The homeoviscous adaptation hypothesis states that the relative abundance of polyunsaturated fatty acids (PUFAs) in membrane phospholipids of ectothermic organisms decreases with increasing temperatures to maintainvital membrane properties. We reared Daphnia magna at 15°, 20°, and 25°C and increasing dietary concentrations of the long-chain PUFA eicosapentaenoic acid (EPA) to test the hypothesis that the well-documented increase in heat tolerance of high-temperature-reared Daphnia is due to a reduction in body PUFA concentrations. Heat tolerance was assessed by measuring the time to immobility at a lethally high temperature (Timm at 37°C), and whole body lipid fluorescence polarization (FP) was used as an estimate of membrane fluidity. At all rearing temperatures, EPA supplementation resulted in an increase in the relative abundance of EPA in body tissues, but only at 15° and 25°C did this result in a decrease in heat tolerance, and only at 20°C was this associated with an increase in membrane fluidity (i.e., decrease in FP). Overall, however, the degree of tissue fatty acid unsaturation correlated well with heat tolerance and FP. Our results support the homeoviscous adaptation hypothesis by showing that cold-reared Daphnia accumulate PUFAs within their body tissues and thus are more susceptible to heat than hot-reared Daphnia accumulating fewer PUFAs. However, our data also point out that further studies are required that elucidate the complex relationships between PUFA supply, membrane fluidity, and heat tolerance in ectotherms.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18346号 / 農博第2071号 / 新制||農||1024(附属図書館) / 学位論文||H26||N4853(農学部図書室) / 31204 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 栗原 達夫, 教授 植田 充美, 教授 小川 順 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Yes / There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. Methods and analysis: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. Ethics and dissemination: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. Trial registration number NCT03428477. / The EMT2 trial is funded by Yorkshire Cancer Research (L387) and is sponsored by the University of Leeds. The EMT2 biospecimen collection is funded by the National Institutes of Health (1R01CA243454-01A1) and is sponsored by the University of Leeds ( governance-ethics@ leeds. ac. uk). Both studies have been adopted to the NIHR Clinical Research Network (CRN) Portfolio (CPMS ID 34700 and 47372, respectively) and have benefited from CRN research staff support.

No description available.

Thesis (PhD (Food Science))--University of Stellenbosch, 2006. / Long-chain polyunsaturated fatty acids (LCPUFA), especially the n-3 LCPUFA metabolic products eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play an important role as regulators in many biological processes. To date hake (Merluccius capensis) heads, a rich source of EPA and DHA, have been discarded at sea. The South African Fisheries Policy Development Committee concerned with the environmental impact of this practice has rendered it undesirable. The high prevalence of under-nutrition amongst children in South Africa can be addressed by the supplementation of their diet with this unexploited fish source. The aim of the current study was to develop a microbiologically safe and sensory acceptable sandwich spread using fish flour prepared from fish heads, as a prime ingredient. The intervention trial aimed to compare the effects of an increased dietary intake of n-3 LCPUFA, specifically DHA, on the blood fatty acid levels and absenteeism (as indicator of immune function), as well as the cognitive status, of the subjects. The microbiological content of the sandwich spread was determined after storage for 20 d at 5°C and 15 d at 25°C. Sensory evaluation was performed by consumers (n = 95; M:F = 44:51; 6 – 9 yr) to determine acceptance of the five different flavours individually incorporated into the sandwich spread to mask the fishy note and to provide different flavour options. For the intervention trial subjects (n = 351) were stratified within class group (A - E) and gender and randomly assigned to two treatment categories, an experimental group (EG; n = 174) receiving 25 g sandwich spread.d-1 (191.66 mg DHA. d-1) and a control group (CG; n = 177) receiving an analogous placebo. On school days (104 d), each subject received two sandwiches consisting of two slices of bread (ca. 60 g), spread with 25 g of either the placebo or the experimental spread. Blood samples were drawn at baseline and post intervention. Plasma fatty acid and red blood cell (RBC) membrane status, C-reactive protein levels, as well as vitamin and micronutrient status, were determined. Trained test administrators conducted a battery of cognitive tests. According to South African Government health standards, the sandwich spread remained microbiologically safe after storage. Male and female consumer respondents revealed a significant difference between gender preferences of the five different spread flavours (p <0.05). Significant treatment effects (p <0.05) were observed in n-3 LCPUFA status of the EG, as well as for their absenteeism from school. The two subtests of the Hopkins Verbal Learning test, Recognition and Discrimination Index, showed significant differences between the EG and CG (p <0.05) post intervention in the Grade 2 subjects. The Spelling tests also showed a significant difference between the two groups (p <0.05). In the current study a microbiologically safe and sensory acceptable sandwich spread was developed and tested during an intervention trial, and could possibly in future, provide a healthier option in the School Nutritional Programme. This study proved that supplementation of children (6 - 9 yr) with n-3 LCPUFA, with specific reference to EPA and DHA from a marine source, could have a beneficial effect on their fatty acid status and absenteeism from school. Based on the outcomes of the Hopkins Verbal Learning test and Spelling test, the current study proved that an n-3 fatty acid-rich spread improved the learning ability and memory of children.

Les dernières données de consommation alimentaire de la population française démontrent que les apports nutritionnels en acide eicosapentaénoïque (EPA) et en acide docosahexaénoïque (DHA) sont nettement inférieurs aux recommandations fixées par l’Agence nationale de sécurité sanitaire, de l’alimentation, de l’environnement et du travail (ANSES). Compte tenu de leurs rôles physiologiques, l’amélioration de leur biodisponibilité est devenue une priorité nutritionnelle. La maitrise des formes de vectorisation des acides gras polyinsaturés à longue chaine de la série n-3 (AGPI-LC n-3) représente une piste d’intérêt afin de répondre à cette problématique. C’est dans ce contexte que s’inscrit ce travail de thèse, visant à étudier l’influence de la forme moléculaire (phospholipides (PL) vs triglycérides (TG)) et/ou supramoléculaire (phase continue, émulsion, liposomes) de vectorisation des AGPI-LC n-3 sur leur devenir métabolique.La démarche expérimentale adoptée a consisté, dans un premier temps, à caractériser les différentes formes de vectorisation des AGPI-LC n-3 par un couplage de méthodes d’analyse physico-chimiques (microscopie optique, granulométrie, mesure des produits primaires et secondaires d’oxydation, lipolyse enzymatique). Les données obtenues ont permis de poser des hypothèses mécanistiques pour l’étude de la biodisponibilité chez le rat. Ainsi, dans un deuxième temps, l’étude in vivo a permis d’aborder (1) l’absorption intestinale des acides gras (AG) suite à un apport en bolus de lipides et (2) l’accrétion tissulaire suite à un régime de 8 semaines.Les résultats indiquent que la forme moléculaire de vectorisation des AGPI-LC n-3 (TG marins vs PL marins, en phase continue) n’influence pas leur absorption intestinale mais plutôt leur incorporation dans les lipides lymphatiques, principaux transporteurs des AG alimentaires dans l’organisme. A l’inverse, la structuration des PL marins en milieu aqueux (émulsion ou liposomes), permet d’améliorer l’absorption de l’EPA et du DHA, de façon spécifique à la nature de la structuration supramoléculaire. Les résultats de l’accrétion tissulaire montrent qu’au terme des 8 semaines de régime, l’enrichissement tissulaire en AGPI-LC n-3 s’effectue de façon différente selon leur forme moléculaire de vectorisation. Ainsi, la consommation de TG marins favorise l’incorporation des AGPI-LC n-3 dans les lipides hépatiques, alors que la supplémentation des régimes en PL marins permet d’orienter le DHA vers le cerveau et la rétine.L’ensemble de ces résultats montre que le choix de la forme moléculaire de vectorisation des AGPI-LC n-3 (PL vs TG) peut être un moyen d'orienter leur incorporation tissulaire, alors que leur structuration supramoléculaire (émulsion ou liposomes), une stratégie pour moduler leur absorption intestinale. / The latest data from the cross-sectional national French dietary study show that dietary intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are significantly lower than those recommended by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES). Considering their physiological roles, improving their dietary intake has became a nutritional priority. The control of the different forms of n-3 long chain polyunsaturated fatty (n-3 LC-PUFA) intake represents an interesting way to address this issue. In this context, this thesis aims at studying the influence of the molecular form (phospholipids (PL) vs triglycerides (TG)) and/or supramolecular form (continuous phase, emulsion, liposomes) of n-3 LC-PUFA towards their bioavailability.The experimental approach consisted in characterizing the different forms of n-3 LC-PUFAs by coupling various physicochemical methods (optical microscopy, granulometry, measurement of primary and secondary oxidation products, enzymatic lipolysis). The data obtained made it possible to propose some mechanistic hypothesis for the bioavailability studies conducted in rat. Thus, in a second step, the in vivo study made addresses (1) the intestinal absorption of fatty acids following a single dose of lipids and (2) the lipid tissue accretion following an 8-week diet.The data obtained from the intestinal absorption study indicate that the molecular form of n-3 LC-PUFA targeting (marine TG vs marine PL, in continuous phase) does not influence their intestinal absorption but rather their incorporation into lymphatic lipids, which are the main carriers for dietary fatty acids in the organism. Conversely, structuring marine PL (emulsion or liposomes) improves the EPA and DHA absorption, but differently according to the supramolecular form. The results concerning tissue accretion show that, after 8-week diet, the tissue enrichment in n-3 LC-PUFA is different according to the molecular form of targeting. The consumption of marine TG favours the incorporation of n-3 LC-PUFA into hepatic lipids, while the supplementation of diets with marine PL targets DHA preferentially to brain and retina.All these results show that the molecular form of targeting (PL vs TG) of n-3 LC-PUFA can be a way for managing their tissue incorporation, whereas the supramolecular organization (emulsion or liposomes) can be envisaged to monitor their intestinal absorption.

Três experimentos foram conduzidos para determinar o efeito de fontes lipídicas nos desempenhos reprodutivo e zootécnico de lambaris e a comparação no perfil de ácidos graxos nos tecidos de lambaris selvagens e de cativeiro. Para o experimento de reprodução e de crescimento foram fornecidas, desde a fase larval até o período reprodutivo (11 meses), três dietas elaboradas com diferentes fontes de óleo: soja (SO); óleo de resíduos de tilápia (TI); óleo de resíduo de salmão (SA). No período reprodutivo, os peixes (36 fêmeas e 72 machos) foram induzidos à desova artificialmente e foram avaliados os parâmetros reprodutivos (volume e número total de ovos, taxas de fertilização e eclosão, diâmetro do ovo e comprimento da larva), bem como, o acompanhamento da regeneração ovocitária pós-desova. Observaram-se ovos e larvas maiores e taxas de fertilização superiores na progênie dos peixes alimentados com dietas contendo óleo de peixe, o que pode estar relacionado aos maiores valores da relação n-3/n-6 encontrados nos ovos. Para o experimento de desempenho zootécnico foram utilizados 192 lambaris sexados (espículas na nadadeira anal do macho), sendo 120 machos (peso médio 2,58 ± 0,13g) e 72 fêmeas (peso médio 4,00 ± 0,09g). O Delineamento utilizado foi o Inteiramente Casualizado em Esquema Fatorial 3 x 2, composto por três dietas (SO, TI, SA) e dois sexos. Verificou-se que as fêmeas apresentaram maior ganho em peso, taxas de conversão alimentar e taxa de eficiência protéica mais satisfatórias quando comparados com os machos, os quais apresentaram maior sobrevivência no final do experimento, independente da dieta fornecida. Para o terceiro experimento foram coletados 30 lambaris fêmeas selvagens e 30 fêmeas provenientes do cultivo. Extraíram-se os lipídios dos tecidos (músculo, ovários e fígado) de cada grupo, os quais foram separados (fases apolar e polar) e determinados os perfis de ácidos graxos. Os resultados foram submetidos a ANOVA e diferenciados pelo teste F. Os lambaris de ambos os grupos apresentaram em média 3,5g.100g-1 de teor de gordura no músculo. Os ovários dos peixes selvagens apresentaram a maior concentração de lipídios (14,447g.100g-1) quando comparados com os de cativeiro (13,181g.100g-1). A dieta não conseguiu suprir a quantidade mínima de importantes ácidos graxos no lipídio total e frações dos tecidos das fêmeas provenientes do cultivo em relação às selvagens. O ácido linolênico, considerado essencial para peixes de água doce, esteve presente em menores quantidades no lipídio total e nas frações polar e apolar nos tecidos dos lambaris cultivados, o que pode estar relacionado com deficiência em dietas comerciais para peixes onívoros. Com base nos resultados observados nos experimentos de reprodução e desempenho, sugere-se a inclusão de óleo de resíduos de tilápia e salmão na ração de peixes de lambaris. Ainda foi observado que os lambaris são capazes de elongar e dessaturar os ácidos graxos com 18 carbonos na cadeia, para a produção de Ácidos Araquidônico (AA), Eicosapentaenóico (EPA) e Docosahexaenóico (DHA), devido às baixas quantidades desses ácidos graxos na dieta e posterior aumento nos tecidos. / Three trials were conducted to determine the effect of lipid sources on lambari reproductive and growth performances as well as to make the comparison in the fatty acid profiles in tissues of lambari wild and captive. For the reproduction and growth performances were provided since the larval stage until the reproductive period (11 months), three diets containing different sources of oil: soybean oil (SO); tilapia waste oil (IT); salmon waste oil ( SA). During the reproductive period, fish (36 females and 72 males) were artificially induced to spawn and the reproduction parameters (volume and total number of eggs, fertilization and hatching rates, egg diameter and larval length) were evaluated, as well as monitoring of oocyte regeneration post-spawning. It were observed larger eggs and larvae and higher fertilization rate in the progeny of fish fed diets containing fish oil, which may be related to higher n-3/n-6 ratio values found in the eggs. For the trial of growth performance were used 192 sexed lambaris (male anal fin spines) with 120 males (mean weight 2.58 ± 0.13g) and 72 females (mean weight 4.00 ± 0.09g). The fish were separated on a random method in a factorial scheme 3 x 2, composed by three diets (SO, TI e SA) and two sexes. It was verified that females had higher weight gain, improved feed conversion and protein efficiency rates than males, which showed higher survival at the end of the trial, regardless of diet. In the third trial were collected 30 wild and 30 captive females. The lipids of tissues (muscle, liver and ovary) were extracted from each group and were separated (polar and non polar) and thus determined the fatty acids profiles. The results were analyzed by ANOVA and F test. The lambaris of both groups had mean of 3.5g.100g-1 in the muscle and the wild fish ovaries showed the highest concentration of lipids (14.447g.100g-1) than farming fish (13.181 g.100g-1). The diet failed to supply the minimum amount of important fatty acids in fractions and total lipids of cultivate females and these evidences were higher in the ovaries. Linolenic acid which is considered essential for freshwater fish, was present in smaller amounts in total lipids and polar and nonpolar fractions in all tissues of the cultivated lambari, which may be related to default in commercial diets for omnivores fish. In view of parameters observed in reproduction and growth trials, it can be suggest the inclusion of waste tilapia and salmon oil in lambari broodstock diet. Also it was observed that lambaris have the capacity elongation and desaturation of fatty acids with 18 carbons in the chain for the Arachidonic Acid (AA), Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) production due to low amount of these fatty acids in the diet and the increase in the tissues.

Made available in DSpace on 2014-07-29T15:23:45Z (GMT). No. of bitstreams: 1 DEBORA CALDAS MARQUES.pdf: 1050150 bytes, checksum: fcd394299d813475550612fa84f0fda8 (MD5) Previous issue date: 2011-06-30 / Introduction: Cancer cachexia is characterized by weight loss, immunosuppression, and is associated with a worse prognosis and quality of life. Objectives: The aim of this study was to evaluate the effects of &#969;-3 supplementation on nutritional and functional status and quality of life of patients with gastrointestinal cancer. Methodology: The placebo group (n = 10) received 7 caps containing 1000 mg soya oil, and the supplement group (n = 11) received 7 caps of 1000 mg fish and flaxseed oil, containing 214.3 mg of EPA and 113.5 mg of DHA, daily, for 14 days. Were assessed weight, body composition, inflammatory and immunological markers, functional status and quality of life. Results: The average weight variation of P group before and after treatment was -0.44 ± 2.7 kg and for S group was 0.07 ± 1.4 kg, with no significant differences. The average BMI of the sample was 20.5 ± 3.4 kg/m2. Significant reduction of serum total protein (p=0.005) and albumin (p=0.011) for the P group, increased levels of CRP (p=0.005), and reduction of TLC (p=0.037). An increase of serum transferrin of S group (p=0.010) and reduced levels of CRP (p=0.033) and cortisolemia (p=0.006). It was found to increase KPS (p=0.020) in group S. No differences were found for functional status, symptoms and global health. Conclusions: This study found results that support the supplementation of &#969;-3 in oncology. However, further investigations are necessary involvement &#969;-3 associated to other therapeutic strategies. / Introdução: A caquexia do câncer é caracterizada pela perda ponderal, imunossupressão, e está associada a um pior prognóstico e qualidade de vida. Objetivos: O objetivo deste estudo foi avaliar o efeito da suplementação de &#969;-3 sobre o estado nutricional, capacidade funcional e qualidade de vida de pacientes com câncer gastrointestinal. Metodologia: O grupo placebo (grupo P) (n=10) recebeu 7 cápsulas de 1000 mg de óleo de soja, e o grupo suplemento (grupo S) (n=11) 7 cápsulas de 1000 mg de óleo de peixe e linhaça, contendo 214,3 mg de ácido eicosapentaenóico e 113,5 mg de ácido docosahexaenóico, diariamente, por 14 dias. Foram avaliados o peso, composição corporal, marcadores inflamatórios e imunológicos, capacidade funcional e qualidade de vida. Resultados: A média de variação de peso do grupo P antes e depois do tratamento foi de -0,44 ± 2,7 kg e do grupo S foi de 0,07 ± 1,4 kg, sem diferença estatística. A média de IMC da amostra foi de 20,5 ± 3,4 kg/m2. Houve redução significativa dos níveis séricos de proteínas totais (p=0,005) e albumina (p=0,011) para o grupo P; aumento dos níveis de proteína C reativa (p=0,005), e redução da Contagem Total de Linfócitos (p=0,037). Verificou-se aumento dos níveis séricos da transferrina do grupo S (p=0,010), bem como redução dos níveis de PCR (p=0,033) e na cortisolemia (p=0,006). Encontrou-se aumento para KPS (p=0,020) no grupo S. Não foram encontradas diferenças para Status funcional, Sintomas e Saúde global. Conclusões: O presente estudo encontrou resultados que dão suporte à suplementação de &#969;-3 em oncologia. No entanto, são necessárias maiores investigações associando os &#969;-3 a outras estratégias terapêuticas.

Doctor of Philosophy / Introduction Cachexia is characterised by a marked weight loss and the presence of anorexia, anaemia, and asthenia. Although cachexia is often associated with the presence and growth of tumour and observed in solid tumours of the upper gastrointestinal tract, its presence is not unique to cancer and is often also present in most chronic, end-stage diseases processes. The loss of body fat, altered lipid metabolism, increase in the resting energy expenditure, and the increased loss of body protein the degree of which is associated with poor survival, are all hallmarks of this detrimental disease. The clinical aspects and consequences of cachexia can simply be summarised as morbidity, debilitating conditions, and mortality. The conditions such as loss of muscle mass, impaired muscle function, fatigue, reduced activity and functional capacity by themselves are enough to severely and significantly affect the patients’ QL. Although different interventional procedures and therapies are available for the treatment of cachexia and its symptoms, effective methods to evaluate their benefits and outcomes have not been tested or investigated. It was, therefore, the aim of this project to use body composition analysis as a clinical tool and evaluate the effectiveness and outcome of interventional and therapeutic procedures in three groups of patients with cancer. Methods Three patient groups were investigated: 1) patients with pancreatic cancer undergoing Whipple’s Procedure, 2) patients with pancreatic cancer undergoing cancer chemotherapy and receiving either EPA or placebo, and 3) patients with malignant mesothelioma undergoing cancer chemotherapy plus thalidomide or thalidomide alone. Body composition analysis techniques were used to assess the changes in TBN, TBF, TBK, and TBW. In addition, the body composition parameters together with clinical measures were also used to determine parameters influencing survival. The malignant mesothelioma patients were randomised into patients who received gemcitabine / cisplatin plus thalidomide and those who received thalidomide alone. The pancreatic cancer patients undergoing chemotherapy were randomised into the group who were receiving EPA and those who were receiving placebo. In addition, these patients were also investigated on the basis of their disease extent where they were separated into two groups of metastatic and locally advanced. Unpaired T-Test and ANOVA were used to determine differences between groups. Kaplan-Meier analysis and Cox’s Regression were used to assess survival in all three patient cohorts. The Whipple’s Procedure patients were separated into those who received a Clear Margin and those who received an Unclear Margin during their resection. Results 1) In the pancreatic cancer patients undergoing Whipple’s Procedure, compared to the base-line, there were highly significant changes in Weight (p=0.006), BMI (p=0.005), and FM (p=0.007) followed by significant changes in %BFat (p=0.016), TBK/Ht (p=0.021), LBM (By TBK) (p=0.023), LBM (Van Loan) (p=0.034), and LBM (Segal) (p=0.038) at the 14 week time-point. At the 26 weeks post-operative time point, the only significant changes were in the FM (p=0.012), %BFat (p=0.003), and BMI (p=0.027) parameters. There was also a deviation between the two groups in their TBN, LBM and TBW content observable in a long-term setting and fat content in the relatively shorter-term. Although the Unclear Margin group had lower body composition values, both groups seem to begin to gradually “equalise” around the 14 weeks post-operative time-point. The survival analysis results for the Whipple’s Procedure patients demonstrated that Margin Status (p=0.001), Fat Mass (p=0.003) and Age (p=0.081) were significant and could influence survival. 2) When the second cohort pancreatic cancer patients undergoing chemotherapy were analysed, they were initially separated according to the extent of their disease The results of the analyses of body composition changes between measurement time-points for the each group separately, suggested that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis showed that the metastatic group are performing “worse” than the locally advanced group especially in term of their Dyspnoea, Nausea & Vomiting, and Sexuality. In addition, the Karnofsky score showed that the metastatic group are not performing as well as the locally advanced group. Furthermore, for the metastatic group there was an increase in the patients’ pain with a decline in mood and general performance as well as increase in gastrointestinal symptoms. Pain Card scores also showed a general increase for the metastatic group and a general decrease for the locally advanced group. When the pancreatic cancer patients undergoing chemotherapy were separated according to whether they received EPA or placebo, the results demonstrated that firstly, due to the fact that the patients were well randomised, the two groups commenced the trial with similar and statistically non-significantly different body composition parameters. Secondly, the two groups were also found to be statistically not different at their corresponding measurement time-points. And thirdly, the patients receiving placebo compared to those receiving EPA lost more Weight, and FM but less TBW throughout the trial. The TBK/Ht (p=0.044), TBK (p=0.042), and LBM (By TBK) (p=0.042), however, showed statistically significant differences where in all three parameters the EPA showed an increase compared to the base-line (pre-chemotherapy). Results of the survival analysis demonstrated that the use of EPA in this group of pancreatic cancer patients did not provide any benefit. In fact, as it was shown in the Kaplan-Meier plot, the group of patients receiving the EPA had a “worse” survival than the group receiving the placebo. The QL results showed that placebo group improved in their functional scales, but increased their Altered Bowel Habit scores with an increase in the perception of pain and decrease in relief from pain. The EPA group, however, showed a decrease in the Loss of Appetite, Dyspnoea, Pain, Pancreatic Pain, and Fatigue, and improvements in Role Functioning and Sexuality. 3) Results of the malignant mesothelioma patients demonstrated that both study arms show similar weight changes. In addition, body composition measurements indicated that the gemcitabine / cisplatin chemotherapy plus thalidomide group had a greater TBN loss and a greater TBW gain than the thalidomide-alone group. This loss of TBN and gain in TBW looked to be “concealed” in the weight. The results of the survival analysis carried out on the mesothelioma patient group suggested that haemoglobin levels (p=0.001), Age (p=0.007), and NI (p=0.008) are the parameters that can influence the survival of patients with malignant mesothelioma undergoing chemotherapy. Conclusions 1) The trend in body composition changes in the Whipple’s Procedure group showed that, although both groups may start with non-significantly different body composition, they tended to grow closer around the 14 week point indicating that the Clear Margin group may lose more than Unclear Margin group. The implications of these findings, therefore, were that once the most appropriate surgical procedure is performed, an adjuvant therapy regimen (such as chemotherapy) at around 14 weeks may have the most impact on the patient’s overall treatment outcome. 2) When the pancreatic cancer patients were separated by the extent of their disease, the results lead to the conclusion that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis concluded that the results may point to a worsening and/or progressing disease which is consistent with classic metastatic disease aetiology. From the results of the pancreatic cancer patients undergoing cancer chemotherapy it was concluded that the use of EPA in this group of pancreatic cancer patients undergoing cancer chemotherapy with gemcitabine results in a non-significant reduction in weight loss, FM loss, and TBW gain with a statistically significant increase in FFM. The results of the survival analysis was, however, contradictory suggesting that patients receiving EPA may have a worse survival than the placebo group. The QL analysis here concluded that that EPA does improve the QL of this group of pancreatic cancer patients. 3) From the malignant mesothelioma group it was concluded that provided that the overall anti-cancer potential of gemcitabine / cisplatin plus thalidomide is comparable with that of thalidomide-alone, then by looking purely from the body composition angle one may be able to suggest the use of thalidomide alone in the treatment of malignant mesothelioma in this group of patients. From the results of the survival analysis, the fact that the Study Arm parameter did not reach statistical significance could indicate that survival in these patients is not affected by the presence or absence of chemotherapy with gemcitabine and cisplatin. The body composition techniques were used here as a tool to monitor changes in various body composition parameters to assess the outcomes, including survival, of the administration of different therapies and interventional procedures in these three groups of cancer patients. For these purposes, these techniques were demonstrated to be an effective and invaluable tool.

The effect of fish consumption on the risk of cardiovascular disease has been extensively studied. Omega-3 fatty acids present in fish, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been found to have beneficial effects through several mechanisms. In addition, selenium, an antioxidant, may be protective. Fish also represents the main human exposure source to the pollutant methylmercury (MeHg), which is associated with elevated cardiovascular risk in previous studies. The aim of this thesis was to evaluate whether MeHg is associated with the risk of myocardial infarction (MI) or stroke, whether EPA+DHA or selenium (Se) have protective associations, and if the overall association between fish consumption and risk of stroke or MI is detrimental or protective. A prospective incident case-control study design was used to study effects on stroke or MI. Three hundred and sixty-nine cases with twice as many matched controls were included in the study on stroke, while 431 cases with 499 controls participated in the MI study, all from the Northern Sweden Health and Disease Study. The data was collected from health examinations of the population from 1986 until 1999. Also, time trends in burdens of mercury (Hg), lead (Pb) and cadmium (Cd) in erythrocytes (Ery) from 1990 to 1999 were examined. The food frequency questionnaire (FFQ) used in the case-control studies was correlated with measurements of fatty acids in erythrocyte membranes as biomarkers of intake. In this northern Swedish population, levels of Ery-Hg and Ery-Pb decreased during the 1990´s, but Ery-Cd decreased only in smoking men. No significant associations were found between Ery-Hg or levels of EPA+DHA and the risk of stroke. Men reporting fish consumption &gt;3 meals/week had an elevated risk of stroke. In the MI study, higher levels of Ery-Hg were associated with lower risk of MI. No clear associations were found for reported fish consumption, levels of EPA+DHA or Ery-Se. The validated FFQ has a fair reliability in estimating intake of fatty acids EPA and DHA. However, the low variation in fish consumption in the general population in combination with different versions of the FFQ (with pre-defined, multiple choice alternatives) decreased the reliability of self-reported fish consumption in the case-control studies on risk of stroke or MI. In conclusion, MeHg has no harmful association regarding the risk of stroke or MI in this population with generally low exposure levels. The protective association regarding risk of MI is probably due to Ery-Hg being a biomarker for consumption of fish, a source of other beneficial nutrients. Thus, in this population the benefits of the nutrients in fish appear to overcome the potential harm of MeHg. The finding of elevated stroke risk related to high fish consumption in men will be investigated further. / PHIME; Public health impact of long-term, low-level mixed element exposure in susceptible population strata