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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

Heme is an efficient dietary iron supplement applied in humans and animals to prevent iron deficiency anemia (IDA). We have recently reported that the use of bovine hemoglobin as a dietary source of heme iron efficiently counteracts the development of IDA in young piglets, which is the common problem in pig industry. Here, we used maternal Polish Large White and terminal sire breed (L990) pigs differing in traits for meat production to evaluate the long-term effect of split supplementation with intramuscularly administered small amount of iron dextran and orally given hemoglobin on hematological indices, iron status, growth performance, slaughter traits, and meat quality at the end of fattening. Results of our study show that in pigs of both breeds split supplementation was effective in maintaining physiological values of RBC and blood plasma iron parameters as well as growth performance, carcass parameters, and meat quality traits. Our results prove the effectiveness of split iron supplementation of piglets in a far-reach perspective.

Radiofrequency hyperthermia is a recently rediscovered oncotherapy rising in popularity. However, lack of a proper thermosensitizer limits current radiofrequency hyperthermia to be only slightly effective, mostly being used as a subsidiary to a standard oncotherapy. Here, we report that iron-dextran delivers iron ion to cancer cells for cancer-selective accumulation of the iron ion, which functions as a thermosensitizer for radiofrequency hyperthermia. Intravenous injection of iron-dextran to tumor-xenografted mice resulted in selective accumulation of iron ion in the targeted cancer cells. The accumulated iron ion in cancer cells dramatically reacted to radiofrequency wave to result in tumor-selective dielectric temperature increment without harming the surrounding normal tissue. The oncotherapeutic effect of was evaluated using tumor-xenografted mice. The overall anticancer efficacy of radiofrequency hyperthermia after injection of iron-dextran as a thermosensitizer in breast cancer-bearing mice was much better than the efficacy of paclitaxel, a standard chemotherapy drug for cancer. Moreover, hyperthermia using iron-dextran as a thermosensitizer completely eradicated cancer in the tumor xenografted mice. This work suggests that iron-dextran is an ideal thermosensitizer for radiofrequency hyperthermia. We believe that the application of iron-dextran as a thermosensitizer would be a major progress in hyperthermia cancer treatments.

Objectives: The role of alpha-lipoic acid in the amelioration of iron overload-induced hepatic damage remains largely under-explored. Therefore, this paper aimed at describing the structural effects of alpha lipoic acid on the liver following iron overload in mice. Methods: After ethical approval, a total of 24 male mice were used. Twenty mice were randomly divided into 2 groups: A and B. Group A rats received 50mg/kg of iron dextran intraperitoneally daily for 49 days while those in group B received a daily oral dose of 100mg/kg alpha lipoic acid by gavage in addition to the treatment in A. Four mice were used as normal controls. At the endpoint of the experiment, the livers were harvested and studied for iron deposition, parenchymal histoarchitecture and hepatocyte densities. Photomicrographs were taken using a digital photomicroscope for morphometric analysis. Results: Treatment of mice with iron led to a distortion of the histoarchitecture of the liver which was attenuated with co-administration of alpha lipoic acid. Additionally, co-treatment of iron with alpha lipoic acid resulted in significant lowering of hepatic iron deposition (p

Simple Summary Post-procedural castration pain control in piglets in Canada is managed with non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ketoprofen. While combining NSAIDs with iron dextran (ID) reduces piglet injections and handling, it is unknown if this will affect NSAID pain control efficacy. This study evaluated the time it takes a pig to navigate an obstacle chute after surgical castration as an objective measure of pain control. The differences in navigation time of pigs given NSAIDs alone or mixed with ID prior to castration were compared. The results indicate that castrated piglets given either NSAIDs alone or mixed with ID navigated the chute as fast as non-castrated piglets, and faster than castrated piglets not given NSAIDs. This provides evidence that when NSAIDs are combined with iron and administered as a single injection, the NSAIDs remain effective at controlling castration pain. Abstract 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.

Chelators are commonly used to remove excess iron in iron-loading disorders. Deferoxamine (DFO) is an effective and safe iron chelator but an onerous parenteral administration regimen limits its routine use. To develop more effective methods for delivering iron chelators, we examined whether amphiphilic copolymer nanoparticles (NPs) could deliver DFO more efficiently. Physical characterization showed a uniform and stable preparation of DFO nanoparticles (DFO-NPs) with an average diameter of 105.3 nm. In macrophage (RAW264.7) and hepatoma (HepG2) cell lines, DFO-NPs proved more effective at depleting iron than free DFO. In wild-type mice previously loaded with iron dextran, as well as Hbbth3/+ and Hfe–/– mice, which are predisposed to iron loading, DFO-NPs (40 mg/kg DFO; alternate days; 4 weeks) reduced hepatic iron levels by 71, 46, and 37%, respectively, whereas the equivalent values for free DFO were 53, 7, and 15%. Staining for tissue iron and urinary iron excretion confirmed these findings. Pharmacoki...

Iron deficiency is presently a serious problem in suckling piglets on pig farms. The most often used method of anaemia prevention in piglets is parenteral administration of iron dextran. Oral iron represents an alternative to this method. The goal of this article is to review current knowledge on oral iron administration in suckling piglets. The substances that can be used for this purpose include iron dextran, iron salts, iron chelates, carbonyl iron, an iron polymaltose complex and iron microparticles. The different methods of oral iron administration in piglets are discussed.

Intravenous bevacizumab decreased mucosal bleeding in some patients with hereditary hemorrhagic telangiectasia (HHT). We treated a 47-year-old male who had HHT, severe epistaxis, and gastrointestinal bleeding, alcoholic cirrhosis, and portal hypertension with intravenous bevacizumab 2.5 mg/kg every 2 weeks. We tabulated these measures weekly during weeks 1–33 (no bevacizumab); 34–57 (bevacizumab); and 58–97 (no bevacizumab): hemoglobin (Hb) levels; platelet counts; units of transfused packed erythrocytes (PRBC units); and quantities of iron infused as iron dextran to support erythropoiesis. We performed univariate and multivariable analyses. We sequenced his ENG and ACVRL1 genes. Epistaxis and melena decreased markedly during bevacizumab treatment. He reported no adverse effects due to bevacizumab. Mean weekly Hb levels were significantly higher and mean weekly PRBC units and quantities of intravenous iron were significantly lower during bevacizumab treatment. We performed a multiple regression on weekly Hb levels using these independent variables: bevacizumab treatment (dichotomous); weekly platelet counts; weekly PRBC units; and weekly quantities of intravenous iron. There was 1 positive association: (bevacizumab treatment; p = 0.0046) and 1 negative association (PRBC units; p = 0.0004). This patient had the novel ENG mutation E137K (exon 4; c.409G→A). Intravenous bevacizumab treatment 2.5 mg/kg every 2 weeks for 24 weeks was well-tolerated by a patient with HHT due to ENG E137K and was associated with higher weekly Hb levels and fewer weekly PRBC units.

The objective of this experiment was to evaluate the blood profile, growth performance, and tissue mineral concentration during the nursery period in weanling pigs that received various dosages of iron at birth. A total of 70 crossbred pigs (weaning BW 6.36 ± 0.92) from 5 different injectable iron dosage treatments administered at birth (0, 50, 100, 200, and 300 mg iron from iron dextran) were used. Pigs were weighed at d 22 (weaning), 23, 24, 25, 29, 38, 44, and 52. Blood was collected from 10 pigs per treatment at the same times as above except for d 44 and analyzed for a complete blood count (CBC). A total of 3 pigs per treatment were euthanized on d 22, 38, and 52 to determine tissue mineral concentration. All pigs were fed a common nursery diet supplemented with 100 mg/kg Fe from ferrous sulfate. All data were subjected to ANOVA with the pig as the experimental unit. As injectable iron dosage at birth increased, hemoglobin concentration (Hb) increased at weaning (linear and quadratic: P < 0.05), to d 29 and then quadratically through (P < 0.05) d 38. Along with the other CBC measurements, Hb was similar between treatments at d 52. There was a quadratic response (P < 0.05) for ADG from d 22 to 52. Although by d 52, final BW peaked (quadratic: P < 0.05) for pigs receiving 100 mg iron. Iron concentration of the liver and spleen were greater (linear: P < 0.05) at weaning as iron injection dosage increased but was greater only in the liver at d 38 (P < 0.05) and the spleen at d 52 (P < 0.05). Results indicate that an iron injection administered shortly after birth is vital for proper growth and hematological functions during the nursery period.

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.

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.

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.

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

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.

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.

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.

Human red blood cells (RBCs) deformability in vitro was assessed during iron dextran (INFeD) loading and/or ethanol co-administration using microfluidic deformability screening. The results showed donor-specific variations in dose dependent deformability shift were revealed below 500 μg/mL iron dextran. Two out of nine blood samples exhibited significant cell stiffening at 500 μg/mL iron dextran loading concentration (p, Singapore-MIT Alliance in Research and Technology (SMART)

Excessive accumulation of iron in the body can lead to organ injury. Some flavonoids which possess high affinity to iron can be used as iron chelators for curing iron overload diseases such as haemochromatosis. In this article, the effects of baicalin and quercetin on different mouse tissues (liver, kidney and heart) afflicted with iron overload-induced injury were studied. It was found that after administration of 500 mg kg⁻¹ iron dextran for 45 days, the degree of oxidative injury in the three organs was different. When iron dextran-induced iron-overloaded mice were fed a diet containing baicalin or quercetin (1% w/w), both flavonoids showed significant effects in suppressing iron overload-induced injury. The efficiencies of both flavonoids on different tissues varied. Both flavonoids caused a significant decrease of iron content in liver and kidney tissues but not in the heart, whereas the flavonoids were more efficient in inhibiting the increase of carbonyl content and the thiobarbituric acid reactive substance levels in heart tissues. The results indicate that the protective effects of baicalin and quercetin on different tissues of iron-overloaded mice are different.

This research was carried out to detect the effect of Sappan Wood Extract (Caesalpinia sappan), Wheat grass and Vitamin E Treatment on the liver structure of iron overload rat (Rattus norvegicus).The method of experimental used Completely Random Design (CRD in triple repetition. The treatment had been carried out orally. Iron dextran with total dose of 1.5 g kg -1 of body were given to rat on the first, fourth, seventh, ten and thirteenth day. Sappan Wood Extract (Caesalpinia sappan)200 mg kg -1 bw, 400 mg kg -1 bw, Wheat grass extract 100 mg kg -1 bw and Vitamin E 60 mg kg -1 bw were given to rat everyday for 15 days. At the seventeenth, rat were killed and their liver were taken. The observed parameters are morphological abnormality including the colour, the contour, ratio between liver weight and body weight as well as histological destruction. The result showed iron dextran treatment was proved the abnormality on morphological and histological desruction. Futhermore, Sappan Wood Extract (Caesalpinia sappan), Wheat grass and Vitamin E Treatment can decrease the morphological abnormality and the liver histological destructionon of iron overload rat. Keywords: Sappan Wood Extract, Wheat grass, Vitamin E, Iron, Morphological abnormality, Histological destruction

Biosusceptometry is a non-invasive procedure for determination of iron overload in a human body; it is essentially an assessment of the diamagnetic (water) and paramagnetic (iron) properties of tissues. We measured in vivo iron overload in the liver region of 12 rats by a room temperature susceptometer. The rats had been injected with sub-toxic doses of iron dextran. A quantitative relationship has been observed between the measurements and the number of treatments. The assessment of iron overload requires evaluating the magnetic signal corresponding to the same rat ideally without the overload. This background value was extrapolated on the basis of the signal measured in control rats versus body weight (R(2) = 0.73). The mean iron overload values for the treated rats, obtained after each iron injection, were significantly different from the means of the corresponding control rats (p0.01). The in vivo measurements have been complemented by chemical analysis on excised livers and other organs (R(2) = 0.89). The magnetic moment of iron atoms in liver tissues was measured to be 3.6 Bohr magneton. Evaluation of the background signal is the limit to the measure; the error corresponds to about 30 mg (1 SD) of iron while the instrument sensitivity is more than a factor of 10 better.

SUMMARY Intravenous iron dextran is widely used in hemodialysis patients receiving erythropoietin (EPO) therapy because of its significant convenience in clinical practice. However, the amount of iron removed by hemodialysis in vivo is unknown. The purpose of this study was to measure the removal of iron dextran in patients undergoing hemodialysis. Six patients were enrolled in this study. All were stable patients treated by hemodialysis for at least 1 month. Both F6 (polysulphone membrane) and GFSplus12 (hemophane membrane) dialyzers were used sequentially in each patient. Each patient received 2 mL of low-molecular-weight iron dextran (Cosmofer® aktieselskab/aksjeselskap and supplied by Zhuhai Schwarz Pharma Company Ltd) intravenously, containing 100 mg of elemental iron, administered during the second hour of dialysis over 30 to 60 minutes. A baseline sample of fresh dialysate was collected before the commencement of dialysis. A control sample of spent dialysate was collected during the first hour of dialysis, before the infusion of low-molecular-weight iron dextran. Then, all spent dialysate after the iron dextran infusion until the end of dialysis was collected. The samples were treated with lanthanum nitrate solution, and the iron content was measured using an atomic-absorptive spectrum method. The iron concentration in the control group was 4.31 ± 2.55 µg/L. After the infusion of iron dextran, the iron concentration in the spent dialysate increased significantly, irrespective of whether an F6 or GFSplus12 dialyzer was used. However, the amount of iron eliminated through the dialyzer was minimal, less than 3% of the infusion dose. There was no significant difference in removal of iron through either the F6 or GFSplus12 dialyzer. These results indicate that the removal of iron dextran by hemodialysis when using either a polysulfphone or hemophane membrane dialyzer is negligible. It is time-efficient and convenient to administer low-molecular-weight iron dextran during hemodialysis.

SUMMARY Intravenous iron administration is an effective method of treating iron deficiency anemia, but there have been concerns about adverse side effects, particularly serious events such as anaphylactic reaction. Several different forms of intravenous iron are available, but few studies have attempted to compare the frequency of adverse events. We carried out a systematic review to assess the frequency of adverse drug events (ADEs) associated with (i) low-molecular-weight intravenous iron dextran and (ii) iron sucrose. We searched several electronic databases; two reviewers screened all studies identified and extracted data. We included 60 studies, but few directly compared adverse events associated with two or more forms of iron, and most were not specifically designed to evaluate adverse events. In general, with the exception of high-molecular-weight iron dextran (HMWID), serious or life-threatening adverse events appeared rare. Several studies showed lower risks of ADEs on low-molecular-weight iron dextran (LMWID) compared with HMWID, and one large review found a reduced risk on LMWID compared with iron gluconate. Two studies showed little difference between iron sucrose and iron gluconate, and two further studies had similar rates of adverse drug events between iron sucrose and LMWID; however, the sample size for most of these studies was too small to draw firm conclusions. Adequately powered direct comparisons of different forms of intravenous iron are required to assess the safety profiles.

PURPOSE: Iron overload may occur due to regular blood transfusions and high intestinal iron absorption. Currently, there is no effective drug without side effects for the treatment of iron excess in thalassemia and other iron storage diseases, except chelation therapy, which is the only safe method for iron excretion. Thus, scientists are more focused on medicinal plants rich in phytochemical compounds for the removal of iron in thalassemia. Therefore this study was managed to discover the therapeutic potential of hydro- alcoholic extract of Allium porrum and Medicago sativa for iron chelating potential. METHODS: Aerial parts of Allium porrum and Medicago sativa werecollected in Yasuj Iran. Rats were divided into seven groups each containing six. Extracts were administrated in four groups (two groups for each extract) by single doses of each plant with 200 and 400 mg / kg body weight by (i.p.) route every other day for28 days. Group 1 as negative control received saline (0.5 ml/kg) by (i.p.) route. Positive control received iron dextran 200 mg/kg body weight. Experimental groups 1 and 2 for each plant extract were fed with 200 and 400 mg/kg, hydro-alcoholic extract respectively via (i.p.) route, 1 h after the injection of iron dextran. Standard group was treated with deferoxamine (DF) 50 mg/kg by (i.p.) route1 h after the injection of iron dextran. Serum iron (SI) and serum total iron binding capacity (TIBC) were determined .The serum ferritin was then measured using enzyme immunoassay ELISA kit for rat. For Analysis of data ANOVA test was used. RESULTS: Hydro-alcoholic extract of Medicago sativa and Allium porrum at 400 mg/kg showed significant (p

Svoboda M., A. Lojek, J. Pola‰kova, R. Ficek, J. Hiemer, J. Drabek: Effect of an Acute Iron Overdose on PMN Cells Chemiluminescence and Indices of Inner Environment in a Swine Model. Acta Vet. Brno 2006, 75: 523-532. The objective of the study was to evaluate the effect of an acute iron dextran administration on polymorphonuclear cells chemiluminescence and indices of inner environment in piglets. Piglets in the experimental group (n = 16) were given 2000 mg (20 ml) Fe 3+ in the form of iron dextran i.m. Piglets in the control group (n = 13) were given the same amount of physiological saline. Blood was taken before administration, and 1, 4 and 24 hours after. Iron application resulted in a ten times higher concentration of iron in blood plasma in the experimental group. No differences in spontaneous, PMA- and OZP-stimulated chemiluminescence were recorded between the two groups. The increased activities of CK, AST and LDH are indicative of a muscle injury at the injection site. No changes indicating liver or kidney injury were reported. Our study provides evidence of a good safety of iron dextran after parenteral administration.

Parenteral iron treatment induces MCP-1 accumulation in plasma, normal kidneys, and in experimental nephropathy. Introduction Monocyte chemoattractant protein-1 (MCP-1) promotes renal inflammation, thereby contributing to acute and chronic nephropathies. Its production is stimulated by oxidative stress. Thus, this study tested whether pro-oxidant iron/carbohydrate complexes, used to treat iron deficiency, induce MCP-1 in renal/extrarenal tissues, in plasma, and in the setting of experimental nephropathy. Methods CD-1 mice received 2 mg of intravenous iron [complexed with dextran (iron dextran), sucrose (iron sucrose), or gluconate (iron gluconate)]. Renal MCP-1 and/or its mRNA were measured 3 hours to 7 days post-iron injection. Iron effects on liver, lung, spleen, and heart MCP-1 mRNA, and on peritoneal lavage fluid MCP-1 concentrations were assessed. Iron pretreatment effects on MCP-1 levels in unilaterally obstructed kidneys vs. contralateral kidneys were determined. Finally, iron gluconate's influence on proximal tubule [human kidney-2 (HK-2)] cell MCP-1 levels was assessed. Results Iron sucrose (the primary test agent) markedly increased plasma and renal MCP-1 levels. It also induced multiorgan MCP-1 mRNA increments (liver > spleen > kidney > lung > heart). Iron gluconate was more potent than iron sucrose; conversely, iron dextran had no discernible effect. The iron dextran and iron sucrose-induced renal MCP-1 mRNA increments (∼4×) were persistent, lasting for at least 3 to 7 days. Iron gluconate raised MCP-1 levels in peritoneal lavage fluid. It also doubled MCP-1 in unilaterally obstructed kidneys (ureteral ligation) without altering contralateral (control kidney) MCP-1 content. Iron gluconate raised HK-2 cell MCP-1, implying a direct proximal tubule effect. Conclusion Iron sucrose and iron gluconate (but not iron dextran) can induce MCP-1 generation in renal and extrarenal tissues, possibly via transcriptional events. This may dramatically impact renal disease-induced MCP-1 increments. Finally, iron can increase peritoneal lavage fluid MCP-1 levels. Whether the above changes have implications for renal disease progression, and/or for peritoneal inflammation/peritoneal dialysis efficiency, are issues which may need to be addressed.

Ex vivo freeze-dried rat muscle tissues, collected at different times t after a single dose of subcutaneously injected iron dextran, have been magnetically characterised. The AC susceptibility of the tissues shows an overall superparamagnetic behaviour and the dependence on t of, especially, the out-of-phase component is remarkably systematic despite the fact that each tissue originates in a different rat individual. The experiments show that the akaganéite (β-FeOOH) nanoparticles contained in the injected drug are progressively degraded in the living tissue and, at times of the order of 1 month and for all the analysed rat individuals, converge to a magnetically well-defined species with much narrower magnetic activation energy distribution than iron dextran. Thorough transmission electron microscopy experiments of the same tissues indicate the presence of oxyhydroxide particles, whose size decreases for increasing t in agreement with the interpretation of the magnetic susceptibility. The conclusions drawn from the magnetic study do well correspond to the properties of the whole tissue since no biochemical extraction work has been done. The AC susceptibility appears to be a valuable and complementary tool in pharmacological studies of iron-containing drugs.

Magnetic and structural analyses have been performed on an iron sucrose complex used as a haematinic agent. The system contains two-line ferrihydrite particles of about 5 nm that are superparamagnetic above approximately 50 K. The observed low-temperature magnetic dynamics of this compound is closer to simple models than in the case of other iron-containing drugs for intravenous use like iron dextran.

Iron's chemical structure and its ability to initiate one-electron reactions are properties that cause it to play a major role in the production and metabolism of oxygen free radicals in biological systems. Oxygen free radicals are conjectured to cause cardiac failure in individuals afflicted with disorders of iron overload. We report on the use of both acyloins and aldehydes as markers of oxidative stress in a murine model of chronic iron-overload cardiomyopathy. Twenty mice were randomized to four treatment groups: (1) control (0.2 mL normal saline ip/mouse/d); (2) 100 mg iron (0.05 mL iron dextran/mouse/d); (3) 200 mg iron (0.1 mL iron dexxtran/mouse/d); (4) 400 mg iron (0.2 mL iron dextran/mouse/d). Significant dose-dependent increases in both total heart aldehyde and total heart acyloin concentrations were found. Furthermore, a significant positive correlation existed between the dose of iron administered and each quantified aldehyde and acyloin found in the heart.

Svoboda M., J. Drabek: Efficiency of Voluntary Consumption of Amino Acid-chelated Iron in Preventing Anaemia of Suckling Piglets . Acta Vet. Brno 2003, 72: 499-507. The aim of the study was to evaluate efficiency of voluntary access to amino acid-chelated iron in the form of mineral supplement in preventing anaemia of piglets. Piglets in group 1 (n = 60) were offered ad libitum the iron mineral supplement (Fe 110 g·kg -1 ) from the 2 nd to the 14 th day of life. Piglets in group 2 (n = 30) were given 200 mg Fe 3+ as iron dextran i.m. on day 3. On day 7, haemoglobin concentration (Hb) (P < 0.05), packed cell volume (P < 0.05), red blood cell count (P < 0.01) and plasma iron concentration ( P < 0.01) in group 1 were lower compared to group 2. On day 14 and 21 no significant differences were found between the two groups. At the time of weaning (day 28), the voluntary access to iron did not prevent 8% of piglets from becoming anaemic (Hb < 80 g·l-1). Body weights were comparable in the 2 groups.

Iron is involved in the formation as well as in the scavenging of reactive oxygen and nitrogen species. Thus, iron can induce as well as inhibit both oxidative and nitrosative stress. It also has a key role in reactive oxygen and nitrogen species-mediated apoptosis. We assessed the differences in tyrosine nitration and caspase 3 expression in the liver, heart, and kidneys of rats treated weekly with intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose and ferric carboxymaltose (40 mg iron/kg body weight) for 5 weeks. Nitrotyrosine was quantified in tissue homogenates by Western blotting and the distribution of nitrotyrosine and caspase 3 was assessed in tissue sections by immunohistochemistry. Ferric carboxymaltose and iron sucrose administration did not result in detectable levels of nitrotyrosine or significant levels of caspase 3 vs. control in any of the tissue studied. Nitrotyrosine and caspase 3 levels were significantly (p

Introduction: Patients who have β-thalassemia, sickle cell anemia, and myelodysplastic syndromes are sustained by long-term blood transfusion therapy. Transfusion therapy results in iron accumulation initially in the liver, spleen and bone marrow. These are the organs responsible for eliminating apoptotic red blood cells. To prevent iron overload, iron must be removed using iron chelators, administered either orally or infused on a daily basis. One strategy to more effectively deliver chelators to the sites of iron accumulation is to encapsulate them in liposomes. Liposomes also accumulate in the liver, spleen and bone marrow; therefore LDFO targets the chelator directly to the iron stores. We tested the hypothesis that the LDFO approach provides highly efficient (moles chelator administered/moles iron removed) iron chelation. If this hypothesis is supported by the data, lower amounts of chelator could be administered to patients, on a less frequent dosing schedule. This would enable LDFO to be used alone or as part of a combination chelation regime to minimize the need for high daily chelator doses. Methods: We prepared two LDFO formulations composed of (hydrogenated soy phosphatidylcholine, HSPC)/cholesterol (60/40) or (palmitoyloleoylphosphatidylcholine, POPC)/cholesterol (55/45). Animal protocols were approved by the institutional review board. We determined the pharmacokinetics of the encapsulated deferoxamine (DFO) in CF-1 female mice by analyzing serum plasma DFO concentrations by HPLC, after dosing LDFO. CF-1 female mice were overloaded with iron by administering IV, hydrogenated iron dextran 100 mg/kg four times, at three day intervals. Twenty-one days after the last iron dose, mice (n=10) were administered the first dose of the LDFO. The LDFO formulations were administered IV three times at 200 mg/kg at 14-day intervals. A control group (n=10) of non-encapsulated DFO was administered by SC infusion from an implantable minipump at 20 mg/kg/day for a total dose of 280 mg/kg DFO over 14 days. Saline controls were dosed on the same schedule as LDFO. Every 24 h, five mice from each group were alternated from the regular cages into metabolic cages and urine and feces collected. The iron concentration in urine and feces was measured by a modified ferrozine-based spectroscopic assay. At the study end, blood was drawn form the mice and standard blood substances were analyzed as an indicator of organ function. Results: The HSPC/cholesterol and POPC/cholesterol LDFO liposomes had 88 nm and 119 nm diameters and encapsulated 354 and 266 g DFO/mole phospholipid respectively. At 6 and 24 h post IV injection, there is 67.0% and 27.2% ID DFO in plasma for HSPC liposomes and 54.2% and 18.1% ID DFO in plasma for POPC liposomes. In treating iron overloaded mice, IV administered LDFO removed 2.3-2.8 times more iron than deferoxamine mesylate (DFO) given by SC continuous infusion. After LDFO treatment, iron was continuously eliminated for 14 days post dosing. At day 14 LDFO-HSPC and LDFO-POPC cumulatively had a 3.1 and 3.5-fold higher iron elimination in urine compared to SC infused DFO and 1.8 and 1.3-fold higher in feces respectively, corrected for background iron using the saline control group. The second and third dose of LDFO at 14-day intervals showed similar iron elimination patterns to the first dose. The iron removal efficiencies were 68% for LDFO-HSPC, 55% for LDFO-POPC and 24% for Free DFO. The liposome composition shifted the relative iron elimination profiles within the liposome groups. Of the two formulations, LDFO-HSPC produced more fecal iron removal while the LDFO-POPC group gave higher urinary iron removal. The iron elimination curves for both liposome formulations were statistically different than the infused DFO curve (p Conclusion: In the iron dextran overload mouse model, a single injection of LDFO greatly accelerates iron elimination compared to two weeks of continuous SC infused DFO at similar cumulative dosages. The high molar efficiency of iron removal could lead to an improved treatment that increases chelator coverage and provides substantially better management of iron overload than current regimes in patients suffering from iron overload conditions. Disclosures Hayes: ZoneOne Pharma, Inc: Employment, Equity Ownership. Noble:ZoneOne Pharma, Inc: Employment, Equity Ownership. Dai:ZoneOne Pharma, Inc: Employment. Working:ZoneOne Pharma, Inc: Equity Ownership. Szoka:ZoneOne Pharma, Inc: Consultancy, Equity Ownership.

The pharmaceutical^ important iron-dextran complexes (ferritin models) were studied by Mössbauer spectroscopy in frozen solution at 87 K and in lyophilized form at 297 and 87 K. The quadrupole splittings of the lyophilized forms of iron-dextran complexes measured at 297 and 87 K were slightly different. The quadrupole splittings of several complexes in lyophilized form and frozen solutions measured at 87 K were also different. Slight differences in the quadrupole split-ting were found for various iron-dextran complexes. Mössbauer spectra of iron-dextran complexes were better fitted using two quadrupole split doublets. Slight differences in the corresponding quadrupole splittings and doublet ratios were observed for various complexes.

Serious adverse events that occur with the administration of iron dextran are due to the high molecular weight preparations. Conclusions that iron sucrose and ferric gluconate are safer than iron dextran may be premature. Published literature comparing safety profiles of available parenteral iron products is reviewed. Administration of iron salts to pre-dialysis patients with chronic kidney disease may not be optimal. We recommend the total dose infusion of low molecular weight iron dextran as an option for iron replacement.

ObjectiveTo determine the influence of iron dextran intraperitoneal administration on the function and histology of the peritoneum in rats undergoing chronic peritoneal dialysis.DesignProspective, randomized experimental study.MaterialsFifty-four Sprague-Dawley rats were divided into five groups: 3 study groups -high dose group (H), n = 12; intermediate dose (M), n = 12; and low dose group (L), n = 12 a dialysis control group (D), n = 12; and a tissue control (C), n = 7.InterventionsThe study groups were given Dianeal containing iron dextran in a concentration of 0.5,0.25, and 0.125 mg/L (groups H, M, and L respectively). Group D was given standard Dianeal. Group C was never dialyzed.Main Outcome MeasuresA 2-hour peritoneal equilibrium test (PET) was performed on the eighth day, at 3 months, and at 6 months. After the final PET, the animals were sacrificed and the peritoneal membrane was evaluated by gross inspection and light microscopy (silver, prussian blue, and trichrome staining).ResultsPeritoneal transport of small solutes followed the same pattern in all groups, increasing over time. The peritonitis index was similar in the groups. No iron deposits or morphologic differences were seen in the gross inspection of the peritoneal cavity. No peritoneal iron deposition was detected in the histological analysis with prussian blue staining. No differences were noted in the light microscopic analysis of the mesothelial cell layer (silver staining), nor did the morphometric analysis of the submesothelial space show any differences in thickness between the groups.ConclusionThese findings suggest the absence of toxic effects of iron dextran on the peritoneal cavity of rats in the concentrat ions studied. Further studies should be performed to evaluate the effectiveness of these dosages delivered intraperitoneally to maintain iron homeostasis.

Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT) counts in CKD patients with iron deficiency anemia (IDA). Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI) between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb), iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg); age 69 ± 12 years and Creatinine 3.3 ± 1.9 mg/dL. All CKD stages were represented (stage 4 commonest). Hgb and Fe stores improved post-TDI (P ≪ 0.001). There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, P = 0.30). The mild reduction in PLT after TDI remained non-significant (P > 0.05) when data was stratified by molecular weight (MW) of iron dextran used (low versus high), as well as by dose administered (

The effect of six independent factors on the stability of i.v. nutritional emulsions was studied. Forty-five i.v. nutritional admixtures were prepared, each containing the following: (1) amino acids (range, 2.5-7%), (2) hydrated glucose (range, 5-20%), (3) lipid emulsion (range, 2-5%), (4) monovalent cations (range, 0-150 meq/L), (5) divalent cations (range, 4-20 meq/L), and (6) trivalent cations (range, 0-10 mg of elemental iron/L). Stability assessments included particle-size analysis, pH determination, and visual inspection. Sizing and counting of fat particles was achieved by using light obscuration and dynamic light scatter methods. Light obscuration and visual assessments were performed at 0, 6, 12, 24, and 30 hours. Dynamic light scatter and pH determinations were performed at 0 and 30 hours. Multiple stepwise regression analysis revealed that trivalent cation concentration was the only variable that affected the stability of nutritional emulsions (p0.00001), accounting for approximately 60% of the potentially dangerous increases in fat particle sizes observed. In addition, a percentage of large fat particles (5 microns in diameter) greater than 0.4% was associated with unstable emulsions. However, this instability was visibly evident only 65% of the time. Changes in mean globule diameter, cream-layer thickness, and pH did not reveal instability in these emulsions. Emulsions in which0.4% of the initial fat concentration consists of particles of5 microns in diameter are likely to become unstable. Of the six factors studied, the trivalent cation in iron dextran was most disruptive to lipid-based parenteral nutrient admixtures.

The combination of two modern spectroscopic techniques was used for comparative microstructural analysis of several iron-dextran complexes which were used or elaborated as drugs for treatment of iron-deficiency anemias. Slight variations of the iron electronic and magnetic structure in different iron-dextran complexes were detected by Mossbauer spectroscopy. The differences of iron core structure and size were shown in studied complexes also. Variations of dextran structure were detected by the positron annihilation technique for investigated irondextran complexes. These results were considered with histological and histochemical data for iron-dextran complexes to compare the differences of their microstructural variations and biochemical pathways.

Application of Mossbauer spectroscopy with a high velocity resolution (4096 channels) for compara- tive analysis of iron cores in a human liver ferritin and its pharmaceutically important models Imferon, Maltofer ® and Ferrum Lek as well as in iron storage proteins in chicken liver and spleen tissues allowed to reveal small variations in the 57Fe hyperfine parameters related to differences in the iron core struc- ture. Moreover, it was shown that the best fit of Mossbauer spectra of these samples required different number of components. The latter may indicate that the real iron core structure is more complex than that following from a simple core-shell model. The effect of different living conditions and age on the iron core in chicken liver was also considered. © 2012 Published by Elsevier B.V.

Both erythropoiesis-stimulating agents and iron treatments are underutilized in peritoneal dialysis (PD) patients. Studies to evaluate safety profiles of various intravenous iron preparations are limited in PD patients compared to hemodialysis. No study in the literature compared safety of low-molecular-weight iron dextran (LMW-ID) with that of iron sucrose in PD patients. We aimed to compare adverse-effect profiles of LMW-ID and iron sucrose with varying dosing schedules in PD patients with a hope to foster use of parenteral iron solutions in PD patients.We retrospectively reviewed patient charts and included patients who were administered iron sucrose or LMW-ID parenterally. Sociodemographic characteristics, clinical features, and pertinent laboratory data were collected. Adverse events which were deemed to be related to infusion of parenteral iron were recorded. We double-checked both physician records and nursing documents for observed adverse events.A total of 167 chronic PD patients were included in the study, and 92 patients were administered LMW-ID, whereas 75 patients were administered iron sucrose. Only one adverse event occurred in a patient who was administered 500 mg iron sucrose in a single infusion.This study showed the comparable safety of LMW-ID in varying doses over that of iron sucrose in PD patients.

Stable 10-hydroxycamptothecin (HCPT) microcrystals with a length of about 5–10 μm and a ζ -potential of −38.5 mV were produced by pH-induced reprecipitation in presence of a stabilizer hydroxypropylmethylcellulose. Sequential layer growth was achieved by the layer-by-layer (LbL) assembly of Fe 3+ and dextran sulfate (DS) on the surface of HCPT microcrystals via both electrostatic interaction and chemical complexation process. The satisfactory drug loading content (67.2 ± 0.82%) as well as high encapsulation efficiency (60.56 ± 0.82%) for four bilayers of Fe 3+ /DS coating was achieved. Both in vitro and in vivo release study revealed that the release time increased as the number of deposited Fe 3+ /DS bilayers increased. These results indicated that such iron–polysaccharide multilayered microcapsules can be a promising approach for the construction of an effective controlled release delivery system of HCPT as well as other drugs with potential cytotoxicity or short half-life time.