A major user group of 4 University of Arkansas for Medical Sciences (UAMS) clinical research scientists, holding 7 current NIH peer-reviewed grants, request a chemical separation and analysis system comprising (a) an Applied Biosystems (AB)/Sciex QTRAP(R) 5500 AM triple Quadrupole/linear ion TRAP mass spectrometer and (b) a Waters Acquity UPLC(R) Ultra-High Performance Liquid Chromatograph. There is infrastructural support from the UAMS Colleges of Medicine and Pharmacy to fully cover post-warranty service contracts through the 3rd post-warranty year, 1 full-time technician/operator for two years, and minor modifications (solvent vent line, pump noise abatement) to an existing LC-MS laboratory. The user group documents a clear need in their NIH grants for improved chromatographic resolution and increased spectrometric sensitivity over that possible on existing UAMS equipment. They conclude from their review of available systems that the Acquity UPLC(R)- QTRAP(R) 5500 AM system can address this need best, and estimate that experiments funded by seven refereed NIH awards will occupy 80% of instrument time. Notably, the NIH-funded projects all rely on one or both of two core methodologies: utilization of (i) L-citrulline and related arginine pathway substrates as metrics of intestinal health and activity;and (ii) stable (heavy) isotopomers of L-phenylalanine, 3-methyl-L-histidine, and other select macronutrients as metrics of protein synthesis and turnover. Since Drs. Wolfe and Deutz, founders of the Center for Translational Research in Aging and Longevity (CTRAL, Donald W. Reynolds Department of Geriatrics, UAMS), jointly have >50 years expertise interpreting the results of these and related metabolite measurements, the user group would situate the requested UPLC-QTRAP system at CTRAL in its existing LC-MS/GC-MS core. That core's director Dr. Thaden has >10 years experience as a bioorganic separations chemist, 5 including day-to-day operation of AB/Sciex triple-quadrupole mass spectrometers and AB/Sciex Analyst(R) software. Citrulline and the amino-acid stable isotopes are powerful metabolic tracers, able to report on health status as it applies to a number of public health issues. The requested system would further understanding and the treatment or palliation of sepsis, radiation-induced gut damage, chronic obstructive lung disease, and fatty acid related substrate-cycling aberrancies associated with cancer, major surgical events, advanced aging, starvation, etc.
Advances in our understanding and treatment of 4 seemingly disparate public health problems share a heavy dependence on instruments able to measure traces of certain research molecules - citrulline, and a family of stable, safe isotopes - in blood, urine and tissue. The health problems, topics of 7 NIH-funded projects at the University of Arkansas for Medical Science (UAMS), are severe damage to the intestines after radiation exposure;sepsis (blood infection) coming from major infection;muscle wasting accompanying chronic obstructive pulmonary disease (COPD);and disturbed fatty acid and protein metabolism associated with a spectrum of conditions, for instance, cancer, advanced aging, enforced inactivity, and major surgical events. The requested QTRAP(r) 5500 AM Mass Spectrometer and Acquity UPLC(r) chromatograph system would appreciably speed progress in these research efforts on sepsis, radioprotective agents, COPD and metabolic substrate cycling here in Central Arkansas.
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