Effect of pyridoxal isonicotinoyl hydrazone and other hydrazones on iron release from macrophages, reticulocytes and hepatocytes

A model consisting of 59Fe-labelled macrophages was developed for screening potential iron-chelating drugs. Mouse peritoneal macrophages, induced by previous intraperitoneal injections of 3% thioglycollate, were labelled in vitro by their exposure to immune complexes of 59Fe-transferrin-antitransferrin antibody. Optimal conditions for macrophage labelling and subsequent 59Fe release were established. Sixty-two aromatic hydrazones, the majority of which had iron binding structures similar to pyridoxal isonicotinoyl hydrazone, were synthesized by condensation of aromatic aldehydes (pyridoxal, salicylaldehyde, 2-hydroxy-1-naphthylaldehyde and 2-furaldehyde) with various acid hydrazides prepared by systematic substitutions on the benzene ring. These compounds were examined for their potential to stimulate 59Fe release from 59Fe-labelled macrophages and also from reticulocytes and hepatocytes loaded with non-heme 59Fe. The majority of hydrazones derived from pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde seemed to be equally effective in both the macrophage and reticulocyte testing systems. However, the pyridoxal hydrazones were much more active in hepatocytes than the other groups of hydrazones. Several compounds proved to be very potent in mobilizing 59Fe. These included hydrazones derived from 2-hydroxy-1-naphthylaldehyde and benzoic acid hydrazide, p-hydroxybenzoic acid hydrazide, 2-thiophenecarboxylic acid hydrazide, and also pyridoxal benzoyl hydrazone, pyridoxal m-fluorobenzoyl hydrazone and pyridoxal 2-thiophenecarboxyl hydrazone.     

Acidic glycosaminoglycans in developing sterno-costal cartilage of the hydrocephalic (ch+/ch+) mouse

The sterno-costal cartilage of the hydrocephalic mouse carrying the autosomal recessive gene (ch+/ch+) has 40 ± 3% of the acidic glycosaminoglycan concentration of the normal control containing the satin marker (+sa/+sa). The acidic glycosaminoglycan concentration of the sterno-costal cartilage in the heterozygous mouse (ch+/+sa) is significantly higher (114 ± 8%) than the normal control. The distribution of the acidic glycosaminoglycans in the sterno-costal cartilage is similar in the normal, heterozygous and homozygous mice at all stages of development studied, (prenatal, newborn and postnatal) being 78 ± 4% chondroitin 4(6)-sulfate and 22% hyaluronic acid and/or keratan sulfate. The concentration of acidic glycosaminoglycans in the sterno-costal cartilage decreases as development progresses in all three gene types of mice. The reduced level of acidic glycosaminoglycans in the sterno-costal cartilage of the autosomal recessive mouse, ch+/ch+, is associated with a defect in the formation of the sternum. The higher than normal acidic glycosaminoglycan concentration in the sterno-costal cartilage of the heterozygous mouse ch+/+sa is associated with delayed calcification of the sternum. This study characterizes the molecular locus of a defect in the extra-cellular matrix of a mouse carrying a lethal gene and may help in understanding proteoglycan disorders (mucopolysaccharidosis) in the human.     

Adverse Effect on Bacteria of Peritoneal Dialysis Solutions that Contain Acetate

Peritoneal dialysis solutions which contained 43 mEq per litre of acetate had a greater antibacterial effect than those containing lactate. Bacteria were isolated from 15 separate clinical infections, each caused by Escherichia coli, Pseudomonas sp., or Staphylo-coccus aureus. Incubation in the dialysate made with acetate substantially reduced the number of viable organisms from all but one of the 45 isolates. It is suggested that solutions made with acetate may provide greater protection from peritonitis.