Optical biosensors have exhibited worthwhile performance in detecting biological systems and promoting significant advances in clinical diagnostics, drug discovery, food process control, and environmental monitoring.

Gemfibrozil increases plasma concentrations of simvastatin and, in particular, its active form, simvastatin acid, suggesting that the increased risk of myopathy in combination treatment is, at least partially, of a pharmacokinetic origin. Because gemfibrozil does not inhibit CYP3A4 in vitro, the mechanism of the pharmacokinetic interaction is probably inhibition of non-CYP3A4-mediated metabolism of simvastatin acid.

ABSTRACT:To explore the mechanism of the interaction between gemfibrozil and cerivastatin, the enzyme mapping of the oxidative metabolism of cerivastatin and the effect of gemfibrozil on cerivastatin metabolism were studied using human liver microsomes and expressed cytochrome P450 (P450) CYP2C8 and 3A4 isoforms.

This article is available online at http://dmd.aspetjournals.org ABSTRACT:To clarify the oxidative metabolism of methadone (R)-and (S)-enantiomers, the depletion of parent (R)-and (S)-methadone and the formation of racemic 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine were studied using human liver microsomes and recombinant cytochrome P450 enzymes. Based on studies with isoform-selective chemical inhibitors and expressed enzymes, CYP3A4 was the predominant enzyme involved in the metabolism of (R)-methadone. However, it has different stereoselectivity toward (R)-and (S)-methadone. In recombinant CYP3A4, the metabolic clearance of (R)-methadone was about 4-fold higher than that of (S)-methadone. CYP2C8 is also involved in the metabolism of methadone, but its contribution to the metabolism of (R)-methadone was smaller than that of CYP3A4. But for the metabolism of (S)-methadone, the roles of CYP2C8 and CYP3A4 appeared equal. Although CYP2D6 is involved in the metabolism of (R)-and (S)-methadone, its role was smaller compared with CYP3A4 and CYP2C8. Using clinically relevant concentrations of ketoconazole (1 M, selective CYP3A4 inhibitor), trimethoprim (100 M, selective CYP2C8 inhibitor), and paroxetine (5 M, potent CYP2D6 inhibitor), these inhibitors decreased the hepatic metabolism of (R)-[(S)-]methadone by 69% (47%), 22% (51%), and 41% (77%), respectively. However, inhibition of the metabolism of (R)-and (S)-methadone by paroxetine was due to inhibition not only of CYP2D6, but also CYP3A4 and, to a minor extent, CYP2C8. The present in vitro findings indicated that CYP3A4, CYP2C8, and CYP2D6 are all involved in the stereoselective metabolism of methadone (R)-and (S)-enantiomers. These data suggest that coadministration of inhibitors of CYP3A4 and CYP2C8 may produce clinically significant drug-drug interactions with methadone.

The combination of DOPO and 2-aminobenzothiazole (ABZ) was designed to develop P/N/S-containing flame retardant DOPO-ABZ, and its chemical structure was confirmed by HRMS, FTIR, and 1H and 31P NMR. The reduced thermal stability of EP/DOPO-ABZ formulations was found through DSC and TGA, as compared to that of EP. Fire properties were evaluated by LOI, UL-94, and cone calorimeter tests, respectively. The results indicated that DOPO-ABZ imparted flame retardance to EP, and that EP/7.5 wt % DOPO-ABZ passed the V-0 rating, and acquired a LOI value of 33.5%; moreover, when the loading of DOPO-ABZ increased to 10 wt %, it could further suppress the heat release and smoke release of the curved epoxy resin. Finally, the flame-retardant mechanism was studied by TG-FTIR and py-GC/MS, disclosing that DOPO-ABZ exerted predominant gaseous-phase activity of fire inhibition via generating phosphorus-containing free radicals and nitrogen/sulfur-containing volatiles.

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ABSTRACT:To evaluate the inhibitory effects of trimethoprim and sulfamethoxazole on cytochrome P450 (P450) isoforms, selective marker reactions for CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were examined in human liver microsomes and recombinant CYP2C8 and CYP2C9. The in vivo drug interactions of trimethoprim and sulfamethoxazole were predicted in vitro using

Stimuli‐responsive micro/nanostructures that can dynamically and reversibly adapt their configurations according to external stimuli have stimulated a wide scope of engineering applications, ranging from material surface engineering to micromanipulations. However, it remains a challenge to achieve a precise local control of the actuation to realize applications that require heterogeneous and on‐demand responses. Here, a new experimental technique is developed for large arrays of hybrid magnetic micropillars and achieve precise local control of actuation using a simple magnetic field. By manipulating the spatial distribution of magnetic nanoparticles within individual elastomer micropillars, a wide range of the magnetomechanical responses from less than 5% to ≈50% for the ratio of the bending deflection to the original length of the pillars is realized. It is demonstrated that the micropillars with different degrees of bending deformation can be configured in any spatial pattern using a photomask‐assisted template‐casting technique to achieve heterogeneous, site‐specific, and programmed bending actuations. This unprecedented local control of the micropillars offers exciting novel applications, as demonstrated here in encryptable surface printing and stamping, direction‐ and track‐programmable microparticle/droplet transport, and smart magnetic micro‐tweezers. The hybrid magnetic micropillars reported here provide a versatile prototype for heterogeneous and on‐demand actuation using programmable stimuli‐responsive micro/nanostructures.