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Dietary docosahexaenoic acid (22:6n-3, DHA) has been shown to exert beneficial effects on coronary heart disease including the prevention of ischemia reperfusion injury. The ability to acutely infuse DHA to the heart to prevent ischemia reperfusion injury is a potentialy valuable tool in planned surgery where reperfusion and/or ischemia will take place including coronary artery bypass surgery and angioplasty. In the present study, hearts from chow-fed (AIN-93M) Sprague Dawley rats (male) 9-12 weeks of age were isolated and artificially perfused. The protocol included: 30 min stabilization period, 30 min global no flow ischemia, 15 min fatty acid infusion with reperfusion, and 75 min reperfusion in the absence of fatty acids. The fatty acid infusions included 10, 20, 40, 60, 80, 100 or 120 µM of either palmitate or DHA complexed to 3% essentially fatty acid free bovine serum albumin as well as a vehicle control. Heart functional data was recorded continuously and total heart infarct volume was determined after staining with triphenyltetrazolium chloride. DHA at 10µM significantly reduced the infarction area at the end of the reperfusion period compared to that observed in the10µM of palmitate and vehicle control conditions. Infarction areas after infusions with DHA or palmitate were similar to controls after 20-60 µM infusions and greater than controls after 80-120 µM infusions, except for the 100 µM palmitate conditions which were similar to the low and high doses. In this model of infusion, 120 µM of fatty acid was the maximum amount of DHA tolerated, as several hearts went into fibrillation and did not recover and failed to complete the reperfusion at concentrations greater than 120 µM of DHA. DHA and palmitate also exerted dose dependent effects on functional parameters. In summary, infusion of DHA and palmitate cause dose dependent effects on heart function.

This research examined the quantitative effects of dietary conjugated linoleic acid (CLA) on juvenile cobia Rachycentron canadum with a mean initial weight of 10g and fed for 8 weeks. Four experimental diets that contained 16% crude lipid and 0%, 0.5%, 1.0% or 2.0% CLA were compared. At the end of the growth trial there was no significant differences in growth parameters. With increased CLA supplement, the body lipid content tended to reduce and protein content was significantly decreased. Increased dietary CLA caused significantly decreased hepatic FAS activity. Hepatic ME activity was decreased significantly in 0.5%, 0.75% and 1% CLA treatment, while no significant effect was detected on hepatic G6PDH activity. Total lipid contents of the liver and visceral fatty depot were significant decreased in 0.5%, 0.75% and 1% CLA treatment. There was a significant decrease in lipid content in the ventral muscle when CLA was supplemented at 0.75%, 1% and 2%. Fish fed 0.5% CLA had a lower adipocyte density in dorsal muscle, while fish fed 2% CLA treatment had a larger size of adipocytes in the liver and dorsal muscle. Gene expression of PPAR-£\ and PPAR-£^ showed no definite trend. Significant deposition of CLA was found in the liver, ventral muscle, dorsal muscle and visceral fatty depot of the cobia. The deposition ratio of cis-9, trans-11 CLA was slightly higher than that of trans-10, cis-12 CLA. Dietary CLA also affected the deposition of other fatty acids. Increased dietary inclusion of CLA significantly increased the total percentages of saturated fatty acids (SFA) but significantly decreased polyunsaturated fatty acids (PUFA). However DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) contents of the visceral fatty depot were significantly increased. In terms of immune response, dietary CLA had no effect on respiratory burst activities of head kidney phagocytes. Serum of fish fed 0.5% CLA had significantly increased lysozyme activities. In conclusion, dietary CLA affected the metabolism of lipid and fatty acid composition of cobia juveniles, and enhanced slightly immune responses. As CLA can deposit in the tissues of cobia, production of CLA-containing fish as a functional food is thus possible in cobia through dietary manipulation. An supplemental rate of 0.5% CLA is the optimal concentration considering fish nutrition and cost effectiveness.

(hCysLT2R) based on a β-galactosidase complementation system. The EC50 values for LTC4 and LTD4 are consistent with previous literature values determined based on radio-labelling affinity assays for hCysLT2R. Activity of a synthetic analogue of LTC4, N-Methyl LTC4 (NMLTC4), gave an EC50 value of 8.5 nM. Also described in this thesis, is the synthesis of a cysLT2R selective antagonist, 3-{[(3- carboxycyclohexyl)amino]carbonyl}-4-{3-{4-(4-phenoxybutoxy)phenyl}- propoxy}benzoic acid. Through the in vitro assay system, this selective antagonist showed a dose-dependent inhibition (IC50 value of 86 nM) when CysLT2R was stimulated with 30 nM of LTD4. Both the selective agonist (NMLTC4) as well as the selective cysLT2R antagonist were also tested in vivo in a localized vascular ear inflammation assay. Results show NMLTC4 is able to promote vascular leakage through stimulation of cysLT2R, and this extravasation can be significantly attenuated by the cysLT2R antagonist. / Thesis (Master, Biochemistry) -- Queen's University, 2011-06-29 22:31:03.11