Abstract

Rodman During this past grant year we have applied our stochastic estimation procedure to the problem of modeling the cellular kinetics of the antiviral nucleoside analogs PMEA and PMPA. The experimental data from this study involved intracellular measurements of these phosphonate analogs and their mono- and diphosphate derivatives, obtained following systemic administration of the parent compounds in monkeys. Our estimation approach allowed us to decouple the (complicated) systemic disposition processes from the cellular events. This was accomplished by using the measured plasma data, together with information on its error variance structure, as the uncertain input to the cellular metabolic process occurring in lymphoid and red blood cells. The model developed for the metabolism of PMPA and PMEA in lymphoid has help to clarify several of the contradictory reports on the metabolism of these compounds observed in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001861-12
Application #
5223750
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Song, Dong; Wang, Haonan; Tu, Catherine Y et al. (2013) Identification of sparse neural functional connectivity using penalized likelihood estimation and basis functions. J Comput Neurosci 35:335-57
Hoppenbrouwers, Toke; Oliveira, Flavia; Sandarupa, Stanislaus et al. (2012) The development of the circadian heart rate rhythm (CHR) in Asian infants. Early Hum Dev 88:555-61
Wang, Xiaoning; Schumitzky, Alan; D'Argenio, David Z (2007) Nonlinear Random Effects Mixture Models: Maximum Likelihood Estimation via the EM Algorithm. Comput Stat Data Anal 51:6614-6623
Gholmieh, Ghassan; Courellis, Spiros; Marmarelis, Vasilis et al. (2007) Nonlinear dynamic model of CA1 short-term plasticity using random impulse train stimulation. Ann Biomed Eng 35:847-57
Gholmieh, Ghassan; Courellis, Spiros; Dimoka, Angelika et al. (2004) An algorithm for real-time extraction of population EPSP and population spike amplitudes from hippocampal field potential recordings. J Neurosci Methods 136:111-21
Ashjian, Peter; Elbarbary, Amir; Zuk, Patricia et al. (2004) Noninvasive in situ evaluation of osteogenic differentiation by time-resolved laser-induced fluorescence spectroscopy. Tissue Eng 10:411-20
Blasi, Anna; Jo, Javier; Valladares, Edwin et al. (2003) Cardiovascular variability after arousal from sleep: time-varying spectral analysis. J Appl Physiol 95:1394-404
Jo, Javier A; Blasi, Anna; Valladares, Edwin et al. (2003) Model-based assessment of autonomic control in obstructive sleep apnea syndrome during sleep. Am J Respir Crit Care Med 167:128-36
Belozeroff, Vasily; Berry, Richard B; Khoo, Michael C K (2003) Model-based assessment of autonomic control in obstructive sleep apnea syndrome. Sleep 26:65-73
Bading, James R; Yoo, Paul B; Fissekis, John D et al. (2003) Kinetic modeling of 5-fluorouracil anabolism in colorectal adenocarcinoma: a positron emission tomography study in rats. Cancer Res 63:3667-74

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