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Four baboons receiving intramuscular iron for 15 months were compared with two control baboons. From the overall two-year observation period the following data emerge: (1) The baboon is a suitable animal for obtaining a massive and chronic iron overload. Liver iron concentrations reached very high levels (ranging from 41.3 to 180.6 mumol/100 mg dry weight vs 1.7 +/- 0.5, mean +/- SEM, in controls), and a major liver iron overload (ie, with concentration values greater than or equal to 18) was present in all four animals for an average period of 16.5 months (range 14-19). (2) When compared with human hepatic iron-overload disorders, iron distribution was similar to that observed in secondary (transfusional) hepatic siderosis since iron deposits were found primarily in sinusoidal cells. However, a marked parenchymal siderosis was also obtained close to that observed in primary (genetic) siderosis. Iron toxicity was present biologically as indicated by an increase in serum transaminases. Histologically, a slight fibrosis was observed in the most heavily iron-overloaded baboon. On the whole, this study of subhuman primates brings new evidence that iron per se has only a minor hepatic damaging effect. It also suggests that the iron-overloaded baboon liver provides a promising tool for the study of liver cell disturbances in human iron overload.
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PMID:Experimental hepatic iron overload in the baboon: results of a two-year study. Evolution of biological and morphologic hepatic parameters of iron overload. 686 91

Effects of dietary iron deficiency on growth, the distribution of hemoglobin (Hb) at rest and during exercise, the characteristics of muscle fiber types, and glycogen depletion patterns were studied in newly weaned male mice. Forty-eight mice were randomly divided into iron-deficient and control diet groups. Severe iron deficiency impaired general growth, but growth was restored following iron repletion. The mean +/- SEM blood Hb concentrations at rest after 7 weeks were 5.8 +/- 0.7 and 12.5 +/- 0.3 g/dl in iron-deficient and control groups, respectively. The mice fed iron-deficient diet for 7 weeks had an increased Hb level of 10.9 +/- 0.5 g/dl 1 week after an i.p. injection of Imferon (1.25 mg Fe). The Hb contents in brain and gastrocnemius as well as whole body were lowered by iron deficiency. Iron-deficient anemic mice tended to increase the percent distribution of Hb to brain during exercise. This value was significantly greater than in control and iron-treated groups. The iron-deficient group had relatively less glycogen than controls, but no significant tendency in glycogen depletion pattern was observed in any fiber types. It is suggested that decreased Hb content in working muscles due, in part, to greater distribution to brain could be one of the limiting factors for work performance in anemic individuals. It is further suggested that decrease in oxidative muscle fibers as well as the decreased concentration and/or activities of oxidative substances may also be one of the limiting factors.
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PMID:Effects of dietary iron deficiency on muscle fiber characteristics and whole-body distribution of hemoglobin in mice. 688 25

Immunologic studies were performed in ten iron-deficient children, aged 12 to 30 months, before and after iron replacement. Chronic infection, malnutrition, and vitamin deficiency were excluded. Mean hemoglobin levels went from 8.2 +/- 0.2 (SEM) to 12.3 +/- 0.3 g/dL after iron replacement. Mean T-cell percentage increased from 50% +/- 3.0% to 58% +/- 3.7%. Absolute numbers of T cells were unchanged. Three children converted negative in vitro proliferative responses to Candida or tetanus antigen. Mean stimulation indexes increased for Candida (6.8 +/- 1.7 to 17.9 +/- 6.7) and tetanus (19.5 +/- 6.0 to 31.7 +/- 8.5). Nine of 16 delayed hypersensitivity skin tests were positive before and ten of ten were positive after iron therapy. The IgG and IgA levels did not change significantly, but IgM levels decreased from 181 +/- 13 to 128 +/- 5 mg/dL. We conclude that T-cell immunity is slightly impaired in pure iron deficiency and that these subtle defects can be corrected with oral iron replacement.
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PMID:Immune function in pure iron deficiency. 698 45

Peritoneal rat macrophages and rabbit polymorphonuclear leukocytes were obtained after thioglycollate or glycogen stimulation. Optimal conditions for phagocytosis were determined by a recently developed quantitative fluorimetric assay. We studied by serial SEM micrographs macrophages and polymorphonuclear leukocytes incubated either in medium or in the presence of different types of phagocytic particles. We compared the morphological aspects of adsorption and phagocytic processes for opsonized microorganisms (Micrococcus lysodeikticus and Candida albicans) with these for inert beads of iron and metallic mercury. Without phagocytosis, in the presence of fresh homologous serum, we observed a progressive development of microvilli or lamellipodia in ruffles and by the end, hypertrophied ruffles appeared at one pole of the cell. We noted extremely well developed ruffles during phagocytosis of opsonized microorganisms. These were practically absent on the macrophages incubated with inert particles. The mean number of adsorbed particles is more elevated in the case of iron and metallic mercury beads than for microorganisms. The rate of ingestion of inert particles was considerably higher than for microorganisms even when they were opsonized. In conclusion, at all stages of the phagocytic process, we observe different morphological features of the macrophages depending on the nature of the phagocytosed particles.
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PMID:SEM morphological studies of phagocytosis by rat macrophages and rabbit polymorphonuclear leukocytes. 699 99

A phosphate redox electrode system (PRES) was designed, constructed, and evaluated for analysis of inorganic phosphate in serum. This system is based on the observed phosphate ion potential of a chemically treated iron wire in a turbulent flow-through cell at constant oxygen tension. We analyzed 110 clinical samples by this technique and with the Technicon SMAC. Of the specimens analyzed, 32% contained abnormal phosphate concentrations. Each was assayed two to four times with the PRES and once with the SMAC. The PRES assay rate was 60 samples/h. Mean phosphorus concentrations (and SEM) were: PRES, range of values for replicate data sets, 30.5-31.0 (0.5-1.1) mg/L; SMAC, 30.8 (1.0) mg/L. Results for the PRES (y) correlated well with those by the SMAC: r = 0.968 to 0.980, estimated slope = 0.99 to 1.03, and estimated intercept = -1.1 to 0.1 mg/L. Differences in results by the two methods were not statistically significant.
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PMID:Analysis of phosphate in serum with the phosphate redox electrode system. 707 36

The absorption of zinc and iron was determined in seven elderly men using the enriched stable isotopes 70Zn and 58Fe. Analyses of isotopic ratios were done using thermal ionization magnetic sector mass spectrometry on chloride solutions of zinc and of iron after separation of zinc from fecal samples by ion exchange and of iron by solvent extraction. Mean apparent zinc absorption in the seven subjects was 17.3 +/- 3.1% (mean +/- SEM) and mean iron absorption was 7.9 +/- 2.5% (mean +/- SEM) when fed a semipurified diet containing 15 mg of zinc and 10 mg of iron daily. Quantities absorbed were equivalent to an average of 2.6 mg of zinc and 0.8 mg of iron per day. These average zinc and iron values are close to previous estimates of endogenous losses of zinc and iron.
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PMID:Use of enriched stable isotopes to determine zinc and iron absorption in elderly men. 708 Oct 87

Liver iron concentrations were determined in 60 alcoholics with liver disease of varying severity, 15 patients with untreated idiopathic hemochromatosis, and 16 control subjects with biliary tract disease. Mean liver iron concentrations (microgram/100 mg dry weight) were significantly greater in the alcoholics (156.4 +/- 7.8 (SEM); P less than 0.05) and in patients with idiopathic hemochromatosis (2094.5 +/- 230.7; P less than 0.01) than in control subjects (53.0 +/- 7.0). Liver iron concentrations of greater than 140 micrograms/100 were found in 17 alcoholics (29%) and in all 15 patients with idiopathic hemochromatosis. Liver iron concentrations greater than 1000 micrograms/100 mg were found in all patients with idiopathic hemochromatosis but in none of the alcoholics. In the alcoholics no relationship existed between liver iron concentrations and the amount of alcohol consumed daily, the length of the drinking history, the amount of beverage iron consumed daily, or the severity of the liver disease. Serum ferritin concentrations reflected iron stores in patients with hemochromatosis and in alcoholics with minimal liver disease. However, in alcoholics with significant liver disease serum ferritin concentrations did not reflect iron stores accurately, although with normal values iron overload is unlikely. Serum iron concentration and percentage saturation of total iron-binding capacity were of little value in assessing iron status in either alcoholics or patients with hemochromatosis. Measurement of the liver iron concentration clearly differentiates between alcoholics with significant siderosis and patients with idiopathic hemochromatosis.
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PMID:Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis. 711 74

Two-3-wk balance studies for zinc, copper, and iron were carried out in six elderly male subjects who were confined to a metabolic unit for a long-term study (12 wk) with constant dietary mineral intake. Average zinc balance was 0.1 +/- 0.05 (mean +/- SEM) and serum zinc increased in all subjects during the course of the study. Average copper balance was 0.06 +/- 0.06 (mean +/- SEM). There was no significant change in serum copper ceruloplasmin, but all were within normal ranges except for elevated serum copper in one subject who appeared to be in negative copper balance. Iron balance appeared to be negative, -0.44 +/- 0.16 (mean +/- SEM), despite improved blood iron parameters in five of six subjects. Results of this long-term balance study suggests that current dietary recommendations of 15 mg of zinc and 2 to 3 mg of copper are adequate for elderly as well as younger adults. However, balance data for individuals must be interpreted with caution, should be used only with other parameters, and should not be relied on exclusively as a basis for dietary recommendations. Additional data are needed to evaluate dietary iron recommendations for elderly men.
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PMID:Zinc, copper, and iron balance in elderly men. 731 65

At the Lawrence Berkeley Laboratory Bevalac Facility, iron nuclei were accelerated to an energy of 600 MeV/amu. The beam of iron thus obtained was used to irradiate living biological specimens in order to study possible microscopic tissue damage with the aid of SEM. The experiments involved total head irradiation of live rats which were subsequently returned to their cages to remain for 1 day and 30 days before further examination. After the 1 day and 30 day waits, both eyes were enucleated and placed in chemical fixative followed by ethanol dehydration and critical point drying. Retinas were carefully removed from the eye cups and loaded separately on aluminum stubs which were sputter coated. SEM of the 1 day and 30 day retinas revealed lesions which were not found at all in control retinas. The 1 day and 30 day retinas manifest regions where outer rod segments were missing or rearranged. A single energetic iron nucleus may be capable of generating a retinal lesion which becomes enlarged as biological processes intervene during the 1 day and 30 day waits. Being composed of highly specialized nerve cells, retinas cannot regenerate following irradiation which severely damages the rod cells. Thus one would expect the observed radiation induced retinal lesions to correspond to permanent tissue damage and possible loss of visual acuity in the intact animal.
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PMID:Some indications of structural damage in retina by heavy ion radiation. 734 28

Heme synthase (ferrochelatase) activity, as determined by the chelation of ferrous iron to protoporphyrin or deuteroporphyrin, is reduced to 10-25% of normal in tissues of patients with protoporphyria. With cultured skin fibroblasts from seven patients with protoporphyria and six normal individuals, the present studies examined the enzymatic defect.Heme synthase activity in normal and protoporphyria fibroblasts had the same pH optimum, showed similar inhibition by divalent metals, and had the highest specific activity in the mitochondrial-enriched fraction. The ultrastructural features and other biochemical parameters of mitochondria were normal in protoporphyria cells, excluding a general mitochondrial defect. Measurement of the rate of deuteroheme formation at different concentrations of substrate demonstrated a significant reduction in the apparent K(m) for deuteroporphyrin in detergent-treated sonicates of protoporphyria fibroblasts compared to normal (7.5 +/- 0.9 muM, mean +/- SEM, vs. 17.4 +/- 1.8), as well as a decrease in the velocity of reaction (mean level was 21% of normal). Studies with intact cells, in which heme synthase activity was estimated indirectly, also indicated that the apparent K(m) for porphyrin substrate was significantly lower in protoporphyria lines. These data show that heme synthase in protoporphyria fibroblasts has markedly reduced catalytic activity despite an increased affinity for porphyrin substrate. This could be caused by either a change in the enzyme protein, or an alteration of its micro-environment.
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PMID:Characterization of deficient heme synthase activity in protoporphyria with cultured skin fibroblasts. 735 82


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