Dietary n-3 polyunsaturated fatty acids (PUFA) have been shown to potently attenuate T cell-mediated inflammation, in part, by suppressing T cell activation and proliferation. Apoptosis is an important mechanism for preventing chronic inflammation by maintaining T cell homeostasis through the contraction of populations of activated T cells. We hypothesized that dietary n-3 PUFA would promote T cell apoptosis, thus, providing an additional mechanism to explain the anti-inflammatory effects. We specifically examined activation-induced cell death (AICD) since it is the form of apoptosis associated with peripheral T cell deletion involved in immunological tolerance and T cell homeostasis. Female C57BL/6 mice were fed diets containing either n-6 PUFA (control) or n-3 PUFA for 14 d. Splenic T cells were stimulated with CD3/CD28, CD3/PMA, or PMA/Ionomycin for 48 h followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide and flow cytometry. Cytokine analyses revealed that n-3 PUFA enhanced AICD only in T cells expressing a Th1-like cytokine profile (high IFN, low IL-4) compared to mice fed the n-6 PUFA control diet. Dietary n-3 PUFA significantly altered the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in T cell membranes. To examine the apparently selective effect of dietary n-3 PUFA on AICD in Th1 cells, CD4+ T cells were polarized in vitro to a Th1 phenotype by culture with IL-4, IL-2, and IL-12 for 2 d, followed by culture with IL-2 and IL-12 for 3 d in the presence of diet-matched homologous mouse serum (MS) to prevent loss of cell membrane fatty acids. Following polarization and reactivation, we observed that n-3 PUFA enhanced Th1 polarization and AICD only in cells cultured in the presence of MS, but not in fetal bovine serum. The n-3 PUFA enhancement of Th1 polarization and AICD was associated with the maintenance of diet-induced changes in EPA (20:5n-3) and DHA (22:6n-3) in plasma T cell membrane lipid rafts. Overall, these results suggest that dietary n-3 PUFA enhance both the polarization and deletion of pro-inflammatory Th1 cells, possibly as a result of alterations in lipid raft fatty acid composition.

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.

[Formulae and special characters can only be approximated here. Please see the pdf version of the Abtract for an accurate reproduction.] Type 2 diabetes at least doubles the risk of cardiovascular disease. This can partly be explained by the increased prevalence of risk factors such as hypertension, dyslipidaemia and obesity. However, the underlying abnormality of insulin resistance and the presence of more recently identified risk factors including endothelial dysfunction, increased inflammation, and increased oxidative stress might also contribute towards the heightened cardiovascular risk. Fish oil, which contains eicosapentaenoic acid (EPA, 20:5 n-3), has wide-ranging beneficial effects on these and other abnormalities, and has reduced cardiovascular mortality in secondary prevention studies. Animal and human studies have recently established that in addition to EPA, docosahexaenoic acid (DHA, 22:6 n-3) also has beneficial effects, and furthermore, may have less detrimental effects than EPA on glycaemic control which has worsened in some fish and fish oil studies involving Type 2 diabetic subjects. Study 1 : This intervention study aimed to determine the independent effects of EPA and DHA on cardiovascular risk factors and glycaemic control in individuals with Type 2 diabetes receiving treatment for hypertension. In a double-blind placebo-controlled trial of parallel design, 59 subjects in good to moderate glycaemic control (HbA1c < 9%) were recruited from media advertising and randomised to 4 g/day of EPA, DHA or olive oil (placebo) for 6 weeks. Thirty-nine men and 12 post-menopausal women aged 61.2±1.2 yrs completed the study. Relative to placebo, and with Bonferroni adjustments for multiple comparisons, serum triglycerides fell by 19% (p=0.022) and 15% (p=0.022) in the EPA and DHA groups respectively. There were no changes in serum total cholesterol, or LDL- and HDL-cholesterol, although HDL2-cholesterol increased 16% with EPA (p=0.026) and 12% with DHA (p=0.05). HDL3-cholesterol fell by 11% (p=0.026) with EPA supplementation and LDL particle size increased by 0.26±0.10 nm (p=0.02) with DHA. Urinary F2-isoprostanes, an in-vivo marker of oxidative stress was reduced by 19% following EPA (p=0.034) and by 20% following DHA. DHA but not EPA supplementation reduced collagen-stimulated platelet aggregation (16.9%, p=0.05) and thromboxane release (18.8%, p=0.03), but there were no significant changes in PAF-stimulated platelet aggregation. Fasting glucose rose by 1.40±0.29 mmol/l (p=0.002) following EPA and 0.98±0.29 mmol/l (p=0.002) following DHA. Neither EPA nor DHA had any significant effect on HbA1c, fasting serum insulin or C-peptide, insulin sensitivity, stimulated insulin secretion, 24-hr ambulatory blood pressure and heart rate, markers of inflammation, and fibrinolytic or vascular function. Study 2 : This study aimed to examine the influence and causes of increased inflammation on vascular function in subjects recruited for Study 1. Compared with healthy controls (n=17), the diabetic subjects (n=29) had impaired flow-mediated dilatation (FMD) (3.9±3.0% vs 5.5±2.4%, p=0.07) and glyceryl-trinitrate mediated dilatation (GTNMD) (11.4±4.8% vs 15.4±7.1%, p=0.04) of the brachial artery. They also had higher levels of the inflammatory markers C-reactive protein (2.7±2.6 mg/l vs 1.4±1.1 mg/l, p=0.03), fibrinogen (3.4±0.7 g/l vs 2.7±0.3 g/l, p<0.001) and tumor necrosis factor-alpha (20.9±13.4 pg/l vs 2.5±1.7 pg/l, p<0.001). In diabetic subjects, after adjustment for age and gender, leukocyte count was an independent predictor of FMD (p=0.02), accounting for 17% of total variance. Similarly, leukocyte count accounted for 23% (p<0.001) and IL-6 for 12% (p=0.03) of variance in GTNMD. Von Willebrand factor, a marker of endothelial cell activation was correlated with leukocyte count (r=0.38, p=0.04), FMD (r=-0.35, p=0.06) and GTNMD (r=-0.47, p=0.009), whilst P-selectin, a marker of platelet activation was correlated with fibrinogen (r=0.58, p=0.001). Conclusion : EPA and DHA have similar beneficial effects on triglycerides, HDL2 cholesterol and oxidative stress in individuals with Type 2 diabetes and hypertension. However, DHA also increases LDL particle size and reduces collagen-stimulated platelet aggregation and thromboxane release, thus offering more potential than EPA as an anti-thrombotic agent. The beneficial effects of both oils were potentially offset by deterioration in glycaemic control. Neither oil affected blood pressure or vascular function. Longer-term studies with major morbidity and mortality as the primary outcome measures are required to assess the overall benefits and risks of EPA and DHA. The cross-sectional observations from Study 2 are consistent with the hypothesis that impaired vascular function in individuals with Type 2 diabetes and hypertension is at least in part secondary to increased inflammation, with associated endothelial and platelet activation.

The thesis deals with beneficial omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their beneficial effects on health. Characteristics, properties and appearance of omega-3 fatty acids may explain some of the mechanisms of their effects on human health manifested not only in the treatment and mitigation of some non-infectious diseases of mass occurrence, but especially in the area of preventive action. Theoretic information used in the first part of this work was obtained from scientific and professional publications and periodicals searched in domestic and international databases of scientific and specialist literature. The part of data collection and analysis compares the intake of omega-3 acids in the form of fish dishes prepared for children in the first half of elementary school, aged 7 to 10 years, in randomly selected school canteens or contracted catering in the European Union with the recommendations of Decree 107/2005 Sb. Ministry of Education.

Made available in DSpace on 2015-04-17T15:03:05Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 503890 bytes, checksum: 99e21ac9bda74afe0bcd03f4094569ee (MD5) Previous issue date: 2010-03-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The literature has several studies showing the anti-inflammatory and protective against cardiovascular disease, the polyunsaturated fatty acids are omega-3 intake of fatty acids has been recommended as a way to prevent heart disease and improve heart function. There are few studies involving the anti-inflammatory effect of fatty acids omega-3, with the inflammatory process triggered by physical stress of great magnitude. The effect of supplementation of polyunsaturated fatty acids (PUFA) omega-3 (n-3) in the immune response and occurrence of muscle damage in soldiers were investigated. Twenty males were divided in two groups and they received capsules contends PUFA n-3 (SUP) (n=10) or placebo (PLA) (n=10) during four weeks. in elapsing of the fourth week of supplementation, the military were submitted to a military camp with caloric ingestion and restricted rest, and elevated physical and psychological stress. The concentration of C-reactive protein (CRP-hs) was used as inflammatory marker and the occurrence of muscle damage by creatine kinase s (CK) activity. Sanguine samples were taken in four moments: 1) before supplementation; 2) before camp; 3) during camp; 4) after camp. During the three weeks of supplementation that preceded the camp s routine, was observed a significant reduction in serum CRP-hs s concentration only in group SUP. A significant increase of CK activity in the after camp, confirmed the character strenuous of this procedure. In spite of not impeding the PCR-us s increase, SUP presented a concentration of PCR-hs significantly smaller than PLA at the end of camp. These results suggest that PUFA n-3 supplementation exercises a protecting effect against the inflammatory process induced by intense physical training and alimentary restriction / A literatura dispõe de vários estudos que comprovam o efeito antiinflamatório e protetor contra doenças cardiovasculares, que os ácidos graxos poliinsaturados Ômega-3 possuem A ingestão destes ácidos graxos tem sido recomendada, como forma de prevenir doenças cardíacas e melhorar a função cardíaca. Existem poucas pesquisas associando o efeito antiinflamatório dos ácidos graxos Ômega-3, com o processo inflamatório desencadeado pelo estresse físico de grande magnitude. O efeito da suplementação de ácidos graxos poliinsaturados (AGPI) omega-3 (n-3) na resposta imunológica e ocorrência de dano muscular em militares foi investigado. Vinte sujeitos foram divididos em dois grupos e receberam cápsulas contendo AGPI n-3 (SUP) (n=10) ou placebo (PLA) (n=10) durante quatro semanas. No decorrer da quarta semana de suplementação, os militares foram submetidos a um acampamento militar com ingestão calórica e repouso restrito e elevado estresse físico e psicológico. A concentração de proteína C-reativa ultra-sensível (PCR-us) foi utilizada como marcador inflamatório e a ocorrência de dano muscular pela atividade da enzima creatinoquinase (CK). Amostras sanguineas foram coletadas em quatro momentos: 1) présuplementação; 2) pré-acampamento; 3) durante o acampamento; 4) pós-acampamento. Durante as três semanas de suplementação e que antecederam o regime de acampamento foi observada uma redução significativa na concentração sérica de PCR-us apenas no grupo SUP. Um aumento significativo da atividade da CK no pós-acampamento confirmou o caráter extenuante deste procedimento. Apesar de não impedir a elevação da PCR-us, o grupo SUP apresentou uma concentração de PCR-us significativamente menor em comparação com o grupo PLA ao final do acampamento. Estes resultados sugerem que a suplementação de AGPI n-3 exercem um efeito protetor contra o processo inflamatório induzido por um regime de treinamento físico intenso e restrição alimentar.

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.

Orientador: Maria Julia Marques / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-19T19:42:06Z (GMT). No. of bitstreams: 1 Machado_RafaelVentura_D.pdf: 18399994 bytes, checksum: 2db06c9364e5b215f2cf4f91753c4d19 (MD5) Previous issue date: 2011 / Resumo: Na distrofia muscular de Duchenne e no camundongo mdx a proteína distrofina está ausente ou é expressa de forma não funcional. Com isso, o complexo distrofina-glicoproteínas se desorganiza, a fibra muscular se torna frágil durante os ciclos de contração e relaxamento muscular, as concentrações intracelulares de cálcio e radicais livres se elevam, resultando em necrose da célula. A inflamação mediada por células do sistema imunológico e citocinas pró-inflamatórias, como o TNF-alfa, é um evento importante diretamente relacionado com a progressão da doença. O ácido eicosapentaenóico (EPA) é um ácido graxo poli-insaturado ômega-3 que promove benefícios em doenças inflamatórias em humanos. No presente trabalho analisamos os efeitos do EPA no estágio inicial da distrofinopatia do camundongo mdx. Camundongos mdx com 14 dias de idade receberam 300 mg/kg/dia de EPA por 16 dias. Os grupos controle mdx e C57BL10 receberam óleo mineral. EPA diminuiu a mionecrose, os níveis séricos da enzima creatinoquinase e o TNF-alfa em músculos esqueléticos distróficos. Sugere-se que o EPA tenha utilidade terapêutica nas distrofinopatias / Abstract: In Duchenne muscular dystrophy (DMD) and in the mdx murine model of DMD, lack of dystrophin leads to myonecrosis and cardiorespiratory failure. The intense inflammatory reaction, mediated by immune cells and TNF-alpha, contributes to the progressive myonecrosis. The eicosapentaenoic acid (EPA) is an omega-3 fatty acid that shows beneficial effects in inflammatory diseases. In the present study, we examined the effects of EPA on the early stages of dystrophy in mdx mice. Mdx mice (14 days old) received EPA at 300 mg/kg EPA for 16 days, while the control mdx mice and C57BL10 received vehicle. EPA treatment decreased creatine kinase and TNF-alpha levels and reduced myonecrosis. The present results support further studies with EPA as a potential therapy for dystrophinopathies / Doutorado / Anatomia / Doutor em Biologia Celular e Estrutural

<p>\ / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Lipids are essential components for fish because they contain fatty acids that are vital for regular growth and health. Fish oil is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential fatty acids for carnivorous fish, and therefore this product has traditionally been used as the main source of lipids in fish feeds. However, with declining fisheries resources worldwide and the rapid expansion of the aquaculture industry pressuring this finite resource, such ingredients are becoming less available and more expensive. It is therefore necessary to explore the utilization of ingredients that are sustainable and competitive alternatives to fish oil in marine finfish feeds. This work investigated the effects of the substitution of fish oil with soybean oil on the growth performance, feed efficiency, fatty acid composition of the liver tissue and some health parameters in juvenile dusky kob, Argyrosomus japonicus; an increasingly popular sciaenid marine aquaculture species in South Africa. Six diets (18 % total lipid and 46 % protein) with increasing percentage substitution of fish oil with soybean oil (1, 14, 28, 42, 56 and 70 %) were fed to juvenile kob. After 84 days of feeding these diets to the fish, no significant differences in fish length and weight between treatments were observed. However, there was a significant trend of a decrease in specific growth rate, ranging from (± standard error) 0.87 ± 0.06 to 0.72 ± 0.04 % body weight day⁻¹, and condition factor, ranging from 1.59 ± 0.03 to 1.54 ± 0.02, with increasing vegetable oil replacement in the diets between days 56 and 84. There were no differences in red blood cell count, haematocrit and haemoglobin concentration after 206 days of feeding. However, visceral fat index (VFI) increased significantly from 1.08 ± 0.17 % for fish fed diets with 28 % soybean oil, to 2.24 ± 0.15 % for fish fed diets with 70 % soybean oil. Similarly, hepatosomatic index (HSI) increased significantly from 0.84 ± 0.08 % to 1.80 ± 0.12 % in the control diet and the 56 % soybean oil diet, respectively. After 206 days of feeding, fish fed diets with 42 to 70 % soybean oil showed greater number of lipid vacuoles in the liver, which were also larger in size, and hepatocytes nuclei were displaced to the cell periphery. The fatty acid composition of the liver tissue strongly corresponded to the fatty acid composition of the diets. Linoleic acid accumulated in the liver of the fish fed increasing soybean oil in the diets. In contrast, EPA and DHA decreased from 13.63 to 1.97 %, and 14.34 to 3.28 %, respectively, in the liver tissue of fish fed diets with increasing soybean oil content; consequently the n-3/n-6 ratio was also significantly reduced with inclusion of vegetable oil in the diets. The trend of decreasing growth rate with increasing oil replacement towards the end of the trial corresponds with increases in VFI, HSI, as well as the fatty acid accumulation and lipid vacuoles in the liver. This suggests that dusky kob is less able to metabolise soybean oil at increased substitution levels which would account for the poorer growth at higher levels. The dependence of fish on dietary marine oil decreased significantly with each inclusion of soybean oil in the diets. Nonetheless, the calculations based on the nutrient ratio presented positive outcomes for all treatments, that is, values of marine oil dependency ratio were below one for all treatments. It is concluded that soybean oil can replace fish oil in formulated diets for dusky kob up to a level of 28 % of total dietary lipids, as evidenced by the good growth and feed efficiency, and no apparent negative health effects observed up to this level.

Purpose: To 1) critically appraise available randomized controlled trials (RTCs) addressing the efficacy of long-chain ω-3 fatty acids as a secondary prevention agent of hypertriglyceridemia, and 2) make recommendations for clinical practice. Data Sources: All RCTs identified from several databases from 1993-2003 were reviewed by two independent reviewers who extracted data from each study and used the previously tested Boyack and Lookinland Methodological Quality Index (MQI) to determine study quality. Results: Ten studies reported long-chain ω-3 fatty acids to be effective in the treatment of hypertriglyceridemia. The average decrease in triglycerides (TG) was 29%, total cholesterol (TC) 11.6%, very low density lipoprotein (VLDL) 30.2%, and low-density lipoprotein (LDL) 32.5%. One study found LDLs to increase by 25%. The average increase in high-density lipoprotein (HDL) was 10%. The overall average MQI score was 36% (26%-54%). Many of the RCTs had serious shortcomings including short duration, lack of a power analysis, no intention to treat analysis, no report of blind assessment of outcome, and lack of dietary control as a confounding variable. Conclusions/Implications: Overall study methodology was weak. Although the evidence supporting the use of long-chain ω-3 fatty acids in the secondary prevention of hypertriglyceridemia is reasonably strong, until there are larger RCTs of stronger methodological quality, it is not recommended to treat hypertriglyceridemia with ω-3 fatty acid supplementation in lieu of lipid lowering medications.