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1.
Iron Oxide Particles Alter Bacterial Uptake and the LPS-Induced Inflammatory Response in Macrophages.
Williams, LJ, Tristram, SG, Zosky, GR
International journal of environmental research and public health. 2020;(1)
Abstract
Exposure to geogenic (earth-derived) particulate matter (PM) is linked to severe bacterial infections in Australian Aboriginal communities. Experimental studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of silica and iron oxide on the inflammatory response and bacterial phagocytosis in macrophages. THP-1 and peripheral blood mononuclear cell-derived macrophages were exposed to iron oxide (haematite or magnetite) or silica PM with or without exposure to lipopolysaccharide. Cytotoxicity and inflammation were assessed by LDH assay and ELISA respectively. The uptake of non-typeable Haemophilus influenzae by macrophages was quantified by flow cytometry. Iron oxide increased IL-8 production while silica also induced significant production of IL-1β. Both iron oxide and silica enhanced LPS-induced production of TNF-α, IL-1β, IL-6 and IL-8 in THP-1 cells with most of these responses replicated in PBMCs. While silica had no effect on NTHi phagocytosis, iron oxide significantly impaired this response. These data suggest that geogenic particles, particularly iron oxide PM, cause inflammatory cytokine production in macrophages and impair bacterial phagocytosis. These responses do not appear to be linked. This provides a possible mechanism for the link between exposure to these particles and severe bacterial infection.
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Iron Infusion and Induced Hypophosphatemia: The Role of Fibroblast Growth Factor-23.
Coppolino, G, Nicotera, R, Cernaro, V, Calimeri, S, Leonardi, G, Cosentino, S, Comi, A, Donato, C, Lucia, CM, Provenzano, M, et al
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2020;(3):258-264
Abstract
The mechanism of action of fibroblast growth factor-23 (FGF23) is becoming increasingly clearer as a result of studies that have defined its structure and pleiotropic effects. Furthermore, data are emerging on the effects exerted on this hormone by iron administration. Ten main iron formulations are recognized (with clear differences in composition and possible reactions of intolerance and anaphylaxis), which are indicated for iron deficiency anemia, including nephropathic subjects, as suggested by medical guidelines. With some types of iron formulation (especially iron carboxymaltose) a particular side effect has been observed: hypophosphatemia, mediated by FGF23. This review aims to draw attention to this correlation and the contradiction represented by the presence of both positive and negative modulation by FGF23, with the effects induced by its increase even after long-term treatment with iron formulation. However, more evidence is needed to understand the reasons for this differential stimulation.
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Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial.
Santer, P, McGahey, A, Frise, MC, Petousi, N, Talbot, NP, Baskerville, R, Bafadhel, M, Nickol, AH, Robbins, PA
BMJ open respiratory research. 2020;(1)
Abstract
BACKGROUND Increased iron availability modifies cardiorespiratory function in healthy volunteers and improves exercise capacity and quality of life in patients with heart failure or pulmonary hypertension. We hypothesised that intravenous iron would produce improvements in oxygenation, exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD). METHODS We performed a randomised, placebo-controlled, double-blind trial in 48 participants with COPD (mean±SD: age 69±8 years, haemoglobin 144.8±13.2 g/L, ferritin 97.1±70.0 µg/L, transferrin saturation 31.3%±15.2%; GOLD grades II-IV), each of whom received a single dose of intravenous ferric carboxymaltose (FCM; 15 mg/kg bodyweight) or saline placebo. The primary endpoint was peripheral oxygen saturation (SpO2) at rest after 1 week. The secondary endpoints included daily SpO2, overnight SpO2, exercise SpO2, 6 min walk distance, symptom and quality of life scores, serum iron indices, spirometry, echocardiographic measures, and exacerbation frequency. RESULTS SpO2 was unchanged 1 week after FCM administration (difference between groups 0.8%, 95% CI -0.2% to 1.7%). However, in secondary analyses, exercise capacity increased significantly after FCM administration, compared with placebo, with a mean difference in 6 min walk distance of 12.6 m (95% CI 1.6 to 23.5 m). Improvements of ≥40 m were observed in 29.2% of iron-treated and 0% of placebo-treated participants after 1 week (p=0.009). Modified MRC Dyspnoea Scale score was also significantly lower after FCM, and fewer participants reported scores ≥2 in the FCM group, compared with placebo (33.3% vs 66.7%, p=0.02). No significant differences were observed in other secondary endpoints. Adverse event rates were similar between groups, except for hypophosphataemia, which occurred more frequently after FCM (91.7% vs 8.3%, p<0.001). CONCLUSIONS FCM did not improve oxygenation over 8 weeks in patients with COPD. However, this treatment was well tolerated and produced improvements in exercise capacity and functional limitation caused by breathlessness. These effects on secondary endpoints require confirmation in future studies. TRIAL REGISTRATION NUMBER ISRCTN09143837.
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Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial.
Womack, R, Berru, F, Panwar, B, Gutiérrez, OM
Clinical journal of the American Society of Nephrology : CJASN. 2020;(9):1251-1258
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Abstract
BACKGROUND AND OBJECTIVES Ferric citrate is an oral medication approved for treatment of iron deficiency anemia in patients with CKD not requiring dialysis. The relative efficacy of ferric citrate versus ferrous sulfate in treating iron deficiency in patients with CKD is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We randomized 60 adults with moderate to severe CKD (eGFR 15-45 ml/min per 1.73 m2) and iron deficiency (transferrin saturation [TSAT] ≤30% and ferritin ≤300 ng/ml) to ferric citrate (2 g three times a day with meals, n=30) or ferrous sulfate (325 mg three times a day, n=30) for 12 weeks. Primary outcomes were change in TSAT and ferritin from baseline to 12 weeks. Secondary outcomes were change in hemoglobin, fibroblast growth factor 23 (FGF23), and hepcidin. RESULTS Baseline characteristics were well balanced between study arms. There was a greater increase in TSAT (between-group difference in mean change, 8%; 95% confidence interval [95% CI], 1 to 15; P=0.02) and ferritin (between-group difference in mean change, 37 ng/ml; 95% CI, 10 to 64; P=0.009) from baseline to 12 weeks in participants randomized to ferric citrate as compared with ferrous sulfate. Similarly, as compared with ferrous sulfate, treatment with ferric citrate resulted in a greater increase in hepcidin from baseline to 12 weeks (between-group difference, 69 pg/ml; 95% CI, 8 to 130). There were no between-group differences in mean change for hemoglobin (0.3 g/dl; 95% CI, -0.2 to 0.8), intact FGF23 (-29 pg/ml; 95% CI, -59 to 0.1), or C-terminal FGF23 (61 RU/ml; 95% CI, -181 to 58). The incidence of adverse events did not differ between treatment arms. CONCLUSIONS As compared with ferrous sulfate, treatment with ferric citrate for 12 weeks resulted in a greater mean increase in TSAT and ferritin concentrations in individuals with moderate to severe CKD and iron deficiency. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With Moderate to Severe Chronic Kidney Disease (CKD) With Iron Deficiency, NCT02888171.
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Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron: The Myocardial-IRON Trial.
Núñez, J, Miñana, G, Cardells, I, Palau, P, Llàcer, P, Fácila, L, Almenar, L, López-Lereu, MP, Monmeneu, JV, Amiguet, M, et al
Journal of the American Heart Association. 2020;(4):e014254
Abstract
Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6-38.7] versus 40 [38-42.1], P=0.025; 1061 [1051-1072] versus 1085 [1074-1095], P=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1-38.5] versus 41.1 [38.9-43.4], P=0.003), but not for T1 mapping (1075 [1065-1085] versus 1079 [1069-1089], P=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.
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Aggregation-dependent electron transfer via redox-active biochar particles stimulate microbial ferrihydrite reduction.
Yang, Z, Sun, T, Subdiaga, E, Obst, M, Haderlein, SB, Maisch, M, Kretzschmar, R, Angenent, LT, Kappler, A
The Science of the total environment. 2020;:135515
Abstract
Microbial Fe(III) reduction plays an important role for biogeochemical carbon and iron cycling in sediments and soils. Biochar is used as a soil amendment to increase fertility and lower N2O/CO2 emissions. It is redox-active and can stimulate microbial Fe(III) mineral reduction. It is currently unknown, however, how the aggregation of cells and Fe(III) minerals with biochar particles influence microbial Fe(III) reduction. Therefore, we determined rates and extent of ferrihydrite (Fh) reduction in S. oneidensis MR-1 cell suspensions with different particles sizes of wood-derived Swiss biochar and KonTiki biochar at different biochar/Fh ratios. We found that at small biochar particle size and high biochar/Fh ratios, the biochar, MR-1 cells and Fh closely aggregated, therefore addition of biochar stimulated electron transfer and microbial Fh reduction. In contrast, large biochar particles and low biochar/Fh ratios inhibited the electron transfer and Fe(III) reduction due to the lack of effective aggregation. These results suggest that for stimulating Fh reduction, a certain biochar particle size and biochar/Fh ratio is necessary leading to a close aggregation of all phases. This aggregation favors electron transfer from cells to Fh via redox cycling of the electron donating and accepting functional groups of biochar and via direct electron transfer through conductive biochar carbon matrices. These findings improve our understanding of electron transfer between microorganisms and Fe(III) minerals via redox-active biochar and help to evaluate the impact of biochar on electron transfer processes in the environment.
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Chitosan-polyglycidol complexes to coating iron oxide particles for dye adsorption.
Iovescu, A, Stîngă, G, Maxim, ME, Gosecka, M, Basinska, T, Slomkowski, S, Angelescu, D, Petrescu, S, Stănică, N, Băran, A, et al
Carbohydrate polymers. 2020;:116571
Abstract
The study sheds light on the interaction between chitosan (Ch) and polyglycidol (PGL) and uses their interpolymer complex in hydrophilic coating of iron oxide particles (M). Preliminary investigations were performed by modeling chitosan and polyglycidol chains interactions using coarse grained beads approximation and molecular dynamics simulations. The results revealed that Ch and PGL chains associate together forming weak strength complexes, which was experimentally confirmed by surface tension, fluorescence and FTIR. The Ch-PGL mixture (C) and sodium dodecylsulfate (S) were used for layer-by-layer preparation of hydrophilic multilayer coatings of M. The successful covering, demonstrated by DLS, Zeta potential, FTIR, EDAX, preserved the particles super-paramagnetic properties. The most stable multilayer nanocomposite (MSCS) efficiently adsorbed methylene blue from water. The Freundlich model fitted well the equilibrium isotherm data, indicating a heterogeneous, multilayer adsorption. Benefiting from both nano-size and magnetic properties, this adsorbent could be an effectively, cheaply and eco-friendly wastewater treatment means.
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Variable surface charge of humic acid-ferrihydrite composite: Influence of electrolytes on ciprofloxacin adsorption.
Urdiales, C, Gacitua, M, Villacura, L, Pizarro, C, Escudey, M, Canales, C, Antilén, M
Journal of hazardous materials. 2020;:121520
Abstract
Antimicrobial compounds are found in a range of environments as pollutants. Here, we evaluated the influence of two common anions, NO3- and PO43-, on ciprofloxacin adsorption on humic acid/ferrihydrite composite (HA-DIG/Fh), synthetic ferrihydrite (Fh), and humic acid (HA-DIG) under controlled pH (7.0), ionic strength (0.1 M) and temperature (25 °C). All materials were characterized by isoelectric point (IEP), while the composite and the iron oxide were characterized by Mössbauer spectroscopy. Kinetic and isotherm adsorption studies were carried out using cyclic voltammetry (in KH2PO4) and square wave voltammetry (in KNO3). The application of kinetic models for both anions revealed Fh to fit to a pseudo second order model (R2 = 0.941); while HA-DIG (R2 = 0.950) and HA-DIG/Fh (R2 = 0.993) were fitted to pseudo first order models. The adsorption results showed a high dependency electrolyte, especially in Fh, where different shape curves (H-type in KNO3 and C-type in KH2PO4) and maximum experimental adsorbed amount Cm were observed. This finding is supported by the distinct IEP values and change in sign of surface charge between the two ions. Finally, results suggest that HA-DIG could be potentially used in environmental remediation to remove antibiotics from natural matrices, though the risk of antibiotic transportation increased with depth in the soil profile.
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Intravenous ferric carboxymaltose for iron deficiency anemia or iron deficiency without anemia after poor response to oral iron treatment: Benefits and risks in a cohort of 144 children and adolescents.
Ozsahin, H, Schaeppi, M, Bernimoulin, M, Allard, M, Guidard, C, van den Ouweland, F
Pediatric blood & cancer. 2020;(10):e28614
Abstract
OBJECTIVE The objective of this single-center observational study was to determine the clinical and hematologic responses to intravenous ferric carboxymaltose (FCM) in a cohort of pediatric patients with poor response to oral iron therapy. The occurrence of adverse events was systematically recorded for up to 96 hours after infusion. STUDY DESIGN A retrospective cohort of 144 consecutive patients aged 18 months to < 18 years with iron deficiency anemia (IDA) or iron deficiency (ID) without anemia was investigated. All patients had failed oral iron therapy. The assessments before and after FCM treatment followed a predefined protocol. RESULTS One hundred of 117 (85 %) of patients with complete data achieved the target ferritin level ≥ 30 µg/L after a single FCM dose. Of 77 patients with IDA and complete data, 38 (49%) showed a complete hematological response within 6-12 weeks; a complete or partial response was achieved by 83%. Clinical symptoms improved in 85% of all patients. In 92% of patients (n = 133 /144), FCM infusion was uneventful. During the 96-hour follow-up, five patients reported potentially related symptoms. No serious adverse events occurred. CONCLUSION The study confirms the safety and efficacy of FCM in children (aged 18 months and older) and adolescents unresponsive to oral therapy, in real-world experience. Single-dose FCM treatment was followed by clinical improvement with advantages of safety, compliance, and lower cost compared with previous generation parenteral iron preparations that had to be administered in fractionated sessions.
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Geochemical and isotopic study of abiotic nitrite reduction coupled to biologically produced Fe(II) oxidation in marine environments.
Benaiges-Fernandez, R, Offeddu, FG, Margalef-Marti, R, Palau, J, Urmeneta, J, Carrey, R, Otero, N, Cama, J
Chemosphere. 2020;:127554
Abstract
Estuarine sediments are often characterized by abundant iron oxides, organic matter, and anthropogenic nitrogen compounds (e.g., nitrate and nitrite). Anoxic dissimilatory iron reducing bacteria (e.g., Shewanella loihica) are ubiquitous in these environments where they can catalyze the reduction of Fe(III) (oxyhydr)oxides, thereby releasing aqueous Fe(II). The biologically produced Fe(II) can later reduce nitrite to form nitrous oxide. The effect on nitrite reduction by both biologically produced and artificially amended Fe(II) was examined experimentally. Ferrihydrite was reduced by Shewanella loihica in a batch reaction with an anoxic synthetic sea water medium. Some of the Fe(II) released by S. loihica adsorbed onto ferrihydrite, which was involved in the transformation of ferrihydrite to magnetite. In a second set of experiments with identical medium, no microorganism was present, instead, Fe(II) was amended. The amount of solid-bound Fe(II) in the experiments with bioproduced Fe(II) increased the rate of abiotic NO2- reduction with respect to that with synthetic Fe(II), yielding half-lives of 0.07 and 0.47 d, respectively. The δ18O and δ15N of NO2- was measured through time for both the abiotic and innoculated experiments. The ratio of ε18O/ε15N was 0.6 for the abiotic experiments and 3.1 when NO2- was reduced by S. loihica, thus indicating two different mechanisms for the NO2- reduction. Notably, there is a wide range of the ε18O/ε15N values in the literature for abiotic and biotic NO2- reduction, as such, the use of this ratio to distinguish between reduction mechanisms in natural systems should be taken with caution. Therefore, we suggest an additional constraint to identify the mechanisms (i.e. abiotic/biotic) controlling NO2- reduction in natural settings through the correlation of δ15N-NO2- and the aqueous Fe(II) concentration.