Orientador: José Angelo Camilli / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-19T19:59:03Z (GMT). No. of bitstreams: 1 Soares_EveliseAline_D.pdf: 3197082 bytes, checksum: ca95784093e801f419ec02ca8aea5020 (MD5) Previous issue date: 2011 / Resumo: Introdução: O tecido ósseo pode sofrer alterações em suas propriedades bioquímicas, morfológicas, bioquímicas e biomecânicas sob a influência de determinadas doenças. Níveis elevados de colesterol e hiperlipidemia podem causar alterações no osso, comprometendo a osteogênese e resistência mecânica. A sinvastatina é um medicamento do grupo de estatinas mais comumente utilizado para o tratamento d hiperlipidemia, reduzindo o nível de colesterol. Além disso, estudos com estatinas têm demonstrado bons resultados na prevenção e tratamento da osteoporose. Objetivos: Avaliar o efeito da hiperlipidemia e da utilização de sinvastatina sobre as propriedades biomecânicas, a estrutura do osso cortical e trabecular e osteogênese em camundongos LDLr(-/-) e selvagens. Métodos: Neste estudo foram utilizados camundongos do tipo selvagem (C57BL6) (Grupo W) e camundongos homozigotos para a ausência do gene receptor LDL (LDLr-/-) (Grupo L), todos do sexo masculino com 3 meses de idade. Os animais foram divididos em dois grupos experimentais, que foram subdivididos em quatro grupos de 12 animais cada: Experimento I (grupo W - ração padrão; Grupo WH - dieta hiperlipídica; Grupo L - ração padrão e Grupo LH - dieta hiperlipídica) e Experimento II tratados com sinvastatina (S) (Grupo WS - ração padrão; Grupo WHS - dieta hiperlipídica; Grupo LS - ração padrão e Grupo LHS - dieta hiperlipídica). Após 15 dias de experimentação um defeito ósseo de 3mm de diâmetro foi produzida cirurgicamente no osso parietal direito em cada animal. No final de 60 dias de experimentação os animais foram sacrificados. O sangue foi coletado e os fêmures e o osso parietal direito foram retirados para estudo histológico e mecânico. Resultados: Os dados obtidos neste estudo originou três artigos. O primeiro artigo "Efeitos da hiperlipidemia sobre as propriedades biomecânicas e morfológicas do fêmur de camundongos LDLr(-/-)" aceito para publicação no Journal of Bone and Mineral Metabolism, o segundo "Efeitos da sinvastatina sobre as propriedades morfométricas e mecânicas no fêmur de camundongos" formatado para submissão ao Journal of Orthopaedic Research e o terceiro artigo "Efeitos da hiperlipidemia e sinvastatina na reparação óssea de defeitos na calvária de camundongos LDLr-/-" esta sendo preparado para a publicação. Conclusão: A dieta hiperlipídica causa alterações na integridade óssea e que o uso da sinvastatina foi eficaz para preservar as propriedades biomecânicas do fêmur nos animais tratados com dieta comercial, no entanto, seu efeito sobre o tecido ósseo pode ser comprometido pela ingestão de uma dieta rica em gorduras. A osteogênese foi restrita nos camundongos LDLr-/-, principalmente nos grupos alimentados com dieta rica em gorduras / Abstract: Introduction: The bone tissue can suffer alterations in their biochemical morphological and biomechanical properties under influence of certain diseases. High levels of cholesterol and hyperlipidemia can cause changes in the bone, compromising osteogenesis and mechanical strength. The simvastatin is a drug of the statins group most commonly used for the treatment of hyperlipidemia, reducing the cholesterol level. Additionally, studies with statins have demonstrated good result in the prevention and treatment of osteoporosis. Objectives: Evaluate the effect of hyperlipidemia and the use of simvastatin on the biomechanical properties, structure of cortical and trabecular bone and osteogeneses in LDLr(-/-) and wild-type mice. Methods: In this study were used wild-type (W) mice (C57BL6) and homozygous mice for the absence of the LDL receptor gene LDLr-/- (L), all male with 3 months of age. The animals were divided into two experimental groups that were subdivided into four groups of 12 animals each: Experiment I (Group W - standard ration; Group WH - high-fat diet; Group L - standard ration; Group LH - high-fat diet) and Experiment II with simvastatin (S) (Group WS - standard ration; Group WHS - high-fat diet; Group LS - standard ration; Group LHS - high-fat diet). After 15 days of experimentation a bone defect measuring 3mm in diameter was surgically produced in the right parietal bone in each animal. At the end of 60 days of experimentation the animals were euthanatized. Blood was collected and the femurs and the right parietal bone were removed for mechanical and histological study. Results: The data obtained in this study originated three articles. The first article "Effect of hyperlipidemia on femoral biomechanics and morphology in LDLr-/- mice" was accepted for publication in the Journal of Bone and Mineral Metabolism, the second "Effects of simvastatin on morphometric and mechanical properties in the femur of mice" was submitted to Journal of Orthopaedic Research and the third article "Effect of hyperlipidemia and simvastatin on bone repair of the calvaria of the LDLr-/- mice" is being prepared for publication. Conclusions: The high-fat diet caused alteration in bone integrity and the treatment with simvastatin was effective in preserving the biomechanical properties and structure of the femur in the animals treated with low-fat diet, however, its effect on bone tissue can be compromised by a high-fat diet. Osteogenesis was reduced in LDLr-/- mice, especially in the high-fat diet groups / Doutorado / Anatomia / Doutor em Biologia Celular e Estrutural

Foi estudado, através de ensaio de tração, o Nb policristalino com teor de hidrogênio de 0 a 50 partes por milhão em peso (ppm-p) nas temperaturas de 223, 273 e 293 K. Os ensaios de tração a velocidades constantes foram realizados com taxas iniciais de deformaçao de 4,2 X 10-5 e 42 X 10-5 s-1 , e os parâmetros de ductilidade e resistência mecânica foram analisados em função da concentração de hidrogênio. Foram também obtidos o coeficiente de sensitividade a taxa de deformação (m) e o volume de ativação (V) através de ensaios de tração, alternando-se abruptamente a taxa de deformação entre os valores acima mencionados, em sucessivos pontos da curva tensão-deformação. Para o cálculo destes dois últimos parâmetros foi proposta uma análise detalhada, considerando-se os efeitos elásticos e o encruamento durante a deformação plástica uniforme. Todo o estudo foi acompanhado por análise fratográfica Que permitiu verificar três comportamentos de ruptura da liga Nb-H, dependendo do teor de hidrogênio e da temperatura. A 223K foi observado que há uma forte redução de ductilidade do Nb para teores de hidrogênio até 10 ppm-p, sendo que para este teor o seu comportamento foi totalmente frágil / Tensile testing at 223, 273 and 293 K was carried out on polycrystalline Nb dopped from 0 to 50 parts per million in weight (ppm-wt) of Hydrogen. The tensile testing at constant velocity was done at 4,2 X 10 -5 and 42 X 10-5 s-1 of initial strain rate, and the ductility and strength parameters was analysed as a function of the hydrogen content. It was also obtained the strain rate sensitivity (m) and the activation volume (V), from tensile testing, cycling between the two above specified strain rates, at several points of the stress-strain curve. For the calculation of this two last parameters it was proposed a detailed analysis, considering the elastic effect and the work hardening during the uniform plastic deformation. All these studies was followed by fratographic analysis that alowed the identification of three rupture behavior for the Nb-H alloy, depending of the temperature and the hydrogen content. At 223 K, it was observed that there is a strong embrittlement of Nb for hydrogen content up to 10 ppm-wt, and for this value the behavior was completely brittle

Foi estudado, através de ensaio de tração, o Nb policristalino com teor de hidrogênio de 0 a 50 partes por milhão em peso (ppm-p) nas temperaturas de 223, 273 e 293 K. Os ensaios de tração a velocidades constantes foram realizados com taxas iniciais de deformaçao de 4,2 X 10-5 e 42 X 10-5 s-1 , e os parâmetros de ductilidade e resistência mecânica foram analisados em função da concentração de hidrogênio. Foram também obtidos o coeficiente de sensitividade a taxa de deformação (m) e o volume de ativação (V) através de ensaios de tração, alternando-se abruptamente a taxa de deformação entre os valores acima mencionados, em sucessivos pontos da curva tensão-deformação. Para o cálculo destes dois últimos parâmetros foi proposta uma análise detalhada, considerando-se os efeitos elásticos e o encruamento durante a deformação plástica uniforme. Todo o estudo foi acompanhado por análise fratográfica Que permitiu verificar três comportamentos de ruptura da liga Nb-H, dependendo do teor de hidrogênio e da temperatura. A 223K foi observado que há uma forte redução de ductilidade do Nb para teores de hidrogênio até 10 ppm-p, sendo que para este teor o seu comportamento foi totalmente frágil / Tensile testing at 223, 273 and 293 K was carried out on polycrystalline Nb dopped from 0 to 50 parts per million in weight (ppm-wt) of Hydrogen. The tensile testing at constant velocity was done at 4,2 X 10 -5 and 42 X 10-5 s-1 of initial strain rate, and the ductility and strength parameters was analysed as a function of the hydrogen content. It was also obtained the strain rate sensitivity (m) and the activation volume (V), from tensile testing, cycling between the two above specified strain rates, at several points of the stress-strain curve. For the calculation of this two last parameters it was proposed a detailed analysis, considering the elastic effect and the work hardening during the uniform plastic deformation. All these studies was followed by fratographic analysis that alowed the identification of three rupture behavior for the Nb-H alloy, depending of the temperature and the hydrogen content. At 223 K, it was observed that there is a strong embrittlement of Nb for hydrogen content up to 10 ppm-wt, and for this value the behavior was completely brittle

This thesis reports on the synthesis and characterisation of various types of oxidised multiwalled carbon nanotubes (O-MWCNTs) modified polymeric membranes. These OMWCNT modified polymeric membranes were then assessed in terms of their remediation potential, in particular for the removal of estrogenic hormones, dissolved proteins and salts from brackish water sources. The fabricated O-MWCNT-based polyethersulfone (PES) membranes were applied as (i) adsorptive membranes, (ii) molecular-sieving membranes and (iii) as membrane substrates for thin-film composite nanofiltration (NF) membrane preparation. The research work commences with the preparation of MWCNTs via a facile catalytic chemical vapour deposition method and their chemical oxidation with strong acids in order to introduce hydrophilic carboxylic (–COOH) and hydroxyl (–OH) surface functional group moieties on the MWCNT outer walls. Intrinsically, MWCNTs are chemically inert and tend to form agglomerated nanoclusters (due to van der Waals interaction forces), which induce further difficulties in their homogenous dispersion in polar solvents (such as N-methyl-2- pyrrolidone and dimethylacetamide) employed to dissolve the polymers in the study. The introduction of these oxygen-containing moieties was therefore necessary to aid the dispersion of MWCNTs in organic solvents and for their enhanced interaction with PES and sulfonated polysulfone (SPSf). The PES/O-MWCNT ultrafiltration (UF) membranes were produced via a non-solvent induced phase separation (NIPS) method and employed in the adsorptive removal of natural hormone estrone (E1). The PES/O-MWCNT UF membranes thus prepared were characterised using SEM, AFM, zeta potential measurements and MWCO experiments. It was found that the adsorption of E1 initially increased with an increase in O-MWCNT content followed by a constant decline on further increments. Moreover, the inclusion of OMWCNTs (0.5 wt.%) in the PES membrane matrix resulted in an increase in the maximum adsorption capacity for E1 compared to pristine PES membrane, i.e., 31.25 mg/g adsorption capacity was achieved for PES/O-MWCNT compared to 23.81 mg/g for bare PES UF membrane. Based on the correlation coefficients, the Freundlich isotherm provided a better fit for the adsorption data and the adsorption kinetics followed the pseudo-second order kinetic model. Interestingly, after five regeneration cycles, the PES/O-MWCNT membranes were found to maintain similar adsorption efficiencies. The PES/O-MWCNT membranes thus prepared, present a viable approach for the removal of natural hormones and other endocrine disruptors present in water systems compared to the use of common adsorbents such as activated carbon, which end up generating large amounts of chemical sludge that require disposal in the environment. The third part of the study focused on the controlled formation of macrovoid-free polyethersulfone/sulfonated polysulfone (PES/SPSf) UF membranes with high water permeabilities, mechanical strength and antifouling properties, in the presence of O-MWCNTs. To date, the majority of polymeric nanocomposite membranes modified with O-MWCNTs as nanofillers, generally have finger-like structures and macrovoids in the membrane sublayer. While the presence of finger-like structures is favoured for the reduction in mass flow resistance, their presence induces mechanically weak points in the membrane and reduces the nanocomposite membranes’ mechanical strength properties and long-term performance stability. As such macrovoid-free PES/SPSf/O-MWCNT membranes were fabricated via the NIPS techniques, using H2O and polyethylene glycol (PEG 20 kDa) as non-solvent additives. The SEM cross-sectional images showed that a fully sponge-like morphology of the PES/SPSf membrane can be achieved in the presence of different loadings of O-MWCNTs. This was attributable to the formation of stronger hydrogen bonds between the SPSf polymer and non-solvent additives i.e., H2O, PEG 20kDa and OMWCNTs. The combination of the macrovoid-free morphology and homogenous distribution of high mechanical strength O-MWCNTs in the membrane matrix provided excellent mechanical strength enhancements for PES/SPSf/O-MWCNT membranes. Additionally, pure water flux initially increased from 598 L/m2 .h to 713 L/m2 .h followed by a decline to 578 L/m2 .h upon further increments in O-MWCNT contents, due to agglomeration of O-MWCNTs at higher loadings. The fabricated PES/SPSf/O-MWCNT membranes also displayed superior antifouling properties (FRR > 90%) and antibacterial properties (99% bacterial killing ratio) against E. coli bacteria. The fabricated support fabricfree PES/SPSf/O-MWCNT UF membranes with macrovoid-free sublayer morphologies displayed attractive features for use as UF membranes in the pre-treatment stages of water treatment and as support substrates for the preparation of TFC membranes. In general, sponge-like and macrovoid-free membrane structures are regarded as unfit for use as support membranes for TFC membrane preparation since they increase the membrane’s resistance to water flow, thereby reducing the overall TFC membrane permeability. This assumption has largely been based on sponge-like and macrovoid-free membranes structures achieved through the use of extremely high polymer concentrations, particularly using polysulfone (PSf) polymer. Hence, the sponge-like structures formed are very dense and less porous. Nevertheless, the macrovoid-free PES/SPSf/O-MWCNT membranes produced in this study, consisted of open cellular network microstructures within the membrane sublayer, which could be visualised at higher SEM magnifications. This part of the work therefore investigated the role of hydrophilic, macrovoid-free PES/SPSf and PES/SPSf/O-MWCNT as support membranes on the performance of TFC NF membranes. The TFC NF membranes were prepared via an efficient interfacial polymerization reaction between piperazine (PIP) and trimesoyl chloride (TMC). The deposition of the polyamide thin-film layer was confirmed by ATR-FTIR, SEM, AFM, contact angle and zeta potential measurements. Membrane performance results showed that TFC NF membranes fabricated on PES/SPSf/O-MWCNT support membranes displayed a 35% improvement in pure water flux with comparable salt rejections from those prepared on bare PES/SPSf support membranes. Salt rejection followed the order of Na2SO4 > MgSO4 > NaCl, which is typical for negatively charged NF membranes. It was established that the presence of hydrophilic O-MWCNTs in the support membrane allowed for the formation of a thin polyamide layer on the top surface of the support membrane, which gave rise to enhanced water permeability of the TFC NF membrane and the possibility of polyamide rejection layer within the support membrane pore channels. To further improve the performance of the TFC NF membranes, in particular, the monovalent/bivalent salt selectivity, a mixture of PIP and 2,4-diaminobenzene sulfonic acid (2,4-DABSA) at different weight ratios was prepared in the aqueous solution and reacted with TMC in the organic phase solution. It was found that the addition of low monomer weight ratio of 2,4-DABSA in the amine mixture, lead to the generation of a sulfonated TFC NF membrane with superior membrane performance in terms of pure water permeability (30.2 L/m2 .h), monovalent/bivalent salt selectivity (𝛼NaCl/Na2SO4 = 25.0) at low operating pressures (3 bar) and salt concentrations in the range of brackish waters. This was attributable to the combined presence of sulfonic acid groups on the membrane surface and the formation of the thin polyamide layer. Moreover, sulfonated TFC NF membranes exhibited good antifouling properties against bovine serum albumin (BSA), with FRR of 96.4% after three cycles of fouling and cleaning, with a fairly stable membrane performance over a 10-day period of pure water flux and Na2SO4 rejection testing. Indeed, the use of a macrovoid-free PES/SPSf/O-MWCNT support membrane did not only provide the mechanical strength for the deposition of TFC NF membrane, but also their open, cellular network microstructure, combined with high hydrophilicity and large surface pore sizes were beneficial in the reduction of polyamide layer thickness, and subsequently in the enhancement of TFC NF membrane performance. The study provided insightful information on lesser known aspects of O-MWCNT incorporated polymeric membranes, with regards to membrane structural configurations in relation to the membrane structure-performance relationships. It has been deduced that (i) the right combination of membrane surface characteristics and adsorbate solution chemistry is necessary for an open UF membrane to display reasonable removal efficiencies for low molecular-weight solutes, (ii) the combination of macrovoid-free membrane morphology with good dispersion of O-MWCNTs in the polymer matrix is necessary to realise significant enhancements in the mechanical properties of sulfonated membrane and (iii) formation of a thin sulfonated polyamide layer on top of the hydrophilic PES/SPSf/O-MWCNT support membrane is necessary to achieve high salt selectivity, and allow for the sulfonated TFC NF membrane to be operated at low pressures. / College of Engineering, Science and Technology