Orientador: José Joaquim Titton Ranzani / Banca: Claudia Valeria S. Brandão / Banca: Georgia Nadalini Rodrigues / Banca: Renato Linhares Sampaio / Resumo: A proposta do presente trabalho foi a de comparar o tratamento convencional a base de colírio com o sistema de liberação controlada no tratamento de ceratites por Staphylococcus aureus por ciprofloxacina. Foram utilizados 20 coelhos, divididos em quatro grupos. Os grupos G1, G3 e G4 foram inoculados com 2,5μl da bactéria (108UFC) no estroma corneano. O grupo G2 não recebeu a aplicação do inóculo. O tratamento foi realizado com solução fisiológica para o grupo G1 (a cada seis horas por cinco dias), micropartículas de poli-lactatoco- glicolato (PLGA) contendo ciprofloxacina nos grupos G2 e G4, e colírio de ciprofloxacina no grupo G3 (a cada seis horas por cinco dias). Humor aquoso foi coletado no quinto dia de tratamento para análise por High-performance liquid chromatography (HPLC) da quantidade de ciprofloxacina na câmara anterior. As concentrações médias obtidas foram de 0,013μg/ml, 0,3μg/ml e 0,03μg/ml para os grupos G2, G3 e G4 respectivamente. Swab e biópsia da superfície ocular foram coletados para cultura no quinto dia de experimento. Apenas um animal do grupo G1 teve cultura positiva para S. aureus no material processado. Exame histopatológico revelou a presença bacteriana em todos os animais do grupo G1 e em dois animais do G3. Também foi constatado uma leve reação inflamatória no local da aplicação do sistema de liberação controlada. A análise dos dados mostrou que o tratamento com as micropartículas de PLGA foi eficaz no tratamento de ceratite bacteriana, eliminando completamente a presença de S. aureus e não sendo completamente biocompatível e biodegradável após cinco dias. / Abstract: The proposal of this study was to compare the conventional treatment with eye drops with the controlled delivery system of PLGA, in the treatment of Staphylococcus aureus keratitis with ciprofloxacin. We used 20 rabbits, divided into four groups. The groups G1, G3 and G4 were inoculated with the bacterial 2.5μl (108UFC) in the corneal stroma. The G2 group did not receive the application of inoculum. The treatment was performed with basic saline solution in G1 (every six hours for five days), microparticles of poly-lactate co-glycolate (PLGA) containing ciprofloxacin in G2 and G4, and ciprofloxacin eye drops in group G3 (every six hours for five days). Aqueous humor was collected on the last day of treatment for analysis by High-performance liquid chromatography (HPLC) of the amount of ciprofloxacin in the anterior chamber. The average concentrations were obtained from 0013μg/ml, 0.3μg/ml and 0.03μg/ml for G2, G3 and G4 respectively. Swab and biopsy of the ocular surface were collected for culture on the fifth day of experiment. Only one animal in the G1 had positive culture for S. aureus in the processed material. Histological examination showed a bacterial presence in all animals of G1 and two animals of G3. It was also noted some light inflammatory reaction at the site of application of the controlled release. Data analysis showed that treatment with the microparticles of PLGA was effective in treating bacterial keratitis, completely eliminating the presence of S. aureus, not being completely biocompatible and biodegradable after five days. / Doutor

A ortopedia e a odontologia têm especial interesse às tecnologias biocompatíveis que apresentam a fase alfa do fosfato tricálcico (α-TCP), pois estas são capazes de formar hidroxiapatita deficiente em cálcio, similar à óssea. Porém, a baixa resistência mecânica limita sua aplicação. A fim de superar essa limitação, foi agregada acrilamida ao cimento α-TCP, com redutor de líquido, originando o cimento α-TCP de dupla pega. A partir disso foram desenvolvidos compostos à base de cimento de α-TCP e α-TCP de dupla pega agregados dos fármacos sulfato de gentamicina, cloridratos de lidocaína, bupivacaína e levobupivacaína e testada sua funcionalidade como sistemas de liberação de fármacos. Não existem dados bibliográficos sobre liberação de fármacos por sistemas de cimento α-TCP de dupla pega. A metodologia utilizada foi qualiquantitativa. Para as diferenças analíticas considerou-se o intervalo de confiança de 95% com nível de significância menor que 5% (p<0,05). O estudo compreendeu três fases. Na Fase 1 foram elaborados corpos de prova à base de cimento α-TCP e α-TCP de dupla pega com e sem (grupo-controle) adição de fármacos. Na Fase 2 os biomateriais estudados foram caracterizados por difração de raios X, espectroscopia de absorção no infravermelho com transformada de Fourier, microscopia eletrônica de varredura, resistência mecânica a compressão axial, densidade, porosidade e absorção de líquido; sendo também proposta a análise da porosidade por meio de imagens. A Fase 3 corresponde ao estudo da cinética da liberação dos fármacos in vitro, onde os corpos de prova foram imersos em solução tampão fosfato pH 7,0 e as amostras analisadas por meio de UV-vis. A liberação do antibiótico também foi avaliada por Espectroscopia de Impedância Eletroquímica (EIS), como proposta inovadora. Conforme os resultados, ambos os cimentos funcionaram como sistemas de liberação dos fármacos. Tanto o sistema hidrogel, quanto os fármacos não modificaram as propriedades estruturais do cimento. O sistema com hidrogel apresentou melhor resistência mecânica. A difusão Fickiana foi o principal mecanismo envolvido no processo de liberação dos fármacos, com menor influência do relaxamento das cadeias. A técnica de EIS mostrou-se promissora para avaliação de liberação de fármacos. / To better regulate it is necessary to know the new Technologies. Orthopedics and dentistry have demonstrated special interest in biocompatible technologies that present the alpha phase of tricalcium phosphate (α-TCP), whit can form calcium-deficient hydroxyapatite (like bone hydroxyapatite). However, its application is limited by the low mechanical resistance. To overcome this limitation, acrylic hydrogel containing liquid reducer was added to the α-TCP cement, resulting in the α-TCP double setting cement. From this, composites of α-TCP and α-TCP double setting cements aggregates of the drugs gentamicin sulfate, lidocaine, bupivacaine and levobupivacaine hydrochlorides were developed and the functionality drug delivery systems was tested. There isn't bibliographic data about drugs release systems by α-TCP double setting cement. Qualitative and quantitative methodologies were applied. For the analytical differences, we considered the 95% confidence interval with a level of significance lower than 5% (p <0.05). It comprised three different phases. In Phase 1, an α-TCP and α-TCP double setting cement specimens were prepared with and without (control group) drugs addition. In Phase 2, the studied biomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, compression mechanical resistance, density, porosity and liquid absorption, being also proposed of the porosity analysis by images. The Phase 3 corresponds to the study of the in vitro drug release kinetics. The specimens were immersed in phosphate buffer solution pH 7.0 and the samples analyzed by UV-vis. As an innovative proposal, drug release was also assessed using Electrochemical Impedance Spectroscopy (EIS). According to the results, both cements functioned as controlled drug delivery systems. The hydrogel improved the properties of cement moreover the drugs did not impair these properties. Fick diffusion was the main mechanism involved in the process of drug release by composites, with a minor influence of polymer chain relaxation. The EIS technique proved to be promising for the evaluation of drug release.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-03-07T12:59:54Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO- CINDY SIQUEIRA BRITTO AGUILERA.pdf: 2705379 bytes, checksum: 97ce59193eca13b16910a462fb383f9b (MD5) / Made available in DSpace on 2017-03-07T12:59:54Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO- CINDY SIQUEIRA BRITTO AGUILERA.pdf: 2705379 bytes, checksum: 97ce59193eca13b16910a462fb383f9b (MD5) Previous issue date: 2016-07-29 / CAPES / Os hidróxidos duplos lamelares (HDL) vêm recebendo grande atenção no desenvolvimento de sistemas de liberação de fármacos, devido à capacidade que esses sólidos inorgânicos apresentam, de intercalar na sua região interlamelar, ou adsorver em sua vasta área superficial, substâncias biologicamente ativas. Os HDL podem ser sintetizados em laboratório por rotas simples e de baixo custo, que permitem o isolamento de sólidos de alta pureza. O antirretroviral zidovudina (AZT) apresenta, como principal limitação, o baixo tempo de meia vida plasmática, sendo necessária a administração de várias doses diárias, e assim favorecendo o surgimento de reações adversas. Nesse contexto, o presente trabalho teve como objetivo o desenvolvimento de sistema de liberação prolongada para o fármaco AZT, utilizando o HDL como carreador. Para isso, foi realizado, a síntese e caracterização de MgAlCl-HDL, e obtenção de sistemas HDL:AZT, através da síntese direta por copreciptação, realizando variações na concentração de AZT no meio reacional e no tempo de agitação durante a síntese. Os materiais obtidos foram caracterizados pelas técnicas de difração de raios-X (DRX), termogravimetria (TG), análise térmica diferencial (DTA), espectroscopia no infravermelho (IV), microscopia eletrônica de varredura (MEV), análises de tamanho de partícula, porosidade e área superficial, além da análise elementar de metais e de carbono, hidrogênio e nitrogênio (CHN). Entre os sistemas HDL:AZT, o obtido com proporção molar 1:1 (Al+3/AZT) no meio reacional e 1 hora de agitação, apresentou o melhor perfil de liberação prolongada do fármaco, alcançando 90% de liberação do AZT em 24 horas de estudo. O MgAl-ClHDL demonstrou ser um carreador biocompatível, além de proporcionar uma diminuição na citotoxicidade do AZT frente a linhagem de macrófagos humanos. Desta forma, o sistema de liberação prolongada obtido, para o fármaco AZT, poderá ser utilizado em formulações farmacêuticas, no intuito de otimizar a terapia antirretroviral atual. / Layered double hydroxides (LDH) have received great attention in the development of drug delivery systems because of the ability these inorganic solids present to intercalate in its interlayer region, or adsorb on its vast surface area, biologically active substances. The LDH can be synthesized in the laboratory by simple and low-cost routes that generate high-purity solids. The antiretroviral zidovudine (AZT) has as its main limitation, low plasma half-life, requiring the administration of multiple daily doses, and thus favoring the appearance of side effects. In this context, the present study aimed to develop sustained release systems for the AZT using LDH as a drug carrier. In order to accomplish this goal, it was carried out the synthesis and characterization of the MgAl-Cl-LDH and obtained the systems LDH:AZT by coprecipitation, with variations of AZT concentration in the reactional medium and stirring time during synthesis. The materials were characterized by the following techniques: X-ray diffraction (XRD), Thermogravimetry (TG), Differential Thermal Analysis (DTA), Infrared Spectroscopy (IR), Scanning Electron Microscopy (SEM), Particle Size Analysis, Porosity and Surface Area, and Elemental Analysis of Metals and Carbon, Hydrogen and Nitrogen (CHN). Among the LDH:AZT systems, the one with molar ratio 1:1 (Al+3/AZT) in the reaction medium and one hour of stirring presented the best sustained drug release profile, reaching the amount of 90% of AZT released within 24 hours of study. The MgAl-Cl-LDH showed to be a biocompatible drug carrier, in addition to providing a decrease in cytotoxicity of AZT against human macrophage lineage cells. Therefore, the sustained release system obtained to AZT may be used in pharmaceutical formulations in order to optimize the current antiretroviral therapy.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13290号 / 論医博第2188号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山下 潤, 教授 木村 剛, 教授 浅野 雅秀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Omnichannel är en term som syftar till att förtydliga kundperspektivet genom att integrera processer för ett sömlöst flöde i alla tillgängliga kanaler. Kanalerna kan bland annat vara fysiska butiker, hemsidor eller appar, där integreringen av flerkanalssystem eftersträvar en friktionsfri och en sömlös köpupplevelse.Syftet med denna studie var att undersöka och diskutera hur IKEA:s e-handel har utvecklats ur ett omnichannel perspektiv genom att beskriva vilka de logistiska processerna är för fysisk distribution. Studien genomfördes som en fallstudie med en kvalitativ metod innehållande intervjuer, ett webbinarium samt sekundärdata som empiriskt underlag.Resultatet visar att IKEA:s strategi för omnichannel- och logistiska processer är i en förändring och anpassning till den växande e-handeln. Omställningen genomförs för attbibehålla flexibilitet och tillgänglighet gentemot sina konsumenter. Vidare noteras att IKEA har hanterat ökningen av e-handel genom att på kort sikt agera för de logistiska utmaningarna, vilket emellanåt har fått långsiktiga lösningar att bortprioriteras för att säkra kundorders. Slutligen visar resultatet att IKEA:s leveranssystem är en flexibel och kundcentrerad del av deras logistiska processer. / Omnichannel is a term that aims to clarify the customer perspective by integrating processes so the customer can interact through all available channels seamlessly. Channels which are used can include physical stores, websites or apps, where the integration of multichannel systems strives for a friction-free and a seamless shopping experience. The purpose of this study was to examine and discuss how IKEA:s e-commerce has developed from an omnichannel perspective by describing the logistical processes for physical distribution. This was carried out using a qualitative method containing interviews, a webinar and secondary data to compose the empirical findings and was carried out as a case study. The result displays that IKEA:s approach to omnichannel and logistical processes is in a procedure of change and adaptation to the growing e-commerce. The transformation is done to maintain flexibility and accessibility towards their consumers. The study notice that IKEA have had to deal with the increase of e-commerce by using rapid actions to be able to manage the logistical challenges, which sometimes cause long-term solutions to be de-prioritized to secure customer orders. Finally, the results show that IKEA:s delivery system is a flexible and customer centric part of their logistical processes.

The aim of this thesis is the proposal of booking a table at a restaurant and ordering food delivery system. The work is divided into 5 chapters. It contains 44 images, 8 tables and 1 appendix. The first chapter describes the objective of the work, methods and processing procedures. In the second chapter is devoted to familiarization with the booking and delivery systems that are available in the market. In the third chapter is done SWOT Analysis for the restaurant La Fiamma in Bratislava. In the fourth chapter is designed and developed the system table reservations at this restaurant and designed the ordering system food delivery as well. The next section describes the economic benefits of implementing the described system. The result of this thesis is the function module table reservations as a part of web portal the restaurant La Fiamma.

In this study, we demonstrated that the CSKSSDYQC-peptide ligand which was identified from a random phage-peptide library through an in vivo phage display technique with rats could prominently improve the transport efficiency of macromolecules, such as large filamentous phage particles (M13 bacteriophage), across the intestinal mucosal barrier. Synthetic CSKSSDYQC-peptide ligands significantly inhibited the binding of phage P1 encoding CSKSSDYQC-peptide ligands to the intestinal mucosal tissue and immunohistochemical analysis showed that the CSKSSDYQC-peptide ligands could be transported across the intestinal mucosal barrier via goblet cells as their specific gateway. Thus, we inferred that CSKSSDYQC-peptide ligand might have a specific receptor on the goblet cells and transported from intestinal lumen to systemic circulation by transcytosis mechanism. These results suggest that CSKSSDYQC-ligand could be a promising tool for development of an efficient oral delivery system for macromolecular therapeutics in the carrier-drug conjugate strategy.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23225号 / 工博第4869号 / 新制||工||1760(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 秋吉 一成, 教授 跡見 晴幸, 教授 大塚 浩二 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

A thesis submitted in partial fulfilment of the requirements for the degree of Masters of Arts in Clinical Psychology at the University of Zululand, South Africa, 2011. / South Africa is at a critical point in the debate about the future of health-care in the occupation-specific dispensation (OSD). It also faces the exodus of valuable human resources that was perceived as greener pastures, as medical practitioners become increasingly dissatisfied with governmental policy, wage negotiations, work-place disillusionment, lack of service delivery, expressions of corruptions, and lack of resources. This research aimed to thematically analyse the experiences, opinions and feelings of medical practitioners in both the public and private health-care sectors as well as explored international trends with the intention of drawing comparisons, highlighting problem areas, and discussion of possible solutions. It was hoped that this research would contribute towards understanding the dynamics that marked the exodus of medical practitioners from South Africa, at a time when change in the health-care system was imminent. In order for the medical practitioners to remain in the current health-care system, a new dialogue would have been opened in which their concerns could be raised and evaluated.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18949号 / 工博第3991号 / 新制||工||1615(附属図書館) / 31900 / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 木村 俊作, 教授 瀧川 敏算, 教授 秋吉 一成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM