Made available in DSpace on 2014-06-11T19:27:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-08-05Bitstream added on 2014-06-13T18:30:59Z : No. of bitstreams: 1 guimaraes_acm_me_guara.pdf: 1463910 bytes, checksum: 86d009497e85e3bccfe639908d568618 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Braquetes ortodônticos são feitos de diversos tipos de materiais, tais como, metais, cerâmicas e polímeros. Entre todos os materiais metálicos, o aço inoxidável é o mais empregado devido ao seu baixo custo associado a sua resistência à corrosão. No ambiente oral, eles estão sujeitos a fluídos agressivos e variações de pH, levando a liberação de íons nos tecidos e fluídos. Modificações na superfície destas ligas foram realizados utilizando tratamentos mecânicos, eletroquímicos, químicos e físicos. O carbono amorfo hidrogenado (a-C: H) preparado para técnicas de deposição apresentam muitas propriedades atraentes como alta dureza, serem químicamente inertes e biocompatíveis. Neste estudo in vitro, filmes de a-C:H foram depositados em braquetes ortodônticos pela técnica de deposição química por plasma de radiofreqüência (PECVD) e inibiu a liberação de íons níquel. Após o tratamento de superfície, os braquetes foram colados em incisivos bovinos com uma resina composta e as amostras foram imersas em soro fisiológico por 30 dias à 37 º C. Durante o tempo de imersão as amostras foram lavadas e imersas em flúor diariamente. Antes da imersão, o arranjo estrutural dos filmes foi analisado por espectroscopia de Raman e medidas do ângulo de contato foram realizadas, a fim de avaliar a molhabilidade da superfície. Espectrometria de absorção atômica foi usada para medir a liberação de elementos a partir de amostras e a análise superficial foi realizada em microscópio eletrônico de varredura (MEV). Os resultados mostraram que o revestimento previne a liberação de Ni dos braquetes nos testes estatísticos e o níquel foi liberado de outros grupos sem tratamento de superfície . A análise de variância não indicou diferença significativa entre os grupos depois do ensaio de cisalhamento. / Orthodontics brackets have been made from a variety of materials such as metals, ceramics and polymers. Among all the metallic materials, stainless steel are the most popular due low cost associated with reasonable corrosion resistance. In oral environment, they are subject aggressive fluids and pH variation can be leave nickel ions release to body tissues and fluids. Surface modifications of these alloys have been realized using mechanical, electrochemical, chemical and physical treatments. Hydrogenated amorphous carbon (a-C:H) prepared by deposition techniques have very attractive properties such as high hardness, chemical inertness and biocompatibility. In this in vitro study, a-C:H films were deposited on orthodontics brackets by r.f. plasmaenhanced chemical vapour deposition (PECVD) from inhibited nickel ions release. After treatment, brackets were bonded to bovine incisors with a composite resin and samples were immersed in physiological serum for 30 days at 37 ºC. During immersion time samples were brushed and/or immersed in mouthwashes daily. Prior immersion, the structural arrangement of films was probed by Raman spectroscopy and contact angle measurements were carried out in order to evaluate the wettability of surface. Atomic absorption spectrophotometry was used to measure the release of elements from the samples and SEM for surface analysis. Results showed that the coating prevents Ni release of brackets for statistic test and nickel was released for others groups. Analysis of variance no indicated significance different among groups after shear testing.

Som musikskapare har jag länge skrivit och producerat musik, men mycket av musiken har aldrig nått sin lyssnare. I denna uppsats har jag valt att skriva om hur processen kan se ut när ny musik ska publiceras och hur marknadsföringen kan se ut. Jag har samlat in data genom att intervjua verksamma inom musikbranschen samt. tagit del av ett podcastavsnitt och webbsidor. Jag har även använt mig av en exempellåt som jag själv varit med och skrivit. Genom processen har jag kommit fram till en analys av PR inom musikbranschen. Jag har tagit upp kommersiell musik, radio, Spotify, samarbeten mellan A&R:s och artister. De resultat jag kommit fram till genom intervjuerna visar även på hur ett kontrakt mellan ett musikbolag och en artist kan se ut. I slutsatsen tar jag upp att det finns många olika sätt att jobba med PR, antingen själv som artist eller med hjälp av ett musikbolag. Jag har även kommit fram till att kontrakt mellan artist och musikbolag kan se väldigt olika ut. Under rubriken Framtida Forskning skriver jag att det vore intressant att analysera vidare i ämnet och kanske gå in mer på siffror och statistik.

La contraction musculaire est provoquée par un relâchement massif de calcium à partir du reticulum sarcoplasmique (RS) des cellules musculaires. Ce relâchement de calcium réalisé par le récepteur de la ryanodine (RyR1), s'effectue dans des structures membranaires spécialisées et très organisées : les triades. Cette architecture spécifique est essentielle à l'activité correcte de RyR1. Cependant, les mécanismes moléculaires mis en jeu dans la formation et le maintien des triades ne sont pas connus. La triadine, qui est une protéine localisée dans la membrane du RS et qui est associée à RyR1, pourrait jouer un rôle dans la structure du reticulum sarcoplasmique pour permettre un relâchement de calcium efficace. L'équipe a montré que l'ablation du gène de la triadine chez la souris induisait une altération des relâchements de calcium et une modification de la forme des triades.Nous avons montré que la triadine pouvait indirectement interagir avec les microtubules et qu'elle pourrait ancrer le RS aux microtubules (Fourest-Lieuvin, J Cell Science, 2012). Par analyse en spectrométrie de masse des protéines co-immunoprécipitées avec la triadine, nous avons identifiéun nouveau partenaire de la triadine, CLIMP-63 qui pourrait être impliqué dans cette fonction. CLIMP-63 est décrite comme une protéine capable d'ancrer le reticulum aux microtubules et de maintenir la forme du reticulum endoplasmique. Nous avons ensuite confirmé son interaction avec la triadine par différentes approches dans différents modèles cellulaires. L'étude et la caractérisation de CLIMP-63 dans le muscle sont tout à fait innovantes et nous avons étudié les conséquences de l'association triadine/CLIMP-63 pour la fonction du muscle et dans la formation ou la maintenance des triades. / Muscle contraction is achieved when an efficient excitation signal at the plasma membrane triggers intracellular calcium release. This process called “excitation-contraction (E-C) coupling” relies on a macromolecular protein complex, spanning the plasma membrane and the sarcoplasmic reticulum (SR), containing the calcium channel of the SR, the ryanodine receptor (RyR1). This calcium release complex is present exclusively in highly organized membrane structures called triads. A triad is composed of two SR terminal cisternae surrounding a plasma membrane transverse-tubule.This architecture is essential to sustain the activity of the calcium channel RyR1, which is located in the membrane of SR terminal cisternae. However, little is known about the molecular mechanisms allowing the formation and maintenance of SR terminal cisternae. Triadin is a member of this complex, present in the SR membrane and interacting with RyR1. Deletion of the triadin gene leads to partial disorganisation of SR membranes in skeletal muscles, with abnormal orientation of part of the triads. Triadin could play a role in the structure of sarcoplasmic reticulum to allow efficient E-C coupling. We have shown that triadin could indirectly interact with the microtubules, and therefore anchor the sarcoplasmic reticulum to the microtubule network (Fourest-Lieuvin, J Cell Science, 2012). Using mass spectrometry analysis of proteins co-immunoprecipitated with triadin, we have identified a new partner of triadin, CLIMP-63 which could be involved in this function. CLIMP-63 is a shaping protein able to mediate the anchoring of the reticulum to microtubules and to maintain the shape of endoplasmic reticulum. We have dissected the interacting domains between CLIMP-63 and triadin, and study the consequences of this association for muscle function, and triad formation or maintenance.

Le doctorant n'a pas fourni de résumé en français. / The research described in this thesis is directed to study an externally stimulated DDS that incorporates a hydrogel as the matrix for the therapeutic agent. The research does not investigate a particular site for the delivery of the therapeutic agent. However, the aim of this research program is to develop various hydrogel formulations with desirable characteristics and structures from which the drug release can be controlled with applied external energy in the form of low-frequency ultrasound. To accomplish this, two types of natural hydrogels from agarose and chitosan and one type of synthetic hydrogel from PVA were fabricated. Parameters that affect the structure were varied for each type of hydrogel in order to study the effect of structural changes on drug loading and release capacity of hydrogels. Next, the obtained hydrogels were assessed for the delivery of Theophylline as the model drug.Among the three types of hydrogels, chitosan was found to have the fastest swelling rates and the higher water uptakes while the least swelling was found with PVA hydrogels and then agarose hydrogels crosslinked at pH 12. Regarding the mechanical stability of hydrogels, the ranking of the elastic modulus was PVA hydrogels (highest), then agarose hydrogels and chitosan copolymers (lowest). It seemed that the more mechanically stable structure of the PVA hydrogels correlated with a reduced mobility of water, in comparison to the greater mobility of water in the mechanically weaker chitosan copolymers.The stimulated and passive release of Theophylline from those hydrogel carriers showed how ultrasound, as an external energy, stimulates and controls the release of the drug. The measurements confirmed that it is only the energy imparted by the longitudinal ultrasonic waves that act on the polymeric network. The mechanism by which the ultrasound affects the release is considered as a form of a ratchet motor. The polymer chains play the role of the “ratchet” steps and the ultrasonic waves accelerate the particle movement in the release media. Hence, once the ultrasound is applied, the particles descend chain-to-chain (i.e. step-by-step) driven down their concentration gradient by the applied energy until they reach the surface of the hydrogel and hence are released into the surrounding media.Increasing the ultrasound intensity vastly accelerates the drug release. Indeed a higher intensity equals a higher energy transferred from the ultrasonic waves to the drug particles, resulting in faster and less controlled release. This also depends on the type of drug carrier structure. If the hydrogel carrier is mechanically stable, such as the PVA samples or the agarose hydrogels crosslinked at pH 12, the effect of high ultrasound intensity is much less compared to a less mechanically stable carrier such as the chitosan blends. Ultrasound applied for a longer period of time increases the amount of drug released, with the consequent effect of increasing the amount of heat generated in the hydrogel. Generally, a longer duration of the applied energy results in a greater amount of energy absorption, and an increase in friction and heat generation. These effects are important considerations in relation to the heat sensitivity of the drug to be delivered and the thermal characteristics of the polymeric carrier.This PhD research has demonstrated that both natural and synthetic hydrogels coupled to an ultrasonic energy source provides a controllable DDS, which provide some novel outcomes and contributions to the body of knowledge in the field of controlled drug delivery.

Localization and characterization of putative mitochondrial methzltransferase acc. No.: Tb10.6k15.0440 in Trypanosoma brucei was performed. Employed molecular methods included immunofluorescence, sub-cellular fractionation and tandem affinity purification. Protein was overexpressed in an E. coli expression system, using an in-fusion expression vector pOPINM with maltose binding protei (MBP) tag.

The oral route of drug administration is most extensively used due to the obvious ease of administration. Verapamil hydrochloride is a WHO listed phenylalkylarnine, L-type calcium channel antagonist that is mainly indicated for cardiovascular disorders such as angina pectoris, supraventricular tachycardia and hypertension. Due to its relatively short half-life of approximately 4.0 hours, the formulation of a sustained-release dosage form is useful to improve patient compliance and to achieve predictable and optimized therapeutic plasma concentrations. Direct compression and wet granulation were initially used as methods for tablet manufacture. The direct compression method of manufacture produced tablets that exhibited formulation and manufacturing difficulties. Mini-tablets containing veraparnil hydrochloride were then prepared by wet granulation using Surelease® E-7-19010.and Eudragit® NE 30D as the granulating agents after which the granules were incorporated with an hydrophilic matrix material, Carbopol® 974P NF. Granule and powder blends were evaluated using the angle of repose, loose and tapped bulk density, Can's compressibility index, Hausner's ratio and drug content. Granules with good flow properties and satisfactory compressibility were used for further studies. Tablets were subjected to thickness, diameter and weight variation tests, crushing strength, tensile strength, friability and content uniformity studies. Tablets that showed acceptable pharmaco-technical properties were selected for further analysis. Drug content uniformity and dissolution release rates were determined using a validated isocratic HPLC method. Initially, USP apparatus 1 and 3 dissolution apparatus were used to determine in-vitro drug release rates from the formulations over a 22-hour period. USP apparatus 3 was finally selected as it offers the advantages of mimicking, in part, the changes in the physicochemical environment experienced by products in the gastro-intestinal tract. Differences in release rates between the test formulations and a commercially available product, Isoptin® SR were observed at different pH's using USP apparatus 1. The release of veraparnil hydrochloride from matrix tablets was pH dependent and was markedly reduced at higher pH values. This may be due, in part, to the poor solubility of veraparnil hydrochloride at these pH values and also the possible interaction of verapamil hydrochloride with anionic polymers used in these formulations. Swelling and erosion behaviour of the tablets were evaluated and differences in behaviour were observed which may be attributed to the physico-chemical characteristics of the polymers used in this study. In-vitro dissolution profiles were characterized by the difference (j1) and similarity factor (j2) and also by a new similarity factor, Sct. In addition, the mechanism of drug release from these dosage forms was mainly evaluated using the Korsmeyer-Peppas model and the kinetics of drug release assessed using other models, including Zero order, First order, Higuchi, HixsonCrowell, Weibull and the Baker-Lonsdale model. Dissolution kinetics were best described by application of the Weibull model, and the Korsmeyer-Peppas model. The release exponent, n, confirmed that drug release from these dosage forms was due to the mixed effects of diffusion and swelling and therefore, anomalous release kinetics are predominant. In conclusion, two test batches were found to be comparable to the reference product Isoptin® SR with respect to their in-vitro release profiles.

Orientador: Odair Aparecido Fernandes / Banca: Enrico de Beni Arrigoni / Banca: Celso Omoto / Banca: Sérgio de Freitas / Banca: Arlindo Leal Boiça Junior / Resumo: Com a adoção de plantas geneticamente modificadas que expressam toxinas de Bacillus thuringiensis há a necessidade de estabelecimento de estratégias para retardar o desenvolvimento da resistência de insetos, tais como áreas de refúgio. Para tanto, informações sobre a dispersão dos insetos alvo desta tecnologia são essenciais para aprimoramento de técnicas de manejo de insetos-praga. Nos estudos de dispersão normalmente são usadas técnicas de marcação-liberação-recaptura. Assim, objetivou-se com este trabalho marcar Diatraea saccharalis e avaliar a capacidade de dispersão de Spodoptera frugiperda. Para a marcação, dois corantes lipossolúveis em diferentes concentrações (100 a 400 ppm), Sudan Red 7B e Solvente Blue, foram adicionados à dieta artificial de D. saccharalis e avaliados sobre parâmetros biológicos do desenvolvimento de lagartas, pupas e adultos (fecundidade e longevidade). A adição dos corantes em dieta artificial fornecida para alimentação de lagartas de D. saccharalis proporcionou a marcação de adultos e ovos em todas as concentrações testadas. No caso da avaliação da capacidade de dispersão de S. frugiperda foram realizados experimentos durante as safras 2005/2006 e 2006/2007. A dispersão se dá por difusão e foi possível registrar distâncias máximas de recaptura de 806 m para machos e 608 m para fêmeas de S. frugiperda. / Abstract: With the adoption of genetically modified plants expressing Bacillus thuringiensis toxins there is a need of establishing strategies to delay the development of insect resistance (e.g. refugee areas). Thus, information on target insects dispersal are essential to improve pest management techniques. In dispersal studies, markingrelease- recapture techniques are usually used. The objective of this work was to mark Diatraea saccharalis and evaluate the dispersal capacity of Spodoptera frugiperda. For marking D. saccharalis, different concentrations (100 to 400 ppm) of two oil soluble dyes (Sudan Red 7B and Solvent Blue) were added to larval artificial diet. Larval and pupal development as well as adult fecundity and longevity were evaluated. The addition of dyes into the diet marked both adults and eggs, regardless the concentration used. For evaluating the dispersal capacity of S. frugiperda, experiments were carried out during 2005/2006 and 2006/2007 growing seasons. Dispersal is diffused and the maximum recapture distances were 806 m for males and 608 m for females of S. frugiperda. / Doutor

Magister Scientiae - MSc / The focus of this study is to synthesize a novel hinged polymer actuator. The linking molecule (hinge) is phenazine with interconnected dipyrrole units. / South Africa

The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.

De nouveaux matériaux, appelés matériaux actifs, se développent actuellement par diverses processus dans plusieurs applications. L'objectif est d'apporter aux matériaux de bases (par exemple : papiers, cartons) de nouvelles fonctionnalités telles que la détection de virus, le relargage de substances actives, le contrôle de la durée de vie etc. L'élaboration de matériaux fonctionnels est un sujet de plus en plus important dans notre société et chez les industries. Les recherches restent cependant encore rares à ce propos et l'expertise des scientifiques est vivement attendue. Par ailleurs, l'intérêt des scientifiques se porte aussi de plus en plus sur l'utilisation de bio-matériaux. Parmi ces derniers, l'intérêt pour les bio nanoparticules est le plus grandissant : les chercheurs voient en effet la possibilité d'élaborer de nouvelles applications à hautes valeurs ajoutées. Cependant, aujourd'hui, l'utilisation de ces nanoparticules dans le contrôle du relargage de substances actives n'est pas encore dominante ni approfondie malgré les premiers résultats prometteurs obtenus avec les nanoparticules. En plus de leurs excellentes propriétés mécaniques et barrières, leur surface spécifique est un point clé et avantageux à considérer pour l'obtention de nouvelles fonctionnalités (introduction de substances actives). Dans le domaine des emballages, les matériaux actifs ont pour objectif de prolonger la durée de conservation des aliments en modifiant les conditions d'emballage. Trois catégories sont différenciées : les emballages absorbeurs (oxygène, humidité), les emballages antimicrobiens et les emballages barrières. Peu de recherches existent actuellement sur les deux premières catégories et d'autres commencent affichant des résultats bien prometteurs. Ainsi, l'objectif de la thèse est donc de comprendre et de développer des bio nanomatériaux fonctionnels innovants en considérant deux aspects : le développement durable et la sécurité alimentaire. Trois sujets seront abordés en détail: - Biomatériaux : fibres de cellulose, bionanoparticules, biomolécules actives - Procédés : greffage, encapsulation, couchage, extrusion, jet d'encre - Propriétés : absorbeur d'oxygène, antimicrobien, contact alimentaire Le phénomène de migration sera un point particulièrement détaillé au long de ces 3 ans ainsi que les caractérisations de propriétés importantes pour le produit final. Différentes stratégies seront ensuite testées et la meilleure solution sera optimisée afin d'arriver à une étude à grand échelle du produit obtenu. / New functional materials, called active materials, are developing with different processes and for several applications. The target is to give new functions like virus detection, active substance release, end of life control...This topic is more and more important in our society and industry. Researches are still rare and more scientific expertise is expected. Meanwhile, use of biobased materials interests more and more scientists. Among biomaterials, the use of bionanoparticles is strongly increasing and high value added applications are targeted. However, their use in release control of active substances has not yet been studied in detail in spite of promising results on barrier properties improvement. Their very high specific area could also be considered as a advantege concerning their use as active material carrier. In packaging field, active materials are materials which change condition of packed product to increase its shelf life by keeping quality and safety. Three main types of active packaging are existing : scavenger systems (02, humidity), anti-microbial systems, barrier systems. Some research studies have just been launched about the two first categories of active packaging with some promising results. The target is then to understand and develop innovative functional bionanomaterials by considering : sustainability and safety. Three topic will be studied in detail : - Biomaterials : cellulose fibers, bionanoparticules (NFC, Wh, SNP), active biomolecules - Process : grafting, encapsulation chitosane, coating, extrusion, ink jet - Properties : 02 scavenger, anti-microbial system, food contact A better understanding of migration and the end-use properties characterization will be main point of the scientific research during the project. Different strategies will be tested and optimisation of best solution will follow by finishing with an up-scaling study.