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The following message was posted to: PharmPK
Does anyone know the maximum tolerated endotoxin (LPS) levels in
chimpanzees?
Thanks for your help.
Kathleen Ministri-Madrid
MedImmune, Inc.
35 West Watkins Mill Road
Gaithersburg, MD 20878
301-527-4379
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The following message was posted to: PharmPK
Kathleen,
To answer your question, you should have some information about the source
of LPS you are dealing with. As you know, LPS are derived from various
Gram-negative bacteria (e.g., E. coli, Klebsiella, Salmonella...and others),
and even within the same species, different strains exist (e.g., 0111:B4,
0127:B8, 026:B6, 055:B5....all under E. coli) based on their virulent
nature and other biochemical markers. Therefore, you need to check your LPS
stock for its lipid A content and LD50 (you can obtain this information from
the supplier). Different assays have been developed to measure LPS levels in
plasma, and Limulus Amebocyte Lysate (LAL) is probably the most commonly
used one. Again, cross comparison of LPS levels determined by various assays
is difficult since they are more likely based on different sources of LPS.
One last though, various animal species have also demonstrated different
tolerability profile to LPS; form example, rats are known to be generally
more resistant to the effect of LPS.
Hope this helps,
Khalid Alkharfy
University of Pittsburgh
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