Orientadores: Maria Isabel Felisberti, Marco-Aurelio De Paoli / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-18T14:10:14Z (GMT). No. of bitstreams: 1 Gutierrez_MiguelChavez_D.pdf: 7288460 bytes, checksum: bbbd520c11973e6ce92e1852b824c208 (MD5) Previous issue date: 2011 / Resumo: Neste trabalho foram desenvolvidos biocompósitos baseados em acetato de celulose e fibras curtas de Curauá. Os compósitos foram preparados por extrusão em escala laboratorial e piloto, sendo estudada a influência do processamento, teor de fibras, teor e tipo de plastificante e tratamento das fibras, sobre as propriedades mecânicas e térmicas. As fibras foram tratadas com solução alcalina ou submetidas à extração com acetona. O tratamento das fibras com solução alcalina resultou em mudanças na rugosidade e do diâmetro das fibras, além da remoção parcial de hemicelulose e lignina. Já as fibras extraídas com acetona apresentaram principalmente uma diminuição do diâmetro. Biocompósitos reforçados com fibras tratadas apresentaram maior modulo elástico e maior condutividade térmica com relação aos compósitos reforçados com fibras não tratadas, sendo este efeito atribuído a uma melhor adesão interfacial. Dentre os plastificantes utilizados, o ftalato de dioctila (DOP) ou citrato de trietila (TEC), o DOP mostrou-se mais eficiente, causando uma diminuição mais acentuada da temperatura de transição vítrea (Tg) e do módulo elástico, resultando em materiais com maior resistência ao impacto em relação as formulações plastificadas com TEC. Os biocompósitos preparados em escala piloto apresentaram maior ganho do módulo elástico com relação à matriz plastificada e maior resistência ao impacto, que aqueles que foram preparados em escala laboratorial, associado principalmente a fibrilação e a diminuição da razão de aspecto das fibrilas. Devido a este fato, o modelo modificado da regra das misturas (ROM) mostrou-se mais adequado para prever o comportamento do módulo elástico dos biocompósitos preparados em escala piloto. A análise termogravimétrica mostrou que a presença das fibras não modifica o comportamento termo-oxidativo do acetato de celulose plastificado. Por último, biocompósitos de acetato de celulose plastificados com DOP apresentaram maior coeficiente de expansão térmica com relação às formulações com TEC, a temperaturas abaixo e acima da Tg. Acima da Tg, biocompósitos reforçados com fibras tratadas apresentaram maiores coeficientes de expansão térmica, devido a capacidade das fibras tratadas em sorver água / Abstract: In this work, biocomposites based on cellulose acetate and short Curaua fibers were prepared by extrusion in pilot and laboratory scale. The influence of processing method, content of fiber, content and type of plasticizer and treatment of the fibers were studied. The fibers were treated with alkali or extracted with acetone. Mercerization may result in partial hemicellulose and lignin extraction and decrease of the roughness and diameter of the fibers. Fiber s extracted with acetone had lower diameter. Biocomposites with treated fibers show higher Young modulus and lower thermal conductivity than composites with pristine fibers, due to better interfacial adhesion. Cellulose acetate was plasticized with dioctyl phthalate (DOP) or triethyl citrate (TEC). DOP is a better plasticizer for cellulose acetate, exhibiting lower glass transition (Tg), lower Young modulus and higher impact strength than formulations with TEC. Biocomposites prepared in pilot scale showed higher Young modulus with respect to the matrix and lower impact strength than composites prepared in laboratory scale, due to fibrilation and decrease in the aspect ratio. From this, the model of the modified rule of mixtures (ROM) was more efficient to predict the results of the Young modulus for composites prepared in pilot scale. In the thermogravimetric analysis, the Curaua fibers do not change the thermo-oxidative behavior of plasticized cellulose acetate. Cellulose acetate biocomposites with DOP showed higher thermal expansion coefficient than formulations with TEC, below and above Tg. Above Tg, biocomposites with treated fibers showed higher thermal expansion coefficients than biocomposites with pristine fibers, due to the ability of treated fibers to absorb water / Doutorado / Físico-Química / Doutor em Ciências

Orientador: Beatriz Eleutério Goi / Coorientador: Valdemiro Pereira de Carvalho Júnior / Banca: Pedro Ivo da Silva Maia / Banca: Ana Maria Pires / Resumo: Nas últimas décadas, a polimerização radicalar controlada (CRP) tem se tornado muito importante, pois permite a síntese de macromoléculas de arquiteturas específicas com um controle sobre as propriedades químicas e físicas. Sendo assim, este trabalho apresenta a síntese de novos complexos de Mn(II) e Fe(II) coordenados à ligantes bases de Schiff bidentados, que são resultantes da condensação do salicilaldeído com as seguintes cicloalquilaminas: (1) Ciclopentilamina, (2) Cicloexilamina, (3) Cicloeptilamina e (4) Ciclooctilamina, de forma que estes possam ser utilizados como mediadores da polimerização radicalar mediada por organometálicos. Os ligantes foram caracterizados pelas seguintes técnicas: espectroscopia de ressonância magnética nuclear de hidrogênio (RMN de 1H), espectroscopia de absorção na região do ultravioleta-visível (UV-Vis) e espectroscopia vibracional na região do infravermelho (FTIR). Já os complexos de Mn(II) e Fe(II) foram caracterizados pelas técnicas de FTIR, UV-Vis, voltametria cíclica (VC) e ponto de fusão (p.f.). Os estudos cinéticos de polimerização foram realizados para os complexos de manganês e ferro. O complexo [MnIIbis(N-Salicilideno-Ciclopentilamina)], Mn(L1)2, apresentou um melhor controle na polimerização do acetato de vinila com menores valores de polidispersidade e a curva de massa molecular (Mn) mais próxima aos valores da curva teórica. Já os complexos de ferro mediadores apresentaram um comportamento mais similar, não havendo muita... / Abstract: In the last decades, controlled radical polymerization (CRP) has become very important, since it facilitates the synthesis of macromolecules of specific architectures with excellent control over the chemical and physical properties. Thus, this work presents the synthesis of new Mn(II) and Fe(II) complexes coordinated with the bidentate Schiff bases ligands, which are the result of the condensation of salicylaldehyde with cycloalkylamines: (1) cyclopentylamine, (2) cyclohexylamine, (3) cycloheptylamine and (4) cyclooctylamine, so that they can be used as mediators of radical polymerization mediated by organometallic (OMRP). The ligands synthesized were characterized by proton nuclear magnetic resonance (1H-NMR) spectroscopy, ultraviolet-visible (UV-Vis) absorption spectroscopy and Fourier-transform infrared spectroscopy (FTIR) techniques. The synthesized Mn(II) and Fe(II) complexes were studied by FTIR, UV-Vis, cyclic voltammetry (CV) and melting point (m.p.). Kinetic polymerization studies were performed for the manganese and iron complexes. The [MnIIbis (N-Salicylidene-Cyclopentylamine)], Mn(L1)2, complex showed a better control in the polymerization of vinyl acetate with lower values of polydispersity and the molecular mass curve (Mn) closer to the values of the theoretical curve. However, the iron mediator complexes presented a more similar behavior, not having much difference in the kinetic curves / Mestre

Current epidemiological data showing that the use of the injectable contraceptive progestin Depotmedroxyprogesterone acetate (DMPA) is associated with increased HIV-1 acquisition is controversial. However, animal and ex vivo data reveal plausible biological mechanisms whereby MPA may increase HIV-1 acquisition. Relatively high levels of endogenous progesterone (P4) found in the luteal phase of the menstrual cycle have also been linked to increased HIV-1 acquisition in animal, clinical and ex vivo models. One of the central hypotheses of the present study was that the mechanism of MPA-induced increase in HIV-1 infection occurs via a different mechanism to that of the luteal phase. Furthermore, MPA has been shown to activate both the glucocorticoid receptor (GR) and its target, the progesterone receptor (PR) isoform B (PR-B), which are both transcription factors and regulate genes involved in immune function. Both the GR and PR are expressed in the cervix, the primary site of heterosexual HIV-1 infection. PR is regulated by endogenous estrogen (E2), of which the concentrations fluctuate throughout the menstrual cycle, and GR expression also varies in response to stress hormones, leading to conditions of varied relative levels of GR/PR. The immune-related consequences of changing the relative levels of GR and PR-B are not well understood. Therefore another hypothesis of this study was that changing the relative levels of GR/PR-B modulates HIV-1 infection and immunomodulatory gene expression in response to the GR/PR agonist, MPA. Since GR and PR-B recognize similar DNA target sequences and may regulate the same genes at the same time, the final hypothesis of the present study was that GR and PR-B reciprocally modulate each other’s activity, through possible association. To investigate the effects of exogenous hormones on HIV-1 infection and mechanisms thereof, peripheral blood mononuclear cells (PBMCs) and TZM-bl cervical cells were used as model systems for HIV-1 infection. These cells were stimulated with P4 and E2 at concentrations mimicking the menstrual cycle phases or with levels of MPA at the upper range of peak serum levels detected in DMPA users. Cells were infected with the R-tropic HIV-1 infectious molecular clone, HIV-1Bal_Renilla and luciferase assays were used to measure HIV-1 infection. Levels of HIV-1 CD4 receptor and CCR5 co-receptor protein or mRNA were measured by flow cytometry or qPCR, respectively, while activation of CD4+ T cells using the activation marker CD69 was measured by flow cytometry in PBMCs. To investigate the effects of changing GR/PR-B levels on HIV-1 infection and immune gene regulation, GR/PR levels were altered in End1/E6E7 immortalized endocervical and HeLa/TZM-bl cervical carcinoma cells by GR siRNA knockdown with or without the simultaneous over-expression of PR-B, and cells were stimulated with MPA or the GR agonist Dexamethasone. mRNA expression iii of key immunomodulatory genes in End1/E6E7 and HeLa cells was measured by qPCR. The modulation of GR activity by PR-B was assessed by promoter-reporter assay in COS1 and U2OS cells over-expressing GR and PR and stimulated with GR- and/or PR-specific ligands. Association of GR and PR-B was measured by co-immunoprecipitation in COS1 and MCF-7 cells, while co-localization of GR and PR-B was measured by confocal microscopy and super-resolution structured illumination microscopy in COS1 cells. MPA significantly increased HIV-1 infection in both PBMCs and TZM-bl cells, while luteal phase hormones did so to a lesser extent. However, MPA but not luteal phase hormones increased the ratio of CD4+/CD8+ T cells in PBMCs. MPA but not luteal phase hormones also increased CCR5 protein expression on CD4+ T cells in PBMCs and total CCR5 mRNA expression in TZM-bl cells. In addition, MPA but not luteal phase hormones increased activation of CD4+ T cells in PBMCs. Using a GR antagonist or GR siRNA, it was shown that the GR but not PR-B is required for MPA-, but not luteal phase hormone-induced increased HIV-1 infection in PBMCs and TZM-bls. The presence of PR-B altered the anti-inflammatory, GR-mediated regulation of some key immunomodulatory genes, including GILZ and IL-6, in End1/E6E7 and HeLa cells in response to MPA. In general, basal (unliganded) expression of immunomodulatory genes exhibited a pro-inflammatory profile in the presence of PR-B. Co-immunoprecipitation assays showed that GR and PR-B appeared to associate. Confocal microscopy suggested GR and PR co-localized in the nucleus in response to GR- and/or PRspecific ligands, while super-resolution microscopy showed that co-localization occurred in select regions within the nucleus. Taken together, MPA increases HIV-1 infection in a manner different from that of luteal phase hormones, most likely involving increased CD4+ T cell frequency (CD4+/CD8+ ratio), activation and increased expression of CCR5 on CD4+ T cells, and requiring the GR. Furthermore, PR-B modulates GR-mediated immune function gene regulation, via potential association and region-specific nuclear co-localization. This suggests that the relative levels of GR/PR may play an important role in determining the inflammatory and immune responses and HIV-1 infection in HIV-1 target cells, both in DMPA users and women not using hormonal contraception.

The fabrication of electrospun nanofibers has sparked great interest in both academia and industry owing to their unique properties, such as a high surface area to volume ratio, porosity, interconnected porous structure, or controllable fiber morphology. They are highly desired in numerous application areas such as filtration, biotechnology, and energy storage. Cellulose acetate is an ester of cellulose, one of the most abundant natural polymers, that is biodegradable, non-toxic, and has good stability. Electrospinning of cellulose acetate has received significant interest in a broad spectrum of applications, including membranes and air filters, drug-delivery systems, scaffolds for tissue engineering, sensors, and batteries. The electrospinning of cellulose acetate predominantly suffers from the use of toxic and hazardous solvents, which makes the final products less suitable for application in biosystems. In this work, the sustainable electrospinning of cellulose acetate has been shown using renewable-based green solvents, dimethyl carbonate, and cyclopentanone. A binary system consisting of these solvents has been applied. The addition of green salts and biosurfactants substantially improved the spinnability of the cellulose-based solutions. Altering the composition of the solvents allowed tuning of the fiber texture from highly porous to smooth fiber morphology. The thermal analysis revealed that the polymer’s thermal behavior had not been influenced by the salt in nanofibers. Incorporating additives into the polymer matrix resulted in enhanced mechanical properties of nanofibers. Uniform cellulose acetate-based porous nanofibers from green solvents and additives could be successfully fabricated, which has not been reported yet. Based on the reported advantageous properties of electrospun CA nanofibers, it may serve as a possible green and biodegradable porous support layer in thin-film composite membranes replacing the conventional fossil-derived polymeric membrane supports.

Multiple Sclerosis (MS) is a chronic and potentially disabling disease of the central nervous system (CNS) in which the immune system attacks the protective myelin layer that surrounds nerve cells. While the majority of individuals diagnosed with MS initially present with a non-progressive relapsing form of the disease, there is significant risk of eventually transitioning to a more progressive form for which there are few effective treatments. Consequently, early intervention with disease-modifying therapies (DMTs) is essential for effective disease management. Newly diagnosed patients are typically started on one of four first-line therapies (beta interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate). Though there are distinct differences between these treatments in regard to efficacy and safety, there is no uniform standard for making decisions about which to initiate treatment with. This review gives an overview of current first-line MS therapies, and seeks to highlight the lack of comparison data and the gaps in the current understanding of disease management, as well as the need for more comprehensive research in these areas.

The following were examined by taking advantage of TRDP using two-phase separation mixed solution: protein separation by the TRDC with the ternary mixed solution of water–acetonitrile–ethyl acetate, optical isomers separation by the TRDC with the ternary solution containing cyclodextrin as a chiral recognition molecule, development of the TRDC with a water–acetonitrile mixed solution containing sodium chloride as a two-phase separation mixed solution instead of the ternary solution, and introduction of the principle of the TRDC to a commercial HPLC system. Furthermore, the peroxioxalate CL detection was for the first time examined by using the ternary mixed solution. The investigation of the TRDP and TRDC, as well as the ternary mixed solution of water–acetonitrile–ethyl acetate, are interesting in view of not only analytical chemistry but also chemical engineering, and physical chemistry. / 博士(工学) / Doctor of Philosophy in Engineering / 同志社大学 / Doshisha University

Organic solvent nanofiltration (OSN) is a membrane-based sustainable alternative to conventional separation techniques because it is non-thermal and energy-efficient. The fabrication of membranes usually includes fossil-based polymers and toxic solvents that present significant challenges. For example, its declining availability, concerns about its degradability and cross-contamination that involve toxicity risks. Nowadays, there is an increasing interest in the development of more sustainable membranes that maintain an optimum performance even in harsh solvents. The aim of my thesis research is to develop stable OSN membranes from cellulose acetate and explore the use of deacetylation reactions. The effect of the degree of acetylation on the membrane performance and stability in different organic solvents was investigated. The chemical composition and morphology were investigated using Fourier Transform Infrared (FTIR), Scanning Electron Microscope (SEM), and Atomic Force Microscopy (AFM). It was found that cellulose acetate membranes with less than 22% acetylation present a satisfactory solvent resistance and rejection in harsh solvents, such as DMF and acetone. In the performance tests were identified two main trends: one for polar protic solvents and one for polar aprotic solvents. This was attributed to their capacity to interact with the membrane via H-bond formation. The molecular weight cutoff (MWCO) was in the range of 735–325 g mol–1 in aprotic solvents and higher than 885 g mol–1 for polar protic solvents. The results found in this research can be translated into a reduce in costs, waste generated, energy required, and time employed in the fabrication of membranes. Also, it opens potential areas in the industry as it can be implemented in harsh solvent environments.

The molecular species of diacylglycerol and alkylacylglycerol of Madin-Darby canine Kidney (MDCK) cells were analyzed to determine the sources of diradylglycerols generated during cell growth and phorbol ester stimulation. MDCK cells in log phase growth contained higher levels of diacylglycerol and alkylacylglycerol than confluent cells. Both subclasses of diradylglycerol showed higher levels of saturated and monoenoic species during log phase. Glycerol incorporation into diradylglycerols was increased during growth, consistent with an increase in their synthesis de novo. Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, caused an increase in the level of diacylglycerol but not alkylacylglycerol. Log phase MDCK cells showed a greater response to TPA treatment than confluent cells. The molecular species of diacylglycerol generated during stimulation with either TPA or dioctanoylglycerol closely resembled the species of phosphatidylcholine. These results indicate that TPA and synthetic diacylglycerol stimulate endogenous diacylglycerol production through the hydrolysis of phosphatidylcholine. In contrast, the higher content of diacylglycerol and alkylacylglycerol in replicating MDCK cells is the result of an increase in their synthesis de novo.

No description available.

Background: HSV-2 was estimated to infect 491 million people worldwide, with women disproportionately affected by HSV-2. Understanding factors that influence susceptibility to HSV-2 in women is important in preventing infections. Through various studies, the progestin-based contraceptive DMPA exhibited immunosuppressive effects, and has shown increased susceptibility to HIV and HSV-2. Studies comparing DMPA to other contraceptives like NET suggest that NET may be safer. In vivo NET effects have not been characterized thoroughly to better understand the effect of NET on susceptibility to HSV-2. Therefore, this study aimed to compare the effects of NET and DMPA in mouse models that affect susceptibility to HSV-2. We hypothesized that NET treated mice will have decreased susceptibility to HSV-2 compared to DMPA but elevated compared to normal mice. Method of study: Ovariectomized mice were treated with DMPA (2mg) and NET (2 mg injections, 2.5 mg pellets or 5 mg pellets) for 10 days and intravaginally immunized with HSV-2 TK-, then intravaginally challenged with WT HSV-2 ~4-7 weeks later. Primary intravaginal WT HSV-2 challenges were conducted in ovariectomized and normal mice after 10 days of DMPA and NET treatment. Viral titers, pathology and survival were examined. Mucus production in the vagina was investigated through immunohistology. Effects of hormones on immune cells were explored in the lymph nodes, spleens, and vaginal tracts through flow cytometry. Results: Increased mucus was consistently observed in the vaginal tracts of mice after treatment with NET 2.5 mg and 5 mg treated mice, but not with DMPA Therefore, NET treated mice displayed reduced viral shedding and delayed pathology compared to DMPA treated mice. No significant changes occurred in immune cells analyzed post DMPA and NET treatment, although there were trends of increased T cells in progestin treated mice. However, more experiments need to be conducted to confirm observed trends. Conclusion: NET treatment in mice results in mucus production in the vaginal tract, a potential mechanism impeding intravaginal HSV-2 infection and could be applied to other STIs. This provides insight into protective effects of NET compared to DMPA allowing women to make informed decisions regarding hormonal contraceptives. / Thesis / Master of Science in Medical Sciences (MSMS)