A family of "click" nucleosides for metal-mediated base pairing: unravelling the principles of highly stabilizing metal-mediated base pairs.

A family of artificial nucleosides has been developed by applying the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. Starting from 2-deoxy-ß-D-glycosyl azide as a common precursor, three bidentate nucleosides have been synthesized. The 1,2,3-triazole involved in all three nucleobases is complemented by 1,2,4-triazole (TriTri), pyrazole (TriPyr), or pyridine (TriPy). Molecular structures of two metal complexes indicate that metal-mediated base pairs of TriPyr may not be fully planar. An investigation of DNA oligonucleotide duplexes comprising the new "click" nucleosides showed that they can bind Ag(I) to form metal-mediated base pairs. In particular the mispair formed from TriPy and the previously established imidazole nucleoside is significantly stabilized in the presence of Ag(I). A comparison of different oligonucleotide sequences allowed the determination of general factors involved in the stabilization of nucleic acids duplexes with metal-mediated base pairs.

Systematic review and quantification of respiratory cancer risk for occupational exposure to hexavalent chromium.

AIM: To investigate the exposure-risk relationship for occupational chromium (VI) exposure and lung cancer in order to establish exposure limits. METHODS: We systematically searched for studies reporting on occupational Cr(VI) exposure and cancers of the respiratory tract. To be included, studies needed to provide data for more than one level of occupational Cr(VI) exposure, adequately consider the confounder smoking and be of adequate methodological quality. Because direct genotoxicity was considered the predominant mechanism of carcinogenesis of Cr(VI), linear models were applied in order to fit risk data. Relative risks were calculated based on these linear regression models and then used to estimate excess absolute risks. RESULTS: Five studies of two cohorts of chromium production workers in Baltimore, Maryland, and Painesville, Ohio, were included. Based on different estimates for the exposure effect, the absolute excess risk was found to be "acceptable" (less than 4 per 10,000 according to the German Committee on Hazardous Substances, "AGS") at a Cr(VI) concentration of 0.1 µg/m(3), and became "intolerable" (more than 4 per 1,000) beyond a Cr(VI) concentration of 1 µg/m(3). CONCLUSION: Occupational exposure limits for Cr(VI) based on excess absolute risks can be derived from published data identified by a systematic literature review.

Determination of arginine and asymmetric dimethylarginine (ADMA) in human plasma by liquid chromatography/mass spectrometry with the isotope dilution technique.

Arginine (ARG) is a substrate for endogenous nitric oxide (NO) production whereas its metabolite, asymmetric dimethylarginine (ADMA), acts as an inhibitor. Sufficient NO production is essential for cardiovascular key functions, thus elevated concentration levels of ADMA are related to a range of cardiovascular diseases. Owing to the lack of reliable methods for the measurement of ARG and ADMA in human plasma, concentration values determined with these methods can differ considerably. We present here a simple and very robust liquid chromatographic/mass spectrometric method for the determination of ARG and ADMA utilizing isotope-labeled internal standards. Sample preparation requires only protein precipitation; the analytes were derivatized with o-phthalaldehyde-mercaptoethanol and separated on a reversed-phase C(18) column with gradient elution. The analytes were detected with an electrospray ionization ion trap instrument working in the full-scan single mass spectrometry mode. Concentration values obtained with this method for healthy controls were ARG = 63.9 +/- 23.9 microM and ADMA = 0.355 +/- 0.066 microM, with a normal range for ADMA from 0.225 to 0.485 microM. The corresponding values for end-stage chronic renal failure patients are ARG = 48.1 +/- 18.5 microM, p < 0.01 and ADMA = 0.673 +/- 0.134 M, p < 0.001.