scholarly journals Addition of Phenylmethylsulfonyl Fluoride Increases the Working Lifetime of the Trout Liver S9 Substrate Depletion Assay, Resulting in Improved Detection of Low Intrinsic Clearance Rates

2020 ◽  
Vol 40 (1) ◽  
pp. 148-161
Author(s):  
John W. Nichols ◽  
Alex D. Hoffman ◽  
Joe A. Swintek ◽  
Steven T.J. Droge ◽  
Patrick N. Fitzsimmons
2009 ◽  
Vol 54 (2) ◽  
pp. 931-933 ◽  
Author(s):  
Unji Lee ◽  
Young H. Choi ◽  
So H. Kim ◽  
Byung K. Lee

ABSTRACT After intravenous or oral administration of 10 mg/kg itraconazole to rats with streptozotocin-induced diabetes mellitus and to control rats, the total area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24) for itraconazole and that for its metabolite, 7-hydroxyitraconazole, were similar between the two groups of rats. This may be explained by the comparable hepatic and intestinal intrinsic clearance rates for the disappearance of itraconazole and the formation of 7-hydroxyitraconazole in both groups of rats.


Toxicology ◽  
2021 ◽  
pp. 152819
Author(s):  
Sherry R. Black ◽  
John W. Nichols ◽  
Kellie A. Fay ◽  
Sharlene R. Matten ◽  
Scott G. Lynn

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Nuttha Lumlertgul ◽  
Anna Hall ◽  
Luigi Camporota ◽  
Siobhan Crichton ◽  
Marlies Ostermann

Abstract Background The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. Methods This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. Results Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. Conclusion EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. Trial registration: NCT03231748, registered on 27th July 2017.


1963 ◽  
Vol 204 (4) ◽  
pp. 655-659 ◽  
Author(s):  
I. MacKay Murray

Intravascular clearance rates of gelatin-stabilized gold were compared with circulating titers of gelatin agglutinins in rats at increasing time intervals after blockading injections of gelatin-stabilized gold and S. marcescens endotoxin. The degree and duration of reticuloendothelial system (RES) blockade against the homologous colloid were directly related to the circulating levels of gelatin agglutinins. In contrast, plasma agglutinins were not decreased in endotoxin-induced blockade against the gelatin-stabilized colloid. In a further experiment, the plasma response to blockading injections of colloidal thorium dioxide, iron oxide, and zymosan was characterized by a transient increase in gelatin agglutinins suggesting the nonspecific release of opsonins from an extravascular source. The findings indicated that clearance rates of gelatin-stabilized colloids were dependent on the total available opsonin in the rat rather than the total circulating opsonin. It is suggested that RES blockade is effected by the prior nonspecific depletion of opsonins from an extravascular reserve which is the major component of the total available opsonin.


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