Inledning: Drygt 5% av barn i Sverige har en uppmärksamhets- och hyperaktivitetsstörning/ Attention Deficit Hyperactivity Disorder(ADHD), och runt 75% av dem medicineras för att minska symptomen av ADHD. Hyperaktivitet, svårigheter att fokusera och koncentrera sig, och impulsivt beteende är några karaktärsdrag hos barn med ADHD. Syfte: Syftet med litteraturöversikten är att se om det finns kostrelaterade behandlingskomplement för att lindra ADHD hos barn. Metod: En litteraturöversikt där tio vetenskapliga originalartiklar har analyserats och delats upp i fyra olika teman. Resultat: En elimineringskost där vissa födoämnen uteslutadess, ett minskat intag av tillsatser (konstgjorda färgämnen och konserveringsmedel) eller ökat intag av omega-3 visade positiva effekter hos en grupp barn med ADHD där symptomen minskade, speciellt hyperaktivitet. Diskussion: Trots att resultaten av studierna visar en positiv effekt hos vissa barn med ADHD så behövs mer grundlig forskning angående elimineringskost, tillsatser och omega-3. Studierna baseras ofta på frågeformulär som fylls i av föräldrarna vilket kan leda till subjektiva resultat som tar bort generaliserbarheten av studierna. De positiva effekterna antyder att komplementära behandlingsmetoder kan finnas genom en förändrad kost, som förbättrar livskvaliteten och minskar biverkningar hos barn med ADHD och samtidigt sänker kostnaderna för samhället. / Introduction: About 5% of all children in Sweden are diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and about 75 % get medication do reduce symptoms. Hyperactivity, difficulties to focus and concentrate and impulsive behavior are typical characteristics for children with ADHD. Aim: The aim with this literature review is to see if complementary treatments based on diet can assist to reduce symptoms of ADHD for children. Method: A literature review that analyses ten original articles which are divided into four different topics. Result: An elimination diet that excludes certain foods, reduced intake of food additives and preservatives or increased intake of omega-3 showed positive effects for a group of children with ADHD as symptoms minimized especially for hyperactivity. Discussion: Even though results of the studies show positive effects for certain children with ADHD, more research is needed that further investigates the effects of elimination diet, food additives and omega-3. The studies were mainly based on questionnaires, filled in by parents, which can lead to subjective results. The positive effects suggest that alternative treatments by changed diet might assist children with ADHD, improving life quality and reducing medication side effects together with reduced costs for society.

Master of Science / Grain Science and Industry / Greg Aldrich / Processing pet food can be beneficial, but can also have adverse effects on shelf-life and nutrient survival. Most affected are supplemental vitamins and essential fatty acids (EFA). Pet food complicates this relative to human foods by combining all elements into the product before processing and requiring an extensive shelf-life (up to 2 years). The objective of this research was to determine the effects of processing, diet, and storage conditions on vitamin (vitamin A, vitamin D₃, vitamin E, folic acid and thiamine) and omega-3 fatty acid (with an emphasis on eicosapentaenoic acid; EPA 20:5n3, and docosahexaenoic acid; DHA; 22:6n3) retention. The research was conducted in two separate experiments. Each experimental diet was produced on a single-screw extruder and triple-pass dryer. Target nutrients were evaluated in premixes in tandem to extruded diets. The vitamin study was conducted as a 3 X 2 X 2 factorial arrangement of treatments with 3 levels of dietary crude protein (CP), 2 screw speeds in the extruder, and 2 levels of time X temperature combinations in the dryer. Vitamins were added at 10 times normal levels to aid in analysis. The EFA study was conducted as a 3 X 3 factorial arrangement of treatments with 3 levels of dietary protein and 3 different omega-3 sources: fish oil, fish meal, or purpose-grown algae rich in DHA. In the vitamin premix study, the quantity of vitamins declined by approximately 50% over 6 months storage in ambient conditions (AMB; 20C, 50%RH), and all except folic acid were lost to some degree in stressed shelf life testing (SSLT; 50C, 70% RH) over 6 weeks. In all cases, the concentration of vitamins in food exiting the extruder and dryer were lower than target levels. As CP increased, the retention was higher (P ≤ 0.05) for vitamins A, E, and folic acid off the extruder (e.g. 225,352 vs. 219,184 and 206,249 IU/kg of vitamin A for high vs. medium and low CP, respectively), and vitamin D₃, E, and folic acid off the dryer (e.g. 9,047 vs. 7,473 and 6,945 IU/kg of vitamin D₃ for high vs. medium and low CP, respectively). During storage of finished pet food in AMB, vitamins A and D₃ were lost (P < 0.05) to the greatest degree (49 and 22%, respectively). The total retention following both processing and AMB storage was 27, 68, 78% for vitamins A, D₃, and E, respectively, while folic acid and thiamine were relatively stable. In SSLT storage, all vitamins except vitamin E were depleted more than 60% (P < 0.05) by 24 weeks, whereas total retention following both processing and SSLT storage was 3, 59, 43, 33, and 7% for vitamins A, D₃, and E, folic acid, and thiamine, respectively. This would suggest that beyond processing losses, the vitamins are relatively stable in premixes and foods if stored in AMB conditions. In the study to evaluate fatty acid stability within a vitamin premix, EPA, DHA, and total omega-3 fatty acids were relatively stable during storage over 6 weeks with losses no greater than 12% in stressed shelf life testing (SSLT; 40C, 70% RH). While in ambient conditions (23C, 50% RH) over 3 months, there was a total loss of EPA, DHA and total fatty acids by 17, 9, and 11%, respectively. Exiting the extruder and dryer, EPA and DHA were not affected by CP level or Omega-3 source. As SSLT storage of finished pet food increased through 24 weeks, EPA, DHA, and total fatty acids declined slightly (P < 0.05; 125, 82 mg/kg for EPA and 77, 60 mg/kg for DHA, and 418, 476 mg/kg for total fatty acids at 0 vs. 24 wk. As time in ambient storage reached 24 months, EPA, DHA, and total fatty acids declined slightly (P < 0.05; 125 vs. 78 mg/kg for EPA and 77 vs. 50 mg/kg for DHA, and 387 vs. 373 for total fatty acids at 0 vs. 24 mo.) Algal-DHA appears to be a stable source of DHA when compared to fish oil and fishmeal. During processing retention of fat soluble vitamins was less than water soluble vitamins, and the omega-3 fatty acids were relatively unaffected. Whereas, vitamins appeared to be more sensitive to temperature during storage and the omega 3 fatty acids more affected by time.

[pt] O mercado brasileiro de energia elétrica é composto basicamente de matrizes hidroelétricas e termoelétricas, sendo que seu fornecimento pode ser contratado em dois ambientes, um de contratação regulamentada e outro livre. Dessa forma o apreçamento da energia é algo complexo e com incertezas, pois seu modelo leva em consideração comportamentos de afluências futuras, além de estimar a utilização de termoelétricas, que possuem fontes de energia mais caras. No Brasil, existem quatro submercados que podem ter preços divergentes. Algumas comercializadoras se utilizam dessa diferença buscando aferir ganhos extraordinários fazendo Swaps. Essa operação consiste em compra e venda de uma mesma quantidade de energia com liquidação fixada em uma determinada data com o preço à vista entre diferentes submercados. Essas empresas utilizam medidas de otimização de carteiras e controle de risco para fazerem operações ótimas, onde há maior probabilidade de maximizar o lucro, tendo o prejuízo máximo sob controle. Esse trabalho tem como objetivo encontrar a carteira de Swaps de energia que maximiza a medida Ômega, usada como avaliador de desempenho, tendo uma expectativa de lucro e com uma restrição de risco com um limite para o Conditional Value at Risk (CVaR), assim auxiliando as comercializadoras a maximizarem seu lucro não ultrapassando seu limite de risco. O estudo levou em consideração valores de previsão reais feitos por modelos fornecidos por órgãos especializados, levando em consideração os dados para os anos de 2012 e 2013 sendo estudadas todas as combinações possíveis de Swaps para a composição da carteira ótima para cada um dos anos estudados. A carteira ótima foi encontrada, no entanto, pode-se concluir que sua composição varia de acordo com os dados simulados não existindo assim uma carteira ótima única devendo essa ser calculada caso a caso. / [en] The Brazilian energy market is composed basically by hydroelectric and thermoelectric energy sources, which can be contracted in two different environments, one regulated and the other free. In this way, the pricing of energy is something complex and uncertain, because its model takes in consideration the behavior of future water affluences, besides estimating the more expensive thermal units. In Brazil, there are four submarkets that have diverging prices and some traders use this difference to reach extraordinary gains by entering into Swap operations. This operation consists of buying and selling a same amount of energy with its liquidation fixed at pre-determined date, at a spot price between different submarkets. These companies use portfolio optimization and risk management methods to reach optimal operations, in which there is a greater probability of maximizing profits, while measuring risk. This study aim to find the portfolio of Swaps that`s maximize the Omega measurement as the performance measurement, has a estimated profit and uses the conditional Value at Risk (CVaR) as the restriction for the risk that can be taken. Its objective is to help traders maximize their profit without exceeding their risk limit. The study took in consideration values from real previsions made by models provided by specialized agencies, taking in consideration all the data for the years of 2012 and 2013, with all the combinations of Swaps being studied. The optimal portfolio was achieved in both cases however, it`s possible to conclude that this composition varies according the input data, not existing thereby a unique optimal portfolio should that be calculated by case.

[pt] A presente tese tem como objetivo estabelecer uma metodologia que permita efetuar uma composição otimizada de uma carteira de ativos reais, determinando os que serão selecionados na carteira, de tal forma que atendam a um conjunto de restrições características da carteira sob análise, e levando em conta a possibilidade de exercer opções reais. Esta otimização se realiza em função da maximização da medida de performance Omega, a qual se define como a relação entre o ganho médio esperada e a perda média esperada da distribuição de retornos ou da distribuição de Valores Presente Líquido (VPL). Esta medida requer que seja previamente definido o nível mínimo de retorno (ou VPL) desejado pelos investidores, que é o limite entre a área de ganhos e a de perdas na distribuição. A medida Omega leva em consideração todos os momentos da distribuição de retornos futuros ou VPL, não se restringindo ao mundo simplificado da Média-Variância. É um fato empírico conhecido que as distribuições de muitas variáveis financeiras não seguem uma distribuição normal e que a maioria dos investidores não possuem funções de utilidade quadrática, fazendo com que a modelagem clássica de composição de carteiras proposta por Markowitz (1952) não seja apropriada nestes casos. Omega permite lidar satisfatoriamente com todo tipo de distribuições, sejam ou não normais. Na presente tese, a abordagem proposta se baseia em métodos numéricos de Simulação de Monte Carlo, para a determinação das distribuições de VPL e o cálculo da medida Omega. / [en] This thesis develops a methodology to determine an optimum composition of a portfolio of real assets. It involves selecting real assets which will be included in the portfolio and taking into consideration all the constraints which apply. The possibility of exercising real options is taken into consideration. The determination of the optimum composition is done by maximizing a performance measure called Omega. Omega measure is defined as the relation between the expected average gain (Expected Chance) vs. the expected average loss (Expected Shortfall) of the returns or Net Present Values (NPV) distribution. This measure requires the decision maker to define previously the minimum desirable level of return or NPV, depending on the context it is being used, which is the border between the gains and losses areas in the distribution. Omega takes into account of all the moments of the distribution of the future returns or NPV, implying it does not restrict to the Mean-Variance world. It is a well known empirical fact that many financial variables don´t follow normal distributions or most investors don´t have quadratic utility functions, which causes the classical model of portfolio composition proposed by Markowitz (1952) inappropriate. The Omega measure can deal satisfactorily in all cases not having normal distributions or even in cases which have normal distributions. In this thesis, the numerical method of Monte Carlo Simulation is used to determine the NPV distribution and calculate Omega measure.

Ácidos graxos polinsaturados Omega-3 (n-3 PUFA) tais como o ácido eicosapentaenóico (C20:5 n-3, EPA) e docosahexaenóico (C22:6 n-3, DHA) reduzem a concentração plasmática de triacilgliceróis em humanos. Entretanto, uma alta proporção desses ácidos graxos na dieta poderia favorecer a susceptibilidade das células à peroxidação, aumentando o risco de desenvolvimento de doenças cardiovasculares. Embora modelos animais não sejam recomendados para avaliar o efeito de n-3 PUFA nas lipoproteínas plasmáticas, estes têm sido amplamente utilizados como modelo para avaliação de dano oxidativo. Diferenças nos procedimentos metodológicos também têm gerado dificuldade na comparação de resultados. Desta forma, o objetivo deste estudo foi aplicar os mesmos procedimentos metodológicos para comparar o efeito da suplementação de n-3 PUFA nos biomarcadores plasmáticos de estresse oxidativo utilizando um modelo humano e um modelo animal. Indivíduos foram aleatoriamente distribuídos em dois grupos num delineamento paralelo duplo cego e receberam uma suplementação de 460,0 mg/dia de n-3 PUFA (OMEGA) contendo 240,0 mg de EPA + 160,0 mg de DHA + 60,0 mg de outros n-3 PUFAs, ou óleo de soja (PLACEBO) durante 6 semanas. Ratos Wistar também foram distribuídos em dois grupos e receberam uma dieta contendo 192,5 mg/dia de n-3 PUFA (FO) sendo 116,3 mg de EPA + 61,5 mg de DHA + 14,7 mg de outros n-3 PUFAs ou óleo de soja (SO) durante 3 semanas. Indivíduos do grupo OMEGA apresentaram maior concentração de malondialdeído (MDA) no plasma medido por TBARS quando comparado aos respectivos valores no baseline. A suplementação com n-3 PUFA não alterou a concentração plasmática de &#945;-tocoferol e a atividade antioxidante determinada pelo método DPPH. Apesar dos animais terem recebido doses 10 vezes maiores de n-3 PUFA (2,9 mg/kcal) quando comparadas aos humanos (0,3 mg/kcal) não foram observadas alterações entre os grupos FO e SO para as concentrações de MDA no plasma e no homogenato de cérebro. Em resumo, pode-se sugerir que o modelo animal usado neste estudo parece não ser o mais adequado para avaliar o estresse oxidativo após intervenções dietéticas com n-3 PUFAs em função de diferenças no metabolismo e nos mecanismos de proteção antioxidante observados entre os dois modelos. / Omega-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic (C20:5 n-3, EPA) and docosahexaenoic (C22:6 n-3, DHA) reduce plasma triacylglycerol concentration in humans. However, higher proportion of these fatty acids in the diet could raise cells lipoperoxidation susceptibility, increasing the cardiovascular disease risk. Although animal models are not recommended to evaluate the effect of n-3 PUFA in plasma lipoproteins, they have been widely used as model for oxidative damage. Difference in methodological proceedings has also caused difficulties to compare data among assays. Thus, the objective of this study was to apply the same methodology to investigate the effect of n-3 PUFA supplementation on oxidative biomarkers in animal and human model. Individuals were randomly assigned in two groups in a parallel double blind design and received a supplement of 460.0 mg/day n-3 PUFA (OMEGA) containing 240.0 mg EPA + 160.0 mg DHA + 60.0 mg other n-3 PUFAs, or soybean oil (PLACEBO) during 6 weeks. Wistar rats were also assigned in two groups and received a diet containing 192.5 mg/day n-3 PUFA (FO) containing 116.3 mg EPA + 61.5 mg DHA + 14.7 mg other n-3 PUFAs or soybean oil (SO) for 3 weeks. Individuals in OMEGA group showed higher malondialdehyde (MDA) concentration in plasma measured by TBARS when compared to their baseline values. N-3 PUFA supplementation did not change plasma &#945;-tocopherol concentration and antioxidant activity determined by DPPH method. Although animals have received a 10-fold higher dose of n-3 PUFA (2.9 mg/ kcal) than humans (0.3 mg/kcal), no alteration was observed between FO and SO groups for plasma and brain homogenate MDA concentration. In summary, it can be suggested that the model used in this study doesn\'t seem appropriate to evaluate oxidative stress after dietetic interventions with n-3 PUFA due to physiological differences involved in lipid metabolism and antioxidant protection observed between both models.

Introdução A Síndrome Metabólica (SM) representa um conjunto de fatores que determinam maior risco para Doença Cardiovascular (DCV), devido principalmente à Resistência à Insulina (RI) e ao estado inflamatório promovido pelo tecido adiposo branco hipertrofiado. Nesse contexto, a condição de dislipidemia favorece o desenvolvimento da aterosclerose, devido a que maiores concentrações de lipoproteína de baixa densidade (LDL) no plasma podem propiciar modificações nessas partículas. Essas modificações podem ter origem oxidativa ou não oxidativa e impactar nas características aterogênicas da LDL. O ômega três tem mostrado efeitos hipolipemiantes e anti-inflamatórios, que podem reduzir o risco cardiovascular de indivíduos com SM. Objetivo:: avaliar o efeito da suplementação de 3g de &#969;-3 por um período de oito semanas sobre a concentração plasmática das partículas de LDL eletronegativas [LDL(-)] e seus anticorpos, assim como monitorar possíveis mudanças nas concentrações das subfrações das LDL. Metodologia: Foram incluídos 115 participantes de ambos os sexos, entre 30 e 74 anos, com SM, separados nos grupos de intervenção com &#969;-3 (n=58) e controle com &#969;-9 (n=57). Foram realizadas análises de perfil lipídico e por meio de ELISA foram avaliadas a concentração de LDL(-) e de antiLDL(-) no plasma dos participantes. O tamanho das subfrações de LDL foi realizado no sistema Lipoprint. O efeito do tempo e das intervenções foi testado por meio do programa SPSS versão 20.0, adotando-se o concentração de significância de p<0,05. Resultados: A suplementação de &#969;-3 teve efeito significativo na redução do % de massa grassa (%MG) e na pressão arterial sistólica (4%) e diastólica (5%). Em relação ao perfil lipídico, ambas intervenções tiveram efeitos significativos de redução de colesterol total (CT), LDL-c, não HDL (nHDL) e triacilglicerois (TG). As concentrações plasmáticas de LDL(-) dos participantes que tomaram ômega 3 apresentaram redução de 21%, enquanto que os que tomaram ômega 9 tiveram redução de 1%. Tal redução foi significativa em relação ao tempo de intervenção (p<0,05), mas não quando o efeito da internveção foi avaliado. Perfil semelhante foi observado para a razão LDL(-)/antiLDL(-), observou-se redução de 22% no grupo ômega 3 e redução de somente 3% no grupo ômega 9. Conclusão: A intervenção com ômega 3 promoveu redução na concentração plasmática de LDL(-), porém não modificou a concentração do anticorpo antiLDL(-) nem o tamanho das subfrações da LDL. / Introduction: The Metabolic Syndrome (MetS) is a combination of factors that determine increased risk for Cardiovascular Diseases (CVD), mainly because of Insulin Resistance (IR) and the inflammatory state promoted by the hypertrophied white adipose tissue. Under this background, the dyslipidemic condition goes together with the developing of atherosclerosis, meaning that higher concentrations of low density lipoprotein (LDL) in plasma promote modifications from different sources in these particles and may have an impact over LDL subfractions, turning them more atherogenic. Omega three has proved hypolipidemic and anti-inflammatory effects, which may reduce cardiovascular risk in MetS individuals. Objetive: evaluate the effect of 3g of fish oil supplementation, 60% EPA and DHA during an eight week period over plasma concentrations of electronegative LDL particles [LDL(-)] and its antibodies, as well as monitoring possible changes in LDL subfractions. Methods: A total number of 115 participants, both sexes, between 30 and 74 years of age, with MetS, were included and separated in the intervention group receiving omega 3 (n=58) and the placebo group with omega 9 (n=57). Biochemical analyses were carried out using ELISA for LDL(-) and antiLDL(-) in plasma. Particle sizes were measured using the Lipoprint system. The effects of time and intervention were analyzed using the statistical program SPSS 20.0, assuming p<0.05 as significant. Results: Omega 3 supplementation had a significant effect in the reduction of fat mass percentage (FM%) and blood pressure, showing a 4% decrease for systolic and 5% decrease for diastolic pressures respectively. Considering the lipid profile, both interventions had significant effects reducing total cholesterol (TC), LDL-c, not HDL (nHDL) and tryacylglycerides (TG). LDL(-) plasma concentrations from the omega 3 group showed 21% reduction while the omega 9 group had only 1% reduction. Such difference was significant considering time (p<0,05), but not while comparing the intervention effect. There was also a change in the antiLDL(-) antibodies; reducing 2% in the omega 3 group and increasing 1% in the omega 9 group. However, those differences were not significant. Similar effects were observed in LDL(-)/antiLDL(-) ratio, showing 22% decrease in the omega 3 group and only 3% in the omega 9 group. Conclusion: Omega 3 intervention promoted a significant reduction in plasmatic LDL(-), however, it didn\'t modify LDL subfraction distribution.

Com a utilização de 18 éguas, adultas, sem raça definida, com peso médio de 521±56 Kg, em delineamento inteiramente casualisado com três tratamentos e seis repetições por tratamento com medidas repetidas no tempo. Os objetivos deste trabalho foi verificar os efeitos da suplementação dietética com ácidos graxos ômegas 3 e ômega 6 sobre a composição do colostro e leite de éguas e transferência imunitária para os potros. Diferenças significativas encontradas foram na qualidade do leite das éguas onde foi observado efeito de tempo (semanas) sobre as variáveis de gordura, proteína, lactose e sólidos totais. Para a variável sólidos totais observou-se efeito do tratamento, semana e da inclusão de óleo na dieta. Observou-se nos potros uma atividade linfoproliferativa, no grupo óleo de soja semelhante ao encontrado no grupo controle, em ambos os períodos analisados. O grupo óleo de linhaça apresentou atividade linfoproliferativa maior do que a encontrada nos dois outros grupos no dia sete. No dia trinta, o grupo de linhaça continuou a apresentar uma maior atividade proliferativa, no entanto sem diferença estatística. A suplementação fonte de óleo aumentou a energia dietética disponível e a resposta proliferativa das éguas do dia sete. Observou-se que a suplementação com óleo de linhaça promoveu um aumento das concentrações dos isótopos IgGa e IgGb no colostro. A concentração média de IgGa no grupo óleo de linhaça foi quase 4 vezes superior aquela encontrada no colostro das éguas do grupo controle e quase 3 vezes superior aquela encontrada no grupo suplementado com óleo de soja com uma significância de. Assim concluímos que o ômega 3 melhorou a posta linfoproliferativa e aumentou a concentração de IgGb, porem não alterou os componentes do leite. / With the use of 18 mares, adult mongrel with a mean weight of 521 ± 56 kg in completely randomized design with three treatments and six replicates per treatment with repeated measures. The objectives of this study was to determine the effects of dietary supplementation with fatty acids omega 3 and omega 6 on the composition of colostrum and milk of mares and foals for immune transfer. Significant differences were found in milk quality mares where was no effect of time (weeks) on the variables of fat, protein, lactose and total solids. For variable total solids was observed effect of treatment week and oil inclusion in the diet. It was observed in foals lymphoproliferative activity in the soybean oil group similar to that found in the control group in both periods analyzed. The group linseed oil lymphoproliferative showed activity greater than that found in the other two groups on day seven. On the thirtieth day, the flaxseed group continued to show a higher proliferative activity, however no statistical difference. The source of oil supplementation increased dietary energy available and the proliferative response of mares of day seven. It was observed that supplementation with flaxseed oil promoted increases in concentrations of isotopes and IgGa IgGb in colostrum. The average concentration of IgGa group in linseed oil was almost 4 times higher than that found in colostrum of mares in the control group and almost 3 times higher than that found in the group supplemented with soybean oil with a significance. Thus we conclude that omega 3 put lymphoproliferative improved and increased the concentration of Ig, but it does not change the components of milk.

Vitamin E ist der Überbegriff für 4 Tocopherole (α, β, γ und δ) sowie 4 Tocotrienole (α, β, γ und δ), die als gemeinsames Merkmal ein Chromanolringsystem sowie eine gesättigte (Tocopherole) bzw. ungesättigte (Tocotrienole) Seitenkette aufweisen. Neben ihrer antioxidativen Wirkung (Schutz von Membranen vor Lipidperoxidaton) konnten für einige Vitamin E - Formen auch eine Reihe von hochspezifischen, nicht-antioxidativen Wirkungen in vitro nachgewiesen werden. Meist bleibt jedoch unklar, ob ein solcher Effekt auch in vivo, also im Tiermodel oder direkt im Menschen, gefunden werden kann. In erster Linie müsste hierbei geklärt werden, ob die jeweilige Vitamin E - Form auch bioverfügbar, also in für eine Wirkung ausreichender Konzentration im Organismus vorhanden ist, oder aber vorher eliminiert und ausgeschieden wird. In dieser Doktorarbeit wurden deshalb wichtige Grundlagen zum Abbau der Tocopherole und Tocotrienole erarbeitet. • In HepG2-Zellen konnte der Abbau der Tocotrienole mit Hilfe flüssig- sowie gaschromatographischer Analysemethoden vollständig aufgeklärt werden. Wie sich hierbei ergab, verläuft der Abbau weitgehend in Analogie zum Abbau der Tocopherole über eine durch Cytochrom P450 katalysierte initiale ω-Hydroxylierung mit 5 nachfolgenden β-Oxidationsschritten. • In vitro konnten in HepG2 – Zellen die Abbauraten der verschiedenen Vitamin E - Formen bestimmt werden. Dies nahmen in folgender Reihenfolge zu: α-Tocopherol < γ-Tocopherol < α-Tocotrienol < γ-Tocotrienol. • Wie sich mit Hilfe eines mit Cytochrom P450 hochangereicherten Homogenats aus Rattenlebern ergab, stellt die initiale ω-Hydroxylierung einen geschwindigkeitsbestimmenden Schritt des Abbaus dar: α-Tocopherol wurde weit langsamer hydroxyliert als alle anderen Vitamin E – Formen. • Der unterschiedliche Abbau von α-Tocopherol und γ-Tocotrienol konnte auch im Mäuseversuch in vivo bestätigt werden. Nach Fütterung von Mäusen mit α-Tocopherol wurden nur geringe Mengen von α-Tocopherolmetaboliten im Urin der Mäuse gefunden, während nach Applikation von γ-Tocotrienol hohe Konzentrationen der γ-Tocotrienolmetabolite nachgewiesen wurden. In Plasma und Leber wiederum wurden (dem Futtergehalt entsprechende) hohe α-Tocopherolkonzentrationen entdeckt, während γ-Tocotrienol selbst nach hoher Gabe nicht oder nur in Spuren nachweisbar war. In HepG2 – Zellen konnte gezeigt werden, dass γ-Tocotrienol eine cytotoxische Wirkung auf die Hepatocarcinoma-Zelllinie HepG2 entfalten kann, indem durch die Aktivierung der proteolytischen Caspase 3 die Induktion des programmierten Zelltodes (Apoptose) ausgelöst wird. Abschliessend lässt sich festhalten, dass der Körper lediglich das natürliche α-Tocopherol vor dem Abbau bewahrt, die anderen Vitamin E – Formen jedoch als Fremdstoffe behandelt und rapide ausscheidet. Als doppelter Schutz vor Verlust des “wertvollen” α-Tocopherol dienen hierbei das α-Tocopherol Transfer Protein sowie die in dieser Arbeit gefundenen Unterschiede im ersten Schritt des Abbaus, der Cytochrom P450 - katalysierten ω-Hydroxylierung. Beides erklärt die bevorzugte Retention von α-Tocopherol im Organsimus und seine hohe Bioaktivität. Will man deshalb in vitro Ergebnisse anderer Vitamin E – Formen auf die in vivo Situation übertragen, muss man die geringe Bioverfügbarkeit dieser Substanzen berücksichtigen. / The vitamin E family is comprised of 4 different tocopherols (Toc: α, β, γ, δ) and 4 different tocotrienols (T3: α, β, χ, δ). All share a hydroxychromanol ring and a saturated (Toc) or unsaturated (T3) side chain. Apart from their role as anti-oxidants (protection of membranes from lipid peroxidation), recent attention has focused on novel molecular, non-antioxidative functions. Numerous specific effects of tocopherols and tocotrienols were uncovered by a large variety of in vitro studies, in vivo - based evidence, however, is scarce. Moreover, little information exists on the bioavailabilty of the different vitamin E - forms. To better understand the biological role of the different tocopherols and tocotrienols, this thesis therefore aimed to address the basic but important aspect of tocopherol and tocotrienol metabolism. • In HepG2 cells, the metabolic pathway of α- and γ-T3 could be elucidated by the identification of all intermediary degradation products by using high performance liquid- as well as gas-chromatography. Thus, tocotrienols are degraded in analogy to tocopherols with an initial ω-hydroxylation and 5 subsequent β-oxidation steps. • In vitro (HepG2 cells), tocotrienols were degraded to a larger extent than tocopherols, and γ-Toc to a larger extent than α-Toc. Differences reached two orders of magnitude with α-Toc < γ-Toc < α-T3 < γ-T3. • By using rat liver microsomes that were highly enriched with cytochrome P450 enzymes, the initial ω-hydroxylation was shown to be a rate limiting step in the degradation of vitamin E: α-Toc is hydrolysed to a much smaller extent than all other vitamin E forms. • The differences in vitamin E metabolism were confirmed in vivo using male mice. After supplementation with α-Toc, only little amounts of α-Toc metabolites were found in urine, while oral administration of γ-T3 led to the rapid excretion of large amounts of γ-T3 metabolites. Correspondingly, in plasma and liver α-Toc levels were high but γ-T3 could hardly be detected. • γ-T3 but no other vitamin E – form was shown to be highly cytotoxic for HepG2 cells. Immunohistochemistry stainings revealed that γ-T3 induced apoptosis by activation of the proteolytic caspase 3. To summarize, α-Toc is metabolized to a much smaller extent than all other vitamin E - forms. Both the α-tocopherol transfer protein as well as the here described differences in the ω-hydroxylation rates provide a double protection for the “valuable” α-Toc from degradation. Both phenomena explain the high retention of α-Toc in the organism and its higher bioactivity, compared to other Vitamin E forms. The differences in the metabolism of vitamin E might therefore lead to an inequivalence of biological activities found in vitro vs. in vivo.

In der Veterinärmedizin verursachen Rotaviren als Jungtiererkrankung vor allem in der Nutztierpraxis hohe ökonomische Verluste. Über die Prävalenz von Rotavirusinfektionen bei Hunden und Katzen ist sehr wenig bekannt, obwohl von den in der Literatur als wechselseitig zwischen Mensch und Tier übertragbaren Viren ein nicht zu unterschätzendes Risiko ausgehen kann. Zunächst wurden retrospektiv Prävalenzdaten über den Nachweis von Rotaviren bei Hunden und Katzen mit Durchfall im Vergleich zu Coronaviren und Parvoviren erhoben. Dazu wurden Kotproben von 2055 Hunden und 1481 Katzen quantitativ auf das Vorhandensein von Rota-, Corona- und Parvovirus untersucht. Desweiteren wurden Aspekte der geographischen Verteilung, der Altersverteilung, mögliche Rasseprädispositionen und das Auftreten saisonaler Erkrankungsgipfel untersucht und ausgewertet. Für Rotavirusinfektionen beträgt die statistische Prävalenz 7% bei Hunden und 8% bei Katzen. Bei Hunden und Katzen konnten signifikant häufiger Dreifachinfektionen nachgewiesen werden. Bei einer Infektion mit Rota- und Coronavirus liegt beim Hund zu 100% auch eine Infektion mit Parvovirus vor. Zweifachinfektionen kamen weniger häufig vor als Monoinfektionen. Alle drei Virusinfektionen kamen bei Hunden statistisch signifikant häufiger in der Altersgruppe ≤ 1 Jahr vor. Ein statistisch signifikant häufiger Rotavirusnachweis konnte bei der Katzenrasse Siam nachgewiesen werden, während keine Hunderasse besonders hervortrat. Im Postleitzahlengebiet 3 konnten im Beobachtungszeitraum von 2000 bis 2006 statistisch signifikant häufiger Rotavirusinfektionen bei Hunden nachvollzogen werden. Es konnte sowohl für Hunde, als auch für Katzen der Trend belegt werden, dass bei steigenden Lufttemperaturen, die Anzahl der Rotavirusinfektionen sinkt. Es kann somit von einer bedingten Saisonalität ausgegangen werden. Im zweiten Teil der Arbeit wurde die Empfänglichkeit von Rotaviren gegenüber kommerziell erhältlichem Typ I Interferon (rFeIFN-ω) in vitro getestet. Zunächst wurde zum Nachweis der Aktivität der Typ I Interferone (rFeIFN-ω, rBoIFN-α, rHuIFN-α) die Expression des Mx Proteins auf Zelllinien felinen, caninen, bovinen und humanen Ursprungs, sowie auf Affenzelllinien untersucht. Es konnte gezeigt werden, dass rBoIFN-α ausschließlich auf Zellen bovinen Ursprungs eine konzentrationsabhängige Expression des Mx Proteins induziert. Das rFeIFN-ω induziert auf Zellen felinen und bei höheren Konzentrationen auch auf Zellen caninen Ursprungs die Expression des Mx Proteins. Das rHuIFN-α zeigt eine konzentrationsabhängige Induktion des Mx Proteins in Zellen humanen, caninen, felinen und bovinen Ursprunges, sowie in Affenzelllinien. Somit konnte in vitro eine Kreuz-Speziesspezifität für rekombinantes humanes Interferon nachgewiesen werden. Zum Nachweis einer immunmodulatorischen Wirkung wurde die Expression der MHC I Oberflächenrezeptoren nach Behandlung mit rFeIFN-ω und rHuIFN-α untersucht. Die Behandlung mit rFeIFN-ω führte ausschließlich in felinen Zellen zu einer konzentrationsabhängigen signifikanten Erhöhung der Rezeptordichte. Die Behandlung mit rHuIFN-α führte zu einer konzentrationsabhängigen signifikanten Erhöhung der Rezeptordichte auf felinen Zellen und in der Affenzelllinie MA104. Die Empfänglichkeit von Rotaviren gegenüber rFeIFN-ω wurde auf der embryonalen felinen Fibroblastenzelllinie (KE-R) und auf der embryonalen felinen Gehirnzelllinine (KG-R) unter steigender Interferonkonzentration (101-104 Einheiten/ml) untersucht. Beide Zelllinien zeigten eine deutliche Reduktion der infizierten Zellen bei steigender Interferonkonzentration. Die antivirale Wirkung war in KE-R Zellen deutlicher ausgeprägt. Dort konnten bereits bei einer Interferonkonzentration von 103 Einheiten/ml keine sichtbar infizierten Zellen mehr nachgewiesen werden, während KG-R Zellen erst bei einer Konzentration von 104 Einheiten/ml keine sichtbar infizierten Zellen mehr nachzuweisen waren. Abschließend wird deutlich, dass Infektionen mit Rotaviren ein vielmals vernachlässigtes Problem in der Veterinärmedizin darstellt, vor allem, wenn man von einer Vergesellschaftung mit den für Hund und Katze pathogenen Viren Corona- und Parvovirus ausgeht. Mit dem rFeIFN-ω steht in vitro eine wirksame antivirale Substanz gegen Rotavirusinfektionen zur Verfügung.

Diets formulated to contain varying ratios of omega 6 to omega 3 fatty acids were fed to exercising yearlings to evaluate bone activity and inflammatory response. Nine Quarter Horse yearlings were arranged within a triplicated 3 X 3 Latin Square experimental design and fed one of three diets. Exercise protocol was designed to stimulate sub-clinical inflammation and normal bone response. Body weight and physical growth measurements were not different between groups (P > 0.05), and feed intake was similar between groups (P > 0.05). Horses consuming soybean oil (SBO) diet had lower fatty acid profiles (% by weight) of C16:0 and C16:1 (P < 0.05) when compared to horses consuming either corn oil (CO) or menhaden/corn oil (MCO) diets. Though numerically different, percentage changes in C16:0 and C16:1 were not different between diets (P < 0.05). Horses consuming MCO had significantly higher measurements of C20:4, C20:5 and C22:6 over the 28 day period when compared to horses consuming SBO or CO. Percent change in mean concentrations of C20:5 were significantly different between the MCO group and the SBO group (P < 0.05) with no observed difference between MCO and CO treatment groups. Overall mean carboxyterminal telopeptide of type I collagen (ICTP) concentrations did not differ between diets (P > 0.05) nor was there a significant change from baseline values when compared to day 28 of the period. Mean Osteocalcin (OC) concentrations did not differ between treatments (P > 0.05). Numerically, OC levels were lower after 14 days, with subsequent increases occurring from day 14 to day 28; however, there was no significant day effect (P > 0.05). Mean measurements of PGE2 and fibrinogen, the two inflammation markers evaluated, did not differ among groups (P > 0.05). However, when fibrinogen data were normalized, horses consuming SBO had a significantly lower change in baseline values of fibrinogen compared to horses fed CO or MCO diets (P< 0.05). In general, horses fed SBO exhibited reduced levels of the inflammatory marker fibrinogen (P< 0.05). No other variable evaluated was influenced by the supplementation of varying ratios of polyunsaturated fatty acids into the equine diet.