Williams model, metabolism

Maslansky, C.J. and Williams, G.M. (1985). Methods for the initiation and use of hepatocyte primary cultures from various rodent species to detect metabolic activation of carcinogens. In In vitro Models for Cancer Research (Webber, M. and Sekely, L., Eds.). CRC Press, Boca Raton, FL, pp. 43-60. 

Absorption, Distribution, Metabolism, and Excretion. Levels of cresols in blood were obtained from a single case report of a dermally exposed human (Green 1975). Data on the toxicokinetics of cresols in animals were contained in two acute oral studies that provided only limited quantitative information on the absorption, metabolism, and excretion of cresols (Bray et al. 1950 Williams 1938). A more complete oral toxicokinetics study, in addition to studies using dermal and inhalation exposure, would provide data that could be used to develop predictive pharmacokinetic models for cresols. Inclusion of several dose levels and exposure durations in these studies would provide a more complete picture of the toxicokinetics of cresols and allow a more accurate route by route comparison, because it would allow detection of saturation effects. Studies of the tissue distribution of cresols in the body might help identify possible target organs. 

Williams, D. R. Computer models of metal biochemistry and metabolism, in Chemical Toxicology and Clinical Chemistry of metals (ed.) Brown, S. S., Savory, J., p. 167, London-New York, Academic Press 1983... 

The desk top computer network is shown in Figure 1. The liquid scintillation counters which we routinely use to generate metabolism data include two Beckman LS-200 series liquid scintillation counters and two Tracor Mark III liquid scintillation counters, however, other LSC makes and models may be interfaced. The Tracor counters are equipped with two standard communications output connectors. One is used to drive the printer, the other is available to the user. The Beckman counters use a unique teletype driver but an interface produced by William Palmer Industries can split the signal and provide a standard communication output. Therefore, all data output from the liquid scintillation counters are available in an electrical standard format, RS-232C. Hardware interfacing was therefore simplified and data collection was a matter of software development. 

The demise of the famous Hodgkin-Huxley theory of nerve conductance brings to mind other Nobel prizes in electrochemically related areas. In 1959 Heyrovsky was recognized for a new analytical method, and this polarography has been the origin of many modem methods of electroanalysis. The award for Nobel Prize to Mitchell in 1978 (for a chemiosmotic model of membrane function) and metabolism seems to have been based on a lack of awareness of a simpler, clearer (prior) model by Williams for interpreting the same functions. The award to Marcus in 1992 for the theory of redox reactions (1956) seems to have lacked awareness of an earlier publication by Weiss that described similar ideas. 

An essentially electrochemical model for metabolism and the formation of adenosine tri-phosphate from adenosine diphosphate was suggested by R. J. P. Williams at Oxford University in 1959.18 It is shown in Fig. 14.40. 

Roper, C.S., D. Howes, P.G. Blain and F.M. Williams (1995). Prediction of the percutaneous penetration and metabolism of dodecyl decaethoxylate in rats using in vitro models. Arch. Toxicol, 69, 649-654. 

Goosen TC, Arimoto R, Gifford E, Ball SE, Hurst SI, Tugnait M, Hollenberg PF, Williams JA. A computational model based on UGTIA inhibition in human liver microsomes predicts the tacrolimus-mycophenolic acid metabolic drug interaction. Drug Metab Rev 2003 35 58. 

Dear GJ, Munoz-Muriedas J, Beaumont C, Roberts A, Kirk J, Williams JP, Campuzano I. Sites of metabolic substitution investigating metabolite structures utilising ion mobility and molecular modelling. Rapid Commun Mass Spectrom. 2010 24 3157-62. 

Del Monte, R, Williams, E., Lebeche, D., Schmidt, U., Rosenzweig, A., Gwathmey, J. K., Lewandowski, E. D., and Hajjar, R. J. 2001. Improvement in smvival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca2 -I- -ATPase in a rat model of heart failure. Circulation, 104,1424-1429. 

Sauvant, D. and S. Giger-Reverdin, 2007a. Empirical modelling by meta analysis of digestive interactions and CH4 production in ruminants. In Ortigues-Maity I., N. Miraux and W. Brand-Williams (eds.). Energy and Protein Metabolism and Nutrition, EAAP Publication No 124, Wageningen Academic Publishers, the Netherlands 561-562. 

Williams, C.B. and T.G. Jenkins, 2003. Adynamic model of metabolizahle energy utilization in growing and mature cattle. I. Metabolizahle energy utilization for maintenance and support metabolism. J. Anim. Sci. 81, 1371-1381. 

---