ABSTRACT
A novel method of carbon fiber microelectrode activation using spark discharge was demonstrated and compared to conventional electrochemical pretreatment by potential cycling. The spark discharge was performed at 800 V between the microelectrode connected to positive pole of the power supply and platinum counter electrode. Spark discharge led both to trimming of the fiber tip into conical shape and to the modification of carbon fiber microelectrode with platinum, as proven by scanning electron microscopy and electron dispersive X-ray spectroscopy. After the characterization of electrochemical properties using ferricyanide voltammetry, the activated electrodes were used for electrochemical analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative stress marker. Subnanomolar detection limits (0.55 nmol L(-1)) in high-performance liquid chromatography were achieved for spark platinized electrodes incorporated into the flow detection cell.
Subject(s)
Carbon/chemistry , Deoxyguanosine/analogs & derivatives , Electrochemical Techniques , 8-Hydroxy-2'-Deoxyguanosine , Carbon Fiber , Deoxyguanosine/blood , Deoxyguanosine/urine , Humans , Hydrodynamics , Microelectrodes , Particle SizeABSTRACT
Fumaric acid esters are thought to improve psoriasis by altering leukocyte, keratinocyte, and/or endothelial functions. To determine specificity, kinetics, and molecular mechanisms of different fumaric acid esters in their ability to inhibit endothelial cell activation, we analyzed CD62E and CD54 expression in endothelial cells in vivo and in vitro. In lesional skin of psoriatic patients, oral fumaric acid ester treatment resulted in a marked reduction of CD62E but not CD54 expression on dermal microvessels. Using human umbilical vein endothelial cells, dimethylfumarate almost completely inhibited tumor-necrosis-factor-induced CD62E, but not CD54 expression at concentrations < or = 70 microM, mimicking the situation in vivo. A 60 min dimethylfumarate preincubation was sufficient to block tumor-necrosis-factor-induced CD62E expression for up to 24 h. In contrast, equimolar concentrations of methylhydrogenfumarate, the hydrolysis product of dimethylfumarate, did not suppress tumor-necrosis-factor-induced CD62E expression. Likewise, all fumaric acid esters other than dimethylfumarate were ineffective. Using CD62E, NF-kappa B, or AP-1-responsive promoter constructs, dimethylfumarate inhibited tumor-necrosis-factor-induced activation of the CD62E and the NF-kappa B but not the AP-1 promoter construct. In summary, at a dose range < or = 70 microM, dimethylfumarate appeared to be a specific inhibitor of CD62E expression in an NF-kappa B-dependent manner.
Subject(s)
Dermatologic Agents/pharmacology , E-Selectin/genetics , Fumarates/pharmacology , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Capillaries/chemistry , Capillaries/drug effects , Capillaries/physiology , Cells, Cultured , Dimethyl Fumarate , E-Selectin/analysis , Endothelium, Vascular/chemistry , Endothelium, Vascular/cytology , Endothelium, Vascular/physiology , Gene Expression/drug effects , Humans , Intercellular Adhesion Molecule-1/analysis , Intercellular Adhesion Molecule-1/genetics , Psoriasis/drug therapy , Psoriasis/physiopathology , RNA, Messenger/analysis , Skin/blood supply , Umbilical Veins/cytologyABSTRACT
Methamphetamine is one of the most frequently abused drugs of today. Due to its stereogenic center, it can exist as single enantiomer. Like many other chiral compounds, methamamphetamine enantiomers exhibit different pharmacological effects on living organisms. For this reason, it is necessary to develop enantioselective and sufficiently sensitive methods of determination. This review focuses on methamphetamine with an accent on analytical chemistry and especially on chiral separations of this toxicologically important compound.
