ABSTRACT
AACOF3 is a trifluomethylketone analog of arachidonic acid, which inhibits phospholipase-A2 (PLA2). AACOCF3 was found to concentration-dependently increase basal aldosterone and corticosterone secretion by dispersed rat zona glomerulosa and zona fasciculata/reticularis cells, respectively, as well as aldosterone and cortisol production by dispersed human adrenocortical cells. Maximal effective concentration was 10(-5) M, and elicited about 2.5-3.0-fold rises in steroid output. 10(-5) M AACOCF3 also enhanced submaximally (10(-15)/10(-12) M), but not maximally (10(-9) M) ACTH-stimulated hormonal secretion. Quantitative HPLC showed that 10(-5) M AACOCF3 evokes similar increases (from 2.0- to 3.0-fold) in the basal release of the entire spectrum of adrenocortical steroids (i.e. both intermediate and definitive products of steroid synthesis), thereby suggesting that AACOCF3 acts on the early steps of steroid synthesis. Accordingly, when pregnenolone metabolism is prevented by cyanoketone, 10(-5) M AACOCF3 increased by about 8-10-fold the production of this steroid. In conclusion, we have demonstrated a side-effect of AACOCF3, which may become relevant in studies where this chemical is used to inhibit PLA2 in tissues able to convert cholesterol to pregnenolone.
Subject(s)
Adrenal Cortex Hormones/biosynthesis , Adrenal Cortex/physiology , Aldosterone/metabolism , Arachidonic Acids/pharmacology , Corticosterone/metabolism , Enzyme Inhibitors/pharmacology , Hydrocortisone/metabolism , Phospholipases A/antagonists & inhibitors , Adrenal Cortex/drug effects , Animals , Cells, Cultured , Humans , Kinetics , Male , Phospholipases A2 , Rats , Rats, Sprague-Dawley , Zona Fasciculata/physiology , Zona Glomerulosa/physiology , Zona Reticularis/physiologyABSTRACT
The results are reported of an epidemiological study carried out in the province of Treviso in north-east Italy. The research was designed to ascertain the sensitization, through an IgE mechanism, to the main allergens present on cattle farms. Also reported are the results of a mite survey undertaken in ten barns in the same region. Investigations revealed a significantly larger degree of sensitization to storage mites among cattle farmers than in the control subjects. This sensitization was well correlated with mite species to be found in cattle barns. However, the frequent co-sensitization to Dermatophagoides offers a topic for further study.
Subject(s)
Agricultural Workers' Diseases/etiology , Asthma/etiology , Mites/immunology , Rhinitis, Allergic, Perennial/etiology , Rhinitis, Allergic, Seasonal/etiology , Adolescent , Adult , Agricultural Workers' Diseases/immunology , Animals , Asthma/immunology , Child , Female , Humans , Immunoglobulin E/analysis , Italy , Male , Middle Aged , Rhinitis, Allergic, Perennial/immunology , Rhinitis, Allergic, Seasonal/immunology , Skin Tests , SmokingABSTRACT
Ha-ras-transformed NIH3T3 fibroblasts were compared with the parental cell line to investigate the influence of the Ha-ras oncogene on cellular chemosensitivity to antineoplastic drugs. Four NIH3T3 cell clones independently transformed by the Ha-ras oncogene, activated by mutation or overexpression, were analyzed: 3 clones were obtained by transfection of NIH3T3 cells with a mutation-activated Ha-ras gene and 1 clone by transfection of a large copy number of the normal Ha-ras proto-oncogene. Chemosensitivity of the transformed clones and of the parental cell line was analyzed when cells were in the same condition of proliferative activity and cell cycle phase distribution. No significant differences in chemosensitivity were observed between transformed and untransformed cell lines to doxorubicin, VP-16, cis-platinum or mitomycin C. Therefore, data suggest that activated Ha-ras oncogenes have no role in sensitivity to these antineoplastic agents.
