1 Omeprazole, a proton pump inhibitor therapeutically administered for the treatment of gastric ulcers, induces the expression of cytochromes P4501A1/2 (CYP1A1/2) through transcriptional activation mediated by the Ah (dioxin)-receptor. Primary cultures of hepatocytes isolated from rabbit, rat, mouse and human livers were compared for CYP1A1/2 mRNA inducibility by omeprazole (1 to 100 μM). 2 Primary cultures of human hepatocytes were the most sensitive to the inducing effects of omeprazole. Rabbit hepatocytes were the only other cells studied that showed induced CYP1A1/2 mRNA expression from a concentration lower than 100 μM (i.e., 10 μM). Rat hepatocytes were the least sensitive to omeprazole induction. The response of mouse hepatocytes to omeprazole treatment was variable, with CYP1A1/2 mRNA expression being induced in only two of the three cultures examined. 3 Differences in the time dependence of CYP1A1/2 mRNA expression were observed between species. In general, after treatment of hepatocytes with omeprazole the levels of CYP1A1 mRNA peaked prior to that of CYP1A2 mRNA. 4 Due to the interspecific variability of CYP1A mRNA inducibility by omeprazole, we conclude that human hepatocytes in culture are probably the only appropriate animal model for prediction of CYP1A induction in humans.
A physonectid siphonophore, Nanomia bijuga, associated with a verticallymigrating deep scattering layer, has been observed with a gasfilled float at depths in excess of 300 meters in the sea. This implies that gas is secreted and maintained in the pneumatophore against a diffusion gradient of 30 atmospheres or more. Analysis of the enclosed gases revealed concentrations of carbon monoxide exceeding 90 percent. Necessary voiding of this gas during a vertical ascent of 300 meters could give rise to a transient population of bubbles which would act as sound-reflecting targets.
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