scholarly journals Exploring the translational disconnect between the murine and human inflammatory response: in vitro analysis of the dose-response relationship of LPS and NFκB activation in murine and human immune cells

Critical Care ◽  
2013 ◽  
Vol 17 (S2) ◽  
Author(s):  
EP McCarron ◽  
I Welters ◽  
D Williams ◽  
D Antoine ◽  
A Kipar
2015 ◽  
Vol 123 (6) ◽  
pp. 1337-1349 ◽  
Author(s):  
Friederike Haerter ◽  
Jeroen Cedric Peter Simons ◽  
Urs Foerster ◽  
Ingrid Moreno Duarte ◽  
Daniel Diaz-Gil ◽  
...  

Abstract Background The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. Methods The dose–response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose–response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose–response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine. Results In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 109 M−1 and Ka = 3.8 × 107 M−1). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate. Conclusions Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.


Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 560-568 ◽  
Author(s):  
G de Klerk ◽  
C Kruiswijk ◽  
AA Hart ◽  
R Goudsmit

Abstract Investigations on the mouse fetal liver cell bioassay for erythropoietin (ESF) have revealed that iron present in test sera significantly dilutes the radiolabel (59Fe) and thus decreases 59Fe incorporation into heme. A method of correction for the influence of iron on the dose-response relationship of human sera is presented. Application of this method made it possible to assay human sera up to culture concentrations of 150 microliter/ml. It was shown that a corrected serum dose-response curve showed parallelism to the curve of an ESF standard preparation. This suggests similarity of the active principles and allows valid estimation of a potency ratio.


Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 560-568
Author(s):  
G de Klerk ◽  
C Kruiswijk ◽  
AA Hart ◽  
R Goudsmit

Investigations on the mouse fetal liver cell bioassay for erythropoietin (ESF) have revealed that iron present in test sera significantly dilutes the radiolabel (59Fe) and thus decreases 59Fe incorporation into heme. A method of correction for the influence of iron on the dose-response relationship of human sera is presented. Application of this method made it possible to assay human sera up to culture concentrations of 150 microliter/ml. It was shown that a corrected serum dose-response curve showed parallelism to the curve of an ESF standard preparation. This suggests similarity of the active principles and allows valid estimation of a potency ratio.


1988 ◽  
Vol 7 (2) ◽  
pp. 129-132 ◽  
Author(s):  
J.C. Sherlock ◽  
M.J. Quinn

Wide discrepancies have been observed between controlled and uncontrolled intake studies of the relationship of blood mercury concentration to intake of mercury. The probable reason for the apparent discrepancies is that the within-subject variation of mercury intake in the uncontrolled studies was almost certainly considerably larger than the within-subject variation in blood mercury concentration; in these circumstances, the apparent slope obtained from a linear regression of blood mercury on intake will invariably be much smaller than the true slope. Studies of the exposure or intake of any substance should therefore include a consideration of the likely within-subject variation in the exposure or intake relative to that in the effect.


2016 ◽  
Vol 31 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Saki Nakamura ◽  
Nao Watanabe ◽  
Naoki Yoshimura ◽  
Sayaka Ozawa ◽  
Keiichi Hirono ◽  
...  

1994 ◽  
Vol 81 (SUPPLEMENT) ◽  
pp. A1351
Author(s):  
M. F. Watcha ◽  
P. J. Bras ◽  
J. Pennant ◽  
G. Cieslak ◽  
D. Burnette

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