scholarly journals The effect of copper excess on iron metabolism in sheep

1978 ◽  
Vol 170 (1) ◽  
pp. 137-143 ◽  
Author(s):  
E C Theil ◽  
K T Calvert
Keyword(s):  
Iron Metabolism ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Fold Increase ◽  
Copper Treatment ◽  
Excess Copper ◽  
High Concentrations ◽  
Copper Excess ◽  
Effect Of Copper ◽  
Haemoglobin Content

Sheep were treated with large amounts of copper (20 mg of CuSO4,5H2O/kg body wt. per day) for 9 weeks to examine the effect of copper excess on iron metabolism. In addition to confirming that massive haemolysis and accumulation of copper occurs in the liver, kidney and plasma after 7 weeks of exposure to excess copper, it was observed that excess copper produced an increased plasma iron concentration and transferrin saturation within 1 week. Further, iron preferentially accumulated in the spleen between 4 and 6 weeks of copper treatment, producing 3-fold increases in the iron content of both the ferritin and non-ferritin fractions. A 3-4 fold increase was also observed in the amount of ferritin that could be isolated from the spleen. The copper treatment had little or no effect on the concentration of iron in the liver and bone marrow. The following properties of erythrocytes were also unaffected by copper treatment: size, haemoglobin content and pyruvate kinase activity, although the erythrocyte concentration of copper increased after 6 weeks. Copper accumulated in the spleen between 6 and 9 weeks, probably owing to the phagocytosis of erythrocytes containing high concentrations of copper. The data suggest that copper excess influences iron metabolism, initially by causing a compensated haemolytic anaemia, and later by interfering with re-utilization of iron from ferritin in the reticuloendothelial cells of the spleen.

scholarly journals Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 482
Author(s):  
Valentina Natalucci ◽  
Edy Virgili ◽  
Federica Calcagnoli ◽  
Giacomo Valli ◽  
Deborah Agostini ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Complex Problem ◽  
Low Grade ◽  
Inflammatory Status ◽  
Line Of Therapy ◽  
Cancer Related Anemia ◽  
Low Grade Inflammation

Cancer is often accompanied by worsening of the patient’s iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.

scholarly journals THE RATE OF BACTERICIDAL ACTION OF PENICILLIN IN VITRO AS A FUNCTION OF ITS CONCENTRATION, AND ITS PARADOXICALLY REDUCED ACTIVITY AT HIGH CONCENTRATIONS AGAINST CERTAIN ORGANISMS

1948 ◽  
Vol 88 (1) ◽  
pp. 99-131 ◽  
Author(s):  
Harry Eagle ◽  
A. D. Musselman
Keyword(s):  
Bacterial Species ◽  
Fold Increase ◽  
Bactericidal Effect ◽  
Penicillin G ◽  
Bacterial Suspension ◽  
Maximal Effect ◽  
Maximal Rate ◽  
Effective Level ◽  
High Concentrations

1. The concentrations of penicillin G which (a) reduced the net rate of multiplication, (b) exerted a net bactericidal effect, and (c) killed the organisms at a maximal rate, have been defined for a total of 41 strains of α- and ß-hemolytic streptococci, Staphylococcus aureus and Staphylococcus albus, Diplococcus pneumoniae, and the Reiter treponoma. 2. The concentration which killed the organisms at a maximal rate was 2 to 20 times the minimal effective level ("sensitivity" as ordinarily defined). With some organisms, even a 32,000-fold increase beyond this maximally effective level did not further increase the rate of its bactericidal effect. However, with approximately half the strains here studied (all 4 strains of group B ß-hemolytic streptococci, 4 of 5 group C strains, 5 of 7 strains of Streptococcus fecalis, 2 of 4 other α-hemolytic streptococci, and 4 of 9 strains of staphylococci), when the concentration of penicillin was increased beyond that optimal level, the rate at which the organisms died was paradoxically reduced rather than increased, so that the maximal effect was obtained only within a relatively narrow optimal zone. 3. There were marked differences between bacterial species, and occasionally between different strains of the same species, not only with respect to the effective concentrations of penicillin, but also with respect to the maximal rate at which they could be killed by the drug in any concentration. Although there was a rough correlation between these two factors, there were many exceptions; individual strains affected only by high concentrations of penicillin might nevertheless be killed rapidly, while strains sensitive to minute concentrations might be killed only slowly. 4. Within the same bacterial suspension, individual organisms varied only to a minor degree with respect to the effective concentrations of penicillin. They varied strikingly, however, in their resistance to penicillin as measured by the times required to kill varying proportions of the cells.

scholarly journals Thunderstorm outflows preceding epidemics of asthma during spring and summer

Thorax ◽  
2001 ◽  
Vol 56 (6) ◽  
pp. 468-471
Author(s):  
G B Marks ◽  
J R Colquhoun ◽  
S T Girgis ◽  
M Hjelmroos Koski ◽  
A B A Treloar ◽  
...  
Keyword(s):  
Pollen Grains ◽  
Ground Level ◽  
Fold Increase ◽  
Underlying Mechanism ◽  
Detailed Examination ◽  
Asthma Exacerbations ◽  
Eastern Australia ◽  
The Difference ◽  
High Concentrations ◽  
Thunderstorm Outflow

BACKGROUNDA study was undertaken to assess the importance of thunderstorms as a cause of epidemics of asthma exacerbations and to investigate the underlying mechanism.METHODSA case control study was performed in six towns in south eastern Australia. Epidemic case days (n = 48) and a random sample of control days (n = 191) were identified by reference to the difference between the observed and expected number of emergency department attendances for asthma. The occurrence of thunderstorms, their associated outflows and cold fronts were ascertained, blind to case status, for each of these days. In addition, the relation of hourly pollen counts to automatic weather station data was examined in detail for the period around one severe epidemic of asthma exacerbations. The main outcome measure was the number of epidemics of asthma exacerbations.RESULTSThunderstorm outflows were detected on 33% of epidemic days and only 3% of control days (odds ratio 15.0, 95% confidence interval 6.0 to 37.6). The association was strongest in late spring and summer. Detailed examination of one severe epidemic showed that its onset coincided with the arrival of the thunderstorm outflow and a 4–12 fold increase in the ambient concentration of grass pollen grains.CONCLUSIONSThese findings are consistent with the hypothesis that some epidemics of exacerbations of asthma are caused by high concentrations of allergenic particles produced by an outflow of colder air, associated with the downdraught from a thunderstorm, sweeping up pollen grains and particles and then concentrating them in a shallow band of air at ground level. This is a common cause of exacerbations of asthma during the pollen season.

MO547ASSOCIATION BETWEEN SERUM INDICES OF IRON METABOLISM AND CARDIOVASCULAR MORBIDITY IN PATIENTS WITH PREDIALYSIS CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Takahiro Imaizumi ◽  
Kenta Murotani ◽  
Takayuki Hamano ◽  
Masafumi Fukagawa
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Metabolism ◽  
Iron Supplementation ◽  
Transferrin Saturation ◽  
Cox Proportional Hazards ◽  
Function Evaluation ◽  
Iron Deficient ◽  
Increased Risk ◽  
Reduced Risk

Abstract Background and Aims Patients with predialysis chronic kidney disease (CKD) have a greater risk of developing cardiovascular disease (CVD) events than the general population. Anaemia is the most frequent comorbidity in pre-dialysis CKD patients and is associated with an increase in CVD events. Iron deficiency is the most frequent cause of erythropoiesis-stimulating agents (ESAs) resistant anaemia in CKD patients and is modifiable by therapeutic intervention. However, the optimal ranges of iron markers are uncertain in predialysis CKD patients. Therefore, we aimed to investigate the association between serum indices of iron metabolism and the incidence of CVD events in patients with predialysis CKD using the CKD-Japan Cohort (CKD-JAC) data. Method We prospectively followed 1550 CKD patients aged 20-75 years with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 for a mean of 4.21 years. We set serum transferrin saturation (TSAT) and ferritin levels as the main exposures to be tested. Our main outcome measures were any of the CVD events including fatal or non-fatal myocardial infarction, congestive heart failure (CHF), angina pectoris, arrhythmia, aorta dissection, cerebrovascular disorder, and peripheral artery diseases identified at each facility and adjudicated by the independent cardiac function evaluation committee. Multivariable Cox proportional hazards regression models were employed to examine the association between serum TSAT or ferritin levels with time to events. Death was considered as a competing risk with the Fine and Gray model. All models were stratified by facilities and adjusted for potential confounders as follows: age, sex, systolic blood pressure, diabetes mellitus, history of CHF, haemoglobin, serum calcium, serum phosphorus, intact parathyroid hormone, eGFR, proteinuria, ESAs, iron supplementation, renin-angiotensin system inhibitors, and beta-blockers. We also applied the multivariable fractional polynomial interaction (MFPI) approach to investigate whether TSAT levels are the effect modifier of the association between iron supplementation and the outcomes. Results In the overall cohort, 208 (13.4 %) patients developed CVD events (including 97 CHF) during the follow-up period (26.6 events/1000 person-year). The incidence rate of CVD events was the highest in the TSAT < 20% category (33.0 events/1000 person-year). Compared to patients in the TSAT > 40% category, those in the TSAT < 20% category demonstrated an increased risk of CVD events (adjusted hazard ratio (AHR): 1.86, 95% confidence interval (CI): 1.06-3.26) and CHF events (AHR: 2.82, 95% CI: 1.15-6.89), respectively. Meanwhile, there was no association between serum ferritin levels and the risk of developing CVD or CHF events. MFPI analyses showed a reduced risk of CVD in patients receiving iron supplementation only in patients with TSAT <20% (P for interaction=0.02). Conclusion Maintaining TSAT >20% could be effective to reduce the risk of developing CVD events (especially CHF) in patients with predialysis CKD. Our analyses also suggest that iron-deficient patients with predialysis CKD may benefit from iron supplementation for reduced risk of CVD events.

Quantitation of reticuloendothelial iron kinetics in humans

1984 ◽  
Vol 247 (5) ◽  
pp. R842-R849 ◽  
Author(s):  
M. Stefanelli ◽  
D. P. Bentley ◽  
I. Cavill ◽  
H. P. Roeser
Keyword(s):  
Binding Capacity ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Ferric Hydroxide ◽  
Equal Proportion ◽  
Dual Isotope ◽  
Plasma Iron ◽  
Storage Pool ◽  
Iron Kinetics

Reticuloendothelial iron kinetics were investigated in a simultaneous dual-isotope study in 10 healthy adult subjects in whom 55Fe-ferric hydroxide phosphate colloid was used to label the reticuloendothelial iron pools, and 59Fe-transferrin was used to define plasma iron kinetics. The simultaneous clearance of 55Fe and 59Fe from plasma and the uptake of each into red blood cells were measured over 14 days. The 55Fe-colloid was cleared almost immediately, and its iron was rapidly released to bind to plasma transferrin. Red cell incorporation of 55Fe was, however, much slower than that of 59Fe bound to transferrin in vitro. The data were analyzed by a new model of reticuloendothelial iron metabolism that contained two reticuloendothelial iron pools; one had a rapid turnover and donated iron to transferrin, and the other, a storage pool, had a slower turnover. The transit pool contained a mean of 164 mumol iron with little variation between subjects, whereas the storage pool was somewhat larger (mean 873 mumol iron) and showed more marked variation between subjects. In general an equal proportion of the iron leaving the transit pool went to transferrin and to the storage pool. The distribution between the two routes did not appear to be related either to plasma iron concentration, latent iron-binding capacity, or transferrin saturation.

scholarly journals Is Transferrin Saturation a Useful Marker of Iron Metabolism in Patients with Chronic Kidney Disease Treated with Hemodialysis?

2019 ◽  
Vol 12 (1) ◽  
pp. 77-82
Author(s):  
Ewa Kwiatkowska ◽  
Martyna Opara ◽  
Sebastian Kwiatkowski ◽  
Leszek Domański ◽  
Małgorzata Marchelek-Myśliwiec ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Metabolism ◽  
Complete Blood Count ◽  
Transferrin Saturation ◽  
Maintenance Hemodialysis ◽  
Study Group ◽  
Ferritin Concentration ◽  
Lower Limit Of Normal

Background: According to the currently applicable KDIGO-2012 and ERBP 2013 guidelines, iron metabolism assessments for patients with Chronic Kidney Disease (CKD) are performed using such parameters as ferritin concentration and Transferrin Saturation (TSAT). Their values are to be treated as a basis on which to decide on providing iron substitution. Patients with Stage 5 CKD on maintenance hemodialysis commonly suffer from malnutrition syndrome and inflammation. One of the markers for malnutrition and inflammation is low transferrin concentration. Our study focused on establishing what percentage of patients this applied to and whether or not the transferrin saturation figure was artificially inflated in such cases. Materials and Methods: The study group included 66 patients with Stage 5 CKD on maintenance hemodialysis. Such data were analyzed as complete blood count, iron and ferritin concentrations, and Transferrin Saturation (TSAT). Other parameters - age, sex, time from their first hemodialysis, and the quality of their dialysis in the last six months – the Kt/V average. Results: It was found that only 12% of the study group patients had their transferrin concentrations above the lower limit of normal. The TSAT value correlated negatively with transferrin concentration. Transferrin concentration correlated negatively with time from first hemodialysis or ferritin concentration, and positively with body weight. Normal transferrin concentration was only seen in patients with ferritin concentrations of up to 400 μg/L. The group was divided according to transferrin concentration of <1.5 g/L or >1.5 g/L. These groups differed significantly in ferritin concentration and transferrin saturation. (p = 0.0005 and p = 0.004, respectively). The 1.5 g/L transferrin concentration point divides patients with mild and medium malnutrition. It is also the minimum transferrin content necessary to achieve hemoglobin values ≥10 g/dL determined using the ROC curve. Conclusion: Low transferrin concentrations cause abnormally high TSAT values. In most patients on maintenance hemodialysis, this marker is not useful for assessing the availability of iron for erythropoiesis.

scholarly journals Role of Roxadustat in Improving Erythropoiesis-Stimulating Agent (ESA)-Resistant Anemia in Patients on Maintenance Hemodialysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-47
Author(s):  
Satoshi Funakoshi
Keyword(s):  
Iron Metabolism ◽  
Conflicts Of Interest ◽  
Hypoxia Inducible Factor ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
Reactive Protein ◽  
Study Results ◽  
Dialysis Vintage ◽  
Patients With Diabetes

Background: Roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, is shown to stimulate erythropoiesis thus improving iron metabolism. Again, while hyperglycemic states are known to be associated with a decreased tissue hypoxia response, to date, roxadustat has not been revaluated for its role in improving anemia in patients with or without diabetes in clinical settings. Methods: A total of 64 hemodialysis patients being treated with epoetin α (9000 units weekly) participated in the study after giving informed consent. They were switched from intravenous epoetin α to oral roxadustat (100 mg 3 times weekly) therapy and were assessed 8 weeks later for improvements in anemia, as well as for changes in parameters for iron metabolism and C-reactive protein (CRP). Results: The study included 39 patients without diabetes (mean age, 71.1 ± 12.1 years; mean dialysis vintage, 7.5 ± 7.4 years; mean GA, 16.2 ± 2.9%) and 27 patients with diabetes (mean age, 70.3 ± 10.3 years; mean dialysis vintage, 5.9 ± 5.5 years; mean GA, 24.9 ± 5.5%). As shown in Table, after 8 weeks the Hb concentration was significantly increased from 10.3 ± 0.8 g/dL at baseline to 10.7 ± 1.3 g/dL in patients without diabetes (P = 0.03) but was not increased in patients with diabetes (from 10.4 ± 0.6 at baseline to 10.5 ± 1.1 g/dL). Again, the serum iron, ferritin concentrations and the transferrin saturation ratio were decreased, irrespective of whether or not they had diabetes, with no change shown in serum CRP level. Conclusion: Switching hemodialysis patients with ESA-resistant anemia from ESA to roxadustat led to improvements in anemia only in those without diabetes, while study results suggested the involvement of mechanisms, other than impaired iron utilization or inflammation, in the impairment of hematopoiesis in those with diabetes. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Iron Management in Multicrystalline Silicon through Predictive Simulation: Point Defects, Precipitates, and Structural Defect Interactions

2013 ◽  
Vol 205-206 ◽  
pp. 15-25 ◽  
Author(s):  
Jasmin Hofstetter ◽  
David P. Fenning ◽  
Douglas M. Powell ◽  
Ashley E. Morishige ◽  
Tonio Buonassisi
Keyword(s):  
Iron Concentration ◽  
Iron Silicide ◽  
Multicrystalline Silicon ◽  
Temperature Profiles ◽  
Photovoltaic Applications ◽  
High Temperature Processing ◽  
High Concentrations ◽  
Defect Interactions ◽  
Simulation Point ◽  
Iron Precipitates

In multicrystalline silicon for photovoltaic applications, high concentrations of iron are usually found, which deteriorate material performance. Due to the limited solubility of iron in silicon, only a small fraction of the total iron concentration is present as interstitial solute atoms while the vast majority is present as iron silicide precipates. The concentration of iron interstitials can be effectively reduced during phosphorus diffusion gettering (PDG), but this strongly depends on the size and density of iron precipitates, which partly dissolve during high-temperature processing. The distribution of precipitated iron varies along the height of a mc-Si ingot and is not significantly reduced during standard PDG steps. However, the removal of both iron interstitials and precipitates can be enhanced by controlling their kinetics through carefully engineered time-temperature profiles, guided by simulations.

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