Iron Injection Research Articles

The use of zero‐valent iron injection to remediate groundwater: Results of a pilot test at the Marshall Space Flight Center

AbstractIn situ treatability studies are being conducted to evaluate various in situ technologies to manage groundwater contamination at the NASA Marshall Space Flight Center in Huntsville, Alabama. The focus of these studies is to evaluate remediation options for contaminated (mostly aerobic) groundwater occurring within the basal portion of a clayey residuum called the rubble zone. The tension‐saturated media and unsaturated media lying above the rubble zone are also being treated where they make up a significant component of the contaminant mass. An in situ chemical reduction field pilot test was implemented (following bench‐scale tests) during July and August 2000. The test involved the injection of zero‐valent iron powder in slurry form, using the FeroxSM process patented by ARS Technologies, Inc. The pilot test focused on trichloroethene (TCE)‐contaminated groundwater within the rubble zone. Maximum pre‐injection concentrations of about 72,800 micrograms per liter (μg/l) were observed and no secondary sources are believed to exist beneath the area. The potential presence of unexploded ordnance forced an implementation strategy where source area injections were completed, as feasible, followed by overlapping injections in a down gradient alignment to create a permeable reactive zone for groundwater migration. Eight post‐injection rounds of groundwater performance monitoring were completed. The results are encouraging, in terms of predicted responses and decreasing trends in contaminant levels. © 2003 Wiley Periodicals, Inc.

Effects of a Direct Injection of Liposoluble Iron into Rat Striatum. Importance of the Rate of Iron Delivery to Cells

For a better understanding of the role of iron imbalance in neuropathology, a liposoluble iron complex (ferric hydroxyquinoline, FHQ) was injected into striatum of rats. The effects of two modalities of iron injections on brain damage, hydroxyl radical ( ” OH) production (assessed by the salicylate method coupled to microdialysis) and tissue reactive iron level (evaluated ex vivo by the propensity of the injected structure for lipid peroxidation) were examined. Rapid injection of FHQ (10 nmoles of 5 mM FHQ pH 3 solution over 1-min period) but not that of corresponding vehicle led to extensive damage associated with increased tissue free iron level in the injected region. Conversely, neither lesion nor free iron accumulation was observed after slow FHQ injection (10 nmoles of a 100 w M FHQ pH 7 solution over 1-h period) as compared to corresponding vehicle injection. Production of ” OH was induced by slow FHQ injection but not by rapid FHQ injection, probably as a result of in vivo abolition of iron-induced ” OH formation by acid pH. Indeed, rapid injection of FAC pH 7 (ferric ammonium citrate, 5 mM in saline) was associated with ” OH formation whereas rapid injection of FAC pH 3 did not. Our results identify the rate of iron delivery to cells as an important determinant of iron toxicity and do not support a major role for extracellular ” OH in damage associated with intracerebral iron injection.

Apoferritin Attenuates Experimental Allergic Encephalomyelitis in SJL Mice

Ferritin has been shown to attenuate iron-catalyzed oxidative damage in several experimental conditions. Since oxidative damage has been implicated in the pathogenesis of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), an animal model of MS, we tested the hypothesis that ferritin would act to attenuate disease. The experimental design was to increase plasma ferritin levels during the active stage of EAE by giving systemic injections of apoferritin and then compare disease activity between these mice and EAE mice administered vehicle. Additional mice received systemic injections of iron, which induces ferritin synthesis, in order to test the effects of exogenous iron on the disease course. Although plasma levels of ferritin were found to be elevated in both apoferritin and iron-injected EAE mice, only apoferritin treatment resulted in a reduction in disease activity compared to EAE mice given vehicle. The suppressive effects of apoferritin administration suggest that the increase in endogenous ferritin levels that have been previously observed in the cerebrospinal fluid of chronic progressive MS patients with active disease might be functioning to limit the severity and spread of tissue damage.

Screening for iron deficiency.

1. Ann Chen Wu, MD* 2. Leann Lesperance, MD, PhD* 3. Henry Bernstein, DO*† 1. *Pediatric Health Associates, Hunnewell Ground Children’s Hospital 2. †Associate Professor of Pediatrics, Harvard Medical School, Boston, MA After completing this article, readers should be able to: 1. Determine the most common cause of iron deficiency in the United States. 2. Describe the pathogenesis of iron deficiency. 3. List populations at high risk for iron deficiency. 4. Outline the common signs and symptoms of iron deficiency. 5. Specify the American Academy of Pediatrics recommendations for screening for iron deficiency. In the March and April issues of Pediatrics in Review, we published a two-part article on managing anemia in a pediatric office practice. This article expands on the various tests for iron deficiency, including some relatively new ones. These articles should be read as complementary.—RJH Iron deficiency is the most common nutritional deficiency in the world, responsible for a staggering amount of ill health, lost productivity, and premature death. Although its prevalence in the United States has declined since the late 1960s, iron deficiency with or without anemia still is seen frequently in infants, toddlers, adolescent females, and women of childbearing age. In fact, iron deficiency anemia remains the most common hematologic disease of infants and children. Anemia is defined as a low hemoglobin (Hgb) concentration or red blood cell (RBC) mass compared with age-specific norms. Anemia may be caused by decreased RBC production, increased RBC destruction, or blood loss. Based on the size of the RBC, hematologists categorize anemia as macrocytic, normocytic, or microcytic. Iron is found in different compartments within the body. Total body iron (measured by ferritin), transport iron (measured by transferrin saturation), serum iron, and other hematologic and biochemical markers are used to describe the degrees of iron deficiency. Iron depletion refers to the earliest stage of diminishing iron stores in the setting of insufficient iron supply. Iron deficiency (without anemia) develops as these iron stores are depleted further and begin to impair Hgb synthesis. Finally, iron deficiency anemia results …

Red cell mass responses to daily erythropoietin and iron injections in the ovine fetus

Objective: Anemic ovine fetuses supplemented with intra-amniotic iron undergo rapid expansion of red cell mass. The present study tested the hypothesis that nonanemic fetuses that were supplemented with daily intra-amniotic iron plus intravascular injections of erythropoietin would experience accelerated erythrocyte production. Study Design: Nine late gestation ovine fetuses received 100 to 120 units of erythropoietin intravascularly plus 10 mg of iron intra-amniotically daily for 7 days (low erythropoietin dose group). Four additional fetuses received 1000 units of erythropoietin plus 10 mg iron daily for the same period (high erythropoietin dose group). Responses were compared with 9 nonsupplemented time-control fetuses. Statistical testing was by 3-factor repeated measures analysis of variance. Results: Immediately after erythropoietin injection, plasma erythropoietin concentration was elevated approximately 25- and 250-fold in the low and high erythropoietin dose groups, respectively. Erythropoietin returned to basal levels by 24 hours after the injection. Plasma iron concentration increased in the low erythropoietin dose group but not in the control or high erythropoietin dose groups. Reticulocyte index increased in both erythropoietin supplemented groups but not in control fetuses. Hematocrit level increased above control by day 5 in the low erythropoietin dose group and by day 2 in the high erythropoietin dose group. Red cell mass increased significantly on supplement day 7 in the low erythropoietin dose group and on day 5 in the high erythropoietin dose group. Fetal blood gases and pH were unchanged with time in all 3 groups. Conclusion: Although daily combined erythropoietin and iron supplements in nonanemic ovine fetuses significantly increased circulating red cell mass in a dose-dependent manner, this increase was small relative to the rapid expansion of red cell mass previously observed after iron supplementation in fetuses with hemorrhage-induced anemia. We speculate that this difference in response may be due to a combination of rapid fetal clearance of erythropoietin plus a relative insensitivity to erythropoietin caused by the absence of other cytokines, which are elevated during fetal anemia. (Am J Obstet Gynecol 2002;186:315-20.)

Reevaluation of the Necessity of Iron Injection to Newborn Piglets

The growth and immune responses to endotoxin lipopolysaccharide (LPS) challenge (20 µg/kg) of piglets with and without a iron dextran injection (Fe, 200 mg/head) two days after birth are compared. Sixty-four newborn piglets from eight litters were allocated randomly to one of four treatments. The control received no iron dextran and only saline (Sal) injection on the second and fifteenth day after birth (Sal-Sal). The remaining three groups received Fe-Sal, Sal-LPS, Fe-LPS treatments respectively. On fifteen days of age, blood samples of piglets were taken at 0 h, 1 h, 2 h and 4 d after saline or LPS injection to determine immune functions and blood characteristics. The trial terminated when the pig reached 56 days and the average daily gain of piglets was then measured. Daily gain, serum immunoglobulin G (IgG) concentration and red blood cell counts did not vary significantly among the four groups at any measuring times. Serum tumor necrosis factor-α (TNF-α) concentration increased sharply 1 h after LPS injection. However, iron injection did not change TNF-α concentration responds to LPS injection. White blood cell counts of two LPS injection groups were significantly lowered 1 h following the injection. In contrast, serum lactoferrin concentration had increased significantly 1 and 2 h post- injection. Furthermore, iron injection produced no further effects on these two criteria. Iron injection increased the hemoglobin (Hb) concentration of piglets at any measuring time, and LPS injection lowered Hb concentration. In conclusion, a 200 mg/head of iron dextran injection on the second day after birth increased Hb concentration, had no detrimental effect on the immune responses and growth of piglets. Moreover, if creep feed (175 mg Fe/kg feed) is provided from d 7 after birth, the Fe-injection does not contribute to overall performance of piglets and may not be a necessity in practice. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 1 : 79-83)

Domain homologues of dopamine beta-hydroxylase and ferric reductase: roles for iron metabolism in neurodegenerative disorders?

One of the defining characteristics of neurodegenerative diseases, including Parkinson's, Alzheimer's and Huntington's diseases, is abnormal accumulations of iron, specifically in affected areas. Following injection of iron in rat brains, a relatively selective lesion of dopamine neurons, similar to parkinsonism, occurs. These observations indicate that Fe(II)-mediated generation of free radical species, by the Fenton reaction, might contribute to the pathoetiology of these diseases. Iron is known to possess multiple roles in the biosynthesis of catecholamines in dopaminergic neurons. These include, as Fe(II), facilitating the production of dopamine from phenylalanine by tyrosine hydroxylase, and as heme, assisting the recycling of ascorbate by cytochrome b-561 required for the generation of norepinephrine from dopamine by dopamine beta-hydroxylase. In this study, it is demonstrated that a human and mouse gene product, stromal cell-derived receptor 2, is a homologue of cytochrome b-561 and duodenal cytochrome b, and is thus predicted to be active as a ferric reductase. Moreover, this protein also contains a domain homologous to the N-terminal regulatory region of dopamine beta-hydroxylase. These findings from sequence analysis lead to a prediction that stromal cell-derived receptor 2 is a catecholamine-regulated ferric reductase active in the brain. Dysfunction of cytochrome b-561 or stromal cell-derived receptor 2, therefore, might predispose individuals to abnormal accumulation of Fe(III) and/or generation of cytotoxic free radicals as a consequence of a rapid cycling between Fe(III) and Fe(II). The hypothesis that aberrant ferric reductase activities are involved in the progression of neurodegenerative diseases should open up new avenues of research, and possibly therapy, for these devastating diseases.

Quantitative analysis of cell death and ferritin expression in response to cortical iron: implications for hypoxia–ischemia and stroke

Iron that is not bound to storage proteins can catalyse the generation of toxic hydroxyl radicals. Iron can be released from brain storage proteins by hypoxic conditions, such as those that accompany stroke, and the situation can be compounded by iron released from hemoglobin in extravasated blood cells. Despite the neurotoxicity of iron, there is little quantitative data concerning the spatio-temporal extent of its toxicity in vivo. The present study measures the effects of a pathologically relevant concentration of iron (1.0 mM) on neuronal death and on ferritin expression in vivo. Injection of iron (1 μl ferric ammonium citrate) into rat parietal cortex resulted in 7.9-fold more ferritin-labeled cells than did control injections of ammonium citrate at 1 day post-injection. This elevated expression continued for at least 1 week. One day after injection, the mean number of Fluoro-Jade-labeled degenerating neurons in 100 μm sections passing through the center of ferric ammonium citrate injection sites was 664±64. This value was 4.5-fold higher than at ammonium citrate injection sites, and this difference increased to 56-fold by day three. By 5 days post-injection, few dying neurons were observed at the control sites, but neurodegeneration continued beyond a week at the iron-injected sites. Thus, iron released during a brief episode of hypoxia–ischemia or during a stroke may be neurotoxic for a protracted period. Therefore, our findings indicate that it may be beneficial to target iron-induced peroxidation throughout the first few weeks following an intracerebral hemorrhage or an hypoxic–ischemic episode.

Experience with a Large Dose (500 MG) of Intravenous Iron Dextran and Iron Saccharate in Peritoneal Dialysis Patients

To compare efficacy in anemia correction and side effects of large doses of intravenous (IV) iron dextran and iron saccharate preparations in peritoneal dialysis (PD) patients. Tertiary-care teaching hospital of University of Toronto. Retrospective analysis of 379 PD patients who attended PD clinics in past 5 years. Of these 379 patients, 62 were selected to receive IV iron based on ferrokinetic markers of iron deficiency, noncompliance to or ineffectiveness of oral iron, or increased erythropoietin (EPO) requirement. Sixty-one patients received two IV iron injections of 500 mg each, 1 week apart, 33 patients received iron dextran, 23 received iron saccharate, and 5 received both iron dextran and iron saccharate. One patient developed anaphylaxis to a test dose of iron dextran and was excluded from further therapy. Blood samples were collected before and 3 and 6 months after iron infusions. At 3 months, the group's average hemoglobin rose from 98.3+/-18.3 g/L to 110.6+/-16.4 g/L (p < 0.0001). Ferritin rose from 104.9+/-115.4 microg/L to 391.5+/-294.1 microg/L (p < 0.0001), and transferrin saturation from 0.17+/-0.07 to 0.26+/-0.19 (p < 0.0001). Erythropoietin requirements fell from 7278.7 IU/week to 5900 IU/week (p < 0.01). Five of the 34 patients who received iron dextran developed minor side effects and 1 patient had anaphylaxis to the test dose. Of the 23 patients who received iron saccharate, 1 had an anaphylactic reaction and 2 had transient chest pain, which subsided without therapy. Overall, there were more side effects with iron dextran (7.4% of injections) compared to the iron saccharate group (4.3% of injections), but this difference was statistically insignificant. Although statistically insignificant, there was an increase in the number of peritonitis episodes during the 6 months after IV iron infusion, especially with iron dextran, compared to the peritonitis episodes during the 6 months before iron infusions. Our study indicates that IV iron in PD patients is effective in restoring iron stores and in decreasing EPO requirements. One anaphylactic reaction occurred in each group. Our data suggest that as much caution be exercised with iron saccharate as with iron dextran. The slight trend toward increased peritonitis rates after iron infusions needs to be investigated in a larger group of patients.

Extracellular amino acid levels measured with intracerebral microdialysis in the model of posttraumatic epilepsy induced by intracortical iron injection

An iron induced model of posttraumatic chronic focal epilepsy in rats was studied with respect to extracellular amino acids, electrophysiology, and morphology, approx. 6 months after intracortical injection of ferrous chloride. Twenty-six of the twenty-eight (93%) rats developed spontaneous epileptiform EEG-activity and electrical cortical stimulation done in eight animals evoked seizure activity in five animals (62.5%). Epileptic brain tissue displayed significantly higher extracellular interictal levels of aspartate (ASP), compared to normal brain, measured with intracerebral microdialysis. The interictal levels of serine (SER) were significantly higher at the lesion side compared to the contralateral cortex in epileptic animals. Spontaneous elevations of ASP and glutamate (GLU) levels up to 8 times the basal level were found in 4/5 (80%). There was no consistent amino acid pattern following the electrically induced seizures, but in association with more intense seizure activity ASP and GLU were elevated. Histopathologically, the necrotic lesions in the cortex contained small vessels and iron pigment loaded astrocytes. Scattered eosinophilic neurons were found in the hippocampus, bilaterally in 37% of the animals. The results show that a focal epileptiform activity developed in a high percentage of animals that received an intracortical iron injection. The observed amino acid changes in epileptic animals may be involved in the development of seizures in this model of posttraumatic epilepsy.

Effect of iron supplementation on oxidative stress and intestinal inflammation in rats with acute colitis.

In this study, we investigated the effect of intraperitoneal iron dextran (100 mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma alpha-tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats.

Effects of an additional iron injection on growth and humoral immunity of weanling pigs

In a 5-week study, 120 crossbred weaning pigs (age 4 weeks) were used to examine the effects of an additional Fe-injection and immunization moment on the growth and humoral immune response. Pigs were allotted to one of eight treatments based on body weight and litter origin. Factors included: (1) single intramuscular injection (day 3 after birth) vs. double intramuscular injection (days 3 and 21 after birth) of 200 mg Fe; (2) antigen challenge (Keyhole limpet hemocyanin (KLH) and ovalbumin (OA) vs. placebo); and (3) immunization moment (day −1 vs. 1 after weaning). All pigs had free access to prestarter diets supplemented with 80 mg kg −1 Fe as FeSO 4·7H 2O. Pigs were housed in a room consisting of 12 pens (ten pigs per pen). During the experiment, blood hemoglobin (Hb) levels and body weight were determined weekly and total Ig, IgG and IgM titers to KLH and OA twice a week. At day 6 after weaning, the blood Hb levels of double injected pigs were higher ( P<0.01) than the blood Hb-levels of the pigs that had received a single Fe-injection. Prior to day 6 and thereafter, blood Hb levels were similar both for single and double injected groups. Throughout the experiment, the additional Fe-injection, and immunization moment had no effect ( P>0.1) on growth and total Ig response to KLH and OA. But the genotype of the pigs affected ( P<0.05) the kinetics of the total Ig response to KLH and OA. In conclusion, an additional injection of Fe one week prior to weaning does not affect body growth, and does not enhance or support the humoral immunity to a T-cell dependent antigen. Furthermore, the suppressing effect of weaning on humoral immunity was not affected by additional Fe.

Zonisamide reduces the increase in 8-hydroxy-2'-deoxyguanosine levels formed during iron-induced epileptogenesis in the brains of rats.

To examine the change of 8-hydroxy-2'deoxyguanosine (8-OHdG) levels, which are used as a marker for oxidative DNA damage, in iron-induced epileptogenic foci of the rat cerebrum. Male Wistar rats were given a cortical injection of ferric chloride, and their 8-OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8-OHdG levels were compared with the nonpretreated rats. Fifteen minutes after ferric chloride solution injection, the level of 8-OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS, in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8-OHdG levels within the cerebrum 30 minutes after iron solution injection. These results indicate that the formation of iron-induced epileptogenic foci in rats is related to DNA-damage-induced reactive oxygen species and that the inhibition of 8-OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts-induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts-induced acute epileptogenesis.

Effects of iron dextran injections on the incidence of abomasal bloat, clinical pathology and growth rates in lambs

A preliminary study revealed significantly lower serum iron concentrations in lambs that developed abomasal bloat about one week later, than in lambs that did not develop bloat. In a subsequent...

Sequential changes in glutamate transporter protein levels during Fe 3+-induced epileptogenesis

Severe head injury in humans causes recurrent seizures; this form of epilepsy appears to correlate with occurrence of parenchymal hemorrhage. Injection of ferric cations, one component of hemoglobin, into rat amygdala, causes lipid peroxidation, and recurrent spontaneous seizures. We wondered whether regulation of extracellular glutamate might be perturbed as a mechanism of chronic epileptogenesis, therefore levels of glutamate transporter proteins GLT-1, GLAST and EAAC-1 were measured in ipsilateral and contralateral hippocampi removed from rats having spontaneous iron-induced limbic seizures. The neuronal transporter EAAC-1 was elevated bilaterally up to 30 days following the microinjection that initiated seizures. The neuronal transporter EAAC-1 was elevated bilaterally up to 30 days following the microinjection that initiated seizures. The glial transporter GLT-1 increased 5 and 15 days after iron injection on the side contralateral to the injection then returned to basal levels 30 days after the lesion. GLAST also showed an initial increase but at 15 and 30 days after injection, when experimental animals were experiencing spontaneous limbic behavioral seizures, this protein was down-regulated. The results suggest that iron-induced epileptogenesis involves alteration in glial glutamate transport that may lead to enhanced excitation within the hippocampus.

The effects of the 21-aminosteroid U-74389G on spatial orientation in rats after a cerebral oligemic episode and iron-induced oxidative stress.

Oligemic episodes and increased iron concentration have both been proposed as being involved in neurodegenerative diseases. In animal models, a combination of both of these might therefore mimic the clinical pathology in humans. In rats, intrastriatal injections of ferric chloride, FeCl3, one week after a 60-minute oligemic episode, produced by bilateral clamping of the carotid arteries under pentobarbital anaesthesia (BCCA) impaired the animals' learning ability in a water maze task. Median adult rats, after intrastriatal 0.3 microg FeCl3, are impaired when challenged during the first three trial blocks, while after 0.06 microg FeCl3, an impairment is seen during the process of habituation to the challenge. Two-year-old animals do not show any learning effect at all after the combination of BCCA and intrastriatal FeCl3. Lazaroid U-74389G, a potent inhibitor of iron-induced lipid peroxidation, totally prevents the learning impairments in both median adult and aged animals, suggesting that iron-induced lipid peroxidation may be responsible for the late learning deficiencies. However, when U-74389G is applied one week after the oligemic episode but without the additional injection of iron, U-74389G on its own also impairs the animals' learning ability. The present animal model, when applied to clinical studies of lazaroids in humans, does seem able to give reliable information concerning the neuroprotective properties of such drugs.

Manipulation of the Rumen Ecosystem to Support High-Performance Beef Cattle - Review -

Standard industry practices with newborn piglets involve the removal of the young from the sow for short periods to undergo procedures such as teeth and tail clipping, iron injections and vaccination. This study was designed to assess whether the stress of teeth and tail clipping had any long-term effects on growth performance. Piglets were allocated to one of two treatments; to have their teeth and tails clipped, plus other routine husbandry practices either on day 0 or 5 postnatally. The implementation of the husbandry practices elicited an acute vocal response from all piglets irrespective of day of treatment. During the 4 hours after teeth and tail clipping on day 5, milk letdown and suckling behaviour were observed. On day 0, there was a disturbance in suckling behaviour of the litter, particularly in piglets on primiparous sows. Within four hours (or 4 suckling events) the treated piglets had resumed suckling in a manner akin to untreated controls. In contrast, on day 5 sows displayed regular letdown within hourly intervals irrespective of parity and most piglets suckled aggressively. There was no difference between treatments for growth to weaning. For liveweight gain to day 70, there was a tendency for an interaction between treatment and sex (P=0.063). This suggested that while there was no difference in female pig growth performance if they were teeth and tail clipped on day 0 or day 5, male pigs tended to perform better if teeth and tail clipping occurred on day 0 rather than day 5. Cortisol concentration on day 70 reflected these growth responses, although not significantly. The acute stress of teeth and tail clipping and associated husbandry procedures does not compromise piglet growth as long as it is performed close to birth.

The effect of intramuscular iron injections on serum ferritin levels and physical performance in elite netballers

The purpose of this study was to determine the effect of iron supplementation by intramuscular injection on both serum ferritin (SF) levels and exercise performance in iron depleted, non-anaemic elite female netballers. Fifteen iron depleted (Serum Ferritin <40 ug x L(-1). Haemoglobin >125 g x L(-1)) subjects (19+/-3 y) first performed their routine test battery: a vertical jump test, a 10s power and 5x6s repeat sprint test on a cycle ergometer and a 20m multi-stage shuttle run. Subjects were matched on the basis of height, mass, and playing position and then assigned to either a Ferritin Group (FG) or Placebo Group (PG) (single blind design). Subjects then underwent a course of 5x2ml intramuscular injections of either Ferrum H (FG) or normal saline (PG) over a period of 8-10 days before repeating the blood and physical performance tests. Five and 10 days following supplementation, SF levels in the FG increased significantly from baseline levels (P<0.05) and were also significantly greater than levels measured in the PG (P<0.01). Haemoglobin levels remained unchanged in both groups. All test scores remained unchanged from baseline values and were not different between the two groups. These results demonstrate that a course of 5x2ml intramuscular iron injections significantly increased SF concentration within 2 weeks without increasing Hb levels, but this rapid elevation did not enhance the physical performance in selected tests of iron depleted, non-anaemic athletes.

Review of issues relating to iron and infection

Use of erythropoietin (EPO) therapy and iron supplementation has improved the management of anemia in patients with end-stage renal disease (ESRD). As more patients receive supplemental iron, however, concerns are being raised about a potential link between iron and infection. There is biologic plausibility for this link, since iron is a growth factor for bacteria and certain host defense mechanisms are iron-sensitive. Animal models show that injection of iron leads to increased susceptibility to bacterial infection. In some studies, patients with high serum ferritin levels have reduced neutrophil function. However, these studies did not determine whether serum ferritin levels were elevated because of increased iron stores or because of infection. If infection is present, it might cause both the elevated serum ferritin levels and the neutrophil dysfunction. Several clinical studies have found an association between high serum ferritin levels and increased infectious risk. In studies that control for important covariates such as use of catheters and previous infections, the infectious risk associated with iron administration or elevated serum ferritin levels is reduced or eliminated. Collectively, these studies suggest that our current understanding of the relationship between iron and infection is incomplete and further studies are needed. There is no reason to alter current iron treatment strategies based on this literature. Am J Kidney Dis 34:s47-s52, 1999. Copyright © 1999 by National Kidney Foundation

Iron accumulation in the substantia nigra in rats visualized by ultrasound

In recent studies, we have found a marked increase in substantia nigra (SN) echogenicity in patients with Parkinson’s disease (PD) using transcranial ultrasound. Because a substantial body of evidence has accumulated indicating a selective elevation of iron in the SN from patients with PD, we set out to test the hypothesis that trace metals like iron could lead to the observed increase of SN echogenicity in PD. Rat brains were scanned after stereotactic injection of iron in different concentrations into the SN and after injecting ferritin, zinc and 6-OHDA alone, and after the addition of desferrioxamine. The amount of iron in the SN was measured spectroscopically. For iron, and partly for 6-OHDA, in different concentrations, a dose–dependent increase of SN echogenicity could be visualized, corresponding to an increase of iron measured by spectroscopy. No increase of echogenicity was visualized after the injection of ferritin and the addition of desferrioxamine to 6-OHDA, though an increase of iron was measured by spectroscopy. Therefore, we conclude that iron not bound to these proteins may lead to an increase of echogenicity of the SN.