Contact dermatitis from N-(α-chlorobenzylidene)phenylhydrazine

N-(alpha-chlorobenzylidene)phenylhydrazine (AC) is both a strong irritant and a powerful sensitizer. 5 out of 6 people at risk fell ill after only once coming into contact with this halogenated hydrazine derivative. As in the first report concerning this problem the compound was used to train chemistry students.     

β-Adrenergic stimulation induces activation of protein kinase C and inositol 1,4,5-trisphosphate increase in epidermis

Abstract Epidermal keratinocytes express β₂-adrenergic receptors on the cell membrane. The binding of the agonists to the β₂-adrenergic receptors regulates activation of adenylate cyclase. This transmembrane signaling system has been regarded to be one of the important pathways for the functions of keratinocytes. We previously reported that β-adrenergic stimulation induced a transient increase of intracellular Ca²⁺ in normal human epidermal keratinocytes. Thus we investigated the effects of epinephrine on another transmembrane signaling system, the phosphatidylinositol signal transduction pathway in pig epidermis. Treatment of pig pure epidermis with epinephrine resulted in a transient increase in inositol 1,4,5-trisphosphate with a peak at 30 s. Epinephrine induced translocation of protein kinase C from cytosol to the membrane fraction. The activation of protein kinase C, translocation of protein kinase C from cytosol to the membrane fraction, was confirmed using the β-adrenergic agonist isoproterenol. Moreover, the effect of epinephrine on the activation of protein kinase C was inhibited by preincubation with propranolol, a β-adrenergic antagonist. The increase in inositol 1,4,5-trisphosphate and translocation of protein kinase C by epinephrine are consistent with the view that β-adrenergic stimulation induces turnover of inositol phospho-lipid in pig epidermis.     

Structure-activity relationships in the murine local lymph node assay for skin sensitization: α,β-diketones

The biological activity of skin-sensitizing chemicals is related to their ability to react, either directly or after metabolic activation, with appropriate skin proteins. For direct acting electrophilic compounds, this ability can be modelled, using the RAI (relative alkylation index) approach, by a combination of electrophilicity and hydrophobicity parameters. Several structure-activity relationships based on this approach have been reported, but most of them cover guinea pig sensitization test data on what chemists would classify as relatively soft electrophilic chemicals. In the present work, an electrophilicity parameter based on Taft substituent constants is derived for hard electrophiles having a reactive carbonyl group, and is used to calculate RAI values for the analysis of sensitization test data obtained in the murine local lymph node assay (LLNA) for a series of alpha, beta-diketones. The sensitization potential of these reactive hard electrophilic carbonyl compounds in the LLNA shows a good correlation with the RAI. Overall, the findings reaffirm our view that physical organic chemistry is the key to understanding why some chemicals sensitize more strongly than others, while some do not sensitize at all, and provide further evidence of the value of the LLNA for SAR studies.