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The medication history among hospitalized patients often relies on patients' self-reports due to insufficient communication between health care professionals. The aim of the present study was to estimate the reliability of patients' self-reported medication use. Five hundred patients admitted to an acute medical department at a Danish university hospital were interviewed on the day of admission about their recent medication use. Blood samples drawn immediately after admission were screened for contents of 5 drugs (digoxin, bendroflumethiazide, amlodipine, simvastatin, glimepiride), and the results were compared to the patients' self-reported medication history. Information on prescribed drugs dispensed from any Danish pharmacy was collected from nationwide real-time pharmacy records. The authors performed home visits in a subgroup of 115 patients 4 weeks after their discharge. Stored drugs were inspected, and patients were interviewed about their drug use. Additional blood samples were drawn for drug analysis. The median age of included patients was 72 years, and 298 patients (60%) were women. Patients reported use of 3 (median) prescription-only medications (range, 0-14) during the structured interview. The congruence between self-report and drug analysis was high for all 5 drugs measured (all kappa >0.8). However, 9 patients (2%) reported use of drugs that were not detected in their blood samples. In 29 patients (6%), the blood samples contained drugs not reported during the structured interview, but 14 of these drugs were registered in either hospital files or pharmacy records. Overall, the sensitivity of information from hospital files, structured interviews, and pharmacy records in identifying drug users was 87% to 93%, with no significant differences between methods. In conclusion, patients' self-reports are reliable when estimating recent use of cardiovascular and antidiabetic drugs.

a b s t r a c tSpecific Se-metabolites have been recognized to be the main elements responsible for beneficial effects of Se-enriched diet, and Se-methylselenocysteine (SeMCys) is thought to be among the most effective ones. Here we show that an engineered Saccharomyces cerevisiae strain, expressing a codon optimized heterologous selenocysteine methyltransferase and endowed with high intracellular levels of S-adenosyl-methionine, was able to accumulate SeMCys at levels higher than commercial selenized yeasts. A fine tuned carbon-and sulfate-limited fed-batch bioprocess was crucial to achieve good yields of biomass and SeMCys. Through the coupling of metabolic and bioprocess engineering we achieved a $ 24-fold increase in SeMCys, compared to certified reference material of selenized yeast. In addition, we investigated the interplay between sulfur and selenium metabolism and the possibility that redox imbalance occurred along with intracellular accumulation of Se. Collectively, our data show how the combination of metabolic and bioprocess engineering can be used for the production of selenized yeast enriched with beneficial Se-metabolites.

Lipid peroxidation induced etheno-DNA adducts are promutagenic and have been suggested to play a causal role in the development of human cancers. Therefore, human biomonitoring of etheno-DNA adducts in urine has been suggested as a potential marker for oxidative stress-related DNA damage. For quantitative determination, a column-switching LC/APCI-MS/MS method was developed for simultaneous analysis of Ade, dC, and dA in human urine. Quantitative validation parameters (precision, within-day repeatability, and betweenday reproducibility) yielded satisfactory results below 10%. Limit of quantification for Ade, dC, and dA was 5.3 fmol, 7.5 fmol, and 1.3 fmol on column, respectively. Mean urinary excretion rates of a six healthy volunteers were 45.8 pmol Ade/24 h, 96.8 pmol dC/24 h, and 18.1 pmol dA/24 h. The demonstrated levels of performance suggest a future applicability of this method to studies of cancer and other diseases related to oxidative stress in humans. To our knowledge, this is the first method described that allows simultaneous determination of Ade, dC, and dA in human urine samples. [2], are also generated endogenously by reactions of DNA with products derived from lipid peroxidation and oxidative stress [3]. These DNA adducts have miscoding potential and specific repair pathways supporting the hypothesis that -DNA adducts play a causal relationship in carcinogenesis [4]. Furthermore, several studies have found elevated -DNA adduct levels in disorders known as risk factors for cancers [5,6]. Therefore -DNA adducts have been proposed as biomarkers for human cancers associated with certain lifestyles or chronic inflammations [4]. Upon DNA repair, -DNA adducts are excreted in the urine and could, in that respect, be used to investigate the body burden of DNA damage.The analytical procedures for urinary DNA adducts are challenging indeed. The presence of many interfering substances in concentrations far greater than those of the DNA adducts demands high selectivity and low limit of quantitation for unequivocal identification and quantification. Methods using high-performance liquid chromatography (HPLC) with fluorescence detection have been used for dA determination [4,7] after immunoaffinity clean-up and a very tedious sample preparation. Furthermore, the internal standard was measured separately. Several etheno-DNA adducts have been determined in urine from healthy humans using gas chromatography-electron capture negative chemical ionization mass spectrometry (GC/EC-NCI/ MS) [8 -11]. Gas chromatography offers the advantage of greater peak resolution compared to conventional LC. However, the requirement for derivatization before analysis is a major limitation. Recently, LC-MS have been employed in determination of etheno adducts from human urine using electrospray ionization (ESI) [12][13][14]. Atmospheric pressure chemical ionization (APCI) has been used for analysis of dA and 1,N 2 -dG in vitro [15] and of dA in human urine [16].In this paper, we report that solid-phase extraction (SPE) for preconcent...

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Selenium (Se) is an essential element for most eukaryotic organisms, including humans. The balance between Se toxicity and its beneficial effects is very delicate. It has been demonstrated that a diet enriched with Se has cancer prevention potential in humans. The most popular commercial Se supplementation is selenized yeast, which is produced in a fermentation process using an inorganic source of Se. Here, we show that the uptake of Se, Se toxic effects and intracellular Se-metabolite profile are largely influenced by the level of sulphur source supplied during the fermentation. A Yap1-dependent oxidative stress response is active when yeast actively metabolizes Se, and this response is linked to the generation of intracellular redox imbalance. The redox imbalance derives from a disproportionate ratio between the reduced and oxidized forms of glutathione and also from the influence of Se metabolism on the central carbon metabolism. The observed increase in glycerol production rate, concomitant with the inhibition of ethanol formation in the presence of Se, can be ascribed to the occurrence of redox imbalance that triggers glycerol biosynthesis to replenish the pool of NAD(+) .