Serum antioxidant capacity, biochemical profile and body composition of breast cancer survivors in a randomized Mediterranean dietary intervention study.

PURPOSE: Increasing evidence suggests that Mediterranean Diet (MD) is correlated with reduced risk of breast cancer (BC) and cancer mortality, since it modifies patients' serum antioxidant capacity, body composition and biochemical parameters. The aim of the study was to investigate whether a dietary intervention based on MD has a beneficial effect on these factors. METHODS: In this intervention study, seventy female BC survivors were randomly assigned to (1) the intervention group (personalized dietary intervention based on MD) and (2) the control group (received the updated American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and ad libitum diet). Both groups were assessed twice [beginning, end of study (after 6 months)] regarding their anthropometric and biochemical parameters, serum vitamin C, vitamin A, a-tocopherol and CoQ10 levels, dietary intake and adherence to MD. An additional intermediate analysis was conducted on participants' body composition and biochemical profile. RESULTS: Concerning the intervention group, body weight, body fat mass, waist circumference, body mass index as well as HDL-cholesterol were significantly decreased (P < 0.2%). An increase was observed in the vitamin C levels in blood (P < 0.2%). In the control group, body weight, body fat mass and serum total cholesterol rose (P < 0.2%). At the end of the study the two groups were significantly different considering blood glucose, vitamin C, polyunsaturated fatty acids, vitamin A and a-tocopherol levels. CONCLUSIONS: This randomized dietary intervention based on MD managed to ameliorate serum antioxidant capacity, body composition, adherence to MD and glycemic profile of postmenopausal BC survivors.

Comparative study of interactions of aliskiren and AT1 receptor antagonists with lipid bilayers.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin is the rate limiting enzyme of the RAAS and aliskiren is a highly potent and selective inhibitor of the human renin. Renin is known to be active both in the circulating blood stream as well as locally, when bound to the (pro)-renin receptor ((P)RR). In this study we have investigated a possible mechanism of action of aliskiren, in which its accumulation in the plasma membrane is considered as an essential step for effective inhibition. Aliskiren's interactions with model membranes (cholesterol rich and poor) have been investigated by applying different complementary techniques: differential scanning calorimetry (DSC), Raman spectroscopy, magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and small- and wide-angle X-ray scattering (SAXS and WAXS). In addition, in silico molecular dynamics (MD) calculations were applied for further confirmation of the experimental data. Aliskiren's thermal effects on the pre- and main transition of dipalmitoyl-phosphatidylcholine (DPPC) membranes as well as its topographical position in the bilayer show striking similarities to those of angiotensin II type 1 receptor (AT1R) antagonists. Moreover, at higher cholesterol concentrations aliskiren gets expelled from the membrane just as it has been recently demonstrated for the angiotensin receptor blocker (ARB) losartan. Thus, we propose that both the AT1R and the (P)RR-bound renin active sites can be efficiently blocked by membrane-bound ARBs and aliskiren when cholesterol rich membrane rafts/caveolae are formed in the vicinity of the receptors.

Interactions of the potent synthetic AT1 antagonist analog BV6 with membrane bilayers and mesoporous silicate matrices.

The present work describes the drug:membrane interactions and a drug delivery system of the novel potent AT1 blocker BV6. This designed analog has most of the pharmacological segments of losartan and an additional biphenyltetrazole moiety resulting in increased lipophilicity. We found that BV6:membrane interactions lead to compact bilayers that may in part explain its higher in vitro activity compared to losartan since such environment may facilitate its approach to AT1 receptor. Its high docking score to AT1 receptor stems from more hydrophobic interactions compared to losartan. X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA) have shown that BV6 has a crystalline form that is not decomposed completely up to 600°C. These properties are desirable for a drug molecule. BV6 can also be incorporated into a mesoporous silicate drug-delivery matrix SBA-15. The properties of the obtained drug-delivery system have been inspected by XRD, (13)C CP/MAS, TGA and nitrogen sorption experiments.