The LYR family consists of proteins of diverse functions that contain the conserved tripeptide ‘LYR’ near the N-terminus, and it includes Isd11, which was previously observed to have an important ...role in iron–sulfur (Fe–S) cluster biogenesis in Saccharomyces cerevisiae. Here, we have cloned and characterized human ISD11 and shown that human ISD11 forms a stable complex in vivo with the human cysteine desulfurase (ISCS), which generates the inorganic sulfur needed for Fe–S protein biogenesis. Similar to ISCS, we have found that ISD11 localizes to the mitochondrial compartment, as expected, but also to the nucleus of mammalian cells. Using RNA-interference techniques, we have shown that suppression of human ISD11 inactivated mitochondrial and cytosolic aconitases. In addition, ISD11 suppression activated iron-responsive element-binding activity of iron regulatory protein 1, increased protein levels of iron regulatory protein 2, and resulted in abnormal punctate ferric iron accumulations in cells. These results indicate that ISD11 is important in the biogenesis of Fe–S clusters in mammalian cells, and its loss disrupts normal mitochondrial and cytosolic iron homeostasis.
Hyperspectral imagery is used to map the distribution of iron and separate iron ore from shale (a waste product) on a vertical mine face in an open-pit mine in the Pilbara, Western Australia. ...Vertical mine faces have complex surface geometries which cause large spatial variations in the amount of incident and reflected light. Methods used to analyse imagery must minimise these effects whilst preserving any spectral variations between rock types and minerals. Derivative analysis of spectra to the 1st-, 2nd- and 4th-order is used to do this. To quantify the relative amounts and distribution of iron, the derivative spectrum is integrated across the visible and near infrared spectral range (430–970nm) and over those wavelength regions containing individual peaks and troughs associated with specific iron absorption features. As a test of this methodology, results from laboratory spectra acquired from representative rock samples were compared with total amounts of iron minerals from X-ray diffraction (XRD) analysis. Relationships between derivatives integrated over the visible near-infrared range and total amounts (% weight) of iron minerals were strongest for the 4th- and 2nd-derivative (R2=0.77 and 0.74, respectively) and weakest for the 1st-derivative (R2=0.56). Integrated values of individual peaks and troughs showed moderate to strong relationships in 2nd- (R2=0.68–0.78) and 4th-derivative (R2=0.49–0.78) spectra. The weakest relationships were found for peaks or troughs towards longer wavelengths.
The same derivative methods were then applied to imagery to quantify relative amounts of iron minerals on a mine face. Before analyses, predictions were made about the relative abundances of iron in the different geological zones on the mine face, as mapped from field surveys. Integration of the whole spectral curve (430–970nm) from the 2nd- and 4th-derivative gave results which were entirely consistent with predictions. Conversely, integration of the 1st-derivative gave results that did not fit with predictions nor distinguish between zones with very large and small amounts of iron oxide.
Classified maps of ore and shale were created using a simple level-slice of the 1st-derivative reflectance at 702, 765 and 809nm. Pixels classified as shale showed a similar distribution to kaolinite (an indicator of shales in the region), as mapped by the depth of the diagnostic kaolinite absorption feature at 2196nm. Standard statistical measures of classification performance (accuracy, precision, recall and the Kappa coefficient of agreement) indicated that nearly all of the pixels were classified correctly using 1st-derivative reflectance at 765 and 809nm. These results indicate that data from the VNIR (430–970nm) can be used to quantify, without a priori knowledge, the total amount of iron minerals and to distinguish ore from shale on vertical mine faces.
Anaemia prevalence in pregnant women of India declined from 57.9% to 50.3% from National Family Health Survey (NFHS)-3 to NFHS-4. However, over the course of that decade, the uptake of iron and folic ...acid (IFA) supplementation for 100 days of pregnancy improved by only 15%. To understand demand side risk factors of anaemia specifically related to IFA intake, an in-depth survey was conducted on pregnant women (n = 436) in 50 villages and wards of Sirohi district of Rajasthan, India. At the demand side, consistent IFA consumption in the previous trimester was inversely and strongly associated with anaemia (OR: 0.26, 95% CI: 0.12, 0.55). Reasons for inconsistent consumption included not registering to antenatal clinic, not receiving IFA tablets from the health worker and perceived lack of need. At the supply side, an analysis of IFA stock data at various levels of the health care (n = 168) providers from primary to tertiary levels showed that 14 out of 52 villages surveyed did not have access to IFA tablets. The closest availability of an IFA tablet for 16 villages, was more than 5 km away. To improve the uptake of IFA supplementation and thereby reduce iron deficiency anaemia in pregnant women, a constant supply of IFA at the village or sub-centre level, where frontline workers can promote uptake, should be ensured.
Iron deficiency is a major public health concern in Ethiopia, where the traditional diet is based on tef injera. Iron absorption from injera is low due to its high phytic acid (PA) content.
We ...investigated ways to increase iron absorption from FeSO4-fortified tef injera in normal-weight healthy women (aged 21–29 y).
Study A (n = 22) investigated the influence on fractional iron absorption (FIA) from FeSO4-fortified injera of 1) replacing 10% tef flour with whole wheat flour (a source of wheat phytase), or 2) adding an isolated phytase from Aspergillus niger. Study B (n = 18) investigated the influence on FIA of replacing FeSO4 in tef injera with different amounts of NaFeEDTA. In both studies, the iron fortificants were labeled with stable isotopes and FIA was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration.
In study A, the median (IQR) FIA from the 100% tef injera meal was 1.5% (0.7–2.8%). This increased significantly (P < 0.05) to 5.3% (2.4–7.1%) on addition of 10% whole wheat flour, and to 3.6% (1.6–6.2%) on addition ofA. niger phytase. PA content of the 3 meals was 0.62, 0.20, and 0.02 g/meal, respectively. In study B, the median (IQR) FIA from the 100% tef injera meal was 3.3% (1.1–4.4%) and did not change significantly (P > 0.05) on replacing 50% or 75% of FeSO4 with NaFeEDTA.
FIA from tef injera by young women was very low. NaFeEDTA was ineffective at increasing iron absorption, presumably due to the relatively low EDTA:Fe molar ratios. Phytate degradation, however, greatly increased during tef fermentation on addition of native or isolated phytases. Replacing 10% tef with whole wheat flour during injera fermentation tripled FIA in young women and should be considered as a potential strategy to improve iron status in Ethiopia.
Fe deficiency and Fe-deficiency anaemia are common in patients with inflammatory bowel disease (IBD). Traditional clinical markers of Fe status can be skewed in the presence of inflammation, meaning ...that a patient's Fe status can be misinterpreted. Additionally, Fe absorption is known to be down-regulated in patients with active IBD. However, whether this is the case for quiescent or mildly active disease has not been formally assessed. The present study aimed to investigate the relationship between Fe absorption, Fe requirements and standard haematological indices in IBD patients without active disease. A group of twenty-nine patients with quiescent or mildly active IBD and twenty-eight control subjects undertook an Fe absorption test that measured sequential rises in serum Fe over 4 h following ingestion of 200 mg ferrous sulphate. At baseline, serum Fe, transferrin saturation, non-transferrin-bound Fe (NTBI), ferritin and soluble transferrin receptor were all measured. Thereafter (30-240 min), only serum Fe and NTBI were measured. Fe absorption did not differ between the two groups (P = 0·9; repeated-measures ANOVA). In control subjects, baseline haematological parameters predicted Fe absorption (i.e. Fe requirements), but this was not the case for patients with IBD. Fe absorption is normal in quiescent or mildly active IBD patients but standard haematological parameters do not accurately predict Fe requirements.
Iron deficiency Camaschella, Clara
Blood,
01/2019, Letnik:
133, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Iron deficiency anemia affects >1.2 billions individuals worldwide, and iron deficiency in the absence of anemia is even more frequent. Total-body (absolute) iron deficiency is caused by ...physiologically increased iron requirements in children, adolescents, young and pregnant women, by reduced iron intake, or by pathological defective absorption or chronic blood loss. Adaptation to iron deficiency at the tissue level is controlled by iron regulatory proteins to increase iron uptake and retention; at the systemic level, suppression of the iron hormone hepcidin increases iron release to plasma by absorptive enterocytes and recycling macrophages. The diagnosis of absolute iron deficiency is easy unless the condition is masked by inflammatory conditions. All cases of iron deficiency should be assessed for treatment and underlying cause. Special attention is needed in areas endemic for malaria and other infections to avoid worsening of infection by iron treatment. Ongoing efforts aim at optimizing iron salts–based therapy by protocols of administration based on the physiology of hepcidin control and reducing the common adverse effects of oral iron. IV iron, especially last-generation compounds administered at high doses in single infusions, is becoming an effective alternative in an increasing number of conditions because of a more rapid and persistent hematological response and acceptable safety profile. Risks/benefits of the different treatments should be weighed in a personalized therapeutic approach to iron deficiency.
Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum ...phosphate concentrations is a frequent side effect of FCM.
To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort.
Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included.
The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM-OR = 20.8; 95% CI, 2.6-166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation.
Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.
There seems to be no report in the literature on the effect of melatonin (MT) in relieving the detrimental effects of combined application of salt stress (SS) and iron deficiency (ID). Therefore, the ...effect of MT on the accumulation/synthesis of endogenous nitric oxide (NO) and hydrogen sulphide (H2S) and how far these molecules are involved in MT‐improved tolerance to the combined application of ID and SS in pepper (Capsicum annuum L) were tested. Hence, two individual trials were set up. The treatments in the first experiment comprised: Control, ID (0.1 mM FeSO4), SS (100 mM NaCl) and ID + SS. The detrimental effects of combined stresses were more prominent than those by either of the single stress, with respect to growth, oxidative stress and antioxidant defense attributes. Single stress or both in combination improved the endogenous H2S and NO, and foliar‐applied MT (100 µM) led to a further increase in NO and H2S levels. In the second experiment, 0.1 mM scavenger of NO, 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide potassium salt (cPTIO) and that of H2S, hypotuarine (HT) were applied along with MT to get further evidence whether NO and H2S are involved in MT‐induced tolerance to ID and SS. MT combined with cPTIO and HT under a single or combined stress showed that NO effect was reversed by the NO scavenger, cPTIO, alone but the H2S effect was inhibited by both scavengers. These findings suggested that tolerance to ID and SS induced by MT may be involved in downstream signal crosstalk between NO and H2S.
PDF
