Linked Life Data

19345693

Source:http://linkedlifedata.com/resource/pubmed/id/19345693

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-7-14
pubmed:abstractText
Environmentally relevant toxic exposures often consist of simultaneous exposure to multiple agents. Methods to predict the expected outcome of such combinations are critical both to risk assessment and to an accurate judgment of whether combinations are synergistic or antagonistic. Concentration addition (CA) has commonly been used to assess the presence of synergy or antagonism in combinations of similarly acting chemicals, and to predict effects of combinations of such agents. CA has the advantage of clear graphical interpretation: Curves of constant joint effect (isoboles) must be negatively sloped straight lines if the mixture is concentration additive. However, CA cannot be directly used to assess combinations that include partial agonists, although such agents are of considerable interest. Here, we propose a natural extension of CA to a functional form that may be applied to mixtures including full agonists and partial agonists. This extended definition, for which we suggest the term "generalized concentration addition," encompasses linear isoboles with slopes of any sign. We apply this approach to the simple example of agents with dose-response relationships described by Hill functions with slope parameter n=1. The resulting isoboles are in all cases linear, with negative, zero and positive slopes. Using simple mechanistic models of ligand-receptor systems, we show that the same isobole pattern and joint effects are generated by modeled combinations of full and partial agonists. Special cases include combinations of two full agonists and a full agonist plus a competitive antagonist.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-11032772, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-11993873, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-12084633, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-12634130, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-13341643, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-14736496, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-15175417, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-15456984, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-16371451, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-16829543, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-3196155, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-6141562, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-7568328, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-7568331, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-8748700, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-8975631, http://linkedlifedata.com/resource/pubmed/commentcorrection/19345693-9508738
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1095-8541
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
259
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
469-77
pubmed:dateRevised
2010-9-23
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Generalized concentration addition: a method for examining mixtures containing partial agonists.
pubmed:affiliation
Department of Environmental Health, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA. gh@bu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural