In this study, an analytical method for the detection and identification of extra virgin olive oil adulteration with four types of oils (corn, peanut, rapeseed, and sunflower oils) was proposed. The variables under evaluation included 22 fatty acids and 6 other significant parameters (the ratio of linoleic/linolenic acid, oleic/linoleic acid, total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), MUFAs/PUFAs). Univariate analyses followed by multivariate analyses were applied to the adulteration investigation. As a result, the univariate analyses demonstrated that higher contents of eicosanoic acid, docosanoic acid, tetracosanoic acid, and SFAs were the peculiarities of peanut adulteration and higher levels of linolenic acid, 11-eicosenoic acid, erucic acid, and nervonic acid the characteristics of rapeseed adulteration. Then, PLS-LDA made the detection of adulteration effective with a 1% detection limit and 90% prediction ability; a Monte Carlo tree identified the type of adulteration with 85% prediction ability.

CYP2C8 non-wild type alleles have a significant prevalence in the East African population studied. The consequent frequency of 3.6% of patients homozygous for slow metabolizer alleles represent a significant fraction of the population potentially in higher risk of adverse effects due to a less efficient metabolism of amodiaquine. As approximately 10(6) first-line treatments are currently performed in Zanzibar per year, this represents a non-negligible absolute number of amodiaquine exposures. This information constitutes a background for the pharmacovigilance programs presently being employed in Zanzibar.

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The interpretation of in vitro cytotoxicity data of Cu(II)-1,10-phenanthroline (phen) complexes normally does not take into account the speciation that complexes undergo in cell incubation media and its implications in cellular uptake and mechanisms of action. We synthesize and test the activity of several distinct Cu(II)-phen compounds; up to 24 h of incubation, the cytotoxic activity differs for the Cu complexes and the corresponding free ligands, but for longer incubation times (e.g., 72 h), all compounds display similar activity. Combining the use of several spectroscopic, spectrometric, and electrochemical techniques, the speciation of Cuphen compounds in cell incubation media is evaluated, indicating that the originally added complex almost totally decomposed and that Cu(II) and phen are mainly bound to bovine serum albumin. Several methods are used to disclose relationships between structure, activity, speciation in incubation media, cellular uptake, distribution of Cu in cells, and cytotoxicity. Contrary to what is reported in most studies, we conclude that interaction with cell components and cell death involves the separate action of Cu ions and phen molecules, not [Cu(phen) n ] species. This conclusion should similarly apply to many other Cu-ligand systems reported to date.

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Cytochrome P4502C19 (CYP2C19) is an important drug-metabolizing enzyme involved in the biotransformation of, for example, proton pump inhibitors and antidepressants. Several in vivo studies have shown that the CYP2C19 activity is inhibited by oral contraceptives, which can cause important drug interactions. The underlying molecular mechanism has been suggested to be competitive inhibition. However, the results presented here indicate that estradiol derivatives down-regulate CYP2C19 expression via estrogen receptor (ER) ␣, which interacts with the newly identified ER-binding half site [estrogen response element (ERE)] at the position Ϫ151/Ϫ147 in the CYP2C19 promoter. In gene reporter experiments in Huh-7 hepatoma cells, the activity of the luciferase construct carrying a 1.6-kb long CYP2C19 promoter fragment cotransfected with ER␣ was down-regulated upon treatment with 17␤-estradiol (EE) or 17␣-ethinylestradiol (ETE) at half-maximum concentrations of 10 Ϫ7 and 10 Ϫ8 M, respectively. Mutations introduced into the ERE half site Ϫ151/Ϫ147 significantly inhibited these ligand-dependent effects. Electrophoretic mobility shift assays and quantitative chromatin immunoprecipitation experiments revealed that estrogen receptor ␣ binds to this element. A significant suppression of CYP2C19 transcription by female sex steroids was confirmed by reverse transcription polymerase chain reaction after hormonal treatment of human hepatocytes. Inhibition experiments using a stable human embryonic kidney 293 CYP2C19 cell line revealed competitive inhibition at much higher concentrations of EE and ETE compared with those required for transcriptional inhibition. These results indicate that both EE and ETE inhibit CYP2C19 expression via an ER␣-dependent regulatory pathway, thus providing a new insight into the molecular mechanism behind the inhibitory effect of oral contraceptives on CYP2C19 activity.

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