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Biomedical subjects

P Saltman

Publications and source records attributed to P Saltman.

At least 55 records · Page 3Linked to original sources

The aerobic reduction of Fe(III) complexes by hemoglobin and myoglobin.

The ability of hemoglobin (myoglobin) to reduce directly low-molecular-weight complexes of Fe(III) to form methemoglobin (metmyoglobin) and the Fe(II)-tris(2,2'-bipyridine) complex under aerobic conditions is described. The reduction is not mediated by superoxide, O-.2, as shown by increased rates under anaerobic conditions and lack of inhibition by superoxide dismutase. The chemical nature of the Fe(III) complex presented influences the rate of reduction; one of the most effective chelating agents of cellular origin is Fe(III) X ATP. This mechanism may be of fundamental importance in the mobilization and utilization of iron in biological systems.

2,2'-Dipyridyl↗

Effects of iron deficiency and exercise on myoglobin in rats.

The effects of iron deficiency and endurance training on muscle myoglobin (Mb), body weights, and blood lactic acid concentration were studied in rats. Fifty animals were divided into four groups: anemic trained (AT), normal trained (NT), anemic sedentary (AS), and normal sedentary (NS). Following 5 weeks of dietary control, the mean hemoglobin values for the AT and AS rats were 0.013 +/- 0.002 mmol X l-1 (8.7 +/- 1.4 g X dl-1) and 0.014 +/- 0.003 mmol X l-1 (9.2 +/- 1.7 g X dl-1) respectively, and did not significantly change throughout the study. AT and NT rats were run on a motor driven treadmill 4 days/week for 6 weeks up to a pre-established time of 90 min. Following the training, body weights of the AT (157 +/- 13 g) and NT (153 +/- 13 g) rats were lower than their respective sedentary groups AS (172 +/- 9 g) and NS (176 +/- 15 g). Resting blood lactic acid concentration following training was lower in both trained groups, AT (3.3 +/- 2.0 mM) and NT (2.3 +/- 1.9 mM) compared to AS (8.2 +/- 2.6 mM) and NS (3.8 +/- 1.6 mM). Training increased Mb concentration in hearts of both the anemic and normal trained groups (AT, 0.66 +/- 0.13 mg X g-1; NT, 0.95 +/- 0.08 mg X g-1) compared to the sedentary groups (AS, 0.44 +/- 0.08 mg X g-1; NS, 0.70 +/- 0.13 mg X g-1). Only the AT rats showed an increase in skeletal muscle Mb. This study provides evidence that myoglobin may limit aerobic metabolism.

Anemia, Hypochromic↗

Retention and distribution of iron added to cow's milk and human milk as various salts and chelates.

Iron supplementation of infant formulas is recommended by most national and international organizations, but the optimal form of supplementation has not been determined. We have compared the bioavailability and tissue distribution of iron from four iron chelates and two commonly used iron salts. Weanling C57BL/6J mice were fed for 1 week an evaporated cow's milk diet supplemented with vitamins and minerals (except for iron). Following the adjustment period, mice were divided into 12 groups of 20 each. Six groups continued to receive the cow's milk diet for 18 hours, while the other six groups were fed a similar diet based on human milk. Individual groups received a single dose of milk radioactively labeled with Fe(II)Cl2, Fe(II)SO4, Fe(III)NTA, Fe(III)EDTA, Fe(III)citrate or Fe(III)lactobionate. Wholebody retention was measured after 4 days; animals were then killed and individual tissues were counted for radioactivity. Iron from FeCl2, FeSO4 and FeNTA were the best retained from both milk diets. Fe citrate had a significantly lower iron retention than all other groups in either diet and is probably not an effective chelate for delivering iron to milk diets. Iron bioavailability was higher from the human milk diets than from the cow's milk diets from all vehicles used except citrate and lactobionate. Absorption of Fe citrate was similar from the two milk diets, while percent retention from Fe lactobionate was higher from cow's milk than from human milk. Tissue distribution of retained iron was similar for the milk diets and among the groups, indicating that, once absorbed, iron from the different vehicles is metabolized in a similar manner.

Animals↗

Transitory hematologic effects of moderate exercise are not influenced by iron supplementation.

A young women's exercise/fitness class tested the idea that administration of supplemental iron would prevent "sports anemia" that may develop during exercise and training and improve iron status of exercising females of menstrual age. Fifteen women (aged 18-37) were selected for each of three treatment groups: (1) no supplemental iron; (2) 9 mg X d-1 of Fe; and (3) 18 mg X d-1 of Fe (1 US Recommended Daily Allowance). Women exercised at approximately 85% of maximal heartrate for progressively increasing lengths of time in a jogging program and worked up to 45 min of exercise 4 d X week-1 for 8 weeks. Hematologic analysis was performed in weeks 1, 5, and 8. A significant decline in hemoglobin (Hb) concentration and hematocrit (Hct) was observed at week 5 when all data were examined without regard for iron intake; these red cell indices returned to pre-exercise levels by week 8. Reduction of mean cell hemoglobin concentration (MCHC) indicated that the midpoint decline was not caused by simple hemodilution during exercise. Serum ferritin (SF) concentration changed in parallel with Hb and Hct. Although the midpoint decline in SF was not statistically significant, it ruled out the possibility that turnover of red cell iron was directed to storage. Lowered MCHC and SF suggested lower availability of iron during the synthesis of a new generation of red cells. Few iron treatment effects of magnitude were observed. Iron did not prevent the midpoint decline in Hb concentration. Iron intake did not affect SF, serum iron, transferrin saturation, or final Hb, and Hct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Adaptations of lactate metabolism in iron-deficient rats.

Effects of dietary iron deficiency on lactate metabolism were studied in weanling female rats. Following an iron-deficient diet for 5 weeks, mean hemoglobin concentration was lowered to 6.4 g/dl relative to 12.2 in the control group. Mean plasma iron levels were 58 and 162 micrograms/dl, respectively. Significantly elevated resting lactate levels were observed in whole blood and plasma from iron-deficient anemic (relative to control) rats. Total activity of lactate dehydrogenase (LDH) was elevated in soleus and gastrocnemius muscles in response to iron deficiency from 269 +/- 51 to 364 +/- 60 (Mean +/- SD) and from 265 +/- 65 to 372 +/- 61 IU . 10(-3) . g-1, respectively. The LDH activity in heart was lowered from 700 +/- 61 to 593 +/- 45 IU . 10(-3) . g-1. The M3H and M2H2 isozymes in soleus were increased from 12.7 +/- 2.8 to 20.4 +/- 5.8% and from 19.4 +/- 6.1 to 28.2 +/- 3.6%, respectively. Similar increase was observed in M2H2 and MH3 in gastrocnemius from 9.8 +/- 0.9 to 14.8 +/- 2.0% and from 17.4 +/- 2.0 to 20.5 +/- 2.3%, respectively. The H4 isozyme was significantly reduced in soleus, gastrocnemius, and plantaris muscles from 27.7 +/- 4.7 to 12.4 +/- 4.4, from 15.8 +/- 1.9 to 7.2 +/- 2.9, and from 10.5 +/- 2.9 to 3.9 +/- 2.1%, respectively. It was suggested that iron-deficiency anemia induces an elevation of lactate production following an increase in total LDH activity and change in LDH isozyme patterns.

Anemia, Hypochromic↗

Trace elements and blood pressure.

Essential trace elements such as zinc, iron, and copper participate in various enzyme reactions directly related to the regulation of blood pressure and indirectly related to generation of oxidative metabolic energy, alterations in blood lipid levels, and alterations in taste acuity. The toxicological action of several heavy metal ions including cadmium, lead, mercury, and thallium can cause hypertension by affecting hormone metabolism, vasoconstriction, and renal tubular function. We conclude, however, that neither deficiencies of essential elements nor the presence of toxic heavy metals are primary causes of hypertension in our population.

Animals↗

Bioavailability of iron- and copper-supplemented milk for Mexican school children.

Fortification of dairy products with trace metals requires use of assimilable compounds that do not catalyze off-flavors due to lipid peroxidation but show good biological availability. The Fe(III) and Cu(II) chelates of the promising chelator, lactobionic acid, have been compared to Fe(II) and Cu(II) salts for their ability to improve hematological status in a mildly anemic population. Fe- and Cu-fortified cow milk was administered to children (aged 6 to 15) in the Durango, Mexico, "school lunch" program. Children drank milk providing 20 mg Fe and 3 mg Cu as ferric/cupric lactobionate ("chelate") or ferrous/cupric chloride ("salt") for 5 of 7 days/wk for 3 months. Supplementation with "salt" and "chelate" raised Hb significantly by 1 and 0.3 g/dl, respectively, above the control (unsupplemented) group. No significant change was observed in incremental serum ferritin, serum Fe, or transferrin saturation, or in final serum Cu. Ferric lactobionate shows poorer bioavailability than ferrous ion in the presence of Cu, but milk can be an excellent vehicle for Fe or Cu supplementation.

Adolescent↗

Mitochondrial NADH dehydrogenase in iron-deficient and iron-repleted rat muscle: an EPR and work performance study.

Iron may affect both respiratory O2 transport and mitochondrial electron transport in the performance of muscle work. This study was designed to elucidate the molecular defect of iron-deficient work performance by identifying heretofore unmeasurable mitochondrial enzymes that are diminished by iron deficiency and may be restored by iron repletion. Female rats were made iron-deficient by dietary control and were repleted by oral iron. Iron deficiency reduced physical work capacity (treadmill running time), haemoglobin (Hb), and mitochondrial iron-sulphur (Fe-S) centres in heart and skeletal muscles; mitochondrial number was unaffected. Oral iron supplementation restored work capacity and Hb within 4 d to normal or near-normal levels, but in general Fe-S centres of mitochondria due to NADH dehydrogenase remained at iron-deficient levels. Subnormal concentrations of mitochondrial iron-dependent NADH dehydrogenase in muscle are not by themselves rate-limiting in work performance.

Anemia, Hypochromic↗

Copper nitrilotriacetate: a potent therapeutic agent in the treatment of a genetic disorder of copper metabolism.

Copper nitrilotriacetate (NTA) was evaluated for its ability to ameliorate effects of the recessive mutant gene crinkled (cr) in mice. Copper-NTA was superior to copper sulfate in increasing postnatal survival and body copper content of offspring of dams supplemented during pregnancy and lactation. Feeding of NTA alone during these periods had no effect on survival. Postnatal supplementation with copper did not increase survival of the mutants. The therapeutic use of copper-NTA, and the necessity for prenatal intervention for successful treatment of the mutant, are discussed in relation to Menkes' syndrome.

Animals↗

Iron(III)--phosphoprotein chelates: stoichiometric equilibrium constant for interation of iron(III) and phosphorylserine residues of phosvitin and casein.

Estimates of the strength of iron binding to model phosphoproteins were obtained from equilibrium dialysis experiments. Iron-free phosvitin (chicken and frog) or alpha sl-casein (cow) was dialyzed against the iron(III) chelates of nitrilotriacetate (NTA), )ethylenedinitrilo)tetraacetate (EDTA), or citrate. Protein-bound metal was measured at equilibrium; competition of chelator and phosphoprotein for iron(III) was determined by reference to comprehensive equilibrium equations presented in the Appendix. Analysis of the iron-binding data for phosvitin suggested that clusters of di-O-phosphorylserine residues (SerP.SerP) were the most probable iron-binding sites. A stoichiometric equilibrium constant of 10(18.0) was calculated for the formation of the Fe3+(SerP.SerP) chelate. When comared on the basis of phosphate content, casein bound iron more weakly than phosvitin. However, if the stoichiometric equilibrium constant for the formation of the casein Fe3+(SerP.SerP) chelate (10(17.5) was adjusted to account for the fact that a smaller percentage of casein phosphoserines occurs in di-O-phosphorylserine clusters, the affinity of casein and phosvitin for iron was very similar. A theoretical comparison showed that the "strengths" of the ferric chelates can be ranked: EDTA greater than phosphoprotein di-O-phosphorylserine greater than citrate greater than NTA.

Animals↗

Removal of cadmium(II) from crystallized ferritin.

The cadmium content of crystallized horse spleen ferritin, usually about 2% by weight without special treatment, can be substantially decreased by prolonged dialysis against certain chelating agents, chaotropic ions, or weakly reducing anions. For example, neutral bisulphite buffer (2M) removed 95% of the bound cadmium of crystallization without affecting the iron content, and may thus be valuable for preparing "metal-free" holoferritin for physical-chemical studies.

Cadmium↗

Degradation of ascorbic acid (vitamin C) in iron-supplemented cows' milk.

The fate of [6-carbon-14] ascorbic acid in iron-supplemented and unsupplemented raw milk was studied by anion-exchange chromatography, which permitted quantitative analysis of the conversion of ascorbate to dehydroascorbate and diketogulonate as a function of time. Iron catalyzed an increase in the rate of autoxidation of ascorbate to dehydroascorbate but did not alter the equilibrium concentrations of ascorbate, dehydroascorbate, and diketogulonate. The conversion of ascorbate to dehydroascorbate and of dehydroascorbate to diketogulonate occurred rapidly even in unsupplemented milk. Thus, trace metal supplementation may not affect materially the vitamin C content of stored milk.

2,3-Diketogulonic Acid↗

Correlation of serum ferritin and liver ferritin iron in the anemic, normal, iron-loaded rat.

We developed a two-site immunoradiometric assay for rat serum ferritin that uses antibody immobilized on agarose. Individual serum ferritin values were significantly correlated with iron stores as determined chemically by liver ferritin iron content. This group correlation was not sufficiently great, however, to allow confident prediction of iron stores in a given animal on the basis of serum ferritin alone. Significant differences in mean liver ferritin iron concentration between groups of rats raised on diets of differing iron content were not always reflected by differences in mean serum ferritin values. Data correlating the serum levels of ferritin and a liver-specific transaminase suggested that hepatocellular death may sometimes contribute ferritin to the serum. Strong postitive correlations between serum ferritin and iron stores in the rat were not observed when serum transaminase levels were in the normal range.

Alanine Transaminase↗

Effect of milk and casein on the absorption of supplemental iron in the mouse and chick.

Milk is an attractive vehicle for introducing iron supplements into iron-deficient infants and children. This study compares the effects of milk and caseins on the whole-body absorption of radioactive iron complexes in an attempt to resolve the controversy over whether milk and its constituent phosphoproteins seriously impair iron absorption. Evidence is presented to clarify the role of the calcium-casein micelles of cow's milk in binding iron donated by the ferric-nitrilotriacetate (NTA) complex. The absorption of iron from isolated Fe(III)-casein complexes was studied in mice as a function of the casein--to--Fe ratio and was compared with the absorption of Fe(III)-NTA at equivalent levels. Even at casein--to--Fe ratios higher than those found in conventional iron-supplemented cow's milk (10-15 mg Fe/qt; casein P:Fe congruent to 34), absorption of iron(III) from the casein or NTA complex was not significantly different. There was no significant difference in the absorption of iron administered to mice and chicks as ferrous ion, ferric-NTA, or ferric fructose; nonfat cow's milk did not inhibit the absorption of these iron compounds. For the chick, in fact, milk significantly enhanced the absorption of iron from the ferric-NTA chelate. In order to affect iron absorption significantly casein would have to be present considerably in excess of that found in conventionally supplemented cow's milk.

Absorption↗