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The Finnish forest workers' trade union and employers' organizations signed their first wage agreement in 1957 and first collective labour agreement in 1962. Many other sectors had concluded such agreements years earlier. This article challenges the widely accepted idea that collective labour agreements were becoming ubiquitous in Finnish industrial relations soon after the Second World War. Forest workers were left out of this process, and up until the late 1950s their wages and working conditions were not determined by the labour market parties but by state authorities – the state legislated and regulated forestry wages. The explanation for the delayed development of labour market practices in this sector can be found in forest work itself as well as the state's active role. This work was, up until the 1960s, done mainly by small farmers who were reluctant to unionize and unable to otherwise promote their interests. The situation changed when professionalization made them more or less full-time forest workers who more often joined the union. At the same time, the state created organizations and institutions which encouraged labour market parties to cooperate. Their shared struggle against political interference pushed labour market parties towards collective bargaining. [ABSTRACT FROM PUBLISHER]

Abstract: Drug metabolism can result in the production of highly reactive metabolites that may form adducts with cellular macromolecules, and thus initiate adverse drug reactions, cause toxicity, and even require the withdrawal of drug from the market. In this study, a 2′-deoxyguanosine (dG)-based chemical trapping test system was developed for use as a fast screening tool for DNA adducting metabolites of new drug candidates. Reactive metabolites were generated from parent compounds in in vitro incubations with phenobarbital-induced mouse liver microsomes, human liver microsomes and different recombinant human CYP enzymes in the presence of dG. The formed dG-adducts were separated, characterized and their stability was studied by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The method was evaluated with six test compounds, aflatoxin B1, estrone, clozapine, tolcapone, ticlopidine and imipramine. Estrone and aflatoxin B1 formed dG adducts with phenobarbital-induced mouse liver microsomes, human liver microsomes and human recombinant CYP enzymes. Adduct formation was also observed with tolcapone when phenobarbital-induced mouse liver microsomes were used as the enzyme source. The stability of each formed adduct was independent of the different enzyme sources. No dG-adducts were identified with ticlopidine, clozapine and imipramine. Compared to other classical DNA reactivity tests, e.g. Ames test, the present surrogate endpoint, the dG adduct, is faster, enables the characterization of the formed compounds, and also permits the investigation of more unstable adducts. [Copyright &y& Elsevier]

Abstract: This paper describes a d-peptide isomer-based trapping assay using an LC/MS ion-trap spectrometer with an electrospray ionization (ESI) source as the analytical tool to study bioactivation of xenobiotics. Reactive metabolites were generated from parent compounds in in vitro incubations with different sources of CYP enzymes. A short d-isomer of gly-tyr-pro-cys-pro-his-pro proved to be a sensitive trapping agent and resistant to proteases. This method was tested with 16 probe substances. Acetaminophen, 1-chloro 2,4-dinitrobenzene, clozapine, diclofenac, imipramine, menthofuran, propranolol, pulegone and ticlopidine all formed d-peptide adducts, which were analogous to the GSH adducts previously described in the literature. New adducts were identified with clopidogrel (–Cl+peptide), nicotine (–CH3+H+peptide), nimesulide (+peptide) and tolcapone (+peptide), i.e., no GSH adducts of those drugs have been described in the literature. No adducts were identified with ciprofloxacin, ketoconazole and verapamil. In the literature no GSH adducts have been described with ciprofloxacin and verapamil. d-Peptide-based trapping proved to be a reliable and reproducible method to identify bioactivated intermediates. d-Peptide is a new and convenient protein trapping agent for use in early phase screening of bioactivation of new chemical entities and evaluation of toxic properties of chemicals. [ABSTRACT FROM AUTHOR]

The serotonin receptor 5-HT ligand 4-[F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide ( p-[F]MPPF) was produced by a simplified method of Le Bars et al. Traditional oil bath heating was compared to microwave heating. Various radioanalytical methods, radio-Thin Layer Chromatography (TLC), High Pressure Liquid Chromatography (HPLC) and Mass Spectrometry (MS), were compared in the evaluation of the labelled product(s). The crude reaction mixture consisted of p-[F]MPPF and 2-4 radioactive by-products eluting after the product fraction, and the reverse-phase HPLC method failed occasionally to separate p-[F]MPPF from the radioactive by-product with close retention time. The heating method had no significant effect on the composition of labelled by-products. In LC-(ESI)-MS analysis of p-[F]MPPF the labelled product was identified with m/ z ratio of 435 ([M + H]). The other HPLC fractions were measured to have following m/ z ratios: (1) 327; 349; (675) (2) 402; 407/408; (791) and (3) 436, suggesting different kind of decomposition of the labelled product and/or the inactive precursor. The ion trap mass spectrometer was sufficient for the qualitative analysis of p-[F]MPPF. However, differentiation of by-products arising from the decomposition of p-[F]MPPF or from its precursor p-MPPNO proved to be challenging. [ABSTRACT FROM AUTHOR]

Interactions between Intralipid dispersion and local anesthetics (bupivacaine, prilocaine, and lidocaine) were investigated. The amount of bupivacaine (the most cardiotoxic analyte of the local anesthetics studied) entrapped in Intralipid in the presence of plasma was studied using an off-line filtration and solid phase extraction method combined with capillary zone electrophoresis for quantification of free unbound bupivacaine. To confirm interactions between the analytes and Intralipid at lower concentrations, direct injection mass spectrometry was used. The use of immobilized Intralipid chromatography-atmospheric pressure ionization–ion trap mass spectrometry in the study of interactions between drugs and Intralipid dispersion is demonstrated. Finally, interactions between Intralipid dispersion and local anesthetics were investigated by electrokinetic capillary chromatography. The electrophoretic mobility of the Intralipid dispersed phase was calculated using the iterative procedure and a homologous series of alkyl phenyl benzoates (C1–C6), and the retention factors for the analytes were determined. [ABSTRACT FROM AUTHOR]