Bakgrund: Hjärtsvikt är vanligt förekommande, ca 26 miljoner i världen och 250 000 i Sverige lever med diagnosen. Hjärtsvikt är ett komplext tillstånd med påverkan på många olika delar av livet. Behandlingen för hjärtsvikt är även detta komplext och att se individens situation är viktigt för framgångsrik behandling. Syfte: Att beskriva patienters upplevelse av att leva med kronisk hjärtsvikt i vardagen. Metod: En litteraturöversikt med 13 kvalitativa artiklar inkluderade de har analyserats med Fribergs femstegsmodell. Resultat: Resultatet visar på hur patienter med hjärtsvikt upplever att deras vardagliga liv har blivit förändrat av hjärtsvikt. Hur de upplever de nödvändiga förändringar de gör för att hantera en vardag med hjärtsvikt. Resultatet presenteras i kategorierna; stöd och kraft från omgivningen, mötet med sjukvården, rädsla samt förändringar i vardagen. Slutsats: Att leva med kronisk hjärtsvikt innebär en påverkan på patientens vardag. Social isolering, trötthet, andnöd, fysiska begränsningar och rädsla inför framtiden är några av de upplevelser som framkommer vid hjärtsvikt. Sjuksköterskan har här möjligheter att stötta och informera patienten att skapa förutsättningar att hantera vardagen med hjärtsvikt. / Background: Heart failure is a common condition, about 26 million in the world and 250 000 in Sweden are living with the diagnosis. Heart failure is a complex condition and have effects on many parts of life. Treatment for heart failure is also complex and to see the individual’s situation is important for a successful treatment.  Aim: To describe patients’ experience of living with heart failure in everyday life. Methods: A literature review with 13 studies included they have been analyzed with the Friberg Five Step-model. Results: The result shows that patients with heart failure experiences that their everyday life has changed because of heart failure. How they experience necessary changes they do to manage everyday life with heart failure. The results is presented in these categories; support and power from the surrounding, meeting the healthcare, fear and changes in everyday life.  Conclusion: Living with chronic heart failure has an impact on the patient's daily life. Social isolation, fatigue, shortness of breath, physical limitations and fear of the future are some of the experiences that emerge in heart failure. The nurse has opportunities to support and inform the patient to create the conditions for managing everyday life with heart failure.

Diese Arbeit umfasst die Präparation sowie Charakterisierung von neuartigen Uran(IV)-Kolloiden, die in nahneutralen pH-Bereichen und unter umweltrelevanten Bedingungen stabilisiert vorliegen. Rückschlüsse auf Stabilitätsverhalten und Partikelgrößenverteilungen wurden durch dynamische Lichtstreuung, Zetapotentialmessungen sowie Ultrafiltration und Ultrazentrifugation in Kombination mit Elementanalysen getroffen. UV-Vis- und Laserfluoreszenzspektroskopie bestätigten den tetravalenten Zustand des Urans bei den Experimenten. Anders als bisherige Untersuchungen vermuten lassen, ist es möglich langzeitstabile Uran(IV)-Kolloide in höheren Konzentrationen zu erzeugen. Durch Zusatz von geochemischen Komponenten, wie Carbonat und Silikat sind diese sedimentationsstabil und im nahneutralen bis basischen pH-Bereich über längere Zeiträume beständig. Dabei zeigte sich, dass gelöstes Silikat bei der Herstellung der Kolloide eine wesentliche Rolle spielt und Uran(IV) bis zu einer Konzentration von 10-3 mol/L, entsprechend 0,238 g/L in Lösungen stabilisieren kann. Diese Urankonzentration ist dabei ca. drei Potenzen höher als für bisher bekannte silikatfreie, wässrige Uran(IV)-Kolloide. Durch die Verwendung unterschiedlicher analytischer Methoden konnte gezeigt werden, dass die Durchmesser der entstandenen Uran(IV)-Kolloide im nanoskaligen Bereich von teilweise unter 20 nm liegen. Durch diesen kolloidalen Zustand kann eine hohe Mobilität in aquatischen Systemen unterstellt werden. Zusätzlich weisen Langzeituntersuchungen darauf hin, dass diese Kolloide in einem abgeschlossenen System über Jahre stabilisiert werden. Je höher dabei das Verhältnis zwischen Silikat- und Uran(IV)-Gehalt und je höher der pH-Wert der Lösung ist, desto kleiner und stabiler sind diese Partikel. Es ist anzumerken, dass sich keine Kolloide in Abwesenheit von Uran(IV) bilden. Silikat ist in der Lage, die negative Oberflächenladung der Uran(IV)-Kolloide im nahneutralen pH-Bereich zu erhöhen. Dies führt zu einer stärkeren elektrostatischen Abstoßung bzw. repulsiven Wechselwirkungen, womit eine bessere Stabilisierung gewährleistet wird. Der isoelektrische Punkt der erzeugten Partikel wird zu niedrigeren pH-Werten verschoben. Extended-X-ray-absorption-fine-structure-Untersuchungen zeigen, dass die innere Struktur der Kolloide durch den steigenden Silikatgehalt bei deren Bildung von U-O-U-Bindungen (entsprechend Uran(IV)oxyhydroxiden) zu U-O-Si-Bindungen verändert wird. Die Koordination in der benachbarten Region von U(IV) in den U(IV)-Silikat-Kolloiden ist vergleichbar mit der des Coffinits, USiO4. Dieses, für tetravalentes Uran noch nicht beschriebene Phänomen, wurde bereits bei silikatstabilisierten Eisen(III)- oder Mangan(III,IV)-Kolloiden beobachtet und als „Sequestrierung“ bezeichnet. Die silikatstabilisierten U(IV)-Kolloide sind in Laborexperimenten unter kontrollierten Bedingungen erzeugt worden, d.h. es ist noch nicht bekannt, ob diese Phasen in der Natur frei auftreten können. Die qualitative Zusammensetzung der Matrix der experimentellen Lösungen (H+, OH-, Na+, HCO3-/CO32-, Silikat) wurde ähnlich der geochemischen Natur von Grund- bzw. Porenwässern gewählt. Dadurch kann prinzipiell von einem Vorhandensein solcher Kolloide in Wässern natürlichen Ursprungs ausgegangen werden. Die Existenz solcher Partikel würde eine Erklärung für das beobachtete Auftreten von Uran(IV)-Kolloiden in anoxischen Porenwässern oder anoxischen Grundwässern liefern. Es ist jedoch zu beachten, dass experimentell die Reduktion von Uran(VI)-Phasen vorausgesetzt wurde und eine anschließende Verdünnung in Anwesenheit von Silikat erfolgt. Umweltbezogene Untersuchungen zur Mobilität und Stabilität in aquatischen Systemen dieser Kolloide waren nicht Gegenstand der Arbeit und so kann eine umweltrelevante Beurteilung dieser neuartigen Uran(IV)-Kolloide in Bezug auf den Eintrag in die Biossphäre noch nicht getroffen werden. Die hier präsentierten Ergebnisse bieten aber die Grundlage für weitere, intensive Untersuchungen zu Möglichkeiten der Mobilisierung und Stabilisierung verwandter Actinide und Schwermetalle und sollten Bestandteil der Sicherheitsanalyse bei der Lagerung radioaktiven Abfälle in tiefen geologischen Formationen sein. / This work includes the preparation and characterization of new uranium(IV) colloids which are formed and stabilized in the near neutral pH range and under environmentally relevant conditions. Conclusions on stability behavior and particle size distributions were drawn based on results obtained by dynamic light scattering, zeta potential measurements, as well as ultrafiltration and ultracentrifugation in combination with element analyzes. Spectroscopic methodes confirmed the tetravalent state of uranium in the experiments. Unlike empirical data, it is possible to generate long-term stable uranium(IV) colloids at higher concentrations. By addition of geochemical components such as carbonate and silicate, they are stable and resistant in the near neutral pH range over a long period. It was found that dissolved silica plays an essential role in the preparation of colloids. Colloid-borne uranium(IV) up to a concentration of 10-3 mol/L, corresponding to 0,238 g/L, is stabilized in solutions. This concentration is about three orders of magnitude higher than so far known silicate-free aqueous uranium(IV) colloids. Through the use of different analytical methods (invasive and non-invasive) it could be shown that the resulting uranium(IV) colloids are in the nanoscalar range. A high mobility can be assumed in aquatic systems. Evidence is provided by photon correlation spectroscopy, ultrafiltration, and ultracentrifugation that uranium(IV) can form silicate-containing colloids of a size lower than 20 nm. The particles are generated in near neutral to slightly alkaline solutions containing geochemical relevant components (carbonate, silicate, sodium ions). They remain stable in aqueous suspension over years. Electrostatic repulsion due to a negative zeta potential in the near-neutral to alkaline pH range caused by the silicate stabilizes the uranium(IV) colloids. The isoelectric point of the nanoparticles is shifted towards lower pH values by the silicate. The higher the silicate to uranium(IV) content ratio and the higher the pH of the solution are, the smaller and more stable (in terms of pH-changes) are the particles. It should be noted that no colloids were formed in absence of uranium(IV). The mechanism of the colloidal stabilization can be regarded as “sequestration” by silicate, a phenomenon well known from heavy metal ions of high ion potential such as iron(III) or manganese(III,IV), but never reported for uranium(IV) so far. Extended X-ray absorption fine structure (EXAFS) spectroscopy showed that U–O–Si bonds, which increasingly replace the U–O–U bonds of the amorphous uranium(IV) oxyhydroxide with increasing silicate concentration, make up the internal structure of the colloids. The next-neighbor coordination of uranium(IV) in the uranium(IV)-silica colloids is comparable with that of coffinite, USiO4. The assessment of uranium behavior in the aquatic environment should take the possible existence of uranium(IV)-silica colloids into consideration. Their occurrence might influence uranium migration in anoxic waters. The silicate-stabilized colloids have been generated in laboratory experiments under controlled conditions; i.e., it is not known yet whether these phases can occur in natural water. The qualitative composition of the matrix of the experimental solutions (H+, OH-, Na+, HCO3-/CO32-, silicate) was chosen similar to the geochemical nature of groundwater. Thereby, it can be assumed that such colloids are present in natural waters. The existence of such particles would provide an ex-planation for the occurrence of uranium(IV) colloids in anoxic pore waters or groundwaters. However, it should be noted that these results were observed by the reduction of uranium(VI) carbonate and dilution in the presence of silicate. Studies on the mobility and stability of these colloids in aquatic systems were not subject of this work and an environmental assessment of these novel uranium(IV) colloids with respect to the entry in the biosphere cannot be taken into account. But the possibilities of mobilization and stabilization can be applied to surrogate actinides and heavy metals, and point to the need for more intensive research in this area.

This master's thesis focuses on the deposition of the king Wenceslas (1361-1419) from the throne of the Holy Roman Empire. The dethronement act was realised in August 1400 by four Rhenish electors (Count Palatine and archbishops of Mainz, Cologne and Trier) after years- long preparations. The first chapter briefly questions the possibility of king's deposition in medieval political thought. The second chapter describes long political fights in the Holy Roman Empire before 1400 and highlights the most important events which finally led to the king's deposition, such as the fight for the controll over the archbishopric of Mainz. The third chapter analyses the legal dimension of the dethronement act and puts forward possible interpretation of its role in the constitutional history of the Holy Roman Empire. The elector's activity can be understood as a part of long-term growth of political power of the electoral college, as it was codified in the Golden Bull of Charles IV.

As Formas Farmacêuticas de Liberação Prolongada (FFLP) têm sido uma alternativa eficaz na terapia, pois proporcionam maior adesão do paciente ao tratamento em função da redução da frequência de dosagem ao longo do dia, sendo sua principal característica, a modulação da liberação/dissolução do fármaco. Entretanto, esta etapa pode ser influenciada por diferentes fatores, dentre eles: os físico-químicos relacionados ao fármaco; os farmacêuticos, principalmente relacionados aos excipientes empregados e às técnicas de obtenção da forma farmacêutica (FF) e os fisiológicos do trato gastrintestinal (TGI), como por exemplo, o pH dos líquidos do TGI, o tempo de esvaziamento gástrico, a motilidade intestinal, entre outros. Desse modo, a avaliação do trânsito da FF no TGI, após a sua administração, permite uma melhor compreensão dos fatores que podem afetar as etapas de liberação/dissolução do fármaco in vivo. Dentre as técnicas empregadas com esse objetivo, destacam-se: a cintilografia e os métodos biomagnéticos. A Biosusceptometria de Corrente Alternada (BAC) é um método biomagnético que tem se mostrado promissor para este tipo de estudo, por ser não invasivo, portátil, livre de radiação ionizante, e por apresentar acurácia e versatilidade. Diante do exposto, o presente trabalho teve como objetivos, desenvolver e caracterizar sob o aspecto biofarmacotécnico in vitro, um sistema de liberação prolongada contendo nimesulida (fármaco-modelo) e marcador magnético (ferrita), visando obtenção de ferramenta para avaliação do trânsito gastrintestinal por meio de técnica biomagnética. Para isto foram desenvolvidas quatro formulações de comprimidos de liberação prolongada contendo nimesulida, ferrita e diferentes concentrações de hidroxipropilmetilcelulose (HPMC): NF1 (30% HPMC); NF2 (23% HPMC); NF3 (17% HPMC) e NF4 (10% HPMC). Essas foram avaliadas quanto ao comportamento de dissolução por meio de ensaios com aparato 4 e avaliação da cinética e da eficiência de dissolução (ED%). Posteriormente, estudos biomagnéticos, in vitro e in vivo, foram conduzidos com emprego da técnica de BAC para a formulação selecionada. Os resultados obtidos mostraram que as 04 formulações desenvolvidas apresentaram porcentagens de dissolução distintas em função das diferentes concentrações de HPMC (NF1 = 13,2%; NF2 = 40,1%; NF3 = 72,5% e NF4 = 91,5%). A formulação NF4, com menor concentração de HPMC, foi escolhida para os estudos por meio de BAC em função dos resultados de ED% (54,3%) e por apresentar comportamento mais próximo de uma formulação de liberação prolongada. Em relação aos resultados de BAC in vitro, destaca-se que a formulação NF4 (10%HPMC) apresentou aumento de área magnética de forma independente do pH do meio, sugerindo que a hidratação/intumescimento da HPMC independe do pH. Em relação à avaliação do trânsito intestinal (estudo in vivo) foram obtidos os seguintes dados: Tempo médio de Residência Gástrica (TTR) - 89 minutos; Tempo médio do Trânsito Orocecal (TTO) - 313 minutos e Tempo médio do Trânsito Intestinal (TTI) - 224 minutos. Os dados de BAC in vivo permitiram observar que o aumento de área magnética atingiu um platô em cerca de 80 minutos após a administração da formulação NF4. A comparação dos dados de BAC in vitro e BAC in vivo, relacionados ao trânsito gastrintestinal, indica que a formulação NF4, após apresentar o ápice de intumescimento, foi capaz de manter sua estrutura permanente ao longo do TGI, favorecendo assim a liberação modulada do fármaco. Os resultados obtidos demonstraram que a formulação desenvolvida foi eficiente para avaliar e caracterizar o trânsito no TGI por meio da técnica de BAC e também permitiram uma estimativa do comportamento do fármaco em relação a solubilidade em cada porção do TGI, proporcionando assim uma ferramenta adequada para avaliação do trânsito do TGI e desenvolvimento de FFLP. / Extended Release (ER) dosage forms have been an effective alternative in therapy, since they provide greater patient adherence to treatment as a function of the reduction of the frequency of dosing throughout the day, its main characteristic being the release / dissolution modulation of the drug. However, this stage can be influenced by different factors, among them: the physical and chemical related to the drug; the pharmacists, mainly related to the excipients employed and the techniques of obtaining the form dosage and the physiological ones of the gastrointestinal tract (GI tract), as for example, the pH of the liquid of the GI tract, gastric emptying time, intestinal motility, among others. Thus, assessment of dosage forms transit in GI tract after its administration allows a better understanding of the factors that may affect the drug release / dissolution steps in vivo. Among the techniques used for this purpose, the following stand out: scintigraphy and biomagnetic methods. Alternating Current Biosensiometry (ACB) is a biomagnetic method that has shown promise for this type of study, since it is non-invasive, portable, free of ionizing radiation, and because of its accuracy and versatility. In view of the above, the aim of this work was to develop and characterize a sustained release system containing nimesulide (study drug) and magnetic marker (ferrite) under the in vitro biopharmaceutical aspect, aiming to obtain a tool to evaluate the GI tract transit through means of biomagnetic technique. For this, four formulations of extended release tablets containing nimesulide, ferrite and different concentrations of hydroxypropylmethylcellulose (HPMC): NF1 (30% HPMC) were developed; NF2 (23% HPMC); NF3 (17% HPMC) and NF4 (10% HPMC). These were evaluated for dissolution behavior by apparatus 4, assays and kinetics and dissolution efficiency (ED%). Subsequently, biomagnetic studies, in vitro and in vivo, were conducted using the ACB technique for the selected formulation. The results showed that the formulations developed showed different percentages of dissolution as a function of the different concentrations of HPMC (NF1 = 13.2%, NF2 = 40.1%, NF3 = 72.5% and NF4 = 91.5%). The NF4 formulation, with a lower concentration of HPMC, was chosen for the ACB studies as a function of ED% results (54,3%) and because of the behavior of a sustained release formulation. In relation to the in vitro ACB results, the NF4 formulation (10% HPMC) showed an increase in magnetic area independently of the pH of the medium, suggesting that the HPMC hydration / swelling is independent of pH. In relation to intestinal transit evaluation (in vivo study) the following data were obtained: Mean Time of Gastric Residency (TTR) - 89 minutes; Mean Time of Orocecal Transit (OCTT) - 313 minutes and Mean Time of lntestinal Transit (TTI) - 224 minutes. ACB data in vivo showed that the increase in magnetic area reached a plateau in about 80 minutes after administration of the NF4 formulation. Comparison of in vitro ACB and ACB data in vivo, related to gastrointestinal transit, indicates that the NF4 formulation, after showing the swelling apex, was able to maintain its permanent structure throughout the GI tract, thus favoring the modulated release of the drug. The obtained results demonstrated that the developed formulation was efficient to evaluate and characterize the transit in the GI tract by means of the ACB technique and allowed a prediction of the behavior of the drug in relation to the solubility in each portion of the GI tract, thus providing a suitable tool for evaluation of the GI tract transit and the development of sustained release formulation.

O progresso de projetos anteriores salientou a necessidade de tratar o problema dos softwares para detecção, a partir de bases de dados de publicações científicas, de tendências emergentes de pesquisa e desenvolvimento. Evidenciou-se a carência de aplicações computacionais eficientes dedicadas a este propósito, que são artigos de grande utilidade para um melhor planejamento de programas de pesquisa e desenvolvimento em instituições. Foi realizada, então, uma revisão dos softwares atualmente disponíveis, para poder-se delinear claramente a oportunidade de desenvolver novas ferramentas. Como resultado, implementou-se um aplicativo chamado Citesnake, projetado especialmente para auxiliar a detecção e o estudo de tendências emergentes a partir da análise de redes de vários tipos, extraídas das bases de dados científicas. Através desta ferramenta computacional robusta e eficaz, foram conduzidas análises de frentes emergentes de pesquisa e desenvolvimento na área de Sistemas Geradores de Energia Nuclear de Geração IV, de forma que se pudesse evidenciar, dentre os tipos de reatores selecionados como os mais promissores pelo GIF - Generation IV International Forum, aqueles que mais se desenvolveram nos últimos dez anos e que se apresentam, atualmente, como os mais capazes de cumprir as promessas realizadas sobre os seus conceitos inovadores. / The progress of previous projects pointed out the need to face some problems of software for detecting emerging research and development trends from databases of scientific publications. It became evident the lack of efficient computing applications dedicated to this purpose that are artifacts of great usefulness to better planning research and development programs in institutions. A review of the currently available software was performed, in order to clearly delineate the opportunity to develop new tools. As a result, a software called Citesnake was implemented, designed particularly to help the detection and study of emerging trends from the analysis of networks of several types extracted from the scientific databases. Using this robust and effective computational tool, analyzes of emerging research and development trends were performed in the field of Generation IV Nuclear Power Generation Systems, in such a way to point out, among the most promising reactor types selected by the GIF - Generation IV International Forum, those that have better evolved over the past ten years and seem to be currently the most capable of fulfilling the promises made on their innovative concepts.

Le règne de Jayavarman IV est traditionnellement associé au site de Koh Ker dans l’histoire du Cambodge ancien. Ce souverain aurait abandonné la capitale angkorienne pour installer le siège de son pouvoir (921-941) à quelque cent vingt kilomètres plus à l’est, dans un lieu certainement peu peuplé – Chok Gargyar –, connu aujourd’hui sous le nom de Koh Ker. A sa mort, vers 944, son successeur Rājendravarman réinstalle la capitale à Angkor sans qu’on puisse vraiment expliquer ce retour : Koh Ker, dès lors abandonné par les rois, semblerait n’avoir pas survécu à cet abandon. Cependant, le nombre, l’importance et la diversité des monuments de la capitale de Jayavarman IV dépassent la période de règne et de construction de ce monarque. Il est donc permis d’admettre que l’abandon total – et immédiat – de Koh Ker par la population, après la disparition du roi, est peu vraisemblable. Son existence, au-delà des deux décennies de règne, semble confirmée par le témoignage de certains monuments dits du "style de Koh Ker", construits loin de l’éphémère capitale, tels le prasat Kravan à Angkor ou le prasat Neang Khmau dans la province de Takeo, pour ne citer que ces deux exemples. Notre travail s’est fixé comme but d’essayer d’étudier le plus de monuments possibles à partir des relevés anciens existants et de nos propres recherches : en effet, si les édifices du groupe de Koh Ker ont été répertoriés, ils n’ont jamais été véritablement analysés. En nous appuyant sur les vestiges, la statuaire et les inscriptions encore in situ nous avons essayé de faire une chronologie des bâtiments et de la statuaire, et d’en préciser le style. Une quarantaine d’inscriptions provenant de différents prasat – Thom, Krachap, Andong Kuk, Banteay Pir Choan, Chen, Damrei, Andong et Dan – renseigne sur les monuments de Koh Ker. Ces inscriptions sont écrites en deux langues – sanskrit et khmer –,évoquant les donations du roi et des dignitaires, l’érection des temples pour les dieux, la liste des esclaves, les noms des districts... Notre recherche, en quatre chapitres, porte donc sur le site de Koh Ker et de son roi Jayavarman IV, sur l’architecture, le décor et l’iconographie développés sous sa souveraineté. Il nous faut toutefois apporter une petite précision : si la zone monumentale de Koh Ker a été déminée en grande partie grâce à des crédits français, cette étude a dû tenir compte de la difficulté imposée par l’absence de chemins conduisant à certains sanctuaires dont la dépollution complète n’a pas pu être encore assurée. / The reign of Jayavarman IV (921-941) is traditionally associated with the site of Koh Ker in the history of ancient Cambodia. This sovereign had left the Angkorian capital to install the seat of his power to some one hundred and twenty kilometers to the east, probably in a sparsely populated place, Chok Gargyar, now known as Koh Ker. At his death, around 944, his successor Rajendravarman reinstalls the capital at Angkor. No one can really explain this return – Koh Ker, abandoned by the kings, seems not to have survived after this abandonment. However, the number, importance and diversity of the monuments of the capital of Jayavarman IV exceed the period of reign and the construction of this monarch. It is therefore permissible to assume that the immediate abandonment of Koh Ker by the people, after the death of the king, is hard to accept. Its existence, beyond the two-decade reign, seems confirmed by the testimony of some monuments so-called "style of Koh Ker" built away from the short-lived capital, such as Prasat Kravan at Angkor or Prasat Neang Khmau in Takeo province, to name just two examples. Our work’s goal is to study as many monuments as possible from existing old records and our own research: indeed, if the buildings of the group of Koh Ker have been identified, they never have been properly analyzed. Studying the remains, the statuary and the inscriptions still in situ we have tried to establish a chronology of the buildings and statuary, and specify the style. Forty inscriptions from different Prasats — Thom, Krachap, Andong Kuk, Banteay Pir Choan, Chen, Damrei, Andong and Dan — provide information on the monuments of Koh Ker. These inscriptions are written in two languages, Sanskrit and Khmer, and mention the donations of the King and various dignitaries, the erection of temples for the gods, a list of slaves and the names of the districts... Divided into four chapters, our research focuses on the site of Koh Ker and its king, Jayavarman IV. The architecture, decoration and iconography developed under his sovereignty are the main objectives of this study. However, we must make a clarification: if the monumental area of Koh Ker has been cleared in large part due to French credit, this study had to take into account the difficulty imposed by the absence of access to some monuments where a full clearance has not yet been secured.

A monoetanolamina (MEA) é um composto bifuncional pertencente à classe dos amino-álcoois, muito utilizado em processos industriais envolvendo a remoção de gases ácidos como SO2 , CO2 e H2S. A resina Amberlite XAD-7 é uma resina não-iônica de polaridade intermediária muito utilizada em procedimentos de pré-concentração de compostos orgânicos e íons metálicos. Neste trabalho, estudou-se a interação entre a superfície da resina XAD-7 e a MEA. Massas conhecidas da resina foram colocadas em contato com soluções de MEA em concentrações conhecidas, sob agitação durante certo intervalo de tempo. A quantidade de MEA adsorvida foi calculada considerando-se a diferença entre a concentração inicial e a concentração remanescente no sobrenadante, ambas obtidas a partir de medidas de absorbância, com utilização da reação de Berthelot modificada. Modelos cinéticos de pseudo-primeira e -segunda ordens, além do modelo de difusão intra-partícula, foram aplicados aos dados experimentais obtidos no estudo cinético. Entre estes modelos aplicados, o de pseudo-segunda ordem apresentou excelente ajuste aos dados experimentais. O estudo realizado em um determinado tempo de contato e variando-se a concentração inicial de MEA forneceu resultados experimentais que foram aplicados a três modelos de isotermas (Langmuir, Freundlich e Dubinin-Radushkevich). Destes ajustes, que mostraram excelente concordância, foram obtidos diferentes parâmetros termodinâmicos que definiram algumas características do processo de adsorção. Finalmente, estudos preliminares evidenciaram a retenção de SO32- na superfície da resina XAD-7 modificada com MEA, mostrando a possibilidade da utilização da XAD- 2 7/MEA para extração de SO32- presente em soluções ou de SO2 recolhido em solução alcalina. / Monoethanolamine (MEA) is a bifunctional compound which belongs to the amino- alcohol group, and it is widely used in industrial \"sweetening process\", which is based on the acidic gas (such as SO2 , CO2 and H2S) absorption. Amberlite XAD-7 is a non-polar resin with an intermediate polarity used to pre-concentrate organic compounds and transition metals. In this work, the interaction between the resin surface and MEA was studied. Known amounts of the resin were kept in contact with aqueous solutions of MEA and shaked under a constant rotation and during some defined intervals of time. The amount of adsorbed MEA was calculated as the difference between the initial concentration and remained concentration in the supernatant solution, which was determined applying the Berthelot´s reaction and the spectrophotometry. Kinetic models of pseudo-first and -second orders and intra-particle diffusion model were applied on experimental data collected from the kinetic study. Among these methods, the pseudo-second order model fulled fit on those experimental data. The experiments carried out under a constant time, but by changing the initial MEA concentration, led to other experimental data which were applied to three different isotherm models (Langmuir, Freundlich e Dubinin-Radushkevich). Each model showed a good fit, and for each one, different thermodynamic parameters were calculated and used to describe some adsorption characteristics. Finally, preliminary studies on the retention of SO32- onto the resin surface, previously modified with MEA, showed the possibility to extract SO32- found in aqueous solutions or SO2 recovered in alkaline media.

Les matériaux composites constitués de fibres de carbone et de résine époxy présentent des propriétés spécifiques remarquables qui les destinent à une utilisation à grande échelle dans de nombreux domaines où des gains de masse sont recherchés, comme le transport. Les réservoirs d’hydrogène de type IV présents dans les véhicules automobiles en sont un exemple. Dans le cadre de la sécurité des biens et des personnes, le risque incendie doit alors être considéré : lorsqu’un réservoir d’hydrogène subit une agression thermique telle qu’un feu, son enveloppe en matériau composite est sujette à décomposition thermique qui, couplée aux transferts de chaleur et à l’endommagement dû au chargement mécanique, peut conduire à l’explosion de la structure. Pour prédire numériquement le comportement des réservoirs dans des situations de charges couplées, thermiques et mécaniques, un modèle construit sur la prise en compte des phénomènes ayant une conséquence majeure sur le comportement du matériau a été développé. Il intègre, dans un cadre thermodynamique, la microfissuration matricielle, la rupture des fibres et des interfaces fibres/matrice ainsi que le délaminage et représente les effets de la température sur les propriétés mécaniques. A cet endommagement mécanique est adjoint la décomposition thermique due aux températures élevées (>350°C). Elle induit des changements de structure du matériau due à la gazéification de la résine époxy, une modification des paramètres thermiques (ce qui a une influence sur les transferts de chaleur) et une perte des propriétés mécaniques.A l’échelle de l’éprouvette, des calculs sont menés afin de déterminer les paramètres des différents sous-modèles. Cela comporte les critères d’initiation et les lois d’évolution des endommagements, les paramètres réactionnels pour la décomposition thermique et les paramètres thermiques (masse volumique, capacité thermique et conductivité) pour chaque état de décomposition. Une méthode est proposée pour fixer les paramètres clés du couplage thermomécanique, à savoir l’influence de la décomposition thermique sur le comportement mécanique. Des calculs entièrement couplés sont également réalisés afin de déterminer le poids de chaque phénomène (température, décomposition thermique et endommagement mécanique) sur la rupture finale du matériau en condition d’exposition au feu.A l’échelle du réservoir hyperbare, des prédictions de pressions d’éclatement, en situation d’incendie et à température ambiante, sont menées. A température ambiante, le rôle de chaque processus d’endommagement dans la pression ultime est évalué afin de déterminer leur nécessité dans la modélisation. Dans des conditions d’incendie, le temps à éclatement est évalué lorsque le réservoir est soumis à différentes pressions internes. Le modèle est capable de prédire correctement la transition entre un mode d’éclatement à haute pression et un mode de fuite par le corps à plus faible pression, dû à la fusion du liner avant que le niveau de contraintes soit critique dans la coque composite et conduise à l’éclatement. Cette approche, mise en place à l’échelle du réservoir, permet donc d’établir la succession des événements menant à son éclatement (ordre et plis d’apparition des endommagements, champ de température dans l’épaisseur l’enveloppe composite, temps à explosion). / Composite materials made of carbon fibres and epoxy resin have remarkable specific properties that make them suitable for large-scale use in many areas where mass savings are required, such as transport. An example is the type IV hydrogen tank in motor vehicles. In the context of the safety of persons, the fire risk must then be considered: when a hydrogen tank undergoes thermal aggression such as a fire, its composite shell is subject to thermal decomposition which, coupled with heat transfers and damage due to mechanical loading, can lead to burst of the structure. To numerically predict the behaviour of tanks subjected to coupled load (thermal and mechanical), a model based on the phenomena having a major impact on the behaviour of the material has been developed. It involves, in a thermodynamic framework, matrix microcracking, fibre failure and fibre/matrix interfaces decohesion as well as delamination and represents the effects of temperature on mechanical properties. To this mechanical damage is added the thermal decomposition due to high temperatures (>350°C). It induces structural changes in the material due to the gasification of the epoxy resin, a change in thermal parameters (which has an influence on heat transfers) and a loss of mechanical properties.At the specimen scale, calculations are carried out to determine the parameters of the different sub-models. This includes initiation criteria and damage evolution laws, reaction parameters for thermal decomposition and thermal parameters (density, thermal capacity and conductivity) for each decomposition state. A method is proposed to determine the key parameters of thermomechanical coupling, namely the influence of thermal decomposition on mechanical behaviour. Fully coupled calculations are also performed to determine the weight of each phenomenon (temperature, thermal decomposition and mechanical damage) on the final failure of the material under fire exposure conditions.At the hyperbaric tank scale, burst pressure predictions, in a fire situation and at room temperature, are carried out. At room temperature, the role of each damage process in the ultimate pressure is evaluated to determine their relative weight in the modelling. Under fire conditions, the time to burst is evaluated when the tank is subjected to different internal pressures. The model is able to correctly predict the transition from a burst mode at high pressure to leak mode at lower pressure due to melting of the liner before the stress level is critical in the composite shell and leads to burst. This approach, implemented at the scale of the tank, therefore makes it possible to establish the sequence of events leading to burst (plies in which damage occurs, temperature field in the composite wall, burst time).

As Formas Farmacêuticas de Liberação Prolongada (FFLP) têm sido uma alternativa eficaz na terapia, pois proporcionam maior adesão do paciente ao tratamento em função da redução da frequência de dosagem ao longo do dia, sendo sua principal característica, a modulação da liberação/dissolução do fármaco. Entretanto, esta etapa pode ser influenciada por diferentes fatores, dentre eles: os físico-químicos relacionados ao fármaco; os farmacêuticos, principalmente relacionados aos excipientes empregados e às técnicas de obtenção da forma farmacêutica (FF) e os fisiológicos do trato gastrintestinal (TGI), como por exemplo, o pH dos líquidos do TGI, o tempo de esvaziamento gástrico, a motilidade intestinal, entre outros. Desse modo, a avaliação do trânsito da FF no TGI, após a sua administração, permite uma melhor compreensão dos fatores que podem afetar as etapas de liberação/dissolução do fármaco in vivo. Dentre as técnicas empregadas com esse objetivo, destacam-se: a cintilografia e os métodos biomagnéticos. A Biosusceptometria de Corrente Alternada (BAC) é um método biomagnético que tem se mostrado promissor para este tipo de estudo, por ser não invasivo, portátil, livre de radiação ionizante, e por apresentar acurácia e versatilidade. Diante do exposto, o presente trabalho teve como objetivos, desenvolver e caracterizar sob o aspecto biofarmacotécnico in vitro, um sistema de liberação prolongada contendo nimesulida (fármaco-modelo) e marcador magnético (ferrita), visando obtenção de ferramenta para avaliação do trânsito gastrintestinal por meio de técnica biomagnética. Para isto foram desenvolvidas quatro formulações de comprimidos de liberação prolongada contendo nimesulida, ferrita e diferentes concentrações de hidroxipropilmetilcelulose (HPMC): NF1 (30% HPMC); NF2 (23% HPMC); NF3 (17% HPMC) e NF4 (10% HPMC). Essas foram avaliadas quanto ao comportamento de dissolução por meio de ensaios com aparato 4 e avaliação da cinética e da eficiência de dissolução (ED%). Posteriormente, estudos biomagnéticos, in vitro e in vivo, foram conduzidos com emprego da técnica de BAC para a formulação selecionada. Os resultados obtidos mostraram que as 04 formulações desenvolvidas apresentaram porcentagens de dissolução distintas em função das diferentes concentrações de HPMC (NF1 = 13,2%; NF2 = 40,1%; NF3 = 72,5% e NF4 = 91,5%). A formulação NF4, com menor concentração de HPMC, foi escolhida para os estudos por meio de BAC em função dos resultados de ED% (54,3%) e por apresentar comportamento mais próximo de uma formulação de liberação prolongada. Em relação aos resultados de BAC in vitro, destaca-se que a formulação NF4 (10%HPMC) apresentou aumento de área magnética de forma independente do pH do meio, sugerindo que a hidratação/intumescimento da HPMC independe do pH. Em relação à avaliação do trânsito intestinal (estudo in vivo) foram obtidos os seguintes dados: Tempo médio de Residência Gástrica (TTR) - 89 minutos; Tempo médio do Trânsito Orocecal (TTO) - 313 minutos e Tempo médio do Trânsito Intestinal (TTI) - 224 minutos. Os dados de BAC in vivo permitiram observar que o aumento de área magnética atingiu um platô em cerca de 80 minutos após a administração da formulação NF4. A comparação dos dados de BAC in vitro e BAC in vivo, relacionados ao trânsito gastrintestinal, indica que a formulação NF4, após apresentar o ápice de intumescimento, foi capaz de manter sua estrutura permanente ao longo do TGI, favorecendo assim a liberação modulada do fármaco. Os resultados obtidos demonstraram que a formulação desenvolvida foi eficiente para avaliar e caracterizar o trânsito no TGI por meio da técnica de BAC e também permitiram uma estimativa do comportamento do fármaco em relação a solubilidade em cada porção do TGI, proporcionando assim uma ferramenta adequada para avaliação do trânsito do TGI e desenvolvimento de FFLP. / Extended Release (ER) dosage forms have been an effective alternative in therapy, since they provide greater patient adherence to treatment as a function of the reduction of the frequency of dosing throughout the day, its main characteristic being the release / dissolution modulation of the drug. However, this stage can be influenced by different factors, among them: the physical and chemical related to the drug; the pharmacists, mainly related to the excipients employed and the techniques of obtaining the form dosage and the physiological ones of the gastrointestinal tract (GI tract), as for example, the pH of the liquid of the GI tract, gastric emptying time, intestinal motility, among others. Thus, assessment of dosage forms transit in GI tract after its administration allows a better understanding of the factors that may affect the drug release / dissolution steps in vivo. Among the techniques used for this purpose, the following stand out: scintigraphy and biomagnetic methods. Alternating Current Biosensiometry (ACB) is a biomagnetic method that has shown promise for this type of study, since it is non-invasive, portable, free of ionizing radiation, and because of its accuracy and versatility. In view of the above, the aim of this work was to develop and characterize a sustained release system containing nimesulide (study drug) and magnetic marker (ferrite) under the in vitro biopharmaceutical aspect, aiming to obtain a tool to evaluate the GI tract transit through means of biomagnetic technique. For this, four formulations of extended release tablets containing nimesulide, ferrite and different concentrations of hydroxypropylmethylcellulose (HPMC): NF1 (30% HPMC) were developed; NF2 (23% HPMC); NF3 (17% HPMC) and NF4 (10% HPMC). These were evaluated for dissolution behavior by apparatus 4, assays and kinetics and dissolution efficiency (ED%). Subsequently, biomagnetic studies, in vitro and in vivo, were conducted using the ACB technique for the selected formulation. The results showed that the formulations developed showed different percentages of dissolution as a function of the different concentrations of HPMC (NF1 = 13.2%, NF2 = 40.1%, NF3 = 72.5% and NF4 = 91.5%). The NF4 formulation, with a lower concentration of HPMC, was chosen for the ACB studies as a function of ED% results (54,3%) and because of the behavior of a sustained release formulation. In relation to the in vitro ACB results, the NF4 formulation (10% HPMC) showed an increase in magnetic area independently of the pH of the medium, suggesting that the HPMC hydration / swelling is independent of pH. In relation to intestinal transit evaluation (in vivo study) the following data were obtained: Mean Time of Gastric Residency (TTR) - 89 minutes; Mean Time of Orocecal Transit (OCTT) - 313 minutes and Mean Time of lntestinal Transit (TTI) - 224 minutes. ACB data in vivo showed that the increase in magnetic area reached a plateau in about 80 minutes after administration of the NF4 formulation. Comparison of in vitro ACB and ACB data in vivo, related to gastrointestinal transit, indicates that the NF4 formulation, after showing the swelling apex, was able to maintain its permanent structure throughout the GI tract, thus favoring the modulated release of the drug. The obtained results demonstrated that the developed formulation was efficient to evaluate and characterize the transit in the GI tract by means of the ACB technique and allowed a prediction of the behavior of the drug in relation to the solubility in each portion of the GI tract, thus providing a suitable tool for evaluation of the GI tract transit and the development of sustained release formulation.

在本實驗室之前的研究中顯示在發炎狀態的大白鼠上以intrathecal (i.t.) 方式給予angiotensin IV (Ang IV) ，Ang IV 是insulin-regulated aminopeptidase (IRAP) inhibitor，可以減少腳掌發炎之大白鼠的疼痛過敏化。然而，這個由Ang IV所產生之效果背後的機制還未被完全釐清。 在這次的實驗中，我們利用由carrageenan引起腳掌腫脹之大鼠進行plantar test來研究Ang IV所產生之抗疼痛過敏化其中可能機制。由於有文獻指出，在發炎狀態的大白鼠上以intrathecal (i.t.) 方式給予oxytocin可產生一劑量相關性的抗疼痛過敏化作用，因此我們推測在大白鼠的脊髓層次上由oxytocin以及Ang IV所個別誘導的抗疼痛過敏化之間可能有關聯性。利用 i.t.單獨給予atosiban (selective oxytocin receptor antagonist) 可以觀察到一個較強烈的疼痛過敏化現象，然而合併給予atosiban，可使Ang IV所產生的抗疼痛過敏化完全被阻斷掉。因此我們推測oxytocin在以intrathecal (i.t.) 方式給予Ang IV而阻斷IRAP的活性，進而產生抗疼痛過敏化作用的過程中是一個主要的IRAP受質。 當我們在carrageenan誘導疼痛過敏化的大白鼠上單獨給予低劑量之oxytocin並沒有產生統計上顯著之抗疼痛過敏作用。然而合併給予oxytocin和Ang IV後，則可以有觀察到Ang IV 能增加並且延長oxytocin所引起的抗疼痛過敏化作用。 就內生性oxytocin來看，電刺激paraventricular hypothalamic nucleus (PVN)已被證實可以增加內生性的oxytocin分泌到脊髓。而這樣的一個神經路徑被發現和疼痛的調節具有很密切的關聯性。從我們的結果中，我們發現在carrageenan誘導疼痛過敏化的大白鼠上，i.t.給予Ang IV可以延長PVN電刺激產生的抗疼痛過敏化作用，由此推測 Ang IV可能可以保護內生性oxytocin不被分解或失去活性。 除了oxytocin之外，IRAP在體外的實驗中被證實可以分解數種具生理活性之peptides 的N-terminal amino acid，其中包括vasopressin, bradykinin 以及 enkephalin等。在這些物質中，bradykinin已被證實在週邊發炎的過程中具有重要的調控效果，若IRAP在週邊組織扮演了一個分解促發炎物質的角色，利用Ang IV也許可以去阻斷IRAP之活性進而增加這些促發炎物質。因此，我們在由carrageenan誘導疼痛過敏化的動物模式上利用腳掌局部注射 Ang IV來探討在發炎部位Ang IV可能的作用。我們猜測Ang IV 可能可以調控不同物質(例如：bradykinin)而在發炎部位產生局部之作用， 但結果顯示在疼痛過敏化以及腫脹程度上，Ang IV並不具有調控週邊組織發炎過程的能力。所以推測Ang IV在週邊發炎位置可能並沒有扮演非常重要的角色。 總而言之，本實驗結果證實了Ang IV以及 oxytocin在發炎大白鼠的脊髓層次上所個別引起之抗疼痛過敏化作用之間具有相關性，其中的機制可能是Ang IV在發炎大白鼠的脊髓層次上藉由抑制IRAP降解oxytocin的活性，進而產生抗疼痛過敏化的效果。 / In our previous study, we showed that intrathecal (i.t.) administration of angiotensin IV (Ang IV), an insulin-regulated aminopeptidase (IRAP) inhibitor, could attenuate hyperalgesia in rats with inflammation. However, the underlying mechanism(s) for this effect of Ang IV was not clarified yet. Using the plantar test in rats with carrageenan-induced paw inflammation, we attempted to investigate the possible mechanism(s) of Ang IV in the present study. Because it has been reported that i.t. administration of oxytocin produced a dose-dependent anti-hyperalgesia effect in rats with inflammation, we speculate that there is a possible correlation between the oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats. Using i.t. co-administered atosiban (a selective oxytocin receptor antagonist), the anti-hyperalgesia effect of Ang IV was completely abolished, although a severer hyperalgesia was observed in rats receiving atosiban alone. This indicates that oxytocin could be the major substrate of IRAP responsible for the anti-hyperalgesia caused by intrathecal administration of Ang IV, which blocked the activity of IRAP. Using i.t. administration of oxytocin in rats with carrageenan-induced hyperalgesia, the anti-hyperalgesia effect of oxytocin was potent and significant. When Ang IV was co-administered with the low dose of oxytocin, a significant enhancing effect of Ang IV on anti-hyperalgesia of oxytocin was observed. In view of the endogenous oxytocin, electrical stimulation of the paraventricular hypothalamic nucleus (PVN) has been proved to cause the increase of oxytocin release at the spinal cord. This neural pathway has been found to be highly related to the modulation of pain. In our results, we found that i.t. administration of Ang IV could prolong the anti-hyperalgesia induced by PVN stimulation. This suggests a possible protective effect of Ang IV on endogenous oxytocin degradation/dysfunctioning. In addition to oxytocin, it was well known that IRAP is able to cleave the N-terminal amino acid from several bioactive peptides in vitro, including vasopressin, bradykinin and enkephalin. Among these substrates, bradykinin has been demonstrated to be an important mediator in peripheral inflammation. It is a pro-inflammatory substance that can be enhanced by Ang IV, if the peripheral IRAP plays a role in its degradation. Therefore, we examined the possible local effect of intraplantarly injected Ang IV on the carrageenan-induced hyperalgesia in the same model. However, our results showed no effect of local Ang IV on hyperalgesia and paw edema, indicating that Ang IV may not be able to regulate the peripheral inflammatory process. Overall, the present study verified the possible interaction between the oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats with inflammation. It suggests that Ang IV may act though the inhibition of the activity of IRAP to reduce the degradation of oxytocin, thereby lead to anti-hyperalgesia in rats with inflammation.