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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.

Iron-dextran may be administered during haemodialysis by slow infusion through the venous access port for the management of iron deficiency in patients treated with erythropoietin. This technique is time-efficient and convenient. The degree to which haemodialysis removes iron-dextran in vivo, however, is unknown. The purpose of this study was to measure the removal of iron-dextran in patients undergoing haemodialysis. Eight patients were enrolled into this open label, single dose, mass transfer study. All were stable patients, treated by haemodialysis for at least 1 month and with a stable baseline average haematocrit of 30.9 ± 1.9%. All 8 patients used aTerumo® 175 cuprammonium dialyser and all received 1g of intravenous iron-dextran infused over 1 hour during dialysis. Dialysate was collected for an average of 160 ± 30 minutes, was concentrated by lyophilisation, and assayed for iron-dextran content by spectrophotometry. The amount of iron-dextran removed by haemodialysis was determined. Six of the 8 patients showed no detectable amounts of iron-dextran in the dialysate, while 2 showed less than 2% of the total dose given. Haemodialysis removed 5mg of iron during a 110-minute session in 1 patient, and 17mg of iron during a 188-minute session in a second patient. Both patients were dialysed with the Terumo® 175 dialyser, reprocessed once. Our study concluded that there is minimal removal of iron-dextran by conventional haemodialysis in vivo. Administration of iron-dextran during haemodialysis is convenient and efficient, and does not warrant a change in dosage schedule.

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 (

Indications for the use of parenteral iron are limited to conditions in which the oral supplementation of iron is not possible or fails. An overview of iron balance and iron requirements is presented to describe situations in which iron supplementation may be required. When parenteral iron supplementation is required, careful attention to proper dosing and administration is necessary to optimize efficacy and safety. The purpose of this article is to review the literature regarding the clinical use of parenteral iron therapy and provide guidelines on dosing and administration. Methods of iron dextran administration, including the IV and intramuscular injection of undiluted drug and total dose infusion, are compared. Complications associated with the use of parenteral iron are also be reviewed. Finally, the use of iron supplementation in patients receiving parenteral nutrition care explored.

An experimental model of haemosiderosis, using the chicken, was developed to examine the distribution of iron in the liver following an injection of iron dextran and to allow calibration of image analysis readings. Image analysis was used as a tool to quantify the stainable iron present in hepatic tissue obtained from wild and captive birds presented for necropsy. A retrospective study of 180 necropsy cases, representing 40 different species of bird, is described. Statistical evaluation of the amount and distribution of stainable iron in the liver tissue of birds from different taxonomic orders indicated that the concentration of iron measured in liver tissue was significantly different in different species of bird. The results of the study showed that hepatic haemosiderosis is a common histological finding in most avian species examined. Although not necessarily associated with overt liver disease, it is often associated with concurrent malignant and infectious diseases. The presence of excess stainable iron in the liver is probably a reflection of an altered iron metabolism associated with increased turnover of tissue iron. This alteration may occur following starvation or trauma.

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 mean (+/- sd) packed cell volume (PCV) of the lambs in a flock mated by 'out-of-season' breeding methods and housed throughout the last six weeks of pregnancy and the whole of the suckling period declined to 23.3 +/- 3.34 per cent when the lambs were a month old, but recovered spontaneously to reach values within the normal range (30 to 35 per cent) before they were weaned at two months. Clinical signs of anaemia were observed in only a few lambs at three weeks old but the PCV values of all the lambs were significantly lower at this time than at weaning. There was no relationship between the PCV values during the two to four weeks after birth and the growth rate of the lambs. The administration of 200 mg iron, as iron dextran, by intramuscular injection to the newborn lambs prevented the decrease in PCV, but had no measurable effect on the health or growth rate of the lambs throughout the suckling period.

Intravenous iron therapy is a useful treatment for the rapid correction of iron deficiency anaemia and can be used to avoid or reduce the requirement for allogeneic blood transfusion. Several intravenous iron preparations are available commercially which differ in cost, mode of administration and side effect profile. There are few data directly comparing the efficacy of these preparations. In this retrospective single-centre study, we present the results from two hundred and eight patients treated using three different iron preparations (iron dextran, iron sucrose and ferric carboxymaltose) and compare the effect on haemoglobin levels and other measures of iron deficiency six weeks after treatment. Within the limitations of our study design, we show a statistically and clinically significant difference in efficacy between these preparations.

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.

Spontaneously-reported rates of adverse events (AEs) of intravenous (i.v.) iron products have not been compared since 2007. AEs in Europe (Eur) and North America (NA) have never been compared. New products have been marketed and many changes in prescribing habits have occurred since then, and the effect on AEs reporting is unclear. It was hypothesized that changing practices for i.v. iron products has caused changes in the rates of serious AEs and large differences exist between Eur and NA. Rates of AEs for three i.v. iron preparations (iron sucrose [IS], ferric gluconate [FG] and high and low MW iron dextran [HMWID, LMWID]) were compared by product and continent from January 1, 2003 to June 30, 2009 for selected countries in Eur and NA, using the Uppsala Monitoring Center's database. Rates of total, anaphylaxis and other serious allergic AEs were calculated as number of AEs divided by i.v. iron sales standardized to 100 mg dose equivalents (DEq) of iron. Quarterly sales (millions of 100 mg DEq of iron) increased from the first quarter 2003 to the end of the second quarter of 2009 by 1% for FG, 16% for IS and 2% for ID. Total AEs for NA plus Eur were similar for FG and IS, but total AEs were 6- to 7-fold higher for ID. Rates of anaphylaxis were 6- to 11-fold higher in Eur plus NA combined for ID than for IS or FG. In NA, there were substantially higher reports for total, anaphylaxis and other serious allergic AEs with FG compared to IS, whereas the reverse was the case in Eur. Odds ratios (OR) showed higher risks of anaphylaxis with FG in NA vs. Eur (OR = 4.40, P0.0001) and lower risks with IS (OR = 0.24, P0.0001). Odds of anaphylaxis with LMWID in Eur vs. FG and IS were 42.08 and 16.92 (both P0.0001), respectively. In NA, odds of anaphylaxis with ID vs. FG and IS were 2.36 and 17.73 (both P0.0001), respectively. Differences between NA and Eur may be related to varied treatment practices. ID had the highest rates of all types of AEs, and IS and FG had a continued trend for lowest rates of AEs.

L’administration de fer dextran à 10 mg/kg intramusculaire (IM) est un traitement empirique couramment recommandé en médecine aviaire lors d’hémorragie ou d’anémie. L’objectif principal de cette étude était d’évaluer les effets de ce traitement sur l’anémie chez les oiseaux de proie. Deux types d’individus ont été utilisés : des crécerelles d’Amérique (Falco sparverius) où une anémie par perte de sang externe aiguë a été créée (deux phlébotomies de 20-40 % du volume sanguin total à un intervalle de 6 h) et des oiseaux de proie sauvages de différentes espèces souffrant d’anémies diverses. L’ensemble des oiseaux a été subdivisé aléatoirement en groupe traitement (fer dextran 10 mg/kg IM) et contrôle (NaCl 0,9% IM). Un suivi dans le temps a été réalisé afin d’étudier leur récupération de l’anémie, la présence d’effets secondaires au traitement et l’impact d’une administration de fer sur ces réserves. Aucune différence significative n’a été observée entre les deux groupes en ce qui concerne les signes cliniques, l’hématocrite, le pourcentage des polychromatophiles/réticulocytes, la densité cellulaire et le fer de la moelle osseuse, la créatine kinase et le fer plasmatique. La majorité des crécerelles ont présenté une myosite au site d’injection du fer. Nos résultats suggèrent qu’une administration de 10 mg/kg de fer dextran IM n’a pas d’effet sur l’érythropoïèse des rapaces souffrant d’anémie par perte de sang externe aiguë, qu’elle provoque une légère inflammation au site d’injection et qu’elle n’influence pas les réserves de fer. Le comptage des réticulocytes en anneau et des polychromatophiles semble être deux méthodes équivalentes., A 10 mg/kg intramuscular (IM) administration of iron dextran is a common empirical treatment recommended in avian medicine for hemorrhage and anemia. The purpose of this study was to evaluate the effects of this treatment on anemia in birds of prey. Two kinds of specimen were used: the American kestrel (Falco sparverius) where an acute external blood loss anemia was created (with two phlebotomies of 20-40 % of the total blood volume at 6 hours interval) and other various species of wild birds of prey suffering from different types of anemia. All subjects were randomized into a treatment (iron dextran 10 mg/kg IM) or a control (NaCl 0,9 % IM) group. Monitoring was carried out to evaluate the evolution of the anemia, presence of side effects and impact of an iron administration on their iron reserve. No significant differences were observed between the two treatment groups for clinical signs, packed cell volume, the percentage of reticulocytes/polychromatophilic erythrocytes, bone marrow cellularity and iron, plasmatic iron and creatine kinase. Most kestrels had a myositis at the iron injection site. Our results suggest that an IM injection of 10 mg/kg iron dextran has no effect on raptor erythropoiesis after an acute external blood loss anemia, that it has no effect on iron reserve, and that it can cause mild inflammation at the injection site. The polychromatophilic erythrocytes and the reticulocytes ring form count were two equivalent methods.

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.

Željezo je jedan od najraširenijih metala u Zemljinoj kori. Hidra je slatkovodna životinja koljena Cnidaria. Toksični učinak željeza na različite organizme bio je već predmet istraživanja, ali ovo je prvo dokumentirano istraživanje o njegovu učinku na hidre. Zelena hidra sadrži u svojim gastrodermalnim mioepitelnim stanicama simbiotsku algu. Jedinke simbiotske zelene hidre bile su tretirane sa šest koncentracija vodene otopine željeznog dekstrana, dok je nesimbiotska smeđa hidra bila tretirana s 14 koncentracija vodene otopine željeznog dekstrana tijekom tri dana. Morfološke promjene su praćene pomoću stereolupe i to migracija jedinki u eksperimentalnoj posudici, promjena oblika tijela, reakcija na mehanički podražaj, odsutnost lovki, lučenje sluzi i nespolno razmnožavanje. Migracija hidri je prvi način izbjegavanja štetnog učinka (mikro)okoliša, nakon čega je uslijedila promjena oblika tijela. Histološke promjene praćene su pomoću svjetlosnog mikroskopa. Morfometrijska istraživanja obuhvaćala su mjerenja površina ektoderma i gastroderma te debljine mezogleje. Depozicije željeza u tkivu hidri su bile vidljive su kao plavo obojenje unutar stanica. Visoke koncentracije željeza uzrokovale su morfološke i histološke promjene i letalni učinak. Zelena hidra je pokazala veću otpornost u preživljavanju od smeđe. Simbioza se pokazala kao evolucijska prednost. Iron is among the most common metals in Earth's crust. Hydra is a freshwater animal that belongs to the phylum Cnidaria. Toxic effect of iron on various organisms has been investigated before but this is the first documented research on its effect on hydras. Green hydra contains symbiotic algae in its gastrodermal myoepithelial cells. Individuals of symbiotic green hydra were treated with six concentrations of aqueous solution of iron dextran, while aposymbiotic brown hydra was treated with 14 concentrations of aqueous solution of iron dextran for three days. Morphological changes migration of individuals in experimental dish, changes of body shape, reaction to mechanical stimuli, tentacle reduction, mucous secretion and asexual reproduction were monitored with stereolupe. Migration of hydras was the first step in evading deleterious microenvironmental conditions, followed by changing its body shape. Histological changes were observed with light microscope. Morphometric analysis included measuring of endoderm and gastroderm surface areas and mesoglea thickness. Iron depositions in hydra tissue were observed as blue staining within cells. High concentrations of iron caused morphological and histological changes and mortality. Green hydra showed a higher level of resistance in surviving than brown hydra. Symbiosis was pointed out as an evolutionary advantage.

We describe a new mass isolation procedure for both pure and stage-specific phagosomes from Tetrahymena thermophila. We prepared magnetic iron dextran particles about 1 μm in diameter to label the phagosomes. The oral apparatus of the cells concentrated these particles so readily that after 1 min the majority of the cells had formed a single phagosome. A short wash removed non-ingested particles, enabling us to follow the age-dependent changes of a single labeled phagosome through the cell. Phagosomes of different ages, including very young and nascent phagosomes, were removed easily from the non-magnetic cell debris of mechanically homogenized cells by means of a permanent magnet. The isolated phagosomes are pure as tested by enzymatic assays and light and electron microscopy. Since the yield of pure phagosomes of all ages is high (∼ 90%), this method could be generally applied for phagosome isolation from ciliates.

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.

Serum amylase activity was analyzed chromogenically (blue starch method) and its isoenzyme was separated by cellulose acetate membrane electrophoresis in newborn pigs comparing with those in adult pigs. Serum amylase activity in newborn pigs was about one half of adults' and increased with age. Serum amylase isoenzymes were separated into 4 fractions from the cathode. The isoenzymes were also classified in 5 types on the basis of the combination of these 4 fractions. Incidences of the fractions and the types were not significantly different between adults and newborns. After the iron dextran treatment, serum amylase activity as well as levels of erythrocytes, hemoglobin and packed cell volume increased. The rates of increase in hemoglobin and packed cell volume were more significant in the double treatment group than in the single treatment group, while serum amylase activity increased similarly in these 2 groups. The increase in serum amylase activity seemed to indicate that the development of amylase-producing organs was reinforced by the iron compound treatment. It is thought that serum amylase activity may be an indicator of healthy growth in newborn pigs.

Current literature supports iron dextran as the only iron preparation compatible with parenteral nutrition (PN). Iron sucrose has been used for iron replacement therapy because of its lower rate of adverse events. The purpose of this study is to determine the physical and chemical stability of iron sucrose in PN.Physical and chemical stability of iron sucrose in nonlipid PN solutions (PN 1 for neonates and PN 2 for patients weighing20 kg) is tested over time in triplicate. Physical stability is determined by visually inspecting each PN solution for particulate matter and by filtering and analyzing each aliquot quantitatively for crystal precipitates. Chemical stability is confirmed if the iron concentrations by mass spectrometry remain within United States Pharmacopeia (USP) standards.Visual clarity is maintained in all PN solutions at hours 0 through 4. PN solution 1 remains clear for hours 8 through 24, whereas PN solution 2 shows an increase in particulate matter by 8 hours. All PN solutions 2 are considered visually incompatible by hour 24. Physical stability of iron sucrose for PN solutions 1 and 2 from hours 0 to 4 is within the USP guidelines for crystalline particulate matter. At hour 24, only solution 1 remains within USP guidelines. Chemical stability data indicate that iron concentrations are maintained throughout the 24-hour time period.The physical stability of iron sucrose in PN is time and concentration dependent. Concentrations0.25 mg/dL showed increasing particulate and should not be added to PN. However, iron sucrose is chemically stable in PN solutions.

The cellular localization of DMT1 and its functional characterization suggest that DMT1 may play an important role in the physiological brain iron transport. But the regulation of DMT1 expression by iron in the brain is still not clearly understood. In this study, both the contents of ferric and ferrous iron as well as DMT1 expression were evaluated in CPu and SN after ICV of 500 μg iron dextran/rat/day for 3 or 7 days. It was found that the iron levels in CPu and SN were not altered obviously until ICV for 7 days. Immunohistochemistry results indicated that the expression of DMT1 (−IRE) in CPu and SN was not altered significantly after 3 days of ICV. Whereas the expression of DMT1 (−IRE) decreased significantly after 7 days of ICV when ferrous iron was increased significantly. Contrary to that of DMT1 (−IRE) in the same regions, there were no significant alterations in DMT1 (+IRE) expression in CPu and SN in spite of the existence of the altered iron levels, compared with that of control groups. The results demonstrate that DMT1 (−IRE) expression was correlated probably with brain iron levels; especially, its regulation was correlated with ferrous iron (not ferric iron) in CPu and SN in adult rats, compared with those of saline-injected control rats. The effect of ferrous iron on the expression of DMT1 (−IRE) in the brain also suggests that it might play a major physiological role in brain iron uptake and transport, but further studies are needed to clarify these issues. Anat Rec, 2009. © 2008 Wiley-Liss, Inc.

Iron deficiency and vitamin A deficiency are both reported to predispose to infection morbidity and to mortality. In both situations, however, the data are insufficient to draw firm conclusions, primarily owing to flaws in the design of the studies. To be sure, these are difficult studies to carry out, and the investigators whose reports have been reviewed should be praised rather than adversely criticized for their efforts. In the case of iron deficiency, there is a further complication in interpretation, that is the suggestion that iron deficiency states may be protective and that conditions of iron overload may predispose to infection. These concepts appear to pertain most convincingly to malaria and Yersinia infections, and to situations in which iron dextran is given parenterally to young children in the first few months of life. There are still two few data to suggest that oral iron is harmful and there is no reason at present that it should not be employed for the correction of iron deficiency anemia.

Iron overload was induced by iron dextran i.v. in clinically healthy adult pigeons, Columbia livia, (n = 8). Hemosiderosis was induced in all treated birds. Two control pigeons received no iron injections. Pigeons did not show clinical signs of iron overload during the 6-wk study. Ultrasound examination of the liver in the pigeons receiving iron dextran was performed on days 0, 13, 28, and 42. No ultrasound images were collected on the control pigeons. Magnetic resonance imaging was performed on days 0, 13, 28, and 42 on all study pigeons and imaging sequences were collected in three different imaging formats: T1, T2, and gradient-recalled echo (GRE). Surgical liver biopsies were performed on pigeons receiving iron dextran on days 2, 16, and 45 (at necropsy). A single liver sample was collected at necropsy from the control birds. Histologic examination, quantitative image analysis, and tissue iron analysis by thin-layer chromatography were performed on each liver sample and compared to the imaging studies. Although hemosiderosis was confirmed histologically in each experimental pigeon, no significant change in pixel intensity of the ultrasound images was seen at any point in the study. Signal intensity, in all magnetic resonance imaging formats, significantly decreased in a linear fashion as the accumulation of iron increased.

The present study describes the application of CZE to investigate the portion of labile iron in the following parenteral formulations: iron gluconate, iron saccharate, and iron dextran. Labile iron was detected as Fe(III)-chelate of EDTA at 246 nm. When EDTA was incubated with the formulations before electrophoresis, labile iron, or chelatable iron, respectively, was detected in all formulations, mostly in iron gluconate and iron saccharate. It was observed that the amount of iron released is time- and pH-dependent. In contrast, when EDTA was separately injected before the formulation sharp peaks of the Fe(III)-chelate were detected only after injection of iron gluconate. This type of labile iron can be described as "electrophoretically free" iron. CE provides thus a new method to characterize potential toxic, labile iron in parenteral iron formulations.

Serum iron concentration and iron saturation of transferrin (Trf) are measures of body iron stores after administration of iron supplements. In clinical and experimental research, the complex determination of Trf was replaced by the simple determination of total iron binding capacity (TIBC). The objective of this work was to define if TIBC could be an adequate measure for Trf in neonatal piglets after i.m. iron administration. Treated piglets received 150 mg of iron-dextran i.m. the first day of life, and were compared to the untreated control group. Prior to iron administration, as well as on days 2, 8 and 12 after iron administration, serum iron and TIBC concentration were analyzed by an automatized chemical analyzer and Trf was determined by densitometry of electrophoretic strips. Our results show that regardless of iron treatment, TIBC is not a measure of Trf concentration in neonatal piglets two days after birth. At day 8 of their life a high correlation coefficient of these two parameters was established in non-treated animals, while in iron-treated piglets the same correlation was established 12 days after iron treatment. Thus, we suggest that in neonatal piglets, TIBC could be used as a measure of Trf concentration only 12 days after i.m. iron treatment. Određivanje statusa gvožđa u organizmu jedinke posle primene određenog preparata ovog mikroelementa moguće je utvrditi određivanjem njegove koncentracije u serumu i zasićenja transferina (Trf) gvožđem. U kliničkoj i eksperimentalnoj praksi složeno određivanje koncentracije Trf zamenjeno je jednostavnim određ ivanjem ukupnog serumskog kapaciteta za vezivanje gvožđa (TIBC). Cilj ovog rada je bio da se na modelu porasta serumskog Fe po i.m. aplikaciji Fe-dextrana novorođenoj prasadi, utvrdi odnos TIBC i Trf po aplikaciji ovog mikroelementa, kako bi se utvrdilo da li visoke doze gvožđa u serumu utiču na vrednost TIBC kao mere za određivanje koncentracije Trf. Vrednosti za serumsko Fe, TIBC i Trf poređene su između grupe životinja koja je odmah po rođenju dobila 150 mg Fe-dextrana i kontrolne grupe u kojoj životoinje nisu tretirane Fe-dextranom. Krv je uzorkovana pre aplikacije Fe-dextrana, drugog, osmog i dvanaestog dana po aplikaciji preparata gvožđa. Koncentracija gvožđa u serumu i TIBC su određivani standarnim kliničkim biohemijskim analizama, dok je koncenracija Trf određena denzitometrijom elektroforetskih traka. Dobijeni rezultati ukazuju da bez obzira na primenu preparata Fe, TIBC nije adekvatna mera za Trf kod novorođene prasadi u prva tri dana po rođenju. Osmog dana života prasadi, utvrđen je visoki stepen korelacije ova dva parametra kod životinja koje nisu bile tretirane, dok je kod tretiranih jedinki taj stepen korelacije postignut dvanaestog dana. Na osnovu izloženih rezultata se može zaključiti da se kod novorođene prasadi TIBC može koristiti kao mera za Trf tek 12 dana nakon i.m. tretmana Fe-dextranom.

The role of parenteral iron therapy has been expanding with the growing use of erythropoietin therapy. Much of the clinical experience regarding the use of IV iron therapy in combination with erythropoietin therapy is based on the hemodialysis patient, but the combination therapy has been used in other patient populations as well. In addition, parenteral iron may be indicated in patients receiving long-term parenteral nutrition and in other clinical situations of iron deficiency when the absorption of iron is impaired or tolerance limited. Once the indication for parenteral iron therapy is established, a selection of the most appropriate agent is required. There are currently 3 parenteral iron preparations available, including iron dextran, sodium ferric gluconate, and iron sucrose. Although all agents have been shown to be effective in correcting iron deficiency, there are differences that exist between them. Both sodium ferric gluconate and iron sucrose have been associated with lower rates of serious adverse reactions than iron dextran, although comparative studies are lacking. In patients with previously documented intolerance to iron dextran, sodium ferric gluconate and iron sucrose have been safely administered. In addition to the immediate and delayed reactions associated with the use of parenteral iron, the risk of iron overload and the potential increased risk of infection are of concern. This article will review the clinical experience of the 3 parenteral iron preparations, discuss safety issues, and provide guidelines on proper dosing and administration.

Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 microg/kg) or sodium nitroprusside (1.0 to 10.0 microg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 +/- 0.74 and -7.93 +/- 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 +/- 0.3 sham vs -3.6 +/- 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity.

To measure the transverse relaxation rate (1/T2) and magnetic susceptibility of the heart in conditions of iron overload by using magnetic resonance (MR) imaging and to correlate these with the tissue iron concentration in a gerbil model.With prior approval by the institutional animal care and use committee, iron overload was induced with one to 15 weekly subcutaneous injections of iron dextran. Nine gerbils had one to five injections, 10 had six to 10, and eight had 13-15. T2 of the whole heart was measured ex vivo (n=27), and the magnetic susceptibility of the tissue was estimated through measurement of the tissue lysate (n=25). The iron level was measured (in milligrams of iron per gram of wet tissue) with chemical analysis after MR imaging. While 1/T2 and magnetic susceptibility are not equivalent measures of the chemically determined tissue iron level, correlations were expected and were identified by using linear regression models.Iron concentration range was 0.28-1.95 mg/g wet tissue. Iron concentration was strongly correlated with 1/T2 (r=0.92, P.001, and the root of the mean squares error of the linear prediction, epsilonRMS, was 0.17 mg Fe/g wet tissue with a repetition time of 700 msec). Iron concentration also was strongly correlated with magnetic susceptibility (r=0.90, P.001, epsilonRMS=0.19 mg Fe/g wet tissue). Multiple regression analysis with combined 1/T2 (with repetition time of 700 msec) and magnetic susceptibility data led to a slight increase in r and decrease in epsilon(RMS) (r=0.93, P.001, epsilonRMS=0.16 mg Fe/g wet tissue).The results of this animal model study demonstrate that 1/T2 and magnetic susceptibility values can be used for estimation of the iron level in the heart.

Intravenous (IV) iron therapy has become an integral part of hemodialysis management during the past several decades, and the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative guidelines recognize that most patients undergoing hemodialysis will require IV iron therapy on a regular basis to reach target hemoglobin (Hgb) levels. There now are three IV iron compounds available in the United States: iron dextran, sodium ferric gluconate, and iron sucrose. Although all have been proven effective for increasing Hgb/hematocrit levels, recent data show differences in their relative safety profiles. During the past two decades, more than 30 deaths have been attributed to the use of IV iron dextran. The two newer compounds available in the United States, sodium ferric gluconate and iron sucrose, have more favorable safety profiles, with the largest prospective safety comparison to date showing sodium ferric gluconate to be similar to placebo in the incidence of serious anaphylactoid-type reactions. This article reviews safety data surrounding the IV iron therapies.

Parenteral supplementation of iron is required in some patients with iron deficiency, including those with oral iron intolerance, chronic uncorrected bleeding, malabsorption, gastrointestinal inflammatory disease, dialysis dependence, or failure to take prescribed oral iron. A more rapid increase in

An injectable iron dextran complex used as a hematinic has been studied using Mossbauer spectroscopy (18–295 K), both as a frozen aqueous solution and in the solid state. The iron in the complex was found to be all high-spin Fe 3+ . The spectra were fitted to a distribution of doublets at room temperature and to a distribution of sextets at low temperatures. There is also a range of temperatures over which both sextet and doublet co-exist. The relatively large distribution of particle sizes gives rise to a broad and asymmetric sextet distribution. The results show that the iron core in the frozen solution and in the solid state is essentially the same species.

Several parenteral iron preparations are now available. This article focuses on iron sucrose, a hematinic, used more widely than any other for more than five decades, chiefly in Europe and now available in North America. Iron sucrose has an average molecular weight of 34 to 60 kd, and after intravenous (IV) administration, it distributes into a volume equal to that of plasma, with a terminal half-life of 5 to 6 hours. Transferrin and ferritin levels can be measured reliably 48 hours after IV administration of this agent. Iron sucrose carries no "black-box" warning, and a test dose is not required before it is administered. Doses of 100 mg can be administered over several minutes, and larger doses up to 300 mg can be administered within 60 minutes. The efficacy of iron sucrose has been shown in patients with chronic kidney disease (CKD) both before and after the initiation of dialysis therapy. Iron sucrose, like iron gluconate, has been associated with a markedly lower incidence of life-threatening anaphylactoid reactions and may be administered safely to those with previously documented intolerance to iron dextran or iron gluconate. Nonanaphylactoid reactions, including non-life-threatening hypotension, nausea, and exanthema, also are extremely uncommon with iron sucrose. Management of patients with the anemia of CKD mandates that we carefully examine the effectiveness and safety of this oldest of iron preparations and the accumulating present-day data regarding it and contemporaneous agents. Am J Kidney Dis 40:1111-1121. © 2002 by the National Kidney Foundation, Inc.

Iron deficiency is the most common cause of a poor response to recombinant human erythropoietin (rHuEPO) in patients receiving long-term dialysis, who are known to absorb oral iron preparations poorly. This retrospective case series reports our preliminary observation of five patients receiving long-term dialysis in a tertiary care university hospital who had responded poorly to rHuEPO because of iron deficiency. These patients also had a history of severe, potentially life-threatening reaction to intravenous iron dextran preparation, but they tolerated the newly available ferric gluconate complex in sucrose with no untoward effects. These results suggest that the parenteral administration of ferric gluconate can be safe for those who require iron therapy and who have had a severe reaction to iron dextran.

Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran.BackgroundParenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.MethodsThis multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.ResultsA total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.ConclusionSFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.

Iron-dextran complexes are pharmaceutically important models of iron-storage protein ferritin. These complexes are used for treatment of iron-deficiency anemias. In this work we present the results of the study of various iron-dextran complexes by Mossbauer spectroscopy and the positron annihilation technique. Mossbauer spectroscopy indicated the differences between the electronic and magnetic structures of iron cores in iron-dextran complexes while positron annihilation showed variations of dextran shells in those complexes. Both techniques appeared to be useful to study microstructural variations in iron-dextran complexes.

Resumo: Experimento realizado com os objetivos de avaliar os efeitos do ferro dextran (FD) sobre os parâmetros sanguineos, niveis de ferro serico e hepático, e desempenho de cabritos de aptidao leiteira. O delineamento utilizado foi o inteiramente casualizado, com quatro tratamentos: T1 - sem aplicação de FD; T2 - aplicacao de FD aos 2 dias de idade; T3 - aplicações de Fd aos 2 e 16 dias e T4 - aplicacoes de FD aos 2, 14 e 30 dias. Nao houve diferencas estatisticas entre tratamentos. Os teores de ferro sericos e hepaticos, ao final do experimento, foram: T1 - 172,09 mg/100ml e 146,25 ppm; T2 - 198,06 mg/100ml e 147,83 ppm; T3 - 186,46 mg/100ml e 253,00 ppm e T4 - 173,12 mg/100ml e 295,75 ppm. Para o desenvolvimento ponderal, os resultados firnais foram: T1 - 9,15 kg;T2 - 9,60 kg; T3 - 9,74 kg e T4 - 10,13 kg. [Effect of iron-dextran on the blood values, level in the liver and performance of the kids milk aptitude]. Abatract: Research was developed to evaluate the effect of iron-dextran (ID) on the blood values (hematocrit and hemoglobin), level serum iron and iron in the liver, and performance of the kids milk aptitude. The experiment was complety randomized with four treatments: Tl - no applications ofthe ID; T2 - applications of the ill at 2 days; T3 - applications of the ID at 2 and 16 days and T4 - applications of the ill at 2, 16 and 30 days. No significant difference was found among for all variables studied. The values for iron serum and livers, at the end of the experiment, were: Tl - 172,09 mg/lOOml e 146,25 ppm; T2 - 198,06 mg/lOOml e 147,83 ppm; T3 - 186,46 mg/lOOml e 253,00 ppm e T4 - 173,12 mg/lOOml e 295,75 ppm. Body weight gain the results final, were: Tl - 9,15 kg; T2 - 9,60 kg; T3 - 9,74 kg e T4 - 10,13 kg.

Sir, Low-molecular-weight iron dextran (cosmoFer® (marketed as INFed® in the USA), Pharmacosmos, Denmark) is available as a total dose infusion (TDI) in the United Kingdom (UK). The use of TDI regimen enables patients to receive their iron dose in one visit as opposed to numerous visits required with other preparations. However, the TDI can take up to 8 h and it would be preferable if the infusion could be safely administered over a shorter duration. The aim of this audit was to evaluate the safety of adopting an accelerated regimen of administering TDI low-molecular-weight iron dextran in comparison to standard rate infusion of the same product.

The objectives of Exp. 1 were to determine the effects of production system and genotype on pig performance and health. Sows were bred, gestated, farrowed, and lactated in either an intensive indoor or an intensive outdoor production system. The three dam genotypes of pigs used in each environment were PIC Camborough-15 (C-15), PIC Camborough Blue (CB), and Yorkshire x Landrace (YL). All pigs received 100 mg of iron dextran at d 3 of age. Pigs raised in the outdoor unit had higher blood hemoglobin (Hb) concentrations on d 28 of age than pigs raised indoors (11.5 +/- .22 vs 8.16 +/- .26 g/dL, P.0001). Outdoor-reared pigs had more white blood cells (WBC) on d 3 than indoor-reared pigs (9.7 +/- .38 vs 8.04 +/- .38 cells/microL x 10(3), P.05), but outdoor pigs had fewer WBC on d 28 of age than indoor-reared pigs (9.8 +/- .5 vs 11.1 +/- .45 cells/microL x 10(3), P.05). Genetic lines did not differ in plasma immunoglobulin G (IgG) concentrations at 3 or 28 d of age. Environment and age influenced pig Hb levels and WBC numbers. The objectives for Exp. 2 were to determine whether C-15-405 pigs reared outdoors or indoors needed supplemental iron or whether they would receive enough environmental iron, and how the lack of supplemental iron may impact pig Hb and immunity. Indoor and outdoor pigs received either no supplemental iron, 100 mg, or 400 mg of iron dextran on d 3 of age. Blood percentage neutrophils and neutrophil: lymphocyte ratio were lower (P.05) indoors, and natural killer cell (NK) activity was greater (P.05) among indoor- than outdoor-reared pigs (NK % cytotoxicity: 15.6 +/- 2.3 vs 9.7 +/- 2.3). Outdoor-reared pigs that received no injected iron had similar Hb at d 28 of age as indoor-reared pigs that received 100 mg of iron dextran (11.1 +/- .36 vs 10.7 +/- .4 g/dL, P = .59). Supplemental iron may not be necessary in an outdoor production system. Outdoor-reared pigs had lower values for some immune measures, but they had similar survival rates as indoor-reared litters.

Supplying adequate iron (Fe) to neonatal pigs to support normal growth and hemato- logical and antioxidant status, while preventing iron toxicity, is a challenge for producers. Three experi- ments were conducted to determine the effect of frequency and route of Fe administration with or without vitamin E ( E ) and selenium (Se) on growth, Fe, and antioxidant status of neonatal pigs. In Exp. 1, 12 pigs from dams with reduced E status were fed a semipurified diet without added Fe from d 3 to d 14 of age. At d 6 of age, pigs received the following i.m. injections: 1 ) FE, 1 mL containing 200 mg of Fe (iron dextran); 2 ) FEE, treatment FE plus 1 mL containing 300 IU of vitamin E (d-a tocopherol); or 3 ) FESEE, 1.03 mL containing 200 mg of Fe (iron dextran), .15 mg of Se (sodium selenite), and 15 IU of vitamin E (d-a tocopherol). Pigs were weighed daily and blood was collected at 3, 7, and 14 d of age. From d 8 to 14, growth was depressed ( P < .05) in pigs injected with FESEE. At 14 d of age, pigs injected with FE or FEE had increased ( P < .05) hemoglobin (Hb) concentra- tion. Ceruloplasmin activity (CP) was greater ( P < .05) at d 7 of age than at d 3 or 14 regardless of treatment. In Exp. 2, 3-d-old pigs (n = 94) received the following: 1 ) FE, 200 mg Fe (iron dextran) i.m.; ( 2 ) FEE, treatment FE plus 300 IU vitamin E i.m.; 3 ) EFE, 300 IU vitamin E i.m. followed by 200 mg Fe (iron dextran) i.m. 24 h later; or 4 ) OFE, 100 mg Fe and 10 mg Cu orally. On d 21 of age, one-half of the pigs in each treatment received a second dose of their respective treatment. Blood samples (n = 60) were obtained on d 3 and 21 of age. Pigs injected with FE, FEE, or EFE had greater ( P < .05) Hb at d 21 than pigs given OFE. Copper/zinc superoxide dismutase (Cu/ZnSOD) activity was greater ( P < .05) at d 21 with OFE than with the other treatments. At 65 d of age, ADG did not differ among treatments. In Exp. 3, pigs (n = 150, in three farrowing groups) were injected with 200 mg of Fe (iron dextran) on d 1 or d 1 and 14. Blood samples were obtained on d 7 and 21 of age. Hemoglobin concentration on d 21 was improved equally by both treatments. Catalase and Cu/ZnSOD activities were increased ( P < .05) on d 21 of the experiment compared with d 7 regardless of treat- ment. Growth was not affected by injection frequency. Results from these experiments indicate that one Fe injection (200 mg) for pigs from sows fed adequate vitamin E will result in adequate growth and hemoglobin concentration with today's improved genetics.

A method for the purification of lysosomes from fibroblasts has been developed which uses endocytosis of superparamagnetic colloidal iron dextran particles followed by separation of the iron-containing lysosomes in a magnetic field. This permitted isolation of lysosomes from fibroblasts from patients with infantile sialic acid storage disorder and other lysosomal storage diseases in which a shift in lysosomal density induced by the storage material prevents purification by centrifugation in a Percoll gradient. The magnetic lysosomes isolated from these cells are very similar to those from normal cells as judged by lysosomal marker enzyme activity and 2D-PAGE analysis of the enriched proteins.

Iron-dextran complexes (IDC) are well known models of the iron storage protein ferritin which are used or elaborated for treatment of iron deficiency anemia. IDC consist of the iron core in the form of FeOOH surrounding with the dextran shell. In the present study we compare the iron state in various IDC including commercial and elaborated samples using Mossbauer spectroscopy. We analyzed IDC from different sources such as Imferon (Benger, USA), Imferon (Fisons, UK), Ferridextran (Leciva, CSSR), Dextrafer (USSR) and elaborated complexes named as IDC26, IDC81, IDC87, IDC3P, IDC4P, IDC6P, IDC8P. These complexes were studied in lyophilized form and solution. Mossbauer spectra of IDC were measured using the high precision spectrometer at 297 K and 87 K for lyophilized IDC and at 87 K for IDC in solution.

Parenteral iron is given to patients in a variety of formulations, including two iron dextran products known as high- (HMW) or low- (LMW) molecular weight iron dextran. Despite more risk of adverse events, HMW iron dextran is sometimes substituted for LMW iron dextran without physician knowledge for