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Stochastic vs. deterministic uptake of dodecanedioic acid by isolated rat livers

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Abstract

Deterministic and stochastic differential equations models of the uptake of dodecanedioic acid (C12) are fitted to experimental data obtained on nine isolated, perfused rat livers. 11500 μg of C12 were injected as a bolus into the perfusing liver solution. The concentrations of C12 in perfusate samples taken over 2 h from the beginning of the experiments were analyzed by High Performance Liquid Chromatography (HPLC).

A two-compartment deterministic model is studied. To include spontaneous erratic variations in the metabolic processes the parameter for the uptake rate is randomized to obtain a stochastic differential equations model. Parameters are estimated in a two-step procedure: first, parameters in the drift part are estimated by least squares; then, the diffusion parameter is estimated using Monte-Carlo simulations to approximate the unknown likelihood function. Parameter estimation is carried out over a wide range of reasonable measurement error variances to check robustness of estimates.

It is concluded that the kinetics of dodecanedioic acid, in the experimental conditions discussed, is well approximated by a model including spontaneous erratic variations in the liver uptake rate.

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References

  • Ait-Sahalia, Y., 2002. Maximum likelihood estimation of discretely sampled diffusions: a closed-form approximation approach. Econometrica 70, 223–262.

    Article  MathSciNet  MATH  Google Scholar 

  • Babayan, V.K., 1987. Medium-chain triglycerides: an update. Lipids 22, 417–420.

    Google Scholar 

  • Bach, A.C., Babayan, V.K., 1982. Medium-chain triglycerides: an update. Am. J. Clin. Nutr. 36, 950–955.

    Google Scholar 

  • Bergseth, S., Hokland, B.M., Bremer, J., 1988. Metabolism of dicarboxylic acids in vivo and in the perfused kidney of rat. Biochim. Biophys. Acta 961, 103–109.

    Google Scholar 

  • Bertuzzi, A., Finotti, E., Mingrone, G. et al., 1993. Sebacic acid binding to human plasma albumin. Biochem. Pharmacol. 45, 697–702.

    Article  Google Scholar 

  • Bertuzzi, A., Gandolfi, A., Salinari, S. et al., 1991. Pharmacokinetic analysis of azelaic acid disodium salt: a proposed substrate for total parenteral nutrition. Clin. Pharmacokinet. 20, 411–419.

    Google Scholar 

  • Bertuzzi, A., Mingrone, G., De Gaetano, A., Gandolfi, A., Greco, A.V., Salinari, S., 1997. Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats. Br. J. Nutr. 78, 143–153.

    Article  Google Scholar 

  • Bertuzzi, A., Mingrone, G., Gandolfi, A. et al., 1995. Pharmacokinetic analysis of dodecanedioic acid in man from bolus data. J.P.E.N. 19, 498–501.

    Google Scholar 

  • Bibby, B.M., Sørensen, M., 1995. Martingale estimation functions for discretely observed diffusion processes. Bernoulli 1, 017–039.

    Google Scholar 

  • De Gaetano, A., Castagneto, M., Mingrone, G. et al., 1994. Kinetics of medium-chain triglycerides and free fatty acids in healthy volunteers and surgically stressed patients. J.P.E.N. 18, 134–140.

    Google Scholar 

  • De Gaetano, A., Mingrone, G., Castagneto, M., Benedetti, G., Greco, A.V., Gasbarrini, G., 1999. Kinetics of dodecanedioic acid triglyceride in rats. Am. J. Physiol. 276, E497–E502.

    Google Scholar 

  • Ditlevsen, S., Sørensen, M., 2004. Inference for observations of integrated diffusion processes. Scand. J. Stat. 31, 417–429.

    Article  MATH  Google Scholar 

  • Elerain, O., Chib, S., Shepard, N., 2001. Likelihood inference for discretely observed non-linear diffusions. Econometrica 69, 959–993.

    Article  MathSciNet  Google Scholar 

  • Florens-Zmirou, D., 1989. Approximate discrete-time schemes for statistics of diffusion processes. Stochastics 20, 547–557.

    MATH  MathSciNet  Google Scholar 

  • Greco, A.V., Mingrone, G., De Gaetano, A. et al., 1997. Uptake of dodecanedioic acid by isolated rat liver. Clin. Chim. Acta 258, 209–218.

    Article  Google Scholar 

  • Kessler, M., 1997. Estimation of an ergodic diffusion from discrete observations. Scand. J. Stat. 24, 211–229.

    Article  MATH  MathSciNet  Google Scholar 

  • Kessler, M., Sørensen, M., 1999. Estimating equations based on eigenfunctions for a discretely observed diffusion process. Bernoulli 5, 299–314.

    Article  MathSciNet  MATH  Google Scholar 

  • Kloeden, P.E., Platen, E., 1999. Numerical Solution of Stochastic Differential Equations. Springer.

  • Mortensen, P.B., 1983. Dicarboxylic acids and lipid metabolism, Ph.D. Thesis, Aarhus University.

  • Øksendal, B., 1998. Stochastic Differential Equations. Springer-Verlag, Berlin.

    Google Scholar 

  • Passi, S., Nazzaro-Porro, M., Picardo, M. et al., 1983. Metabolism of straight, saturated medium chain-length (c9–c12) dicarboxylic acids. J. Lipid Res. 24, 1140–1147.

    Google Scholar 

  • Pedersen, A.R., 1994. Uniform residuals for discretely observed diffusion processes. Technical Report 292, Department of Theoretical Statistics, University of Aarhus.

  • Pedersen, A.R., 1995. A new approach to maximum likelihood estimation for stochastic differential equations based on discrete observations. Scand. J. Stat. 22, 55–71.

    MATH  Google Scholar 

  • Pedersen, A.R., 2000. Estimating the nitrous oxide emission rate from the soil surface by means of a diffusion model. Scand. J. Stat. 27, 385–403.

    Article  MATH  Google Scholar 

  • Pedersen, A.R., 2001. Likelihood inference by Monte Carlo methods for incompletely discretely observed diffusion processes. Technical Report 1, Department of Biostatistics, University of Aarhus.

  • Poulsen, R., 1999. Approximate maximum likelihood estimation of discretely observed diffusion processes. Technical Report 29, Centre for Analytical Finance, University of Aarhus.

  • Prakasa Rao, B.L.S., 1999. Statistical Inference for Diffusion Type Processes. Arnold Publishers, London.

    MATH  Google Scholar 

  • Sandstrom, R., Hyltander, A., Korner, U., Lundholm, K., 1993. Structured triglycerides to postoperative patients: a safety and tolerance study. J.P.E.N. 17, 153–157.

    Google Scholar 

  • Seber, G.A.F., Wild, C.J., 1989. Nonlinear Regression. Wiley, New York.

    MATH  Google Scholar 

  • Sheiner, L.B., Beal, S.L., 1985. Pharmacokinetic parameter estimates from several least squares procedures: superiority of extended least squares. J. Pharmacokinet. Biopharm. 13, 185–201.

    Article  Google Scholar 

  • Sørensen, M., 2000. Prediction-based estimating functions. Econometrics J. 3, 123–147.

    Article  MATH  Google Scholar 

  • Spector, A.A., 1975. Fatty acid binding to plasma albumin. J. Lipid Res. 16, 165–179.

    Google Scholar 

  • Tataranni, P.A., Mingrone, G., De Gaetano, A. et al., 1992. Tracer study of metabolism and tissue distribution of sebacic acid in rats. Ann. Nutr. Metab. 36, 296–303.

    Article  Google Scholar 

  • Tserng, K.Y., Jin, S.J., 1991. Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates, a stable isotope tracer study. J. Biol. Chem. 266, 2924–2929.

    Google Scholar 

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Correspondence to Susanne Ditlevsen.

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Ditlevsen, S., de Gaetano, A. Stochastic vs. deterministic uptake of dodecanedioic acid by isolated rat livers. Bull. Math. Biol. 67, 547–561 (2005). https://doi.org/10.1016/j.bulm.2004.09.005

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  • DOI: https://doi.org/10.1016/j.bulm.2004.09.005

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