Saccharated Iron Oxide Research Articles

Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation.

Hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, iron overload is a frequent adverse effect of allo-HSCT and is associated with poor prognosis. In the present study, we investigated hematopoiesis in iron-overloaded mice and elucidated the effects of iron overload on the bone marrow (BM) microenvironment. Iron-overloaded BALB/C mice were generated by injecting 20 mg/mL saccharated iron oxide intraperitoneally. Hematoxylin-eosin staining was performed to evaluate the effects of an iron overload in mice. BM cells obtained from C57BL/6 mice were transplanted into irradiated BALB/C mice (whole-body irradiation of 4 Gy, twice with a 4-hours interval) by tail vein injection. Two weeks after allo-HSCT, the hematopoietic reconstitution capacity was evaluated in recipients by colony-forming assays. Histopathological examinations showed brown-stained granular deposits, irregularly arranged lymphocytes in the liver tissues, and blue-stained blocks in the BM collected from mice received injections of high-dose saccharated iron oxide (20 mg/mL). Iron-overloaded mice showed more platelets, higher-hemoglobin (HGB) concentration, fewer granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte colony-forming units (CFU-E), and mixed granulocyte/erythrocyte/monocyte/megakaryocyte colony-forming units (CFU-mix) than healthy mice. Iron-overloaded recipients presented with reduced erythrocytes and HGB concentration in peripheral blood, along with decreased marrow stroma cells, CFU-GM, CFU-E, and CFU-mix relative to healthy recipients. Taken together, our findings demonstrate that iron overload might alter the number of red blood cells after transplantation in mice by destroying the BM microenvironment, thereby affecting the recovery of BM hematopoietic function.

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.

Iron-induced hypophosphatemia: an emerging complication.

Iron-induced hypophosphatemia is a well documented side-effect but associated complications are largely neglected, because the results from single dosing studies suggest that transient decreases in plasma phosphate concentrations are asymptomatic and fully reversible. However, an increasing number of case reports and case series suggest that some patients develop severe and symptomatic hypophosphatemia. Long-term complications from hypophosphatemia include osteomalacia and bone fractures, which can result from repeated intravenous administration of certain high-dose iron preparations. Results from clinical trials suggest that the highest risk for the development of hypophosphatemia is associated with ferric carboxymaltose, iron polymaltose, and saccharated iron oxide. Clinical studies show that renal phosphate wasting mediated by increased fibroblast growth factor 23 causes hypophosphatemia after iron therapy. Impaired renal function therefore protects from hypophosphatemia, whereas the highest incidences and most severe manifestations have been reported in patients in whom the underlying cause of iron deficiency cannot be corrected. Diagnosis of iron-induced hypophosphatemia requires clinical suspicion. Treatment is guided by the severity of hypophosphatemia, and most patients will require oral or intravenous phosphate substitution. Future treatment options could involve therapeutic anti-FGF23 antibody (KRN23). Prevention and correction of vitamin D deficiency represents a supportive treatment option.

Intravenous iron in the treatment of an˦mia of pregnancy

Summary Ferrivenin, a stable saccharated oxide of iron, has been given to 25 an˦mic pregnant women. All showed a rapid response to treatment, the h˦moglobin increasing, in almost all cases, by 8% in the first week of treatment. The results are contrasted with those obtained with iron by mouth. It apparently required almost 40 mg. of elemental iron to increase the h˦moglobin by 1% in an an˦mic pregnant woman. In 2 cases the an˦mia was refractory to iron by mouth after prolonged treatment, but it responded satisfactorily to intravenous iron. Only 1 case showed a severe reaction, which appeared to be due to vagal stimulation. This may have been related to the irregular attendance of the patient for treatment, there being an interval of twelve days between the previous injection and the date of the reaction.

肺における鉄代謝に関する研究

In order to clarify the role of alveolar macrophages (alv Mφ) in the iron metabolism of the lung, ultrastructural findings of cells obtained by bronchoalveolar lavage were studied by transmission electron microscopy in rats after inhalation of saccharated iron oxide and welding fumes as well as a patient with welder's lung.Alv Mφ of rats which had inhaled saccharated iron oxide formed phagosomes and secondary lysosomes 4 hours after inhalation. The first day after inhalation, many ferritin particles were seen in cytosol and formed a diffuse patterns; 19% of alv Mφ had ferritin particles in a paracrystalin arrangement in the secondary lysosomes. Electron micrographs of alv Mφ at 3, 6, 14, and 28 days after inhalation showed an increase of the cells with ferritin particles. Alv Mφ of rats which had inhaled welding fumes phagocytized those iron particles and also synthesized ferritin particles in the cytosol and secondary lysosomes 6 days after inhalation. Numerous ferritin particles were seen in the cytosol and secondary lysosomes of alv Mφ from a patient with welder's lung as well. These results suggest that inhaled iron was phagocytized by alv Mφ and stored in the cytosol by binding with apoferritin which was synthesized by the ribosomes.

<i>Tigriopus japonicus</i>の消化管における栄養物質の吸収形態

The absorptive function of the alimentary canal of Tigriopus japonicus was investigated using lipids, saccharated iron oxide, and ferritin as tracers. Light and electron microscopic examinations revealed that nutritive substances were absorbed only in the mid-gut. Lipids were absorbed by the non-vacuolated cells by means of transmembrane absorption and accumulated in lipid vacuoles of the non-vacuolated cells and lipid storing tissues of the body. Positive Berlin blue reaction by absorbed iron was found in all the mid-gut epithelial cells. Ferritin was absorbed only by the vacuolated cells by means of endocytosis. These tracer substances were found to be absorbed more actively in the mid-gut in the metasome than that in the urosome. These results indicate that there are differences in mode and degree of absorption between the mid-gut in the metasome and that in the urosome.

Biochemical surface components of Brugia pahangi microfilariae.

The sheath and cuticle of microfilariae of Brugia pahangi were examined by electron microscopy and the presence of various proteins, carbohydrate and enzymes sought. The epicuticle of microfilariae consists of a pentalaminate structure (24.0 +/- 1.4 nm), a cortex (13.7 +/- 3.6 nm) and a basal zone (27.8 +/- 4.8 nm) which is often banded in appearance. The pentalaminate layers are not continuous at the base of the interannular grooves. The sheath and the epicuticle of B. pahangi stained positively with concanavalin A and saccharated iron oxide. The sheath of approximately 50% of microfilariae showed activity for acid phosphatase, 5' nucleotidase and peroxidase, but not for ATPases, alkaline phosphatase or esterase. No enzymes were detected in the epicuticle although the cortex and basal layers of the cuticle did show enzymic activity. Structures beneath the cuticle in the main body of the worms contained considerable enzymic activity. Microfilariae directly isolated from the blood of infected cats were found by immunochemical means to carry serum proteins on their sheaths but not on their cuticles. These studies extend the definition of the outer structures of microfilariae and confirm that they significantly differ in morphology and enzyme content from typical mammalian cell membranes.

Hypophosphatemia induced by intravenous administration of Saccharated iron oxide.

Forty milligrams saccharated iron oxide was given intravenously, daily, to nine iron-deficient patients with moderate to severe anemia. During the 14-42 days of treatment, levels of serum inorganic phosphorus (Pi) decreased significantly and in a stepwise manner (before vs 1 week, P less than 0.005; 1 week vs 2 weeks, P less than 0.01). Seven of the nine patients became hypophosphatemic within 2 weeks and the other two within 4 weeks. In parallel with the decline in serum Pi, the phosphate clearance increased and tubular reabsorption of phosphate decreased. Reversion to normal levels was delayed in patients treated for the longer period.

Fusion of Host Cell Secondary Lysosomes with the Parasitophorous Vacuoles of Leishmania mexicana‐inlected Macrophages

Secondary lysosomes of cultured mouse peritoneal macrophages were labeled with the electron-dense colloid saccharated iron oxide; the identity of the labeled structures was checked by the Gomori reaction for acid phosphatase. Amastigotes of Leishmania mexicana mexicana derived from mouse lesions were used to infect these macrophages in vitro. In electron micrographs of thin sections of infected macrophages the labeled secondary lysosomes were seen fused with the parasitophorous vacuoles without preventing subsequent multiplication of the parasites. A similar fusion probably occurs in vivo, and may provide a pathway through which not only nutrients but also drugs and host antibodies could reach the intracellular parasite.

Iron Therapy by Intravenous Infusion of Saccharated Iron Oxide

International Journal of Clinical PracticeVolume 27, Issue 4 p. 133-135 Clinical Trials Iron Therapy by Intravenous Infusion of Saccharated Iron Oxide A. D. Efstratopoulos* MD, A. D. Efstratopoulos* MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this authorCh. D. Tountas MD, Ch. D. Tountas MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this authorG. E. Merikas MD, G. E. Merikas MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this authorZ. Komninos MD, Z. Komninos MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this author A. D. Efstratopoulos* MD, A. D. Efstratopoulos* MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this authorCh. D. Tountas MD, Ch. D. Tountas MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this authorG. E. Merikas MD, G. E. Merikas MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this authorZ. Komninos MD, Z. Komninos MD Second Medical Department of University of Athens, “Ippokration” General Hospital, Athens, GreeceSearch for more papers by this author First published: 01 April 1973 https://doi.org/10.1111/j.1742-1241.1973.tb08999.x Note: The intravenous saccharated iron oxide used is not marketed in Great Britain — Editors.) Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume27, Issue4April 1973Pages 133-135 RelatedInformation

The passage of extracellular tracers through the follicular epithelium of lizard ovaries

AbstractLanthanum, a tracer of extracellular space in fixed tissue, readily traverses the follicular epithelium of the lizard Anolis carolinensis. Saccharated iron oxide injected into living lizards and peroxidase administered in vitro pass through the extracellular spaces of the follicular epithelium and accumulate in the zona pellucida. Micropinocytotic uptake of iron and peroxidase by the oocyte occurs in larger follicles which show signs of yolk accumulation. These findings confirm the morphological absence of sealing junctions in the follicular epithelium and demonstrate an extracellular route whereby materials carried in the circulation may reach the oocyte without passing through the cytoplasm of follicular cells.

Ultrastructure of the gingiva of rabbits

The gingival sulcus wall of Dutch Belted rabbits was used to study vascular transudation and exudation with Pelikan ink as a tracer for light microscopy and saccharated iron oxide as an electron microscopic tracer. The marker was apparently transported by numerous plasmalemmal vesicles, and also passed through the interendothelial junctions. The sulcular fluid was an inflammatory exudate rather than a transudate. Ultrastructural alterations of the gingiva following inflammation were studied. The interepithelial space increased more on the sulcular than the attached gingival side. The wider interepithelial space in the sulcular area and the non-keratinizing nature of this tissue may have contributed to the ease of passage of the gingival fluid in that region.

Fibrinogen derivatives in particle aggregation by peritoneal contents

Summary Supernatants of peritoneal washings of normal mice and solutions of human or murine fibrinogen aggregated carbon in indian ink, colloidal saccharated iron oxide and suspensions of polystyrene latex, but did not clump thorotrast or colloidal gold. In peritoneal washings allowed to stand, the ability to aggregate tended to appear and then disappear; solutions of purified fibrinogen became active after dilution and standing. Fibrinolytic digestion of carbon clumped by mouse peritoneal supernatants or by fibrinogen, released soluble products possessing the serological specificity of fibrinogen. Early fibrinogen degradation products are thought to be the agents in peritoneal washings causing aggregation of the particles.

Influence of x irradiation on the survival to trauma.

It was previously shown that animals made trauma-resistant by prior exposure to drum trauma or by the injection of a protective factor associated with the reticuloendothelial system (Res) were protected against the lethal effects of whole-body irradiation (1). To further understand this interrelationship, it was felt necessary to study the effect of prior irradiation on the response to trauma. This is also of interest in view of the fact that the consequences to man of simultaneous exposure to radiation and trauma seem far more severe than the exposure to either stress alone (2, 3). Preliminary data on these effects have been reported elsewhere (4). Materials and Methods Young adult rats of the CF-Nelson strain (140–175 g) were used in these experiments. Whole-body irradiation was administered by a therapeutic x-ray unit operated at 200 kVp and 15 mA with a filter of 0.5 mm Cu and 1 mm AI. The half-value layer was equivalent to 0.9 mm Cu. The skin-to-target distance was 40 cm and the dose delivered to the position of the center of the body, as measured by a Victoreen dosimeter, was 40 R/min. in air. Unanesthetized rats were irradiated in a Lucite cage on a rotating table. Shielding of the rats was accomplished with small sheets of lead (1/8 in. thick) molded and placed over the midsection or the exteriorized spleen of the anesthetized animal during irradiation. Measurements with a Victoreen dosimeter indicated that shielded animals received less than 4 per cent of the radiation dosage. Rats were traumatized by exposing them to drum trauma in a modified Noble-Collip tumbling apparatus as previously described (5). With this method, trauma is applied in a controlled graded manner, after which a typical picture of shock develops, uncomplicated by infection, hemorrhage, or anesthesia (6). Rats are placed in cylindrical drums, 15 inches in diameter and 8 inches deep, with two blunt triangular projections. Eighteen drums revolve simultaneously at 40 rpm, allowing control and experimental animals to be tumbled under identical conditions. After 650 revolutions approximately 70 per cent of the rats survive, whereas after 725 turns approximately 30 per cent survive. Animals succumb shortly after removal from the drum. Rats receiving repeated sublethal doses of trauma acquire a resistance to the stress and withstand lethal doses (1200 revolutions) without mortality (7). These trauma-resistant animals are able to maintain homeostasis by stabilizing their metabolic processes. Impairment of the phagocytic activity of the Res was produced by blockading the reticuloendothelial elements with colloidal agents. This method physically overloads the phagocytic cells of the liver and spleen so that no further uptake occurs during a distinct time interval. Animals were injected via the jugular vein with 12 mg (in 0.6 ml volume) of Proferrin, a saccharated iron oxide, or 77 mg (0.3 ml) of Thorotrast, a stabilized colloidal suspension of thorium dioxide. Control animals received equal volumes of physiological saline by the same route.

Localization of radioiodinated endotoxin in organs of mice and rabbits: effect of thorotrast, trypan blue, endotoxin and carbon administered intravenously.

THE splenic uptake of intravenously introduced sheep erythrocyte stroma in mice is increased if certain finely divided agents (carbon, trypan blue, saccharated iron oxide, thorotrast, polystyrene latex) are injected by the same route simultaneously or before the administration of the stroma1. It seemed of interest to investigate whether the distribution of endotoxin in organs was altered in similar conditions.

An investigation of some properties of endothelium related to capillary permeability.

The muscle capillaries of hearts taken directly from rats and mice, or perfused in vitro through the coronary vessels, were investigated by electron microscopy. The electron-dense marker particles ferritin and saccharated iron oxide were introduced into the blood or perfusion fluid. Versene, enzymes, surface active agents, and inhibitors of metabolism were added to the perfusion fluid, and perfusion was also carried out at 0 °C. Caveolae and vesicles were present in the endothelium of perfused hearts after all these measures; in damaged cells they disappeared in parallel with the cell and nuclear membranes. Particles entered caveolae and vesicles from the lumen under all conditions of perfusion. With saccharated iron oxide it was not certain w hat proportion of particles entering caveolae from the lumen passed right through the cell, since some of the particles in external caveolae could have come from accumulations in the basement membrane. Small numbers of ferritin molecules seemed to traverse the cell by the caveolae and vesicles in perfused hearts and in the whole animal. Groups or chains of communicating caveolae and vesicles were often seen. The cells remained closely apposed and the junctions intact in all preparations. Saccharated iron oxide passed into the junctions. In perfused hearts a variable amount left the vessels by this route, which was probably the main source of accumulations in the basement membrane and extravascular structures. Very little ferritin entered the junctions either in the intact animal or in vitro . The basement membrane was largely removed by papain and by impure preparations of collagenase but was not clearly affected by the other enzymes used. The removal of calcium from the perfusion fluid caused the basement membrane to separate from the endothelium.

The uptake of particulate matter by endothelial cells.

Ferritin and particles of saccharated iron oxide are ingested and segregated in endothelial cells. The ferritin is taken up in Kupffer cells by coated vesicles but it may also pass directly through the cell membrane. It is segregated in membrane-bounded bodies of varied appearance, but particles are also seen free in the cytoplasm. Ferritin is taken up by endothelium in the adrenal, spleen, aorta, heart, intestine and brain and is often to be found concentrated in multivesicular bodies.

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.

Hemoglobin Regeneration in Severe Iron-Deficiency Anemia

Severe iron deficiency anemia can be corrected very nearly as fast by several inexpensive preparations of oral iron as by iron dextran injection or saccharated iron oxide. The average rate of increase in hemoglobin concentration in 28 women who ingested ferrous sulfate, ferrous gluconate, or ferrous fumarate in amounts which provided 180 to 220 mg of iron per day was 0.25 gm/ 100 ml/day compared to 0.28 gm/100 ml/day in 14 who received iron dextran injection intramuscularly and 0.33 gm/100 ml/day in 14 who were treated with saccharated iron oxide given by intravenous infusion. Ferrous sulfate, ferrous fumarate, or ferrous gluconate in a daily dose containing about 200 mg of iron are very satisfactory for treating most cases of severe iron deficiency anemia.

膠質粒子の血管壁通過と組織内貯溜に関する研究

The deposition and passage of colloidal particles on and across the endothelial wall of sinusoids, their persistence in the parenchyma as well as their transportation to the regional lymph nodes have been studied, after an intravenous injection of a lage amount of India ink and saccharated iron oxide. The injected colloidal particles are rapidly taken up for the most part by the stellate cells of Kupffer lining the sinusoids and accumlate in their cell bodies, However, a part of colloidal particles are transported to the portal lymph nodes that receive the effluent lymph from the liver, after passing through the intercellular gaps of the sinusoidal endothelium and entering into the lymph stream in the space of Disse. The chemically stable carbon particles are gradually brough together into large masses formed by coalescence of carbon-laden phagocytes-either stellate cells in the liver or reticular cells in the portal lymph nodes-and persisted for a long time. The colloidal particles of saccharated iron dioxide, on the other hand, appear to be gradually metabolized, after having been phagocytized by either stellate cells in the liver or reticular cells in the portal lymph nodes, and disappear within a month or two. A small amount of carbon particles appear to be taken up by the liver cells during period from 1 to 30 days after the injection.