display vectors indicated that AHSV-9 VP7-144 vector may be most suitable for the display of foreign epitopes/peptides as it consistently yielded the largest component of correctly folded proteins. Furthermore, considering that large amounts of correctly folded chimeric VP7 proteins occurred in the insoluble component of each the VP7 display proteins, this study emphasize that use of solubility assays alone does not provide adequate information regarding the potential of a display vector for vaccination purposes. / Dissertation (MSc)--University of Pretoria, 2013. / Genetics / unrestricted