- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 12:41:36+12:00
- Desc:
- committing version02 of brown_choe_shanahan_czeisler_1997
- Permanent Source URI:
- http://models.cellml.org/workspace/brown_choe_shanahan_czeisler_1997/rawfile/da0e0bccce386ed877801b79dc94d5cef2687652/brown_choe_shanahan_czeisler_1997.cellml
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<!-- FILE : brown_model_1997.xml
CREATED : 6th July 2007
LAST MODIFIED : 6th July 2007
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Brown et al.'s 1997 mathematical model of diurnal variations in human plasma melatonin levels.
CHANGES:
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<title>A mathematical model of diurnal variations in human plasma melatonin levels</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
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This model can be solved but the output has not been checked against the publication.
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ValidateCellML verifies this model as valid CellML but detects unit inconsistencies.
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
In animals melatonin plays an important role in processing environmental photic information (such as the day length) that can determine the timing of reproduction and other seasonally regulated behaviours. Although the function of the hormone in humans is less well understood, its diurnal pattern is well described. It peaks during the late evening, declines by early morning, and is at its lowest point at midmorning. The 8 to 14 hour period of elevated melatonin levels depend on light exposure patterns, and seems to correlate with circadian rhythms. As such, it has been suggested that plasma melatonin levels could be used as a quantitative marker of the human circadian system.
</para>
<para>
Melatonin is synthesised in the pineal gland where its precursor tryptophan is converted to serotonin, and then to melatonin. The rate determining step in this synthesis pathway is the governed by the activity of N-acetylserotonin (NAT), and the activity of this enzyme is controlled by the suprachiasmatic nuclei of the hypothalamus, the main mammalian circadian pacemaker. Melatonin is not stored in the pineal gland. Once synthesised melatonin diffuses into the systemic circulatory system. From the plasma it is absorbed by various tissues and is cleared by the liver.
</para>
<para>
In their mathematical model of diurnal variations in human plasma melatonin levels, described here in CellML, Brown <emphasis>et al.</emphasis> incorporate four governing factors:
<itemizedlist>
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<para>1) circadian control of the onset and offset of melatonin synthesis;</para>
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<para>2) the rates of melatonin a) synthesis in pineal gland, b) infusion into the plasma, and c) clearance by the liver;</para>
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<para>3) experimental artifact introduced by the melatonin immunoassay error; and</para>
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<para>4) the environmental lighting conditions under which the melatonin levels are measured.</para>
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<caption>Schematic diagram of the components and variables in a mathematical model of human melatonin. Diurnal rhythm of melatonin is observed in the plasma compartment. A represents N-acetylserotonin activity in the pineal gland, H1 is the concentration of melatonin in the pineal gland, betaI is the plasma melatonin infusion rate, H2 is the plasma concentration of melatonin, and betaC is the clearance rate of plasma melatonin.</caption>
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<para>
The complete original paper reference is cited below:
</para>
<para>
A mathematical model of diurnal variations in human plasma melatonin levels, Emery N. Brown, Yong Choe, Theresa L. Shanahan, and Charles A. Czeisler, 1997,
<emphasis>American Journal of Physiology; Endocrinology and Metabolism</emphasis>
, 272, E506-E516. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9124558&query_hl=1&itool=pubmed_docsum">PubMed ID: 9124558</ulink>
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Brown et al.'s 1997 mathematical model of diurnal variations in human plasma melatonin levels.
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