Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age

Objective: To examine the effects of iron deficiency and its treatment by iron supplementation or a high iron diet on fatigue and general health measures in women of childbearing age. Design: Randomised controlled trial to compare supplement and dietary treatment of iron deficiency. Subjects: 44 iron deficient (serum ferritin < 15 mug/L or serum ferritin 15-20 mug/L, plus two of the following: serum iron < 10 mu mol/L, total iron binding capacity > 68 mu mol/L or transferrin saturation < 15%) and 22 iron replete (hemoglobin greater than or equal to 120 g/L and serum ferritin > 20 mug/L) women 18 to 50 years of age were matched for age and parity. Interventions: Iron deficient women were randomly allocated to either iron supplementation or a high iron diet for 12 weeks. Measures of Outcome: Iron deficient and iron replete participants had iron studies performed and completed the Piper Fatigue Scale (PFS) and the SF-36 general health and well-being questionnaire at baseline (TO), following the 12 week intervention (TI) and again after a six-month non-intervention phase (T2). The SF-36 includes measures of physical (PCS) and mental (MCS) health and vitality (VT). Results: MCS and VT scores were lower and PFS scores were higher for iron deficient women (diet and supplement groups) than iron replete women at baseline. Both intervention groups showed similar improvements in MCS, VT and PFS scores during the intervention phase, but mean increases in serum ferritin were greater in the supplement than the diet group. PCS scores were not related to iron status. Conclusions: Treatment of iron deficiency with either supplementation or a high iron diet results in improved mental health and decreased fatigue among women of childbearing age.

Dietary treatment of iron deficiency in women of childbearing age

Background: The Australian Iron Status Advisory Panel advocates dietary intervention as the first treatment option for mild iron deficiency [serum ferritin (SF) = 10-15 mug/L]. However, there appear to be no studies on the efficacy of dietary treatment for iron deficiency. Objective: We compared the effects of iron supplementation and of a high-iron diet on serum ferritin (SF) and hemoglobin in iron-deficient women of childbearing age. Design: Forty-four iron-deficient women (SF < 15 mug/L or SF = 15-20 mug/L plus serum iron < 10 mu mol/L and total-iron-binding capacity > 68 mu mol/L) and 22 iron-replete women (hemoglobin greater than or equal to 120 g/L and SF > 20 mug/L) matched for age and parity categories were enrolled and completed 7-d weighed food records at baseline. The iron-deficient women were randomly allocated to receive iron supplementation (105 mg/d; supplement group) or a high-iron diet (recommended intake of absorbable iron: 2.25 mg/d; diet group) for 12 wk. Hematologic and dietary assessments were repeated at the end of the intervention and again after a 6-mo follow-up. Results: Mean SF in the supplement group increased from 9.0 +/- 3.9 mug/L at baseline to 24.8 +/- 10.0 mug/L after the intervention and remained stable during follow-up (24.2 +/- 9.8 mug/L whereas the diet group had smaller increases during the intervention (8.9 +/- 3.1 to 11.0 +/- 5.9 mug/L) but continued to improve during follow-up (to 15.2 +/- 9.5 mug/L). Mean hemoglobin tended to improve in both intervention groups, but the change was only significant in the supplement group. Conclusions: In iron-deficient women of childbearing age, a high-iron diet produced smaller increases in SF than did iron supplementation but resulted in continued improvements in iron status during a 6-mo follow-up.

Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers

Background: Alcohol increases body iron stores. Alcohol and iron may increase oxidative stress and the risk of alcohol-related liver disease. The relationship between low or safe levels of alcohol use and indices of body iron stores, and the factors that affect the alcohol-iron relationship, have not been fully characterized. Other aspects of the biological response to alcohol use have been reported to depend on iron status. Methods: We have measured serum iron, transferrin, and ferritin as indices of iron stores in 3375 adult twin subjects recruited through the Australian Twin Registry. Information on alcohol use and dependence and smoking was obtained from questionnaires and interviews. Results: Serum iron and ferritin increased progressively across classes of alcohol intake. The effects of beer consumption were greater than those of wine or spirits. Ferritin concentration was significantly higher in subjects who had ever been alcohol dependent. There was no evidence of interactions between HFE genotype or body mass index and alcohol. Alcohol intake-adjusted carbohydrate-deficient transferrin was increased in women in the lowest quartile of ferritin results, whereas adjusted gamma -glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase values were increased in subjects with high ferritin. Conclusions: Alcohol intake at low level increases ferritin and, by inference, body iron stores. This may be either beneficial or harmful, depending on circumstances. The response of biological markers of alcohol intake can be affected by body iron stores; this has implications for test sensitivity and specificity and for variation in biological responses to alcohol use.

Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population

Background: Heterozygotes for the C282Y mutation of the HFE gene may have altered hematology indices and higher iron stores than wild-type subjects. Methods: We performed a cross-sectional analysis of 1488 females and 1522 males 20-79 years of age drawn from the Busselton (Australia) population study to assess the effects of HFE genotype, age, gender, and lifestyle on serum iron and hematology indices. Results: Male C282Y heterozygotes had increased transferrin saturation compared with the wild-type genotype. Neither male nor female heterozygotes had significantly increased ferritin values compared with the wild-type genotype. Younger (20-29 years) wild-type males, but not heterozygous males, had significantly lower ferritin values than wild-type males in the older age groups. Compound heterozygous subjects had increased means for serum iron, transferrin saturation, corpuscular volume, and corpuscular hemoglobin compared with the wild-type genotype, and the males also had increased ferritin values (medians 323 vs 177 mug/L; P = 0.003). In both male and female wild-type subjects, an increased body mass index was associated with decreased serum iron and transferrin saturation and increased ferritin values. There was a significant increase in ferritin concentrations in both genders with increasing frequency of red meat consumption above a baseline of 1-2 times per week and alcohol intakes >10 g/day. Conclusions: Male C282Y heterozygotes had significantly increased transferrin saturation values. Compound heterozygous (C282Y/H63D) subjects formed a separate category of C282Y heterozygotes in whom both iron and red cell indices were significantly increased compared with the wild-type genotype. (C) 2001 American Association for Clinical Chemistry.

The effect of channel geometry and wall boundary conditions on the formation of extrusion surface instabilities for LLDPE

It is believed that surface instabilities can occur during the extrusion of linear low density polyethylene due to high extensional stresses at the exit of the die. Local crack development can occur at a critical stress level when melt rupture is reached. This high extensional stress results from the rearrangement of the flow at the boundary transition between the wall exit and the free surface. The stress is highest at the extrudate surface and decreases into the bulk of the material. The location of the region where the critical level is reached can determine the amplitude of the extrudate surface distortion, This paper studies the effect of wall slip on the numerically simulated extensional stress level at the die exit and correlates this to the experimentally determined amplitude of the surface instability. The effect of die exit radius and die wall roughness on extrusion surface instabilities is also correlated to the exit stress level in the same way. Whereas full slip may completely suppress the surface instability, a reduction in the exit stress level and instability amplitude is also shown for a rounded die exit and a slight increase in instability is shown to result from a rough die wall. A surface instability map demonstrates how the shear rate for onset of extrusion surface instabilities can be predicted on the basis of melt strength measurements and simulated stress peaks at the exit of the die. (C) 2001 Elsevier Science B.V. All rights reserved.

Response of a scleractinian coral, Stylophora pistillata, to iron and nitrate enrichment

The purpose of this study was to determine whether the addition of iron alone or in combination with nitrate affects growth and photosynthesis of the scleractinian coral, Stylophora pistillata, and its symbiotic dinoflagellates. For this purpose, we used three series of two tanks for a 3-week enrichment with iron (Fe), nitrate (N) and nitrate + iron (NFe). Two other tanks were kept as a control (C). Stock solutions of FeCl3 and NaNO3 were diluted to final concentrations of 6 nM Fe and 2 muM N and continuously pumped from batch tanks into the experimental tanks with a peristaltic pump. Results obtained showed that iron addition induced a significant increase in the areal density of zooxanthellae (ANOVA, p = 0.0013; change from 6.3 +/- 0.7 x 10(5) in the control to 8.5 +/- 0.6 x 10(5) with iron). Maximal gross photosynthetic rates normalized per surface area also significantly increased following iron enrichment (ANOVA, p = 0.02; change from 1.23 +/- 0.08 for the control colonies to 1.81 +/- 0.24 mu mol O-2 cm(-2) h(-1) for the iron-enriched colonies). There was, however, no significant difference in the photosynthesis normalized on a per cell basis. Nitrate enrichment alone (2 muM) did not significantly change the zooxanthellae density or the rates of photosynthesis. Nutrient addition (both iron and nitrogen) increased the cell-specific density of the algae (CSD) compared to the control (G-test, p = 0.3 x 10(-9)), with an increase in the number of doublets and triplets. CSD was equal to 1.70 +/- 0.04 in the Fe-enriched colonies, 1.54 +/- 0.12 in the N- and NFe-enriched colonies and 1.37 +/- 0.02 in the control. Growth rates measured after 3 weeks in colonies enriched with Fe, N and NFe were 23%, 34% and 40% lower than those obtained in control colonies (ANOVA. p = 0.011). (C) 2001 Elsevier Science B.V. All rights reserved.

Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins

The membrane-bound ceruloplasmin homolog hephaestin plays a critical role in intestinal iron absorption. The aims of this study were to clone the rat hephaestin gene and to examine its expression in the gastrointestinal tract in relation to other genes encoding iron transport proteins. The rat hephaestin gene was isolated from intestinal mRNA and was found to encode a protein 96% identical to mouse hephaestin. Analysis by ribonuclease protection assay and Western blotting showed that hephaestin was expressed at high levels throughout the small intestine and colon. Immunofluorescence localized the hephaestin protein to the mature villus enterocytes with little or no expression in the crypts. Variations in iron status had a small but nonsignificant effect on hephaestin expression in the duodenum. The high sequence conservation between rat and mouse hephaestin is consistent with this protein playing a central role in intestinal iron absorption, although its precise function remains to be determined.

On the nonlocality of the quantum channel in the standard teleportation protocol

By exhibiting a violation of a novel form of the Bell-CHSH inequality, Żukowski has recently established that the quantum correlations exploited in the standard perfect teleportation protocol cannot be recovered by any local hidden variables model. In the case of imperfect teleportation, we show that a violation of a generalized form of Żukowski's teleportation inequality can only occur if the channel state, considered by itself, already violates a Bell-CHSH inequality. On the other hand, the fact that the channel state violates a Bell-CHSH inequality is not sufficient to imply a violation of Żukowski's teleportation inequality (or any of its generalizations). The implication does hold, however, if the fidelity of the teleportation exceeds ≈ 0.90. © 2001 Elsevier Science B.V. All rights reserved.

A common inhibitory binding site for zinc and odorants at the voltage-gated K+ channel of rat olfactory receptor neurons

This study compared the effects of zinc and odorants on the voltage-gated K+ channel of rat olfactory neurons. Zinc reduced current magnitude, depolarized the voltage activation curve and slowed activation kinetics without affecting inactivation or deactivation kinetics. Zinc inhibition was potentiated by the NO compound, S-nitroso-cysteine. The pH- and diethylpyrocarbonate-dependence of zinc inhibition suggested that zinc acted by binding to histidine residues. Cysteine residues were eliminated as contributing to the zinc-binding site. The odorants, acetophenone and amyl acetate, also reduced current magnitude, depolarized the voltage activation curve and selectively slowed activation kinetics. Furthermore, the diethylpyrocarbonate- and pH-dependence of odorant inhibition implied that the odorants also bind to histidine residues. Zinc inhibitory potency was dramatically diminished in the presence of odorants, implying competition for a common binding site. These observations indicate that the odorants and zinc share a common inhibitory binding site on the external surface of the voltage-gated K+ channel.

The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state

Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

Ivermectin, an unconventional agonist of the glycine receptor chloride channel

The effects of the antihelmintic, ivermectin, were investigated in recombinantly expressed human alpha (1) homomeric and alpha (1)beta heteromeric glycine receptors (GlyRs), At low (0.03 muM) concentrations ivermectin potentiated the response to sub-saturating glycine concentrations, and at higher (greater than or equal to0.03 muM) concentrations it irreversibly activated both alpha (1) homomeric and alpha (1)beta heteromeric GlyRs. Relative to glycine-gated currents, ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc. The insensitivity to strychnine could not be explained by ivermectin preventing the access of strychnine to its binding site. Furthermore, the elimination of a known glycine- and strychnine-binding site by site-directed mutagenesis had little effect on ivermectin sensitivity, demonstrating that the ivermectin- and glycine-binding sites were not identical. Ivermectin strongly and irreversibly activated a fast-desensitizing mutant GlyR after it had been completely desensitized by a saturating concentration of glycine. Finally, a mutation known to impair dramatically the glycine signal transduction mechanism had little effect on the apparent affinity or efficacy of ivermectin, Together, these findings indicate that ivermectin activates the GlyR by a novel mechanism.