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

Structure and thermal behaviour of (SPY-5-12)-(2-aminoethanol-n)(2-aminoethanol-N,O)-bis(theophyllinato)copper(ii)dihydrate: a model for DNA-metal interactions

The title compound (1) is obtained by mixing aqueous 2-aminoethanol solutions of theophylline and copper(II) salt. According to the single crystal data the CU2+ ion is pentacoordinated and located in a slightly distorted square pyramidal configuration. Four short Cu-N bonds to two N(7) of the theophyllinate anions and to two nitrogen atoms of a monodentate and a bidentate 2-aminoethanol ligands are almost in the plane, while a longer Cu-O bond to oxygen of the bidentate 2-aminoethanol in the apex at distance 2.350(8) Angstrom A. When heated in air or in an inert atmosphere, 1 undergoes a five-step decomposition process studied by TG, DSC and evolved gas detection (EGD). The solid intermediates of the thermal decomposition were detected by FTIR and powder X-ray diffraction. First the water molecules then the mono-and bidentate 2-aminoethanol ligands are released in the order of their binding energy, showing a strong structure-stability correlation. Afterwards chemical degradation of theophyllinato ligands occurs and is accompanied in air by an intense oxidation process resulting in CuO formation. (C) 1997 Elsevier Science Ltd

Assessment Reservoir Temperature of West Georgian Geothermal Deposit by Application of Silica-Enthalpy Mixing Method

This study to use geochemical techniques to evaluate geothermal reservoir in West Georgia. About Thirty thermal water samples were taken from existing thermal boreholes on the territory of West Georgia. The samples revealed the majority have Na-K-HCO3 composition compared to just some of them Na-K-Cl-SO4 and Ca-MgSO4-Cl. Water-type changes from Sulfate-Chloride to bicarbonate from the West to the East were also observed. Reservoir temperature estimations by silica-enthalpy method is 130 ºC, 163 ºC, 212 ºC. The results of this and other current studies manifest the need for further researches and the steps and methodology thereof

Potent antiproliferative cembrenoids accumulate in tobacco upon infection with Rhodococcus fascians and trigger unusual microtubule dynamics in human glioblastoma cells.

Though plant metabolic changes are known to occur during interactions with bacteria, these were rarely challenged for pharmacologically active compounds suitable for further drug development. Here, the occurrence of specific chemicals with antiproliferative activity against human cancer cell lines was evidenced in hyperplasia (leafy galls) induced when plants interact with particular phytopathogens, such as the Actinomycete Rhodococcus fascians.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe