Made available in DSpace on 2018-08-01T21:34:59Z (GMT). No. of bitstreams: 1 tese_10421_Dissertação_Emmanoel Loss Dias.pdf: 1989385 bytes, checksum: 17589b2593a44ffae93864b2f8f67fe7 (MD5) Previous issue date: 2016-09-05 / PAM3CSK4 (PAM) é um agonista sintético de TLR1/2 composto por um lipopeptídeo triaciletado que imita a lipoproteína de bactérias e que apresenta uma potente capacidade em induzir atividade pró-inflamatória mediada por ativação de NF-kB. No presente estudo, foi investigada a capacidade da imunização intranasal com antígenos totais de promastigotas de L. amazonensis (LaAg) associados ao adjuvante PAM em potencializar a resposta imune imunogênica antígeno em camundongos. Assim, camundongos BALB/c foram imunizados por via intranasal (instilação nasal) com 20 μg de LaAg associados com 20 μg do adjuvante PAM em doses intervaladas por 7 dias. PBS, LaAg ou PAM sozinhos foram utilizados como controle. A dosagem das transaminases e da creatinina no soro animais demonstraram a biocompatibilidade e segurança da combinação LaAg/PAM. Os camundongos vacinados com LaAg/PAM demostraram maior reação de hipersensibilidade cutânea tardia (DTH) 24 e 48 horas, respectivamente, após a injeção de 20 μg de LaAg na pata traseira, quando comparado ao grupo controle. Além disso, em comparação aos outros grupos, os esplenócitos de animais vacinados com LaAg/PAM produziram mais IFN-γ, TNF-α e IL-4 depois do reestimulo in vitro com o antígeno LaAg (50 μg/mL). Células analisadas ex vivo, demonstraram que a combinação LaAg/PAM não alterou a frequência das populações de células CD4+ e CD8+ de memória e totais no baço. A vacinação com LaAg/PAM foi capaz de induzir a redução no parasitismo do fígado, em comparação com o grupo não tratado. Os animais vacinados com LaAg/PAM demostraram um aumento significativo na produção de IFN-γ e a diminuição na produção de IL-4 nos sobrenadantes do baço. Além disso, observou-se um aumento significativo na produção de NO nos sobrenadantes do fígados dos animais vacinados com LaAg/PAM. Em conjunto, nossos dados demonstram, pela primeira vez a possibilidade de imunização intranasal com os antígenos totais de L. amazonensis (LaAg) associados com PAM como um mecanismo eficaz de indução de imunogenicidade.

Thesis (doctoral)--University of Göteborg, 1983. / Extra t.p. with thesis statement inserted. Includes the author's five published papers. Includes bibliographical references.

Thesis (doctoral)--University of Göteborg, 1983. / Extra t.p. with thesis statement inserted. Includes the author's five published papers. Includes bibliographical references.

Made available in DSpace on 2016-08-29T15:34:58Z (GMT). No. of bitstreams: 1 tese_7846_DISSERTAÇÃO FINAL - CORREÇÕES + Ficha + Parecer _Reparado_2.pdf: 1750239 bytes, checksum: 6771fcd952a5a0a0f802782437acdc1c (MD5) Previous issue date: 2014-07-11 / O dimetil dioctadecil amônio (DDA) é um composto quaternário de amônio, formado por um lípido anfifílico sintético ligado a duas cadeias hidrofóbicas de alquilo de 18 carbonos, que mostrou efetivo efeito adjuvante, promovendo respostas imunes humoral e celular contra diversos agentes patogênicos, incluindo Mycobacterium tuberculosis e Chlamydia trachomatis. Neste presente trabalho, nós investigamos a capacidade do adjuvante CAF associado a antígenos totais de Leishmania amazonenses (LaAg) em induzir respostas imunogênicas e protetoras no desafio contra L. chagasi. Assim, camundongos BALB/c foram imunizados por via intranasal com 25 mg de LaAg livre ou associado a 150 mg de CAF em 2 doses intervaladas por 15 dias. A dosagem de transaminases e creatinina no soro dos animais demonstraram a biocompatibilidade e segurança da associação LaAg/CAF. Além disso, observamos significativas produções de IFN-g e NO por esplenócitos estimulados com antígenos do parasito, além de significativas respostas linfoproliferativas e maior percentagem de células de memória (TCD4+ CD44+ CD62L+). Níveis aumentados de IgG total e das subclasses específicas (IgG1 e IgG2a) também foram observadas no grupo vacinado com LaAg associado ao CAF, quando comparado aos controles. De forma semelhante, camundongos vacinados com a formulação e desafiados 15 dias após o reforço com L. chagasi, apresentaram uma significativa diminuição da carga parasitária no baço e fígado, associada a uma maior produção de IFN-g, respostas linfoproliferativas significativamente aumentadas. Juntos, nossos dados demonstraram pela primeira vez viabilidade da vacinação intranasal com LaAg associado ao CAF, como um efetivo mecanismo para a vacinação contra a leishmaniose visceral. Palavras chave: L. chagasi, imunização intranasal, LaAg, CAF, resposta imune.

Emulsions are widely used as topical formulations in the pharmaceutical and cosmetic industry. They are thermodynamically unstable and require emulsifiers to stabilize them physically. A literature survey has revealed that emulsifiers could have an effect on topical delivery. Therefore, the overall aim of this research project was to investigate and to understand the various effects of biopolymers, chosen for this study as emulsifiers, on the release and the topical delivery of an active ingredient from emulsion-based delivery systems. Emulsions were stabilized by either whey protein alone or in combination with chitosan or carrageenan. Salicylic acid was chosen as a model drug. Furthermore, the emulsions were prepared at three different pH values (pH 4, 5 and 6) in order to introduce different charges to the polymeric emulsifiers and subsequently determine the effect of pH on release as well as on dermal and transdermal delivery. Emulsion characteristics, such as droplet size, zeta potential, viscosity and stability against creaming and coalescence were ascertained. In addition, turbidity was determined to evaluate the degree of insoluble complex formation in the aqueous phase of the emulsions. A high pressure liquid chromatographic (HPLC) method was validated for the quantitative determination of salicylic acid in the release, skin and transdermal perfusate samples. Nine emulsions were formulated, utilizing the layer-by-layer (LbL) self-assembly technique, from which the release of salicylic acid was determined. These release studies were conducted, utilizing nitrocellulose membranes (0.2 μm pore size) with the use of Franz-type diffusion cells in four replicates per formulation over a time period of 8 hours. Based on the emulsion characterization and release data, six formulations, including the oil solution, were chosen to determine dermal and transdermal delivery of salicylic acid. During the diffusion studies, the effect of different pH (whey protein pH 4.00, 5.00 and 6.00), different polymers and different polymer combinations were investigated. These diffusion studies were conducted with the use of dermatomed (thickness ~400 μm), human abdominal skin and Franz-type diffusion cells over a period of 24 hours. The characterization of the emulsions revealed no significant differences in the droplet size and viscosity between the various formulations. All emulsions showed stability towards coalescence over a time period of 7 days; however, not all the emulsions showed stability towards creaming and flocculation. The results of the release studies indicated that an increase in emulsion droplet charge could have a negative effect on the release of salicylic acid from these formulations. In contrast, positively charged emulsion droplets could enhance the dermal and transdermal delivery of salicylic acid from emulsions. It was hypothesized that electrostatic complex formation between the emulsifier and salicylic acid could affect the release, whereas electrostatic interaction between emulsion droplets and skin could influence dermal/transdermal delivery of the active. Furthermore, the degree of ionization of salicylic acid played an important role in the dermal and transdermal delivery of salicylic acid from the various emulsions. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Emulsions are widely used as topical formulations in the pharmaceutical and cosmetic industry. They are thermodynamically unstable and require emulsifiers to stabilize them physically. A literature survey has revealed that emulsifiers could have an effect on topical delivery. Therefore, the overall aim of this research project was to investigate and to understand the various effects of biopolymers, chosen for this study as emulsifiers, on the release and the topical delivery of an active ingredient from emulsion-based delivery systems. Emulsions were stabilized by either whey protein alone or in combination with chitosan or carrageenan. Salicylic acid was chosen as a model drug. Furthermore, the emulsions were prepared at three different pH values (pH 4, 5 and 6) in order to introduce different charges to the polymeric emulsifiers and subsequently determine the effect of pH on release as well as on dermal and transdermal delivery. Emulsion characteristics, such as droplet size, zeta potential, viscosity and stability against creaming and coalescence were ascertained. In addition, turbidity was determined to evaluate the degree of insoluble complex formation in the aqueous phase of the emulsions. A high pressure liquid chromatographic (HPLC) method was validated for the quantitative determination of salicylic acid in the release, skin and transdermal perfusate samples. Nine emulsions were formulated, utilizing the layer-by-layer (LbL) self-assembly technique, from which the release of salicylic acid was determined. These release studies were conducted, utilizing nitrocellulose membranes (0.2 μm pore size) with the use of Franz-type diffusion cells in four replicates per formulation over a time period of 8 hours. Based on the emulsion characterization and release data, six formulations, including the oil solution, were chosen to determine dermal and transdermal delivery of salicylic acid. During the diffusion studies, the effect of different pH (whey protein pH 4.00, 5.00 and 6.00), different polymers and different polymer combinations were investigated. These diffusion studies were conducted with the use of dermatomed (thickness ~400 μm), human abdominal skin and Franz-type diffusion cells over a period of 24 hours. The characterization of the emulsions revealed no significant differences in the droplet size and viscosity between the various formulations. All emulsions showed stability towards coalescence over a time period of 7 days; however, not all the emulsions showed stability towards creaming and flocculation. The results of the release studies indicated that an increase in emulsion droplet charge could have a negative effect on the release of salicylic acid from these formulations. In contrast, positively charged emulsion droplets could enhance the dermal and transdermal delivery of salicylic acid from emulsions. It was hypothesized that electrostatic complex formation between the emulsifier and salicylic acid could affect the release, whereas electrostatic interaction between emulsion droplets and skin could influence dermal/transdermal delivery of the active. Furthermore, the degree of ionization of salicylic acid played an important role in the dermal and transdermal delivery of salicylic acid from the various emulsions. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

The recent growth in the ambit of modern wireless communication and in particular WLAN (Wireless Local Area Network) systems has created a niche for novel designs that have the capacity to send and/or receive arbitrary orthogonal polarizations. The designs should also be able to support dual-band functionality, while maintaining a compact structure. The first aim of this dissertation was thus to develop a dual-band single radiating element that can cover the 2.4 GHz (2.4 – 2.484 GHz) band and the 5.2 GHz (5.15 – 5.85 GHz) band for the IEEE 802.11b and IEEE 802.11a WLAN standards respectively. Dual-frequency elements such as stacked-, notched- and dichroic patches have been considered, but due to the size and the high cross-polarization levels associated with these designs, the design process was propelled towards various dipole and monopole configurations. The attributes of various designs were compared, where the double Rhombus antenna pregnant with dual-band and dual-polarization potential was used as basis in the development of the DBDP (Dual-Band Dual-Polarized) antenna design. The single-element design exhibited wide bandwidths, good end-fire radiation patterns and relatively high gain over the 2.4/5.2 GHz bands. A two-element configuration was also designed and tested, to firstly increase the gain of the configuration and secondly to facilitate the transformation of the dipole design into a dual-polarized configuration. The second aim of this dissertation was to develop a dual-polarized array, while making use of only two ports, each pertaining to a specific polarization and to implement the design on a single-dielectric-layer substrate. Most dual-polarized structures such as circular, square and annular microstrip antenna designs only support one band, where multi-dielectric-layer structures are the norm. The disadvantages associated with multi-layered designs, such as fabrication difficulties, high costs, high back lobes and the size of the arrays, further supported the notion of developing an alternative configuration. The second contribution was thus the orthogonal interleaving of the two-element array configurations, to address the paucity of single-dielectric-layer dual-band dual-polarized designs that can be implemented with only two ports. This design was first developed and simulated with the aid of the commercial software package CST Microwave Studio® and the results were later corroborated with the measured data obtained from the Compact Antenna Range at the University of Pretoria. AFRIKAANS : Die onlangse groei in die area van moderne draadlose kommunikasie en met spesifieke verwysing na DLAN (Draadlose Lokale Area Netwerk) stelsels, het ‘n nis vir nuwe ontwerpe geskep. Daar word van hierdie nuwe ontwerpe die kapasiteit verlang om verskeie ortogonale polarisasies te stuur en/of te ontvang in samewerking met dubbel-band eienskappe, terwyl ‘n kompakte struktuur nogsteeds aandag moet geniet. Die eerste doel met hierdie verhandeling was dus die ontwikkeling van ‘n dubbel-band enkel stralingselement wat instaat is om die 2.4 GHz (2.4 – 2.484 GHz) band en die 5.2 GHz (5.15 – 5.85 GHz) band wat as die IEEE 802.11b en die IEEE 802.11a DLAN standaarde respektiewelik bekend staan, te bedek. Dubbel-frekwensie elemente soos onder andere die gepakte-, merkkepie- en dichromatiese strook antenne was as moontlike oplossings ondersoek, maar die grootte en hoë kruispolarisasie wat gewoonlik met hierdie ontwerpe gepaard gaan, het die ontwerpsproses in die rigting van verskeie dipool en monopool konfigurasies gestoot. Die aantreklike eienskappe van die verskeie ontwerpe was met mekaar vergelyk, waar die dubbel Rhombus antenna, verwagtend met dubbel-band dubbel-polarisasie potensiaal, as basis vir die ontwikkeling van die DBDP (Dubbel-Band Dubbel-Polarisasie) antenna ontwerp gebruik is. Die enkelelementontwerp het wye bandwydtes, goeie direktiewe stralingspatrone en relatiewe hoë wins oor die 2.4/5.2 GHz bande geopenbaar. Die twee-element konfigurasies was ook ontwerp en getoets om eerstens die wins van die konfigurasie te verhoog en tweedens om die transformasie na ‘n dubbel-gepolariseerde konfigurasie te fassiliteer. Die tweede doel van hierdie verhandeling was om ‘n dubbel-gepolariseerde elementopstelling met net twee poorte te ontwikkel, waar elkeen verantwoordelik is vir ‘n spesifieke polarisasie, en te implementeer op ‘n enkel-diëlektriese-laag substraat. Die meeste dubble-polarisasiestrukture, soos onder andere die sirkulêre-, vierkantige- en ringvormige antenne ontwerpe, kan net een frekwensieband onderhou en word gewoonlik met behulp van meervoudige-diëlektriese-laagstrukture geimplementeer. Die negatiewe eienskappe soos onder andere die vervaardigingsmoeilikhede, hoë kostes, hoë teruglobbe en die grootte van die meervoudige-elementopstellings wat aan hierdie meervoudige-diëlektriese-laagontwerpe behoort, het verder die denkbeeld van ‘n alternatiewe konfigurasie bekragtig. Die tweede hoofbydrae was dus die ortogonale insleuteling van die twee-element meervoudige-elementopstelling konfigurasies om die geringheid van enkel-diëlektriese-laag dubbel-band dubbel-polarisasie ontwerpe, wat net met twee poorte geïmplementeer kan word, te adresseer. Hierdie ontwerp was eers met behulp van die kommersiële sagtewarepakket CST Microwave Studio® ontwikkel en gesimuleer, waarna die resultate bevestig was deur meetings by die Kompakte Antenna Meetbaan van die Universiteit van Pretoria. / Dissertation (MEng)--University of Pretoria, 2011. / Electrical, Electronic and Computer Engineering / unrestricted