Changes In Iron Content Research Articles

Increased iron deposition of deep cerebral gray matter structures in hemodialysis patients: A longitudinal study using quantitative susceptibility mapping.

The cerebral iron overload in hemodialysis patients has been reported in a previous study, in which the evaluation of the changes in iron content could be affected by the cross-sectional analysis. To investigate the longitudinal changes of iron deposition in hemodialysis patients using quantitative susceptibility mapping (QSM) and correlate these findings with the longitudinal changes of neurocognitive function and clinical factors. Prospective; longitudinal. In all, 34 patients and 30 healthy controls (HCs); the mean follow-up interval was 22 ± 7 months. 3.0T, susceptibility-weighted imaging (SWI). QSM reconstructed from original phase data of SWI was used to measure the susceptibility of gray matter structures including bilateral caudate nucleus (CN), globus pallidus (GP), putmen (PUT), red nucleus (RN), substantia nigra (SN), dentate nucleus (DN), thalamus (THA), pulvinar of thalamus (PT). The Mini-Mental State Examination (MMSE) test and clinical factors were recorded. Analysis of covariance adjusting for age and gender as covariates or a paired t-test for the differences in susceptibility, MMSE scores, and clinical factors among baseline, follow-up patients, and HCs. Correlation and stepwise regression analysis for the relationship between susceptibility, MMSE scores, and clinical factors. The susceptibility of bilateral CN, GP, PUT, RN, SN, DN, THA, PT in follow-up patients was significantly higher than that in baseline between patients and HCs except for left THA (all P < 0.05; Bonferroni corrected). MMSE scores significantly negatively correlated with the susceptibility of bilateral CN, PUT, and RRN in the baseline examination and bilateral CN, PUT, RN, and DN in the follow-up examination (all P < 0.05; false discovery rate [FDR] corrected). The follow-up interval, creatinine, phosphorus, and calcium were independent factors for the increased susceptibility of some nuclei (all P < 0.05). The iron deposition of gray matter nuclei in hemodialysis patients increased over roughly a 2-year period and may be a risk factor for neurocognitive impairment. Creatinine and abnormal calcium-phosphorus metabolism were independent risk factors for abnormal iron deposition. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:786-799.

Longitudinal study of multiple sclerosis lesions using ultra-high field (7T) multiparametric MR imaging.

Pathophysiology of multiple sclerosis (MS) lesions is dynamic and changes over time. The purpose of this exploratory study was to determine the longitudinal changes in MS lesions over time on ultra-high field MR imaging. Nine patients with MS underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo-T2*-weighted imaging on 7T MRI at baseline and after ~2.4 years of follow-up. Morphologic imaging characteristics, signal intensity patterns and quantitative susceptibility mapping (QSM) values of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on T2*-weighted images and/or SWI as well as hyperintense signal on QSM. Lesions were considered "non-iron-laden" if they were hyperintense on T2*/SWI and isointense or hyperintense on QSM. Total of 162 non-iron-laden and 29 iron-laden lesions were observed at baseline. No change in baseline lesion size during follow up was recorded in 92.7%; no change in lesion-vessel relationship in 86.5%; and no change in signal intensity pattern in 96.9% of lesions. Three lesions which were non-iron-laden at baseline, exhibited iron at follow-up. In two iron-laden lesions, redistribution of iron content was observed at follow-up. Two-thirds of these iron-laden lesions showed an increase in QSM at follow-up relative to baseline, and the remaining one-third exhibited decrease in QSM. Most of the newly formed lesions (11/13, 84.6%) at follow-up were iron-laden. 7T multiparametric MRI is a useful tool for tracking the evolution of MS lesions, especially with regard to changes in iron content.

Iron overload involved in the enhancement of unloading-induced bone loss by hypomagnetic field.

During deep-space exploration missions, astronauts will be exposed to abnormal space environments including microgravity and hypomagnetic field (HyMF) that is 10,000 times weaker than geomagnetic field (GMF). It is well known that microgravity in space can induce bone loss; however, it is ill-defined whether HyMF involved in this process. Herein, we aimed to investigate the combined effects of HyMF and microgravity on bone loss. A mouse model of hindlimb suspension (HLU) was adopted to simulate microgravity-induced bone loss, that was exposed to a hypomagnetic field of <300 nanotesla (nT) generated by a geomagnetic field-shielding chamber. Besides, a recent study showed that HLU induced bone loss was orchestrated by iron overload. Therefore, the changes of iron content in unloading-induced bone loss under HyMF condition were detected simultaneously. The results showed HyMF exacerbated the loss of bone mineral content (BMC), induced more detrimental effects on microstructure of cancellous bone but not cortical bone and yielded greater negative effects on biomechanical characteristics in mice femur under unloading status. Concomitantly, there was more iron accumulation in serum, liver, spleen and bone in the combined treatment group than in the separate unloading group or HyMF exposure group. These results showed that HyMF promoted additional bone loss in mice femur during mechanical unloading, and the potential mechanism may be involved in inducing iron overload of mice.

Changes in myocardial iron content following administration of intravenous iron (Myocardial-IRON): Study design.

Treatment with intravenous ferric carboxymaltose (FCM) has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure and iron deficiency. However, the underlying mechanisms for these beneficial effects remain undetermined. The aim of this study is to quantify cardiac magnetic resonance changes in myocardial iron content after administration of intravenous FCM in patients with heart failure and iron deficiency and contrast them with parameters of heart failure severity. This is a multicenter, double-blind, randomized study. Fifty patients with stable symptomatic heart failure, left ventricular ejection fraction <50%, and iron deficiency will be randomly assigned 1:1 to receive intravenous FCM or placebo. Intramyocardial iron will be evaluated by T2* and T1 mapping cardiac magnetic resonance sequences before and at 7 and 30 days after FCM. After 30 days, patients assigned to placebo will receive intravenous FCM in case of persistent iron deficiency. The main endpoint will be changes from baseline in myocardial iron content at 7 and 30 days. Secondary endpoints will include the correlation of these changes with left ventricular ejection fraction, functional capacity, quality of life, and cardiac biomarkers. The results of this study will add important knowledge about the effects of intravenous FCM on myocardial tissue and cardiac function. We hypothesize that short-term (7 and 30 days) myocardial iron content changes after intravenous FCM, evaluated by cardiac magnetic resonance, will correlate with simultaneous changes in parameters of heart failure severity. The study is registered at http://www.clinicaltrials.gov (NCT03398681).

Iron Starvation Conditions Upregulate Ehrlichia ruminantium Type IV Secretion System, tr1 Transcription Factor and map1 Genes Family through the Master Regulatory Protein ErxR.

Ehrlichia ruminantium is an obligatory intracellular bacterium that causes heartwater, a fatal disease in ruminants. Due to its intracellular nature, E. ruminantium requires a set of specific virulence factors, such as the type IV secretion system (T4SS), and outer membrane proteins (Map proteins) in order to avoid and subvert the host's immune response. Several studies have been conducted to understand the regulation of the T4SS or outer membrane proteins, in Ehrlichia, but no integrated approach has been used to understand the regulation of Ehrlichia pathogenicity determinants in response to environmental cues. Iron is known to be a key nutrient for bacterial growth both in the environment and within hosts. In this study, we experimentally demonstrated the regulation of virB, map1, and tr1 genes by the newly identified master regulator ErxR (for Ehrlichia ruminantium expression regulator). We also analyzed the effect of iron depletion on the expression of erxR gene, tr1 transcription factor, T4SS and map1 genes clusters in E. ruminantium. We show that exposure of E. ruminantium to iron starvation induces erxR and subsequently tr1, virB, and map1 genes. Our results reveal tight co-regulation of T4SS and map1 genes via the ErxR regulatory protein at the transcriptional level, and, for the first time link map genes to the virulence function sensu stricto, thereby advancing our understanding of Ehrlichia's infection process. These results suggest that Ehrlichia is able to sense changes in iron concentrations in the environment and to regulate the expression of virulence factors accordingly.

Changes in Iron Absorption After Roux-en-Y Gastric Bypass

Iron deficiency is one of the most common deficiencies that may occur after Roux-en-Y gastric bypass (RYGB). Little is known about the optimal treatment of post-RYGB iron deficiency. The aim of this study is to evaluate the changes in iron absorption characteristics after RYGB for two oral iron formulations, one presented in tablet form and one as in the form of a solution. Iron absorption in 24 obese women was studied before and 1month after RYGB. Twelve patients were tested with a single dose of 600mg ferrous fumarate in tablet form (195mg of elementary iron, group 1), and 12 patients received a single dose of 1390mg ferrous gluconate as a solution (160mg of elementary iron, group 2). Serum iron levels were measured before (T0) and every hour after ingestion of the supplement (T1-T9). Before surgery, iron absorption was similar for the two supplements (P = 0.71). However, RYGB was associated with a decrease in fumarate iron absorption (P < 0.001) but did not affect gluconate iron absorption (P = 0.13). Postoperative absorption of fumarate iron was significantly lower than gluconate iron at T1 (P < 0.05), but the overall difference over 9h did not reach statistical significance (P = 0.53). RYGB adversely affects the absorption of ferrous fumarate tablets but not that of solubilized ferrous gluconate. A solubilized supplement is therefore preferred as the supplement of first choice after RYGB.

Differences in circulating non-transferrin-bound iron after oral administration of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal iron stores

Background. The adverse interactions between iron supplements and malaria have driven the assessment of new therapeutic options for anemia prophylaxis in areas holoendemic for falciparum malaria.Objective. To determine the responses of circulating non-transferrin-bound iron (NTBI) and plasma iron to three different oral iron compounds – ferrous sulfate, sodium iron ethylenediaminetetraacetate (NaFeEDTA), and iron polymaltose (IPM) – in women with marginal iron stores.Methods. Serum samples from 10 Guatemalan women with marginal iron stores were collected every 90 minutes over a period of 270 minutes, after the individually randomized administration of 100 mg of iron from each of the three studied iron compounds or water alone. Serum iron concentration was quantified by the ferrozine method, and circulating NTBI concentration was determined with a fluorometric competitive binding assay. Kinetic responses and maximal cumulative changes in serum concentrations of iron and NTBI were compared between the four treatments. Comparison was made with data from the same protocol in iron-adequate men.Conclusions. The administration of the two “slow-release” iron compounds, NaFeEDTA and IPM, resulted in a highly significant suppression of the appearance of NTBI in the circulation in the postsupplement period. These two bioavailable forms of iron supplement could represent a safe option for supplementation in malarial areas. The slope of the iron – NTBI relationship is steeper in men than in women.

Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms

IntroductionIron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. AimTo explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. ResultsMice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (−83%) and of luteinizing hormone (−86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE−/−, resembling human hemochromatosis. ConclusionsIED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload.

Stability of ferrous-iron-rich bridgmanite under reducing midmantle conditions

Our current understanding of the electronic state of iron in lower-mantle minerals leads to a considerable disagreement in bulk sound speed with seismic measurements if the lower mantle has the same composition as the upper mantle (pyrolite). In the modeling studies, the content and oxidation state of Fe in the minerals have been assumed to be constant throughout the lower mantle. Here, we report high-pressure experimental results in which Fe becomes dominantly Fe2+ in bridgmanite synthesized at 40-70 GPa and 2,000 K, while it is in mixed oxidation state (Fe3+/∑Fe = 60%) in the samples synthesized below and above the pressure range. Little Fe3+ in bridgmanite combined with the strong partitioning of Fe2+ into ferropericlase will alter the Fe content for these minerals at 1,100- to 1,700-km depths. Our calculations show that the change in iron content harmonizes the bulk sound speed of pyrolite with the seismic values in this region. Our experiments support no significant changes in bulk composition for most of the mantle, but possible changes in physical properties and processes (such as viscosity and mantle flow patterns) in the midmantle.

A Regulatory Role for “MFehi” Macrophages In Adipose Tissue Iron Homeostasis

Abstract Macrophages are the predominant immune cell in adipose tissue (AT) and exhibit phenotypic variability depending on the obesity state of the tissue. Lean AT contains a population of anti-inflammatory “M2” AT macrophages (ATMs), whereas, obesity is associated with an influx of inflammatory “M1” ATMs. The role of M2 ATMs in maintenance of a healthy lean state is relatively undefined. Our lab has previously published the discovery of the “MFehi” population of M2 ATMs, which has a two-fold increase in intracellular iron content and exhibits increased expression of genes involved in iron uptake (e.g. CD163), storage and release. This population composes 25% of M2 ATMs and exists in both lean and obese mouse and human AT. It remains unknown whether MFehi contribute to AT iron metabolism. To better understand how MFehi are regulating iron in AT, we provided iron through diet and by IP injection and predicted that MFehi compensate for excess iron to protect adipocytes from iron overload. We found that only MFehi take up the iron, and their gene expression corresponds with this uptake. Furthermore, there is no change in iron content or gene expression in adipocytes. Even though the MFehi change their gene expression in obese AT, we still observed that they are able to compensate for excess iron in the tissue. To determine the impact of MFehi on the systemic metabolic state, we depleted M2 ATMs in mice with cytotoxic CD163-targeted liposomes. Our preliminary studies have revealed CD163-targeted liposomes as a novel technique to target CD163-expressing M2 ATMs. These studies will allow us to characterize the role of the MFehi population in maintaining healthy adipocyte iron concentrations and, thereby, insulin sensitivity.

Abstract TP348: Quantitative Serial Neuroimaging of Iron in the Intracerebral Hemorrhage Pig Model

Objective: To serially quantify changes of iron concentration within hematomas in the intracerebral hemorrhage (ICH) pig model using non-invasive R2* and quantitative susceptibility mapping (QSM) MRI methods. Introduction: Hemolysis-related release of hemoglobin/heme/free iron after ICH causes cytotoxic injury. An accurate post hemorrhage assessment of iron would be valuable to develop strategies to prevent secondary damage. The T2* relaxation rate (R2* =1/T2*) on MRI depends on the regional oxy- versus deoxyhemoglobin. Post-ICH excess of deoxyhemoglobin has been applied as a quantitative marker to estimate iron in the brain. However, quantitative susceptibility mapping (QSM) is a new MRI technique that can quantify iron concentration within the hematoma by measuring induced magnetic susceptibility. Using R2* mapping and QSM in a large animal ICH model, we measured spatiotemporal changes in iron concentration in the brain. Methods: Lobar ICH was induced by infusion of 2.5 ml autologous blood in 8 Yorkshire pigs with average age/wt of 4-6wk/12.5±2.5kg. MRI was obtained at days 1 and 7. A 3D anatomical and multi-echo gradient echo images were obtained on a clinical 3.0 T Philips Ingenia MRI system. Parametric R2* and susceptibility maps were generated. Regions of interest were placed within hematoma and contralesional CSF. Results: R2* measurements in the hematoma at day 1 and day 7 were 41.3 ± 7.3 and 37.7 ± 7.7 s -1 , respectively, whereas the corresponding susceptibility measurements were 0.75± 0.3 and 0.70 ± 0.5 ppm. The CSF R2* were 5.53 ± 2.1 and 6.85 ± 2.4 s -1 , whereas susceptibility showed 0.06 ± 0.16 and 0.02 ± 0.03 ppm at the two time points. Both R2* and QSM showed no significant change in iron concentration within the hematoma ROI with p-value of 0.18 and 0.72 over a week. Absence of hyperintense regions remote from the hematoma in susceptibility maps suggested lack of diffuse iron deposition. Good correlation was observed between R2* and QSM (correlation coefficient 0.83 and 0.78 within hematoma, and -0.66 and -0.07 within CSF, at day 1 and 7, respectively). Conclusion: R2* and especially QSM, with their ability to provide quantitative iron content, are valuable tools to test new ICH treatments particularly targeting iron in this large animal model.

Changes in brain iron concentration after exposure to high-altitude hypoxia measured by quantitative susceptibility mapping

Hypoxia can induce physiological changes. This study aims to explore effects of high-altitude (HA) hypoxia on cerebral iron concentration. Twenty-nine healthy sea-level participants were tested shortly before and after approximately 4-week adaptation to the HA environment at fQinghai-Tibet Plateau (4200m), and were re-investigated after re-adaptation to the sea-level environment one year later. Iron concentration was quantified with quantitative susceptibility mapping (QSM), and the results were compared with transverse relaxation rate (R*2) measurements. The variations of magnetic susceptibility indicate that the iron concentration in gray matter regions, especially in basal ganglia, including caudate nucleus, putamen, globus pallidus and substantia nigra, increases significantly after HA exposure. This increase appears consistent with the conclusion from R*2 value variations. However, unlike QSM, the R*2 value fails to demonstrate the statistical difference of iron content in red nucleus. The re-investigation results show that most variations are recovered after sea-level re-adaptation for one year. Additionally, hemisphere- and gender-related differences in iron concentration changes were analyzed among cerebral regions. The results show greater possibilities in the right hemisphere and females. Further studies based on diffusion tensor imaging (DTI) suggest that the fractional anisotropy increases and the mean diffusivity decreases after HA exposure in six deep gray matter nuclei, with linear dependence on iron concentration only in putamen. In conclusion, the magnetic susceptibility value can serve as a quantitative marker of brain iron, and variations of regional susceptibility reported herein indicate that HA hypoxia can result in significant iron deposition in most deep gray matter regions. Additionally, the linear dependence of DTI metrics on iron concentration in putamen indicates a potential relationship between ferritin and water diffusion.

Inulin-type fructans trigger changes in iron concentration and activity of bone metabolism biomarkers in blood plasma of growing pigs

Inulin-type fructans trigger changes in iron concentration and activity of bone metabolism biomarkers in blood plasma of growing pigs

The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss

Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1+IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver.

REGULARITIES OF PROTEOLYSIS OF PACKED LIVESTOCK RED BLOOD CELLS

Actual methods for anti-anemic preparation producing are characterized by a number of weak points: significant hemoglobin losses during hemolysis; difficulties in achieving a high hemoglobin purity level; expensive and complex instrumentation etc. A promising direction of this research is a study of a possibility to get iron-containing mass from meat-producing animals’ blood through hydrolysis with acetic and citric acids. The author studies a correlation dependence of acid concentration on amine nitrogen mass fraction, heme iron, hydrolysis level. For packed pork blood cells, the highest amine nitrogen values are typical under the use of acetic and citric acids with mass fraction of 10%, which corresponds to 357 mg/100 cm3 under the duration of 10 hours for citric acid and 305 mg/100 cm3 under the duration of 8 hours for acetic acid. Under packed cattle blood cells hydrolysis, the highest amine nitrogen values are typical under the use of 10% citric acid solution and 10% acetic acid solution, which corresponds to 268 mg/100 cm3 i 229 mg/100 cm3 respectively. Iron yield has positive increasing dynamics. 11-12 hour hydrolysis is relatively stable, the changes in iron content are insignificant, which means that hydrolysis time increase makes no sense. Favourable conditions for hydrolysis are: mass fraction of citric acid - 10%, mass fraction of citric acid - 5%, mass fraction of acetic acid - 10%, temperature - 50 ± 1°C, process time - 12 hours.

Possibilities of Using Al-Si-Mg Alloys with Higher Fe Content for Demanding Castings

The present article describes the effect of adding iron into melt, and its impact on the microstructure, chemical composition and mechanical properties of AlSi7Mg0.3 alloy. Higher iron content is typical of the so-called secondary alloy, which becomes increasingly used by a growing number of manufacturers in the production process of high-quality castings. The behaviour of AlSi7Mg0.3 alloy with high Fe content has not been scientifically investigated and sufficiently described, therefore working with secondary alloy is very problematic when focusing on high-sophistication castings for the automotive industry. In general, iron is unwanted in aluminium alloys, and its content should be kept as low as possible. The only exception is the process of pressure die casting where we can tolerate iron content up to 1 wt. %. In gravity casting of Al-Si-based alloys, the critical iron content changes mainly depending on the silicon content. The experimental part of this article investigates the impact of gradual addition of iron into AlSi7Mg0.3 alloy on the content of the main alloying elements such as, in particular, Si and Mg. In order to eliminate the negative effect of iron in the alloy, we used in the experiment the correctors Ni and Cr in the form of AlNi20 and AlCr20 master alloys.

Accumulation of iron in the putamen predicts its shrinkage in healthy older adults: A multi-occasion longitudinal study

Accumulation of non-heme iron is believed to play a major role in neurodegeneration of the basal ganglia. In healthy aging, however, the temporal relationship between change in brain iron content and age-related volume loss is unclear. Here, we present the first long-term longitudinal multi-occasion investigation of changes in iron content and volume in the neostriatum in a sample of healthy middle-aged and older adults (N=32; ages 49–83years at baseline). Iron content, estimated via R2* relaxometry, increased in the putamen, but not the caudate nucleus. In the former, the rate of accumulation was coupled with change in volume. Moreover, greater baseline iron content predicted faster shrinkage and smaller volumes seven years later. Older age partially accounted for individual differences in neostriatal iron content and volume, but vascular risk did not. Thus, brain iron content may be a promising biomarker of impending decline in normal aging.

A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a subcutaneous on changes in susceptibility-weighted imaging-filtered phase assessment of lesions and subcortical deep-gray matter in relapsing-remitting multiple sclerosis.

Studies have shown a relationship between increased iron content and clinical progression, cognitive impairment, and brain atrophy in patients with multiple sclerosis. Altered phase, as determined by susceptibility-weighted imaging (SWI), can potentially capture iron content changes. The objective of this study was to investigate phase changes in white matter (WM) lesions and subcortical deep-gray matter (SDGM) of patients with relapsing-remitting (RR) MS treated with interferon beta-1a administered subcutaneously versus untreated healthy controls (HCs). We conducted a 24-week, nonrandomized, open-label pilot study of 23 patients with RRMS receiving interferon beta-1a administered subcutaneously and 15 HCs. Patients were imaged on a 3T scanner at baseline, 12, and 24 weeks; changes in phase behavior in WM lesions and regional SDGM [mean phase of low-phase voxels (MP-LPV)], and in SDGM volumes, were measured. Between- and within-group changes were tested using nonparametric statistics adjusted for multiple comparisons. The number (p = 0.003) and volume (p < 0.001) of phase WM lesions both significantly decreased among RRMS patients over 24 weeks. At baseline, MP-LPV was lower (suggestive of greater iron content) in total SDGM among RRMS patients versus HCs (p = 0.002). Week 24 MP-LPV changes from baseline were not significantly different between groups in total SDGM or any region except the putamen (-0.0025 radians in RRMS patients versus 0.0035 radians in HCs; p = 0.041). Over 24 weeks, phase lesions were reduced significantly in the RRMS group. These preliminary results suggest that SWI-filtered phase may become a useful tool for monitoring RRMS disease activity.

Iron Overload in the Face of Anemia

Several distinct congenital disorders can lead to tissue-iron overload with anemia including β-thalassemia and sickle cell disease. We show that intestinal absorption of iron is highly increased and significantly contributes to tissue iron accumulation in these disorders. The present work describes a novel pathway by which oxygen sensing transcription factors are highly upregulated in iron overload anemias and are subsequently essential for the increase intestinal iron absorption. Oxygen signaling is mediated through well-conserved hypoxia driven transcription factors, hypoxia-inducible factor (HIF)1a and HIF2a. In the intestine, HIF2a directly activates divalent metal transporter 1 (DMT1), duodenal ferric reductase (DcytB), and Fpn1, which are iron transporters critical for adaptive changes in iron absorption. We demonstrate that HIF2a and its downstream target gene, DMT1 are essential for iron accumulation in mouse models of β-thalassemia and sickle cell disease. Furthermore, studies of thalassemic mouse model with established iron overload demonstrated that loss of intestinal HIF2a and DMT1 signaling led to decreased tissue iron accumulation in the livers. Interestingly, disrupting intestinal HIF2a not only improves tissue iron accumulation, but a marked improvement of anemia was also observed. These novel findings suggests that inhibition of HIF2a signaling pathway could be a novel and robust treatment strategy for several conditions that cause iron overload with anemia. DisclosuresNo relevant conflicts of interest to declare.

Improvement of brightness of kaolin by superconducting magnetic separation and characterization of the impurities

AbstractIn the present study, changes of iron content, brightness, particle size, mineralogy and paramagnetic properties of kaolins before and after superconducting high gradient magnetic separation (SHGMS) were investigated. The Fe2O3 contents of the feed decreased by 56% after 3.5T SHGMS with 1# steel wool, but higher magnetic intensity to 5.5T did not remove additional iron. The ISO brightness of the kaolin sample after SHGMS was improved from 56.9% to 76.7%. The D50 value of the magnetic rejects was 35% larger compared to the feed. Large particles might block the micro-pores in the steel wool matrix. Compared to the feed, the dark or red impurities significantly decreased in the non-magnetic product. Paramagnetic species in the kaolin sample were sensitive to SHGMS. The resonances at g = ~2.0 and g = 4.0 decreased significantly in the concentrate compared to the feed in the ESR spectra. Iron components in the non-magnetic product were more likely to be non-paramagnetic. The results are useful for understanding the SHGMS in kaolin treatment, and might be a guide for optimizing process parameters.