Bone status and fracture rates were evaluated in two Yugoslav populations with very different dietary habits. In district A (Podravina) the daily calcium intake was about twice that in district B (Istra). There were similar but smaller differences in the intakes of other nutrients. In district B metacarpal cortical width was reduced in all age groups of both sexes but the difference tended to decrease with age. The proximal femur fracture rate was higher in district B than district A but there was no difference between the forearm fracture rates in the two districts. Our results confirm that bone mass at any age is clearly the result of age and sex and most probably other genetically determined factors but also show that this expression is nutrition related. The data suggest that nutrition (in particular the calcium intake) is an important determinant of bone mass in young adults but seems to have little effect on age-related bone loss in either males or females. The main determinant of cortical bone mass in the elderly seems to be the cortical bone mass in middle life. The proximal femur fractures of old people reflect declining cortical bone mass but the distal forearm fractures of middle-aged women are unrelated to cortical bone mass or nutritional status.

The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.

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The metabolism and toxicity of lead, cadmium, mercury, and manganese in the postnatal period was studied in rats. Absorption, whole body retention, and organ distribution of 203Pb, "1115Cd, 203Hg, and 54Mn were determined after oral and parenteral administration of these radioisotopes. The acute oral toxicity (LD50) was determined after a single application of metal chlorides. The results obtained in sucklings show a very high intestinal absorption of all metals which is partly attributed to milk diet; a higher whole body retention, higher blood levels and a much higher accumulation in the brain; and a higher oral toxicity. These results indicate age specific differences in the pharmacokinetics of metals in sucklings. It seems reasonable to consider the early neonatal age as a critical period for metal accumulation and therefore for metal toxicity. The results are interpreted on the basis of current concepts of developmental physiology and pharmacology and suggestions for future research trends are made.

In studying the mode of action of magnesium ions on intercellular transmission (for literature see Engbaek, 1952), sympathetic ganglia offer a means of testing directly whether changes in the output of acetylcholine from the preganglionic nerve endings contribute to the failure of transmission. We have, in fact, found that the failure of ganglionic transmission produced by magnesium ions is accompanied by a decrease in the amount of acetylcholine liberated as a result of preganglionic stimulation. This finding is in agreement with the work of del Castillo & Engbaek (1954) who recently showed that neuromuscular block produced by magnesium ions is mainly of prejunctional origin.The blocking action of magnesium ions is relieved by calcium ions, and we have found that these two cations have opposite effects on the output of transmitter from the preganglionic nerve endings. The output of transmitter per nerve volley may be more than doubled by suitably increasing the concentration of calcium in Locke's solution. METHODS Anaesthesia in cats was induced with ethyl chloride and ether and maintained by intravenous injection of chloralose (0-1 g/kg). The superior cervical ganglion was prepared for perfusion by the conventional method with the modifications suggested by Perry (1953). The preganglionic cervical sympathetic trunk was stimulated through platinum electrodes with square voltage pulses of