Additional benefit in CVD risk indices derived from the consumption of fortified milk when combined with a lifestyle intervention.

OBJECTIVE: The current study aimed to evaluate the effect of fortified milk combined with a lifestyle and counselling programme on several CVD risk factors after a 3-month dietary intervention. DESIGN: Hypercholesterolaemic adults were randomized to a group supplemented with low-fat milk that was enriched with phytosterols, α-linolenic and linoleic fatty acids, vitamins and antioxidants (enriched milk group, EMG: n 40), a placebo milk group (PMG: n 36) or a control group (CG: n 25). The EMG and PMG consumed respectively 500 ml of enriched milk or placebo milk daily and attended biweekly counselling sessions over a 3-month period. SETTING: Harokopio University, Athens, Greece. SUBJECTS: A sample of 101 hypercholesterolemic adults aged 40-60 years. RESULTS: Regarding lifestyle changes, total and saturated fat intakes decreased significantly in both intervention groups compared with the CG (P < 0·005). Furthermore, total steps were increased (P = 0·029) and BMI was decreased (P = 0·017) significantly in both intervention groups compared with the CG. Regarding biochemical indices, EPA content in erythrocyte membranes increased (P < 0·001) while serum C-reactive protein decreased (P = 0·003) significantly in both intervention groups compared with the CG. Finally, significant increases in plasma folic acid and vitamin B12 levels and a significant decrease in homocysteine levels were observed in the EMG compared with the PMG and CG (all P < 0·001). A favourable change in LDL cholesterol:HDL cholesterol was also observed in the EMG and tended to be significant compared with the PMG and CG (P = 0·066). CONCLUSIONS: The present study showed that consumption of fortified milk accompanied with lifestyle counselling induces extra benefits in terms of LDL cholesterol:HDL cholesterol and serum homocysteine levels.

Differential inhibition of group IVA and group VIA phospholipases A2 by 2-oxoamides.

Inhibitors of the Group IVA phospholipase A(2) (GIVA cPLA(2)) and GVIA iPLA(2) are useful tools for defining the roles of these enzymes in cellular signaling and inflammation. We have developed inhibitors of GVIA iPLA(2) building upon the 2-oxoamide backbone that are uncharged, containing ester groups. Although the most potent inhibitors of GVIA iPLA(2) also inhibited GIVA cPLA(2), there were three 2-oxoamide compounds that selectively and weakly inhibited GVIA iPLA(2). We further show that several potent 2-oxoamide inhibitors of GIVA cPLA(2) containing free carboxylic groups (Kokotos et al. J. Med. Chem. 2002, 45, 2891-2893) do not inhibit GVIA iPLA(2) and are, therefore, selective GIVA cPLA(2) inhibitors.

Synthesis and activity of 2-oxoamides containing long chain beta-amino acids.

2-Oxoamides based on long chain beta-amino acids were synthesized. 1-Benzyl substituted long chain amines, needed for such synthesis, were synthesized starting from Boc-phenylalaninol. The oxidative conversion of a phenyl group to a carboxyl group was used as the key transformation synthetic step. The compounds synthesized were studied for their activity against GIVA PLA(2), and were proven to be weak inhibitors.