In recent years there has been an exponential increase in tungsten demand, potentially increasing human exposure to the metal. Currently, the toxicology of tungsten is poorly understood, but mounting evidence suggests that both the elemental metal and its alloys have cytotoxic effects. Here, we investigate the association between tungsten and cardiovascular disease (CVD) or stroke using six waves of the National Health and Nutrition Examination Survey (NHANES).
Objective To determine the association of different types of meat intake and meat associated compounds with overall and cause specific mortality.Design Population based cohort study.Setting Baseline dietary data of the NIH-AARP Diet and Health Study (prospective cohort of the general population from six states and two metropolitan areas in the US) and 16 year follow-up data until 31 December 2011.Participants 536 969 AARP members aged 50-71 at baseline.Exposures Intake of total meat, processed and unprocessed red meat (beef, lamb, and pork) and white meat (poultry and fish), heme iron, and nitrate/nitrite from processed meat based on dietary questionnaire. Adjusted Cox proportional hazards regression models were used with the lowest fifth of calorie adjusted intakes as reference categories.Main outcome measure Mortality from any cause during follow-up.Results An increased risk of all cause mortality (hazard ratio for highest versus lowest fifth 1.26, 95% confidence interval 1.23 to 1.29) and death due to nine different causes associated with red meat intake was observed. Both processed and unprocessed red meat intakes were associated with all cause and cause specific mortality. Heme iron and processed meat nitrate/nitrite were independently associated with increased risk of all cause and cause specific mortality. Mediation models estimated that the increased mortality associated with processed red meat was influenced by nitrate intake (37.0-72.0%) and to a lesser degree by heme iron (20.9-24.1%). When the total meat intake was constant, the highest fifth of white meat intake was associated with a 25% reduction in risk of all cause mortality compared with the lowest intake level. Almost all causes of death showed an inverse association with white meat intake.Conclusions The results show increased risks of all cause mortality and death due to nine different causes associated with both processed and unprocessed red meat, accounted for, in part, by heme iron and nitrate/nitrite from processed meat. They also show reduced risks associated with substituting white meat, particularly unprocessed white meat.
The structural description of disordered systems has been a longstanding challenge in physical science. We propose an atomic cluster alignment method to reveal the development of three-dimensional topological ordering in a metallic liquid as it undercools to form a glass. By analyzing molecular dynamic (MD) simulation trajectories of a Cu(64.5)Zr(35.5) alloy, we show that medium-range order (MRO) develops in the liquid as it approaches the glass transition. Specifically, around Cu sites, we observe “Bergman triacontahedron” packing (icosahedron, dodecahedron and icosahedron) that extends out to the fourth shell, forming an interpenetrating backbone network in the glass. The discovery of Bergman-type MRO from our order-mining technique provides unique insights into the topological ordering near the glass transition and the relationship between metallic glasses and quasicrystals.
Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anaemia
- Annals of oncology : official journal of the European Society for Medical Oncology / ESMO
- Published over 5 years ago
Background Intravenous (i.v.) iron can improve anaemia of chronic disease and response to erythropoiesis-stimulating agents (ESAs), but data on its use in practice and without ESAs are limited. This study evaluated effectiveness and tolerability of ferric carboxymaltose (FCM) in routine treatment of anaemic cancer patients. Patients and methods Of 639 patients enrolled in 68 haematology/oncology practices in Germany, 619 received FCM at the oncologist’s discretion, 420 had eligible baseline haemoglobin (Hb) measurements, and 364 at least one follow-up Hb measurement. Data of transfused patients were censored from analysis before transfusion. Results The median total iron dose was 1000 mg per patient (interquartile range 600-1500 mg). The median Hb increase was comparable in patients receiving FCM alone (1.4 g/dl [0.2-2.3 g/dl; N = 233]) or FCM + ESA (1.6 g/dl [0.7-2.4 g/dl; N = 46]). Patients with baseline Hb up to 11.0 g/dl and serum ferritin up to 500 ng/ml benefited from FCM treatment (stable Hb ≥11.0 g/dl). Also patients with ferritin >500 ng/ml but low transferrin saturation benefited from FCM treatment. FCM was well tolerated, 2.3% of patients reported putative drug-related adverse events. Conclusions The substantial Hb increase and stabilisation at 11-12 g/dl in FCM-treated patients suggest a role for i.v. iron alone in anaemia correction in cancer patients.
Aim: To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol. Materials & methods: Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology. Results: An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time. Conclusion: Ferumoxytol can be used for in vivo tracking of stem cells with MRI. Original submitted 28 February 2012; Revised submitted 8 November 2012.
- Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
- Published about 5 years ago
BACKGROUND: Nanotechnology is receiving enormous funding. Very little however is known about the health dangers of this technology so far. Chronic tonsillitis is one of a number of diseases called idiopathic. Among other factors, the tonsils are exposed to suspended particles in inhaled air including nano particles. The objective of this study was to detect and evaluate metallic particles in human tonsil tissue diagnosed with chronic tonsillitis and in amniotic fluid as a comparison. METHODS: Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) was used for identification of solid particles in a total of 64 samples of routinely analyzed biopsy and cytologic material. RESULTS: Almost all samples were found to contain solid particles of various metals. The most frequent, regardless of diagnosis, were iron, chromium, nickel and aluminium. The size, determined using SEM, varied from around 500 nm to 25 µm. The majority formed aggregates of several micrometers in size but there were a significant number of smaller (sub-micrometer or nano-sized) particles present. The incidence of metallic particles was similar in child and adult tissues. The difference was in composition: the presence of several metals in adults was due to occupational exposure. CONCLUSIONS: The presence of metallic particles in pathologically altered tissues may signal an alternative causation of some diseases. The ethiopathogenic explanation of these diseases associated with the presence of nano-sized particles in the organism has emerged into a new field of pathology, nanopathology.
- Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række
- Published almost 5 years ago
BACKGROUND Iron deficiency and iron deficiency anaemia are frequent problems in both the primary and the specialist health services. It is important to detect iron deficiency and to determine the causal relationship because iron deficiency may be secondary to a serious disease. The diagnosis of iron deficiency is largely based on biochemical and haematological laboratory findings, but there is no standardisation or consensus on the interpretation of these findings.METHOD Non-systematic search in the PubMed database with a discretionary selection of articles, based on the authors' knowledge of the field.RESULTS Ferritin measurement is the most important analysis in the study of iron deficiency, but there is no consensus on the diagnostic cut-off. It is usual in Norway today to use a ferritin level of < 12 - 20 μg/L, but at this low level the sensitivity for detecting iron deficiency is very low. A number of studies show that if the diagnostic cut-off is increased to the order of 30 μg/L the sensitivity is significantly higher for only a small reduction in specificity.INTERPRETATION When studying iron deficiency as a cause of anaemia, the diagnostic cut-off for detecting deficiency should be higher than that used today. The ferritin level increases with inflammation and ought in practice to be considered in conjunction with the CRP level. The level of transferrin receptor in plasma increases with iron deficiency without being influenced by inflammation and is therefore a good supplement to ferritin measurement. Measurement of iron, transferrin and transferrin saturation provides little information additional to that provided by ferritin in iron deficiency studies.
Magnetotactic bacteria form magnetite from a phosphate-rich ferric hydroxide via nanometric ferric (oxyhydr)oxide intermediates
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 4 years ago
The iron oxide mineral magnetite (Fe3O4) is produced by various organisms to exploit magnetic and mechanical properties. Magnetotactic bacteria have become one of the best model organisms for studying magnetite biomineralization, as their genomes are sequenced and tools are available for their genetic manipulation. However, the chemical route by which magnetite is formed intracellularly within the so-called magnetosomes has remained a matter of debate. Here we used X-ray absorption spectroscopy at cryogenic temperatures and transmission electron microscopic imaging techniques to chemically characterize and spatially resolve the mechanism of biomineralization in those microorganisms. We show that magnetite forms through phase transformation from a highly disordered phosphate-rich ferric hydroxide phase, consistent with prokaryotic ferritins, via transient nanometric ferric (oxyhydr)oxide intermediates within the magnetosome organelle. This pathway remarkably resembles recent results on synthetic magnetite formation and bears a high similarity to suggested mineralization mechanisms in higher organisms.
Iron is an essential component in many protein complexes involved in photosynthesis, but environmental iron availability is often low as oxidized forms of iron are insoluble in water. To adjust to low environmental iron levels, cyanobacteria undergo numerous changes to balance their iron budget and mitigate the physiological effects of iron depletion. We investigated changes in key protein abundances and photophysiological parameters in the model cyanobacteria Synechococcus PCC 7942 and Synechocystis PCC 6803 over a 120 hour time course of iron deprivation. The iron stress induced protein (IsiA) accumulated to high levels within 48 h of the onset of iron deprivation, reaching a molar ratio of ∼42 IsiA : Photosystem I in Synechococcus PCC 7942 and ∼12 IsiA : Photosystem I in Synechocystis PCC 6803. Concomitantly the iron-rich complexes Cytochrome b6f and Photosystem I declined in abundance, leading to a decrease in the Photosystem I : Photosystem II ratio. Chlorophyll fluorescence analyses showed a drop in electron transport per Photosystem II in Synechococcus, but not in Synechocystis after iron depletion. We found no evidence that the accumulated IsiA contributes to light capture by Photosystem II complexes.
The effects of microbial iron reduction and oxidation on the immobilization and mobilization of copper was investigated in a high concentration of sulfate with synthesized Fe(III) minerals and red earth soils rich in amorphous Fe (hydr)oxides. Batch microcosm experiments showed that red earth soil inoculated with subsurface sediments had a faster Fe(III) bioreduction rate than pure amorphous Fe(III) minerals and resulted in quicker immobilization of Cu in the aqueous fraction. Coinciding with the decrease of aqueous Cu, SO4(2-) in the inoculated red earth soil decreased acutely after incubation. The shift in the microbial community composite in the inoculated soil was analyzed through denaturing gradient gel electrophoresis. Results revealed the potential cooperative effect of microbial Fe(III) reduction and sulfate reduction on copper immobilization. After exposure to air for 144 h, more than 50% of the immobilized Cu was remobilized from the anaerobic matrices; aqueous sulfate increased significantly. Sequential extraction analysis demonstrated that the organic matter/sulfide-bound Cu increased by 52% after anaerobic incubation relative to the abiotic treatment but decreased by 32% after oxidation, indicating the generation and oxidation of Cu-sulfide co-precipitates in the inoculated red earth soil. These findings suggest that the immobilization of copper could be enhanced by mediating microbial Fe(III) reduction with sulfate reduction under anaerobic conditions. The findings have an important implication for bioremediation in Cu-contaminated and Fe-rich soils, especially in acid mine drainage (AMD)-affected sites.