A range of new analogues of the promising iron chelator pyridoxal isonicotinoyl hydrazone was prepared and assessed for activity in reducing hepatocyte iron, mechanism of action and potential in iron-chelation therapy. A total of 45 compounds were synthesized by condensation of aromatic aldehydes (pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde) with various acid hydrazides prepared by systematic substitutions on the benzene ring or by the replacement of the ring with an acetyl, pyridyl, furoyl or thiophene moiety. The effects of these compounds on 59Fe uptake and intracellular distribution in hepatocytes in culture and on 59Fe mobilization from prelabeled hepatocytes were assessed. Toxicity, lipophilicity and the ability to chelate plasma transferrin-bound 59Fe were also evaluated. Several compounds were much more active than pyridoxal isonicotinoyl hydrazone and may have clinical potential. These included pyridoxal benzoyl hydrazone, pyridoxal p-methoxybenzoyl hydrazone, pyridoxal m-fluorobenzoyl hydrazone and pyridoxal 2-pyridyl hydrazone. All were more effective at reducing iron uptake than mobilizing hepatocyte iron; they also may act primarily on the transit iron pool rather than on storage iron. Other compounds (e.g., salicylaldehyde p-t-butyl-benzoyl hydrazone) redistributed ferritin-59Fe to different intracellular sites but had little net effect on hepatocyte iron levels.
Meta-analytic examination of I28 false consensus effect issues supports the hypothesis that the "Golden Section" (61.8% group size) approximates the level of actual consensus that separates overestimation of consensus (group size < 61.8%) from underestimation (group size > 61.8%). Overestimation of the actual percentage of others who endorse one's own view increases as actual consensus decreases from 61.8%, and underestimation increases as it exceeds 61.8%. The form of the response (viz, a yes or no answer to a question) moderates this conclusion. The Golden Section holds for majorities and minorities defined by agreement with an issue. For majority and minority groups defined by disagreement, the inflection point is higher. Contrary to Mullen and Hu (1988), for agreeing majorities, the slope for consensus underestimation as a function of increased majority size does not differ from that of minority overestimation.
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