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Fp'CO)+PF6-, 3e [Fp' = (s5-CsMe5)Fe(CO),], is synthesized by reaction of Fp'Br with CO (40 atm) and AlC13 or by reaction of Fp', with Cp2Fe+PF6-in THF under CO (1 atm). Oxidation of Fp', with Cp2Fe+PF6in various coordinating solvents S (THF, acetone, acetonitrile, pyridine) gives (Fp'S)+PFf (3a-d) in high yields. Reaction of (Fp'THF)+PF6-, 3a, with various ligands L (PPh3, P(OPh)3, CO) gives (Fp'L)+PF6-, 3 e g , in high yields; the reaction fails with olefins. 3a also gives Fp'H, 5, with NaBH4 and Fp'SC(S)NMe2, 6a, with NaS2CNMe2, but 6a is obtained in better yield from 3e. Bimetallic complexes [FpSC(NEt& S-.Fp']+PF6-, 6c, and [CpFe(s6-C6Me5CH2)Fp']+PF6-, 7, are also obtained by reaction of 3a with FpSC-(S)NEt2 and Cp(s5-C6Me5CH2)Fe, respectively. Photolysis of 3e or (Fp'NCMe)+PF6-, 3c, in CH3CN gives a 80% yield of the thermally stable, air-sensitive complex [CP'F~(NCM~)~]+PF{, 9, as deep purple crystals.Without degassing, this photolytic reaction gives dark red [Cp'Fe(NCMe),(CO)]+PF6-, 10, also obtained from 9 under 1 atm of CO at 20 "C. 9 also reacts with PPh3 to give [Cp'Fe(NCMe),(PPh3)]+PF6-, 11, with dppe to give [Cp'Fe(NCMe)(s2-dppe)]+PF6-, 12, and with cyclooctatetraene (COT) to give [Cp'Fe($-COT)]+PF6-, 13. The reaction of CO with 11 and 12 gives respectively [Cp'Fe(CO),(PPh3)]+PF{, 3f, also obtained from 3e and PPh3 in refluxing acetone, and [Cp'Fe(CO)(s2-dppe)]+PF -15. Fp'-K+, 16a, obtained from Fp', and K mirror, gives Fp'CH3, 17, upon alkylation with CH31 and $e'-Na+, 16b, obtained from Fp', and Na/Hg, gives Fp'CH20CH3, 18, upon alkylation with C1CH20CH3.

The recently cloned Δ6-desaturase is known to catalyse the first step in very-long-chain polyunsaturated fatty acid biosynthesis, i.e. the desaturation of linoleic and α-linolenic acids. The hypothesis that this enzyme could also catalyse the terminal desaturation step, i.e. the desaturation of 24-carbon highly unsaturated fatty acids, has never been elucidated. To test this hypothesis, the activity of rat Δ6-desaturase expressed in COS-7 cells was investigated. Recombinant Δ6-desaturase expression was analysed by Western blot, revealing a single band at 45kDa. The putative involvement of this enzyme in the Δ6-desaturation of C24:5n-3 to C24:6n-3 was measured by incubating transfected cells with C22:5n-3. Whereas both transfected and non-transfected COS-7 cells were able to synthesize C24:5n-3 by elongation of C22:5n-3, only cells expressing Δ6-desaturase were also able to produce C24:6n-3. In addition, Δ6-desaturation of [1-14C]C24:5n-3 was assayed invitro in homogenates from COS-7 cells expressing Δ6-desaturase or not, showing that Δ6-desaturase catalyses the conversion of C24:5n-3 to C24:6n-3. Evidence is therefore presented that the same rat Δ6-desaturase catalyses not only the conversion of C18:3n-3 to C18:4n-3, but also the conversion of C24:5n-3 to C24:6n-3. A similar mechanism in the n-6 series is strongly suggested.

Objective: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). Design, patients: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). Interventions: 1/ Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6–8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. Baseline population: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. Discussion: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

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-This study was designed to investigate the effect of myristic acid on the biosynthesis and metabolism of highly unsaturated fatty acids, when it is supplied in a narrow physiological range in the diet of the rat (0.2-1.2% of total dietary energy). Three experimental diets were designed, containing 22% of total dietary energy as lipids and increasing doses of myristic acid (0.71, 3.00 and 5.57% of total fatty acids). Saturated fat did not exceed 31% of total fat and the C18:3 n-3 amount in each diet was strictly equal (1.6% of total fatty acids). After 7 weeks, the diets had no effect on plasma cholesterol level but greatly modified the liver, plasma and adipose tissue saturated, monounsaturated and polyunsaturated fatty acid profiles. Firstly, daily intakes of myristic acid resulted in a dose-dependent tissue accumulation of myristic acid itself. Palmitic acid was significantly increased in the tissues of the rats fed the higher dose of myristic acid. A dose-response accumulation of tissue C16:1 n-7 as a function of dietary C14:0 was also shown. Secondly, a main finding was that, among n-3 and n-6 polyunsaturated fatty acids, a dose-response accumulation of liver and plasma C20:5 n-3 and C20:3 n-6 (two precursors of eicosanoids) as a function of dietary C14:0 was shown. This result suggests that dietary myristic acid may participate in the regulation of highly unsaturated fatty acid biosynthesis and metabolism.dietary myristic acid / highly unsaturated FA biosynthesis and metabolism / rat

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