The Impact of the Combined Effect of Inhalation Anesthetics and Iron Dextran on Rats' Systemic Toxicity.

Disruption of any stage of iron homeostasis, including uptake, utilization, efflux, and storage, can cause progressive damage to peripheral organs. The health hazards associated with occupational exposure to inhalation anesthetics (IA) in combination with chronic iron overload are not well documented. This study aimed to investigate changes in the concentration of essential metals in the peripheral organs of rats after iron overload in combination with IA. The aim was also to determine how iron overload in combination with IA affects tissue metal homeostasis, hepcidin-ferritin levels, and MMP levels according to physiological, functional, and tissue features. According to the obtained results, iron accumulation was most pronounced in the liver (19×), spleen (6.7×), lungs (3.1×), and kidneys (2.5×) compared to control. Iron accumulation is associated with elevated heavy metal levels and impaired essential metal concentrations due to oxidative stress (OS). Notably, the use of IA increases the iron overload toxicity, especially after Isoflurane exposure. The results show that the regulation of iron homeostasis is based on the interaction of hepcidin, ferritin, and other proteins regulated by inflammation, OS, free iron levels, erythropoiesis, and hypoxia. Long-term exposure to IA and iron leads to the development of numerous adaptation mechanisms in response to toxicity, OS, and inflammation. These adaptive mechanisms of iron regulation lead to the inhibition of MMP activity and reduction of oxidative stress, protecting the organism from possible damage.

Effects of a second iron-dextran injection administered to piglets during lactation on differential gene expression in liver and duodenum at weaning.

Six female littermate piglets were used in an experiment to evaluate the mRNA expression in tissues from piglets given one or two 1 mL injections of iron dextran (200 mg Fe/mL). All piglets in the litter were administered the first 1 mL injection < 24 h after birth. On day 7, piglets were paired by weight (mean body weight = 1.72 ±â€…0.13 kg) and one piglet from each pair was randomly selected as control (CON) and the other received a second injection (+Fe). At weaning on day 22, each piglet was anesthetized, and samples of liver and duodenum were taken from the anesthetized piglets and preserved until mRNA extraction. differential gene expression data were analyzed with a fold change cutoff (FC) of |1.2| P < 0.05. Pathway analysis was conducted with Z-score cutoff of P < 0.05. In the duodenum 435 genes were significantly changed with a FC ≥ |1.2| P < 0.05. In the duodenum, Claudin 1 and Claudin 2 were inversely affected by + Fe. Claudin 1 (CLDN1) plays a key role in cell-to-cell adhesion in the epithelial cell sheets and was upregulated (FC = 4.48, P = 0.0423). Claudin 2 (CLDN2) is expressed in cation leaky epithelia, especially during disease or inflammation and was downregulated (FC = -1.41, P = 0.0097). In the liver, 362 genes were expressed with a FC ≥ |1.2| P < 0.05. The gene most affected by a second dose of 200 mg Fe was hepcidin antimicrobial peptide (HAMP) with a FC of 40.8. HAMP is a liver-produced hormone that is the main circulating regulator of Fe absorption and distribution across tissues. It also controls the major flows of Fe into plasma by promoting endocytosis and degradation of ferroportin (SLC4A1). This leads to the retention of Fe in Fe-exporting cells and decreased flow of Fe into plasma. Gene expression related to metabolic pathway changes in the duodenum and liver provides evidence for the improved feed conversion and growth rates in piglets given two iron injections preweaning with contemporary pigs in a companion study. In the duodenum, there is a downregulation of gene clusters associated with gluconeogenesis (P < 0.05). Concurrently, there was a decrease in the mRNA expression of genes for enzymes required for urea production in the liver (P < 0.05). These observations suggest that there may be less need for gluconeogenesis, and possibly less urea production from deaminated amino acids. The genomic and pathway analyses provided empirical evidence linking gene expression with phenotypic observations of piglet health and growth improvements.

Iron deficiency anemia (IDA) in neonatal piglets is a problem that occurs unless there is intervention with exogenous iron. The most common method to prevent IDA is with an iron injection within 48 h of birth. However, the iron from the first injection will only support normal iron status in the piglets for ~4 kg of growth. As a result, with faster-growing piglets and larger litters, many piglets weaned today are iron deficient which results in slower growth and poor immunity. Pigs never fully recover nor grow at the same rate as those that have sufficient iron status. The aim of this study was to evaluate the effects of one or two injections of iron dextran on the differences in gene expression and metabolic pathway changes in the small intestine and liver of nursing piglets. At weaning, samples of liver and duodenum underwent genome-wide RNA sequencing. The data obtained were statistically analyzed to determine which genes and metabolic pathways were affected. There were 362 and 435 genes significantly changed in the liver and duodenum, respectively, due to a second dose of iron dextran on day 7 after birth.

A second iron injection administered to piglets during lactation improves hemoglobin concentration, growth performance, and carcass characteristics at slaughter.

An experiment was conducted to evaluate the effects of a second injection of iron dextran administered on days 6 to 8 of age. A total of 144 crossbred pigs (equal barrows and gilts; initial age 6 to 8 d; initial body weight [BW] = 2.86 ± 0.01 kg) were assigned to either the control (CON) or an added-injection treatment (+Fe). Pigs were paired by sex and BW within a litter and randomly assigned to the iron treatment within each pair. All pigs had received an initial intramuscular (IM) injection of iron dextran (200 mg Fe) <24 h after birth. Pigs assigned to the +Fe treatment received a second IM injection of iron dextran (200 mg Fe) on days 6 to 8. All pigs were weaned at 22 to 25 d, housed 6 pigs/pen, and received a common corn-soybean meal diet. BW and feed disappearance were recorded every 2 wk. Hemoglobin (Hb) concentrations were measured at birth, initiation of experiment (days 6 to 8), weaning, and the end of the nursery and end of the study. At the end of the study, 1 pig/pen (n = 12 pigs/treatment), closest to the pen mean was selected and slaughtered for carcass characteristic measures. The individual pig served as the experimental unit for BW, Hb, average daily gain (ADG), and carcass characteristic data whereas the pen served as the experimental unit for average daily feed intake, and gain/feed ratio data. The +Fe pigs had a greater Hb at weaning (13.1 vs. 10.7 g/dL, respectively; P < 0.01) and end of the nursery (12.1 vs. 11.7 g/dL, respectively; P = 0.01) compared to CON pigs. During the finisher period, +Fe pigs had a greater ADG (0.94 vs. 0.91 kg, respectively; P = 0.05) compared to CON pigs. Overall, pigs receiving the second iron injection had an ~4% increase in ADG (P = 0.04) from weaning to the end of study. The cumulative improvement in ADG from weaning to the end of study observed for +Fe group resulted in +Fe pigs having a heavier BW at the end of the study (~3 kg; P = 0.04). Following slaughter, +Fe pigs had ~7.2% heavier trimmed loin (P = 0.04) compared to the CON pigs. In conclusion, administering a second iron injection resulted in greater Hb at weaning and the end of the nursery as well as improved growth performance from weaning to the end of study weight and increased carcass weight at slaughter.

The study aimed to evaluate the effects of a second iron dextran injection administered to piglets before weaning on hemoglobin concentration (Hb), growth performance, and carcass measures. Treatments included: a single iron injection administered within 24 h after birth (CON) and two iron injections (+Fe), one administered within 24 h after birth followed by a second iron injection administered 6 to 8 d after birth. Administering a second iron injection before weaning resulted in increased Hb at weaning and the end of the nursery period. Furthermore, pigs receiving a second iron injection had a greater average daily gain from weaning to final market weight which resulted in a final bodyweight difference of ~3 kg. The increased slaughter weight observed for pigs receiving a second iron injection was associated with an increase in trimmed loin yield. In the current study, providing a second iron injection before weaning was a practical method to improve weaning Hb in early life and resulted in a faster overall growth from weaning to the end of the study.

An Analytical Method for Determination of Total Iron in Pharmaceuticalgrade Intravenous Iron Colloidal Complexes by Redox-Potentiometry.

BACKGROUND: Iron carbohydrate complexes are colloidal dispersions made up of polynuclear Fe(III)-oxyhydroxide cores surrounded by a carbohydrate shell that stabilizes the complex in iron colloidal formulations. The current study provides an improved method that is precise, accurate, and linear for quantifying total iron in most Iron Carbohydrate Colloid Drug Products. METHODS: Redox iodometry with a potentiometric determination is used to evaluate total iron in intravenous formulations. The visual indicator approach is more prone to fluctuations at endpoint calculations. Hence, the voltage potential approach is widely accepted as it is more accurate and sensitive. It tracks the actual change in activity that coincides with the equivalence point that is finally considered an endpoint. The principle is based on the idea that ferric iron in formulation reduces to ferrous iron in the presence of the iodide, which oxidizes to iodine. The released iodine is titrated using sodium thiosulfate. RESULTS: The proposed method was precise, with %RSD (relative standard deviation) not more than 1. The method was linear between 80% and 120%, with a linear regression of 0.999. The percent recovery ranged from 98.20 to 99.98 for the concentration ranges of 80-120. The method's robustness was checked by various analysts using different reagent grades. CONCLUSION: The proposed potentiometric determination method was precise, accurate, linear, and sensitive. The method was successfully validated, and the total iron content determined for commercial batches agrees with the iron claim on the label. Therefore, this method can be adapted widely for total iron content determination in any Intravenous formulation currently available on the market. The proposed method is more accessible at the Quality Control facilities on an industrial scale.

Effect of iron dextran dispersible tablets on heart failure patients with iron deficiency / 中国临床药理学与治疗学

AIM: To evaluate the clinical effect of Iron Dextran Dispersible Tablets on patients with chronic heart failure who reduced ejection fraction after 24 weeks. METHODS: From January 2020 to June 2022, forty-five patients with heart failure complicated with iron deficiency and reduced ejection fraction were selected as the research objects. According to the random number table, they were randomly divided into control group and observation group.The control group was given routine anti-heart failure treatment such as Sacubitril Calsartan sodium tablets, while the observation group was given iron dextran dispersible tablets 50 mg three times a day on the basis of the anti-heart failure treatment of the control group for 8 weeks. The 6-minute walking distance, Hemoglobin, Serum Ferritin, N-terminal B-type natriuretic peptide precursor, Left Ventricular Ejection Fraction, Left Ventricular end Diastolic Diameter and 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score and clinical summary score were compared between the two groups. RESULTS: There was no significant difference in baseline data between the two groups (P > 0.05). After treatment, the 6-minute walking distance in the observation group was longer than that in the control group, while the serum ferritin level in the observation group was higher than that in the control group. The N-terminal pro-B-type natriuretic peptide level in the two groups was lower than that before treatment, and the left ventricular end diastolic diameter was shorter than that before treatment, and the left ventricular ejection fraction, clinical comprehensive score and symptom score were higher than that before treatment. The difference was statistically significant (P 0.05). CONCLUSION: Iron Dextran Dispersible Tablets can improve the exercise endurance and quality of life of patients with chronic heart failure who reduced ejection fraction after 24 weeks.

Desolvation Synergy of Multiple H/Li-Bonds on an Iron-Dextran-Based Catalyst Stimulates Lithium-Sulfur Cascade Catalysis.

Traditional lithium-sulfur battery catalysts are still facing substantial challenges in solving sulfur redox reactions, which involve multistep electron transfer and multiphase transformations. Here, inspired by the combination of iron dextran (INFeD) and ascorbic acid (VC) as a blood tonic for the treatment of anemia, a highly efficient VC@INFeD catalyst is developed in the sulfur cathode, accomplishing the desolvation and enrichment of high-concentration solvated lithium polysulfides at the cathode/electrolyte interface with the assistance of multiple H/Li-bonds and resolving subsequent sulfur transformations through gradient catalysis sites where the INFeD promotes long-chain lithium polysulfide conversions and VC accelerates short-chain lithium polysulfide conversions. Comprehensive characterizations reveal that the VC@INFeD can substantially reduce the energy barrier of each sulfur redox step, inhibit shuttle effects, and endow the lithium-sulfur battery with high sulfur utilization and superior cycling stability even under a high sulfur loading (5.2 mg cm-2 ) and lean electrolyte (electrolyte/sulfur ratio, ≈7 µL mg-1 ) condition.

Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS: We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS: Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

Effects of Volatile Anaesthetics and Iron Dextran on Chronic Inflammation and Antioxidant Defense System in Rats.

Iron, as an essential microelement, is involved in cell proliferation, metabolism, and differentiation. It also modulates the fate and function of macrophages in hematopoiesis and macrophage-mediated inflammatory responses. On the other hand, anesthetics can affect the inflammatory process by modulating the response to stress or the functions of immune cells. The aim of this paper is to understand how excessive iron intake alters physiological, functional characteristics of peripheral tissues and whether different anesthetics can alter cell metabolism regarding oxidative stress (OS) and inflammation through regulation of macrophage polarization. Y59 rats were injected intraperitoneally with iron dextran solution at a dose of 50 mg/kg or were exposed to inhaled anesthetics sevoflurane and isoflurane and their combination for 28 days every other day. The results show that the use of anesthetics reduces the rat's organ weight and increases OS in peripheral tissues, leading to M1 macrophage polarization. Excessive iron intake leads to increased OS, inflammation, and an increased ratio of IL-12/IL-10 cytokines to the M1 macrophage phenotype. Iron, in combination with sevoflurane, has a protective effect in tissues showing the M2 phenotype of macrophages. The combination of iron dextran and isoflurane in rats leads to an increase in the erythropoiesis process made possible through the induction of hypoxia.

Low Molar Mass Dextran: One-Step Synthesis With Dextransucrase by Site-Directed Mutagenesis and its Potential of Iron-Loading.

Iron dextran is a common anti-anemia drug, and it requires low molar mass dextran as substrate. In this work, we selected 11 amino acid residues in domain A/B of DSR-MΔ2 within a 5-angstrom distance from sucrose for site-directed mutagenesis by molecular docking. Mutation of Q634 did not affect the enzyme catalytic activity, but showed an obvious impact on the ratio of low molecular weight dextran (L-dextran, 3,000-5,000 Da) and relatively higher molecular weight dextran (H-dextran, around 10,000 Da). L-dextran was the main product synthesized by DSR-MΔ2 Q634A, and its average molecular weight was 3,951 Da with a polydispersity index <1.3. The structural characterization of this homopolysaccharide revealed that it was a dextran, with 86.0% α(1→6) and 14.0% α(1→4) glycosidic linkages. Moreover, L-dextran was oxidized with NaOH and chelated with ferric trichloride, and an OL-dextran-iron complex was synthesized with a high iron-loading potential of 33.5% (w/w). Altogether, mutation of amino acids near the sucrose binding site of dextransucrase can affect the chain elongation process, making it possible to modulate dextran size.

A retrospective study of the safety and efficacy of low molecular weight iron dextran for children with iron deficiency anemia.

BACKGROUND: Iron deficiency anemia (IDA) affects millions of children worldwide. Oral iron replacement is effective but often poorly tolerated. Intravenous iron has been demonstrated to have utility in all ages, but pediatric use remains limited. Low molecular weight iron dextran (LMWID) has a dosing range capable of replacing iron deficits in a single infusion and has been evaluated in small pediatric cohorts, but additional safety and efficacy data are limited. Here, we evaluate the safety and efficacy of LMWID in association with an electronic medical record (EMR)-based effort to optimize dosing. PROCEDURE: A retrospective IRB-approved investigation of LMWID utilization at a tertiary pediatric hospital between January 1, 2016 and March 31, 2020 was undertaken to evaluate the therapeutic efficacy and frequency/severity of infusion-related adverse event (AE) in children and adolescents receiving LMWID. Patient demographics and LMWID dosing characteristics were collected, and primary outcome measures included laboratory response and the incidence/severity of any infusion-related events. The utilization of an EMR-based nomogram for LMWID dosing was also evaluated. RESULTS: A total of 254 infusions for 191 patients were included (ages 0.7-20.9 years), most with IDA. LMWID replaced at least 75% of the estimated iron deficit in a single infusion for 76% of patients. The mean hemoglobin and ferritin increases were 2.1 g/dl and >100 ng/ml, respectively. Infusion-related AEs were rare, occurring in only 12/254 (4.7%) of infusions and 67% during the test dose; each rapidly resolved without long-term sequelae. No AEs occurred in those <10 years of age. Premedication use markedly decreased with nomogram use without a change in AE rate. CONCLUSIONS: In a large institutional cohort, LMWID was well tolerated in children and adolescents, with most patients having their total iron deficits relieved in a single infusion. These data support expanded use of LMWID in the management of pediatric iron deficiency.

Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.

Rationale: Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear. Objectives: To evaluate the safety and efficacy of parenteral iron replacement in PAH. Methods: In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight <66.7 kg) or saline as placebo, and 17 patients in China received iron dextran (Cosmofer) (20 mg iron/kg body weight) or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by a serum ferritin <37 µg/L or iron <10.3 µmol/L or transferrin saturations <16.4%. Results: Both iron treatments were well tolerated and improved iron status. Analyzed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6-minute walk test) or cardiopulmonary hemodynamics, as assessed by right heart catheterization, cardiac magnetic resonance, or plasma NT-proBNP (N-terminal-pro hormone brain natriuretic peptide) at 12 weeks. Conclusions: Iron repletion by administration of a slow-release iron preparation as a single infusion to patients with PAH with iron deficiency without overt anemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).

Assessing Pain Control Efficacy of Meloxicam and Ketoprofen When Compounded with Iron Dextran in Nursing Piglets Using A Navigation Chute.

The efficacy of analgesics such as meloxicam and ketoprofen to control pain in piglets when mixed with iron dextran (ID) before injection is unknown. The purpose of this study was to compare perceived pain in castrated piglets treated 1 h before castration with either of these drugs alone, or when mixed with ID, by observing the time it takes for piglets to navigate a chute. Piglets were divided into seven treatment groups (n = 25 piglets per treatment group) including castration with analgesia (meloxicam or ketoprofen), castration with analgesic plus ID, castration without analgesic or ID, sham handled and given ID, and sham handled alone. Piglets were placed in a short chute and their time to navigate the chute was recorded at four timepoints following castration. Piglets given meloxicam or ketoprofen, with or without ID did not differ from each other in their chute navigation times. Additionally, these piglets did not differ from treatment groups that were not castrated. Piglets castrated without analgesia had significantly longer navigation times. These results indicate that meloxicam or ketoprofen, whether mixed with ID prior to injection or not, provide similar analgesic efficacy.

Consequences of parenteral iron-dextran loading investigated in minipigs. A new model of transfusional iron overload.

Patients with blood transfusion-dependent anemias develop transfusional iron overload (TIO), which may cause cardiosiderosis. In patients with an ineffective erythropoiesis, such as thalassemia major, common transfusion regimes aim at suppression of erythropoiesis and of enteral iron loading. Recent data suggest that maintaining residual, ineffective erythropoiesis may protect from cardiosiderosis. We investigated the common consequences of TIO, including cardiosiderosis, in a minipig model of iron overload with normal erythropoiesis. TIO was mimicked by long-term, weekly iron-dextran injections. Iron-dextran loading for around one year induced very high liver iron concentrations, but extrahepatic iron loading, and iron-induced toxicities were mild and did not include fibrosis. Iron deposits were primarily in reticuloendothelial cells, and parenchymal cardiac iron loading was mild. Compared to non-thalassemic patients with TIO, comparable cardiosiderosis in minipigs required about 4-fold greater body iron loads. It is suggested that this resistance against extrahepatic iron loading and toxicity in minipigs may at least in part be explained by a protective effect of the normal erythropoiesis, and additionally by a larger total iron storage capacity of RES than in patients with TIO. Parenteral iron-dextran loading of minipigs is a promising and feasible large-animal model of iron overload, that may mimic TIO in non-thalassemic patients.

Evaluation of the reported rates of hypersensitivity reactions associated with iron dextran and ferric carboxymaltose based on global data from VigiBase™ and IQVIA™ MIDAS® over a ten-year period from 2008 to 2017.

Objectives: It is hypothesized that the risk of hypersensitivity reactions (HSRs) may be lower with ferric carboxymaltose than iron dextran because of its non-dextran carbohydrate moiety. This study compares the risk of HSRs between iron dextran and ferric carboxymaltose.Methods: This was a retrospective pharmacoepidemiological study with a case-population design covering 2008-2017. Global exposure data were estimated using IQVIA™ sales data. Spontaneously reported HSR data were retrieved from the World Health Organization database (VigiBase™) using different search criteria including: the Standardized MedDRA® Query (SMQ) 'Anaphylactic reaction'; type I-IV HSR terms; narrow terms for anaphylactic/anaphylactoid reactions; and cases with a fatal outcome.Results: Total exposure in 100 mg doses was 117.3 million for iron dextran and 84.2 million for ferric carboxymaltose. The relative risk (with 95% confidence interval) for ferric carboxymaltose versus iron dextran was 4.18 (3.88-4.50) for SMQ Anaphylactic reaction; 12.9 (9.90-16.7) for type I-IV HSRs; 1.72 (1.45-2.04) for anaphylactic/anaphylactoid reactions; and 1.92 (1.24-2.99) for death.Conclusion: The risk of spontaneously reported HSRs was consistently higher with ferric carboxy-maltose than with iron dextran over the period 2008-2017. Thus, this study does not support that dextran-free intravenous irons are associated with fewer HSRs than iron dextran.

Safety and Efficacy of Intravenous Iron Sucrose versus Low Molecular Weight Iron Dextran for Treatment of Iron Deficiency Anemia in Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the efficacy, side effects, and clinical outcomes between parenteral iron sucrose complex (ISC) and low-molecular-weight iron dextran (LMWID) for iron deficiency anemia (IDA) in pregnancy. METHODS: The study was conducted in a Malaysian tertiary hospital for a period of 1 year. Forty pregnant women with IDA between 24 and 38 weeks of gestation were randomized into two groups receiving treatment with either ISC or LMWID. RESULTS: No significant difference was found between the groups in terms of demographic data, parity, and mean gestational age. A mean total of 835 ± 150 mg doses of ISC and 656 ± 382 mg doses of LMWID were administered (P = 0.0001). Adverse events were reported in five patients who received LMWID and none in those treated with ISC (P = 0.024). The mean hemoglobin (Hb) level increment 2 weeks post treatment was higher among those who received ISC than in those who received LMWID. The ISC group demonstrated an increase of 1.91 ± 1.10 g/dL (from 8.43 ± 1.03 g/dL to 10.29 ± 0.90 g/dL) compared with the LMWID group at 1.39 ± 0.54 g/dL (from 8.61 ± 0.70 g/dL to 9.92 ± 0.88 g/dL, P = 0.023). All participants in both groups delivered at term. The estimated blood loss during delivery was significantly higher in the LMWID group (359 ± 247 mL) than in the ISC group (280 ± 100 mL, P = 0.026). Otherwise, no significant difference was observed in terms of Hb level during delivery and the perinatal outcomes for both groups. CONCLUSION: Parenteral ISC is more effective than LMWID in treating maternal IDA, and it is associated with fewer adverse events.

One Iron Injection Is Not Enough-Iron Status and Growth of Suckling Piglets on an Organic Farm.

Suckling piglets cannot satisfy their demand for the essential trace element iron from sows' milk alone, which is poor in iron. Therefore, iron is usually supplemented by injecting 200 mg iron (as iron dextran) on day 3 post natum. However, the longer suckling period in organic pig herds leads to iron intake from feed starting later. We hypothesized that one iron injection is not enough for organically reared piglets, and that a second and third injection would improve their iron status and growth. On an organically certified experimental farm, 288 piglets from 32 litters were allocated to three treatments with one iron injection on day 3, two injections on day 3 and 14 and three injections on day 3, 14 and 21 post natum, respectively. One injection resulted in the lowest hematocrit and serum iron levels until day 28 post natum and the lowest daily weight gains until weaning, while piglets receiving two or three iron injections did not differ from each other. Based on these observations, we conclude that one iron injection is not enough to ensure adequate iron supply and unimpaired growth of organically reared piglets, and additional iron supply is necessary.

Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies.

OBJECTIVE: Restless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity. METHOD: The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0. RESULTS: This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21-5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score. CONCLUSION: The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.

Iron is Responsible for Production of Reactive Oxygen Species Regulating Vasopressin Expression in the Mouse Paraventricular Nucleus.

Reactive oxygen species (ROS) act as signaling molecules for maintaining homeostasis, particularly in the regulation of body-fluid balance in the paraventricular nucleus (PVN) of the hypothalamus. However, there has been little discussion regarding the source of ROS generation in this hypothalamic region. Because iron is the most abundant metal in the brain, we hypothesized that iron may act as a source of ROS, which regulate vasopressin (VP) expression. In the present study, we compared the amount of iron in the PVN to that in other forebrain regions of normal ICR mice, and examined the relationship among iron, ROS, and VP in the PVN of the iron-overloaded with iron dextran and iron-chelated mice with deferoxamine. The amount of iron in the PVN was significantly higher than in any of the forebrain regions we examined. The amount of iron in the PVN was significantly increased in iron-overloaded mice, although not in iron-chelated mice. These results suggest that the PVN exhibits high iron affinity. Both ROS production and VP expression in the PVN of iron-overloaded mice were significantly increased relative to levels observed in control mice. VP concentration in blood of iron-overloaded mice was also significantly higher than that of control mice. Interestingly, iron overload did not alter the expression of nitric oxide synthase, another modulator of VP expression. Taken together, our results suggest that high levels of iron in the PVN induce the production of ROS, which regulate VP expression, independent of nitric oxide signaling.

Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial.

STUDY OBJECTIVE: To test safety, efficacy, and cost-effectiveness of total dose infusion (TDI) of low molecular weight (LMW) iron dextran for treatment of iron deficiency anemia (IDA) during pregnancy in comparison to oral ferrous fumarate. DESIGN: Prospective interventional randomized controlled trial (RCT). Design classification. Canadian Task Force II3. SETTING: Antenatal clinic and causality unit of a tertiary care referral facility and University Hospital. PATIENTS: A total 66 anemic pregnant women (hemoglobin level between 7-10 g/dl). INTERVENTION: Administration of a LMW iron dextran as a TDI (group A) or Oral iron ferrous fumarate 60 mg elemental iron three times daily (group B) followed by remeasurement of hemoglobin after 4 weeks. MEASURES AND MAIN RESULTS: The main outcome measure was clinical and laboratory improvement of anemia after 4 weeks of starting the therapy. Both groups showed a significant clinical improvement of anemia 4 weeks post-therapy. However, the first improvement of symptoms was significantly faster in group A. Complete blood count (CBC) as well as all iron indices were improved in both groups after 4 weeks of therapy, but were significantly better in group A than B. Side effects in group B were mainly gastrointestinal (GIT) while one case of mild hypersensitivity to TDI and another one case of local reaction at the site of injection were reported in group A. CONCLUSIONS: It is concluded that despite being equally effective in improving both clinical and laboratory evidence of IDA, TDI allows iron restoration with a single dose faster than oral iron therapy with a reasonable safety profile. It is a good example of office one-stop therapy. Nevertheless, noninvasive selfusage at home is a clear advantage of the cheaper oral iron therapy which makes it the first choice for treating IDA in the second and third trimesters of pregnancy in tolerable cases.