Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2018-08-20T12:17:43Z No. of bitstreams: 1 2010 - Diogo Joffily.pdf: 993690 bytes, checksum: c5e8df7300d4f2e09eb55e7f60f4f1a9 (MD5) / Made available in DSpace on 2018-08-20T12:17:43Z (GMT). No. of bitstreams: 1 2010 - Diogo Joffily.pdf: 993690 bytes, checksum: c5e8df7300d4f2e09eb55e7f60f4f1a9 (MD5) Previous issue date: 2010-09-17 / The state of Rio de Janeiro is in the national and international route of the traffic of wild animals. The numbers of apprehensions in this state are raised and the CETAS-RJ receives a great number of animals per year. Projects of release and reintroduction of wild animals combined with scientific research must gain space so that destination of these animals to the natural environment can occur in an objective way. The objective of the study was to develop procedures for release, with individuals of Aratinga leucophthalma species, taking in consideration behavior characteristics, the social structure, the alimentary habits and to accomplish the monitoring of the animals during the release and the post-release, looking for results that come to aid in future projects. The work was accomplished at three different places: the CETAS-RJ, ocurred the handling before the release and the study of the feeding in captivity; the campus of the UFRRJ, where field work related with the feeding in free life was don; and in the RPPN S?o Benedito Farm in Rio Claro-RJ, where the release and the post-release monitoring ocurred. The work was accomplished between September 2008 and July 2010. The handling before the release was done by the preparation of a nursery to house 30 animals. The animals were grouped by flight capacity and domestication level. This stage was also composed by the accomplishment of clinical and labs exams, individual demarcation of the animals through rings and sexing exam. Of the selected animals there was prevalence of males. According to the clinical exams was not verified any aspect to make unfeasible the work. The study of the feeding in captivity was made through analysis of the supplied food and the amount of leftovers, verifying the preference through the alimentary behavior. Preference of the birds was revealed by the sunflower seed and the need of the maintenance and elaboration of new balanced diets appropriated to release programs. The field work tried to describe the alimentary items of species from the Psittacidae family. The importance of exotic vegetable species was revealed as food source for birds of the Psittacidae family in the campus. From the ten alimentary items observed only three were from native species. The release was accomplished by the model of soft release, after a period of acclimatization in the release area, which preceded the opening of the nursery. After the opening of the nursery a food support was maintained inside and outside of the nursery and the monitoring was accomplished collecting data in daily accomp. The birds went increasing gradually the distance traveled after the release and they were incorporating themselves to groups from the area. The soft release model used in this work guaranteed the success in the process of rehabilitation of these birds. The food supports maintained after the opening of the nursery were extremely important to guarantee the nutrition of the birds during the first days after the release, and to give them strength for recognition of the area and to look for new food sources. / O Rio de Janeiro est? na rota nacional e internacional do tr?fico de animais silvestres. S?o elevados os n?meros de apreens?es realizadas nesse estado e o CETAS-RJ recebe um grande n?mero de animais por ano. Projetos de soltura e reintrodu??o de animais silvestres, aliados a pesquisas cient?ficas devem ganhar espa?o nesse cen?rio para que o retorno desses animais ? natureza ocorra de forma objetiva e segura. O objetivo do estudo foi desenvolver procedimentos para soltura, atrav?s de experimentos com indiv?duos da esp?cie Aratinga leucophthalma, levando em considera??o suas caracter?sticas comportamentais, estrutura social, h?bitos alimentares e ainda, realizar o monitoramento dos animais durante a soltura e o per?odo p?s-soltura, buscando resultados que venham auxiliar futuros projetos. O trabalho foi realizado em tr?s locais diferentes sendo eles: o CETAS-RJ, onde ocorreu o manejo antes da soltura e o estudo da alimenta??o em cativeiro; o campus da UFRRJ, onde foi feito o trabalho de campo relacionado com a alimenta??o em vida livre; e a RPPN Fazenda S?o Benedito em Rio Claro-RJ, onde ocorreu a soltura e o monitoramento p?s-soltura. O per?odo de desenvolvimento do projeto foi entre setembro de 2008 e julho de 2010. O manejo pr?soltura foi constitu?do pelo preparo de um viveiro para alojar 30 indiv?duos de A. leucophthalma. Os animais foram selecionados de acordo com sua capacidade de v?o e o n?vel de domestica??o. Esta etapa foi composta ainda pela realiza??o de exames cl?nicos e laboratoriais, pela marca??o individual dos animais atrav?s de anilhas e a sexagem. Dos animais selecionados, houve predom?nio de machos em rela??o a f?meas. No tocante a exames cl?nicos realizados, n?o foi constatado nenhum aspecto que pudesse inviabilizar o trabalho. O estudo da alimenta??o em cativeiro foi feito atrav?s da an?lise do alimento fornecido e a quantidade de sobra, verificando a prefer?ncia atrav?s do comportamento alimentar. Foi revelada prefer?ncia das aves pela semente de girassol e a necessidade da manuten??o e elabora??o de novas dietas balanceadas, voltadas para programas de soltura. O trabalho de campo buscou descrever os itens alimentares de esp?cies da fam?lia Psittacidae. Foi revelada a import?ncia de esp?cies vegetais ex?ticas como fonte de alimento para aves da fam?lia Psittacidae no campus da UFRRJ. Dos dez itens alimentares observados apenas tr?s eram provenientes de esp?cies nativas. A soltura foi realizada pelo modelo de soltura branda, ap?s um per?odo de aclimata??o na ?rea de soltura, que antecederam a abertura do viveiro. Foram mantidos suportes alimentares dentro e fora do viveiro durante a soltura e o monitoramento, que foi realizado atrav?s de acompanhamento di?rio e coleta de dados. As aves foram gradualmente aumentando as dist?ncias percorridas ap?s a soltura e foram se incorporando a bandos da regi?o. O modelo de soltura branda, utilizado neste trabalho, garantiu sucesso no processo de reintrodu??o dessas aves. Os suportes alimentares mantidos ap?s a abertura do viveiro foram de fundamental import?ncia para garantir a nutri??o das aves nos primeiros dias ap?s a soltura, dar-lhes for?as para reconhecimento da ?rea em que foram soltas bem como buscar novas fontes de alimento.

O processo de microencapsulação vem sendo bastante aplicado em alimentos e um dos objetivos que vem se destacando atualmente é o controle da liberação do agente ativo no tempo e local desejado. Portanto, o objetivo do trabalho foi microencapsular agentes refrescantes (xilitol e mentol) a aplicá-los em gomas de mascar, objetivando prolongar a duração da sensação de refrescância. Xilitol e mentol foram microencapsulados utilizando o método de coacervação complexa. As microcápsulas foram caracterizadas quanto ao tamanho médio, morfologia (microscopia ótica, confocal e eletrônica de varredura), cor instrumental, higroscopicidade, umidade, atividade de água (Aw), solubilidade em água, isotermas de sorção, espectroscopia no infravermelho por transformada de Fourier (FTIR), comportamento térmico (por Caloria Diferencial de Varredura - DSC), eficiência de encapsulação e controle de liberação. As gomas de mascar foram produzidas no laboratório de pesquisa e desenvolvimento de uma indústria de alimentos. Oito formulações foram produzidas, sendo quatro com as microcápsulas e quatro com os ingredientes livres. As gomas foram analisadas em relação à umidade, Aw e cor instrumental; por meio da análise do perfil de textura (TPA) avaliou-se a dureza, elasticidade, mastigabilidade e a coesividade das gomas. Análise de tempo-intensidade (TI) das gomas de mascar foi realizada com 19 provadores treinados para avaliar a duração da sensação de refrescância fornecida por esses ingredientes. As microcápsulas obtidas apresentaram características adequadas para aplicação em alimentos, como tamanho médio de partículas de aproximadamente 100 µm e baixos valores de umidade, Aw, solubilidade e higroscopicidade. Por meio da microscopia confocal e da análise de FTIR confirmou-se que os núcleos foram completamente encapsulados pelo material de parede, demonstrando o sucesso da técnica empregada. A eficiência de encapsulação foi alta para o mentol, mas relativamente baixa para o xilitol. Por meio da análise de DSC constatou-se que o xilitol e o mentol passam do estado cristalino para o estado amorfo após o processo de microencapsulação, o que não interfere nas propriedades do mentol, mas no caso do xilitol sim, pois sua refrescância é atribuída ao seu calor de dissolução endotérmico. As gomas de mascar apresentaram baixos valores de Aw e umidade, o que favorece a estabilidade microbiológica. Em relação ao perfil de textura, observou-se que a presença do xilitol melhorou os parâmetros de textura das gomas, pois as gomas produzidas com este composto apresentaram os menores valores de dureza, mastigabilidade e elasticidade. A presença das microcápsulas não interferiu significativamente em nenhum dos parâmetros de textura analisados. A análise de TI confirmou que as microcápsulas foram hábeis para promover liberação gradual do mentol e do xilitol, pois a refrescância das gomas de mascar contendo as microcápsulas durou mais tempo que as gomas de mascar com os ingredientes livres. / The microencapsulation process has been widely applied in food and one of the aims that have been highlighted is to control the release of the active agent at the desired time and local. Therefore, the objective was to microencapsulate cooling agents (menthol and xylitol) to apply them in chewing gum, aiming to prolong the feeling of freshness. Xylitol and menthol were microencapsulated using complex coacervation method. The microcapsules were characterized by particle size, morphology (optical microscopy, confocal and scanning electron), instrumental color parameter, hygroscopicity, moisture, water activity (Aw), solubility, sorption isotherms, Fourier transform Infrared Spectroscopy (FTIR), thermal behavior (Differential Scanning Calorie -DSC), encapsulation efficiency and release control. The chewing gums were produced in the research and development laboratory of a food industry. Eight formulations were produced, four with microcapsules and four with free ingredients. The gums were analyzed for moisture, Aw and instrumental color parameter; by texture profile analysis (TPA) was evaluated hardness, springiness, chewiness and cohesiveness of the gum. Analysis of time-intensity (TI) of chewing gum was conducted with 19 trained panelists to evaluate the duration of the freshness sensation provided by such ingredients. The microcapsules obtained had characteristics suitable for application in foods such as average particle size of approximately 100 µm and low levels of humidity, Aw, solubility and hygroscopicity. By confocal microscopy and FTIR analysis it was confirmed that the cores were completely encapsulated by wall material, ensuring the success of the technique. The encapsulation efficiency was high in menthol microcapsules but relatively low for xylitol microcapsules. By the DSC analysis it was found that xylitol and menthol crystalline state transform to the amorphous state after the microencapsulation process, which does not affect the properties of menthol, but in the xylitol yes, because their freshness is attributed to its endothermic heat of dissolution. Chewing gums showed low values of Aw and moisture, which favors the microbiological stability. Through TPA, was observed that the presence of xylitol improved the texture parameters of the gums because the gums produced with this compound showed the lowest hardness, chewiness and elasticity. The presence of the microcapsules was not significantly influenced the texture parameters analyzed. Time-Intensity analysis confirmed that the microcapsules were able to promote gradual release of menthol and xylitol, because the freshness of chewing gum containing microcapsules lasted longer than the chewing gum free ingredients.

L’érosion des stocks naturels de Paracentrotus lividus, oursins comestibles de Méditerranée, malgré les mesures actuelles réglementant les captures, soulève des inquiétudes sur la pérennité de son exploitation et sur l'équilibre des écosystèmes. En 2009, à la demande des pêcheurs professionnels, des gestionnaires de la ressource et de la communauté d’agglomération Toulon Provence Méditerranée (TPM), l'Institut Océanographique Paul Ricard et l'Équipe de Biologie Moléculaire Marine du laboratoire PROTEE (Université de Toulon), ont engagé un travail de recherche visant à mieux comprendre l'influence des processus naturels et anthropiques qui façonnent les populations naturelles, dans le but d'améliorer les stratégies de soutien aux populations, notamment par le réensemencement de juvéniles d'oursins.L'objectif du travail de thèse a été de (i) caractériser l'état des stocks sauvages de l'aire toulonnaise et de leurs dynamiques par la mise en place du suivi démographique bisannuel à long terme de huit stations références, (ii) de développer les méthodes de production de juvéniles en écloserie et (iii) d'évaluer l'efficacité du repeuplement et son impact sur les populations naturelles. Compte-tenu du cycle de vie bentho-pélagique de P. lividus, nous avons inscrit cette problématique dans une échelle régionale.Les résultats obtenus permettent de dresser un premier état des lieux de la structuration et des fluctuations d'abondances des peuplements de P. lividus sur l'aire toulonnaise et démontrent la fragilité des stocks naturels vis à vis des captures. La maîtrise complète du cycle de vie en aquaculture a été obtenue, notamment en optimisant les conditions d’élevage au stade critique de la métamorphose. Enfin, les repeuplements expérimentaux, réalisés à l'échelle pilote, ont présenté un succès variable selon les sites mais potentiellement important, sans aucun effet sur la structuration et la diversité génétique des stocks naturels. Le travail engagé et les premiers résultats sont discutés dans le contexte de la conservation et de l'exploitation durable de cette ressource naturelle. Ils constituent en outre un préalable indispensable aux réflexions sur l’ajustement ou la mise en place de nouvelles actions de gestion des populations et de la ressource. / Despite current measures regulating captures, the erosion of natural stocks of the edible Paracentrotus lividus sea urchin of Mediterranean Sea, raises concerns about the sustainability of its exploitation and the stability of the associated ecosystem. In 2009, upon request of professional fishermen, resource managers and the urban district of Toulon Provence Méditerranée, we have initiated a program of research to better understand the influence of natural and anthropogenic processes that shape natural populations. The objectives of the thesis were (1) to monitor the demographic evolution of P. lividus communities on eight sites of the Toulon area between 2011 and 2013 before and after the legal harvesting period, (2) to develop a reliable method of production of P. lividus juveniles in hatchery and (3) to evaluate the effectiveness of restocking at a pilot scale and assess its potential impact over natural populations. Given the long larval phase in the bentho-pelagic cycle of this species, we monitored the genetic diversity of P. lividus populations at a regional scale.The data and results acquired during this work first provide an initial evaluation of the structure, abundance and fluctuation of followed P. lividus populations along the Toulon coast and demonstrate the vulnerability of natural stocks towards harvesting. In addition, complete control over the whole life cycle in batch was achieved through optimization of cultural and food parameters, especially at the critical stage of settlement and metamorphosis. Finally, experimental restocking trials demonstrated varying success depending on the site, but potentially significant, without apparent effect on the genetic diversity of wild stocks. Results obtained in this thesis are discussed in the context of conservation and sustainable exploitation of this natural resource. They are also a prerequisite to discussion on the adjustment or implementation of new management guidelines.

The mesolimbic dopamine (DA) system projects from the ventral tegmental area (VTA) to structures associated with the limbic system, primarily the nucleus accumbens (NAc). This system has been implicated in the rewarding effects of drugs of abuse. Many drugs of abuse act in the VTA, the NAc, or both. Dopamine neurons in the VTA that project to the NAc, and the GABA neurons that inhibit DA neurons locally in the VTA or project to the NAc, play an important role in mediating addiction to various drugs of abuse, in particular alcohol. There is a growing body of evidence of co-dependence of nicotine and ethanol drug abuse. Given this evidence, it is possible that both ethanol and nicotine target similar receptors in the NAc. The GABA-A and GABA-B receptors have also been implicated in the modulation of ethanol's reinforcing properties (Anstrom, Cromwell, Markowski, & Woodward, 2003; Besheer, Lepoutre, & Hodge, 2004; Colombo et al., 2000; Moore & Boehm, 2009; Stromberg, 2004; Walker & Koob, 2007). Thus, there is a growing literature suggesting that GABA receptors are implicated in ethanol reward. In these studies, we evaluated the possibility of co-dependence of nicotine and ethanol by activity on a similar receptor in the NAc. In addition, we evaluated the role of GABA modulation of DA release, in particular GABA-A receptors and GABA-B receptors, in modulating DA release in the NAc with acute ethanol exposure. The rationale for this study was predicated on the belief that advancement in the understanding of the brain mechanisms underlying the recreational use and abuse potential of alcohol will pave the way for more effective treatment strategies that could reverse alcohol dependence and co-dependence and save lives and resources throughout the world.

Methamphetamine (METH) is a highly addictive substance that is highly prevalent in today’s society, with over 1 in 20 adults over 26 having taken it at least once. While it is known that METH, a common psychostimulant, acts on both the mesolimbic dopamine (DA) and nigrostriatal DA systems by affecting proteins involved in DA reuptake and vesicular packaging, the specific mechanism of what is known as METH neurotoxicity remains obscure, but has been shown to involve oxidative stress. Studies have shown that reactive oxygen species act on the same proteins that METH affects. Oxidative species have also been known to catalyze the formation of melanins in dopaminergic cells. We explore this link more fully here. In an in vitro system, oxidative species (including Fe3+, an inorganic catalyst for oxidative stress), enhance the rate of melanization of DA. Methamphetamine increased oxidative stress in an in vivo model. Additionally, METH enhanced phasic (stimulated) DA release and caused an electrically-independent efflux of DA. Lidocaine abolished phasic DA release, but did not affect METH-induced DA efflux, indicating action-potential dependent and independent mechanisms behind METH’s effects. The sigma-1 receptor antagonist BD 1063 significantly attenuated METH’s effect on DA release. Depletion of intracellular calcium (Ca2+) reserves also attenuated METH-enhancement of DA release. We investigated the role of oxidative species in METH-induced DA efflux. Reduced glutathione (the substrate for glutathione peroxidase) and 4-hydroxy-TEMPOL (a superoxide dismutase mimetic) blocked METH’s effect on DA release, suggesting that a reactive oxygen species (ROS), most likely superoxide, is necessary for METH-induced DA efflux. Finally, oxidative stress as well as acute METH impairs the vesicular monoamine transporter 2 (VMAT2) by S-glutathionylation modification of Cys-488, highlighting VMAT2 as a likely regulator of METH’s effects on electrically independent DA release. These findings help outline a model in which METH induces DA release in the NAc through a signaling cascade involving the sigma receptor and ROS signaling molecules.

Groupers (Epinephelidae: Epinephelinae) are apex predators within many reef communities worldwide. Grouper landings contribute significantly to global fisheries, and many populations are suffering from unsustainable levels of exploitation. The large size, site specificity and catchability of most groupers increase susceptibility to fishing pressure, and a large number of grouper species throughout the world are currently overfished. Multiple species are listed as endangered or threatened, and many have suffered local extirpations across their range. Removal of these upper level predators can significantly alter community structure and result in second order effects that may have critical ecological implications. The economic and ecological value of groupers is significant, and data regarding the abundance, habitat and behavior of these exploited species are necessary in order to implement realistic and effective management strategies. Atlantic Goliath Grouper (Epinephelus itajara) historically occurred in tropical and subtropical waters from the west coast of Africa to the east coast of Florida, south to Brazil, and throughout the Caribbean Sea and Gulf of Mexico. As one of the world's largest groupers, individuals are known to reach at least 37 years of age, and may grow to sizes exceeding 2.5 meters and 400 kilograms. The life history and behavioral characteristics of this species amplify vulnerability to exploitation, and Atlantic Goliath Grouper harvest was banned in U.S. waters in 1990 after a noted sharp decline in population numbers. The species has responded encouragingly to protective measures; however, the population's recovery and present status with U.S. waters should be thoroughly evaluated before altering regulatory guidelines. Traditional fishery-dependent data are not available (i.e., landings data); thus estimates of population demographics and recovery are dependent upon directed, fishery independent research efforts. It was the goal of this project to provide information regarding demographics, movement patterns, effects of catch and release angling, and feeding behavior of Atlantic Goliath Grouper within the central eastern Gulf of Mexico. The majority of research involving Atlantic Goliath Grouper began after the stock was already overfished, resulting in the absence of an existing "baseline" with which to compare current population parameters. Replication of visual surveys over a range of depths and habitat types provided an index of abundance for specific sites, and allowed for quantification of the size distribution of individuals. Atlantic Goliath Grouper were most abundant at high relief, high volume artificial reefs within the study area, and the majority of individuals observed were 80 - 160 cm in total length. Knowledge of fish movement, behavior and habitat associations has been used to exploit many species of fish; thus, this knowledge is critical for the creation of regulatory guidelines regarding conservation. Protection from harvest does not immediately imply that fishing mortality is negligible. As opportunistic ambush predators, Atlantic Goliath Grouper are relatively easy to catch on hook and line, and the species is often targeted for sport or caught incidentally during angling efforts for other reef fish species. Acoustic tracking allowed for continuous monitoring of individuals for several years after catch and release events. Barotrauma severity increased with capture depth, but immediate mortality was not observed during this study. Additionally, the length of total monitoring period was not affected by the severity of barotrauma, which suggests that with proper handling, Atlantic Goliath Grouper are not subject to high levels of release mortality in the study area (at depths < 40 m). However, strong site fidelity of Atlantic Goliath Grouper to artificial reefs increases susceptibility to fishing pressure and amplifies interactions with anglers, so the chronic effects of repeated capture remain unclear. Description and quantification of goliath grouper feeding behavior may allow for innovative suggestions to decrease the probability of catch and release mortality, and potentially offer new tactics to reduce opportunistic predation upon hooked fish. Kinematic analysis of Atlantic Goliath Grouper feeding sequences demonstrated that they are capable of modulating feeding behavior based upon prey activity level and position within the water column. Individuals exhibited larger maximum gapes and more rapid feeding sequences when presented with mobile live food. Immobile (dead) food was primarily consumed through suction, and strikes upon these items were characterized by slower, closer approaches, smaller maximum gapes and longer bite durations. It is hopeful that the information presented herein will provide insight regarding the ecology of Atlantic Goliath Grouper and can be applied to future management efforts involving this protected species.

Upon vascular injury, activated blood platelets fuse their granules to the plasma membrane and release cargo to regulate the vascular microenvironment, a dynamic process central to platelet function in many critical processes including hemostasis, thrombosis, immunity, wound healing, angiogenesis etc. This granule- plasma membrane fusion is mediated by a family of membrane proteins- Soluble N-ethyl maleimide Attachment Receptor Proteins(SNAREs). SNAREs that reside on vesicle (v-SNAREs) /Vesicle-Associated Membrane Proteins(VAMPs) interact with target/t-SNAREs forming a trans-bilayer complex that facilitates granule fusion. Though many components of exocytic machinery are identified, it is still not clear how it could be manipulated to prevent occlusive thrombosis without triggering bleeding. My work addresses this question by showing how the rates and extents of granule secretion could be regulated by various v-SNAREs. We also show that the granule cargo decondensation is an intermediate to secretion that also contributes to rates of cargo release. Platelets contain four major VAMP isoforms (-2, -3, -7, and -8), however, VAMP-8 and -7 play a primary role while VAMP-2 and -3 are ancillary in secretion. To exploit this heterogeneity in VAMP usage, platelet-specific V-2/3-/- and V-2/3/8-/- mouse models were generated and characterized to understand how secretion influences hemostasis. We found that each VAMP isoform differentially contributes by altering the rates and extents of cargo release. The loss of VAMP-2 and -3 had a minimal impact while the loss of VAMP-2, -3 and -8 significantly reduced the granule secretion. Platelet activation and aggregation were not affected though the spreading was reduced in V-2/3/8-/- platelets indicating the importance of secretion in spreading. Though coagulation pathways were unaltered, PS exposure was reduced in both V-2/3-/- and V-2/3/8-/- platelets suggesting diminished procoagulant activity. In vivo experiments showed that V-2/3/8-/- animals bled profusely upon tail transaction and failed to form occlusive thrombus upon arterial injury while V-2/3-/- animals did not display any hemostatic deficiency. These data suggest that about 40-50% reduction in secretion provides protection against thrombosis without compromising hemostasis and beyond 50% secretion deficiency, the animals fail to form functional thrombi and exhibit severe bleeding. Additionally, detailed structural analysis of activated platelets suggests that the post-stimulation cargo dissolution depends on an agonist concentration and stimulation duration. This process is VAMP-dependent and represents intermediate steps leading to a full exodus of cargo. Moreover, we also show that VAMP-8 is important for compound fusion events and regulates fusion pore size. This is a first comprehensive report that shows how manipulation of the exocytic machinery have an impact on secretion and ultimately on hemostasis. These animals will be instrumental in future investigations of platelet secretion in many other vascular processes.

Glaucoma is the leading cause of blindness in the United States accounting for 9-12% of all cases of blindness. Currently, the front line treatment for glaucoma are prostaglandins that may have to be taken up to several times a day. Even with proper treatment, roughly 11% of the patients using the treatment are non-compliant and lose their vision. In this project, ForSight Laboratories has developed a pharmaceutical drug delivering implant with the capability of sustaining long-term release of a prostaglandin as a new way to treat the condition. This project reports the product development of a polymer drug matrix with a controlled release in order to better treat glaucoma. Accompanying product development, a mathematical model was created in order to strengthen the understanding of the dosage profile and to predict long term dosages.

Jusqu'à aujourd'hui, le traitement des maladies oculaires postérieures, telles que la dégénérescence maculaire liée à l'âge, la rétinopathie diabétique et l'uvéite, reste difficile. L'œil avec ses différentes barrières oculaires est bien protégé des agressions extérieures. Ces barrières réduisent également la biodisponibilité des médicaments pour le vitré. Après une administration topique, seule une quantité limitée (0,001 - 0,0004 %) permet d'atteindre le vitreux. Ceci est causé par exemple par une dilution des larmes et une faible perméabilité cornéenne du médicament. Après une administration systémique ou orale, les barrières hémato-oculaires empêchent le médicament d'entrer et seulement environ 2 % du médicament administré se trouve dans le vitré. Afin d'atteindre des concentrations thérapeutiques, une dose élevée doit être administrée, ce qui augmente le risque d'effets secondaires. La façon la plus efficace de traiter les maladies postérieures restent l'injection intravitréenne. Cependant, de petites molécules lipophiles comme la dexaméthasone peuvent facilement se diffuser à travers la rétine et les barrières oculaires et ont donc une demi-vie limitée de quelques heures seulement. Étant donné que de nombreuses maladies postérieures sont chroniques, une injection intravitréenne fréquente serait nécessaire. Chaque injection comporte des risques de décollement de la rétine, d'hémorragie et d'autres effets secondaires. Les implants biodégradables pour administration intravitréenne peuvent prolonger la libération du médicament et en diminuer les effets secondaires. PLGA est un polymère largement utilisé qui est biocompatible et biodégradable. Il peut également soutenir la libération du médicament de quelques jours à plusieurs mois. Dans cette étude, les implants de formation in situ (ISFI) et les implants préformés préparés par extrusion à chaude ont été étudié en profondeur. L'objectif de ce travail était (i) d'étudier l'impact du volume du rejet (ii) évaluer le comportement de libération, de gonflement et de dégradation des implants préformés préparés avec différentes charges de médicament et différents types de polymères, (iii) visualiser la libération de médicament et l'absorption d'eau des implants préformés et de l'ISFI en utilisant des médicaments modèles colorés et (iv) étudier l'effet des quantités variables des différents additifs sur les caractéristiques essentielles de l'ISFI. Ces informations peuvent aider à fabriquer des implants avec différents profils de libération. Nos études montrent que l'ISFI est assez robuste en ce qui concerne les différents volumes de l'humeur vitreuse que l'on peut rencontrer in vivo. Cependant, le poids moléculaire et la concentration du polymère ont une forte influence sur la morphologie et le gonflement de l'implant. Par conséquent, la dégradation et la libération du médicament sont affectées. Pour les implants préformés, le gonflement "orchestre" la libération du médicament. Au début, seule une quantité limitée d'eau peut se diffuser dans les implants. Ainsi, seules des quantités insignifiantes du médicament sont dissoutes et peuvent être libérées. Lorsque le PLGA commence à se dégrader, le polymère devient plus hydrophile et de plus grandes quantités d'eau peuvent pénétrer. Ce gonflement du polymère facilite la dissolution et la diffusion du médicament et déclenche la libération du médicament. Les études utilisant des médicaments modèles colorés corroborent le rôle de la pénétration de l'eau et de la dissolution du médicament pour les implants préformés. En ce qui concerne l'ISFI, il a visualisé l'importance de la concentration du polymère sur la structure interne de l'implant qui en résulte et par conséquent l'absorption d'eau et la libération du médicament. Le comportement de gonflement et la morphologie de l'ISFI pourraient également être modifiés de manière significative en utilisant différents additifs. L'effet global sur la libération du médicament a été limité. / Until today, the treatment of posterior eye diseases, such as age-related macular degeneration, diabetic retinopathy and uveitis, remains challenging. The eye with its different ocular barriers is well protected from external factors. Those barriers also reduce the bioavailability of drugs to the vitreous. After a topical administration, only a limited amount (0.001 – 0.0004 %) reaches the vitreous. This is caused by for example reflexive blinking, tear dilution and a low corneal permeability of the drug. After a systemic or oral administration, the blood-aqueous and the blood-retinal barrier hinder the drug from entering and only around 2 % of the administered drug is found in the vitreous. In order to reach therapeutic concentrations, a high dose has to be given which in turn increases the risk for systemic side effects. The most efficient way to treat posterior diseases remains the intravitreal injection. However, small lipophilic molecules like dexamethasone can easily diffuse through the retina and the blood-ocular barriers and, thus, have a limited half-life of just a few hours. Since many of the posterior diseases are chronic, a frequent intravitreal injection would be necessary. Every intravitreal injection bears the risks for retinal detachment, hemorrhage, and other side effects. Biodegradable implants for intravi-treal administration can prolong the drug release and in turn decrease the side effects. Poly(lac-tic-co-glycolic acid) (PLGA) is a widely used polymer that is biocompatible and biodegrada-ble. It can also sustain the drug release from a few days up to several months. In this study, in-situ forming implants (ISFI) and pre-formed implants prepared via hot melt extrusion were studied in depth. The aim of this work was (i) to study the impact of the volume of the release medium, polymer type and concentration as well as drug content of different ISFI, (ii) to eval-uate the drug release, swelling and degradation behavior of pre-formed implants prepared with different drug loadings and polymer types, (iii) to visualize the drug release and water uptake of ISFI and pre-formed implants using colored model drugs and (iv) to investigate the effect of varying amounts of different additives on key features of ISFI. This knowledge can help to manufacture implants with different release profiles. Our studies show that ISFI are rather ro-bust regarding different volumes of the vitreous humor that could be encountered in vivo. How-ever, the polymer molecular weight and polymer concentration have a strong influence on the morphology and swelling behavior of the implants. Consequently, the degradation and drug release are affected. For pre-formed implants the swelling “orchestrates” the drug release. In the beginning only limited amounts of water can diffuse into the implants. Thus, only insignif-icant amounts of the drug are dissolved and can be released. When the PLGA starts to degrade, the polymer becomes more hydrophilic and bigger amounts of water can penetrate. This poly-mer swelling facilitates drug dissolution and diffusion and initiates the drug release. The studies using colored model drugs corroborate the role of water penetration and drug dissolution for pre-formed implants. Concerning ISFI, it visualized the importance of the polymer concentra-tion on the resulting inner implant structure and consequently the water uptake and drug release. The swelling behavior and morphology of ISFI could also be significantly altered using differ-ent additives. The overall effect on the drug release was limited.

Living in counties where manufacturers release environmental toxins, such as those tracked by the Environmental Protection Agency's (EPA) toxic release inventory (TRI), may elevate infants' health risks. Because infant mortality (IM) is a strong indicator of a population's health status, it is an important topic in public health research. The purpose of this research was to examine the potential relationships between IM, community size, and factors related to mothers' SES in counties where more than 25,000 pounds of annual toxic air releases occur. The dependent variable was IM per 1,000 live births in a given community for each of the 3 years included in this analysis (1987, 1995, and 2004). The independent variables included county size and factors related to mother's SES (education, age, ethnicity, and marital status). The theoretical framework consisted of Mosley and Chen's framework for exploring child survival. Archival, publicly available data were pulled from (a) the EPAs TRI data, and (b) linked birth and infant death files from the National Center for Health Statistics. The researcher followed a quantitative, retrospective cross-sectional design and conducted 3 linear regression models to test the research questions. Results indicated that an increase in community size was significantly associated with an increase in IM. Regarding the relationships between IM and the 4 different maternal characteristics (education, age, ethnicity, and marital status) included in the analysis, findings were mixed for the 3 years examined. Despite these unexpected findings, the overall results from this investigation, when considered alongside findings from previous research on IM, indicate that policy changes and interventions are needed to reduce socioeconomic disparities in IM, and to save the lives of more infants.