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Regenerating System (regenerating + system)
Selected AbstractsComparison of DNA-Reactive Metabolites from Nitrosamine and Styrene Using Voltammetric DNA/Microsomes SensorsELECTROANALYSIS, Issue 9 2009Sadagopan Krishnan Abstract Voltammetric sensors made with films of polyions, double-stranded DNA and liver microsomes adsorbed layer-by-layer onto pyrolytic graphite electrodes were evaluated for reactive metabolite screening. This approach features simple, inexpensive screening without enzyme purification for applications in drug or environmental chemical development. Cytochrome P450 enzymes (CYPs) in the liver microsomes were activated by an NADPH regenerating system or by electrolysis to metabolize model carcinogenic compounds nitrosamine and styrene. Reactive metabolites formed in the films were trapped as adducts with nucleobases on DNA. The DNA damage was detected by square-wave voltammetry (SWV) using Ru(bpy) as a DNA-oxidation catalyst. These sensors showed a larger rate of increase in signal vs. reaction time for a highly toxic nitrosamine than for the moderately toxic styrene due to more rapid reactive metabolite-DNA adduct formation. Results were consistent with reported in vivo TD50 data for the formation of liver tumors in rats. Analogous polyion/ liver microsome films prepared on 500,nm silica nanoparticles (nanoreactors) and reacted with nitrosamine or styrene, provided LC-MS or GC analyses of metabolite formation rates that correlated well with sensor response. [source] Stereoselective synthesis of L-[15N] amino acids with glucose dehydrogenase and galactose mutarotase as NADH regenerating systemJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 4 2008Maria Chiriac Abstract We have developed an efficient stereospecific enzymatic synthesis of L-[15N]-valine, L-[15N]-leucine, L-[15N]-norvaline, L-[15N]-norleucine and L-[15N]-isoleucine from the corresponding ,-keto acids by coupling the reactions catalysed by leucine dehydrogenase and glucose dehydrogenase/galactose mutarotase. Giving high yields of L-amino acids, the procedure is economical and easy to perform and to monitor at a synthetically useful scale (1,10,g). Copyright © 2008 John Wiley & Sons, Ltd. [source] Comparative oxidative metabolic profiles of clomipramine in cats, rats and dogs: preliminary results from an in vitro studyJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007C. LAINESSE The objectives of this in vitro study were to describe cytochrome-dependent metabolism of clomipramine in canine and feline microsomes, compare metabolic profiles between cats, rats and dogs, and investigate a potential gender-related difference in metabolic activity between male and female cats. Pooled liver microsomes were incubated with clomipramine, where species and gender-specific reactions were initiated by the addition of a nicotinamide adenine dinucleotide phosphate regenerating system and quenched with methanol at 0, 5, 15, 30, 45 and 60 min, and 0, 30, 60, 90, 120, 180, 240 and 360 min respectively. Liquid chromatography tandem mass spectrometry was used to measure clomipramine and its metabolites. Preliminary results showed that cat microsomes biotransformed clomipramine slower and less efficiently than rat and dog microsomes. Moreover, gender differences in metabolic profiles suggested that male cat microsomes may be less efficient demethylators and hydroxylators than female cat microsomes. As gender metabolic differences may carry clinical significance for this antidepressant, further studies are warranted. [source] Microvessels Promote Motor Nerve Survival and Regeneration Through Local VEGF Release Following Ectopic ReattachmentMICROCIRCULATION, Issue 8 2004SHAWN E. BEARDEN ABSTRACT Objectives: Nerves and blood vessels form a close association during embryogenesis. Growth and guidance factors initially attributed to either nerves or vessels are now known to affect both tissues; prominent among these is vascular endothelial growth factor (VEGF). The authors investigated whether axons would associate with blood vessels in a regenerating system and questioned whether VEGF is integral to neurotization following axotomy. Methods: In hamsters 8,12 weeks of age, the accessory nerve (CN XI) to the retractor muscle of the cheek pouch was cut and the proximal stump was reattached ectopically onto the muscle. Vascular casting and immunolabeling were used to quantify the extent of neurovascular association during regeneration. A role for VEGF was investigated using immunolocalization of VEGF and its receptor (sVEGFR2) as well as local sequestration of VEGF with soluble receptor (sVEGFR1). Results: Regenerating axons aligned with microvessels of the vasa nervorum along a "chaperone" region during outgrowth from the reattachment site and while entering the muscle. In this ,1-mm region, VEGF protein was expressed by growing microvessels despite a ,50% reduction (p < .05) in total muscle VEGF concentration. VEGFR2 was expressed by regenerating axons and growth cones. Sequestration of VEGF by sVEGFR1 impaired neurotization by ,40% (p < .05). The chaperone region ended where regenerating microvessels anastomosed with the native microcirculation and their expression of VEGF protein diminished. Conclusions: Regenerating axons and blood vessels align during outgrowth from ectopic reattachment. This interaction dissipates as vascular anastomoses form with established microvessels and axons target muscle fibers. Local production of VEGF by growing microvessels supports motor nerve survival and regeneration. [source] |