Magister Scientiae - MSc / In electrochemical oxidation treatment of wastewater, the electrode material is an important parameter in optimizing oxidative electrochemical processes, since the mechanism and products of several anodic reactions are known to depend on the anode material. The electrochemical oxidation of benzaldehyde, nitrobenzene and m-cresol on bare boron-doped diamond (BDD) electrode was investigated. Cytochrome c was then electrochemically immobilsed onto the functionalized BDD electrode by cyclic voltammetry. Oxidation and reduction reaction mechanism of each flavonoid was studied. There was one oxidation and reduction peaks for quercitin and catechin respectively, and two oxidation and two reduction peaks for rutin. The cytochrome c modified BDD electrode showed good sensitivity for all three flavonoids and low detection limits i.e. 0.42 to 11.24 M as evaluated at oxidation and reduction peaks, respectively. / South Africa

Submitted by Socorro Pontes (socorrop@ufersa.edu.br) on 2017-03-02T14:51:05Z No. of bitstreams: 1 ChristianeMCR_TESE.pdf: 1824459 bytes, checksum: 8d67db5817b6096ad2d44e2a3043a10d (MD5) / Approved for entry into archive by Vanessa Christiane (referencia@ufersa.edu.br) on 2017-03-21T15:02:11Z (GMT) No. of bitstreams: 1 ChristianeMCR_TESE.pdf: 1824459 bytes, checksum: 8d67db5817b6096ad2d44e2a3043a10d (MD5) / Made available in DSpace on 2017-03-21T15:02:28Z (GMT). No. of bitstreams: 1 ChristianeMCR_TESE.pdf: 1824459 bytes, checksum: 8d67db5817b6096ad2d44e2a3043a10d (MD5) Previous issue date: 2016-03-03 / Emepa - Empresa Estadual de Pesquisa Agropecuária / The social and economic importance of yellow mombin is due to the marketing of its raw fruits and derivatives. The non-existence of commercial clones and the high plant size are the main obstacles to its rational cultivation being necessary to make the cloning a viable instrument through the interspecific rootstocks in order to downsize the plants heights. Studies done with yellow mombin grafted onto rootstocks of yellow mombin and hog-plum did not markedly downsize the plant height but these clones were not evaluated in other enviroments. The yellow mombin shows potential for remedies. In the pharmaceutical industry it is used as phytotherapics against the Herpes virus. In works done with this species some bioactive compounds were found in the leaves such as flavonoids and tannins. Although this potential, some researches on chemical characterization and genetic diversity among genotypes are incipient. The objective of this study was to evaluate the vegetative growth of yellow mombin clones grafted onto interspecific rootstocks in different environments and the genetic diversity as to bioactive compounds among accessions of the Emepa-PB´s germplasm bank. In order to evaluate the clones development two trials with a completely randomized block design were performed. The trial 1 was conducted in a 3 x 4 x 3 factorial design with four repetitions, totaling 36 treatments, being three different interspecific rootstocks with yellow mombin (S. mombin), hog-plum (S. tuberosa) and coarse mombin (S. venulosa), four graftings of yellow mombin clones (Itaitinga, Gereau, Lagoa Redonda and Genipabu) and three different places (João Pessoa, PB, Ipanguaçu, RN and Itabuna, BA). The trial 2 was conducted in a 4 x 3 factorial design, with four repetitions, totaling 12 treatments. Three graftings of yellow mombin (Emepa 8.2, Emepa 8.6 and Emepa 20) obtained from the grafting between yellow mombin clones, grafted onto yellow mombin, plus one genotype of ungrafted yellow mombin, were used in the same places. The evaluated variables for the two trials at the 8, 39 and 46 months old were plant height, stem circumference, crown spread, crown format, number of branches and percentage of dead plants. The conclusions are that the environment, the grafting and the rootstocks did not influence the size and vigor of the clones allowing the identification of the morphological characteristics variations in each environment; that in Trial 1, for the three enviroments, the graftings of yellow mombin onto yellow mombin, hog-plum and coarse mombin rootstocks did not form clones with ideal sizes so that they cannot be recommended for commercial plantation; that in Trial 2, in the three enviroments, the Emepa 8.2 showed smaller size, bigger crown spread, major number of branches, 100% crown in a spread format and it can be recommended for new studies and later multiplication for commercial plantation. Leaves and barks of 27 yellow mombin accessions of the Emepa´s germplasm bank, in João Pessoa, PB, were used. The extractions were performed with methanol and the identification and quantification of bioactive compounds were checked through the High-Performance Liquid Chromatography (HPLC). For the grouping of accessions were used the Principal Components Analysis (PCA) and the UPGMA method. The standardized Euclidean distancewas used as a measure of genetic diversity. Rutin, quercetin, ellagic acid and geraniin compounds were quantified in leaves and ellagic acid and geraniin compounds were quantified inbarks. The highest amounts were found in leaves. Seven groups were formed. The accession group A3 was the most divergent with high amounts of rutin, quercetin and ellagic acid in leaves. The conclusion is that there is variability among accessions and it must be preserved and exploited through the genetic improvement programs / A importância socioeconômica da cajazeira é devido à comercialização dos frutos e do consumo de seus derivados. A inexistência de clones comerciais e o porte alto da planta constituem-se em entraves ao seu cultivo racional, necessitando viabilizar a clonagem com porta-enxertos interspecíficos visando reduzir o porte das plantas. Estudos realizados com a cajazeira enxertada na própria espécie e em umbuzeiro não demonstraram a diminuição significativa do porte da planta. No entanto, esses clones não foram avaliados em outros ambientes. A cajazeira apresenta potencial para medicamentos. Na indústria farmacêutica é utilizada como fitoterápico contra o vírus do Herpes. Em trabalhos realizados por outros pesquisadores, foram identificados compostos bioativos nas folhas tais como flavonoides e taninos. Apesar desse potencial, as pesquisas sobre a caracterização química e a divergência genética entre os genótipos são incipientes. O objetivo deste trabalho foi avaliar o desenvolvimento de clones de cajazeira enxertados sobre porta-enxertos interespecíficos em diferentes ambientes e a diversidade genética quanto a compostos bioativos entre acessos do banco de germoplasma da Emepa-PB. Para avaliação do desenvolvimento dos clones, foram realizados dois ensaios em delineamento inteiramente casualizado. O Ensaio 1 foi conduzido em esquema fatorial 3 x 4 x 3, com quatro repetições, totalizando 36 tratamentos, sendo três porta-enxertos interespecíficos com cajazeira (S. mombin), umbuzeiro (S. tuberosa) e cajazeira-grande (S. venulosa), quatro enxertos de clones de cajazeira (Itaitinga, Gereau, Lagoa Redonda e Genipabu), e três locais (João Pessoa, PB, Ipanguaçu, RN e Itabuna, BA). O Ensaio 2 foi conduzido em esquema fatorial 4 x 3, com quatro repetições, totalizando 12 tratamentos. Foram utilizados três exertos de acessos de cajazeira (Emepa 8.2, Emepa 8.6 e Emepa 20) enxertados sobre cajazeira, mais um pé-franco de cajazeira, nos mesmos locais. As variáveis avaliadas, aos 8, 39 e 46 meses de idade, para os Ensaios 1 e 2, foram altura de planta, perímetro de caule, largura e formato de copa, número de ramos e mortalidade de plantas. Concluiu-se que o ambiente, os enxertos e os porta-enxertos de espécies de Spondias influenciaram no desenvolvimento dos clones, permitindo identificar variabilidade nas características morfológicas em cada ambiente; no Ensaio 1, nos três ambientes, a enxertia da cajazeira sobre porta-enxertos de cajazeira, cajazeira-grande e umbuzeiro não formaram clones com porte ideal para recomendação comercial; no Ensaio 2, nos três ambientes, o clone Emepa 8.2 apresentou menor porte, maior largura de copa, maior número de ramos e 100% de formato de copa esgalhada, podendo ser recomendado para novos estudos e posterior multiplicação para exploração comercial. Para avaliação da diversidade genética, foram utilizadas folhas e cascas de cajazeira de 27 acessos do banco de germoplasma da Emepa, em João Pessoa, PB. As extrações foram realizadas com metanol e a quantificação foi determinada por Cromatografia Líquida de Alta Eficiência (CLAE). Para o agrupamento dos acessos utilizou-se a Análise de Componentes Principais (ACP) e o método aglomerativo UPGMA. Foi utilizada a distância euclidiana média padronizada como medida de dissimilaridade genética. Foram quantificados nas folhas os compostos rutina, quercetina, ácido elágico e geraniina e foram quantificados nas cascas os compostos ácido elágico e geraniina. Os maiores valores foram obtidos nas folhas. Foram formados 7 grupos. O acesso A3 foi o mais divergente com valores elevados de rutina, quercetina e geraniina nas folhas. Concluiu-se que há variabilidade entre os acessos e que esta deve ser preservada e explorada em programas de melhoramento genético / 2017-02-24

The work has been inquired into the problem of content determination of phenolic substances in medicinal plants traditionally used in Czech Republic. Phenolic substances belong to a group of natural compounds, which are purely plant origin. Flavonoids are a part of this extensive group of compounds. As for flavonoids, most attention is paid to quercetin and rutin. It is caused by their easy availability and very significant biological activity. These compounds embody a lot of positive biological effects. They have expressive antioxidant properties, inhibit lipid peroxidation, scavenge free oxygen radicals and bond into the chelates they inactivate some prooxidant metal ions. The latest researches have shown that thanks to their properties natural flavonoids can occurence of chronical diseases, such as arterosklerosis, cardiovascular or tumor disorder. Flavonoids are exploited both in traditional and modern medicine. Same other studies have evidenced that valuable sources of these biologically effective substances are traditionally used medicinal plants. Content of phenolic substances was determined by method of micellar electrokinetic capillary chromatography (MECC) and liquid chromatography (HPLC) in collection of 8 medicinal plants usually used in Czech Republic. For analysis was used freeze-dried and dried plant material. In freeze-dried material was found the highest content of total quercetin in Filipendula ulmaria L. (14200 mg/kg of dry weight) and in Betula pendula Roth. (11800 mg/kg of dry weight). The highest content of rutin contained Sambucus nigra L. (17700 mg/kg of dry weight). Similar values was measured in dried plant material. The content of total quercetin and rutin during drying was unchanged.

The thesis deals with measuring the content of chosen phenolic substances in some specimen of the genera Chenopodium L. and Atriplex L. Two independent analytical methods were used to determine the content of phenolic substances, namely the Micellar Electrokinetic Capillary Chromatography (MECC) method and the High - Performance Liquid Chromatography (HPLC) method. Two cultured species of the genera Spinacia and Atriplex, three freely growing specimen of the genus Chenopodium and three freely growing species of the genus Atriplex were analysed. The analysis concerned the leaves and the inflorescence of these species.The total content of quercetin and rutin was determined by the MECC method. The highest total content of quercetin was found in the leaves of the Garden Orache (4240 mg/kg of dry matter), the lowest total content of quercetin was found in the inflorescence of the Atriplex prostrata DC. (19.6 mg/kg of dry matter). Rutin was only found in four samples, the rest of the samples contained rutin in quantities below the limit of quantification. The highest content of rutin was found in the leaves of the Lamb´s Quarters (868 mg/kg of dry matter).

Acute pancreatitis (AP) is a severe disease in about 20% of patients, causing hospitalization and death, mainly due to associated systemic complications. The treatment of this condition is still insufficient to control the intrinsic inflammatory process and is focused on managing the complications and symptoms of patients. Among the many factors involved in AP, the inflammatory response and oxidative stress can be highlighted. In this context, rutin is presented as a natural substance with important potential to treat AP, by considering its anti-inflammatory and antioxidant activities. The aim of this study is to investigate the pharmacological effects of rutin on experimental AP induced by L-arginine administration in mice. Adult male Swiss mice (25-30 g) were used in this study and all experiments were approved by this institution´s Ethics Committee in Animal Research (43/2012). For the induction of AP, mice received 2 injections of L-arginine (8%, 4 g/kg, i.p., with an interval of 1 h). The control group received the same volume of saline (0.9%) instead of L-arginine. Mice submitted to AP induction were treated with rutin (37.5, 75 or 150 mg/kg, p.o.) or saline (vehicle) after 24, 36, 48 and 60 h of the first injection of L-arginine. The control group was treated with vehicle at the same time points. The euthanasia occurred after 72 h of induction and was accompanied by blood and organ (pancreas, lung, liver and kidney) collection. We investigated parameters that permitted us to infer about pancreatic and systemic inflammation and evaluate serum concentrations of pancreatic enzymes, abdominal hyperalgesia and oxidative stress. In animals injected with L-arginine, it was detected the increase of inflammatory and biochemical parameters that confirmed the induction of AP, when compared with saline-injected animals. The treatment with rutin reduced the myeloperoxidase activity in pancreas (p<0.001 for 37.5, 75 or 150 mg/kg), but not in lung, reduced the pancreatic edema index (p<0.001 for 37.5 mg/kg and p<0.05 for 75 and 150 mg/kg) and the serum concentration of amylase (p<0.001 for 75 and 150 mg/kg). From these experiments, we chose the dose of 75 mg/kg for the next steps. In this way, treatment with this dose of rutin also reduced the serum lipase (p<0.001), C reactive protein (p<0.001) and interleukin-6 (p<0.001) concentrations, as well as decreased the abdominal hyperalgesia (p<0.05), when compared with Vehicle + L-arginine group after 72 h of L-arginine injection. The administration of rutin also diminished lipid peroxidation induced by L-arginine in pancreas, liver and kidney (p<0.001) and increased both the activity of catalase in pancreas (p<0.001), glutathione peroxidase in pancreas (p<0.05) and superoxide dismutase in pancreas (p<0.01) and liver (p<0.05). Besides, it decreased the expression of 3-nitrotyrosine in pancreas (p<0.05). Altogether, these results demonstrate that rutin exert anti-inflammatory, antinociceptive and antioxidant actions during AP induced by L-arginine, which are suggestive that this flavonoid is of interest for developing future studies or approaches focused on new alternatives to treat AP in humans. / A pancreatite aguda (PA) é uma doença grave em cerca de 20% dos casos, que causa hospitalização e óbito dos pacientes devido às complicações sistêmicas associadas. Seu tratamento clínico tem se mostrado insuficiente para controlar o processo inflamatório intrínseco da doença e é focado no manejo dos sintomas e complicações. Dentre os diversos fatores envolvidos na PA, destacam-se a resposta inflamatória e o estresse oxidativo. Neste contexto, a rutina, um flavonoide conhecido por suas atividades antioxidante e anti-inflamatória, apresenta-se como uma substância natural em potencial a ser utilizada no tratamento da PA. Assim, o objetivo do presente estudo foi investigar os efeitos farmacológicos da rutina em modelo de pancreatite aguda experimental induzida por L-arginina em camundongos. Foram utilizados camundongos Swiss machos adultos (25-30 g) e os procedimentos foram aprovados pelo Comitê de Ética em Pesquisa com Animais da UFS (43/2012). Para a indução da pancreatite os animais receberam duas injeções de L-arginina (8%, 4 g/kg, i.p., com intervalo de 1 h entre elas). O grupo controle recebeu duas injeções de salina (0,9%, i.p.). Os animais submetidos à indução da pancreatite foram tratados com rutina (37,5, 75 ou 150 mg/kg, v.o.) ou salina (veículo), após 24, 36, 48 e 60 h da 1° injeção de L-arginina. O grupo controle foi tratado com veículo nos mesmos tempos. A eutanásia dos animais foi realizada 72 h após a indução, com subsequente coleta de sangue e de órgãos (pâncreas, pulmão, fígado e rim). Foram avaliados parâmetros que permitiram inferir sobre o quadro inflamatório pancreático e sistêmico e avaliar as concentrações séricas de enzimas pancreáticas, a hiperalgesia abdominal e o estresse oxidativo. Os animais que receberam as injeções de L-arginina apresentaram aumento significativo dos parâmetros inflamatórios e bioquímicos preditivos de pancreatite, quando comparados aos animais que receberam salina. O tratamento com rutina reduziu a atividade de mieloperoxidase no pâncreas (p<0,001 para 37,5, 75 ou 150 mg/kg), mas não no pulmão, reduziu o índice de edema pancreático (p<0,001 para 37,5 mg/kg e p<0,05 para 75 e 150 mg/kg) e a concentração sérica de amilase (p<0,001 para 75 e 150 mg/kg). A partir destes resultados a dose de 75 mg/kg foi escolhida para ser utilizada nos experimentos posteriores. O tratamento com esta dose de rutina também diminuiu as concentrações séricas de lipase (p<0,001), proteína C reativa (p<0,001) e de interleucina 6 (p<0,001), bem como reduziu a hiperalgesia abdominal (p<0,05), após 72 h da injeção de L-arginina, quando comparados ao grupo L-arginina + Veículo. O tratamento com rutina (75 mg/kg) também reduziu a peroxidação lipídica induzida pela L-arginina em pâncreas, fígado e rim (p<0,001) e aumentou a atividade de catalase pancreática (p<0,001),de glutationa peroxidase (p<0,05) de superóxido dismutase no pâncreas (p<0,01) e no fígado (p<0,05), além de diminuir a expressão de 3-nitrotirosina no pâncreas (p<0,05). Estes resultados evidenciam que a rutina exerce efeito anti-inflamatório, antinociceptivo e antioxidante durante a PA induzida por L-arginina, os quais sugerem que este flavonoide seja de interesse para abordagens ou estudos futuros objetivando novas alternativas no tratamento da PA em humanos.

Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Rutin is a flavonoid widely reported in the literature for its antioxidant properties, anti-inflammatory, vasoprotective, antithrombogen, among others. However, its low solubility in aqueous media reduces its bioavailability orally and, therefore, transdermal administration proves to be promising. Thus, the present work aimed to obtain, characterize and evaluate an activity and antioxidant activity of a gel. PLO (Pluronic Lecithin Organogel) containing rutin for transdermal administration.The analytical methodology for rutin quantification was developed and validated by high performance liquid chromatography (HPLC). Initially it was evaluated as an influence of the concentration of Polaxamer 407, obtained by the extrusion method with the aid of syringes, in front of the centrifugation test. The formulation that remained stable after the test was characterized by partical size determination, in vitro release study, in vitro skin penetration study, in vitro skin adhesion study. Also assessed for stability for 60 days at varying temperatures and at predetermined times, physico-chemical characteristics such as pH, density, viscosity and spreadability, as well as organoleptic characteristics, were evaluated. The antioxidant activity of the formulation was evaluated by the TRAP and TAR methods, comparing it with a positive control, Trolox. The results demonstrate that a formulation with higher concentration of Polaxamer is more stable and that is why it was characterized. The partical size were perfect for dermal administration. The formulation demonstrated controlled release of the drug after 24 hours, being able to permeate as deeper layers of the skin and to be absorbed into the systemic circulation, in addition to good adhesion to the skin surface. During the accelerated stability study, as formulations stored at low temperature, they underwent small variations in density, viscosity and spreadability relative to those stored at room temperature, while the pH remained stable throughout and favorable for application in skin. However, as observed variations were not sufficient to cause visual signs of instability. As for the antioxidant activity, a formulation showed greater activity in relation to the Trolox control and the free rutin, but it was not able to sustain an activity for a longer time, presenting a lower TAR value than Trolox. Thus, a chosen formulation has been shown capable of promoting a permeation of the rutin by transdermal route in a controlled manner, as well as being stable at an ambient temperature and having more significant antioxidant activity than the free rutin, and is therefore promising to administration of rutin by this route. / A rutina é um flavonoide bastante estudado devido principalmente as suas propriedades antioxidantes, anti-inflamatória, vasoprotetora e antitrombogência. No entanto, sua baixa solubilidade em meio aquoso reduz sua biodisponibilidade por via oral e, portanto, a administração por via transdérmica pode ser uma alternativa promissora. Dessa forma, o presente trabalho teve por objetivo obter, caracterizar e avaliar a estabilidade e a atividade antioxidante de um gel contendo Pluronic Lecithin Organogel (PLO) contendo rutina, para administração pela via transdérmica. A metodologia analítica para quantificação de rutina foi desenvolvida e validada por cromatografia líquida de alta eficiência (CLAE). Inicialmente foi avaliado qual a influência da concentração do Polaxamer 407, obtidos pelo método de extrusão com auxílio de seringas, frente ao teste de centrifugação. A formulação que permaneceu estável após o teste foi caracterizada através da determinação do tamanho de partícula, estudo de liberação, penetração cutânea e adesão à pele, todos in vitro. Foi também avaliada a estabilidade do produto durante 60 dias em variadas temperaturas em tempos pré-determinados, além das análises físico-químicas, como pH, densidade, viscosidade e espalhabilidade, bem como características organolépticas. A atividade antioxidante da formulação foi determinada pelos métodos TRAP e TAR, em comparação com um controle positivo, o Trolox. Os resultados demonstraram que a formulação contendo maior concentração de Polaxamer é mais estável e por isso esta foi caracterizada. O tamanho de partícula encontrado foi 4,33 μm e o sistema se mostrou homogêneo, ideal para administração cutânea. A formulação demonstrou liberação controlada do fármaco após 24 horas, sendo capaz de permear as camadas mais profundas da pele e ser absorvida para circulação sistêmica, além de boa adesão à superfície da pele. Durante o estudo de estabilidade acelerada, as formulações armazenadas em baixa e alta temperatura, sofreram pequenas variações na densidade, na viscosidade e na espalhabilidade, em relação àquelas armazenadas a temperatura ambiente, enquanto que o pH se manteve estável durante todo o tempo e favorável à sua aplicação na pele. Além disso, as variações observadas não foram suficientes para provocar alterações visuais de instabilidade. Quanto à atividade antioxidante, a formulação demonstrou maior atividade em relação ao controle Trolox e à rutina livre, porém de forma não duradoura, apresentando valor de TAR menor que o Trolox. Sendo assim, a formulação escolhida, demonstrou-se capaz de promover a permeação da rutina por via transdérmica de forma controlada, bem como estabilidade a temperatura ambiente e com atividade antioxidante significativa, sendo considerada então promissora a administração da rutina por esta via. / São Cristóvão, SE

La maladie de Crohn et la rectocolite hémorragique font partie des maladies inflammatoires chroniques de l'intestin (MICI). Le principal objectif des traitements anti-inflammatoires est de favoriser la délivrance du principe actif localement, spécifiquement sur les zones enflammées et de limiter les effets indésirables. Ainsi, plusieurs systèmes à libération colonique de molécules actives ont été développés. Parmi eux, les pellets présentent de nombreux avantages par rapport aux formes solides unitaires conventionnelles. Dans un premier temps, des pellets comptant une substance anti-inflammatoire naturelle et nutritive, la rutine, ont été développés. L'intérêt de cette molécule est de réduire considérablement les effets secondaires qui constituent un véritable problème dans les traitements actuels des MICI. Les pellets ont été enrobé avec les polysaccharides naturels se dégradant avec la flore colonique. Les études in vitro ont démontré une libération minimale du principe actif au niveau de l'estomac et du petit intestin. Par contre, une libération rapide et totale a été observée lors de l'exposition des pellets dans les conditions du milieu colonique. Les résultats des tests in vivo ont démontré que la rutine a atténué considérablement l'inflammation au niveau de colon et les pellets enrobés ont été aussi efficaces que les pellets d'acide 5-aminosalicylique (5-ASA) commercialisés. L'administration orale de rutine via les pellets enrobés et préparés avec le chitosan semble être une approche prometteuse, permettant la libération du principe actif au niveau des zones enflammées, pour le traitement des MICI tout en réduisant les effets secondaires. Le deuxième but de notre travail était d'élucider l'impact du chitosan, un polymère mucoadhésif, sur l'efficacité thérapeutique. Les pellets de 5-ASA ont été préparés à partir de cellulose microcristalline avec ou sans chitosan. Un enrobage constitué d'un polymère pH dépendant,1' Eudragit® FS, a ensuite été réalisé autour du noyau. Les tests de dissolution ont montré que le principe actif n'était pas libéré du pellet après 2 h en milieu acide. En revanche,la libération était rapide dans un milieu simulant l'environnement colonique. Les tests ex vivo avec les pellets contenant le chitosan ont montré des propriétés mucoadhésives importantes qui ont été confirmées par la concentration élevée du métabolite de 5-ASA dans les tissus coloniques des rats. De plus, nous avons a démontré que les pellets permettaient d'atténuer de façon significative l'inflammation du côlon. Ainsi, les pellets bioadhésifs enrobés possèdent des propriétés bénéfiques supplémentaires pour la libération du 5-ASA au niveau du côlon par rapport à des formes multidoses commercialisées pour le traitement des MICI. / Crohn's disease and ulcerative colitis are two related but distinct chronic inflammatory disorders of gastrointestinal tract (GIT), commonly denoted as inflammatory bowel disease(IBD). The main goal of the anti-inflammatory treatment of this disorder is to achieve maximal drug concentration in inflamed area and reduce systemic adverse effects. For this purpose several colon-spécifie drug delivery systems have been investigated. In addition, the design of pellets as oral drug delivery systems may provide many advantages over single unit preparations and thus improve patient compliance. It is well known that most existing treatments of IBD are associated with significant side effects and for this reason the formulation with a " food like " composition was designed. In the first part of our study, therapeutic efficiency of rutin/chitosan pellets with coatings based on natural polysaccharides degraded by colonie microbiota compared to commercialized 5-aminosalicylic acid (5-ASA) pellets was investigated. Release profiles ofcoated pellets showed a minimal drug release in simulated stomach and small intestine following by rapid drug release upon exposure to the colonie fluid. The results from in vivo testing showed that rutin attenuated efficiently inflammation in the colon and coated pellets were as effective as 5-ASA pellets in mitigating experimental colitis. The studies demonstrated that rutin administration via chitosan core coated pellets seems to be apromising approach for colon-specific delivery since they could interact easily with the mucin layer and deliver drug especially to the inflamed colonie area to relieve symptoms of IBD omitting side effects related to conventional treatment. The second objective of this thesis was to explore the impact of additional mucoadhesive polymer chitosan in the pellets core on the therapeutic efficiency. For this purpose, 5-ASA loaded pellets were produced by extrusion/spheronisation method and subsequently coated with pH-sensitive polymer Eudragit® FS. No drug release at pH 1.2within 2 h, and release as intended in the simulated distal ileum and colon was observed. Chitosan-core pellets showed efficient mucoadhesive properties in ex vivo bioadhesion testing which were also confirmed by increased concentration of 5-ASA metabolite in the colonie tissues in rats. The pellets were tested in preexisting colitis and the results revealed significant attenuation of the colonie inflammation. We can conclude, that bioadhesive chitosan-corepellets showed additional beneficial properties for colonie 5-ASA delivery in the treatment of IBD over marketed dosage formulation.

This is a bachelor thesis in information design, focusing on spatial design. This study examens the situation of remote study from home during the covid-19-pandamic. With a spatial perspective regarding new routines, and with a focus on zones, boundaries and transitions between studies and free time. How does the transition from having lessons on campus to only having lessons digitally from home effect the user? What approaches are there to use to ease the situation. How can the differences between free time and studies be communicated in a clearly and informative way? The study addresses contemporary and past research as well as theories, regarding activity- based offices, boundaries, transitions and notations. The study addresses also the execution and results of methods, including a questionnaire, user test and interview, and the AEIOU- method. The projects design process with its different phases is also addressed, where the structure of the project model and the design process were an important and interesting component that contributed to the continued work on the project. Based on all this a design proposal is produced in form of a concept, with the purpose of being a support for student and facilitate the situation when it comes to remote study from home. / Detta är ett examensarbete inom informationsdesign, med inriktning rumslig gestaltning. Projektet undersöker situationen av att studera digitalt hemifrån under Covid-19-pandemin. Med ett rumsligt perspektiv gällande nya rutiner, och med fokus på zoner, gränser och övergångar mellan studier och fritid. Hur påverkas användaren av omställningen av att ha övergått till att genomföra studierna digitalt hemifrån, från att tidigare varit på plats på campus för att ha lektioner? Vilka tillvägagångsätt finns det att använda för att underlätta situationen. Hur kan skillnaden mellan fritid och studier kommuniceras på ett tydligt och informativt sätt? Rapporten tar upp samtida och tidigare forskning samt teorier, gällande bland annat aktivitetsbaserade kontor, gränser, övergångar och notationer. Rapporten tar även upp genomförande och resultat av metoder, vilket inkluderar frågeformulär, användartest och intervju, samt AEIOU-metoden. Även projektets designprocess med olika faser och moment lyfts i rapporten, där uppbyggnaden av projektmodeller och designprocessen var en viktig och intressant komponent som även de bidrog till det fortsatta arbetet med projektet. Och utifrån allt detta tas slutligen ett gestaltningsförslag fram som ska understödja studenter och underlätta situationen av att studera digitalt hemifrån, i form av ett koncept.

Biologists and physicians study complex biologic phenomena in which they use advanced imaging methods. They acquire images containing a lot of information which must be extracted in a correct way. This requires computer skills and knowledge in image processing methods which they seldom have. To overcome the problem, this master thesis aimed to develop a routine for artefact correction and information extraction from images acquired in a research project at the Karolinska Institutet in Stockholm. By developing the routine, the thesis showed how software developed for images of human can be applied to images of rats. The routine handles formatting issues and artefact corrections, calculates diffusion metrics, and performs statistical tests on spatially aligned magnetic resonance images of rats acquired with diffusion weighted echo planar imaging. The routine was verified by analysing the images that it had processed and was considered to create reliable images. Future studies within the field should focus on developing atlases of rats and continue the work with identifying how software developed for images of human can be applied to images of rats. / Biologer och läkare studerar komplexa biologiska processer för vilket de använder avancerade bildgivande metoder. De samlar bilder som innehåller mycket information vilken måste extraheras på ett korrekt sätt. Detta kräver god datorvana och kunskaper inom bildprocessning, vilket de sällan har. För att komma runt problemet, syftade den här masteruppsattsen till att utveckla en rutin för artefaktkorrigering och informationsextrahering från bilder tagna i ett forskningsprojekt vid Karolinska Institutet i Stockholm. Genom att utveckla rutinen, visar uppsattsen hur mjukvaror utvecklade för bilder av människa kan appliceras på bilder av råtta. Rutinen hanterar formatteringsproblem och artefaktkorrigering, beräknar diffusionsmått, och utför statistiska tester på spatiellt matchade magnetresonansavbildningar tagna med diffusionsviktade ekoplana metoder. Rutinen verifierades genom att analysera bilder som den processat och det konstaterades att den skapar korrekta bilder. Framtida studier inom området bör fokusera på att utveckla atlaser av råttor och fortsätta identifieringen av hur mjukvaror utvecklade för bilder av människa kan appliceras på bilder av råtta.

Biologists and physicians study complex biologic phenomena in which they use advanced imaging methods. They acquire images containing a lot of information which must be extracted in a correct way. This requires computer skills and knowledge in image processing methods which they seldom have. To overcome the problem, this master thesis aimed to develop a routine for artefact correction and information extraction from images acquired in a research project at the Karolinska Institutet in Stockholm. By developing the routine, the thesis showed how software developed for images of human can be applied to images of rats. The routine handles formatting issues and artefact corrections, calculates diffusion metrics, and performs statistical tests on spatially aligned magnetic resonance images of rats acquired with diffusion weighted echo planar imaging. The routine was verified by analysing the images that it had processed and was considered to create reliable images. Future studies within the field should focus on developing atlases of rats and continue the work with identifying how software developed for images of human can be applied to images of rats. / Biologer och läkare studerar komplexa biologiska processer för vilket de använder avancerade bildgivande metoder. De samlar bilder som innehåller mycket information vilken måste extraheras på ett korrekt sätt. Detta kräver god datorvana och kunskaper inom bildprocessning, vilket de sällan har. För att komma runt problemet, syftade den här masteruppsattsen till att utveckla en rutin för artefaktkorrigering och informationsextrahering från bilder tagna i ett forskningsprojekt vid Karolinska Institutet i Stockholm. Genom att utveckla rutinen, visar uppsattsen hur mjukvaror utvecklade för bilder av människa kan appliceras på bilder av råtta. Rutinen hanterar formatteringsproblem och artefaktkorrigering, beräknar diffusionsmått, och utför statistiska tester på spatiellt matchade magnetresonansavbildningar tagna med diffusionsviktade ekoplana metoder. Rutinen verifierades genom att analysera bilder som den processat och det konstaterades att den skapar korrekta bilder. Framtida studier inom området bör fokusera på att utveckla atlaser av råttor och fortsätta identifieringen av hur mjukvaror utvecklade för bilder av människa kan appliceras på bilder av råtta.