Iron Injection Research Articles

Iron-induced necrotic brain cell death in rats with different aerobic capacity.

Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Our recent study demonstrated that ICH-induced brain injury was greater in low capacity runner (LCR) than in high capacity runner (HCR) rats. The present study examines whether iron-induced brain injury differs between LCRs and HCRs. Adult male LCR and HCR rats had an intracaudate injection of iron or saline. Rats were euthanized at 2 and at 24 h after T2 magnetic resonance imaging, and the brains were used for immunostaining and Western blotting. LCRs had more hemispheric swelling, T2 lesion volumes, blood-brain barrier disruption, and neuronal death at 24 h after iron injection (p < 0.05). Many propidium iodide (PI)-positive cells, indicative of necrotic cell death, were observed in the ipsilateral basal ganglia of both HCRs and LCRs at 2 h after iron injection. PI fluorescence intensity was higher in LCRs than in HCRs. In addition, membrane attack complex (MAC) expression was increased at 2 h after iron injection and was higher in LCRs than in HCRs. The PI-positive cells co-localized with MAC-positive cells in the ipsilateral basal ganglia. Iron induces more severe necrotic brain cell death, brain swelling, and blood-brain barrier disruption in LCR rats, which may be related with complement activation and MAC formation.

Monitoring recovery from iron deficiency using total hemoglobin mass.

Using hemoglobin concentration ([Hb]) to diagnose borderline iron deficiency and monitor the progress of its treatment is difficult because of the confounding effects of plasma volume. Because hemoglobin mass (Hbmass) is not affected by plasma volume, it may be a more sensitive parameter. The aim of this study was to monitor Hbmass, iron storage, and maximal oxygen consumption (V˙O2max) during and after oral iron therapy in subjects with severe and moderate iron deficiency. Three groups of female recreational athletes were monitored for at least 22 wk, as follows: 1) severe iron deficiency group (SID) (n = 8; ferritin, ≤12 ng·mL), 2) moderate iron deficiency group (MID) (n = 14; ferritin, ≤25 ng·mL), and 3) control group (n = 8; ferritin, >25 ng·mL). Hbmass and iron status were determined before, during, and up to 12 wk after at least 10 wk of oral iron supplementation. In total, five V˙O2max tests were performed before, during, and after the supplementation period. Hbmass increased markedly in the SID group (15.6% ± 11.0%, P < 0.001) and slightly in the MID group (2.2% ± 3.7%, P < 0.05) by the end of the supplementation period and remained at this level for the following 12 wk. [Hb] and Hbmass were similarly affected, but Hbmass was more closely related to mean corpuscular volume and mean corpuscular hemoglobin than [Hb]. The SID group incorporated 534 ± 127 mg of iron into ferritin and hemoglobin, whereas the MID group incorporated 282 ± 68 mg of iron. V˙O2max increased only in the SID group by 0.20 ± 0.18 L·min (P < 0.05) and was closely related to Hbmass (P < 0.01). Hbmass is a sensitive tool for monitoring recovery from iron deficiency anemia and assessing the effectiveness of iron supplementation in individuals with severe or moderate iron deficiency.

Impact of the simultaneous implementation of husbandry procedures on suckling piglets

In addition to castration, further husbandry procedures are performed in piglets during the first week of life without anaesthesia. The aim of the present study was to investigate the pain-induced stress of the husbandry procedures castration, tail docking and ear tagging performed in piglets in combination in comparison with castration or handling alone. Furthermore, the effect of the presurgical administration of the nonsteroidal anti-inflammatory drug meloxicam alone or in combination with iron was investigated. The levels of pain and stress were evaluated based on cortisol and catecholamine concentrations, as well as from behavioural observations. The compatibility and the effect of combined drug administration were assessed, and the daily weight gain and blood iron level were determined. When comparing the application procedures, the slight changes observed at the iron injection site were reduced by 40% when using the mixture. After performing all three husbandry procedures without administration of meloxicam (KSO group), higher cortisol concentrations were induced for up to 4hours compared to the handling (H) and castration (K) groups. In piglets receiving meloxicam or the mixture of iron and meloxicam presurgically, the cortisol concentration was significantly reduced for 0.5 hours after castration and up to 4hours following all three husbandry procedures when compared to piglets without medication (groups K and KSO, respectively). The results indicate that the blood cortisol concentration significantly rose due to multiple pain and distress when combining castration, ear tagging and tail docking. Application of meloxicam before performing these husbandry procedures reduced pain equally to its application before castration alone. The application of a mixed preparation of iron and meloxicam did not affect the efficacy of either drug and improved the local tolerance of the iron injection.

Intravenous iron administration and hypophosphatemia in clinical practice.

Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed.

Role of Hemoglobin and Iron in Hydrocephalus After Neonatal Intraventricular Hemorrhage

Neonatal germinal matrix hemorrhage/intraventricular hemorrhage is common and often results in hydrocephalus. The pathogenesis of posthemorrhagic hydrocephalus is not fully understood. To explore the potential role of hemoglobin and iron released after hemorrhage. Artificial cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme oxygenase-1 (HO-1) expression, and the presence of iron were evaluated 24 and 72 hours after injection. A subset of animals was treated with an iron chelator (deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle size and cell death were evaluated. Intraventricular injection of hemoglobin and iron resulted in ventricular enlargement at 24 hours compared with the injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme precursor, did not result in ventricular enlargement after injection into the ventricle. HO-1, the enzyme that releases iron from heme, was increased in the hippocampus and cortex of hemoglobin-injected animals at 24 hours compared with aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased hemoglobin-induced ventricular enlargement and cell death. Intraventricular injection of hemoglobin and iron can induce hydrocephalus. Treatment with an iron chelator reduced hemoglobin-induced ventricular enlargement. This has implications for the pathogenesis and treatment of posthemorrhagic hydrocephalus. aCSF, artificial cerebrospinal fluidDAB, 3,3'-diaminobenzidine-4HClGMH-IVH, germinal matrix hemorrhage/intraventricular hemorrhageHO-1, heme oxygenase-1ICH, intracerebral hemorrhagePBS, phosphate-buffered salineSVZ, subventricular zoneTBST, tris-buffered saline with Tween 20.

Impact of transmammary-delivered meloxicam on biomarkers of pain and distress in piglets after castration and tail docking.

To investigate a novel route for providing analgesia to processed piglets via transmammary drug delivery, meloxicam was administered orally to sows after farrowing. The objectives of the study were to demonstrate meloxicam transfer from sows to piglets via milk and to describe the analgesic effects in piglets after processing through assessment of pain biomarkers and infrared thermography (IRT). Ten sows received either meloxicam (30 mg/kg) (n = 5) or whey protein (placebo) (n = 5) in their daily feedings, starting four days after farrowing and continuing for three consecutive days. During this period, blood and milk samples were collected at 12-hour intervals. On Day 5 after farrowing, three boars and three gilts from each litter were castrated or sham castrated, tail docked, and administered an iron injection. Piglet blood samples were collected immediately before processing and at predetermined times over an 84-hour period. IRT images were captured at each piglet blood collection point. Plasma was tested to confirm meloxicam concentrations using a validated high-performance liquid chromatography-mass spectrometry method. Meloxicam was detected in all piglets nursing on medicated sows at each time point, and the mean (± standard error of the mean) meloxicam concentration at castration was 568.9±105.8 ng/mL. Furthermore, ex-vivo prostaglandin E2 (PGE2) synthesis inhibition was greater in piglets from treated sows compared to controls (p = 0.0059). There was a time-by-treatment interaction for plasma cortisol (p = 0.0009), with meloxicam-treated piglets demonstrating lower cortisol concentrations than control piglets for 10 hours after castration. No differences in mean plasma substance P concentrations between treatment groups were observed (p = 0.67). Lower cranial skin temperatures on IRT were observed in placebo compared to meloxicam-treated piglets (p = 0.015). This study demonstrates the successful transfer of meloxicam from sows to piglets through milk and corresponding analgesia after processing, as evidenced by a decrease in cortisol and PGE2 levels and maintenance of cranial skin temperature.

Reliability of operational data from pig herds and performance ratings by veterinarians and pig farmers collected during telephone interviews for the evaluation of a PCV2 piglet vaccination.

BackgroundThe aim of the present study was to evaluate the feasibility of using a telephone survey in gaining an understanding of the possible herd and management factors influencing the performance (i.e. safety and efficacy) of a vaccine against porcine circovirus type 2 (PCV2) in a large number of herds and to estimate customers’ satisfaction.ResultsDatasets from 227 pig herds that currently applied or have applied a PCV2 vaccine were analysed. Since 1-, 2- and 3-site production systems were surveyed, the herds were allocated in one of two subsets, where only applicable variables out of 180 were analysed. Group 1 was comprised of herds with sows, suckling pigs and nursery pigs, whereas herds in Group 2 in all cases kept fattening pigs. Overall 14 variables evaluating the subjective satisfaction with one particular PCV2 vaccine were comingled to an abstract dependent variable for further models, which was characterized by a binary outcome from a cluster analysis: good/excellent satisfaction (green cluster) and moderate satisfaction (red cluster). The other 166 variables comprised information about diagnostics, vaccination, housing, management, were considered as independent variables. In Group 1, herds using the vaccine due to recognised PCV2 related health problems (wasting, mortality or porcine dermatitis and nephropathy syndrome) had a 2.4-fold increased chance (1/OR) of belonging to the green cluster. In the final model for Group 1, the diagnosis of diseases other than PCV2, the reason for vaccine administration being other than PCV2-associated diseases and using a single injection of iron had significant influence on allocating into the green cluster (P < 0.05). In Group 2, only unchanged time or delay of time of vaccination influenced the satisfaction (P < 0.05).ConclusionThe methodology and statistical approach used in this study were feasible to scientifically assess “satisfaction”, and to determine factors influencing farmers’ and vets’ opinion about the safety and efficacy of a new vaccine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0260-1) contains supplementary material, which is available to authorized users.

Reduced transport potential of a palladium-doped zero valent iron nanoparticle in a water saturated loamy sand

Direct in situ injection of palladium-doped nanosized zero valent iron (Pd-NZVI) particles can contribute to remediation of various environmental contaminants. A major challenge encountered is rapid aggregation of Pd-NZVI and hence very limited mobility. To reduce aggregation and concurrently improve particle mobility, the surface of bare Pd-NZVI can be modified with stabilizing surface modifiers. Selected surface-modified Pd-NZVI has shown dramatically improved stability and transport. However, little is known regarding the effects of aquifer grain geochemical heterogeneity on the transport and deposition behavior of surface-modified Pd-NZVI. Herein, the mobility of surface stabilized Pd-NZVI in two granular matrices representative of model ground water environments (quartz sand and loamy sand) was assessed over a wide range of environmentally relevant ionic strengths (IS). Carboxymethyl cellulose (CMC), soybean flour and rhamnolipid biosurfactant were used as Pd-NZVI surface modifiers. Our results show that, both in quartz sand and loamy sand, an increase in solution IS results in reduced Pd-NZVI transport. Moreover, at a given water chemistry, Pd-NZVI transport is notably attenuated in loamy sand implying that geochemical heterogeneity associated with loamy sand is a key factor influencing Pd-NZVI transport potential. Experiments conducted at a higher Pd-NZVI particle concentration, to be more representative of field conditions, show that rhamnolipid and CMC are effective stabilizing agents even when 1 g/L Pd-NZVI is injected into quartz sand. Overall, this study emphasizes the extent to which variation in groundwater chemistry, coupled with changes in aquifer geochemistry, could dramatically alter the transport potential of Pd-NZVI in the subsurface environment.

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism

AbstractExpression of hepcidin, the hepatic hormone controlling iron homeostasis, is regulated by bone morphogenetic protein (BMP) signaling. We sought to identify which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is responsible for regulating hepcidin gene expression. We studied Bmpr2 heterozygous mice (Bmpr2+/−), mice with hepatocyte-specific deficiency of BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum hepcidin and iron levels, and tissue iron levels did not differ in wild-type mice, Bmpr2+/− mice, and mice in which either BMPR2 or ActR2a was deficient. Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene expression and serum hepcidin levels leading to severe iron overload. Iron injection increased hepatic hepcidin mRNA levels in mice deficient in either BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression. These results suggest that BMP type II receptors, BMPR2 and ActR2a, have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism.

Genetic analysis of the individual pig behaviour in backtests and human approach tests

The most recent development in pig production has focused increasingly on the well-being of the individual pig and animal-friendly housing conditions, i.e. the launch of the group housing of sows in the EU. In this regard, however, standard procedures which may be stressful to the animals and thus have an impact on their health and welfare (i.e. mixing, iron injections, vaccinations) are undertaken in all commercial farm production. Therefore, there is a need to assess individual pig behaviour in such situations and furthermore to take into consideration differences related to age. Hence, in this study, pigs were evaluated for their response to two standardised stress situations—the backtest and the human approach test. The data were collected on one research farm using German Landrace, Large White and crossbred pigs. The backtest (n=1382) was performed on pigs at 12 and 19 days of age and the number of escape attempts (NEA), the duration of escape attempts (DEA) and the latency to the first escape attempt (LEA) were recorded. Additionally, the human approach test was performed four times with weaned pigs (n=1317) and once with gilts (n=272) while recording the latency (LC) of the pigs to touch the human. The heritabilities of the different traits were estimated univariately and correlations between all observed variables were obtained from bivariate analyses with the average information-restricted, maximum-likelihood procedure as implemented in the DMU software package. The random litter effect had the largest impact on the LEA backtest variable (15%). Smaller values for NEA and DEA were obtained. The LEA backtest variable and the LC variable of the human approach test of weaned pigs and gilts were not influenced by the litter effect. The highest heritability was estimated for LEA (h2=0.29) and NEA (h2=0.19), followed by DEA (h2=0.10) and the heritability of the human LC approach test variable of weaned pigs was similar with h2=0.20. However, the heritability of the LC of gilts was low (h2=0.03) but the estimation provide no reliable values due to the small number of gilts. The genetic correlations between LEA and DEA were very high (rp=−0.88). Also, the first and second backtests for all variables were highly genetically correlated (rp=0.69–0.90). This means that the variables and the first and second backtests shared the same genetic base. Therefore, performing just one backtest is sufficient for practical breeding purposes. The genetic correlations between four LC human approach test variables of the weaned pigs were very high (rp=0.65–0.87) especially between consecutive tests. Hence, under practical conditions, the performance of one human approach test might be sufficient since the behaviour shown in all the human approach tests with weaned pigs depended on the same genetic base. The genetic correlations between backtest variables and human approach test variables of weaned pigs and gilts were very low, which indicates that both tests partly measure different behavioural patterns and that the reactions of the pigs in the tests were not related.

Conceptual Site Model Development and Phased Remedy Implementation to Achieve Vapor Screening Goals at a Former Dry Cleaner

Tetrachloroethene (PCE) releases at a former dry cleaner resulted in impacts to soil and shallow groundwater beneath and adjacent to the building. Subsurface impacts led to vapor intrusion with PCE concentrations between 900 and 1,200 micrograms per cubic meter (μg/m3) in indoor air. The migration pathways of impacted soil vapor were evaluated through implementation of a helium tracer test and vapor sampling of an exterior concrete block wall. Results confirmed that the concrete block wall acted as a conduit for vapor intrusion into the building. A combination of remediation efforts focused on mass reduction in the source area as well as mitigation efforts to inhibit vapor migration into the building. Excavation of soils beneath the floor slab and installation of a spray-applied vapor barrier resulted in PCE concentrations in indoor air decreasing by over 97.9 percent. Operation of an active ventilation system installed under the floor slab and groundwater remediation via injections of nano-scale zero valent iron (nZVI) further reduced PCE concentrations in indoor air by over 99.8 percent compared to baseline conditions. While significant reductions of PCE concentrations in groundwater were observed within two months after injection, maximum reductions to PCE concentrations in indoor air were not observed for an additional 12 months. © 2014 Wiley Periodicals, Inc.

Identification and characterization of a Macrobrachium nipponense ferritin subunit regulated by iron ion and pathogen challenge

Ferritin, a major iron storage protein in most living organisms, plays a crucial role in iron metabolism. In this study, the ferritin subunit MnFer was identified in the oriental river prawn (Macrobrachium nipponense) and functionally characterized. The full-length cDNA of MnFer is 999 bp in size with a 122-bp 5′-untranslated region (UTR), a 364-bp 3′-UTR and a 513-bp open reading frame that encodes a protein possessing 171 amino acids and a deduced molecular weight of 19.40 kDa. Prawn ferritin transcripts are expressed in muscle, heart, hepatopancreas, gill, hemocytes, ovary and testis. Quantitative real-time PCR revealed that the abundance of ferritin transcript was highest in the hepatopancreas followed by muscle. Ferritin transcript expression in muscle increased six-fold 3 h after the injection of iron. In the gill, a four-fold increase in ferritin transcript expression was detected 3 h post-injection; the expression remained elevated for 48 h. Heart ferritin mRNA expression increased up to seven-fold at 24 h post-injection. No significant difference was found in the hepatopancreas. The iron binding capacity of recombinant ferritin protein was also demonstrated in this study. In hemocyte experiments, the transcriptional expression of MnFer showed the strongest response to Aeromonas hydrophila. As a whole, our study suggested that the ferritin from M. nipponense may play critical roles in cellular and organismic iron homeostasis along with in innate immune defense.

Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

Electrically released iron for fouling control in membrane bioreactors: A double-edged sword?

Iron injection through electrolytically mediated oxidative dissolution of an iron electrode has been proposed as a convenient means of inducing coagulation of wastewater contaminants and thereby reducing the extent of membrane fouling in membrane bioreactors (MBRs). In order to investigate the effect of electrically released iron on membrane fouling propensity, alginate was selected as a model soluble microbial product, and the impact of electrolyzed iron on the specific resistance to filtration (SRF) quantified for a range of electrolysis times. It was confirmed that ferrous iron (Fe(II)) was initially released with concentration increasing proportionally with time of application of electric current in agreement with Faraday's Law. The fouling propensity of alginate increased at early loading times due to the formation of alginate gels and highly stabilized colloidal species. The presence of calcium ions was found to exacerbate this gelation process as a result of i) alginate bridging by Ca2+ ions, and ii) the reduced capacity of the alginate to bind iron and stabilize iron oxide particles. Significant reduction in fouling propensity was observed at higher iron loadings as a result of the formation of substantive amounts of iron oxides which, most likely, adsorbed alginate and prevented gel formation.

Transport of carbon colloid supported nanoscale zero-valent iron in saturated porous media

Injection of nanoscale zero-valent iron (nZVI) has recently gained great interest as emerging technology for in-situ remediation of chlorinated organic compounds from groundwater systems. Zero-valent iron (ZVI) is able to reduce organic compounds and to render it to less harmful substances. The use of nanoscale particles instead of granular or microscale particles can increase dechlorination rates by orders of magnitude due to its high surface area. However, classical nZVI appears to be hampered in its environmental application by its limited mobility. One approach is colloid supported transport of nZVI, where the nZVI gets transported by a mobile colloid. In this study transport properties of activated carbon colloid supported nZVI (c-nZVI; d50=2.4μm) are investigated in column tests using columns of 40cm length, which were filled with porous media. A suspension was pumped through the column under different physicochemical conditions (addition of a polyanionic stabilizer and changes in pH and ionic strength). Highest observed breakthrough was 62% of the injected concentration in glass beads with addition of stabilizer. Addition of mono- and bivalent salt, e.g. more than 0.5mM/L CaCl2, can decrease mobility and changes in pH to values below six can inhibit mobility at all. Measurements of colloid sizes and zeta potentials show changes in the mean particle size by a factor of ten and an increase of zeta potential from −62mV to −80mV during the transport experiment. However, results suggest potential applicability of c-nZVI under field conditions.

Nanoscale zero-valent iron flakes for groundwater treatment

Even today the remediation of organic contaminant source zones poses significant technical and economic challenges. Nanoscale zero-valent iron (NZVI) injections have proved to be a promising approach especially for source zone treatment. We present the development and the characterization of a new kind of NZVI with several advantages on the basis of laboratory experiments, model simulations and a field test. The developed NZVI particles are manufactured by milling, consist of 85 % Fe(0) and exhibit a flake-like shape with a thickness of <100 nm. The mass normalized perchloroethylene (PCE) dechlorination rate constant was 4.1 × 10−3 L/g h compared to 4.0 × 10−4 L/g h for a commercially available reference product. A transport distance of at least 190 cm in quartz sand with a grain size of 0.2–0.8 mm and Fe(0) concentrations between 6 and 160 g/kg (sand) were achieved without significant indications of clogging. The particles showed only a low acute toxicity and had no longterm inhibitory effects on dechlorinating microorganisms. During a field test 280 kg of the iron flakes was injected to a depth of 10–12 m into quaternary sand layers with hydraulic conductivities ranging between 10−4 and 10−5 m/s. Fe(0) concentrations of 1 g/kg (sand) or more [up to 100 g/kg (sand)] were achieved in 80 % of the targeted area. The iron flakes have so far remained reactive for more than 1 year and caused a PCE concentration decrease from 20.000–30.000 to 100–200 µg/L. Integration of particle transport processes into the OpenGeoSys model code proved suitable for site-specific 3D prediction and optimization of iron flake injections.

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

Thrombin and iron are two major players in intracerebral hemorrhage-induced brain injury and our recent study found that thrombin contributes to hydrocephalus development in a rat model of intraventricular hemorrhage (IVH). This study investigated the role of red blood cell (RBC) lysis and iron in hydrocephalus after IVH. There were three parts to this study. First, male Sprague-Dawley rats received an injection of saline, packed, or lysed RBCs into the right lateral ventricle. Second, rats had an intraventricular injection of iron or saline. Third, the rats received intraventricular injection of lysed RBCs mixed with deferoxamine (0.5 mg in 5 μL saline) or saline. All rats underwent magnetic resonance imaging at 24 hours and were then euthanized for brain edema measurement, western blot analysis, or brain histology. We found that intraventricular injection of lysed RBCs, but not packed RBCs, resulted in ventricular enlargement and marked increases in brain heme oxygenase-1 and ferritin at 24 hours. Intraventricular injection of iron also resulted in ventricular enlargement and ventricular wall damage 24 hours later. Coinjection of deferoxamine reduced lysed RBC-induced ventricular enlargement (P<0.01). These results suggest that iron, a degradation product of hemoglobin, has an important role in hydrocephalus development after IVH.

Two Kinds of Ferritin Protect Ixodid Ticks from Iron Overload and Consequent Oxidative Stress

Ticks are obligate hematophagous parasites that have successfully developed counteractive means against their hosts' immune and hemostatic mechanisms, but their ability to cope with potentially toxic molecules in the blood remains unclear. Iron is important in various physiological processes but can be toxic to living cells when in excess. We previously reported that the hard tick Haemaphysalis longicornis has an intracellular (HlFER1) and a secretory (HlFER2) ferritin, and both are crucial in successful blood feeding and reproduction. Ferritin gene silencing by RNA interference caused reduced feeding capacity, low body weight and high mortality after blood meal, decreased fecundity and morphological abnormalities in the midgut cells. Similar findings were also previously reported after silencing of ferritin genes in another hard tick, Ixodes ricinus. Here we demonstrated the role of ferritin in protecting the hard ticks from oxidative stress. Evaluation of oxidative stress in Hlfer-silenced ticks was performed after blood feeding or injection of ferric ammonium citrate (FAC) through detection of the lipid peroxidation product, malondialdehyde (MDA) and protein oxidation product, protein carbonyl. FAC injection in Hlfer-silenced ticks resulted in high mortality. Higher levels of MDA and protein carbonyl were detected in Hlfer-silenced ticks compared to Luciferase-injected (control) ticks both after blood feeding and FAC injection. Ferric iron accumulation demonstrated by increased staining on native HlFER was observed from 72 h after iron injection in both the whole tick and the midgut. Furthermore, weak iron staining was observed after Hlfer knockdown. Taken together, these results show that tick ferritins are crucial antioxidant molecules that protect the hard tick from iron-mediated oxidative stress during blood feeding.

Long-term efficacy of postpartum intravenous iron therapy.

Background. The potential benefits of administering a dose of intravenous iron in patients with moderate postpartum anaemia rather than oral iron alone remains unproven. Aims. To determine whether a single injection of intravenous iron followed by a 6-week course of oral iron is as effective over 6 months in restoring normal haemoglobin levels and replenishing iron stores in women with moderate postpartum anaemia as a course of oral iron alone in women with mild postpartum anaemia. Materials and Methods. Retrospective two-arm cohort study in women with mild postpartum anaemia (haemoglobin 9.6–10.5 g/dL) prescribed iron daily for 6 weeks (N = 150) and women with moderate postpartum anaemia (haemoglobin 8.5–9.5 g/dL), given a single 500 mg injection of intravenous iron followed by iron daily for 6 weeks (N = 75). Haemoglobin and ferritin were measured 6 months postpartum. Results. Haemoglobin returned to similar mean levels in both groups. Ferritin levels were statistically significantly higher in the intravenous + oral group (57.7 ± 49.3 μg/L versus 32.9 ± 20.1 μg/L). Conclusions. Despite lower baseline haemoglobin, intravenous iron carboxymaltose was superior to oral iron alone in replenishing iron stores in moderate postpartum anaemia and may prove similarly beneficial in mild postpartum anaemia.

Nanoscale intracortical iron injection induces chronic epilepsy in rodent

We studied the electrophysiological, hemodynamic, and cytomorphological consequences of microhemorrhagic brain injury induced by a nanoscale iron injection. Of particular interest were the etiology, development, and treatment of epilepsy associated with this injury. We developed an animal model of chronic epilepsy using nanoscale injection into the adult mouse cortex. Although injection of nanoamounts of iron did not cause clear cell death or damage in the cortex, it elicited varying degrees of spontaneous epileptiform events that could be recorded under anesthesia 3 months postinjection. The influence of these chronic epileptiform events on neurovascular coupling was probed by directly stimulating the cortex ipsilateral to the epileptic focus and by measuring cerebral blood volume simultaneously in both hemispheres using intrinsic signal optical imaging. The ipsilateral hemodynamic response was dramatically lower in animals that exhibited longer, more frequent epileptiform events, but it was unchanged in animals displaying infrequent, short events. In contrast, the contralateral hemodynamic response was augmented in all iron-injected animals compared with the control group. These abnormal hemodynamic responses in chronically epileptic animals were correlated with the degree of reduction in the number of GABAergic interneurons. Therefore, nanoscale iron injection, which mimics some aspects of microhemorrhagic brain injury, generated chronic, yet varying, degrees of spontaneous epileptiform events. Moreover, the severity of the epileptiform events corresponded to the degree of reduction in GABAergic interneurons in the iron-injected hemisphere and the level of autoregulatory dysfunction of cerebral blood flow. © 2013 Wiley Periodicals, Inc.