Tools for studying the roles of CYP2B6, CYP2C8, and CYP3A5 in drug metabolism have recently become available. The level of interest in these enzymes has been elevated because investigations have revealed substrate promiscuity and/or polymorphic expression. In this study, we aimed to develop a single cocktail inhibition assay for the three enzymes and assess its utility in drug discovery. Buprop...

Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during ...

Scientific paradigms have a tendency to rise fast and decline slowly. This asymmetry reflects the difficulty in developing a truly original idea, compared to the ease at which a concept can be eroded by numerous modifications. Here we formulate a model for the emergence and spread of ideas which deals with this asymmetry by constraining the ability of agents to return to already abandoned conce...

We report results from an empirical study of the anisotropic structure of eroding landscapes. By constructing a novel correlation function, we show quantitatively that small-scale channel-like features of landscapes are coupled to the large-scale structure of drainage basins. We show additionally that this two-scale interaction is scale-dependent. The latter observation suggests that a commonly...

Randomized trials are an excellent research design with major advantages. However, randomized trials are not immune to biases, and inferences from them may be sometimes flawed or irrelevant. The present review addresses, in brief, some of the major threats to the credibility and relevance of the results of clinical trials: power problems, biases affecting internal validity (poor design, conduct...

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzym...