Idebenone is an antioxidant, a synthetic derivative of coenzyme Q10, with several applications, such as neuroprotection. However, this drug has low solubility in water, besides is irritant substance and has chemical instability. Hence, idebenone-loaded nano-organized systems have been developed, such as polymeric nanocapsules (NC). Vegetable oils containing antioxidants such as coconut oil and palm oil can be interesting for the composition of these particles. In this way, the aim of this work was to develop NC suspensions containing different oils as core (palm, coconut or medium chain triglycerides) for delivery of neuroprotective agent idebenone in order to compare the behavior of these systems concerning physico-chemical stability, photostability, controlled release, and conversion to redispersible solid dosage forms (lyophilized products). The nanocapsules were prepared by interfacial deposition of preformed polymer. As the results, it was possible to prepare poly(Ɛ-caprolactone) NC suspensions and palm oil (PO/PCL) or Eudragit® RS100 and coconut oil (OC/EUD) containing idebenone (1.0 mg/mL) with appropriate physico-chemical characteristics. Parameters such as the proportion of aqueous phase/organic phase, type of both surfactant (low HLB) and polymer influenced the optimization of these systems. For comparison, corresponding formulations were prepared with medium chain triglycerides (TCM/PCL or TCM/EUD), using the same conditions. The suspensions had an average diameter between 166 and 216nm, low polydispersity index (0.085 to 0.142), positive or negative zeta potential, depending on the characteristics of the polymer, and high encapsulation efficiency. The maintenance of average particle diameter and low polydispersity index have be verified during stability study (room temperature and exposed or not to light) for 75 days. However, the idebenone content significantly decreased in this period, with influence on the type of polymer. Thereafter, photostability study has shown that the suspensions NC OP/PCL (UVC/UVA) and TCM/PCL (UVA) were able to significantly reduce the degradation of idebenone (content: 53,7-76,1%) compared to an aqueous micellar (content: 31,2-63,1%) dispersion containing the drug. In addition, these systems were able to promoting drug controlled release (t1/2 26 h), without burst effect, showing monoexponential profile (t1/2< 3.0 h for free drug). The lyophilization of suspensions, employing trehalose as soluble carbohydrate, resulted in suitable and redispersible products (content of 96-100%, less than 3.6% moisture; 0.8-1.2 index), presenting several spherical structures, including in colloidal range, featuring the presence of NC in these dried products. In the stability study (room temperature/protection from light and moisture), it was observed that the lyophilized products were able to delay or decrease the degradation of idebenone compared to suspensions of origin, regardless of the both type of polymer (PCL/EUD) and oil (OP/OC/TCM). In conclusion, the developed systems are promising for the controlled release of neuroprotective drug idebenone. / A idebenona é um antioxidante, derivado sintético da coenzima Q10, com várias aplicações, como em neuroproteção. No entanto, este fármaco possui baixa solubilidade em água, potencial irritativo e instabilidade química, fato que tem despertado o interesse em sua associação a sistemas nano-organizados. Dentre estes, destacam-se as nanocápsulas poliméricas (NC). Óleos vegetais, contendo compostos antioxidantes, como óleo de coco e de palma, podem ser interessantes para a composição destas partículas. Neste sentido, o objetivo deste trabalho foi desenvolver suspensões de NC contendo diferentes óleos como núcleo (palma, coco ou triglicerídeos de cadeia média), almejando à veiculação do neuroprotetor idebenona, de forma a comparar o comportamento dos sistemas quanto à estabilidade físico-química, fotoestabilidade, controle de liberação, além da conversão em formas farmacêuticas sólidas redispersíveis (liofilizados). As NC foram preparadas pelo método de deposição interfacial de polímero pré-formado. Conforme os resultados, foi possível preparar suspensões de NC de poli(ε-caprolactona) e óleo de palma (OP/PCL) ou de Eudragit® RS100 e óleo de coco (OC/EUD), contendo idebenona (1,0 mg/mL), com características físico-químicas adequadas, sendo que fatores como proporção das fases aquosa/orgânica, tipo de tensoativo de baixo EHL e de polímero influenciaram a otimização dos sistemas. Para fins comparativos, formulações correspondentes foram preparadas com triglicerídeos de cadeia média (TCM/PCL ou TCM/EUD), empregando as mesmas condições. As suspensões apresentaram diâmetros médios entre 166 e 216 nm, baixos índices de polidispersão (0,085-0,142), potencial zeta positivo ou negativo, dependendo das características do polímero e elevada eficiência de encapsulamento. Quando estas suspensões foram submetidas a estudo de estabilidade, à temperatura ambiente e expostas ou não à luz, durante 75 dias, verificou-se manutenção dos diâmetros médios de partículas e baixos índices de polidispersão. Entretanto, o teor de idebenona decaiu significativamente neste período, com influência significativa do tipo de polímero. Após, estudo de fotoestabilidade demonstrou que as suspensões de NC OP/PCL (UVC/UVA) e TCM/PCL (UVA) foram capazes de reduzir significativamente a degradação da idebenona (teor remanescente: 53,7-76,1%) em comparação a uma dispersão micelar aquosa contendo o fármaco (teor remanescente: 31,2-63,1%), além de promoverem liberação controlada da mesma (t1/2 26 h), sem efeito burst, com perfil ajustado ao modelo monoexponencial (t1/2<3,0 h para fármaco livre). A liofilização das suspensões, empregando trealose, um carboidrato solúvel, resultou em produtos adequados (teor entre 96-100 %; umidade inferior a 3,6 %), redispersíveis (índice de ressuspensão entre 0,8-1,2) e com a presença de inúmeras estruturas esféricas, inclusive na faixa coloidal, caracterizando a presença das NC nestes produtos secos. No estudo de estabilidade (temperatura ambiente/proteção da luz e da umidade), observou-se que os produtos liofilizados foram capazes de retardar ou diminuir significativamente a degradação da idebenona em comparação às suspensões de origem, independentemente do tipo de polímero (PCL/EUD) e de óleo (OP/OC/TCM). Sendo assim, os sistemas desenvolvidos são promissores para a liberação controlada do neuroprotetor idebenona.

Thesis submitted in fulfilment of the requirement for the degree Doctor of Technologiae (Biomedical Technology) in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology Supervisor: Prof J van Rooyen Co-supervisor: Prof JL Marnewick Bellville October 2013 / Cardiovascular disease (CVD) is without a doubt one of the most challenging health issues of our time and accounts for the highest number of deaths in both developed and developing countries. Despite the huge strides that have been achieved in the diagnosis and therapeutic intervention of CVD, the disease burden still remains enormous. Therefore, this calls for novel and innovative interventions to curb the surge of CVD. The use of plant based food with bioactive phytochemicals,has a great potential to reduce the incidence of CVD, specifically in resource-strained countries. Red palm oil (RPO) and the indigenous herbal tea, rooibos have previously been shown to exhibit potential cardioprotective effects. Their health promoting properties have largely been attributed to their antioxidant and anti-inflammatory activities and emerging evidence also showed that they have the potential to modulate cell signalling events. Substancial scientific evidence proposes oxidative stress and inflammation to play an important role in the pathogenesis of cardiovascular disease. Hence, natural plant extracts such as RPO and rooibos could be recommended as adjuvants to clinical therapy to reduce the morbidity and mortality associated with CVD. This thesis reports on three studies investigating the cardiovascular protective effects that chronic feeding of either RPO, rooibos or their combination have on 1) antioxidant enzymes and the NO-cGMP pathway in myocardial tissue of spontaneous hypertensive rats, 2) the modulation of systemic and myocardial inflammation and 3) the myocardial ischaemic/reperfusion tolerance in a rat model of lypopolysaccharide induced inflammation. The aim of the first study was to investigate the effect of RPO on cardiac function in sponteneously hypertensive rats. The role of the nitric oxide cyclic-guanosine monophosphate(NO-cGMP) pathway, (as determined by the nitric oxide (NOS) activity) and the antioxidant defence system (selected antioxidant enzymes) were also investigated. Cardiac function was monitored at stabilization and reperfusion using the Langendorff perfusion system. Antioxidant enzymes were determined from left ventricular tissue, while total NOS activity was determined in the aorta and left ventricular tissue. The results show that RPO offered cardiac protection as evidenced by improved left ventricular developed pressure (LVDevP), maximum velocity of pressure rise (+dp/dt) max and fall (-dp/dt) max during reperfusion in sponteneously hypertensive rats (SHR) compared to their control counterparts. Improved function in SHR was associated with increased myocardial superoxide dismutase 2 (SOD2) protein expression compared to the normotensive rats. There was differential modulation of the NOS activity by RPO, an increase in NOS activity was observed in the aorta while a reduction in the activity of NOS was observed in the left ventricular tissue of both RPO supplemented normotensive and hypertensive rats compared to their respective control groups. These results argue a role for elevated NO production in the aorta for endothelial function maintenance. Increased SOD2 protein might lead to reduced oxidative stress. Thus, NO-cGMP pathway and antioxidant defense systems synergistically acted to restore cardiovascular function in SHR. The aim of the second study was to investigate the effect of RPO and rooibos supplementation on the modulation of systemic and myocardial inflammation in a rat model. As RPO and rooibos contain different types of antioxidants which reside and exert their biological effects in different cellular compartments, the combination of these two natural food compounds has the potential to enhance the spectrum of available dietary antioxidants in different cellular compartments, which could result in a better protection against certain pathological conditions such as inflammation. The Langendorff system and the lypopolysaccharide (LPS)-induced inflammatory model were used to determine if RPO and rooibos could protect against the negative effect of LPS-induced inflammation on baseline cardiac function. Both inflammation and dietary supplementation did not have any effect on baseline cardiac functional parameters. Our results show that administration of LPS resulted in elevated plasma levels of IL-1β in supplemented and non-supplemented rats indicating that an inflammatory response was triggered in the LPS-treated rats. However, this increase in IL-1β was counteracted by concurrent elevation of plasma IL-10 in LPS-induced rats consuming either rooibos or RPO alone. Furthermore the combination of RPO and rooibos enhanced myocardial IL-10 levels in LPS-induced rats. This data shows a difference in response to LPS injection between the myocardium and the systemic circulation. The results indicate that the combination of these two natural food substances exhibit potential anti-inflammatory properties which could be beneficial in clinically relevant conditions where inflammation plays a role. Having shown that dietary intervention with RPO and rooibos had the potential to modulate the inflammatory response in the model of inflammation at basal conditions, we then proceeded to the third study to specifically establish if dietary RPO when supplemented alone will improve functional recovery and reduce infarct size in LPS-treated hearts. The Langendorff perfusion system was employed for determination of cardiac function and infarct size. The roles of NFkB, p38 MAPK and the myocardial antioxidant defence systems were investigated as potential mechanisms of protection. LPS-treatment caused significant increases in myocardial IL-1 β indicating that inflammation was induced. However, the levels of myocardial IL-10 was reduced in LPS-treated hearts compared to the non-treated hearts. Intervention with dietary RPO resulted in improved functional recovery and reduced infarct size, in both healthy hearts and in the LPS-treatment group. The RPO-induced cardio-protection was associated with increases in myocardial protein expression of the antioxidant enzymes, SOD1, SOD2, GPX1 as well as increased p38 phosphorylation during reperfusion. LPS treatment increased myocardial protein expression of NFkB p65 which was reversed by RPO supplementation. Reduction of myocardial NFkB protein expression, increased p38 phosphorylation and elevated mitochondrial antioxidant (SOD2 and GPX1) as well as cytosolic enzymes (SOD 1) are proposed as potential mechanisms underlying the RPO-induced cardio-protection in this model. Based on these study results, for the first time, having included vasculature aspects in the cardio-protective effects of RPO we have shown that the NO-cGMP pathway and antioxidant defense systems may act synergistically to restore cardiovascular function in spontaneously hypertensive rats. Results from the second study also provide the first scientific evidence that RPO in combination with rooibos (a flavonoid rich endemic herbal tea) could have potential anti-inflammatory activities at systemic as well as myocardial level, which may be beneficial in clinically relevant conditions where inflammation plays a role. From the third study it can be concluded that dietary RPO improved myocardial tolerance to ischaemia-reperfusion injury in a model of inflammation.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Purpose: Breast cancer is one of the most frequent and fatal diseases women all around the globe are challenged with today. In women, breast cancer has the highest mortality rate of all cancers and the incidence rate is on the increase. It is estimated that by the year 2025, 19.3 million women will become a victim of this grave health problem. This disease is a result of the formation of malignant tumours caused by genetic alterations that are involved in the proliferation of cells, cellular differentiation and the disturbance in homeostasis which subsequently leads to the abnormal multiplication and growth of cells. Breast cancer is considered a multifactorial disease with various risk factors such as age, radiation exposure, hormone therapy, oral contraceptives, dietary factors, environmental exposure and genetic predispositions. Breast cancers can be subdivided and classified based on their cellular surface receptors such as Estrogen Receptors, Progesterone Receptors and Human Epidermal Growth Factor Receptor 2. Of the various subtypes, the triple-negative breast cancer subtype which is negative for all 3 surface receptors and presents as the most aggressive form of breast cancer with a poor prognosis. Between 10-20% of all breast cancer cases are classified as triple-negative breast cancer. Due to the hormonal status of triple-negative breast cancer, treatment options are limited and thus of great concern. Chemotherapy remains the most common treatment modality, but prognosis is poor with relapse within years ultimately leading to poor survival outcome. Due to this lack of effective treatment plans, an alternative treatment with minimal side effects and better survival remains an imperative area to explore. A wide scope of literature highlights red palm oil and its health benefits, with its growth inhibitory potential drawing great attention. Red palm oil, extracted from the Elaeis guineensis palm tree is red in colour due to the abundance of carotenoids, tocotrienols and tocopherols found in the oil. Various compounds make up the oil such as lycopene, carotenes, vitamin E and coenzyme Q10. Most studies have researched the effects of vitamin E extracted from the oil as a contributor to its growth inhibitory activity. This study focuses on the effects of the commercial red palm oil as a whole with all its compounds on the proliferation of breast cancer cells as well as the effect it has on various genes associated with breast cancer. Method: This study investigated the effect of red palm oil concentrations (1, 10, 100, 500 and 1000 μg/ml) on breast cancer cells—MCF-7 and MDA-MB-231 with comparison to a non-cancerous cell line—MCF-12A for 24-, 48- and 72-hour treatment periods. The parameter investigated was cell proliferation through the CCK-8 cell proliferation assay and the morphology following red palm oil treatment was observed and captured. Additionally, this study also investigated the effect of red palm oil on the expression of Human Mammaglobin (hMAM) and Maspin genes through the PCR assay and results visualised through agarose gel electrophoresis. Data was statistically analysed using GraphPad version 6.0 software. Results: Following treatment of red palm oil, no apparent changes in the cell morphology was observed despite using variable treatment concentrations over variable times for MCF-7, MDA-MB-231 and MCF-12A cells relative to their respective controls. Immortalised MCF-12A cells showed a significant increase in proliferation with the varying treatment concentrations, but more prominently with the highest concentration at 24, 48 and 72 hours. MCF-7 cells showed significant decreases at 24 and 72 hours. Decreased proliferation was observed at all dosages used, particularly at 10, 100, and 500 μg/ml. Furthermore, MDA-MB-231 cells demonstrated a gradual increase in cell proliferation for the 3 selected time periods in the varying concentrations. Additionally, red palm oil did not alter the gene expression of Maspin at any of the varying treatments for MDA-MB-231 nor MCF-7 cells. However, changes in hMAM gene expression were observed at treatment concentration of 100 μg/ml in MDA-MB-231 cells that were incubated for 24 and 48 hours. However, the hMAM expression was not affected in treated MCF-7 cells. Conclusion: Red palm oil, as an alternative dietary oil, seems to have potential growth inhibitory properties as demonstrated by the change in the cell proliferation of the MCF-7 cells. Literature show that various individual compounds extracted from red palm oil have anti-proliferative and inhibitory effects on breast cancer cells making them good candidates for therapy. However, this study concludes that red palm oil as a whole component would not be a suitable therapeutic agent for highly aggressive triple-negative breast cancer.

This study analysed the impact of the palm oil industry on smallholder and subsistence farmers in the Rumonge region of Burundi, the second poorest country in the world. Burundi has widespread poverty and suffers severe capacity constraints, and skill shortages brought about, in part, by ethnic civil war, political conflict and internal displacement. Ingrained animosity has disrupted farming, escalated poverty and hampered development projects such as palm oil farming. Little research has been conducted into the causes and possible solutions to these problems. Using sustainable development theory and agricultural development theory, this study addressed this gap by considering the potential benefits of sustainable palm oil production in the context of the socio-economic challenges facing Burundi. Using qualitative and quantitative methods, the study targeted four villages of Rumonge District, including Kizuka, Busaga, Dama and Birimba. A combined total of 300 respondents was derived from these four villages. Findings of the quantitative study suggest that palm oil had a positive impact on the social and economic lives of rural communities in Rumonge District;. However, challenges remained in capacity, farming skills and resources. Results from qualitative interviews and focus groups confirmed that earnings from palm oil could be used to support education, skills transfer through family ties; and employment of local people. However, from the perspective of environmentalist activists, it was indicated that while palm oil generated economic benefits for local communities, at the same time traditional farming methods led to pollution and degradation of the natural environment. Qualitative findings further showed that small-scale palm oil farmers faced numerous challenges which often led to the failure of some of their ventures, such as access to funds, lack of technical support, lack of knowledge in utilising business networking, low skills levels, limited understanding of land rights issues, civil conflicts and rising production costs. Additional problems were noted regarding environmental problems and the disappearance of wildlife. The study confirmed the need for small-scale farmers to be adequately capacitated with information, training, resources and technical support to be able to use sustainable farming methods in order to enhance yields. The study contributes to knowledge by identifying how rural smallholder farmers can design more extended longer-term plans to improve their livelihoods, particularly concerning how palm oil production can address the socio-economic problems facing the people of Burundi. / Development Studies / D. Phil. (Developmental Studies)

Current mass consumption and production patterns have led to an unsustainable use of natural resources, including freshwater, which is one the most crucial natural resources for people and the planet. Agricultural production systems are alone responsible for 72 percent of all global water withdrawals. Therefore, companies with an agricultural supply chain, such as IKEA, play an important role in minimising the negative impacts on water due to agricultural production. In order to do so, companies need to conduct assessments to become aware of their contribution and thereafter develop water targets and strategies on how to mitigate and minimise the company’s water impacts. Several different guidances, methodologies, and tools aiding companies in how to do this have recently been developed, however there is not yet one common established methodology. Therefore, this research project aimed to test and evaluate a new assessment methodology and tool for IKEA, by conducting a water risk assessment on water availability of the sourcing locations of two of IKEA’s key agricultural raw materials: soy and palm oil, and identifying mitigation possibilities, in order to aid in the company’s further work with achieving a sustainable water management and material sourcing, and developing water targets and strategies. Soy is a prioritised raw material to work with in terms of environmental and social risk, and through the conducted water risk assessment, a high risk for water depletion was identified in many of the company’s most likely sourcing locations. The water risk assessment results for palm oil indicated no significant risk for water depletion in any of the sourcing locations. The high water depletion risk scores of the hotspots were found to most likely be due to several different causes, both climatic conditions and anthropogenic activities, including agriculture. Therefore, it was identified that there are possibilities for a company, such as IKEA, to aid in mitigating the water availability challenge of the hotspots through the company’s agricultural supply chain. For example, a few agricultural management practices for increasing the water use efficiency suitable for the different hotspots could be recommended and incentivised by the company to the local farmers of the hotspot sourcing locations. The WRA methodology used in this research project, following the guidance for setting enterprise water targets by Reig et al. (2021), was assumed suitable for IKEA to use and incorporate into a more comprehensive environmental assessment methodology for agricultural raw materials in order to develop water targets and strategies. The Aqueduct Food tool was assumed to be a robust tool for water risk assessment, and can be a suitable tool for IKEA to use to quickly gain a high-level picture of a material, location or water risk of specific interest. The water risk assessment results will mainly be useful in the future, when more comprehensive environmental assessments of agricultural raw materials have been conducted, and the water use has been assessed to a greater extent. Future research is needed to be conducted in order to confirm the results and recommendations of this research project, as well as to further complement the results for the needs of IKEA. This future research includes conducting field studies of the identified hotspots and the operations of the local farms, and conducting an equivalent water risk assessment of the two materials and sourcing locations on the water quality. / Nuvarande masskonsumtion och produktionsmönster har lett till en ohållbar användning av naturresurser, inklusive sötvatten, som är en av de mest avgörande naturresurserna för människor och planeten. Jordbruk står ensam för 72 procent av alla globala vattenuttag. Därför har företag med en jordbruksförsörjningskedja, som IKEA, en viktig roll i att hjälpa till att minska de negativa effekterna på vatten från jordbruk. För att kunna göra det behöver företag utföra bedömningar för att bli medvetna om sin vattenpåverkan och därefter utveckla vattenmål och strategier för hur de kan minimera den påverkan. Det har nyligen utvecklats flera olika vägledningar, metodiker och verktyg som hjälper företag att göra detta, men det finns ännu inte en gemensam etablerad metodik. Därför hade detta forskningsprojekt som syfte att testa och utvärdera en ny bedömningsmetodik och ett nytt verktyg för IKEA, genom att genomföra en riskbedömning av vattentillgången för produktionsplatserna för två av IKEAs viktigaste jordbruksråmaterial: soja och palmolja, och genom en litteraturstudie identifiera möjligheter att minska vattenpåverkan, för att bidra till företagets fortsatta arbete med att uppnå en hållbar vattenanvändning och materialförsörjning i jordbruksförsörjningskedjan och att utveckla vattenmål och strategier. Soja är ett prioriterat råmaterial att arbeta med gällande miljömässiga och sociala risker, och genom den genomförda bedömningen av vattenrisker identifierades en hög risk för vattenbrist på många av de produktionsplatser som företaget mest troligen köper in ifrån. Riskbedömningsresultaten för palmolja indikerade ingen signifikant risk för vattenbrist på någon av de produktionsplatser som företaget troligen köper in ifrån. Den höga risken för vattenbrist i de identifierade hotspotsen visade sig troligen bero på flera olika orsaker, både klimatförhållanden och antropogena aktiviteter, inklusive jordbruk. Därför identifierades det att det finns möjligheter för ett företag, som IKEA, att kunna hjälpa till att mildra vattentillgänglighetsutmaningen i hotspotsen genom företagets jordbruksförsörjningskedja. Till exempel kan ett par olika jordbruksförvaltningsmetoder för att öka vattenanvändningseffektiviteten som är lämpliga för de olika hotspotsen rekommenderas och uppmuntras av företaget till de lokala bönderna. Den WRA-metodik som används i detta forskningsprojekt, som följde vägledningen för att sätta upp vattenmål för företag av Reig et al. (2021), antogs lämplig för IKEA att använda och integrera i en mer omfattande miljöbedömningsmetodik för jordbruksråmaterial för att utveckla vattenmål och strategier. Aqueduct Food-verktyget antogs vara ett robust verktyg för riskbedömning för vatten och kan vara ett lämpligt verktyg för IKEA att använda för att snabbt få en översikt av ett material, en plats eller en vattenrisk av specifikt intresse. Riskbedömningsresultaten kommer främst att vara användbara i framtiden, när mer omfattande miljöbedömningar av jordbruksråvaror har gjorts och vattenanvändningen har bedömts i större utsträckning. Framtida forskning behövs för att bekräfta resultaten och rekommendationerna i detta forskningsprojekt, samt för att ytterligare komplettera resultaten för IKEAs behov. Denna framtida forskning inkluderar att genomföra fältstudier av de identifierade hotspotsen och de lokala sojafarmernas verksamhet, och att genomföra en likvärdig riskbedömning för vatten av de två materialen och produktionsplatserna som utförts i detta forskningsprojekt för vattenkvaliteten.

Traditionally, fish meal (FM) and fish oil (FO) have been used extensively in aquafeeds, mainly due to their excellent nutritional properties. However, various reasons dictate the use of sustainable alternatives and the reduction of the dependence on these commodities in fish feeds. Hence, the aim of the present thesis was to investigate the effects of the replacement of FM and FO with two vegetable oils (VO) and an oilseed meal on the growth performance, feed utilization, nutrient and fatty acids (FA) digestibility and tissue FA composition and metabolism in three commercially important European fish species. Specifically, in Experiment I crude palm oil (PO) was used to replace FO in diets for rainbow trout. In Experiments II and III FO was replaced with rapeseed oil (RO) in diets for Atlantic salmon at various dietary protein/lipid levels aiming also at further reductions of FM by using low protein (high lipid) diet formulations. In Experiments II and III the fish were reared at low and high water temperatures, respectively, in order to elucidate, also, the potential effects of temperature. Lastly, the effects of the replacement of FM with full fat soya meal (FFS) in Atlantic cod were investigated in Experiment IV. The results of the present thesis showed no negative effects on growth performance and feed utilization in rainbow trout when FO was replaced with PO. The dietary inclusion of RO improved the growth of Atlantic salmon, possibly, due to changes in the nutrient and FA digestibilities and FA catabolism while, the growth and feed utilization were unaffected by the dietary protein/lipid level. However, the growth of Atlantic cod was affected negatively by the replacement of FM with FFS. The proximate composition of the fish whole body was in most cases unaffected by dietary treatments. The changes in dietary formulations affected the dietary FA compositions and resulted in significant changes in the fish tissue FA compositions. It was clearly shown that the fish tissue total lipid FA composition reflects the FA composition of the diet, although specific FA were selectively utilized or retained in the tissues by the fish. These may have serious implications not only for fish metabolism and growth but also for the quality of the final product, especially in terms of possible reductions of n-3 HUFA.

This diploma thesis aims to illuminate the issue of global climate change, its progression and describes the components of the climate system. The thesis addresses the impact of greenhouse gases on the climate system, the phenomenon of global warming, and the consequences along with their manifestations in the nature itself. The paper includes one chapter solely dedicated to the characterisation of environmental protection in historical context, with emphasis on the climate protection. The chapter also mentions a number of key international agreements and conferences. The second part of the thesis is concerned with the Indonesian legislation on climate protection in Indonesia. It also describes the global-scale impacts of selected activities and mentions number of international agreements and Indonesian regulation seeking to tackle the issue of climate change.

Land ist eine kritische Ressource für nachhaltige Entwicklung, doch ihre relative Knappheit erfordert Abwägungen, die für eine Gestaltung von nachhaltiger und gerechter Politik identifiziert werden müssen. Diese ist empirisch herausfordernd, da Landressourcen in verschiedenen abgelegenen lokalen Bedingungen genutzt werden und über voneinander abhängigen globalen Märkten gehandelt werden. Diese Dissertation trägt mit drei empirischen Studien zu dieser Identifizierungsbemühung bei. Das erste Kapitel hinterfragt das Potenzial von Preisanreizen zur Eindämmung der Entwaldung für Ölpalmplantagen in Indonesien. Die Ergebnisse deuten darauf hin, dass machbare marktbasierte Eingriffe in der vorgelagerten Palmöl-Lieferkette die nicht regulierte Entwaldung effektiv und gerecht reduzieren könnten, die ansonsten dem globalen Bedarf folgen würde. Das zweite Kapitel untersucht die Ausbreitungsmechanismen, durch die Schocks auf globalen Landressourcenmärkten indirekt zu Landnutzungsänderungen führen. Die Ergebnisse bestätigen einen globalen Verdrängungsmechanismus und etablieren einen kausalen Zusammenhang zwischen den Renewable Fuel Standards (RFS) in den Vereinigten Staaten und der Ausweitung bedeutender landwirtschaftlicher treibender Kräfte der Entwaldung in pan-tropischen Gebieten. Das dritte Kapitel erforscht die Auswirkungen der RFS auf internationale Unterernährung. Die Ergebnisse zeigen, dass der disruptive Effekt der Nachfrage-Schocks durch die RFS dank ihrer Vorhersehbarkeit abgemildert wird. Dennoch werden Bedenken bezüglich der Ernährungssicherheit in Ländern erhoben, in denen die Lebensmittelversorgung von Importen abhängt, insbesondere im Falle unerwarteter Schocks auf den globalen Märkten für Landressourcen. / Land is a critical resource for sustainable development, but its relative scarcity implies trade-offs that need to be identified to design sustainable and fair policy. This task is challenging empirically, because land resources are used in a variety of remote local conditions, and they are traded through interdependent global markets. This thesis contributes three empirical studies to this identification effort. The first chapter questions the potential of price incentives to mitigate deforestation for oil palm plantations in Indonesia. The results indicate that feasible market interventions upstream the palm oil supply chain could effectively and equitably mitigate unregulated deforestation otherwise left to follow global demand. The second chapter tests the propagation mechanisms through which shocks on global markets for land resources indirectly cause land use change. The results corroborate a global scale displacement mechanism specifically, and they establish a causal link between the Renewable Fuel Standards (RFS) in the United States and the expansion of major agricultural drivers of deforestation in pan-tropical areas. The third chapter explores the impact of the RFS on international undernourishment. The results indicate that the disruptive effect of the demand shocks by the RFS is mitigated by their predictability. Yet, this raises concerns about food security in countries where calorific supply depends on imports, in the case of unexpected shocks on global markets for land resources.