ABSTRACT
Radiocontrast media can induce vascular endothelial cell apoptosis. Apoptotic damage to the vascular endothelium is an important mechanism in vascular disease. Several growth factors with anti-apoptotic effects may help protect the vascular endothelium from apoptosis. The present study evaluated whether the radiocontrast agent iopromide induces apoptosis in human umbilical vein endothelial cells and also whether angiopoietin-1 (Ang1) protects against iopromide-induced apoptosis through the p70 S6 kinase-dependent signaling pathway. Iopromide induced apoptosis in vascular endothelial cells in a dose-dependent manner. Ang1 reduced iopromide-induced apoptosis in a dose-dependent manner. Wortmannin and LY294002, phosphatidylinositol 3'-kinase inhibitors, decreased the Ang1-induced anti-apoptotic effect. Ang1 mediates the activation of mTOR/ribosomal protein p70 S6 kinase through phosphatidylinositol-3' kinase. Wortmannin and rapamycin, an inhibitor of mTOR, suppressed Ang1-induced p70 S6 kinase phosphorylation and partially inhibited the Ang1-induced anti-apoptotic effect. These results suggest that Ang1 may protect vascular endothelial cells from iopromide-induced apoptosis through phosphatidylinositol 3'-kinase and mTOR/S6 kinase. Pretreatment with Ang1 could help maintain normal vascular endothelial cell integrity before and during systemic radiocontrast administration.
Subject(s)
Angiopoietin-1/metabolism , Apoptosis/drug effects , Contrast Media/pharmacology , Endothelial Cells/drug effects , Iohexol/analogs & derivatives , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Analysis of Variance , Angiopoietin-1/pharmacology , Animals , Cattle , Cell Culture Techniques , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/cytology , Endothelium, Vascular/cytology , Enzyme Activation/drug effects , Humans , Iohexol/pharmacology , Mannitol/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Time Factors , Umbilical Veins/cytologyABSTRACT
We conducted this experiment to assess the effect of saline injection in electrochemical therapy. Platinum electrodes using direct current were inserted into egg white or liver parenchyma. Pure water or 0.9%, 3%, or 26% sodium chloride were injected into various objects to compare with the control group (no injection). Power was set at 10 V. In the egg-white experiment, gas bubbles and coagulated protein developed around the electrodes. In ex vivo liver, frothy reddish debris developed around the cathodes, while a hardening and shrunken surface occurred around the anodes. The pH was 14 around the cathodes, 0 around the anodes. The electric current, the amount of coagulated protein, and the severity of tissue damage were all in proportion to the concentrations of the injected saline. The volume destroyed in the 26% saline group was 8.1 times larger than that of the control group. Therefore, injected saline, especially saturated saline, can enhance the effect of electrochemical therapy.
Subject(s)
Electric Stimulation Therapy/methods , Sodium Chloride , Animals , Egg White , Electrodes , Hydrogen-Ion Concentration , In Vitro Techniques , Liver , Neoplasms/therapy , SwineABSTRACT
[formula: see text] A new approach to a suitably functionalized tricyclic core of sarains has been developed by means of Katritzky's cycloaddition using 3-oxidopyridinium betaines. A key step was the regioselective differentiation of the two nearly identical hydroxy groups derived from oxidative cleavage of the double bond in 8 to afford 14. A stereocontrolled construction of the tricyclic core 20 of sarains containing the requisite side chain at C-3' was achieved by an intramolecular conjugate addition.
