A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Double-diffusive and Soret-induced convection of a micropolar fluid in a vertical channel

AbstractThis paper reports an investigation of the fully developed natural convection heat and mass transfer of a micropolar fluid in a vertical channel. Asymmetric temperature and concentration boundary conditions are applied to the walls of the channel. The cases of double diffusion and Soret-induced convection are both considered. The governing parameters for the problem are the buoyancy ratio and the various material parameters of the micropolar fluid. The resulting non-dimensional boundary value problem is solved analytically in closed form using MAPLE software. A numerical solution of the time dependent governing equations is demonstrated to be in good agreement with the analytical model. The influence of the governing parameters on the fluid flow as well as heat and solute transfers is demonstrated to be significant

Microwave-assisted synthesis and magnetic properties of M-SrFe 12 O 19 nanoparticles

International audienceHard magnetic materials a b s t r a c t Strontium hexaferrite nanoparticles were synthesized by a microwave-assisted hydrothermal process. The variation of structure, morphology and magnetic properties of the as-produced particles and after annealing temperatures were carefully analysed. Pure M-SrFe 12 O 19 powders were synthesized at T = 200 °C using a heating rate of 25 °C.min À1. The particles exhibited a magnetic coercivity of 95 kA.m À1 (m 0 Hc = 0.12 T), explained by the shape of the particles that crystallized as very thin platelets with a micrometer size diameter and a very high aspect ratio in which a competition between shape and magnetocrystalline anisotropy takes place. The coercivity was strongly enhanced with Hc = 360 kA.m À1 (m 0 Hc = 0.445 T) by annealing at the optimum temperature of 1000 °C. In order to optimize the particle morphology and magnetic properties after annealing, the heating rate of the microwave synthesis was increased. At T = 200 °C using a heating rate of 40 °C.min À1 the particle exhibited a size in the range 20–100 nm. The powder crystallized as a mixture of hexaferrite and ferrihydrite. After annealing at 1000 °C, M-SrFe 12 O 19 with a small amount of hematite (<15%) was obtained. The coercivity was strongly enhanced to reach the value Hc = 465 kA.m À1 (m 0 Hc = 0.585 T)