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FN, a 29-year-old gravida 3 Para 2+2 female (with no live child), member of Jehovah’s Witness sect had emergency Caesarean section under general anaesthesia with endotrachael intubation for abruptio placentae at 35 weeks of gestation. Preoperative and postoperative packed cell volume (PCV) was 28% and 9% respectively. She received erythropoietin and iron dextran infusions. Patient developed anaemic heart failure on 3rd post-operative day which was managed successfully. She recovered completely and was discharged home on the 28th post-operative day. Management dilemmas specific to the Jehovah’s Witness parturient with abruptio placentae are discussed.

In pigs, iron deficiency anemia (IDA) is the most prevalent deficiency disorder during the early postnatal period, frequently developing into a serious illness. On the other hand, in humans, only low-birth-weight infants, including premature infants, are especially susceptible to developing IDA. In both human and pig neonates, the initial cause of IDA is low birth iron stores. In piglets this shortage of stored iron results mainly from genetic selection over the past few decades for large litter sizes and high birth weights. As a consequence, pregnant sows cannot provide a sufficient amount of iron to the increasing number of developing fetuses. Supplementation with iron is a common practice for the treatment of IDA in piglets. For decades, the preferred procedure for delivering iron supplements during early life stages has been through the intramuscular injection of a large amount of iron dextran. However, this relatively simple therapy, which in general, efficiently corrects IDA, may generate toxic effects, and by inducing hepcidin expression, may decrease bioavailability of supplemental iron. New iron supplements are considered herein with the aim to combine the improvement of hematological status, blunting of hepcidin expression, and minimizing the toxicity of the administered iron. We propose that iron-deficient piglets constitute a convenient animal model for performing pre-clinical studies with iron supplements.

Anestetici su vrste lijekova u plinovitom, tekućem ili drugom obliku, čija je funkcija uvođenje i/ili održavanje anestezije s ciljem olakšavanja kirurških i drugih bolnih zahvata. Izofluran ima brzo farmakološko djelovanje i apsorbanciju, te potiče brz oporavak nakon anestezije. Međutim, dugotrajno izlaganje anesteticima djeluje negativno na periferne organe i tkiva, te potiče upalu, oksidacijski stres, nekrozu i apoptozu vodeći pojavnosti neurodegenerativnih bolesti poput Alzheimerove i Parkinsonove bolesti. Željezo je neizostavni dio živućeg organizma i poremećajem njegove homeostaze nastaje redoks aktivno željezo koje utječe na stvaranje ROS-a, ozljeda tkiva, poremećaja rasta stanica, te u konačnici na pojavu oksidacijskog stresa. Temeljem navedenog, cilj rada jest istražiti utjecaj primjene anestetika izoflurana samog i/ili združenog sa željezo dekstranom na razinu oksidacijskog stresa i posljedične upale na uzorcima tkiva jetre, slezene i bubrega. Dobiveni rezultati ukazuju da dugotrajna primjena izoflurana i željezo-dekstrana samog ili u kombinaciji povećava razinu oksidacijskog stresa i upale u stanicama jetre, bubrega i slezene te vodi njihovom oštećenju na što ukazuje povećanje biokemijskih parametara u serumu te hemoliza eritrocita. Anesthetics are types of medicines in a gaseous, liquid or other form, whose function is the introduction and/or maintenance of anesthesia with the aim of facilitating surgical and other painful interventions. Isoflurane has rapid pharmacological activity and absorbance, and stimulates rapid recovery after anesthesia. Long-term exposure to anesthetic acts negatively on peripheral organs and tissues, stimulates inflammation, oxidative stress, necrosis, and apoptosis leading to neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Iron is an indispensable part of the living organism and the disorder of its homeostasis produces redox active iron that affects the formation of ROS, tissue injury, cell growth disorder, and ultimately the appearance of oxidative stress. The aim of the study was to investigate the effect of isoflurane itself and/or the combination of iron dextran on the level of oxidative stress and consequent inflammation on liver, spleen and kidney tissues. The obtained results indicate that long-term use of isoflurane and iron-dextran alone or in combination increases the level of oxidative stress and inflammation in the liver, kidney and spleen cells and leads to their impairment, indicating an increase in biochemical parameters in serum and hemolysis of erythrocyte.

El objetivo de esta investigación fue evaluar el efecto de diferentes protocolos de administración de hierro en la prevención de anemia en lechones, a través de variables hematológicas como cantidad de hematíes (RBC), hemoglobina (HB), hematocrito (HT0), índices eritrocitarios (VCM, HCM, CHCM), ferritina (FT) y transferrina (TF). El estudio se realizó en el Centro Experimental Uyumbicho, Pichincha (Ecuador). Se utilizó un total de 27 lechones (Landrace x Yorkshire x Pietrain) distribuidos en un diseño completamente aleatorizado en tres tratamientos (T). En T1 se aplicó hierro-dextrano (100 mg/ml), a una única dosis de 2 ml al tercer día de edad; T2 hierrodextrano (100 mg/ml), 1 ml a los días 3 y 7 de edad; y T3 hierro dextrano (200 mg/ml), 1 ml al día 3 de edad. Adicionalmente se evaluó el peso vivo a los 28 días de edad (destete). Las muestras de sangre fueron tomadas 4 días después de la aplicación. Se encontraron diferencias (p0,05). Respecto al peso vivo no hubo diferencias entre los grupos evaluados (p>0,05). Se concluye que la aplicación de dos dosis de hierro-dextrano (100 mg/dl a los 3 y 7 días de edad), fue más efectiva para prevenir la anemia, como lo reflejan los valores de hematíes, hemoglobina y hematocrito. El peso vivo del lechón no se vio favorecido por ninguno de los tratamientos aplicados.

Background: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). Methods: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. Results: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. Conclusion: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.

RESUMO Com o objetivo de avaliar o uso de diferentes fontes de ferro na prevenção da anemia ferropriva e no desempenho em leitões lactentes, dividiram-se 202 leitões em cinco tratamentos: FD - aplicação intramuscular de 200mg de ferro dextrano no terceiro dia de idade; T24 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 19º dia; T48 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 48 horas; T72 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 72 horas; SA - suplemento alimentar ultraprecoce rico em ferro quelatado em pó (SAUP) fornecido do terceiro ao 11º dia, com intervalo de 48 horas. O ferro dextrano aplicado no terceiro dia de vida e a suplementação com terra e SAUP foram eficientes para garantir o desempenho de leitões no período de aleitamento e não influenciaram no consumo de ração nem na taxa de viabilidade. As diferentes fontes de ferro estudadas não influenciaram o leucograma e foram eficientes na prevenção da anemia ferropriva e no desempenho dos leitões lactentes. Com relação às concentrações de hemoglobina e hematócrito, os animais suplementados com ferro dextrano apresentaram valores superiores quando comparados aos que recebem terra e SAUP.

Parental iron supplementation in neonatal piglets is a routine management to solve anemia but may cause welfare problems. The aim of this study was to assess behavior responses generated after oral or parenteral iron supplementation. Parenteral supplementation consisted of 200 mg of iron dextran intramuscular. The novel oral iron supplement was a combination of encapsulated nonheme/heme iron (252 mg of total iron) delivered orally. Two litters formed by 11, 2-day-old piglets were assigned to each treatment. The litters were video recorded for 6 hours, 3 before and 3 after iron supplementation. Scan sampling every 3 minutes was used to register the occurrence of 7 behaviors. The highest overall percentage of time was allocated to resting, 46.5% (167.4 minutes) for the parenteral group and 42.4% (152.6 minutes) for the oral group; and suckling 24.6% (88.6 minutes) for the parenteral group and 27.8% (100.1 minutes) for the oral group. Resting time was higher after 1 hour of iron supplementation in the parenteral group 51.9% (31.1 minutes) vs. 33.8% (19.7 minutes). In conclusion, the oral iron supplementation resulted in a higher behavioral disruption in neonatal pigs, probably associated to increased handling time and aversive flavor of the supplement.

Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15mg/kg; maximum of 1000mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia.

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.

In pigs, iron deficiency anemia (IDA) is the most prevalent deficiency disorder during the early postnatal period, frequently developing into a serious illness. On the other hand, in humans, only low-birth-weight infants, including premature infants, are especially susceptible to developing IDA. In both human and pig neonates, the initial cause of IDA is low birth iron stores. In piglets this shortage of stored iron results mainly from genetic selection over the past few decades for large litter sizes and high birth weights. As a consequence, pregnant sows cannot provide a sufficient amount of iron to the increasing number of developing fetuses. Supplementation with iron is a common practice for the treatment of IDA in piglets. For decades, the preferred procedure for delivering iron supplements during early life stages has been through the intramuscular injection of a large amount of iron dextran. However, this relatively simple therapy, which in general, efficiently corrects IDA, may generate toxic effects, and by inducing hepcidin expression, may decrease bioavailability of supplemental iron. New iron supplements are considered herein with the aim to combine the improvement of hematological status, blunting of hepcidin expression, and minimizing the toxicity of the administered iron. We propose that iron-deficient piglets constitute a convenient animal model for performing pre-clinical studies with iron supplements.

There exists a need for accurate, non-invasive point-of-care tests to detect body iron burden. This study investigated the use of x-ray fluorescence (XRF) measurements of skin iron as a marker for organ iron content in rats. This study also evaluated a novel application of a commercial XRF device, commonly used in mining and construction, as a rapid, portable, and non-invasive measurement tool. Rats (n = 32) were loaded with iron dextran and the iron signal of each animal’s skin, liver, and kidney was measured using a conventional XRF system. A quadratic correlation was observed between liver and skin iron signal (R2 = 0.92) and a linear correlation was observed between kidney and skin iron signal (R2 = 0.65). As such, it is concluded that skin iron content can act as a marker for both liver and kidney iron content. The same skin samples were measured using the portable XRF device and compared to the liver and kidney samples measured in the conventional XRF system. Again, a quadratic correlation was observed between liver and skin iron signal (R2 = 0.91) and a linear correlation was observed between kidney and skin iron signal (R2 = 0.83). Thus, the portable XRF device can provide rapid non-invasive, skin XRF measurements. Dosimetry was performed using the portable XRF device to assess the radiological hazard associated with its use. The average skin equivalent dose from this device is 30 ± 10 mSv/min, when the device is collimated and operated at 40 kV. In conclusion, skin iron XRF measurements can act as a surrogate marker for liver iron content, and can be measured using a commercial XRF device for a portable, fast, and non-invasive measurement.

There is increasing clinical evidence to suggest a suppressive effect on hematopoiesis in myelodysplastic syndrome patients with iron overload. However, how iron overload influences hematopoiesis in myelodysplastic syndrome (MDS) remains unknown. Here, the RUNX1S291fs-transduced bone marrow mononuclear cells were yielded and transplanted into lethally irradiated recipient mice together with radioprotective bone marrow cells to generate MDS mice. Eight weeks post transplantation, the recipient mice received an intraperitoneal injection of 0.2 mL iron dextran at a concentration of 25 mg/mL once every other day for a total of 8 times to establish an iron overload model. In the present study, we show that iron overload impairs the frequency and colony-forming capacity of normal hematopoietic stem and progenitor cells, especially in erythroid, in MDS mice, which is due, at least in part, to growth differentiation factor 11-induced reactive oxygen species, shortening survival of MDS mice. Given that we are the first to construct an iron overload model in MDS mice, we hope this model will be helpful for further exploring the influence and mechanism of iron overload on MDS.

Iron-deficiency anaemia (IDA) is a serious health problem in neonatal piglets and is controlled by routine application of iron in various formulations. The efficacy and safety of two iron-containing products for the prevention of IDA in suckling piglets were compared in a randomised, parallel study. Newborn piglets were treated with 200 mg iron supplied by intramuscular injection in the neck as either Forceris (gleptoferron; n=13) or Uniferon 200 (iron dextran; n=12) 24–48 hours after birth. Blood samples were collected before and after treatment (2nd, 18th and 31st day of life) for complete haematology. The treatments were well tolerated with only mild transient swelling observed in two piglets (Forceris group). Piglets treated with Forceris had significantly higher haemoglobin, haematocrit, mean corpuscular volume and haemoglobin concentration values, as well as significantly higher plasma iron and transferritin saturation and a lower total iron binding capacity than those treated with Uniferon. No animals in the Forceris group but 17 per cent of piglets in the Uniferon group had haemoglobin levels

BACKGROUND: The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT. METHODS: We used a 6-week-old female BDF1 (H-2(b/d)) and a male C57/BL6 (H-2(b)) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings. RESULTS: ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P

This study was conducted to compare effects of dietary administration of iron dextran and bacterial-iron on growth performance, fecal microbial flora, and blood profiles in sows and their litters. A total of 20 multiparous sows (Landrace × Yorkshire) were randomly allotted into two treatments: (i) ID (basal diet, piglets were injected with iron dextran); (ii) BR (basal diet + bacterial-iron; bacterial-iron was given to sows, piglets were not injected with iron dextran). There were five replicates per treatment with two sows per replicate. No differences were observed on sow and piglet growth performance, fecal microbial flora as well as sow blood profiles between ID and BR treatments. In piglets, blood iron, red blood cell and hemoglobin concentrations in ID treatment were higher (P

Iron deficiency anemia is one of the major nutritional deficiency disorders. Iron deficiency anemia occurs due to decreased absorption of iron from diet, chronic blood loss and other associated diseases. The importance of iron and deleterious effects of iron deficiency anemia are discussed briefly in this review followed by the transdermal approaches to deliver iron. Transdermal delivery of iron would be able to overcome the side effects associated with conventional oral and parenteral iron therapy and improves the patient compliance. During preliminary investigations, ferric pyrophosphate and iron dextran were selected as iron sources for transdermal delivery. Different biophysical techniques were explored to assess their efficiency in delivering iron across the skin, and in vivo studies were carried out using anemic rat model. Transdermal iron delivery is a promising approach that could make a huge positive impact on patients suffering with iron deficiency.

A total of 253 reports of adverse reactions to veterinary medicinal products were received during the year 2016 representing a decrease of 13% compared to the previous year (292 reports). The majority of the reports described reactions affecting companion animals (178 dogs and 32 cats) as well as cattle (17 reports) and horses (10 reports). Most of the reactions reported were linked to the use of antiparasitics (145 reports), hormone products (26 reports) and antiinfectives (10 reports). 32 reports were generated from consultations with Tox Info Suisse in Zürich and involved mainly the excessive intake of flavoured tablets and, in some cases, the use of reconverted products (applied to another species than that authorized). Five signals were identified from the reports, which resulted in revisions of the product information in the sections addressing contraindications or adverse reactions.Im Jahr 2016 wurden 253 Meldungen zu unerwünschten Wirkungen von Tierarzneimitteln eingereicht, was eine Abnahme von 13% gegenüber dem Vorjahr (292 Meldungen) bedeutet. Am häufigsten wurden Reaktionen bei Kleintieren (178 Hunden und 32 Katzen) sowie bei Rindern/Kälbern (17 Meldungen) und Pferden (10 Meldungen) eingereicht. Die am häufigsten betroffenen Medikamentengruppen waren Antiparasitika (145 Meldungen), Hormonpräparate (26) und Antiinfektiva (10). 32 Fälle, die von Tox Info Suisse übermittelt wurden, betrafen mehrheitlich die Aufnahme von Tierarzneimitteln mit Aromastoffen in Überdosis sowie einige Umwidmungen. Aus den gesammelten Meldungen wurden 5 Signale identifiziert, welche zur Anpassung der Arzneimittelinformation der betroffenen Präparate in den Rubriken „unerwünschte Wirkungen“ oder „Kontraindikationen“ führten.En 2016, 253 annonces d’effets indésirables de médicaments vétérinaires ont été enregistrées, ce qui représente une diminution de 13% par rapport à l’année précédente (292 annonces). Ce sont principalement des annonces concernant des réactions chez les petits animaux (178 chiens et 32 chats) ainsi que chez les bovins (17) et les chevaux(10) qui ont été faites. Les groupes de médicaments les plus souvent impliqués étaient les antiparasitaires (145 annonces), les préparations hormonales (26) et les anti-infectieux (10). 32 cas transmis par Tox Info Suisse, concernaient principalement la prise en surdose de médicaments aromatisés ainsi que quelques reconversions. Cinq signaux issus de l’ensemble de ces annonces ont été identifiés, qui ont conduit à une adaptation des informations des produits concernés dans les rubriques „effets indésirables“ ou „contre-indications“.Nel 2016 sono state inoltrate 253 notifiche di effetti indesiderati di medicamenti per uso veterinario. Questo rappresenta rispetto allo scorso anno (292 notifiche), una diminuzione del 13%. Principalmente sono state inoltrate notifiche relative a reazioni nei piccoli animali (178 cani e 32 gatti), nei bovini e vitelli (17 notifiche) e nei cavalli (10 notifiche). I gruppi di medicinali maggiormente messi in causa sono gli antiparassitari (145 notifiche), i preparati ormonali (26) e gli antiinfettivi (10). Al Tox Info Suisse sono stati trasmessi 32 casi, riguardanti principalmente l’ingestione in sovradosaggio di medicinali ad uso veterinario contenenti aromi e alcuni medicamenti con cambiamento di destinazione. Tra tutte le notifiche sono stati identificati 5 segnali che hanno portato ad un adeguamento delle informazioni del preparato in questione nelle rubriche “effetti indesiderati” oppure “controindicazioni”.

The possibility of preventing the negative metabolic effects of megestrol acetate in the body of cats using it as a means to suppress the manifestations of the estrous cycle was investigated. It was found that in cats, which are used megestrol acetate for 7 days after dosing hemoglobin level decreased to 1.17 times, and on the fourteenth day was 1.33 times. It was determined that increasing the number of eosinophils in animals which megestrol acetate is used 2.7 times at 14 hours after dosing, animals receiving the drug protective iron eosinophils increased by 2.2 times on the fourteenth day after administration. In cats, the group which used megestrol acetate ALT activity increased by 16.9 % on the fourth day after the beginning of the experiment, 33.6 % on the 7th, and by 55.6 % on the fourteenth day after the administration of the drug as compared to the initial activity, whereas the animals which were used tread means the phenomenon was not observed. We found that increased levels of glucose in the animals of the first group by 14 % on the 4th day, 22 % on the 7th day and 22.4 % on the 14th day after the drug compared with the baseline values. It is found that the use of iron dextran solution in a dose of 7.5 mg / kg concurrently with megestrol acetate significantly reduces blood biochemical shift in profile in cats. It is shown that iron with simultaneous application of megestrol acetate formulation prevents a sharp decrease in the number of erythrocytes and increase of eosinophils in the blood of cats.

The additive, ‘Iron dextran 10%’, is a liquid preparation containing iron dextran (25%, of which 10% is total iron), sodium chloride (1.5%), phenol (0.4%) and water (73.1%). Iron dextran 10% is considered safe for suckling piglets when given at an oral dose of 1 mL/kg body weight (bw) once in each of the first 2 weeks of life; this dose corresponds to 100 mg Fe/kg bw. The administration of iron dextran 10% to piglets deficient in vitamin E and/or selenium is considered a risk. The oral use of iron dextran 10% in suckling piglets does not pose any safety concerns to consumers, provided that the conditions identified as safe for the target animal are respected. Iron dextran 10% is considered a respiratory sensitiser and may be harmful if inhaled; however, exposure by inhalation is not expected; therefore, the risk is considered to be negligible. Iron dextran 10% is an irritant to skin and eyes; a risk by skin sensitisation cannot be excluded. The presence of phenol in the additive should be considered to pose a hazard for users. The use of the additive for suckling piglets at the proposed level does not pose a safety concern to the environment. The available studies with orally administered iron dextran indicate that the additive is a bioavailable source of iron for suckling piglets; however, the efficacy of the additive when given to newborn pigs as proposed via water for drinking (voluntary intake) has not been demonstrated. The Panel proposed some recommendations regarding the dextran used in the manufacture of the additive and the procedure for administering the additive to piglets.

Thank you providing the opportunity to reply to the Comment on our recent paper.Strom and Andreasen, who are employees of Pharmacosmos, a Danish-based pharmaceuticalcompany that commercializes iron dextran and iron isomaltoside 1000, criticize our work as it cannotbe directly extrapolated to the clinical setting. However, as elucidated below, this was never thepurpose of this scientific paper.In response to Strom and Andreasen, I would like to state that, as clearly mentioned in theintroduction, the experiments described in Neiser et al. [1] were triggered by the criticism [2]of our previous work published in 2011 [3]. Specifically, the methodology (reverse single radialimmunodiffusion assay) and the use of only one specific anti-dextran antibody were criticized.Thus, the new experiments reported in [1] were carried out with a new antibody (produced by theservice provider GenScript) and a different technique (Enzyme-Linked Immunosorbent Assay, ELISA).Moreover, in order to make sure that the results were unbiased, the ELISA experiments were carriedout by GenScript with blinded samples.In contrast to what Strom and Andreasen stated in their Comment, the basis of this study wasthe general consensus that high molecular weight iron dextran complexes, most of which are nolonger marketed, display higher rates and generally more severe hypersensitivity reactions [4–6].Thus, it was evident to start with the investigation of the reactivity of some of the newer intravenousiron products with anti-dextran antibodies. We were not aware of the study by Kreimeier et al. [7]that reports a single clinical case of an antibody-mediated reaction to hydroxyethyl-starch (HES).Nevertheless, despite the fact that carboxymaltose is a branched starch derivative, because of theextensive substitution (hydroxyethyl) in HES, the two compounds are not comparable. Investigation ofthe reactivity of various intravenous iron preparations, and in particular ferric carboxymaltose, againstanti-HES antibodies would be of interest, but is clearly outside the scope of the work described in [1].I would also like to emphasize that in [1], as well as in all our previous publications on thistopic [3,8], we did not make any claim regarding the clinical relevance of these experiments. Conversely,we repeatedly stated that the mechanism of intravenous iron-induced hypersensitivity reactions hasnot been elucidated yet and that more studies are needed to unravel the mechanism(s). Nevertheless,it is intriguing that a number of recent studies have come to the conclusion that the frequencyof hypersensitivity reactions is higher with dextran-based intravenous iron preparations (not onlywith the old high molecular weight compounds) than with non-dextran containing products [9–12].Noteworthy, these reports are in disagreement with the paper mentioned by Strom and Andreasen [6],which, incidentally, was published online more than a month after our final draft was accepted.Taken together, these contrasting reports support the fact that, because of the low incidence of

Background Medial vascular calcification is a specific complication in chronic kidney disease (CKD) patients although its pathogenesis is poorly understood. The administration of iron (Fe), generally used for the treatment of anemia in CKD patients, induces oxidative stress. Fe loading possibly affects the progress of vascular calcification in uremia. We investigated the effect of Fe on vascular calcification and its mechanism in uremic rats. Method Thirty-two rats were divided into four groups: untreated rats (controls), rats fed a standard diet with Fe administration (Fe group), rats fed an adenine-enriched diet (uremic group), and rats fed an adenine-enriched diet with Fe administration (uremic + Fe group). Iron dextran was administered once a week for 5 weeks intraperitoneally. Morphological alterations and vascular calcification-associated factors in the aortic wall were evaluated. Results No aortic calcification was observed in the control group although uremic rats developed severe vascular calcification. Fe loading suppressed vascular calcification in the uremic groups. Expressions of runt-related transcription factor 2 (Runx2), single-strand (ss)DNA and phosphate transporter (Pit)-1 were increased in the uremic rats compared to the control rats. In the uremic group, Fe administration did not show any effect on ssDNA expression, but reduced Runx2 and Pit-1 expressions. Conclusion Fe suppressed the development of vascular calcification through the prevention of Pit-1 and vascular smooth muscle cell osteoblastic transdifferentiation.

Suckling piglets cannot satisfy their demand for the essential trace element iron from sows&rsquo, 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.

Purpose To determine the feasibility of liver iron quantification by 3 Tesla (T) MRI using a novel iron overload rabbit model. Materials and Methods Forty-two rabbits underwent iron dextran loading from 1 to 15 weeks. MRI signal intensity ratio (SIR) was measured using a gradient-echo sequence, and R2(1/T2) measured using an eight-echo spin-echo sequence at 3T. Ex vivo hepatic pathology was obtained for all rabbits studied. Postmortem assessments of liver iron concentration (LIC) were conducted in an atomic absorption spectrophotometer. MRI measures were fitted against LIC using linear regression for 30 of the iron-loaded rabbits. The remaining 12 iron-loaded rabbits were used to test the prediction accuracy of the derived models. Results LIC was linearly correlated to both liver-to-muscle SIR (r = −0.845) and R2 (r = 0.965) in a range achieved in this study (LIC < 10 mg/g dry tissue) at 3T. By regression, the linear equations were determined as: (1) Y1 = 10.581−5.924X1 (Y1: LIC, X1:SIR); (2) Y2 = −1.273+0.103X2 (Y2:LIC, X2:R2). In the 12 test rabbits, the predicted LICs using the derived equations agreed well with the results obtained using the spectrophotometer. Conclusion Both SIR and R2 are highly correlated with LIC in a novel rabbit model. MRI quantification of liver iron overload is feasible at 3T. J. Magn. Reson. Imaging 2013;38:1585–1590. © 2013 Wiley Periodicals, Inc.

Iron deficiency is one of the most prevalent and serious health issues among people all over the world. Iron-dextran (ID) colloidal solution is one among the very few US Food and Drug Administration (FDA)-approved iron sources for parenteral administration of iron. Parenteral route does not allow frequent administration because of its invasiveness and other associated complications. The main aim of this project was to investigate the plausibility of transdermal delivery of ID facilitated by microneedles, as an alternative to parenteral iron therapy. In vitro permeation studies were carried out using freshly excised hairless rat abdominal skin in a Franz diffusion apparatus. Iron repletion studies were carried out in hairless anemic rat model. The anemic rats were divided into intact skin (control), microneedle pretreated, and intraperitoneal (i.p.) groups depending on the mode of delivery of iron. The hematological parameters were measured intermittently during treatment. There was no improvement in the hematological parameters in case of control group, whereas, in case of microneedle pretreated and i.p. group, there was significant improvement within 2-3 weeks. The results suggest that microneedle-mediated delivery of ID could be developed as a potential treatment method for iron-deficiency anemia.

Background Various techniques used to assess brain iron concentrations have demonstrated the presence of low iron stores in patients with restless legs syndrome (RLS). Previous open-label and randomized studies generally support the value of iron treatment for RLS symptoms. Only one of these studies assessed iron therapy response to changes in brain iron status. The current study was designed to assess the effect of iron therapy on RLS symptoms and on CSF measures of brain iron status. Methods Idiopathic RLS patients drawn from the Korean population received four weekly intravenous (IV) doses of 250 mg low-molecular weight iron dextran for a total dose of 1 g. One week after the last dose, any subject on RLS medication tapered off the RLS medications. Blood and CSF samples were taken to measure iron parameters at baseline and again, three weeks after the last dose. We have been following their response to the drug for two years after treatment. Results Twenty-five patients (age 55.2 ± 9.3, 18 female) enrolled in this study without serious adverse reactions. Seventeen of the 25 patients (68%) showed moderate or complete improvement of all RLS symptoms after treatment based on the Korean-translated versions of the International RLS Severity scale (K-IRLS). Changes in the K-IRLS did not correlate significantly with changes in CSF ferritin. The response to IV iron could not be predicted by patients’ demographics, or by blood or CSF iron baseline characteristics. RLS symptom improvement started between one and six weeks after treatment and the treatment benefits lasted from one month to 22 months. Fourteen patients, (56%) completely stopped all medications, for a mean duration of 31.3 ± 33.1 weeks. These results are comparable to those from a prior study with high molecular weight dextran. Conclusions Intravenous low-molecular weight iron dextran produced significant improvement of RLS symptoms in a majority of patients without any significant adverse effects. Serious anaphylaxis occurs with high molecular weight, but rarely, if ever, with this low molecular weight dextran. Given apparent comparable efficacy the low molecular weight and not the high molecular weight iron dextran, should be considered for RLS treatment. Although changes in CSF ferritin were seen following therapy, these changes were not related to clinical improvements.

Several intravenous iron complexes are available for the treatment of iron deficiency anemia (IDA). Iron dextran (DEX) is associated with an elevated risk of potentially serious anaphylactic reactions, whereas others must be administered in several small infusions to avoid labile iron reactions. Ferric carboxymaltose (FCM) is a nondextran intravenous iron which can be administered in high single doses. A randomized, open label, and multicenter comparison of FCM to DEX in adults with IDA and baseline hemoglobin of ≤11.0 g/dL was conducted. A total of 160 patients were in the safety population (FCMn=82; DEXn=78). Adverse events, including immune system disorders (0% in FCM versus 10.3% in DEX,P=0.003) and skin disorders (7.3% in FCM versus 24.4% in DEX,P=0.004), were less frequently observed in the FCM group. A greater portion of patients in the FCM group experienced a transient, asymptomatic decrease in phosphate compared to patients in the DEX group (8.5% in FCM versus 0% in DEX,P=0.014). In the FCM arm, the change in hemoglobin from baseline to the highest observed level was 2.8 g/dL, whereas the DEX arm displayed a change of 2.4 g/dL (P=0.20). Treatment of IDA with FCM resulted in fewer hypersensitivity-related reactions than DEX.

The objective of this study was to evaluate the effect of chelated iron supplementation on gestating and lactating sows and on their suckling and weaned piglets. Reproductive traits, piglet performance, hematological parameters, and the iron concentrations in colostrum, milk, and stillborn livers were measured. Ninety-six sows were subjected to one of three treatment groups. Group T1 comprised pregnant and lactating sows treated with diets supplemented with inorganic iron (551 mg Fe/kg) and suckling piglets administered 200 mg of injectable iron dextran. Group T2 was the same as T1, except that sows after 84 days of gestation, lactating sows, and suckling piglets were fed a diet supplemented with 150 mg Fe/kg of chelated iron, and suckling piglets were administered injectable iron dextran. Group T3 was the same as T2 but without injectable iron dextran for suckling piglets. During the nursery phase, all of the weaned piglets were penned with their original groups or treatments and received isonutritive and isocaloric feeds. Piglets from the T2 and T3 groups also received an additional 150 mg Fe/kg of chelated iron via their feed. There were no differences among the treatments for reproductive traits or the iron concentrations in the colostrum, milk, or liver. The piglets that did not receive the injectable iron dextran showed the poorest performance during the pre-and post-weaning phases and showed the poorest hematological parameters of the suckling piglets. The chelated iron supplementation is insufficient to meet piglet demand. The iron dextran supply is necessary for suckling and weaned piglets.