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This mixture is a potent constrictor of the bronchial air-way musculature. These leukotrienes together with leukotriene B4, also cause vascular permeability and attraction and activation of leukocytes and are important regulators in many diseases involving inflammatory or immediate hypersensitivity reactions, such as asthma. Leukotrienes are vasoactive and 5-lypoxigenase as been found in artherial walls. Evidence supports a role for lipoxins in vasoactive and immunoregulatory function. (Murray R.K. et al., 2003). Resolvin was discovered in vivo during the resolution phase of inflammation in exudates from inflamed tissues in a mouse model. The main task of resolvin E1 appears to be to serve as a counterregulator to proinflammatory mediators and turn down acute inflammatory processes before too much damage is done to normal tissue (Arita M. et al., 2005). Isofurans are nonclassic eicosanoids formed nonenzymatically by free radical mediated peroxidation of arachidonic acid. The isofurans are similar to the isoprostanes and are formed under similar conditions, but contain a substituted tetrahydrofuran ring. The concentration of oxygen affects this process; at elevated oxygen concentrations, the formation of isofurans is favored whereas the formation of isoprostanes is disfavored (Roberts L.J. et al., 2004). The isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of essential fatty acids (primarily arachidonic acid) without the direct action of cyclooxygenase (COX) enzyme. These nonclassical eicosanoids possess potent biological activity as inflammatory mediators that augment the perception of pain. These compounds are accurate markers of lipid peroxidation in both animal and human models of oxidative stress (Evans A,R. et al., 2000). The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in evolution and which has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide) and 2arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB1 receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behaviour and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system and microcirculation (Rodriguez de Fonseca F. et al., 2005). 5. BIOMARKERS OF OMEGA-3 FATTY ACID NUTRITIONAL STATUS The association of dietary fats with diseases risk or outcome could be determined from epidemiological studies and/or from food frequency questionnaires; however the FA composition of the plasma lipids and the membranes of platelets and erythrocytes provides a better assessment of the the dietary intake of the long-chain n-3 FAs (Bjerve K.S. et al., 1993; Andersen L.F. et al., 1996; Innis S.M. et al., 1988, Brown A.J. et al., 1991). Other investigators have utilized adipose tissue obtained by percutaneous biopsy, for which the turnover time for FAs has been estimated to be 1–3 years; however it must be pointed out that this procedure is not only invasive but also time consuming (Field C.J. et al., 1984). Marckmann P. et al. (1995) found adipose tissue DHA and docosapentaenoic acid (C22:5, DPA) levels to be much higher than that of EPA, although the food record estimates of dietary EPA and DHA intakes were both considerably higher than that of DPA. The apparent discrepancy may have resulted from the elongation of EPA to the less metabolically active DPA. In this study, the DHA content of adipose tissue provided a better marker of fish and marine n-3 FA intake than did EPA, a result that was also obtained by Tjønneland A. et al. (1993). Two other studies provided a comparison of data from food-frequency questionnaires, diet records, and subcutaneous adipose tissue FA content in American postmenopausal women 21
and men, respectively (London S.J. et al., 1991, Hunter D. et al., 1992). Both showed significant correlations between the percentage of n-3 FAs in adipose tissue, and the percentage of n-3 FAs in the diet, as determined by a food-frequency questionnaire. In the study of American males, dietary intakes were also assessed by 7-day diet records, which are generally regarded as more accurate. However, this method of evaluation gave a similar level of correlation to that obtained with the semi-quantitative food-frequency questionnaire, suggesting that the less complex method provides an equally reliable assessment. In neither study were separated the data collected for EPA and DHA and so, there were no results upon which to judge the relative importance of the two n-3 FAs as markers of n-3 FA intake. One point deserves a critical consideration: the evaluation of n-3 FA intake used in this and other epidemiological studies do not distinguish between the types of fish consumed, which, given the wide variations in n-3 content of fish, may reduce the sensitivity of the obtained results. Although the analysis of adipose tissues is necessary to evaluate dietary FA intake over extended periods of time and is unaffected by temporary variations in diet, their acquisition is not amenable to the large-scale sampling required for many epidemiological studies, and the presence of large amounts of nonessential FAs can obscure the relatively low levels of n- 3 FAs. With this in mind, it is encouraging that a carefully executed comparative study by Godley P.A. et al. (1996) found that the EPA and DHA contents of adipose tissue aspirates and erythrocyte membranes had similar correlations with fish consumption, as estimated by a food-frequency questionnaire. PUFA status in Human can be assessed on several blood lipid classes. Erythrocyte phospholipids fatty acid status presents several advantages: (1) it is a reflexion spread over time of habitual dietary fat intake in relation to the biological half life of erythrocytes (Romon M. et al., 1995); (2) the level of EPA can be used as a specific marker for the intake of fish and fish oil ( Brown A.J. et al., 1990); (3) phospholipids are a model of fatty acid incorporation into a cellular membrane; (4) it gives an image of hepatic and extrahepatic fatty acid metabolism; (5) erythrocyte phospholipids are in equilibrium with structural phospholipids of tissues; (6) it has been correlated reasonably well with the food- frequency questionnaire (ffq) for the dietary intakes of polyunsaturated fatty acids (Parra M.S. et al., 2002). However the ffp is time consuming and tedious and can lack accuracy in comparison with the precision of erythrocyte fatty acid measurements. Our studies on the AA/EPA ratio determined on whole-blood as a biomarker of fatty acid intake or supplementation, demonstrate, as also described below, its good correlation with erythrocyte phospholipids composition and its reliability. 6.OMEGA-6/OMEGA-3 PUFA BALANCE AND CHRONIC DISEASES Unbalance PUFA status is observed in numerous conditions and especially in diseases chronic and/or degenerative accompanied by deficiency of the antioxidant system. Thus, the early diagnosis of such impairment is of crucial importance, since it is recognized that the dietary PUFA balance could help in the prevention and the control of such diseases. 6.1. Smoking, hormonal contraception, pregnancy and premenstrual syndrome Free radicals generated in cigarette smoke are known to deplete antioxidants and may result in increased lipid peroxidation which leads to decreased concentrations of long chain PUFA. This may be due to an inhibitory effect of tobacco, or its metabolites on erythrocyte fatty acid metabolism as their PUFA content was decreased. The negative effect of cigarette smoking on PUFA stores may be one further mechanism by which cigarette smoking promotes vascular disease (Pawlosky R. et al., 1999). A potential adverse effect of hormonal contraception on erythrocyte fatty acid status has been observed by increasing some saturated fatty acids such as C16:0 and decreasing other 22
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Page 5 and 6: 10 kg/day of EPA+DHA 2:1 as in Oil4
Page 7 and 8: SUMMARY 1. Olive oil - a strong ant
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Page 11 and 12: acid incorporated into cell membran
Page 13 and 14: Supplementation with omega-3 were l
Page 15 and 16: 18:3 ω-3 ALA 18:2 ω-6 LA Δ6-desa
Page 17 and 18: Figure 3: The cell membrane. The ce
Page 19 and 20: In animal cells cholesterol is norm
Page 21: Figure 5: The three groups of eicos
Page 25 and 26: 6.3. Hypertension Different mechani
Page 27 and 28: function in the dopaminergic synaps
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Page 31 and 32: 8. CLINICAL STUDIES AT THE UNIVERSI
Page 33 and 34: effects were found also in our expe
Page 35 and 36: In the 1994 Diagnostic and Statisti
Page 37 and 38: REFERENCES � Adams P.B., Sinclair
Page 39 and 40: � Byers T., Gieseker K.(1997) Iss
Page 41 and 42: consumption and questionnaire data
Page 43 and 44: � Leitzmann M.F., Stampfer M.J.,
Page 45 and 46: anxiety. Journal of the American Ac
Page 47 and 48: � Thapar A., O’Donovan M., Owen
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