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PubMed1991

Dextran magnetite as a liver contrast agent.

The superparamagnetic particle dextran magnetite was studied as a liver tumor contrast agent for magnetic resonance imaging (MRI). The effects of dextran magnetite on the longitudinal (T1) and transverse (T2) relaxation times in liver, spleen, and an implanted rat liver tumor were measured at 0.47 T (IBM/Bruker PC-20 relaxometer) over the dose range of 23 to 69 mumol Fe/kg. Dextran magnetite substantially reduced the T2 of the liver and spleen, but not of the tumor, thereby providing a basis for improved tumor imaging. The T1 of the tumor was not affected following injection of dextran magnetite in the dose range studied, while the spleen T1 was reduced substantially more than the T1 of the liver. Histological studies using the iron reaction for Prussian blue clearly showed dextran magnetite in the liver and spleen, but not in the tumor. While dextran magnetite was sequestered in macrophages in both liver and spleen, the distribution in the liver was more diffuse (70 microns average particle separation) than that in the spleen (25 microns separation). The lack of a T1 effect in the liver is consistent with the fact that a majority of the water in the tissue cannot diffuse to the relaxational centers on the time scale of the liver's intrinsic T1 (280 ms). In the spleen, however, the dextran magnetite is more densely packed in the red pulp allowing a significant fraction of the water to be relaxed by a T1 mechanism. Spin-echo images of the implanted tumor (mammary adenocarcinoma. R3230AC) in the livers of Fischer 344 rats were obtained at 0.50 T (Siemens Magnetom). The tumor-to-liver contrast was improved for both T1 and T2-weighted spin-echo images after intravenous injection of the dextran magnetite contrast agent. The contrast determined from these images agreed with that predicted by the measured T1 and the T2 (Hahn spin-echo) values. In addition, gradient-echo T2-weighted images with good contrast were obtained in a much shorter imaging time than was needed for T2-weighted spin-echo images. These results demonstrate that the MRI contrast enhancement observed with dextran magnetite is based on its selective uptake and distribution in the macrophages in the liver and spleen and that this agent has substantial potential as a superparamagnetic MR contrast agent.

Adenocarcinoma↗
PubMed2007

Evaluating SPIO-labelled cell MR efficiency by three-dimensional quantitative T2* MRI.

An in vitro MR-assay for superparamagnetic iron oxide (SPIO) particle cell labelling assessment via three-dimensional quantitative T(2) (*) MR microscopy was proposed. On high-resolution images, and due to the high susceptibility difference between the particles and the surrounding medium, SPIO internalized in cells induces signal loss which may be counted and measured on T(2) (*) maps. The increase in both labelled cell percentage and the average perturbation volume with an added amount of iron in the incubation medium proved that intracellular iron uptake is dependent upon the initial concentration of incubation iron. It also proved that the observed increases in total cellular iron uptake measured by inductively coupled plasma optical emission spectroscopy are due to both an increase in the iron mass per cell and also an increase in labelled cell concentration. MR results were compared with Prussian blue staining histology. The sensitivity of the MR methodology was then used to distinguish labelling differences for two different types of particle coating. The MRI-assay we proposed is a compulsory tool to optimize labelling efficiency in order to improve in vivo cell detection. Key parameters for detection, such as the percentage of cell labelling, the effect on the image for a given amount of internalized iron and labelling distribution among a cell population, are easily obtained. The comparison of different contrast agents for labelling one cell type, the assessment of one type of contrast agent for labelling different cell types and/or the evaluation of labelling strategies, are possible without having recourse to classical methods, and provide improved accuracy, since the principle is based on intracellular relaxivity.

Animals↗
PubMed2001

The usefulness of serum transferrin receptor and ferritin for assessing anemia in rheumatoid arthritis: comparison with bone marrow iron study.

OBJECTIVES: This study was aimed at investigating the usefulness of serum transferrin receptor (sTfR) and ferritin in anemic patients with rheumatoid arthritis (RA) compared with bone marrow storage iron and other tests for anemia. METHODS: Fifty-five anemic RA patients underwent anemia study. Bone marrow iron stain was performed in 18 patients. sTfR and serum ferritin levels were compared with bone marrow iron stores. RESULTS: (1) Mean sTfR concentration was 2.63+/-1.91 mg/L, (2) sTfR correlated with most indicators of anemia, (3) sTfR showed no correlation with CRP and ESR, whereas ferritin did, and (4) sTfR was higher in the "iron depleted" subgroup than in the "iron nondepleted" subgroup in bone marrow study. CONCLUSION: The measurement of sTfR and ferritin is useful in finding the cause of anemia in RA and is a possible substitute for invasive bone marrow iron study.

Anemia, Iron-Deficiency↗
PubMedDate not supplied

Transfection of neuroprogenitor cells with iron nanoparticles for magnetic resonance imaging tracking: cell viability, differentiation, and intracellular localization.

PURPOSE: Magnetic resonance imaging (MRI) can track labeled cells in the brain. The use of hemagglutinating virus of Japan envelopes (HVJ-Es) to effectively introduce the contrast agent to neural progenitor cells (NPCs) is limited to date despite their high NPC affinity. PROCEDURES: HVJ-Es and Lipofectamine 2000 were compared as transfection vehicles of superparamagnetic iron oxide (SPIO). Labeled NPCs were examined for iron content, MRI signal change, and fundamental cell characteristics. Prussian Blue staining was used after differentiation to determine SPIO localization. RESULTS: HVJ-Es transfected up to 12.5 +/- 8.8 times more SPIO into NPCs. HVJ-Es do not affect cell viability or differentiation capability. Superparamagnetic iron oxide was disseminated in both the soma and neurites. CONCLUSIONS: These findings indicate that HVJ-Es are an effective vehicle for SPIO transfection of NPCs. The intracellular localization after differentiation raises the question as to the capability of MRI to distinguish cell migration from axonal or dendritic growth in vivo.

Animals↗
PubMed1988

Histochemical demonstration of iron but not aluminum in a case of dialysis-associated osteomalacia.

A patient undergoing hemodialysis is described in whom osteomalacia developed despite protracted treatment with calcitriol. Appropriately stained biopsy sections exhibited iron at all marrow-osteoid interfaces and a small fraction of trabecular mineralization fronts. Aluminum, the metal usually associated with osteomalacia in patients undergoing hemodialysis, was not histochemically demonstrable, even though spectrophotometrically measured bone aluminum content was substantial. These observations suggest two interpretations: iron may have caused osteomalacia through effects on bone cells and at mineralization fronts; alternatively, aluminum may have caused osteomalacia while remaining histochemically undetectable. It is possible that both metals exerted toxic effects simultaneously.

Aluminum↗
PubMed1988

A study on the cytoplasmic granules of the pericardial gland cells of some bivalve molluscs.

The pericardial glands of three bivalve molluscs are composed of convoluted epithelium that appears as pouches on the auricles of Mytilus and as tubules in the connective tissue at the anterior-lateral sides of the pericardial cavity of Mercenaria and Anodonta. The pericardial gland cells are attached to each other by many randomly placed desmosome-like cell junctions and gap junctions. Belt-desmosomes that are characteristic of epithelial cells were not observed. The basal membrane of these cells is invaginated producing complex interdigitating cytoplasmic processes and filtration slits. The pericardial gland cells stain for the presence of iron with Prussian blue stain. Electron-dense and electron-lucent granules of various diameters are present in the cytoplasm. Many electron-dense granules contain ferritin-like particles in which the presence of iron has been demonstrated by microanalysis. It is suggested that these particles are the iron storage protein ferritin since they contain iron, and are water soluble, heat stable, and morphologically similar to mammalian ferritin. Ferritin particles are probably both synthesized and broken down by the pericardial gland cells; thus the pericardial gland cells may be involved in iron homeostasis in these molluscs.

Animals↗
PubMed1998

Iron-rich foci in chronic viral hepatitis.

Stainable iron in the liver (hemosiderosis) is most commonly seen in individuals with homozygous genetic hemochromatosis, prior transfusion, hemolysis, porphyria cutanea tarda, and chronic alcohol-induced liver disease. In chronic viral hepatitis, however, significant hepatocellular hemosiderosis is uncommon. This report describes unusual foci of hepatocellular hemosiderosis ("iron-rich foci" or IRF) in liver biopsy specimens from three patients with chronic hepatitis with or without cirrhosis (two hepatitis C-related, one hepatitis B-related). IRF present within the lobular parenchyma or cirrhotic nodules contrasted sharply with the immediately adjacent hemosiderin-negative liver tissue. Serum iron indices were abnormal in all three patients, but homozygous hemochromatosis was ruled out based on the hepatic iron concentration and hepatic iron index for each case. These cases highlight the potential for irregular iron storage in chronic viral liver disease and possible confusion with genetic hemochromatosis. The possible pathogenesis of IRF and the relationship of iron storage to the outcome of interferon therapy in chronic viral hepatitis are discussed.

Biopsy↗
PubMed2001

Application of Prussian blue-based optical sensor in pharmaceutical analysis.

Optical flow-through cell-detector with incorporated transparent chemosensitive layer of Prussian blue has been applied in simple, single-channel flow-injection system for pharmaceutical analysis. The reductant analyte converts the Prussian blue based sensing layer to Prussian white form, and the attendant color change is used for sensing. Discoloration of the film is spectrophotometrically detected at 720 nm wavelength. The flow injection system has been successfully used for selective determination of ascorbic acid in simple and complex pharmaceuticals. The method is free from interferences caused by various ions and active ingredients commonly found in pharmaceuticals. The flow-through sensor is useful for spectrophotometric flow-injection analysis of intensively colored and turbid samples. The results of medicine analysis are comparable to those obtained using reference pharmacopeal method. The analytical system could be also used for determination of cysteine and hydrogen peroxide in medicines.

Ascorbic Acid↗
PubMed2003

Prussian Blue based screen printed biosensors with improved characteristics of long-term lifetime and pH stability.

The promising advantages of Prussian Blue (PB) as catalyst and of the thick film screen printing technology have been combined to assemble sensors with improved characteristics for the amperometric determination of H(2)O(2). PB-modified screen printed electrodes were applied to detect H(2)O(2) at an applied potential of -0.05 V versus the internal screen printed Ag pseudoreference electrode, showing a detection limit of 10(-7) mol l(-1), a linearity range from 10(-7) to 5x10(-5) mol l(-1), a sensitivity of 234 microA mmol l(-1) cm(-2), and a high selectivity. Improved stability at alkaline pH values was also observed, which made possible their use with enzymes having an optimum basic pH. Then, the immobilisation of a single enzyme (glucose oxidase (GOD) or choline oxidase (ChOX)) or of two enzymes, acetylcholinesterase (AchE) coimmobilised with ChOX, has been performed on the surface of PB modified screen-printed electrodes (SPEs) using glutaraldehyde and Nafion. ChOX has been selected as an example of enzyme working at alkaline pH. The choline biosensors showed a detection limit of 5x10(-7) mol l(-1), a wide linearity range (5x10(-7)-10(-4) mol l(-1)), a high selectivity and a remarkable long term stability of 9 months at 4 degrees C, and at least 4 weeks at room temperature. Similar analytical characteristics and stability were observed with the acetylcholine biosensors.

Biosensing Techniques↗
PubMed2003

Sensor and biosensor based on Prussian Blue modified gold and platinum screen printed electrodes.

Gold (Au) and platinum (Pt) screen-printed electrodes were modified with Prussian Blue (PB) for the development of amperometric sensors selective for hydrogen peroxide detection. The sensors exhibited sensitivities towards H(2)O(2) equal to 2 A M(-1) cm(-2) for Au and 1 A M(-1) cm(-2) for Pt electrodes. The sensors were also employed as the basis for construction of glucose biosensors through further modification with crystallised glucose oxidase immobilised in a Nafion membrane. In order to improve the operational stability of the modified electrodes a buffer solution containing tetrabutylammonium toluene-4-sulfonate was used. The long-term performance of the sensors and biosensors were evaluated by continuous monitoring of hydrogen peroxide and glucose solutions (50 microM and 1 mM, respectively) in the flow-injection mode for 10 h.

Biosensing Techniques↗
PubMed1979

The distribution of glutathione in the rat liver lobule.

A quantitative cytochemical method was developed for measuring the GSH (reduced glutathione) content of hepatocytes in different regions of the rat liver lobule. Use of this method enabled us to show that GSH is not evenly distributed within the rat liver lobule. The hepatocytes located within 100 micrometer of the central vein contain much less GSH than do those in other regions of the rat liver lobule. We suggest that this partially explains the peculiar susceptibility of these cells to electrophilic attack by toxic metabolites formed via the microsomal cytochrome P-450 system.

Animals↗
PubMed2003

Neuromelanin associated redox-active iron is increased in the substantia nigra of patients with Parkinson's disease.

Degeneration of dopaminergic neurones during Parkinson's disease is most extensive in the subpopulation of melanized-neurones located in the substantia nigra pars compacta. Neuromelanin is a dark pigment produced in the dopaminergic neurones of the human substantia nigra and has the ability to bind a variety of metal ions, especially iron. Post-mortem analyses of the human brain have established that oxidative stress and iron content are enhanced in association with neuronal death. As redox-active iron (free Fe2+ form) and other transition metals have the ability to generate highly reactive hydroxyl radicals by a catalytic process, we investigated the redox activity of neuromelanin (NM)-aggregates in a group of parkinsonian patients, who presented a statistically significant reduction (- 70%) in the number of melanized-neurones and an increased non-heme (Fe3+) iron content as compared with a group of matched-control subjects. The level of redox activity detected in neuromelanin-aggregates was significantly increased (+ 69%) in parkinsonian patients and was highest in patients with the most severe neuronal loss. This change was not observed in tissue in the immediate vicinity of melanized-neurones. A possible consequence of an overloading of neuromelanin with redox-active elements is an increased contribution to oxidative stress and intraneuronal damage in patients with Parkinson's disease.

Aged↗
PubMed2001

Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.

DNA↗
PubMed2006

Erythrocyte plasma membrane redox system in human aging.

Eukaryotic cells display a plasma membrane redox system (PMRS) that transfers electrons from intracellular substrates to extracellular electron acceptors. The physiologic importance of PMRS is still not fully understood. The authors have carried out studies to determine the activity of PMRS in human erythrocytes as a function of age and correlate the activity with total plasma antioxidant capacity in an effort to understand the role of PMRS in human aging. The study was carried out on 80 normal healthy subjects of both genders between the ages of 18 and 85 years. The activity of erythrocyte PMRS was estimated by following the reduction of ferricyanide. The total antioxidant capacity of the plasma was estimated in terms of Ferric Reducing Ability of Plasma (FRAP) values. A significant (p < 0.0001) positive correlation (r = 0.7797) is observed between PMRS activity of erythrocytes and human age. There is an age-dependent decrease in total plasma antioxidant capacity measured in terms of FRAP values. A highly significant correlation is observed between PMRS activity and plasma FRAP values. The authors hypothesize that the increased PMRS in erythrocytes during aging may be a protective mechanism of the system for efficient extracellular DHA reduction and ascorbate recycling under condition of increased oxidative stress.

Adolescent↗
PubMed1985

Total phospholipid analysis in human milk without acid digestion.

A colorimetric method for measuring the organic phosphorus in human milk without acid digestion was studied. Human milk samples were assayed and compared to phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin standards. Spectral and calibration curves prepared from phospholipid standards were equivalent. Absorption maxima occurred between 720 and 740 nm. A reproducibility study of twenty total lipid samples had a coefficient of variation of 3.8%. Phosphorus ranged from 4.7 to 5.5 micrograms with a mean +/- SD of 5.2 +/- 0.2 micrograms P. The recovery of phosphatidylcholines added to 10 mg samples of human milk triacylglycerols ranged from 99.0 to 102.1%. The results from the new method were comparable to those obtained by a modified Fiske and Subbarow method for measuring inorganic phosphorus after sulfuric acid digestion of the milk lipids. We concluded that the new method provides a satisfactory alternative for the determination of organic phosphorus in human milk.

Acids↗
PubMed2006

Gastric siderosis: patterns and significance.

Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and fundic glandular epithelium, which in 1 patient eventually led to the diagnosis of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described in hemochromatosis patients, alcoholics, and in association with iron medications. However, the prevalence of various patterns of iron deposition in the gastric mucosa and their clinical significance have not been studied in detail. The 2 index cases mentioned above and 500 additional consecutive gastric biopsies examined over a period of 8 months at our institution were stained for iron by the Prussian blue method. In addition, all patients with genetic hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003 who also had gastric biopsies were identified from the surgical pathology files and included in the study (n = 3). The location of iron deposition [stromal cells (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular] was recorded and subjectively graded as 1+ to 3+ according to the severity of deposition within the mucosa. Relevant histologic changes (inflammation, presence of H. pylori, ulceration) and clinical features were reviewed. Three patterns of GS were identified: A) "nonspecific GS" with predominant iron deposition in the stromal cells including macrophages, and focally in epithelium; B) "iron-pill gastritis" with often mild gastritis and reactive gastropathy type changes, and mostly extracellular deposition with focal stromal cells and epithelial deposition; and C) predominant deposition in antral and fundic glandular epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+ to 3+). A history of oral iron medication was present in 2 (n = 11, 0.4%) patients with pattern A, in all patients with pattern B (n = 4, 100%), and in none of patients with pattern C (n=3, 0%). Varying degrees of mucosal inflammation were noted in patients with pattern A cases, and 2 had evidence of active Helicobacter pylori infection. Of the 3 cases with known hemochromatosis, only one gastric biopsy showed pattern C GS (1+). In conclusion, gastric mucosal siderosis is relatively uncommon (3%) but is important to look for as it may lead to a diagnosis of hemochromatosis in some cases. Three patterns are recognized: A) a "nonspecific" stromal cell predominant pattern, which may be associated with gastric inflammation, possibly prior mucosal hemorrhages or iron medications; B) extracellular coarse clumps of crystalline iron deposition associated with oral iron medications, mild gastritis, and reactive gastropathy type changes ("Iron-pill gastritis"); and C) gastric glandular siderosis, which may be associated with systemic iron overload/hemochromatosis.

Biopsy↗