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RESUMO Com o objetivo de avaliar o uso de diferentes fontes de ferro na prevenção da anemia ferropriva e no desempenho em leitões lactentes, dividiram-se 202 leitões em cinco tratamentos: FD - aplicação intramuscular de 200mg de ferro dextrano no terceiro dia de idade; T24 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 19º dia; T48 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 48 horas; T72 - terra à vontade fornecida aos leitões a cada 24 horas do terceiro ao 10º dia e do 11º ao 19º dia, com intervalo de 72 horas; SA - suplemento alimentar ultraprecoce rico em ferro quelatado em pó (SAUP) fornecido do terceiro ao 11º dia, com intervalo de 48 horas. O ferro dextrano aplicado no terceiro dia de vida e a suplementação com terra e SAUP foram eficientes para garantir o desempenho de leitões no período de aleitamento e não influenciaram no consumo de ração nem na taxa de viabilidade. As diferentes fontes de ferro estudadas não influenciaram o leucograma e foram eficientes na prevenção da anemia ferropriva e no desempenho dos leitões lactentes. Com relação às concentrações de hemoglobina e hematócrito, os animais suplementados com ferro dextrano apresentaram valores superiores quando comparados aos que recebem terra e SAUP. ABSTRACT In order to evaluate the use of different sources of iron to prevent iron deficiency anemia and to appraise the performance of suckling piglets, we sorted 202 piglets in five treatments. ID - intramuscular injection of 200mg of iron dextran on the third day of age; T24 - free daily access to land provided to piglets every 24 hours from the third to the nineteenth day; T48 - free daily access to land provided to piglets every 24 hours from the third to the tenth day and from day 11 to day 19 with an interval of 48 hours; T72 - free daily access to land provided to piglets every 24 hours from the third to the tenth day and from day 11 to day 19 with an interval of 72 hours; FS - Food supplement rich in iron-chelating powder (SAUP) available from the third to the eleventh day with an interval of 48 hours. The iron dextran applied on the third day of life as well as the supplementation with land and SAUP were effective to ensure the performance of piglets during the lactation period and did not affect feed intake or the viability rate. The different sources of iron studied did not influence the WBC (White Blood Cell) and succeded in preventing iron deficiency anemia and performance of suckling piglets. Regarding the concentrations of hemoglobin and hematocrit, the animals supplemented with iron dextran showed higher values when compared to those who receive land and SAUP.

A total of 25 clinically anaemic pups aged 3-5 months were randomly divided into 5 equal groups. Pups in Group T5 were treated with single i/m injection of iron dextran and served as control group. Pups in Group T1 were transfused with fresh blood and those of Group T2, T3, and T4 received 7, 14 and 21 days preserved (4-6oC) blood, respectively, @ 20 ml/kg body weight as a single therapy. The clinico-biochemical parameters before blood transfusion showed significant increase in pulse and respiration rates, and significant decrease in total protein, albumin and blood glucose concentration. After 24, 72 and 120 hrs of blood transfusion, a significant improvement in the clinicobiochemical parameters approaching to normal values was observed, whereas no significant change was noticed in anemic control group treated with single i/m injection of iron dextran. It was concluded that blood transfusion, irrespective of fresh or stored blood, can improve clinicobiochemical status and thus is considered as an important life saving measure in severely anemic dogs.

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)

Reports of pica for uncooked rice (ryzophagia) in adults who reside in European and derivative countries are uncommon. We evaluated and treated two nonpregnant women with pica for uncooked basmati rice. Both women reported fatigue, abdominal discomfort after consuming large quantities of uncooked basmati rice, and hair loss. One woman was from India and the other was from Pakistan. Both women were vegetarians. Basmati was the local rice in their native countries and their usual rice in the USA. Both women had tooth damage due to eating uncooked rice and iron deficiency with microcytic anemia attributed to menorrhagia and multiparity. Ryzophagia and other manifestations (except tooth damage) resolved after iron dextran therapy. We review and discuss other reports of ryzophagia associated with iron deficiency, pregnancy, race/ethnicity, geographic origin, and local traditions. We conclude that adults with ryzophagia in European and derivative countries are likely to be non-Europeans.

Purpose An analysis of reported adverse events (AEs) among patients using i.v. iron products, including the newer agent ferumoxytol, is presented. Methods All AE reports to the Food and Drug Administration (FDA) citing iron sucrose, ferric gluconate, high- and low-molecular-weight iron dextran products, or ferumoxytol from October 2009 through June 2010 were evaluated. The rates of various classifications of reported AEs were calculated on a per-unit-sold basis and, for comparison of products supplied in different unit sizes, also in terms of 100-mg dose equivalents (DEq) of iron. Results A total of 197 reported AEs were identified (a cumulative rate of 14.1 AEs per million units sold). The rates of all AE classifications combined ranged from 5.25 to 746 per million units sold for iron sucrose and ferumoxytol, respectively; using the other method of calculation, the rates ranged from 5.24 per million DEq (iron sucrose) to 147 per million DEq (ferumoxytol). Relative to iron sucrose and sodium ferric gluconate, ferumoxytol was associated with significantly elevated risks of death (odds ratio [OR], 475 and 156, respectively; p < 0.0001), serious nonfatal AEs (OR, 263 and 121, respectively; p < 0.0001), and all evaluated AE classifications combined (OR, 142 and 109, respectively; p < 0.05). Conclusion Analysis of reports submitted to FDA revealed large differences among i.v. iron products in reported deaths, serious AEs, other major AEs, and other AEs. Iron sucrose and sodium ferric gluconate were associated with much lower rates of AEs per million units sold than iron dextran or ferumoxytol, which were associated with the highest rates of all reported AE classifications.

Aim: To study the effect of iron dextran injection on growth performance of crossbred and desi piglets under farm and village conditions. Materials and Methods: The experiments were conducted in Pig Breeding Farm, Ranchi Veterinary College, Ranchi and different villages on crossbred and desi preweaned piglets. The piglets were divided into three treatment groups as T 1 (control), T2 (injected iron dextran @ 1 ml (50mg) I/M twice at 3rd and 14th days of age) and T3 (injected iron dextran @ 2 ml 2 3 (100mg) I/M once at 3rd day of age). Results: The average body weight of crossbred piglets in farm condition of T1 , T2 and T3 groups at weaning (8 week) were 7.162±0.365, 9.985±0.281 and 9.572±0.295 kg, respectively. The piglets of T2 group showed better performance over T3 and T1 groups in farm and village conditions on crossbred and desi piglets. Conclusion: On the basis of present findings it may be concluded that irondextran (50mg/ ml) injection should be given to all piglets @ 1 ml I/M during preweaning period at 3rd and 14th day of age for better growth of piglets. [Vet World 2012; 5(10.000): 599-602]

Resume Introduction Le fer dextran de bas poids moleculaire peut etre administre en une perfusion unique d’une dose totale correspondante a la carence en fer. L’objectif de cette etude observationnelle etait de determiner si l’administration unique d’une dose totale de fer dextran permettait de corriger la carence martiale du patient en dialyse peritoneale pendant une duree de quatre mois. Patients et methodes Les patients traites par dialyse peritoneale depuis plus de trois mois et ayant une anemie (hemoglobine Resultats Douze des dix-sept patients inclus terminaient l’etude. La dose totale moyenne administree etait de 742 ± 150 mg sans effet indesirable rapporte. Quatre mois apres l’injection on observait une augmentation significative de la moyenne de l’hemoglobinemie (10,1 ± 0,7 g/dL vs 11,4 ± 1,2 g/dL, p Conclusion Chez le patient traite par dialyse peritoneale, le fer dextran de faible poids moleculaire en injection unique d’une dose totale permet de corriger l’anemie ferriprive pendant une duree de quatre mois.

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.

For more than 50 years, iron dextran has been the mainstay of parenteral iron therapy in the United States. In October 2009, the Food and Drug Administration expanded its existing black box warning that cautioned practitioners to administer a test dose first because of the risk of anaphylactic, often fatal adverse reactions. It further modified the warning, stating that fatal reactions can still occur even in patients who tolerated the test dose. As a result, health care providers have sought safer alternatives to parenteral iron dextran when oral iron repletion is not an option. The purpose of this review is to discuss the currently available formulations, with a focus on the needs of the pediatric patient, in whom there is limited experience in using products other than iron dextran.

Iron-induced cardiovascular disease is the leading cause of death in iron-overloaded patients. Deferasirox is a novel tridentate oral chelator that exhibits a half-life suitable for once-daily dosing; however, little is known regarding the effectiveness of this agent in preventing iron-induced cardiovascular disease. Adult male Mongolian gerbils were randomly divided into 3 groups: control, iron overload, and iron overload followed by deferasirox treatment. Iron-overloaded animals received iron dextran 100 mg/kg intraperitoneally (ip)/5 days for 10 weeks, while deferasirox was given 100 mg/kg per d orally (po) for 9 months post iron loading. Cardiac and aortic iron levels were determined by inductively coupled plasma atomic emission spectrometry. Gerbil electro- and echocardiograms were obtained in anesthetized animals at regular intervals. Compared to control animals, iron concentration was 3.3- and 2.4-fold higher in iron-overloaded heart and aorta, respectively (P.05). Deferasirox treatment reduced cardiac and aortic iron levels by 32% and 35%, respectively (P.05). These results were consistent with the decrease in cellular iron deposition observed with Prussian Blue iron staining. Iron-overloaded gerbils were found to exhibit frequent arrhythmias including premature ventricular contractions, supraventricular tachycardia, and recurrent ventricular tachycardia. In addition, echocardiographic assessment demonstrated iron overload-associated increase in left ventricular dimensions including left ventricular posterior wall dimension (LVPWd: 49%), left ventricular internal dimension (LVIDd: 26%), and left ventricular septum thickness (LVSd: 42%). These parameters were significantly reduced with deferasirox treatment (LVPWd: 23%, LVIDd: 24%, and LVSd: 27%). Iron overload was also associated with reduced ejection fraction (EF: by 30%) and fractional shortening (FS: by 23%) in comparison with controls (P.05). With deferasirox treatment, these values were higher (EF: by 30%, FS: by 28%) compared to iron-overloaded group. These findings suggest that deferasirox may be useful for attenuating iron-induced changes in cardiac structure and function.

Sir,Thanks to Dr Abbas for his interest in our recently published paper entitled “Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for t...

Summary Iron resorption from intramuscular injection of an iron dextran complex (Fedex) is almost complete in piglets one week after injection. The excess of resorbed iron is stored in liver and spleen. The stored iron is made available for the growing pig since half of the iron recorded on the 14th day after injection is used during the third week. The remaining iron stores might well be enough to cover the needs for the fourth week also, although it is not absolutely necessary for the pigs at this age. Zusammenfassung Eisenresorption und Eisenreserven bei Ferkeln nach intramuskularer Injektion von 59Fe-Dextran Eine Woche nach intramuskularer Injektion des Eisen-Dextran-Komplexes Fedex ist die Eisenresorption bei Ferkeln fast vollstandig. Der uberschus des resorbierten Eisens wird in der Leber und der Milz gespeichert. Dieses Depoteisen ist wahrend der Wachstumsphase der Schweine verfugbar, denn die Halfte des Eisens, das nach 14 Tagen noch gemessen werden konnte, wurde wahrend der dritten Woche verbraucht. Wir glauben, das das verbleibende Eisendepot ausreichen wurde, um auch den Bedarf der vierten Woche zu decken. Das ist bei Schweinen dieses Alters allerdings nicht mehr unbedingt notig. Resume Resorption et depot du fer chez des porcelets apres l'injection intramusculaire du 59Fe-Dextran La resorption du fer chez des pourceaux apres l'injection intramusculaire du Fedex, complexe du fer-dextran, etait presque totale une semaine apres l'application. L'exces du fer resorbe fut depose dans le foie et la rate. Le depot du fer etait accessible pour les pourceaux en developpement puisque la moitie des reserves constatees le 14ieme jour etait utilisee au cours de la troisieme semaine. Nous croyon que le reste du fer mis en depot est suffisant pour couvrir les besoins en fer au cours de la quatrieme semaine, quoique cela ne soit pas absolument indispensable pour les pourceaux de cet âge. Resumen Reabsorcion de hierro y almacenamiento de hierro en lechones despues de inyeccion intramuscular de 59Fe-Dextrano En lechones inyectados con Fedex, complejo de hierrodextrano, la reabsorcion de este compuesto fue casi completa despues de una semana de haber sido inyectados. El exceso del hierro reabsorbido fue almacenado en el higado y el bazo. El hierro almacenado fue accesible para el desarrollo de los lechones, puesto que la mitad de las reservas constatadas en el catorceavo dia fue utilizada durante la tercera semana. Creemos que el resto de la cantidad de hierro es suficiente para cubrir tambien las necesidades de hierro durante la cuarta semana, aunque esto no es absolutamente necesario para los lechones de esta edad.

Effects of iron dextran injections on anemia developed in theileriosis were evaluated in calves experimentally infected with Theileria sergenti . Splenectomized animals were inoculated with parasitized erythrocytes from donor animals, and the course of anemia, methemoglobin concentrations of erythrocytes (MetHb, an indicator for blood oxidation), serum iron and erythropoietin concentrations were determined. At the time that packed cell volume (PCV) became 20-25% , 23-41 days after infection, iron dextran (1g of iron per day) was intramuscularly injected into animals for 3 days and 10 days in the separated trials. The course of anemia in a treated group was compared with that in each control group with no treatment. In the 3-day treatment trial, no statistical differences were detected in the state of anemia between the treated and control groups at any sampling time points. However, in the 10-day treatment trial, the treated group showed higher erythrocyte counts in the peak stage of anemia 2-3 weeks after initiation of treatment, and higher PCV and hemoglobin levels in the convalescent stage of anemia 6-8 weeks after initiation of treatment, than the control group. MetHb and serum erythropoietin levels increased transiently and similarly in the two groups at the time of developing anemia. The treated group showed higher serum iron levels 1 and 7-10 weeks after initiation of treatment than the control group. The present study indicated that the 10-day treatment with iron dextran in the developing stage of anemia was effective to suppress the reduction of erythrocytes in the peak stage of anemia, and to improve the recovery of PCV and hemoglobin levels in the convalescent stage of anemia caused by T. sergenti infection., 小型ピロプラズマ病貧血に対するデキストラン鉄製剤（鉄剤）の効果を解析した. 摘脾牛に原虫寄生赤血球を接種して感染させ, 貧血経過, 赤血球メトヘモグロビン濃度（MetHb, 血液酸化指標）, 血清鉄, エリスロポエチン濃度を測定した. 原虫感染後23～ 41 日に血球容積（PCV）が20 ～ 25％となった時点で, 投与群に鉄剤1g を3 日間, あるいは 10 日間筋肉内に投与する試験を個別に実施し, それぞれの非投与の対照群との比較を行った. その結果, 3 日間投与試験では貧血経過に群間の差はみられなかった. しかしながら10 日間投与試験では, 貧血極期となった投与開始後2 ～ 3 週の赤血球数, および貧血回復期である投与開始後6 ～ 8 週のPCV およびヘモグロビン濃度が投与群で大きかった. MetHbは両群同様の一過性増加を示し, 投与群特有の増加はみられなかった. 血清鉄濃度は投与開始後1 週と7 ～ 10 週に投与群で大きかった. 血清エリスロポエチン濃度は両群で貧血進行期に同様に増加した. これらの結果から, 原虫実験感染牛の貧血進行期に鉄剤を10 日間投与することにより, 貧血極期の赤血球数減少の緩和と貧血回復期のPCV およびヘモグロビン濃度の改善に効果があることが検証された.

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.

Iron replacement for iron-deficiency anemia has historically been accomplished with the use of oral iron therapy. Although oral iron is appropriate for most iron-deficiency anemia patients, many patients do not respond to or may be intolerant of oral iron, or may experience bleeding of sufficient magnitude to require higher iron doses than that achievable with oral iron. Intravenous iron therapy is a useful option for these latter patients. Three intravenous iron products are recommended: low-molecular weight iron dextran (INFeD), ferric gluconate (Ferrlecit), and iron sucrose (Venofer). These intravenous iron products have superior safety profiles compared to high-molecular weight iron dextran. The Food and Drug Administration's approval of erythropoietic-stimulating agents to treat certain types of anemia has increased usage of intravenous iron for functional iron deficiency. This review summarizes the current status of intravenous iron products and discusses their advantages and disadvantages in treating both absolute and functional iron deficiency.

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.

Background/Aims: Fast intravenous (i.v.) iron administration during hemodialysis (HD) is associated with the augmentation of oxidative stress and the increase in inflammatory biomarkers, which are also induced by the hemodialysis procedure itself. The aim of this study was to investigate if slow i.v. iron administration would aggravate the status of oxidative stress and inflammatory biomarkers during a hemodialysis session. Methods: Twenty dialysis patients 30–92 years of age that were iron replete and had values for hemoglobin, transferrin saturation and serum ferritin among recommended goals were evaluated in three separate hemodialysis sessions. In the first session patients did not receive any iron treatment, whereas during the second and the third session patients received slow (60 min) i.v. infusions of 100 mg of iron sucrose and 100 mg of iron dextran, respectively. Blood samples were drawn before the hemodialysis session, 15 min after the end of iron administration and at the end of the hemodialysis session in all occasions, for the measurement of markers of oxidant stress (oxidized LDL and ischemia-modified albumin) and inflammation (high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-α). Results: Oxidized LDL was not significantly altered during hemodialysis and this pattern was similar between the three occasions studied. In contrast, ischemia-modified albumin was significantly increased and this effect was also not different between the net hemodialysis and the occasions of iron administration. High-sensitivity CRP, IL-6 and TNF-α were all significantly elevated during hemodialysis and again both types of iron administration did not produce significant changes in this pattern. Conclusion: We did not find an increase in the markers of oxidation/inflammation studied, after slow i.v. iron administration during hemodialysis session.

Svoboda M., J. Drabek: Intramuscular versus Subcutaneous Administration of Iron Dextran in Suckling Piglets. Acta Vet. Brno 2007, 76: S11-S15. The aim of the study was to compare the development of red blood cell indices after subcutaneous versus intramuscular administration of iron dextran to suckling piglets during early postnatal period. The piglets in group I (n = 17) were injected subcutaneously (into groin) with 200 mg Fe 3+ as iron dextran on day 3 of life. In group II (n = 16), the piglets received intramuscular injection (into gluteal muscles) of 200 mg Fe 3+ as iron dextran on day 3 of life. In group III (n = 10), the piglets did not receive any iron till the age of 3 days. The blood was taken and analyzed (Hb, PCV, RBC, MCV, MCH, MCHC, Fe) on days 3, 7, 14, 21, 28 and 35. Haematological indices of piglets in group III were characteristic for hypochromic anaemia. Anaemia in group III had a detrimental effect on the growth rate of piglets. The development of red blood cell indices and iron concentration in blood plasma in subcutaneously treated piglets did not differ significantly from that of intramuscularlytreated group. Both treatments prevented development of anaemia. Haemoglobin, packed cell volume, anaemia, neonatal

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.

To evaluate in RLS patients the efficacy and safety of repeated infusions of iron in order to maintain symptomatic improvements achieved with a prior single 1000 mg infusion of iron.Subjects who had demonstrated initial improvement in RLS symptoms after a single 1000 mg infusion of iron were evaluated monthly for serum ferritin and RLS severity. If symptoms returned at any time in the 2-year period after initial iron treatment, supplemental 450 mg iron gluconate infusions could be given, provided the ferritin was300 mcg/l. The primary outcome measures were side effect profile, duration (weeks) of sustained improvement, and rate of change of serum ferritin.Ten subjects received the initial single 1000 mg dose of iron dextran, but only five subjects were eligible to receive supplemental iron infusions. RLS symptoms returned on average 6 months after the initial 1000 mg infusion. Because of noncompliance with monthly visits one subject was dropped after receiving three supplemental iron infusions. Because of a ferritin300 mcg/l, a second subject was dropped after having received one supplemental treatment. Three subjects completed the 2-year period of the study, having received between two and four courses of supplemental iron. After the initial 1000 mg iron infusion, the ferritin declined on average 6.6 mcg/l/week, which was substantially higher than the predicted value of1 mcg/l per week. The rate of ferritin decline decreased toward normal with repeated IV iron treatments: the average rate of decline in ferritin for the last treatment course was 2.3 mcg/l/wk. The slower the rate of ferritin decline the more prolonged the symptom improvements.Supplemental iron treatments can sustain previously achieved improvements with a single IV iron treatment, but achieving high ferritin levels was not in themselves a guarantee of sustained improvements. The most notable finding was the post-infusion changes in serum ferritin and its implication for altered iron excretion.

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.

Parenteraliron is recommended for patients withfunctional iron deficiency and when oraliron is ineffective, and will be required bypatients on haemodialysis. The introduction of ferumoxytol(Rienso) brings to five the number of 2ironformulations for intravenous administra -tion in the UK; the others are ferric car-boxymaltose (Ferinject), iron dextran(CosmoFer), iron isomaltoside (Monofer)and iron sucrose (Venofer).

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.

To assess the accuracy of liver iron content (LIC) quantification and grading ability associated with clinical LIC stratification using virtual iron concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit model.Fifty-one rabbits were prepared as iron-loaded models by intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC images were derived from an iron-specific algorithm. Postmortem LIC assessments were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation between VIC and LIC was analyzed. VIC were stratified according to the corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g. Diagnostic performance of stratification was evaluated by receiver operating characteristic analysis.VIC linearly correlated with LIC (r = 0.977, P 0.01). No significant difference was observed between VIC-derived LICs and ICP (P 0.05). For the four clinical LIC thresholds, the corresponding cutoff values of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity (100%) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g.Virtual iron concentration imaging on DECT showed potential ability to accurately quantify and stratify hepatic iron accumulation in the iron overload rabbit model.• Virtual iron concentration (VIC) linearly correlates with liver iron content (LIC). • VIC accurately quantifies LIC. • VIC accurately grades LIC based on clinical LIC stratification.

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.

The aims of the study were to evaluate the effect of iron-dextran injection given on the first, third or fourth day after birth on haematology in piglets. An advanced automated blood analyser; Technicon H*1® , which performs a complete blood cell count and leukocyte differential counts was used to analyse the blood. Six litters of Norwegian Landrace x Yorkshire piglets were included in the study. The day after birth (day 1), half of the piglets in each litter (split litters) were injected subcutaneously with 180 mg iron as iron-dextran (1·5 ml Idofer ® ). The untreated piglets from two of the litters were injected with the same amount of iron-dextran on day 3, and those from the remaining four litters on day 4. The piglets were weighed and blood samples collected on days 1, 3 or 4, 7, 14 and 21. Erythropoiesis, but not leukocyte count, responded to injection on day 1 compared with injection on the third or fourth day. The difference between groups in haematological parameters was greatest on day 7. The two groups of piglets treated on day 1 had a haemoglobin concentration (Hb) ±SD of 92 g litre –1 (±9) and 94 g litre –1 (±9), and the piglets treated on day 3 had a Hb of 81 g litre –1 (±7) and the one treated on day 4 had a Hb of 78 g litre –1 (±7) on day 7. On days 14 and 21 there were no differences between groups. This study indicates that some piglets were anaemic and responded to subcutanous iron injection on day 1.

Iron deficiency in patients with renal failure. The anemia of renal failure is caused by the lack of sufficient quantities of endogenous erythropoietin. With the availability of recombinant human erythropoietin (rHuEPO), however, it has become apparent that to achieve a given target, hematocrit requires proper management of iron replacement, as well as the administration of rHuEPO. Iron deficiency, either absolute or functional, will occur in most, if not all, patients on hemodialysis receiving rHuEPO because of the increased demand for iron driven by the accelerated erythropoiesis that occurs with exogenous rHuEPO administration, coupled with ongoing blood losses from dialyzer and tubing, blood sampling, gastrointestinal blood loss, and blood losses at the time of dialysis needle placement and removal. Blood loss is less of a problem in patients on peritoneal dialysis, but poor iron intake and increased demand for iron are also seen, the latter in patients receiving rHuEPO. It is essential, therefore, for renal health professionals to understand iron metabolism in dialysis patients in order to properly balance the therapy of renal anemia with rHuEPO and supplemental iron.

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.

Background Cutaneous siderosis is accumulation of iron in the dermis and the subcutaneous tissue secondary to extravasation of an intramuscular or intravascular iron injection. It presents as varying shades of brown macules with no distinct contours. The hyperpigmentation is permanent without treatment. Objective Q-switched lasers have been used effectively to treat lentigines and tattoos however, there is little data on the treatment of cutaneous siderosis with lasers. Our objective was to effectively treat cutaneous siderosis with a Q-switched alexandrite laser. Results A 50-year-old female had received nine injections of intramuscular iron dextran, one injection every 2 weeks alternating right buttock and left buttock over the course of 5 months. A couple of weeks after her 9th injection which was on the left, she noted brown hyperpigmentation in the injection area with the left worse than the right. She waited 3 months for the hyperpigmentation to self-resolve before presenting in our clinic. We utilized the Q-switched alexandrite laser to treat the patient with a test spot. One week later, there was nice partial clearance from the test spot so we commenced full treatment of the hyperpigmentation. There was significant improvement after the first treatment and she has been treated 4 times with continued improvement over the past 2 months. Conclusion The Q-switched alexandrite laser is a useful tool in the treatment of cutaneous siderosis secondary to iron injection. Lasers Surg. Med. 47:386–387, 2015. © 2015 Wiley Periodicals, Inc.