ABSTRACT:Berberine, one of the most commonly used natural products, exhibits a poor plasma concentration-effect relationship whose underlying mechanisms remain largely unclear. This study was designed to test the hypothesis that extensive first-pass elimination and abundant tissue distribution of berberine may be its specific pharmacokinetic properties. For that, four different dosing routes, intragastric, intraduodenal, intraportal, and intravenous, were used to investigate the gastric, intestinal, and hepatic first-pass elimination of berberine. After intragastric dosing, approximately half of berberine ran intact through the gastrointestinal tract and another half was disposed of by the small intestine, leading to an extremely low extent of absolute oral bioavailability in rats (0.36%). Moreover, the major berberine metabolites were identified and quantified in rat enterocyte S9 fractions, portal vein plasma, and intestinal perfusates; plasma concentrations and tissue distribution of berberine and its major metabolites were determined as well. Data indicated that M1, M2 glucuronide, and M3 were the major metabolites generated from the small intestine and that there was a 70-fold increase in the ratio of the area under the concentration-time curve value for berberine (liver versus plasma). We conclude that intestinal first-pass elimination of berberine is the major barrier of its oral bioavailability and that its high extraction and distribution in the liver could be other important factors that lead to its low plasma levels in rats.

Human cytochrome P450 (CYP) 3A subfamily members (mainly CYP3A4 and CYP3A5) mediate the metabolism of approximately half all marketed drugs and thus play a critical role in the drug metabolism. A huge number of studies on CYP3A-mediated drug metabolism in humans have demonstrated that CYP3A activity exhibits marked ethnic and individual variability, in part because of altered levels of CYP3A4 expression by various environmental factors and functionally important polymorphisms present in CYP3A5 gene. Accumulating evidence has revealed that CYP3A4 and CYP3A5 have a significant overlapping in their substrate specificity, inducers and inhibitors. Therefore, it is difficult to define their respective contribution to drug metabolism and drug-drug interactions. Furthermore, P-glycoprotein and CYP3A are frequently co-expressed in the same cells and share a large number of substrates and modulators. The disposition of such drugs is thus affected by both metabolism and transport. In this review, we systematically summarized the frequently used CYP3A probe drugs, inducers and inhibitors, and evaluated their current status in drug development and research.

ESports, also known as competitive video gaming, has seen tremendous growth over the past few years. Several studies have been conducted that examined the potential cognitive benefits of playing video games, but few have examined the psychosocial factors needed to perform at the highest level of competitive video gaming. In this study, the researchers aimed to identify specific mental obstacles players face and any mental techniques gamers already utilize by conducting a qualitative content analysis. Interviews with five high-level competitive League of Legend players were conducted to shed light on their experiences. The interviews resulted in two high order themes. Those high order themes were the following: techniques used to achieve optimal performance and obstacles encountered by competitive gamers. The data collected can be used by a wide population in both the performance psychology field and the eSports realm, more specifically, future mental skills consultants working with League of Legends players, gamers themselves, and academics who wish to serve, improve, or study those involved in an emerging performance domain.

We present a facile two-stage UV/UV activation method for the polymerization of off-stoichiometry thiol-eneepoxy, OSTE1, networks. We show that the handling and processing of these epoxy-based resins is made easier by introducing a material with a controlled curing technique based on two steps, where the first step offers excellent processing capabilities, and the second step yields a polymer with suitable endproperties. We investigate the sequential thiol-ene and thiolepoxy reactions during these steps by studying the mechanical properties, functional group conversion, water absorption, hydrolytic stability, and thermal stability in several different thiol-ene-epoxy formulations. Finally, we conclude that the curing stages can be separated for up to 24 h, which is promising for the usefulness of this technique in industrial applications. INTRODUCTIONThe huge impact of thermoset polymers in applications ranging from biological implants to airplane building materials stems from the ability to precisely control their curing behavior while simultaneously allowing for tuned final properties. Epoxy resins belong to a particular versatile family of polymers that are widely used in industrial applications exhibiting good mechanical end-use properties, excellent bonding to a variety of substrates, and good chemical resistance. Considerable effort has been devoted to develop a plethora of different epoxies with end-properties optimized for many different applications.

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