Injection Of Iron Oxide Research Articles

Pharmaceutical stability of colloidal saccharated iron oxide injection in normal saline

BackgroundColloidal saccharated iron oxide injection is used for the treatment of iron deficiency anemia in patients with a poor oral intake. Because of the poor stability of the colloid particle, there have been concerns regarding its compatibility with various injections in clinical practice. To assess the stability of colloidal saccharated iron oxide in normal saline as a diluent, pharmaceutical stability analyses were conducted using various concentrations of glucose and sodium chloride (NaCl).MethodsColloidal saccharated iron oxide injection was diluted in three different diluents (5% glucose solution, normal saline, and 10% NaCl solution), and its appearance, colloid particle diameter, and pH were assessed. Free iron ions, which cause adverse effects, such as nausea and vomiting, were separated from the colloid particle using a dialysis membrane for 24 h, and their concentration was determined.ResultsNo difference in the appearance, colloid diameter, and free iron ion fraction was observed after dilution in 5% glucose solution and normal saline. Conversely, an increased colloid aggregation and iron ion release were observed after dilution in 10% NaCl solution. Although iron colloid is unstable in acidic conditions (pH 4.0–6.0), normal diluents such as 5% glucose and normal saline did not cause colloid destabilization by pH change (pH > 8.0).ConclusionNormal saline may be used as a diluent of colloidal saccharated iron oxide injection as well as glucose solution, which is recommended by the pharmaceutical company. Therefore, normal saline can be used as a diluent of colloidal saccharated iron oxide injection in patients with an underlying disease, such as diabetes mellitus, who are difficult to use glucose solution as a diluent.

Investigation the effect of Fe3O4 nanoparticles on liver and stress oxidative parameters at the presence of magnetic field in rat

Objective(s): This study was designed to evaluate the effect of Fe3O4 nanoparticles at presence of a constant magnetic field on rat liver and some stress oxidative parameters.Materials and Methods: Fe3O4 nanoparticles were synthesized by co-precipitation method using iron chloride (III) and iron sulphate (II). The nanoparticles properties were studied by XRD and TEM. Fourty male wistar rats were randomly divided into four groups. First group was injected with normal saline (control). Second group was injected with Fe3O4 nanoparticles (100 mg/kg). Third group was treated under a constant magnetic field and fourth group was treated with both of Fe3O4 nanoparticles injection and constant magnetic field (all injections are intra peritoneally). Liver parameters (ALT, AST, Total protein, Bilirubin) and some stress oxidative parameters such as SOD and GPX were measured for all groups, 15 and 30 days post injection.Results: The size of the synthesized nanoparticles was determined 14 nm. The crystalline structure of the nanoparticles was spinel. Serum concentration of ALT and AST were changed in some groups compared with the control group. At the presence of constant magnetic field and iron oxide injection, the amount of total protein and bilirubin significantly increased compared with that of control group. The enzyme activity of SOD and GPX haven’t changed compared to the control group.Conclusion: The results of this investigation show that this concentration of iron oxide nanoparticles (100 mg/kg) have not irreversible toxic effects at the level of liver parameters. Also, they have not any serious effects on the SOD and GPX enzyme activity even at presence of a constant magnetic field.

Cellular magnetic resonance imaging for the differentiation of infectious and degenerative vertebral disorders: Preliminary results

To evaluate macrophage imaging using the ability of superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) to differentiate infectious vertebral osteomyelitis and degenerative disk-related inflammatory endplates. The in vivo demonstration of the different distribution of macrophages in those two disorders may allow a more accurate characterization of vertebral endplate abnormalities than classical extracellular MR changes. In 12 patients with endplate abnormalities (six cases of bacteriologically proven spondylodiscitis, six cases of disk degeneration-related endplate changes), two MRI sessions were realized: before and 24 hours after injection of SPIO. The signal-to-noise ratio (SNR) of endplates were qualitatively and quantitatively compared on pre- and post-SPIO injection T1 and T2-weighted (T2w) MR images (Wilcoxon signed rank test). In the infection group, the SNR of abnormal endplates showed a significant signal loss on T2w MR images (P = 0.03) but not on T1w images (P = 0.46). In the degenerative spine group, no significant signal loss was observed on T1 (P = 0.6) nor on T2w MR images (P = 0.6). Signal loss was only visually observable in abnormal endplate in one patient of the spondylodiscitis group on T2w MR images. MRI of the spine with iron oxide injection differentiates infection from aseptic inflammation on quantitative analysis, but the use of SPIO makes direct visual evaluation less satisfactory.

Longitudinal Tracking of Recipient Macrophages in a Rat Chronic Cardiac Allograft Rejection Model With Noninvasive Magnetic Resonance Imaging Using Micrometer-Sized Paramagnetic Iron Oxide Particles

Long-term survival of heart transplants is hampered by chronic rejection (CR). Studies indicate the involvement of host macrophages in the development of CR; however, the precise role of these cells in CR is unclear. Thus, it is important to develop noninvasive techniques to serially monitor the movement and distribution of recipient macrophages in chronic cardiac allograft rejection in vivo. We have employed a rat heterotopic working-heart CR model for a magnetic resonance imaging experiment. Twenty-one allograft (PVG.1U-->PVG.R8) and 9 isograft (PVG.R8-->PVG.R8) transplantations were performed. Recipient macrophages are labeled via intravenous injection of micron-sized paramagnetic iron oxide particles (0.9 microm in diameter) at a dose of 4.5 mg Fe per rat 1 day before transplantation. Serial in vivo magnetic resonance images were acquired for up to 16 weeks. The migration of labeled recipient cells in our CR model, in which cardiac CR is evident at 3 weeks and most extensive by 16 weeks after transplantation, can be assessed with the use of in vivo magnetic resonance imaging for >100 days after a single micron-sized paramagnetic iron oxide injection. The location and distribution of labeled recipient cells were confirmed with magnetic resonance microscopy and histology. This approach may improve our understanding of the immune cells involved in CR and the management of heart transplantation. Moreover, this study demonstrates the feasibility of noninvasively observing individual targeted cells over long time periods by serial in vivo magnetic resonance imaging.

Cardiovascular MRI: A Literature Review

Substrate-based catheter ablation of post-myocardial infarction ventricular tachycardia requires delineation of the scarred myocardium, typically using an electroanatomic mapping (EAM) system. Cardiac magnetic resonance imaging (MRI) might facilitate this procedure by localizing this myocardial scar. In a series of in vitro and in vivo experiments, the authors evaluated the feasibility of integrating 3D MRI and EAM data to guide real-time left ventricular (LV) catheter manipulation. A custom program was employed to integrate 3D MRI datasets with real-time EAM. Initially, a plastic model of the LV was used to determine the optimal alignment/registration strategy. To determine the in vivo accuracy of the registration process, ablation lesions were directed at iatrogenic MRI-visible ‘‘targets’’ (iron oxide injections) within normal porcine LVs. Finally, this image integration strategy was assessed in a porcine infarction model by targeting ablation lesions to the scar border. Results: The in vitro experiments revealed that registration of the LV alone results in inaccurate alignment due primarily to rotation along the chamber’s long axis. Inclusion of the aorta in the registration process rectified this error. In the iron oxide injection experiments, the ablation lesions were 1.8 ± 0.5 from the targets. In the porcine infarct model, the catheter could be reliably navigated to the mitral valve annulus, and the ablation lesions were uniformly situated at the scar borders.

Spatial specificity of cerebral blood volume-weighted fMRI responses at columnar resolution

The spatial specificity of functional magnetic resonance imaging (fMRI) signals to columnar architecture remains uncertain. At columnar resolution, the specificity of intrinsic cerebral blood volume (CBV) response to orientation-selective columns in isoflurane-anesthetized cats was determined for CBV-weighted fMRI signals after injection of iron oxide at a dose of 10 mg Fe/kg. CBV-weighted fMRI data were acquired at 9.4 T with an in-plane resolution of 156 × 156 μm 2 in area 18 during visual stimulation at two orthogonal orientations. A 1-mm-thick imaging slice was selected tangential to the cortical surface. Regions with large CBV changes in response to two orthogonal orientation gratings were highly complementary. Maps of iso-orientation domains in response to these gratings were highly reproducible, suggesting that CBV-weighted fMRI has high sensitivity and specificity. The average distance between iso-orientation domains was 1.37 ± 0.28 mm ( n = 10 orientations) in an anterior–posterior direction. CBV-weighted fMRI signal change in the iso-orientation domains induced by preferred orientation was 1.69 ± 0.24 ( n = 10) times larger than that induced by orthogonal orientation. Our data demonstrate that CBV regulates at a submillimeter columnar scale and CBV-weighted fMRI has sufficient specificity to map columnar organization in animals.

Integration of cardiac magnetic resonance imaging with three-dimensional electroanatomic mapping to guide left ventricular catheter manipulation: Feasibility in a porcine model of healed myocardial infarction

In a series of in vitro and in vivo experiments, we evaluated the feasibility of integrating three-dimensional (3D) magnetic resonance imaging (MRI) and electroanatomic mapping (EAM) data to guide real-time left ventricular (LV) catheter manipulation. Substrate-based catheter ablation of post-myocardial infarction ventricular tachycardia requires delineation of the scarred myocardium, typically using an EAM system. Cardiac MRI might facilitate this procedure by localizing this myocardial scar. A custom program was employed to integrate 3D MRI datasets with real-time EAM. Initially, a plastic model of the LV was used to determine the optimal alignment/registration strategy. To determine the in vivo accuracy of the registration process, ablation lesions were directed at iatrogenic MRI-visible "targets" (iron oxide injections) within normal porcine LVs (n = 5). Finally, this image integration strategy was assessed in a porcine infarction model (n = 6) by targeting ablation lesions to the scar border. The in vitro experiments revealed that registration of the LV alone results in inaccurate alignment due primarily to rotation along the chamber's long axis. Inclusion of the aorta in the registration process rectified this error. In the iron oxide injection experiments, the ablation lesions were 1.8 +/- 0.5 mm from the targets. In the porcine infarct model, the catheter could be reliably navigated to the mitral valve annulus, and the ablation lesions were uniformly situated at the scar borders. These data suggest that registration of pre-acquired magnetic resonance images with real-time mapping is sufficiently accurate to guide LV catheter manipulation in a reliable and clinically relevant manner.

Double contrast MRI of thermally ablated liver metastases.

To investigate the ability of double contrast MRI (enhancement with iron oxide and gadopentetate dimeglumine) to increase the difference in contrast between various tissues after thermal ablation of liver metastases. 12 patients were imaged after MR-guided laser-induced thermotherapy (LITT). Imaging was performed with a 1.5T MR system. Nonenhanced, iron oxide-enhanced and double contrast images were acquired using T (1)-weighted GRE and T (2)-weighted TSE sequences. Iron oxide imaging was performed 10 min after injection of 1.4 ml ferucarbotran (Resovist(R), Schering AG Berlin, Germany) and double contrast imaging 60 sec after the additional injection of 0.1 mmol/kg body weight gadopentetate dimeglumine (Magnevist(R), Schering AG Berlin, Germany). Qualitative and quantitative assessment was performed on induced necroses, residual or recurrent tumor tissue and metastatic tissue untreated at the time of the study. Iron oxide-enhanced T (1) GRE images demonstrated the highest contrast between ablated hyperintense tissue and iron accumulating and resultant hypointense liver parenchyma. Due to Gd enhancement, double contrast T (1)-weighted GRE images displayed the highest change in signal intensity in vital tumor tissue compared to ablated tissue and iron oxide accumulating liver parenchyma (p < 0.01). First observations indicate that LITT of hepatic metastases can be better followed with double contrast MRI, which displays increased contrast due to Gd enhancement of perfused tumor tissue and signal intensity loss in iron oxide accumulating hepatic parenchyma. Induced necrosis does not change its signal intensity at all after injection of iron oxide and Gd-containing contrast media.

Mechanisms of accumulation of small particles of iron oxide in experimentally induced osteosarcomas of rats: a correlation of magnetic resonance imaging and histology. Preliminary results.

This study was conducted to investigate the distribution and kinetics of small particles of iron oxide in osteosarcoma-like tumors. Magnetic resonance (MR) imaging was performed in eight athymic nude rats with an experimentally induced osteosarcoma of the right hind leg immediately after intravenous injection of a superparamagnetic iron oxide preparation. Five animals received 150 mumol iron oxide/ kg and three received 50 mumol iron oxide/kg. The iron oxide preparation consisted of polythylenglycol-coated particles with a core diameter of 6 to 8 nm. The MR images were correlated with histologic slices of the tumors. The tumors accumulated iron oxide rapidly. A marked decrease in signal intensity, preferentially along the periphery of the tumor, was followed by a partial return of the signal intensity within the first minute. The maximum signal decrement throughout the entire tumor exceeded 41% and 21% with one dose each of 150 mumol iron/kg and 50 mumol iron/kg, respectively. The rate of return depended on the injected dose and tumor area, with the signal intensity approaching the initial value before the injection of iron oxide after 45 minutes. Histologic correlation only showed deposition of contrast medium in the proliferative areas of the tumors, mainly confined to the tumor margin. In addition to a predominantly extracellular deposition, intracellular storage could be detected. The findings help to advance the understanding of the distribution and kinetics of intravenous-injected small particles of iron oxide in osteosarcoma-like tumors. A first-pass accumulation of iron oxide could be documented by MR imaging in the periphery of osteosarcomas. Due to sieving of iron oxide particles by liver, spleen, and bone marrow, the signal intensity at 45 minutes after the injection of iron oxide returned to 89% (150 mumol iron oxide/kg) and 95% (50 mumol iron oxide/kg) of the preinjection intensity.

Wall surface leakage effects on magnetohydrodynamic power generator performance

Internal surface-leakage effects on magnetohydrodynamic power generator performance were studied using a combined experimental and analytical approach. A method to determine the wall resistance and slag layer conductivity distributions from seed shutoff test data is introduced. These measured resistance values were then utilized in generator performance analyses. Calculated generator variables were compared with measured data to verify the modeling approach. Finally, these calculated results were used to investigate the distribution of internal leakage currents as a function of generator size, generator operating conditions, and iron oxide injection rates. An advantage of this analysis methodology is the ability to differentiate wall leakage from apparent leakage effects in the measured test data.

Desilconization reaction of pig iron with high FeO containing blast furnace slag under pressurized and coke-coexisting condition.

For the quantitative investigation of the desiliconization inside blast furnace by the iron oxide injection through tuyeres, fundamental researches on the desiliconization reaction by high FeO containing slag under pressurized and coke-coexisting condition were performed by the use of a pressurized high frequency furnace. Under coke-coexisting condition, FeO not only reacts with silicon in hot metal but also simultaneously reacts with coke through the direct reduction reaction and the decrease of temperature and the increase of total pressure accelerates the desiliconization reaction through suppression of the direct reduction reaction. The increase of the amount of slag and the increase of slag basicity result in the enhancement of the desiliconization.Based on the results of fundamental researches, an unsteady state desiliconization mathematical model was developed with consideration of the coupled reactions of desiliconization and direct reduction and successively applied to the quantitative analysis of the coupled reactions.A test operation with dry iron ore dust was performed under almost constant pig iron temperature at Wakayama No. 4 blast furnace. A decrease of silicon content of 0.09% was obtained by the iron ore injection rate of 32 kg/pt without carryover of the injected iron ore to the hearth. Accordingly, the desiliconization by the iron ore injection was verified in the commercial test operation.

Dephosphorization kinetics and reaction region in hot metal during lime injection with oxygen.

To improve dephosphorization of hot metal by the lime injection process, it is necessary to clarify the dissolution mechanism of blown-in CaO in hot metal, the mechanism o f dephosphorization reaction and the region where the reaction takes place. For this purpose, a single-crystal lime lump immersion test and a lime powder injection test were made. Lime lumps after immersion tests, reaction products adhered to Al2O3 tubes immersed into hot metal and collected slag samples by steel samples were analyzed by EPMA.In hot metal, CaO starts to dissolve due to penetration o f FetO and MntO. Then, the dephosphorization reaction initiates between {CaO-Fe (Mn)tO}l and phosphorus, and the latter is fixed as (CaO-SiO2 P2O5)s in the reaction layers. Dephosphorization takes place mainly in the vicinity of the oxygen blowing nozzle.The slagging rate of solid CaO decreases with increasing distance between the nozzle and the suspending position of CaO since carbon in hot metal consumes oxygen. The dephosphorization rate also decreases with increasing distance since FetO in {CaO-Fe (Mn)tO}l is reduced by carbon.It is concluded that the increases both in the slagging rate of solid lime and oxygen potential in the bath is necessary to enhance the dephosphorization rate and in this sense, the injection of iron oxide with oxygen is effective.

Electron microscopy of the effect of gram-negative endotoxin on the blood-brain barrier.

AbstractStudies with the light microscope (Am. J. Path., 34: 631, '58) indicated that an injection of endotoxin into the carotid artery of a rabbit alters the blood‐brain barrier allowing the distribution of subsequently injected colloidal iron throughout the cerebral cortex. The present investigation by electron microscopy determined the distribution of the colloidal iron oxide in the normal and endotoxin altered cerebral capillaries of rabbits. Four hours prior to the intracarotid injection of saccharated iron oxide the animal received an injection via the same artery of either 50 μg gram‐negative endotoxin or a control dose of normal saline. The animals were sacrificed at times from 15 minutes to two hours after the injection of iron oxide and samples of the cerebral cortex were processed for electron microscopy by routine methods. In those animals that did not receive endotoxin, the colloidal iron was limited to the lumen of the cerebral capillaries and occasional large endothelial vacuoles. None of the iron was found in the endothelial pinocytotic vesicles. In the endotoxin animals the iron oxide particles were found in quantity in the capillary endothelium phagosomes, the basement membrane, and in astrocytes and their processes. The fine structure of the cerebral capillary is reviewed and evidence is presented in support of the hypothesis that the barrier mechanism for colloidal tracers lies in a unique property of the brain's endothelial pinocytotic vesicles.

STUDIES ON THE DRUG-FASTNESS OF RAT-BITE FEVER SPIROCHETE, &lt;i&gt;SPIROCHAETA MORSUS-MURIS&lt;/i&gt;

If mice infected with rat-bite fever spirochete, either the human or ermine strain, are repeatedly treated with a neotrepol (bismuth preparation), it is not difficult to produce the spirochete resistant to bismuth. The biological modification in the bismuth- fast strain thus produced was studied by its comparison with the original strain in virulence and chemotherapeutic biology. We carried out the present experiments with the ermine strain of Spirochaeta morsus-muris and the results obtained are summarized as follows:1. The rat-bite fever spirochete rendered resistant to neotrepol is also resistant to the other bismuth preparations, as muthanol and casbis. This neotrepol-fastness therefore may be considered as the bismuth-fastness.2. The Bi-fast strain is still resistant to bismuth after 50 passages through mice for about 2 years.3. This Bi-fastness developed in the mouse body is positively retained, if the resistant strain is transferred to the rat body.4. When mice infected with the Bi-fast strain are repeatedly treated with compounds of the other groups than bismuth preparation, the Bi-resistance occasionally disappears. For example, the Bi-resistant strain seemingly returns to the original sensitive strain after 10 treatments with neosalvarsan (1: 1000), while this result is not as clearly noticeable with silver salvarsan and germanin (Bayer 205). Trypaflavin and parafuchsin exert no influence upon this Bi-fastness.5. Between the resistant and sensitive strains, there is no obvious distinction in virulence, whenever normal mice, rats and guinea pigs are used. If mice previously splenectomized are employed, however, the Bi-fast strain shows a slightly higher virulence in animals thus treated than in mice untreated. The original spirochete does not show such a result.6. When the reticulo-eudothelial system of mice is blocked by an injection of iron oxide saccharated or Indian ink, either the blocked or normal animals, contract with the same readiness the infection with both the resistant and sensitive strains.7. The Bi-fast strain, compared with the original, was found to be more sensitive to germanin and neosalvarsan.8. Between the Bi-resistant and sensitive strains the development of germanin-fastness having been compared, the resistant spirochete remained still sensitive to germanin even after 10 applications, while the original strain became tolerant to it after 5 treatments. Such a proves clearly that the Bi-fast strain is more susceptible to germanin than the original is.9. The Bi-fast spirochete shows also an increase of resistance to the combined therapy of neotrepol and germanin, where a drug of the other group as germanin is administered with this bismuth preparation. Here it is interesting to note that the Bi-resistant strain is decidedly more susceptible to the combined of germanin and neotrepol than to the single application of germanin. Is this due to the so-called antimutative action (Morgenroth and Freund) of germanin ?10. Whenever parafuchsin, ethylviolet or tryparosan as the I substance and 1: 1000 of neosalvarsan as the II substance are used, the phenomenon (Browning and Gulbransen) is not observable in mice infected with both the Bi-fast and original strains. Here also the resistant strain shows a higher susceptibility to the combined of I and II substances than does the original strain.11. Parafuchsin (especially 1: 500, 1: 1000) being combined with 1: 500 of neosalvarsan, however, the chemotherapeutic interference tends to take place only in mice infected with the Bi-resistent strain.12. In mice whose reticulo-endothelial system is previously blocked with Indian ink, the infecting spirochete, either Bi-fast or original, shows an increased tolerance to the treatment of neosalvearsan. On the other hand, such an increase of tolerance is not detected in splenectomized mice.