Preclinical PK and PD studies on 2'-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model.

Antisense oligonucleotides (AONs) are being developed as RNA therapeutic molecules for Duchenne muscular dystrophy. For oligonucleotides with the 2'-O-methyl-phosphorothioate (2OMePS) RNA chemistry, proof of concept has been obtained in patient-specific muscle cell cultures, the mouse and dog disease models, and recently by local administration in Duchenne patients. To further explore the pharmacokinetic (PK)/pharmacodynamic (PD) properties of this chemical class of oligonucleotides, we performed a series of preclinical studies in mice.

Relations between sulphate, ammonia, nitrate, acidity and trace element concentrations in tree bark in The Netherlands.

Bark flakes were sampled in a biomonitoring survey throughout The Netherlands. Tree species used were oak (65 samples) and 'non-oak' (58 samples) (poplar, elm, willow). Bark elemental analysis was carried out for As, Br, Ca, Cd, Ce, Co, Cr, Cs, Fe, Hg, K, La, Na, Ni, Pb, Rb, Sb, Sc, Se, Sm, Th, and Zn.

Moss interspecies comparisons in trace element concentrations.

Within the framework of a European-scaled moss survey, various moss species were sampled throughout The Netherlands [NL], Germany [D], and Switserland [CH], and used in moss interspecies comparisons of elemental concentrations. Moss species considered were Pleurozium schreberi [NL,D,CH], Brachythecium rutabulum [NL], Hypnum cupressiforme [D,CH], Hylocomium splendens [D,CH], and Scleropodium purum [D]. Element analysis was carried out directly (The Netherlands, Instrumental Neutron Activation Analysis: As, Br, Ce, Cr, Cs, Fe, La, Mn, Na, Rb, Sc, Se, Sm, Th, Ti, V and Zn), or after sample digestion (The Netherlands, ICP-MS: Pb, Germany, AAS/ICP-AES: Cd, Cr, Cu, Fe, Ni, Pb, Ti, V, and Zn; Switzerland, ICP-AES/ICP-MS: Co, V, and Zn).

Factor analysis of trace-element data from tree-bark samples in The Netherlands.

Monte Carlo-assisted factor analysis has been applied to a data set of 20 trace-element concentrations in tree-bark samples obtained from 123 locations in The Netherlands, with the aim to investigate the suitability of bark as a biomonitor for air pollution. A Monte Carlo approach was used to give more insight to the uncertainties and significance levels of the factor analysis results. Notwith-standing a rather strong influence of soil material on the concentration levels, factor analysis enabled the identification of five significant pollution source types, all of which corresponded with source types found in an earlier biomonitoring study in The Netherlands using epiphytic lichens.