Poorly water-soluble and insoluble chemical agents are routinely investigated in the pharmaceutical industry for pharmacological activity, but many of these are never commercialized due to inadequate dissolution and subsequent low oral bioavailability following oral administration. The bioavailability of many hydrophobic active pharmaceutical ingredients (APIs) can be increased by enhancing their aqueous dissolution. Spray-Freezing into Liquid (SFL) is a novel particle engineering technology that has been demonstrated in the following studies to significantly enhance the dissolution of insoluble APIs. The ultimate goal throughout the studies was to produce micronized SFL powders where the inherently insoluble API would be completely dissolved in aqueous dissolution media within a minimal amount of time (less than ca. 10 minutes). The SFL particle engineering technology is a novel process that was developed, investigated and optimized in order to broaden its applications in pharmaceutical drug delivery systems. Micronized SFL powders were compared head-to-head with powders produced from milling, co-grinding with excipients and slow freezing of liquids containing dissolved API and excipients followed by lyophilization. To strengthen the applicability of the SFL particle engineering technology, studies were conducted where micronized SFL powders were exposed to various stability storage conditions, and characterized to determine the influences of the exposure conditions and time on the physicochemical properties of the powder containing the API. The utility of the SFL process was further enhanced by developing an atmospheric freeze-drying (ATMFD) technique to obtain dry micronized SFL powders. Micronized SFL powders dried by ATMFD were compared to micronized SFL powders dried by vacuum-freeze drying to determine any changes in physicochemical properties or dissolution profiles as a function of the drying technique utilized. The usefulness of the SFL particle engineering technology was broadened when it was found that highly concentrated emulsions could be processed by SFL to produce micronized powders that rapidly wetted and dissolved in dissolution media. Micronized SFL powders produced from emulsion were investigated and compared to slowly frozen agglomerates from emulsion and a micronized SFL powder from solution. As a result of the following studies, the enabling examples using the SFL platform were designed to illustrate applications of the SFL technology as a tool to enhance the aqueous dissolution of poorly water-soluble and insoluble APIs. Therefore, it was demonstrated that this novel particle engineering technology is a feasible method that may be used in the pharmaceutical industry to solve the ever-present solubility and dissolution problems associated with poorly water-soluble or insoluble APIs, or chemical agents being investigated for pharmacological activity as future APIs / text

L'objectif de ce travail de thèse est de développer de nouveaux agents tensioactifs, capables de s'auto-assembler sous forme de micelles permettant de solubiliser les principes actifs insolubles, en vue de leur administration par voie intraveineuse. Cette étude a permis la synthèse, la caractérisation physico-chimique ainsi que l'évaluation toxicologique in vitro et in vivo de nouveaux agents tensioactifs d'origine naturelle. Au cours de cette étude, différentes familles de tensioactifs ont été évaluées. Ces nouveaux agents tensioactifs sont composés d'une partie hydrophobe de type cholestérol, sels biliaires ou lipides, associée via une fonction amide à une partie hydrophile dérivée d'acides aminés tels que la lysine, la glutamine ou l'acide glutamique.Ces travaux expérimentaux ont permis d'étudier l'influence de la flexibilité de la partie hydrophobe sur la capacité de solubilisation des tensioactifs. Cette étude a montré que l'efficacité de solubilisation est reliée à la flexibilité de la partie hydrophobe. L'utilisation d'agents tensioactifs composés d'une chaîne lipidique saturée flexible a permis de solubiliser efficacement le principe actif insoluble avec un taux de charge de 46 % (m/m). Les tensioactifs composés de lipides saturés sont donc plus efficaces en termes de solubilisation que les dérivés de stéroïdes ou de lipides polyinsaturés, moins flexibles. Les études de toxicité ont mis en évidence la relation ente la structure chimique des tensioactifs et leur toxicité, en particulier vis-à-vis des membranes cellulaires. L'introduction de doubles liaisons en configuration cis dans la partie lipidique des tensioactifs permet de diminuer leur interaction avec les membranes cellulaires et donc leur toxicité mais diminue également leur capacité de solubilisation. Le développement de nouveaux agents tensioactifs nécessite donc de trouver un compromis entre la capacité de solubilisation et la toxicité des tensioactifs.

Το κίνητρο της παρούσας εργασίας είναι η μελέτη των μηχανισμών καταβύθισης μέσω της in-situ ανάμειξης και καταβύθισης δυσδιάλυτων αλάτων( ανθρακικό ασβέστιο) πάνω στις επιφάνειες αλλά και κατά μήκος των πορώδων υλικών. Οι επικαθίσεις δυσδιάλυτων αλάτων σε πορώδη σχηματισμούς, αποτελεί ένα σημαντικό πρόβλημα σε βιομηχανικές εφαρμογές. Για παράδειγμα, στην παγκόσμια βιομηχανία πετρελαίου και φυσικού αερίου πολλές περιοχές άντλησης πετρελαίου αντιμετωπίζουν τεράστιο πρόβλημα επικαθίσεων αλάτων, με αποτέλεσμα την δραματική μείωση της παραγωγής πετρελαίου. Επιπλέον, προβλήματα εναπόθεσης αλάτων μειώνουν την εκμετάλλευση γεωθερμικής ενέργειας, τη διάρκεια ζωής μεμβρανών αφαλάτωσης, καθώς και την απομόνωση του CO2 σε υπόγεια πηγάδια, κτλ. Οι επικαθίσεις αλάτων σε πηγάδια άντλησης πετρελαίου προέρχονται είτε από απευθείας καταβύθιση των διαλυμένων αλάτων που βρίσκονται στο νερό που υπάρχει σε υπόγειες κοιλότητες και καταβυθίζονται εξαιτίας της διαφοροποίησης των τοπικών συνθηκών(κυρίως πίεσης και θερμοκρασίας), είτε από τις μεγάλες ποσότητες νερού που χρησιμοποιείται για την εκτόπιση του πετρελαίου στα πηγάδια παραγωγής. Ένα από τα σημαντικότερα προβλήματα που αντιμετωπίζουν οι εταιρίες εξόρυξης πετρελαίου είναι οι μειωμένοι ρυθμοί άντλησης λόγω της μείωσης του τοπικού πορώδους και της διαπερατότητας από τη δημιουργία και την ανάπτυξης επικαθίσεων στα πηγάδια εξόρυξης. Οι επικαθίσεις αλάτων μπορούν επιπλέον να φράξουν τις σωληνώσεις ή να σχηματίσουν ένα λεπτό στρώμα στα τοιχώματα των σωληνώσεων που χρησιμοποιούνται στην παραγωγή. Ο σχηματισμός επικαθίσεων έχει σαν αποτέλεσμα την δημιουργία λειτουργικών προβλημάτων και δυσκολιών, που οδηγούν σε επιπλέον κόστος και σε εξαιρετικές περιπτώσεις στην εγκατάλειψη του πηγαδιού άντλησης πετρελαίου. Αρχικά έγινε μελέτη της αυθόρμητης καταβύθισης του ανθρακικού ασβεστίου σε αντιδραστήρες διαλείποντος έργου. Μελετήθηκε επίσης και η επίδραση της ίδιας ποσότητας άμμου σε διαφορετικούς αρχικούς υπερκορεσμούς κατά την αυθόρμητη καταβύθιση του ανθρακικού ασβεστίου. Καθ’ όλη τη διάρκεια των πειραμάτων συλλέγονταν δείγματα από τον αντιδραστήρα και ανιχνευόταν η μείωση της συγκέντρωσης των ιόντων ασβεστίων με τη μέθοδο της ατομικής απορρόφησης. Από τη μείωση της συγκέντρωσης των ιόντων ασβεστίου υπολογίστηκε ο ρυθμός καταβύθισης και στη συνέχεια η φαινόμενη τάξη της αντίδρασης και η σταθερά ταχύτητας. Σε όλα τα πειράματα ανιχνεύτηκε με περίθλαση ακτίνων Χ και ηλεκτρονική μικροσκοπία σάρωσης, ο ασβεστίτης ως η μοναδική καταβυθιζόμενη φάση. Κατά την αυθόρμητη καταβύθιση του ανθρακικού ασβεστίου απουσία άμμου, ο κύριος μηχανισμός καταβύθισης βρέθηκε ότι είναι η επιφανειακή διάχυση των δομικών μονάδων σε κατάλληλες θέσεις στην επιφάνεια των κρυστάλλων, ενώ στα πειράματα παρουσία ποσότητας άμμου οι κρύσταλλοι αναπτύσσονται με βάση το πολυπυρηνικό πρότυπο. Στην παρούσα εργασία μελετάται επίσης η διεργασία καταβύθισης του δυσδιάλυτου άλατος του ανθρακικού ασβεστίου (CaCO3) σε δισδιάστατα πορώδη δοκίμια Plexiglas®. Μέσω της οπτικής παρατήρησης της ανάπτυξης των επικαθίσεων, επιχειρήθηκε η εξαγωγή ποιοτικών και ποσοτικών πληροφοριών που αφορούν τους μηχανισμούς και τον τρόπο με τον οποίο αναπτύσσονται οι κρύσταλλοι ανθρακικού ασβεστίου στα τοιχώματα του προσομοιωτή πορώδους μέσου κάτω από ρεαλιστικές συνθήκες ροής, θερμοκρασίας και συγκέντρωσης. Δύο ευδιάλυτα διαλύματα χλωριούχου ασβεστίου, CaCl2, και όξινου ανθρακικού ασβεστίου, NaHCO3, αναμιγνύονταν λίγο πριν την είσοδό τους στο πορώδες μέσο με τη βοήθεια εμβολοφόρων αντλιών. Η καταβύθιση του ανθρακικού ασβεστίου λάμβανε μέρος μέσα στο πορώδες γραμμικό μέσο. Χρησιμοποιώντας ένα οπτικό μικροσκόπιο σε συνδυασμό με βιντεοκάμερα ήταν δυνατή η παρακολούθηση και η καταγραφή των κρυστάλλων που εμφανίζονταν καθώς και η ανάπτυξη τους κατά μήκος του καναλιού, στις θέσεις 2 cm, 6 cm, 8 cm και 10 cm από την είσοδο του. Σε κάθε θέση μετρήθηκε η μεταβολή του pH και της συγκέντρωσης του ασβεστίου με το χρόνο και επιπλέον καταγράφηκε ο σχηματισμός των κρυστάλλων του ανθρακικού ασβεστίου με τη βοήθεια της κάμερας του μικροσκοπίου. Για τη μέτρηση της συγκέντρωσης των ιόντων ασβεστίων χρησιμοποιήθηκε η φασματοφωτομετρία ατομικής απορρόφησης ενώ ο υπολογισμός του μεγέθους των κρυστάλλων έγινε με τη βοήθεια του προγράμματος Adobe Photoshop CS5.1. Κατά την διάρκεια του πειράματος ο υπερκορεσμός μειωνόταν κατά μήκος του καναλιού, ως αποτέλεσμα της in situ ανάμειξης των διαλυμάτων του χλωριούχου ασβεστίου και ανθρακικού νατρίου. Τέλος, κοντά στην είσοδο του καναλιού ο αριθμός και το μέγεθος των κρυστάλλων που καταβυθιστήκαν ήταν μεγαλύτερο, συγκριτικά με αυτούς που καταβυθιστήκαν κοντά στην έξοδο. / The deposition of sparingly soluble salts in porous formations is a severe problem encountered in industrial applications. For example, in international oil and gas industry many oil fields in operation face the major problem of scale which reduces dramatically oil production. Moreover, scaling problems limit the utilization of geothermal energy, the operational life of desalination membranes, in CO2 sequestration in subsoil wells, etc. Scale deposits encountered in oil fields are formed either by direct precipitation of the dissolved salts present in the formation water and precipitate because of the change of the local conditions (mainly pressure and temperature) or because of the large quantities of the injection water used for the displacement of the oil in the production wells. In the course of scale formation and development at wellbores, both local porosity and permeability may be reduced resulting in lower oil recovery rates. Scale deposits may also block flow by clogging perforations or by forming a thick layer on the wall of the production tubing. The formation of scales may result in a series of operational problems and difficulties, and in turn, result to additional capital cost, substantial operating cost and in extreme cases in the abandonment of the oil wells. The injection water (sea water) used in oil production is a stream most often incompatible with the well formation water. Mixing the incompatible streams interact chemically resulting in the precipitation of minerals. The high concentrations of SO42- in sea water and the low concentrations of Ba2+/Sr2+ in the formation waters constitute solutions where the concentrations of SO42- are low while the concentrations of Ca2+, Ba2+ and Sr2+ are high. Mixing of these streams, there is a high probability of CaSO4, BaSO4 and/or SrSO4 precipitation. Some of the more common ions frequently encountered in oil field waters and cause precipitation in incompatible waters are Ca2+, Ba2+, Sr2+, Fe2+, HCO3- and SO42-. In most cases, the low solubility and tenaciously adhering calcium carbonate and barium sulfate scale deposits are the most commonly salts found in well scale deposits. Knowledge of the mechanisms underlying the formation of scale deposits and the concomitant effects on the changes of the local porosity and permeability is of paramount importance for the efficient design of scale control processes. On the other hand there are beneficial applications involving the precipitation of insoluble salts. The controlled precipitation of sparingly soluble salts may be used for the effective consolidation of unconsolidated or poorly consolidated formations, like the sandy soils or granular materials (applications: protection of cultivated soils from erosion by raining water, protection of sandy reservoirs from the intrusion of sand grains within the oil wells, waterproofing of underground constructions, e.g. tunnels or other concrete constructions, etc). The main motivation for the present work is the investigation of the precipitation mechanisms through in-situ mixing and the precipitation of sparingly soluble salts (calcium carbonate) in porous materials. The proposed method may be applicable for the prevention of sand entrainment into well bores during oil production in poorly consolidated oil reservoirs. In the present study two series of experiments were done in order to investigate the kinetics of calcium carbonate precipitation in batch reactors using calcium chloride and sodium bicarbonate as the initial reagents in the absence and presence of sand. In all supersaturated solutions used in the present work, the stoichiometric of total calcium ions to total bicarbonate ions was equal to 1:1. During the experiments samples were taken, filtered through membrane filters and analyzed for total calcium by atomic absorption spectroscopy. The analysis of the kinetic data showed that in spontaneous precipitation experiments the crystals grow with spiral mechanism (n=2) and in the presence of sand kinetics data were best fitted by the polynuclear model (n>2). At the end of each experiment, the fluid suspension was filtered with a 0.22 μm filter and the solids were collected, dried at room temperature, and characterized by powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). Finally, also a series of experiments were done using two dimensional porous (Plexiglas®) medium models in which insoluble salts were nucleated from supersaturated solutions. Through the direct observation of the evolution of the deposits it was attempted to obtain qualitative and quantitative information concerning the mechanisms and pattern of deposition and growth of calcium carbonate scale on pore walls under realistic geometrical, flow, temperature and concentration conditions. Two soluble salts of calcium chloride, CaCl2, and sodium bicarbonate, NaHCO3, were mixed just before the injection point using syringe pumps. Precipitation of calcium carbonate took place within the porous medium. Using an optical microscope in combination with a video- camera it was possible to monitor crystal appearance and growth at a steady state. The growth of the calcium carbonate crystals in different positions within the etched linear porous medium as a function of time was observed. The visual observation of the crystal growth took place in different positions along the channel (2 cm, 6 cm, 8 cm and 10 cm from the inlet of the channel). In every position the changes of the pH and calcium concentration were measured and the formation of crystals was recorded through image capture. During the flow of the mixture through the channel, supersaturation decreased as a result of the in situ mixing of calcium and bicarbonate ions. As it was expected precipitation was favoured near the inlet of the cell and few crystals were precipitated near the outlet. Furthermore, the size of the crystal was bigger near the inlet of the channel in comparison to the crystals that have precipitate near the outlet of the channel.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study aimed to evaluate the effect of inclusion of concentrated dietary fiber as prebiotic agent in diets on metabolic, immune responses, performance parameters, deposition of nutrients and production of digestive enzymes of juvenile silver catfish. Concentrates were prepared from dietary fiber citrus pulp, biomass of yeast brewery and grain included in linseed and mixed diets followed a diet containing the prebiotic commercial mananoligossacarids base Actigen® and control treatment without added prebiotic agent. For 50 days, 600 juvenile silver catfish with average initial weight of 3.54±0.53 g were kept in a water recirculation system with two biological filters, settling box, heating and 20 tanks with a capacity of 230 liters. Were randomly assigned to 30 fish per experimental unit, which were fed the experimental diets, three times a day (8:00, 13:00 and 17:00) to apparent satiation. At the end of the experiment the animals were subjected to biometrics were collected blood, liver, mucous, intestine and data length and weight, beyond a sample of fish. The experimental design was a randomized, with five treatments and four replications, the data were subjected to analysis of variance and means were compared by Tukey test (P<0.05). Cholesterol levels, total protein, globulin and mucoprotein were higher in animals fed yeast autolysate and linseed fiber in the diet. A higher amount of liver glycogen in fish fed with control diet and Actigen®, the liver protein content was higher (P<0.05) in a diet containing linseed fiber. Fish fed diets containing yeast autolysate and linseed fiber were superior (P<0.05) to the other treatments tested, as well as higher crude protein values and deposited body fat. Animals fed diets containing citrus pulp showed lower performance and nutrient deposition. The yield of body, digestive indices and production of digestive enzymes were not affected by the tested treatments. The yeast autolysate and linseed fibers provide a prebiotic effect when added to diets for juvenile silver catfish, since they benefit the immune system and provide improved performance and deposition of nutrients by the animal. / Este trabalho teve como objetivo avaliar o efeito da inclusão de fibra alimentar concentrada como agente prebiótico em dietas sob as respostas metabólicas, imunológicas, parâmetros de desempenho, deposição de nutrientes e produção de enzimas digestivas de juvenis de jundiá. Foram avaliados concentrados de fibra alimentar preparados a partir da polpa cítrica, biomassa de levedura de cervejaria e grão de linhaça e incluídos em dietas mistas, além de uma dieta contendo o prebiótico comercial a base de mananoligossacarídeos Actigen® e uma dieta controle sem adição de agente prebiótico. Durante 50 dias, 600 juvenis de jundiá com peso médio inicial de 3,54±0,53g foram mantidos em um sistema de recirculação de água dotado de dois filtros biológicos, caixa de decantação, reservatório de água, aquecimento e 20 tanques com capacidade de 230 litros. Distribuiu-se ao acaso 30 peixes por unidade experimental, os quais receberam as dietas experimentais, três vezes ao dia (8:00, 13:00 e 17:00 horas) até a saciedade aparente. Ao final do experimento os animais foram submetidos a biometria onde coletou-se sangue, fígado, muco e intestino dos peixes, além de dados de peso e comprimento e uma amostra de peixes. O delineamento experimental o inteiramente casualizado, com cinco tratamentos e quatro repetições, os dados foram submetidos a análise de variância e as médias comparadas pelo teste de Tukey (P<0,05). Os níveis de colesterol, proteína total, globulina e mucoproteína, foram superiores nos animais alimentados com autolisado de levedura e fibra de linhaça na dieta. Observou-se maior quantidade de glicogênio hepático nos peixes alimentados com dieta controle e Actigen®, o conteúdo de proteína hepática foi superior (P<0,05) para os animais que receberam dieta contendo fibra de linhaça. Os peixes alimentados com dietas contendo autolisado de levedura e linhaça fibra apresentaram desempenho superior (P<0,05) aos demais tratamentos testados, bem como maiores valores de proteína bruta e gordura corporal depositada. Animais alimentados com dietas contendo polpa cítrica mostraram menor desempenho e deposição de nutrientes. O rendimento de carcaça, índices digestivos e produção de enzimas digestivas não foram afetados pelos tratamentos testados. O autolisado de levedura e a fibra de linhaça proporcionam efeito prebiótico quando adicionados a dietas para juvenis de jundiá, uma vez que beneficiam o sistema imune e proporcionam maior desempenho e deposição de nutrientes pelos animais.

Submitted by Claudia Rocha (claudia.rocha@udesc.br) on 2017-12-14T12:26:27Z No. of bitstreams: 1 PGEF17MA077.pdf: 4440058 bytes, checksum: 3e93f4228f2cb823f57ec2cc6afed76a (MD5) / Made available in DSpace on 2017-12-14T12:26:27Z (GMT). No. of bitstreams: 1 PGEF17MA077.pdf: 4440058 bytes, checksum: 3e93f4228f2cb823f57ec2cc6afed76a (MD5) Previous issue date: 2017-02-24 / Capes / The addition of water-repelling polymers as soil-borers aims to increase soil water retention capacity, providing better quality of seedlings, not making them dependent on climatic conditions throughout the year. In this way, the objective of the present work was to evaluate the effect of hydrogel use in the planting of Eucalyptus sp. In pots, related to different water management, seeking to provide information on the efficiency of hydrogel use simulating field conditions. The work was separated into four species (Eucalyptus urograndis of clonal origin, Eucalyptus urograndis of seminal origin, Eucalyptus dunnii and Eucalyptus benthamii). The experiment was conducted in the municipality of Lages - SC, in the forest nursery of the CAV / UDESC, conducted in a DIC, factorial scheme, where the levels of factor "A" referred to the absence and presence of hydrogel and levels of factor " B "to water management (Irrigation only at planting, 8 days, 4 days and daily). After planting until the end of the experimental period, the evaluation of the symptoms of water stress, morphological characteristics, chlorophyll content, soil water content and gas exchange were performed. Statistical differences were assessed by analysis of variance followed by the Scott-Knott or Tukey test.) At the end of the experiment, the development of the seedlings was evaluated through the increase in diameter and height, dry biomass. The determination of the available water retention curve was also performed. As a result, the use of the hydrogel provided a significant increase in water retention in the soil, consequently a delay in the symptoms of water stress, increasing the rate of survival over time. Deficit water, in the absence of the hydrogel, resulted in reductions in height, diameter, leaf area, dry biomass and chlorophyll indexes, being a limiting factor for stomatal opening, contributing to the decrease in carbon assimilation by photosynthesis. The lower the water availability, the lower the values of A, gs and E, and the WUE increased when the water availability decreased. In general, the results obtained in relation to the use of hydro-ether polymers confirm the information that the addition of hydrogels in the soil optimizes the water availability and can reduce the mortality problems in the planting / A adição de polímeros hidroretentores como condicionadores de solo visam aumentar a capacidade de retenção de água no solo, propiciando melhor qualidade das mudas, não as tornando dependentes das condições climáticas ao longo do ano. Desta forma, o objetivo do presente trabalho foi avaliar o efeito do uso do hidrogel no plantio de mudas de Eucalyptus sp. em vasos, relacionados com diferentes manejos hídricos, buscando fornecer informações sobre a eficiência do uso do hidrogel simulando condições de campo. O trabalho foi separado em quatro espécies (Eucalyptus urograndis de origem clonal, Eucalyptus urograndis de origem seminal, Eucalyptus dunnii e Eucalyptus benthamii). O experimento foi conduzido no município de Lages – SC, no viveiro florestal do CAV/ UDESC, realizado em DIC, esquema fatorial, onde os níveis do fator “A” referiram-se a ausência e a presença de hidrogel e os níveis do fator “B” ao manejo hídrico (irrigação somente no plantio, 8 dias, 4 dias e diariamente). Depois do plantio até o fim do período experimental foram realizadas avaliações da sintomatologia do estresse hídrico, características morfológicas, teores de clorofila, teor de água no solo e trocas gasosas. As diferenças estatísticas foram avaliadas segundo análise de variância seguidas do teste de Scott-Knott ou Tukey. Ao final do experimento foi avaliado o desenvolvimento das mudas através do incremento em diâmetro e altura, biomassa seca. Também realizou-se a determinação da curva de retenção de água disponível. Como resultado, o uso do hidrogel proporcionou um aumento significativo na retenção de água no solo, consequentemente um atraso nos sintomas de estresse hídrico, aumentando a taxa de sobrevivência ao longo do tempo. O estresse hídrico, na ausência do hidrogel, resultou em reduções na altura, diâmetro, área foliar, biomassa seca e índices de clorofila, sendo um fator limitante para a abertura estomática, contribuindo para a queda na assimilação de carbono pela fotossíntese. Quanto menor a disponibilidade de água, menor os valores de A, gs e E, sendo que o WUE aumentou quando diminuiu a disponibilidade de água. Em geral, os resultados obtidos com relação ao uso de polímeros hidroretentores confirmam a informação que a adição de hidrogéis no solo otimiza a disponibilidade de água, podendo diminuir os problemas de mortalidade no plantio

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19025号 / 農博第2103号 / 新制||農||1030(附属図書館) / 学位論文||H27||N4907(農学部図書室) / 31976 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 加納 健司, 教授 植田 和光, 教授 植田 充美 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Submitted by Eunice Novais (enovais@uepg.br) on 2018-05-07T18:58:48Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Keli Guera.pdf: 1614668 bytes, checksum: 870a9f0b3528b9a4706861308ce7024c (MD5) / Made available in DSpace on 2018-05-07T18:58:48Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Keli Guera.pdf: 1614668 bytes, checksum: 870a9f0b3528b9a4706861308ce7024c (MD5) Previous issue date: 2018-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O sistema integrado de produção agropecuária (SIPA), tem sido uma prática que pode melhorar os atributos químicos do solo e otimizar a adubação de sistemas de produção. Todavia, os solos brasileiros são altamente intemperizados, com elevada acidez e baixa disponibilidade em P. Dessa forma, estratégias que resultem em aumento da eficiência do uso de fósforo contribuem para a produção de alimentos de maneira sustentável. Os objetivos desse trabalho foram: (i) analisar os atributos químicos do solo, ao longo do tempo, decorrente da aplicação anual na superfície de fosfatos de diferentes solubilidades e; (ii) avaliar as concentrações de P disponível no solo pelos extratores Mehlich-1 e resina trocadora de íons (RTI), a longo prazo, decorrente da aplicação de fosfatos em SIPA. O experimento foi instalado no município de Castro-PR, em abril/2009, em um Cambissolo Háplico argiloso. Foi empregado delineamento experimental em blocos casualizados, em esquema fatorial incompleto (3 x 3 +1), com quatro repetições. Os tratamentos consistiram de três fontes de P [superfosfato triplo (SFT), fosfato natural reativo - Arad (FNR) e termofosfato magnesiano (TFM)] e três doses de P (60; 120 e 180 kg ha-1), além do controle (sem adição de P2O5). Amostras de terra das camadas de 0-5, 5-10, 10-15, 15-20 e 20-30 cm foram coletadas aos 24, 36, 48 e 60 meses após o início do experimento, e os seguintes atributos químicos foram avaliados: pH, concentrações de Ca, Mg e K trocáveis, saturação por bases (V%) e concentrações de P disponível pelos extratores Mehlich-1 e RTI. A aplicação de TFM proporcionou aumento de pH do solo, elevação da V% e eficiência no fornecimento de Mg2+ às plantas. As concentrações de P disponíveis no solo pelo extrator Mehlich-1 foram maiores com o uso de FNR superestimando as concentrações de P. O uso de diferentes fontes fosfatadas não influenciou as concentrações de RTI, mostrando-se como o extrator de P mais adequado para prever as concentrações deste nutriente, independente da solubilidade do fertilizante fosfatado utilizado. Em condições de solo adequadamente conservado e manejado, a aplicação anual de fosfatos em superfície pode garantir a manutenção da fertilidade do solo a longo prazo. A renovação do sistema radicular decorrente do pastejo animal, maior produção de ácidos orgânicos e a deposição de excretas favoreceram a melhoria dos atributos químicos do solo e aumento da concentração de P, ao longo do tempo. / O sistema integrado de produção agropecuária (SIPA), tem sido uma prática que pode melhorar os atributos químicos do solo e otimizar a adubação de sistemas de produção. Todavia, os solos brasileiros são altamente intemperizados, com elevada acidez e baixa disponibilidade em P. Dessa forma, estratégias que resultem em aumento da eficiência do uso de fósforo contribuem para a produção de alimentos de maneira sustentável. Os objetivos desse trabalho foram: (i) analisar os atributos químicos do solo, ao longo do tempo, decorrente da aplicação anual na superfície de fosfatos de diferentes solubilidades e; (ii) avaliar as concentrações de P disponível no solo pelos extratores Mehlich-1 e resina trocadora de íons (RTI), a longo prazo, decorrente da aplicação de fosfatos em SIPA. O experimento foi instalado no município de Castro-PR, em abril/2009, em um Cambissolo Háplico argiloso. Foi empregado delineamento experimental em blocos casualizados, em esquema fatorial incompleto (3 x 3 +1), com quatro repetições. Os tratamentos consistiram de três fontes de P [superfosfato triplo (SFT), fosfato natural reativo - Arad (FNR) e termofosfato magnesiano (TFM)] e três doses de P (60; 120 e 180 kg ha-1), além do controle (sem adição de P2O5). Amostras de terra das camadas de 0-5, 5-10, 10-15, 15-20 e 20-30 cm foram coletadas aos 24, 36, 48 e 60 meses após o início do experimento, e os seguintes atributos químicos foram avaliados: pH, concentrações de Ca, Mg e K trocáveis, saturação por bases (V%) e concentrações de P disponível pelos extratores Mehlich-1 e RTI. A aplicação de TFM proporcionou aumento de pH do solo, elevação da V% e eficiência no fornecimento de Mg2+ às plantas. As concentrações de P disponíveis no solo pelo extrator Mehlich-1 foram maiores com o uso de FNR superestimando as concentrações de P. O uso de diferentes fontes fosfatadas não influenciou as concentrações de RTI, mostrando-se como o extrator de P mais adequado para prever as concentrações deste nutriente, independente da solubilidade do fertilizante fosfatado utilizado. Em condições de solo adequadamente conservado e manejado, a aplicação anual de fosfatos em superfície pode garantir a manutenção da fertilidade do solo a longo prazo. A renovação do sistema radicular decorrente do pastejo animal, maior produção de ácidos orgânicos e a deposição de excretas favoreceram a melhoria dos atributos químicos do solo e aumento da concentração de P, ao longo do tempo.

Nickel is a widely used metal in industrial and commercial applications, being both workable and highly resistant to corrosion. Certain nickel compounds are known human carcinogens, but not all nickel compounds are equally hazardous. A robust method of assessing the carcinogenic potential of various nickel compounds is needed in order to determine safe occupational exposure levels. This work attempts to develop an in vitro mammalian cell culture method for assessing the carcinogenic and toxic potential of nickel compounds by metabolic and cell cycle analysis. Two cell lines, C3H/10T1/2 and MRC-5, were used. Measurements of extracellular metabolites by enzymatic methods and HPLC were combined with cell counts and cell cycle and apoptosis analysis by flow cytometry. This work shows that nickel sulphate can elicit a metabolic response similar to that of organic carcinogens, though the underlying mechanisms are likely different. / Vale Canada Limited, NSERC

Made available in DSpace on 2015-03-03T14:03:54Z (GMT). No. of bitstreams: 1 Sarah_DVM_DISSERT_PARCIAL.pdf: 746876 bytes, checksum: f638a2adc04ebb6e7a39258725abbfde (MD5) Previous issue date: 2009-09-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Uma glucana insol?vel foi isolada de fermento biol?gico (Saccharomyces cerevisiae), o qual foi submetido a um tratamento com base e o res?duo acidificado. An?lises qu?micas e resson?ncia magn?tica nuclear (NMR) em uma e duas dimens?es (1D e 2D) mostraram que uma ?-(1 3) glucana linear foi purificada, a qual n?o estava contaminada com outros carboidratos, prote?nas ou compostos fen?licos. Os efeitos desta glucana na cicatriza??o de feridas foi avaliado em ?lceras venosas humanas por an?lise histopatol?gica ap?s 30 dias de tratamento. A ?-(1 3) glucana favoreceu a cicatriza??o das ?lceras, promovendo o aumento da hiperplasia epitelial, das c?lulas inflamat?rias, angiog?nese e prolifera??o fibrobl?stica. Este foi o primeiro estudo que investigou o efeito da ?-(1 3) glucana na cicatriza??o de ?lceras venosas em humanos. Os achados sugerem que a glucana ? um potente modificador da resposta biol?gica na cicatriza??o de feridas

Made available in DSpace on 2017-07-10T17:48:19Z (GMT). No. of bitstreams: 1 Anderson_Luiz_de_Carvalho.pdf: 587976 bytes, checksum: b32e719d7c585ab266c2d3e3f274f426 (MD5) Previous issue date: 2010-05-21 / An experiment was realized to compare different methods to determine nutrient digestibility of a dry kibble diet for ocelots (Leopardus pardalis). Total collection (TC) and internal markers were used to study the digestibility of dry matter (DM), crude protein (CP), ether extract (EE), nitrogen-free extract (NFE) and gross energy (GE) of a commercial feline diet with 30.8 % of CP and 23.8% of EE. Acid insoluble ash (AIA), crude fiber (CF) and acid detergent fiber (ADF) were the marker methods used to estimate the apparent digestibility of DM, CP, EE, NFE and GE. Six adult animals, male (n=4) and females (n=2), with average weight of 12.45 ± 1.37 Kg, received the diet during 10 days prior to the total collection period. The AIA method showed no difference from TC (P>0.05) and can be used to determine digestibility coefficients for ocelots. The CF and ADF markers underestimated the digestibility obtained by total collection method and are not recommended to estimate these coefficients in ocelots (P<0.05). It is concluded that the CIA indicator can be used as an alternative to determine the digestibility of dry kibble diets for ocelots / Neste experimento foram comparados os métodos de coleta total de fezes (CT) e indicadores internos para determinar os coeficientes de digestibilidade aparente da matéria seca (MS), proteína bruta (PB), extrato etéreo (EE), extrativo não nitrogenado (ENN) e energia bruta (EB) de ração para jaguatiricas (Leopardus pardalis). A dieta utilizada foi uma ração comercial, ajustada para gatos domésticos, com 30,8 % de PB e 23,8% de EE. Os indicadores internos avaliados foram a cinza insolúvel em ácido (CIA), fibra bruta (FB) e fibra em detergente ácido (FDA). Seis animais adultos, machos (n=4) e fêmeas (n=2), com peso médio (± desvio padrão) de 12,45 ± 1,37 Kg, receberam gradativamente a ração experimental na dieta habitual até o início do experimento e foram submetidos a um período de adaptação de 10 dias anteriores à CT que foi de 12 dias. O método de CIA não apresentou diferença em relação ao de CT (P> 0,05) para todas as variáveis analisadas, enquanto os indicadores FB e FDA subestimaram os coeficientes de digestibilidade obtidos pelo método de CT (P< 0,05). Conclui-se que o indicador CIA pode ser utilizado como alternativa para determinar coeficientes de digestibilidade de dietas para jaguatiricas