Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein.

PubMed

Jorgensen, Josh M; Yang, Zhenyu; Lönnerdal, Bo; Chantry, Caroline J; Dewey, Kathryn G

2017-06-01

Background: Ferritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied. Objective: We aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and α1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California. Methods: This is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP. Results: At 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin ( r = 0.07 and -0.06; n = 114 at 2 wk; -0.14 and -0.14; n = 95 at 17 wk) or hepcidin ( r = 0.18 and -0.03 at 2 wk; -0.05 and -0.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP ( P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02]. Conclusion: Lower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states. © 2017 American Society for Nutrition.

Iron stores and obesity are negatively associated with ovarian volume and anti-Müllerian hormone levels in women with polycystic ovary syndrome.

PubMed

Yang, Jehn-Hsiahn; Chou, Chia-Hung; Yang, Wei-Shiung; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

2015-12-01

Obesity and insulin resistance are associated with increased iron stores, but have conflicting effects on ovarian reserve in women with polycystic ovary syndrome (PCOS). Iron-catalyzed oxidative stress might be detrimental to ovarian tissue and granulosa cell function. In this study we determined the association between body iron stores, obesity, and ovarian reserve in women with PCOS. One hundred and fifty-six women diagnosed with PCOS according to Rotterdam criteria and 30 normoweight healthy control women were enrolled in this cross-sectional study. Ovarian volume, total antral follicle count, and the anti-Müllerian hormone (AMH) level were measured as an indicator of ovarian reserve. Ferritin and transferrin-bound iron levels were significantly higher in women with PCOS than normoweight controls. Obese women with PCOS had higher ferritin levels (p = 0.006), but lower AMH levels (p < 0.0001) than nonobese women with PCOS. Using univariate analysis, the AMH level and mean ovarian volume were inversely related to the ferritin level, homeostasis model assessment of insulin resistance, and body mass index in women with PCOS. Body mass index and ferritin level remained significantly correlated with a lower AMH level and reduced ovarian volume, respectively, after considering other confounding variables. An elevated ferritin level and obesity were negatively associated with ovarian volume and the AMH level, respectively, in women with PCOS. Copyright © 2015. Published by Elsevier B.V.

Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation

PubMed Central

Oliveira, Marina G.; Mesquita, Eliene D. D.; Silva, Elisangela; Rauwerdink, Anneloek; Cobelens, Frank; Oliveira, Martha M.; Kritski, Afrânio

2017-01-01

Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Methods Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Results Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. Conclusions CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. PMID:28384354

Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still's disease: A multicenter retrospective study.

PubMed

Kirino, Yohei; Kawaguchi, Yasushi; Tada, Yoshifumi; Tsukamoto, Hiroshi; Ota, Toshiyuki; Iwamoto, Masahiro; Takahashi, Hiroki; Nagasawa, Kohei; Takei, Shuji; Horiuchi, Takahiko; Ichida, Hisae; Minota, Seiji; Ueda, Atsuhisa; Ohta, Akihide; Ishigatsubo, Yoshiaki

2018-01-11

Heme oxygenase (HO)-1 is a heme-degrading enzyme highly expressed in monocyte/macrophage, serum levels of which may be promising biomarker for adult-onset Still's disease (AOSD). We here report data on the use of serum ferritin and HO-1 levels in AOSD. Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD patients. Three independent experts judged whether the patients were definite AOSD depending on the clinical information. These 91 'definite AOSD' patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. Serum ferritin and HO-1 levels were measured using ELISA. Associations between clinical symptoms, serum ferritin, and HO-1 were explored. Multivariate regression analysis was performed to identify independent variables associated with definite AOSD diagnosis. Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia. Receiver operating characteristic analysis identified optimal levels of serum ferritin (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p = .013), suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status. Multivariate analysis identified neutrophilia, RF/ANA negativity, sore throat, and elevated serum HO-1 as independent variables associated with AOSD diagnosis. We confirmed that serum ferritin and HO-1 serve as highly specific and sensitive biomarkers for AOSD. A future prospective study with large sample size is necessary to determine whether these biomarkers could be included in Yamaguchi's Criteria.

Iron Status and the Acute Post-Exercise Hepcidin Response in Athletes

PubMed Central

Peeling, Peter; Sim, Marc; Badenhorst, Claire E.; Dawson, Brian; Govus, Andrew D.; Abbiss, Chris R.; Swinkels, Dorine W.; Trinder, Debbie

2014-01-01

This study explored the relationship between serum ferritin and hepcidin in athletes. Baseline serum ferritin levels of 54 athletes from the control trial of five investigations conducted in our laboratory were considered; athletes were grouped according to values <30 μg/L (SF<30), 30–50 μg/L (SF30–50), 50–100 μg/L (SF50–100), or >100 μg/L (SF>100). Data pooling resulted in each athlete completing one of five running sessions: (1) 8×3 min at 85% vVO2peak; (2) 5×4 min at 90% vVO2peak; (3) 90 min continuous at 75% vVO2peak; (4) 40 min continuous at 75% vVO2peak; (5) 40 min continuous at 65% vVO2peak. Athletes from each running session were represented amongst all four groups; hence, the mean exercise duration and intensity were not different (p>0.05). Venous blood samples were collected pre-, post- and 3 h post-exercise, and were analysed for serum ferritin, iron, interleukin-6 (IL-6) and hepcidin-25. Baseline and post-exercise serum ferritin levels were different between groups (p<0.05). There were no group differences for pre- or post-exercise serum iron or IL-6 (p>0.05). Post-exercise IL-6 was significantly elevated compared to baseline within each group (p<0.05). Pre- and 3 h post-exercise hepcidin-25 was sequentially greater as the groups baseline serum ferritin levels increased (p<0.05). However, post-exercise hepcidin levels were only significantly elevated in three groups (SF30–50, SF50–100, and SF>100; p<0.05). An athlete's iron stores may dictate the baseline hepcidin levels and the magnitude of post-exercise hepcidin response. Low iron stores suppressed post-exercise hepcidin, seemingly overriding any inflammatory-driven increases. PMID:24667393

Elevated serum ferritin concentration is associated with incident type 2 diabetes mellitus in a Chinese population: A prospective cohort study.

PubMed

Chen, Ling; Li, Yufeng; Zhang, Fang; Zhang, Simin; Zhou, Xianghai; Ji, Linong

2018-05-01

We aimed to evaluate the association between serum ferritin levels and incident type 2 diabetes mellitus risk in a Chinese population. This cohort study assessed 2225 Chinese individuals aged 25-75 years. Diabetes mellitus was diagnosed using the 1999 World Health Organization definition with a median follow-up period of 20 months. Cox proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals (CI) for incident diabetes when serum ferritin concentrations increased by one standard deviation. During the follow-up period, 112 cases (62 men and 50 women) of type 2 diabetes mellitus were identified. Baseline serum ferritin levels were higher in the diabetes than the non-diabetes group. After adjusting for age, body mass index, waist circumference, mean arterial pressure, fasting plasma glucose, fasting insulin, hemoglobin A1c, total cholesterol, high-density lipoprotein cholesterol, alanine transaminase and triglyceride levels, family history of diabetes mellitus, pork meat consumption, neutrophil/lymphocyte ratio, education, and annual household income, the hazard ratios for incident diabetes corresponding to one standard deviation increase in serum ferritin levels were 1.17 (95% CI 1.03, 1.34), 1.20 (95% CI 1.003, 1.43), and 1.03 (95% CI 0.82, 1.31) for the total population, men, and women, respectively. High serum ferritin levels were associated with a higher risk of incident type 2 diabetes mellitus independent of traditional risk factors in the total population and men. Copyright © 2018 Elsevier B.V. All rights reserved.

The Impact of Iron Overload in Patients with Acute Leukemia and Myelodysplastic Syndrome on Hepatic and Endocrine functions.

PubMed

Yassin, Mohamed A; Soliman, Ashraf; De Sanctis, Vincenzo; Hmissi, Saloua M; Abdulla, Mohammad Aj; Ekeibed, Yeslem; Ismail, Omer; Nashwan, Abdulqadir; Soliman, Dina; Almusharaf, Mohammed; Hussein, Redwa

2018-04-03

Patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusion usually have an elevated serum ferritin. These findings have led to the suggestion that iron overload is common and may have deleterious effects in these patients. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. Therefore, we measured the liver iron content (LIC) by the FerriScan® method and investigated the liver function and some endocrine tests in 27 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). Using FerriScan® method, the normal mean LIC levels are: 4.3 ± 2.9 mg Fe/g dry weight (d.w.). In our patients, the mean serum ferritin level was 1965 ± 2428 ng/mL. In our patients, the mean total iron in the blood received by them was 7177 ± 5009 mg. In 6 out of 27 patients LIC was > 7 mg Fe/g d.w. and in 11/27 serum ferritin was > 1000 ng/ml. Measuring fasting blood glucose revealed 3/27 with diabetes mellitus and 4/27 with impaired fasting glucose (IFG). All patients had normal serum concentrations of calcium, parathormone (PTH), free thyroxine (FT4) and thyrotropin (TSH). Four patients had elevated serum alanine transferase (ALT). LIC was correlated significantly with ferritin level (r = 0.5666; P < 0.001) and the cumulative amount of iron in the transfused blood (r = 0.523; P <0.001). LIC was correlated significantly with ALT (r = 0.277; P = 0.04) and fasting blood glucose (FBG) was correlated significantly with the amount of iron transfused (r = 0.52, p < 0.01) and ALT level (r = 0.44; P< 0.01). The age of patients did not correlate with LIC, FBG or ALT. In conclusions, these results contribute to our understanding of the prevalence of dysglycemia and hepatic dysfunction in relation to parenchymal iron overload in patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusions.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

PubMed

Coelho-Borges, Silvia; Cheinquer, Hugo; Wolff, Fernando Herz; Cheinquer, Nelson; Krug, Luciano; Ashton-Prolla, Patricia

2012-01-01

Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population

PubMed Central

Gordeuk, Victor R.; Reboussin, David M.; McLaren, Christine E.; Barton, James C.; Acton, Ronald T.; McLaren, Gordon D.; Harris, Emily L.; Reiss, Jacob A.; Adams, Paul C.; Speechley, Mark; Phatak, Pradyumna D.; Sholinsky, Phyliss; Eckfeldt, John H.; Chen, Wen-Pin; Passmore, Leah; Dawkins, Fitzroy W.

2013-01-01

How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 μg/L (men), >200 μg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but <4 g. In conclusion, serum ferritin >900 μg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 μg/L in male C282Y homozygotes is predictive of moderately increased iron stores. PMID:18429050

Soybean Ferritin Expression in Saccharomyces cerevisiae Modulates Iron Accumulation and Resistance to Elevated Iron Concentrations

PubMed Central

de Llanos, Rosa; Martínez-Garay, Carlos Andrés; Fita-Torró, Josep; Romero, Antonia María; Martínez-Pastor, María Teresa

2016-01-01

ABSTRACT Fungi, including the yeast Saccharomyces cerevisiae, lack ferritin and use vacuoles as iron storage organelles. This work explored how plant ferritin expression influenced baker's yeast iron metabolism. Soybean seed ferritin H1 (SFerH1) and SFerH2 genes were cloned and expressed in yeast cells. Both soybean ferritins assembled as multimeric complexes, which bound yeast intracellular iron in vivo and, consequently, induced the activation of the genes expressed during iron scarcity. Soybean ferritin protected yeast cells that lacked the Ccc1 vacuolar iron detoxification transporter from toxic iron levels by reducing cellular oxidation, thus allowing growth at high iron concentrations. Interestingly, when simultaneously expressed in ccc1Δ cells, SFerH1 and SFerH2 assembled as heteropolymers, which further increased iron resistance and reduced the oxidative stress produced by excess iron compared to ferritin homopolymer complexes. Finally, soybean ferritin expression led to increased iron accumulation in both wild-type and ccc1Δ yeast cells at certain environmental iron concentrations. IMPORTANCE Iron deficiency is a worldwide nutritional disorder to which women and children are especially vulnerable. A common strategy to combat iron deficiency consists of dietary supplementation with inorganic iron salts, whose bioavailability is very low. Iron-enriched yeasts and cereals are alternative strategies to diminish iron deficiency. Animals and plants possess large ferritin complexes that accumulate, detoxify, or buffer excess cellular iron. However, the yeast Saccharomyces cerevisiae lacks ferritin and uses vacuoles as iron storage organelles. Here, we explored how soybean ferritin expression influenced yeast iron metabolism, confirming that yeasts that express soybean seed ferritin could be explored as a novel strategy to increase dietary iron absorption. PMID:26969708

Ferritin for the Clinician

PubMed Central

Knovich, Mary Ann; Storey, Jonathan A.; Coffman, Lan G.; Torti, Suzy V.

2009-01-01

Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage. PMID:18835072

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.

PubMed

Kukulj, Suzana; Jaganjac, Morana; Boranic, Milivoj; Krizanac, Simun; Santic, Zarko; Poljak-Blazi, Marija

2010-06-01

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

Obese women less likely to have low serum ferritin, Nicaragua

PubMed Central

Wendt, Amanda S; Jefferds, Maria E; Perrine, Cria G; Halleslevens, Patricia; Sullivan, Kevin M

2015-01-01

Objective To examine the association between overweight and obesity and serum ferritin among women of reproductive age (15–49 years) in Nicaragua, considering the effect of α1-acid glycoprotein (AGP), a marker of inflammation. Design We analysed data from the 2004–05 Nicaraguan Integrated Surveillance System for Nutrition Interventions. Three logistic regression models were analysed with low serum ferritin (<15 μg/l) as the dependent variable: (i) overweight or obese status and covariates; (ii) model 1 plus AGP; and (iii) model 1 restricted to only women with normal AGP levels (≤1·0 g/l). Setting Nicaragua. Subjects Included in this analysis were 832 non-pregnant mother/caregivers (15–49 years) surveyed in 2004–2005. Results In the sample, prevalence of overweight and obesity was 31·8 % and 19·2 %, respectively, and 27·6 % had low serum ferritin. In model 1, the adjusted OR of low serum ferritin was 0·74 (95 % CI 0·52, 1·05) for overweight women and 0·42 (95 % CI 0·26, 0·65) for obese women. In model 2, AGP was significantly independently associated with low serum ferritin (adjusted OR=0·56, 95 % CI 0·34, 0·92) while the adjusted OR for overweight and obesity were largely unchanged. Excluding women with elevated AGP did not appreciably affect the relationship between overweight or obesity and low serum ferritin (model 3). Conclusions Overall, in this population of reproductive-age women, obese women were less likely to have low serum ferritin levels, and this was independent of inflammation as measured by AGP. PMID:24848519

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study.

PubMed

Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev; Badmaev, Vladimir

2017-01-01

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis.

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1–Risk Myelodysplastic Syndrome—A Small, Investigative Study

PubMed Central

Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev; Badmaev, Vladimir

2017-01-01

Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. Aim: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Method: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. Results: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. Discussion: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis. PMID:29147080

Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial.

PubMed

Ong, Sim Y; Gurrin, Lyle C; Dolling, Lara; Dixon, Jeanette; Nicoll, Amanda J; Wolthuizen, Michelle; Wood, Erica M; Anderson, Gregory J; Ramm, Grant A; Allen, Katrina J; Olynyk, John K; Crawford, Darrell; Ramm, Louise E; Gow, Paul; Durrant, Simon; Powell, Lawrie W; Delatycki, Martin B

2017-12-01

The iron overload disorder hereditary haemochromatosis is most commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from any randomised trials, current evidence is insufficient to determine whether individuals with hereditary haemochromatosis and moderately elevated serum ferritin, should undergo iron reduction treatment. This trial aimed to establish whether serum ferritin normalisation in this population improved symptoms and surrogate biomarkers. This study was a multicentre, participant-blinded, randomised controlled trial done at three centres in Australia. We enrolled people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years, with moderately elevated serum ferritin, defined as 300-1000 μg/L, and raised transferrin saturation. Participants were randomly assigned, via a computer-generated random number, to undergo either iron reduction by erythrocytapheresis (treatment group) or sham treatment by plasmapheresis (control group). Randomisation was stratified by baseline serum ferritin (<600 μg/L or ≥600 μg/L), sex, and study site. Erythrocytapheresis and plasmapheresis were done every 3 weeks, the number of procedures and volume of red cells or plasma removed determined on the basis of each patient's haemoglobin, haematocrit, and serum ferritin concentration, as well their height and weight. In the erythrocytapheresis group, the target was to reduce serum ferritin to less than 300 μg/L. The number of procedures for the control group was based on the initial serum ferritin and prediction of decrease in serum ferritin of approximately 120 μg/L per treatment. The primary outcome was patient-reported Modified Fatigue Impact Scale (MFIS) score, measured at baseline and before unblinding. Analyses were by intention to treat, including the safety analysis. The trial is registered with ClinicalTrials.gov, number NCT01631708, and has been completed. Between Aug 15, 2012, and June 9, 2016, 104 participants were randomly assigned to the treatment (n=54) and control (n=50) groups, of whom 94 completed the study (50 in the treatment group and 44 in the control group). Improvement in MFIS score was greater in the treatment group than in the control group (mean difference -6·3, 95% CI -11·1 to -1·4, p=0·013). There was a significant difference in the cognitive subcomponent (-3·6, -5·9 to -1·3, p=0·0030), but not in the physical (-1·90 -4·5 to 0·63, p=0·14) and psychosocial (-0·54, -1·2 to 0·11, p=0·10) subcomponents. No serious adverse events occurred in either group. One participant in the control group had a vasovagal event and 17 participants (14 in the treatment group and three in the control group) had transient symptoms assessed as related to hypovolaemia. Mild citrate reactions were more common in the treatment group (32 events [25%] in 129 procedures) compared with the control group (one event [1%] in 93 procedures). To our knowledge, this study is the first to objectively assess the consequences of iron removal in individuals with hereditary haemochromatosis and moderately elevated serum ferritin. Our results suggest that serum ferritin normalisation by iron depletion could be of benefit for all individuals with hereditary haemochromatosis and elevated serum ferritin levels. National Health and Medical Research Council (Australia). Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of a workplace hemochromatosis screening program.

PubMed

Stave, G M; Mignogna, J J; Powell, G S; Hunt, C M

1999-05-01

Hemochromatosis is a common inherited disorder of iron metabolism with significant health consequences for the employed population. Although screening for hemochromatosis has been recommended, workplace screening programs remain uncommon. In the first year of a newly initiated corporate screening program, 1968 employees were tested. The screening algorithm included measurement of serum iron and transferrin and subsequent ferritin levels in those employees with elevated iron/transferrin ratios. Thirteen percent of men and 21% of women had elevated iron/transferrin ratios. Of these, 14 men and 2 women had elevated ferritin levels. Of these 16, three had liver biopsies and all three have hemochromatosis. The cost of the screening program was $27,850. The cost per diagnosis was $9283 and the cost per year of life saved was $928. These costs compare very favorably with other common workplace screening programs. Several barriers to obtaining definitive diagnoses on all patients with a positive screening result were identified; strategies to overcome these barriers would further enhance the cost effectiveness of the program. We conclude that workplace hemochromatosis screening is highly cost effective and should be incorporated into health promotion/disease prevention programs.

Chromium ion release from stainless steel pediatric scoliosis instrumentation.

PubMed

Cundy, Thomas P; Delaney, Christopher L; Rackham, Matthew D; Antoniou, Georgia; Oakley, Andrew P; Freeman, Brian J C; Sutherland, Leanne M; Cundy, Peter J

2010-04-20

Case-control study. To determine whether serum metal ion levels and erythrocyte chromium levels in adolescents with stainless steel spinal instrumentation are elevated when compared with 2 control groups. Instrumented spinal arthrodesis is a common procedure to correct scoliosis. The long-term consequences of retained implants are unclear. Possible toxic effects related to raised metal ion levels have been reported in the literature. Thirty patients who underwent posterior spinal arthrodesis with stainless steel instrumentation for scoliosis (group 1) were included. Minimum postoperative duration was 3 years. Serum chromium, molybdenum, iron, and ferritin levels were measured. Participants with elevated above normal serum chromium levels (n = 11) also underwent erythrocyte chromium analysis. Comparisons were made with 2 control groups; 10 individuals with scoliosis with no spinal surgery (group 2) and 10 volunteers without scoliosis (group 3). All control group participants underwent serum and erythrocyte analysis. Elevated above normal serum chromium levels were demonstrated in 11 of 30 (37%) group 1 participants. Elevated serum chromium levels were demonstrated in 0 of 10 participants (0%) in group 2 and 1 of 10 (10%) in group 3. There was a statistically significant elevation in serum chromium levels between group 1 and group 2 participants (P = 0.001). There was no significant association between groups 1, 2, and 3 for serum molybdenum, iron, and ferritin levels. Erythrocyte chromium measurements were considered within the normal range for all participants tested (n = 31). Raised serum chromium levels were detected in 37% of patients following instrumented spinal arthrodesis for correction of scoliosis. This new finding has relatively unknown health implications but potential mutagenic, teratogenic and carcinogenic sequelae. This is especially concerning with most scoliosis patients being adolescent females with their reproductive years ahead.

Ferritin levels predict severe dengue.

PubMed

Soundravally, R; Agieshkumar, B; Daisy, M; Sherin, J; Cleetus, C C

2015-02-01

Currently, no tests are available to monitor and predict severity and outcome of dengue. To find potential markers that predict dengue severity, the present study validated the serum level of three acute-phase proteins α-1 antitrypsin, ceruloplasmin and ferritin in a pool of severe dengue cases compared to non-severe forms and other febrile illness controls. A total of 96 patients were divided into two equal groups with group 'A' comprising dengue-infected cases and group 'B' with other febrile illness cases negative for dengue. Out of 48 dengue-infected cases, 13 had severe dengue and the remaining 35 were classified as non-severe dengue. Immunoassays were performed to evaluate the serum levels of acute-phase proteins both on the day of admission and on the day of defervescence. The efficiency of individual proteins in predicting the disease severity was assessed using receiver operating characteristic curve. The study did not find any significant difference in the levels of α-1 antitrypsin between the clinical groups. A significant increase in the levels of ceruloplasmin around defervescence in severe cases compared to non-severe and other febrile controls was observed and this is the first report describing the potential association of ceruloplasmin and dengue severity. Interestingly, a steady increase in the level of serum ferritin was recorded throughout the course of illness. Among all the three proteins, the elevated ferritin level could predict the disease severity with highest sensitivity and specificity of 76.9 and 83.3 %, respectively, on the day of admission and the same was found to be 90 and 91.6 % around defervescence. On the basis of this diagnostic efficiency, we propose that ferritin may serve as a potential biomarker for an early prediction of disease severity.

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African-Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

PubMed Central

Rivers, Charles A.; Barton, James C.; Gordeuk, Victor R.; Acton, Ronald T.; Speechley, Mark R.; Snively, Beverly M.; Leiendecker-Foster, Catherine; Press, Richard D.; Adams, Paul C.; McLaren, Gordon D.; Dawkins, Fitzroy W.; McLaren, Christine E.; Reboussin, David M.

2007-01-01

The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (≥300 μg/L in men and ≥200 μg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P = 0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P = 0.047); corresponding differences were not observed among women. This appeared to be unrelated to self-reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P = 0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. PMID:17276706

Hemochromatosis detection in a health screening program at an Alabama forest products mill.

PubMed

Barton, James C; Cheatwood, Susan M; Key, Timothy J; Acton, Ronald T

2002-08-01

We analyzed hemochromatosis detection in a 11.5-year multiphasic health screening program at a forest products mill. There were 2199 participants: 2032 Whites (1506 men, 526 women) and 167 African Americans (124 men, 43 women); 85.0% of employees were screened. Iron and transferrin saturation were measured in a serum biochemistry profile on specimens obtained after overnight fasting; ferritin was measured in participants with elevated iron concentrations or transferrin saturation > 48%. Participants with elevated ferritin levels underwent further evaluation. Eight White men were diagnosed to have hemochromatosis (frequency 0.0039 in Whites, 0.0053 in White men). The estimated cost per case detected was $8826. Family members of two participants with hemochromatosis were also diagnosed to have hemochromatosis or iron overload. We conclude that detecting hemochromatosis in a workplace multiphasic health screening program is efficacious and economical.

The Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes - the EPIC-InterAct Study

PubMed Central

Podmore, Clara; Meidtner, Karina; Schulze, Matthias B; Scott, Robert A; Ramond, Anna; Butterworth, Adam S; Di Angelantonio, Emanuele; Danesh, John; Arriola, Larraitz; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Cross, Amanda J; Dahm, Christina C; Fagherazzi, Guy; Franks, Paul W; Gavrila, Diana; Grioni, Sara; Gunter, Marc J; Gusto, Gaelle; Jakszyn, Paula; Katzke, Verena; Key, Timothy J; Kühn, Tilman; Mattiello, Amalia; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez-Cantalejo, Emilio; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke MW; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; van der Schouw, Yvonne T; Feskens, Edith JM; Forouhi, Nita G; Sharp, Stephen J; Riboli, Elio; Langenberg, Claudia; Wareham, Nicholas J

2016-01-01

Objective Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores for T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate associations of ferritin, transferrin saturation (TSAT), serum iron and transferrin with T2D incidence, to clarify the role of iron in the pathogenesis of T2D. Research and Design Methods The EPIC-InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron and transferrin with incident T2D in 11,052 cases and a random sub-cohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. Results Higher levels of ferritin and transferrin were associated with a higher risk of T2D [HR in men and women, respectively: 1.07 (95% CI: 1.01; 1.12) and 1.12 (1.05; 1.19) per 100 μg/L higher ferritin level; 1.11 (1.00; 1.24) and 1.22 (1.12; 1.33) per 0.5 g/L higher transferrin level] after adjustment for age, centre, BMI, physical activity, smoking status, education, hsCRP, ALT and GGT. Elevated TSAT (≥45% versus <45%) was associated with a lower risk of T2D in women [0.68 (0.54; 0.86)] but was not statistically significantly associated in men [0.90 (0.75; 1.08)]. Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (pinteraction<0.01). Conclusions The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D. PMID:26861925

Circulating ferritin concentrations and risk of type 2 diabetes in Japanese individuals.

PubMed

Akter, Shamima; Nanri, Akiko; Kuwahara, Keisuke; Matsushita, Yumi; Nakagawa, Tohru; Konishi, Maki; Honda, Toru; Yamamoto, Shuichiro; Hayashi, Takeshi; Noda, Mitsuhiko; Mizoue, Tetsuya

2017-07-01

Higher iron storage has been linked to an increased risk of type 2 diabetes, but little is known about the mediator of this association. Here, we prospectively investigated the association between circulating ferritin, a marker of iron storage, and the incidence of type 2 diabetes among Japanese individuals. The participants were 4,754 employees who attended a comprehensive health check-up in 2008-2009 and donated blood for the study. During 5 years of follow up, diabetes was identified based on plasma glucose, glycated hemoglobin and self-report. Two controls matched to each case on sex, age and date of check-up were randomly chosen using density sampling, giving 327 cases and 641 controls with ferritin measurement. Cox proportional hazards regression was used to estimate the hazard ratio while adjusting for a series of potential confounders or mediators. Elevated serum ferritin levels were associated with a significantly increased risk of type 2 diabetes, with the hazard ratio adjusted for known risk factors in the highest vs lowest quartile of 1.42 (95% confidence interval: 1.03-1.96). This association was unchanged after adjustment for C-reactive protein and adiponectin, but attenuated after adjustment for liver enzyme and insulin resistance (hazard ratio 1.04). The ferritin-diabetes association was confined to non-obese participants. These results suggest that elevated iron storage is associated with increased risk of type 2 diabetes in normal weight individuals, and that this association is partly mediated through liver dysfunction and resulting insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Iron Indices in Bottlenose Dolphins (Tursiops truncatus)

PubMed Central

Mazzaro, Lisa M; Johnson, Shawn P; Fair, Patricia A; Bossart, Greg; Carlin, Kevin P; Jensen, Eric D; Smith, Cynthia R; Andrews, Gordon A; Chavey, Patricia S; Venn-Watson, Stephanie

2012-01-01

Bottlenose dolphins can have iron overload (that is, hemochromatosis), and managed populations of dolphins may be more susceptible to this disease than are wild dolphins. Serum iron, total iron-binding capacity (TIBC), transferrin saturation, and ferritin were measured in 181 samples from 141 dolphins in 2 managed collections and 2 free-ranging populations. Although no iron indices increased with age among free-ranging dolphins, ferritin increased with age in managed collections. Dolphins from managed collections had higher iron, ferritin, and transferrin saturation values than did free-ranging dolphins. Dolphins with high serum iron (exceeding 300 μg/dL) were more likely to have elevated ferritin but not ceruloplasmin or haptoglobin, demonstrating that high serum levels of iron are due to a true increase in total body iron. A time-series study of 4 dolphins with hemochromatosis that were treated with phlebotomy demonstrated significant decreases in serum ferritin, iron, and TIBC between pre- and posttreatment samples; transferrin saturation initially fell but returned to prephlebotomy levels by 6 mo after treatment. Compared with those in managed collections, wild dolphins were 15 times more likely to have low serum iron (100 μg/dL or less), and this measure was associated with lower haptoglobin. In conclusion, bottlenose dolphins in managed collections are more likely to have greater iron stores than are free-ranging dolphins. Determining why this situation occurs among some dolphin populations and not others may improve the treatment of hemochromatosis in dolphins and provide clues to causes of nonhereditary hemochromatosis in humans. PMID:23561885

Lipid peroxidative damage in the erythrocytes and elevation of serum LDL-cholesterol, apolipoprotein-B, ferritin and uric acid with age and in coronary heart disease patients.

PubMed

El-Gebali, H H; Tahir, S A; Haider, S S; El-Fakhri, M M

2000-02-01

To determine the normal serum levels of LDL-cholesterol, apolipoprotein-B, ferritin, uric acid, and the extent of erythrocytes lipid peroxidation in healthy control group subjects and to compare them with coronary heart disease patients. Secondly, to study the effects of age and sex on these parameters. The blood samples from 150 healthy Libyan control group subjects (110 men and 40 women) were classified into 3 groups according to their age. Group I consisted of 76 subjects with an age range from 20 to 35 years. Group II consisted of 45 subjects with an age range from 36 to 50 years. Group III consisted of 29 subjects with an age range from 51 to 74 years. The blood samples from these groups were analyzed for LDL-cholesterol, apolipoprotein-B, ferritin and uric acid levels. Lipid peroxidation was compared in the erythrocytes of 56 selected healthy control group subjects (31 men and 11 women) of the aforementioned age groups. These parameters have shown age-dependent elevation in their levels. Meanwhile, LDL-cholesterol and Apolipoprotein-B levels in female subjects were higher than those of males. However, lipid peroxidation in the erythrocytes has revealed a statistically significant increase with increasing age. The comparison between 93 selected, sex and age matched, healthy control group subjects with 87 selected coronary heart disease patients (55 men and 45 women) with an age range from 30 to 74 years (49.6+13.25) has demonstrated significantly higher concentration of LDL-cholesterol, Apolipoprotein-B, ferritin and uric acid in coronary heart disease patients than those of healthy control group subjects. Meanwhile, lipid peroxidation was also significantly enhanced in coronary heart disease patients compared with healthy control group subjects. Our study has revealed that an increase in the lipid peroxidation in erythrocytes with age and during coronary heart disease, makes red cell membranes more vulnerable to free radical damage via formation of reactive oxygen species. It is thus likely that peroxidative damage may be contributing to an increase in serum LDL-cholesterol, Apolipoprotein-B, probably after its oxidative modification, increase in ferritin and hyperuricemia in coronary heart disease patients.

DIVALENT METAL TRANSPORTER-1 REGULATION BY IRON AND VANADIUM MODULATES HYDROGEN PEROXIDE-INDUCED DNA DAMAGE IN LUNG CELLS

EPA Science Inventory

The divalent metal transporter-1 (DMT1) participates in the detoxification of metals that can damage lung epithelium. Elevated iron levels increase the expression of DMT1 in bronchial epithelial cells stimulating its uptake and storage in ferritin, thus making iron unavailable t...

Management strategies of iron accumulation in a captive population of black rhinoceroses (Diceros bicornis minor).

PubMed

Mylniczenko, Natalie D; Sullivan, Kathleen E; Corcoran, Michelle E; Fleming, Gregory J; Valdes, Eduardo V

2012-09-01

During routine health screens for black rhinoceroses (Diceros bicornis minor) in a captive setting, serum iron and ferritin were analyzed as well as total iron binding capacity and total iron saturation. Trends for ferritin and percent iron saturation showed steady increases since 2003 in four of four animals (three males; one female) with two animals (one male; one female) consistently showing higher elevations over conspecifics. The historical diet had been comprised of a commercial or in-house complete pelleted feed; several species of fresh browse, Bermuda grass, alfalfa and timothy hays, as well as enrichment and training items (apples, carrots, sweet potatoes, and a small amount of leafy greens and vegetables). In 2009, one of the three male rhinoceroses showed a threefold increase in ferritin and concurrently exhibited clinical signs of lethargy, decreased appetite, and disinterest in training. The lone female showed a twofold increase; she also became reproductively acyclic in the prior year. The male was immobilized for examination and phlebotomy. During the same time period, a new version of the complete pelleted feed, with a reduced amount of iron, was introduced. Subsequent to the diet change, the male's ferritin levels have consistently declined, and the female started cycling again. Even with these corrective steps to reduce iron levels, levels of iron saturation remained high, and ferritin levels were still above 1,500 ng/ml. Therapeutic phlebotomy was instituted via a rigorous training program that allowed phlebotomies over a 30-min time frame. This was possible because of a long-term training program for the animals, consistent training personnel, routine collection of samples on a monthly basis, and general comfort level of the animals in the restraint chute. The results of this integrated approach showed some significant improvements and an overall positive impact on the animals.

Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis.

PubMed

Tonial, Cristian T; Garcia, Pedro Celiny R; Schweitzer, Louise Cardoso; Costa, Caroline A D; Bruno, Francisco; Fiori, Humberto H; Einloft, Paulo R; Garcia, Ricardo Branco; Piva, Jefferson Pedro

The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24h (D1), and 72h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p=0.046) and higher maximum inotropic score (p=0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p=0.047), pediatric intensive care unit stay (p=0.020), duration of mechanical ventilation (p=0.011), maximum inotropic score (p=0.001), and fewer ventilator-free hours (p=0.020). Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

PubMed

Kim, Taehee; Rhee, Connie M; Streja, Elani; Obi, Yoshitsugu; Brunelli, Steven M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-02-01

The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory. In a 5-year (January 2007–December 2011) cohort of 81 864 incident US hemodialysis patients, we examined changes in ferritin averaged over 3-month intervals using linear mixed effects models adjusted for intravenous iron dose, malnutrition and inflammatory markers. We then examined ferritin trends across strata of baseline ferritin level, dialysis initiation year, cumulative iron and ESA use in the first dialysis year and baseline hemoglobin level. In models adjusted for iron dose, malnutrition and inflammation, mean ferritin levels increased over time in the overall cohort and across the three lower baseline ferritin strata. Among patients initiating dialysis in 2007, mean ferritin levels increased sharply in the first versus second year of dialysis and again abruptly increased in the fifth year independent of iron dose, malnutrition and inflammatory markers; similar trends were observed among patients who initiated dialysis in 2008 and 2009. In analyses stratified by cumulative iron use, mean ferritin increased among groups receiving iron, but decreased in the no iron group. In analyses stratified by cumulative ESA dose and baseline hemoglobin, mean ferritin increased over time. While ferritin trends correlated with patterns of iron use, increases in ferritin over time persisted independent of intravenous iron and ESA exposure, malnutrition and inflammation.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Uncoupled iron homeostasis in type 2 diabetes mellitus.

PubMed

Altamura, Sandro; Kopf, Stefan; Schmidt, Julia; Müdder, Katja; da Silva, Ana Rita; Nawroth, Peter; Muckenthaler, Martina U

2017-12-01

Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis. Consistent with this finding, we also observed an increase in circulating iron and ferritin levels. Our analysis of db/db mice demonstrates that this model recapitulates the systemic alterations observed in patients. Interestingly, db/db mice show an overall hepatic iron deficiency despite unaltered expression of ferritin and the iron importer TfR1. In addition, the liver correctly senses increased circulating iron levels by activating the BMP/SMAD signaling pathway even though hepcidin expression is decreased. We show that increased AKT phosphorylation may override active BMP/SMAD signaling and decrease hepcidin expression in 10-week old db/db mice. We conclude that the metabolic alterations occurring in T2DM impact on the regulation of iron homeostasis on multiple levels. As a result, metabolic perturbations induce an "iron resistance" phenotype, whereby signals that translate increased circulating iron levels into hepcidin production, are dysregulated. T2DM patients show increased circulating iron levels. T2DM is associated with inappropriately low hepcidin levels. Metabolic alterations in T2DM induce an "iron resistance" phenotype.

Plasma Levels of Aminothiols, Nitrite, Nitrate, and Malondialdehyde in Myelodysplastic Syndromes in the Context of Clinical Outcomes and as a Consequence of Iron Overload

PubMed Central

Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

2014-01-01

The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001) , homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease. PMID:24669287

Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in myelodysplastic syndromes in the context of clinical outcomes and as a consequence of iron overload.

PubMed

Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

2014-01-01

The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001), homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease.

Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

PubMed

Zheng, Y; Gao, L; Wang, D; Zang, D

2017-08-01

The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fever of unknown origin (FUO): CMV infectious mononucleosis or lymphoma?

PubMed

Cunha, Burke A; Chawla, Karishma

2018-07-01

Fever of unknown origin (FUO) refers to fevers of > 101 °F that persist for > 3 weeks and remain undiagnosed after a focused inpatient or outpatient workup. FUO may be due to infectious, malignant/neoplastic, rheumatic/inflammatory, or miscellaneous disorders. The FUO category determines the focus of the diagnostic workup. In the case presented of an FUO in a young woman, there were clinical findings of both CMV infectious mononucleosis or a lymphoma, e.g., highly elevated ESR, elevated ferritin levels, and elevated ACE level, β-2 microglobulins. The indium scan showed intense splenic uptake. Lymph node biopsy, PET scan, and flow cytometry were negative for lymphoma. CMV infectious mononucleosis was the diagnosis, and she made a slow recovery.

PERIODIC LIMB MOVEMENTS AND RESTLESS LEGS SYNDROME IN CHILDREN WITH A HISTORY OF PREMATURITY

PubMed Central

Cielo, Christopher M.; DelRosso, Lourdes M.; Tapia, Ignacio E.; Biggs, Sarah N.; Nixon, Gillian M.; Meltzer, Lisa J.; Traylor, Joel; Kim, Ji Young; Marcus, Carole L.

2017-01-01

Introduction Little is known about which children are at increased risk for restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). Polysomnographic data from the Caffeine for Apnea of Prematurity-Sleep (CAPS) study showed a high prevalence of elevated periodic limb movement index in a cohort of ex-preterm children, but the clinical importance of this finding, such as association with RLS, is unknown. We hypothesized that ex-preterm children would have a high prevalence of RLS and PLMD. Methods Ex-preterm children enrolled in CAPS, now aged 5-12 years, completed home polysomnography and standardized questionnaires. A diagnosis of RLS or PLMD was established by participants meeting the International Classification of Sleep Disorders, 3rd edition criteria based on questionnaires and polysomnograms. Clinically available serum ferritin levels were assessed. Results 167 participants underwent polysomnography and completed all questionnaires. The overall prevalence of RLS was 14/167 (8.4%). An additional 13 subjects (7.8%) were found to have PLMD. Of the 26 participants who had >5 periodic limb movements/hour, 7 (26.9%) had RLS and 13 (50%) had PLMD. Serum ferritin levels were <50 mcg/L (range 11 to 38.4) for all 8 participants referred for testing. Conclusions Children with a history of prematurity have a high prevalence of RLS, particularly those with elevated periodic limb movements. Iron deficiency likely contributes to RLS and PLMD symptoms in this population. Clinicians evaluating ex-preterm children with sleep disturbances should evaluate for RLS and PLMD. Further studies including serum ferritin evaluation are needed to confirm these findings. PMID:28215268

Ferritin accumulation under iron scarcity in Drosophila iron cells.

PubMed

Mehta, A; Deshpande, A; Bettedi, L; Missirlis, F

2009-10-01

Ferritins are highly stable, multi-subunit protein complexes with iron-binding capacities that reach 4500 iron atoms per ferritin molecule. The strict dependence of cellular physiology on an adequate supply of iron cofactors has likely been a key driving force in the evolution of ferritins as iron storage molecules. The insect intestine has long been known to contain cells that are responsive to dietary iron levels and a specialized group of "iron cells" that always accumulate iron-loaded ferritin, even when no supplementary iron is added to the diet. Here, we further characterize ferritin localization in Drosophila melanogaster larvae raised under iron-enriched and iron-depleted conditions. High dietary iron intake results in ferritin accumulation in the anterior midgut, but also in garland (wreath) cells and in pericardial cells, which together filter the circulating hemolymph. Ferritin is also abundant in the brain, where levels remain unaltered following dietary iron chelation, a treatment that depletes ferritin from the aforementioned tissues. We attribute the stability of ferritin levels in the brain to the function of the blood-brain barrier that may shield this organ from systemic iron fluctuations. Most intriguingly, our dietary manipulations demonstrably iron-depleted the iron cells without a concomitant reduction in their production of ferritin. Therefore, insect iron cells may constitute an exception from the evolutionary norm with respect to iron-dependent ferritin regulation. It will be of interest to decipher both the physiological purpose served and the mechanism employed to untie ferritin regulation from cellular iron levels in this cell type.

DETERMINATION OF FERRITIN AND HEMOSIDERIN IRON IN PATIENTS WITH NORMAL IRON STORES AND IRON OVERLOAD BY SERUM FERRITIN KINETICS

PubMed Central

SAITO, HIROSHI; TOMITA, AKIHIRO; OHASHI, HARUHIKO; MAEDA, HIDEAKI; HAYASHI, HISAO; NAOE, TOMOKI

2012-01-01

ABSTRACT We attempted to clarify the storage iron metabolism from the change in the serum ferritin level. We assumed that the nonlinear decrease in serum ferritin was caused by serum ferritin increase in iron mobilization. Under this assumption, we determined both ferritin and hemosiderin iron levels by computer-assisted simulation of the row of decreasing assay-dots of serum ferritin in 11 patients with normal iron stores free of both iron deficiency and iron overload; chronic hepatitis C (CHC) and iron deficiency anemia after treatment, and 11 patients with iron overload; hereditary hemochromatosis (HH) and transfusion-dependent anemias (TD). We determined the iron removal rates of 20 and 17 mg/day by administering mean doses of deferasirox at 631 and 616 mg/day in 2 TD during the period of balance of iron addition and removal as indicated by the serum ferritin returned to the previous level. The ferritin-per-hemosiderin ratio was almost the same in both HH and CHC. This matched the localized hepatic hemosiderin deposition in CHC with normal iron stores. We detected the ferritin increased by utilizing the hemosiderin iron in iron removal and the ferritin reduced by transforming ferritin into hemosiderin in iron additions. The iron storing capacity of hemosiderin was limitless, while that of ferritin was suppressed when ferritin iron exceeded around 5 grams. We confirmed the pathway of iron from hemosiderin to ferritin in iron mobilization, and that from ferritin to hemosiderin in iron deposition. Thus, serum ferritin kinetics enabled us to be the first to clinically clarify storage iron metabolism. PMID:22515110

H-Ferritin Is Preferentially Incorporated by Human Erythroid Cells through Transferrin Receptor 1 in a Threshold-Dependent Manner

PubMed Central

Sakamoto, Soichiro; Kawabata, Hiroshi; Masuda, Taro; Uchiyama, Tatsuki; Mizumoto, Chisaki; Ohmori, Katsuyuki; Koeffler, H. Phillip; Kadowaki, Norimitsu; Takaori-Kondo, Akifumi

2015-01-01

Ferritin is an iron-storage protein composed of different ratios of 24 light (L) and heavy (H) subunits. The serum level of ferritin is a clinical marker of the body’s iron level. Transferrin receptor (TFR)1 is the receptor not only for transferrin but also for H-ferritin, but how it binds two different ligands and the blood cell types that preferentially incorporate H-ferritin remain unknown. To address these questions, we investigated hematopoietic cell-specific ferritin uptake by flow cytometry. Alexa Fluor 488-labeled H-ferritin was preferentially incorporated by erythroid cells among various hematopoietic cell lines examined, and was almost exclusively incorporated by bone marrow erythroblasts among human primary hematopoietic cells of various lineages. H-ferritin uptake by erythroid cells was strongly inhibited by unlabeled H-ferritin but was only partially inhibited by a large excess of holo-transferrin. On the other hand, internalization of labeled holo-transferrin by these cells was not inhibited by H-ferritin. Chinese hamster ovary cells lacking functional endogenous TFR1 but expressing human TFR1 with a mutated RGD sequence, which is required for transferrin binding, efficiently incorporated H-ferritin, indicating that TFR1 has distinct binding sites for H-ferritin and holo-transferrin. H-ferritin uptake by these cells required a threshold level of cell surface TFR1 expression, whereas there was no threshold for holo-transferrin uptake. The requirement for a threshold level of TFR1 expression can explain why among primary human hematopoietic cells, only erythroblasts efficiently take up H-ferritin. PMID:26441243

Iron and ADHD: Time to Move beyond Serum Ferritin Levels

ERIC Educational Resources Information Center

Donfrancesco, Renato; Parisi, Pasquale; Vanacore, Nicola; Martines, Francesca; Sargentini, Vittorio; Cortese, Samuele

2013-01-01

Objective: (a) To compare serum ferritin levels in a sample of stimulant-naive children with ADHD and matched controls and (b) to assess the association of serum ferritin to ADHD symptoms severity, ADHD subtypes, and IQ. Method: The ADHD and the control groups included 101 and 93 children, respectively. Serum ferritin levels were determined with…

[The usefulness of evaluation of: ferritin, ultrasensitive CRP and tissue specific polypeptide 18th (TPS) in assessment of therapy efficacy in patients with nasal polyps].

PubMed

Pałac, Jacek; Bratek, Szczepan; Partyka, Robert; Misiołek, Maciej

2014-01-01

Chronic rhinosinusitis with nasal polyps is social, clinical and cost-effective problem, by reason of bothersome symptoms, chronic nature of the disease, tendency to recur and lack of satisfying treatment. The aim of this study is assessment of suitability of hsCRP, ferritin and blood levels in nasal polyps patients in evaluation of treatment efficacy. The study enrolled 38 patients between 20 and 68 years of age. Patients were divided into 2 groups. Levels of ultrasensitive CRP ferritin and TPS have been measured in all patients. The ultrasensitive CRP levels have been measured by chemiluminescence method. Ferritin levels have been measured by MEIA method. The TPS levels have been measured by chemiluminescence method. Comparison of mean ferritin levels in both study groups in each stage of observation shows the significant difference of mean values in only 6 weeks after surgery. Mean ferritin level is significantly lower in group I than in group II (p<0.05). Mean hsCRP levels vary from one corresponding to ferritin levels. Statistically significant difference between study groups in 2nd and 6th week after surgery has been ascertained (p<0.05). Similarly, like in ferritin levels, the TPS levels are significantly different in 6th week after surgery. Analysis of ferritin, hsCRP and TPS serum levels indicates that these may be useful in assessment of treatment efficacy in patients with nasal polyps. Rise of the chosen inflammatory state parameter level in the postoperative monitoring and anti-inflammatory treatment introduction in nasal polyps patients may inhibit the recurrence of the disease. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

Serum ferritin levels are associated with arterial stiffness in healthy Korean adults.

PubMed

Ha, Ji Yoon; Kim, Min Kyung; Kang, Shinae; Nam, Ji Sun; Ahn, Chul Woo; Kim, Kyung Rae; Park, Jong Suk

2016-08-01

Although an association between serum ferritin and atherosclerosis has been suggested, limited epidemiologic data are available regarding the association between ferritin and arterial stiffness in healthy adults. A total of 2932 healthy subjects were enrolled in this study. Anthropometric and biochemical profiles including ferritin were measured. The arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Serum ferritin levels were classified into quartiles and baPWV values gradually increased with each ferritin quartile. Multiple regression analysis showed that ferritin levels were independently correlated with baPWV. After adjusting for multiple risk factors, as compared with the lowest quartile, the odds ratios for high baPWV (>75(th) percentile) were 1.15 (0.84-1.56), 1.37 (0.97-1.73), and 1.46 (1.29-2.17) among men (p for trend < 0.05) and 1.24 (0.87-1.79), 1.53 (1.09-2.16), and 1.80 (1.25-2.82) among women (p for trend < 0.05), for the second, third, and fourth quartiles of ferritin, respectively. In conclusion, serum ferritin levels are independently associated with arterial stiffness in healthy Korean adults. © The Author(s) 2016.

Periodic limb movements and restless legs syndrome in children with a history of prematurity.

PubMed

Cielo, Christopher M; DelRosso, Lourdes M; Tapia, Ignacio E; Biggs, Sarah N; Nixon, Gillian M; Meltzer, Lisa J; Traylor, Joel; Kim, Ji Young; Marcus, Carole L

2017-02-01

Little is known about the pediatric population at an increased risk of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). Polysomnographic data from the Caffeine for Apnea of Prematurity-Sleep (CAPS) study showed a high prevalence of elevated periodic limb movement index (PLMI) in a cohort of ex-preterm children, but the clinical importance of this finding, such as association with RLS, is unknown. We hypothesized that ex-preterm children would have a high prevalence of RLS and PLMD. Ex-preterm children enrolled in CAPS, now aged 5-12 years, completed home polysomnography (PSG) and standardized questionnaires. A diagnosis of RLS or PLMD was established by participants meeting the International Classification of Sleep Disorders, 3rd edition, criteria based on questionnaires and polysomnograms. The clinically available serum ferritin levels were assessed. In total, 167 participants underwent polysomnography and completed all questionnaires. The overall prevalence of RLS was 14/167 (8.4%). An additional 13 subjects (7.8%) were found to have PLMD. Of the 26 participants who had PLMI > 5/h, seven (26.9%) had RLS and 13 (50%) had PLMD. The serum ferritin levels were <50 mcg/L (range -38.4) for all eight participants referred for testing. Children with a history of prematurity have a high prevalence of RLS, particularly those with elevated periodic limb movements. Iron deficiency likely contributes to RLS and PLMD symptoms in this population. Clinicians evaluating ex-preterm children with sleep disturbances should evaluate for RLS and PLMD. Further studies including serum ferritin evaluation are required to confirm these findings. Copyright © 2016 Elsevier B.V. All rights reserved.

Mathematical modeling of the dynamic storage of iron in ferritin

PubMed Central

2010-01-01

Background Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Results Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. Conclusions The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption. PMID:21047430

Mathematical modeling of the dynamic storage of iron in ferritin.

PubMed

Salgado, J Cristian; Olivera-Nappa, Alvaro; Gerdtzen, Ziomara P; Tapia, Victoria; Theil, Elizabeth C; Conca, Carlos; Nuñez, Marco T

2010-11-03

Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.

Association of serum ferritin levels with immunological status and clinical staging of HIV patients: a retrospective study

NASA Astrophysics Data System (ADS)

Saragih, R. H.; Mardia, A. I.; Purba, G. C. F.; Syahrini, H.

2018-03-01

Serum ferritin has long known as an acute phase reactant during inflammation. It works as an oxidative stress marker beside its role in the storage of intracellular iron. The increase of serum ferritin levels (SFL) has been reported found in HIV patients. It remains unclear though whether it causes, or is the cause, to the progressivity of the disease. The purpose of this study was to find the association between the SFL and the progressivity of the HIV disease. A retrospective study of 91 patients was carried out at the Haji Adam Malik Central General Hospital. All of the study population were HIV positive inpatients admitted from January to December 2016. The data needed to be all obtained from the patient’s medical records. The WHO Clinical Staging System was used to assess the HIV clinical staging. An inverse relationship was found between the SFL with the immunological status of the HIV patients (r=-0.213) based on their CD4+ count. There was no association found between the SFL with the clinical staging of the HIV patients (p=0.953). The elevated SFL is a feature found in HIV-diagnosed patients with the low CD4+ count, and it affects the progressivity of the disease.

Neonatal hemochromatosis. Case series from Bahrain.

PubMed

Isa, Hasan M; Mohamed, Afaf M

2013-12-01

To review clinical presentations, diagnosis, response to treatment, and outcome of infants with neonatal hemochromatosis (NH). This is a retrospective review of all cases admitted to the Pediatric Department at Salmaniya Medical Center, Manama, Bahrain between March 2008 and May 2011. The diagnosis was based on serum iron and ferritin, alpha-fetoprotein levels (AFP), liver and buccal biopsies, and abdominal MRI scan. Ten patients (8 males and 2 females) were diagnosed with NH. Two patients were intrauterine growth restriction (IUGR) and 6 were preterm. The median birth weight was 1.700 grams. The median age at presentation was 16 days, and at diagnosis was 23 days. Two patients had positive consanguinity. Clinical presentations of the infants were hepatosplenomegaly (n=5), ascites (n=3), and hypoglycemia (n=6). All patients had raised ferritin levels, prolonged prothrombin time, and 9 patients had high serum iron and serum AFP. Abdominal MRI showed iron overload in the liver (n=8). Liver biopsies showed evidence of hemochromatosis (n=3). Buccal biopsies stained positive for iron (n=1). Eight patients received antioxidant therapy and survived. Two patients passed away. Neonatal hemochromatosis is a rare liver disease of newborns with a spectrum of clinical severity. Elevated serum ferritin and AFP support the diagnosis after excluding other causes of neonatal liver failure. The use of antioxidant therapy helps to improve the outcome.

Increased serum ferritin levels are independently related to incidence of prediabetes in adult populations.

PubMed

Meng, G; Yang, H; Bao, X; Zhang, Q; Liu, L; Wu, H; Du, H; Xia, Y; Shi, H; Guo, X; Liu, X; Li, C; Su, Q; Gu, Y; Fang, L; Yu, F; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Wu, Y; Niu, K

2017-04-01

To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. This prospective cohort study (n=7380) with a mean follow-up of 3.07 years (range: 1-7, 95% CI: 3.03-3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90-1.40), 1.20 (0.97-1.48), 1.41 (1.14-1.73) and 1.73 (1.41-2.11); and for women, 1.00, 1.01 (0.74-1.38), 0.68 (0.48-0.96), 0.84 (0.61-1.15) and 1.07 (0.80-1.45), respectively. Similar results were also observed for mean ferritin levels. Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels. Copyright © 2016. Published by Elsevier Masson SAS.

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

PubMed Central

Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

2015-01-01

Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?

PubMed

Barut, Sener; Dincer, Fatma; Sahin, Idris; Ozyurt, Huseyin; Akkus, Mehmet; Erkorkmaz, Unal

2010-01-01

Serum ferritin is one of the markers indicating hemophagocytosis that may have a role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). This study was designed to determine any correlation between serum ferritin and routine diagnostic laboratory markers of CCHF, and to investigate the relationship between serum ferritin levels and disease severity. Sixty-six patients with CCHF admitted to the hospital during the spring and summer months of 2006 and 2007 were included in the study. Serum ferritin levels were measured in sera obtained during the initial days of hospitalization. Data from 53 patients showing decreasing platelet counts over the first three days were used for further analysis and these patients were divided into two groups according to disease severity: group A included severe cases with lowest platelet counts < or =20x10(9)/l and group B included mild cases with lowest platelet counts >20x10(9)/l. Forty patients (60.6%) were male (mean age 43+/-17 years). Three patients died, thus the fatality rate was 4.5%. Fifty-one patients (77.3%) had abnormal serum ferritin levels, with levels above 500 ng/ml in 62.1%. There was a significant negative correlation between ferritin levels and concordant platelet counts (p<0.001; r=-0.416) and ferritin was also found to be positively correlated with aspartate aminotransferase (p<0.001; r=0.625), alanine aminotransferase (p<0.001; r=0.479), and lactate dehydrogenase (p<0.001; r=0.684). Group A had higher ferritin levels than group B (p < 0.001). Receiver operating characteristic analysis revealed that a ferritin level of > or =1862ng/ml had a sensitivity of 87.5% and a specificity of 83.8% in differentiating severe cases from mild ones. Increased serum ferritin levels may suggest a significant role of hemophagocytosis in the pathogenesis of CCHF and may be a useful marker for diagnosis, disease activity, and prognosis. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy.

PubMed

Mast, Alan E; Schlumpf, Karen S; Wright, David J; Johnson, Bryce; Glynn, Simone A; Busch, Michael P; Olbina, Gordana; Westerman, Mark; Nemeth, Elizabeta; Ganz, Tomas

2013-08-01

Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (≥3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized ≥4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (>45.7 ng/mL) or decreasing hepcidin and low ferritin (>26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (>26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone. Clinicaltrials.gov identifier: NCT00097006.

Ferritin Blood Test: MedlinePlus Lab Test Information

MedlinePlus

... https://medlineplus.gov/labtests/ferritinbloodtest.html Ferritin Blood Test To use the sharing features on this page, please enable JavaScript. What is a Ferritin Blood Test? A ferritin blood test measures the level of ...

Ferritin levels and risk of heart failure - the Atherosclerosis Risk in Communities Study

PubMed Central

Silvestre, Odilson M.; Gonçalves, Alexandra; Junior, Wilson Nadruz; Claggett, Brian; Couper, David; Eckfeldt, John H.; Pankow, James S.; Anker, Stefan D.; Solomon, Scott D.

2016-01-01

Aims Severe iron overload is associated with cardiac damage, while iron deficiency has been related to worse outcomes in subjects with heart failure (HF). This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a community-based cohort. Methods and results We examined 1,063 participants who were free of heart failure from the Atherosclerosis Risk in Communities (ARIC) study in whom ferritin serum levels were measured at baseline (1987–1989). The participants (mean age 52.7 ± 5.5 years, 62% women), were categorized in low (<30 ng/mL; n=153), normal (30–200 ng/mL in women and 30–300 ng/mL in men; n=663) and high (>200 ng/mL in women and >300 ng/mL in men; n=247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF. After 20.9±4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared to participants with normal ferritin levels, participants with low ferritin levels had a higher risk of HF (HR= 2.24, 95% CI= 1.15–4.35; p=0.02) as did those with high ferritin levels (HR=1.81, 95% CI=1.01–3.25; p=0.04), after adjusting for potential confounders. Notably, low ferritin levels remained associated with incident HF even after excluding subjects with anemia (HR= 2.28, 95% CI= 1.11–4.68; p= 0.03). Conclusion Derangements in iron metabolism, either low or high ferritin serum levels, were associated with higher risk of incident HF in a general population, even without concurrent anemia. These findings suggest that iron imbalance might play a role in the development of HF. PMID:27976478

Ferritin levels and risk of heart failure-the Atherosclerosis Risk in Communities Study.

PubMed

Silvestre, Odilson M; Gonçalves, Alexandra; Nadruz, Wilson; Claggett, Brian; Couper, David; Eckfeldt, John H; Pankow, James S; Anker, Stefan D; Solomon, Scott D

2017-03-01

Severe iron overload is associated with cardiac damage, while iron deficiency has been related to worse outcomes in subjects with heart failure (HF). This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a community-based cohort. We examined 1063 participants who were free of heart failure from the Atherosclerosis Risk in Communities (ARIC) Study in whom ferritin serum levels were measured at baseline (1987-1989). The participants (mean age 52.7 ± 5.5 years, 62% women), were categorized in low (<30 ng/mL; n = 153), normal (30-200 ng/mL in women and 30-300 ng/mL in men; n = 663), and high (>200 ng/mL in women and >300 ng/mL in men; n = 247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF. After 21 ± 4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared with participants with normal ferritin levels, participants with low ferritin levels had a higher risk of HF [hazard ratio (HR) = 2.24, 95% confidence interval (CI) 1.15-4.35; P = 0.02] as did those with high ferritin levels (HR = 1.81, 95% CI 1.01-3.25; P = 0.04), after adjusting for potential confounders. Notably, low ferritin levels remained associated with incident HF even after excluding subjects with anaemia (HR = 2.28, 95% CI 1.11-4.68; P = 0.03). Derangements in iron metabolism, either low or high ferritin serum levels, were associated with higher risk of incident HF in a general population, even without concurrent anaemia. These findings suggest that iron imbalance might play a role in the development of HF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

PubMed Central

Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

2016-01-01

Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

Relationship between Serum Ferritin Levels and Dyslipidemia in Korean Adolescents

PubMed Central

Kim, Young-Eun; Roh, Yong-Kyun; Ju, Sang-Yhun; Yoon, Yeo-Joon; Nam, Ga-Eun; Nam, Hyo-Yun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo

2016-01-01

Background Ferritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young. Methods We analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009–2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels. Results In boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls. Conclusion Serum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor. PMID:27070153

Effect of RBC concentrate transfusions on serum ferritin content in children with acute leukaemia.

PubMed

Bebeshko, V G; Bruslova, E M; Tsvietkova, N M; Iatsemirskii, S M; Puchkareva, T I; Gonchar, L A; Krukovska, V V; Zelinska, A V; Mishchenko, L P

2013-01-01

To study the serum ferritin levels in children with acute leukemia, depending on the number of transfusions of RBC concentrate and period of disease. We studied the red blood count, serum iron and ferritin levels in 54 patients with acute leukemia before chemotherapy, at the time of a standardized treatment protocol, and after transfusions of RBC concentrates. In the debute of acute leukemia just before treatment lauch the serum ferritin in 81.5% of children was 2.3-2.5 higher than normal. The need for transfusion of RBC concentrates was higher under serum ferritin level exceeding 500 ng/mL. The association was established between ferritin content and age of the children, variant of acute leukemia and period of the disease. The level of serum ferritin can be used as a marker of ferrokinetic status for timely diagnosis of iron overload in children with acute leukemias and for application of treatment-and-prophylactic actions. Bebeshko V. G., Bruslova K. M., Cvjetkova N. M., Jacemyrskyj S. M., Pushkarova T. I., Gonchar L. O., Krukovska V. V., Zelinska A. V., Mishhenko L. P., 2013.

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing.

PubMed

Karaboyas, Angelo; Zee, Jarcy; Morgenstern, Hal; Nolen, Jacqueline G; Hakim, Raymond; Kalantar-Zadeh, Kamyar; Zager, Philip; Pisoni, Ronald L; Port, Friedrich K; Robinson, Bruce M

2015-10-07

Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time. Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation. Copyright © 2015 by the American Society of Nephrology.

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing

PubMed Central

Zee, Jarcy; Morgenstern, Hal; Nolen, Jacqueline G.; Hakim, Raymond; Kalantar-Zadeh, Kamyar; Zager, Philip; Pisoni, Ronald L.; Port, Friedrich K.; Robinson, Bruce M.

2015-01-01

Background and objectives Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Design, setting, participants, & measurements Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients’ changes in ferritin over time. Results Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009–2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. Conclusions In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation. PMID:26286925

Ferritin Levels in Colombian Children: Findings from the 2010 National Nutrition Survey (ENSIN).

PubMed

Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Martínez-Torres, Javier; González-Ruíz, Katherine; Lobelo, Felipe

2016-04-05

Low ferritin is associated with many adverse health outcomes and is highly prevalent worldwide. The aim of this study was to describe the key findings related to plasma ferritin levels to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. We analyzed cross-sectional data from 6650 Colombian children between the ages of 5 and 12. Plasma ferritin levels were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. All analyses were conducted considering the complex nature of the sample. Of the children assessed, 3.5% had low ferritin, defined as levels <12 µg/L. A multivariate logistic regression analysis revealed increased risks for low ferritin levels among black or Afro-Colombian ethnic group and for those living in the northern, western and southern regions of the country. In conclusion, a significant prevalence of anemia caused by low ferritin levels was found and various sociodemographic factors were associated with this finding in Colombia. Continued surveillance and implementation of interventions to improve dietary patterns among the identified high-risk groups should be considered. Implementing these recommendations can help reduce manifestations of iron deficiency (e.g., delays in infant and child development) and thus improve public health.

Ferritin Levels in Colombian Children: Findings from the 2010 National Nutrition Survey (ENSIN)

PubMed Central

Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Martínez-Torres, Javier; González-Ruíz, Katherine; Lobelo, Felipe

2016-01-01

Low ferritin is associated with many adverse health outcomes and is highly prevalent worldwide. The aim of this study was to describe the key findings related to plasma ferritin levels to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. We analyzed cross-sectional data from 6650 Colombian children between the ages of 5 and 12. Plasma ferritin levels were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. All analyses were conducted considering the complex nature of the sample. Of the children assessed, 3.5% had low ferritin, defined as levels <12 µg/L. A multivariate logistic regression analysis revealed increased risks for low ferritin levels among black or Afro-Colombian ethnic group and for those living in the northern, western and southern regions of the country. In conclusion, a significant prevalence of anemia caused by low ferritin levels was found and various sociodemographic factors were associated with this finding in Colombia. Continued surveillance and implementation of interventions to improve dietary patterns among the identified high-risk groups should be considered. Implementing these recommendations can help reduce manifestations of iron deficiency (e.g., delays in infant and child development) and thus improve public health. PMID:27058547

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease.

PubMed

Koppe, Tiago; Doneda, Divair; Siebert, Marina; Paskulin, Livia; Camargo, Matheus; Tirelli, Kristiane Michelin; Vairo, Filippo; Daudt, Liane; Schwartz, Ida Vanessa D

2016-03-01

The clinical utility of serum ferritin as a biomarker of disease severity and prognosis in Gaucher disease (GD) is still debated. Here, we aimed to evaluate ferritin and its relation to clinicolaboratory parameters of GD patients seen at the Reference Center for Gaucher Disease of Rio Grande do Sul, Brazil, so as to gather evidence on the utility of ferritin as a biomarker of this condition. A retrospective chart review was performed collecting pre-and posttreatment data from GD patients. Eighteen patients with ferritin levels available before and after treatment were included in the study. Nine of these participants were males, and seventeen had type I GD. All patients were given either enzyme replacement (n = 16) or substrate reduction therapy (n = 2), and ferritin was found to decrease from 756 [318-1441] ng/mL at baseline to 521 [227-626] ng/mL (p=0.025) after 28.8 month soft treatment. Serum ferritin levels did not correlate with measures of disease severity, but showed an association with age at onset of treatment (ρ= 0.880; n = 18; p < 0.001). In conclusion, although serum ferritin did not correlate with disease severity, after a median 28.8 months of treatment, clinical outcomes had clearly improved, and ferritin levels had decreased.

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

PubMed

Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

2013-02-01

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels.

PubMed

Wofford, Joshua D; Chakrabarti, Mrinmoy; Lindahl, Paul A

2017-03-31

Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from 57 Fe-enriched mice were evaluated by Mössbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood, whereas the other was due to [Fe 4 S 4 ] 2+ clusters and low-spin Fe II hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE -/- mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE -/- livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2 -/- hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the heart from the mother contained low ferritin and normal levels of mitochondrial iron. High-spin Fe II ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mössbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Association between serum ferritin and glaucoma in the South Korean population.

PubMed

Lin, Shuai-Chun; Wang, Sophia Y; Yoo, Chungkwon; Singh, Kuldev; Lin, Shan C

2014-12-01

Evidence suggests that altered iron metabolism may be associated with oxidative damage to several organ systems, including the eye. Supplementary iron consumption is also associated with greater odds of self-reported glaucoma. To investigate the association between serum ferritin level and the likelihood of a glaucoma diagnosis in a cross-sectional, population-based study. Data were collected from 17,476 participants in the first and second years of the Fifth Korea National Health and Nutrition Examination Survey, a cross-sectional study of the South Korean population conducted from January 1, 2010, through December 31, 2011. Data pertaining to the serum ferritin level were aggregated and divided into quartiles. Demographic, comorbidity, and health-related behavior information was obtained via interview. The presence or absence of glaucoma. The definition of glaucoma was based on criteria established by the International Society of Geographical and Epidemiological Ophthalmology. Participants whose serum ferritin level was greater than 61 ng/mL (to convert to picomoles per liter, multiply by 2.247) had significantly higher odds of a glaucoma diagnosis when compared with those with a level less than 31 ng/mL, after adjustment for potential confounders (ferritin levels of 31-61 ng/mL: odds ratio [OR], 1.17; 95% CI, 0.84-1.62; ferritin levels of 62-112 ng/mL: OR, 1.60; 95% CI, 1.16-2.20; and ferritin levels of 113-3018 ng/mL: OR, 1.89; 95% CI, 1.32-2.72). Our study reveals that a higher serum ferritin level was associated with greater odds of glaucoma in a representative sample of the South Korean population, even at levels normally observed in the general population. This novel finding may help elucidate the pathogenesis and lead to novel therapeutic approaches for glaucomatous disease.

Ferritin Levels and Their Association With Regional Brain Volumes in Tourette's Syndrome

PubMed Central

Gorman, Daniel A.; Zhu, Hongtu; Anderson, George M.; Davies, Mark; Peterson, Bradley S.

2008-01-01

Objective A previous small study showed lower serum ferritin levels in subjects with Tourette's syndrome than in healthy subjects. The authors measured peripheral iron indices in a large group of Tourette's syndrome and comparison subjects and explored associations of ferritin levels with regional brain volumes. Method Ferritin was measured in 107 children and adults (63 Tourette's syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome, 32 comparison). Magnetic resonance imaging scans were used to measure volumes of the basal ganglia and cortical gray matter. Results Ferritin and serum iron were significantly lower in the Tourette's syndrome subjects, although still within the normal range. No association was found between tic severity and either iron index. In the Tourette's syndrome subjects, ferritin did not correlate significantly with caudate volume but did correlate positively with putamen volume. In the comparison subjects, ferritin correlated inversely with caudate volume but did not correlate significantly with putamen volume. Irrespective of diagnosis, ferritin correlated positively with volumes of the sensorimotor, midtemporal, and subgenual cortices. Conclusions The lower peripheral ferritin and iron levels in persons with Tourette's syndrome are consistent with findings in other movement disorders and suggest that lower iron availability may have a causal role in the pathophysiology of tic disorders. Lower iron stores may contribute to hypoplasia of the caudate and putamen, increasing vulnerability to developing tics or to having more severe tics. Lower iron stores may also contribute to smaller cortical volumes and consequently to reduced inhibitory control of tics. PMID:16816233

The prognostic value of biological markers in paediatric Hodgkin lymphoma.

PubMed

Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Buffardi, Salvatore; Garaventa, Alberto; Bottigliero, Gaetano; Bianchi, Maurizio; Zecca, Marco; Locatelli, Franco; Pession, Andrea; Pillon, Marta; Favre, Claudio; D'Amico, Salvatore; Provenzi, Massimo; Trizzino, Angela; Zanazzo, Giulio Andrea; Sau, Antonella; Santoro, Nicola; Murgia, Giulio; Casini, Tommaso; Mascarin, Maurizio; Burnelli, Roberta

2016-01-01

Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

PubMed

Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

2015-01-01

HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

Fever of unknown origin (FUO) due to Legionnaire's disease.

PubMed

Muñoz-Gómez, Sigridh; Cunha, Burke A

2015-01-01

Fevers of unknown origin (FUOs) may be due to any of over 200 different disorders. We present a most unusual case of an FUO in a returning traveler from the Dominican Republic. Work-up for Q fever, Brucellosis, Bartonella, malaria and HIV were negative, but very highly elevated ESRs and ferritin levels suggested possible Legionnaire's disease. This is the third reported case of Legionnaire's disease presenting as an FUO. Copyright © 2015 Elsevier Inc. All rights reserved.

Limitations of serum ferritin to predict liver iron concentration responses to deferasirox therapy in patients with transfusion-dependent thalassaemia.

PubMed

Porter, John B; Elalfy, Mohsen; Taher, Ali; Aydinok, Yesim; Lee, Szu-Hee; Sutcharitchan, Pranee; El-Ali, Ali; Han, Jackie; El-Beshlawy, Amal

2017-03-01

In transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. This post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox. Serum ferritin responses (decreases) occurred in 73% of patients, 80% of whom also have decreased LIC. However, 52% of patients without a serum ferritin response did decrease LIC and by >1 mg Fe/g dw (median 3.9) in 77% of cases. Absolute serum ferritin and LIC values correlated significantly only when serum ferritin was <4000 ng/mL (r = 0.59; P < 0.0001) and not at higher levels (≥4000 ng/mL; r = 0.19). Serum ferritin response was accompanied by decreased LIC in 89% and 70% of cases when serum ferritin was <4000 or ≥4000 ng/mL, respectively. As serum ferritin non-response was associated with LIC decrease in over half of patients, use of liver MRI may be particularly useful for differentiating true from apparent non-responders to deferasirox based on serum ferritin trends alone. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

Erythrocytapheresis compared with whole blood phlebotomy for the treatment of hereditary haemochromatosis

PubMed Central

Sundic, Tatjana; Hervig, Tor; Hannisdal, Signe; Assmus, Jörg; Ulvik, Rune J.; Olaussen, Richard W.; Berentsen, Sigbjørn

2014-01-01

Background Hereditary haemochromatosis may result in severe organ damage which can be prevented by therapy. We studied the possible advantages and disadvantages of erythrocytapheresis as compared with phlebotomy in patients with hereditary haemochromatosis. Materials and methods In a prospective, randomised, open-label study, patients with hereditary haemochromatosis were randomised to bi-weekly apheresis or weekly whole blood phlebotomy. Primary end-points were decrease in ferritin levels and transferrin saturation. Secondary endpoints were decrease in haemoglobin levels, discomfort during the therapeutic procedure, costs and technicians’ working time. Results Sixty-two patients were included. Thirty patients were randomised to apheresis and 32 to whole blood phlebotomy. Initially, ferritin levels declined more rapidly in the apheresis group, and the difference became statistically highly significant at 11 weeks; however, time to normalisation of ferritin level was equal in the two groups. We observed no significant differences in decline of transferrin saturation, haemoglobin levels or discomfort. The mean cumulative technician time consumption until the ferritin level reached 50 μg/L was longer in the apheresis group, but the difference was not statistically significant. The cumulative costs for materials until achievement of the desired ferritin levels were three-fold higher in the apheresis group. Conclusion Treatment of hereditary haemochromatosis with erythrocytapheresis instead of whole blood phlebotomy results in a more rapid initial decline in ferritin levels and a reduced number of procedures per patient, but not in earlier achievement of target ferritin level. The frequency of discomfort was equally low with the two methods. The costs and, probably, technician time consumption were higher in the apheresis group. PMID:24333062

Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome

PubMed Central

Cozzi, Anna; Santambrogio, Paolo; Privitera, Daniela; Broccoli, Vania; Rotundo, Luisa Ida; Garavaglia, Barbara; Benz, Rudolf; Altamura, Sandro; Goede, Jeroen S.; Muckenthaler, Martina U.

2013-01-01

The ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient’s fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS. PMID:23940258

Autoimmune Hepatitis: Diagnostic Dilemma When It Is Disguised as Iron Overload Syndrome.

PubMed

Acharya, Gyanendra K; Liao, Hung-I; Frunza-Stefan, Simona; Patel, Ronakkumar; Khaing, Moe

2017-09-01

Elevated serum ferritin level is a common finding in iron overload syndrome, autoimmune and viral hepatitis, alcoholic and nonalcoholic fatty liver diseases. High transferrin saturation is not a common finding in above diseases except for iron overload syndrome. We encountered a challenging case of 73-year-old female who presented with yellowish discoloration of skin, dark color urine and dull abdominal pain. Initial laboratory tests reported mild anemia; elevated bilirubin, liver enzymes, and transferrin saturation. We came to the final diagnosis of autoimmune hepatitis after extensive workups. Autoimmune hepatitis is a rare disease, and the diagnosis can be further complicated by a similar presentation of iron overload syndrome. Markedly elevated transferrin saturation can simulate iron overload syndrome, but a liver biopsy can guide physicians to navigate the diagnosis.

Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis.

PubMed

Yeap, Bu B; Divitini, Mark L; Gunton, Jenny E; Olynyk, John K; Beilby, John P; McQuillan, Brendan; Hung, Joseph; Knuiman, Matthew W

2015-04-01

Iron overload predisposes to diabetes and higher ferritin levels have been associated with diabetes. However, it is unclear whether ferritin reflects differences in iron-related parameters between diabetic and nondiabetic persons. We examined associations of serum ferritin, iron and transferrin saturation with Type 2 diabetes in adults without genetic predisposition to iron overload. Cross-sectional analysis of community-dwelling men and women aged 17-97 years from the Busselton Health Survey, Western Australia. Men and women carrying genotypes associated with haemochromatosis (C282Y/C282Y or C282Y/H63D) were excluded. Serum ferritin, iron and transferrin saturation were assayed. There were 1834 men (122 with diabetes, 6·6%) and 2351 women (141 with diabetes, 6%). In men, higher serum ferritin was associated with diabetes after adjusting for age, smoking, alcohol, cardiovascular history, body mass index (BMI), waist, blood pressure, lipids, C-reactive protein (CRP), adiponectin, alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) [odds ratio (OR): 1·29 per 1 unit increase log ferritin, 95% confidence interval (CI) = 1·01-1·65, P = 0·043]. In women, higher serum ferritin was associated with diabetes [fully adjusted OR: 1·31 per 1 unit increase log ferritin, 95% CI = 1·04-1·63, P = 0·020; 1·84 for tertile (T) 3 vs T1, 95% CI = 1·09-3·11]. Neither iron levels nor transferrin saturation were associated with diabetes risk in men or women. Higher ferritin was not associated with insulin resistance in nondiabetic adults. In adults, higher ferritin levels are independently associated with prevalent diabetes while iron and transferrin saturation are not. Ferritin is a robust biomarker for diabetes risk, but further investigation is needed to clarify whether this relationship is mediated via iron metabolism. © 2014 John Wiley & Sons Ltd.

Evaluation and association of serum iron and ferritin levels in children with dental caries.

PubMed

Venkatesh Babu, N S; Bhanushali, Parin Vasant

2017-01-01

Iron deficiency anemia accounts for 90% of all types of anemia in the world. Although the prevalence has declined in recent years, it remains an important pediatric public health problem. Iron deficiency has also been associated with dental caries. It impairs salivary gland function causing reduced salivary secretion and buffering capacity leading to increased caries activity. The aim of the study is to explore an association between dental caries and serum levels of iron and ferritin in children aged 3-12 years. Subjectsand Methods: The study group included 120 children, hospitalized for uncomplicated medical problems. Blood reports were evaluated to determine serum iron and ferritin levels. Dental caries experience was assessed using deft index. The collected data were tabulated and analyzed using Student's t-test and Pearson's correlation coefficient. Out of 120 children, 38 children showed low serum iron levels of which 31 children had dental caries and nine out of 15 children in the high serum iron level group showed dental caries. High ferritin levels were seen in three children among which two children were caries-free and only one child had a low ferritin level who also had a positive deft score. Based on the results, it was concluded that there is an inverse association between serum iron levels and dental caries whereas there is no association between serum ferritin levels and dental caries.

Quantitating Iron in Serum Ferritin by Use of ICP-MS

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Gillman, Patricia L.

2003-01-01

A laboratory method has been devised to enable measurement of the concentration of iron bound in ferritin from small samples of blood (serum). Derived partly from a prior method that depends on large samples of blood, this method involves the use of an inductively-coupled-plasma mass spectrometer (ICP-MS). Ferritin is a complex of iron with the protein apoferritin. Heretofore, measurements of the concentration of serum ferritin (as distinguished from direct measurements of the concentration of iron in serum ferritin) have been used to assess iron stores in humans. Low levels of serum ferritin could indicate the first stage of iron depletion. High levels of serum ferritin could indicate high levels of iron (for example, in connection with hereditary hemochromatosis an iron-overload illness that is characterized by progressive organ damage and can be fatal). However, the picture is complicated: A high level of serum ferritin could also indicate stress and/or inflammation instead of (or in addition to) iron overload, and low serum iron concentration could indicate inflammation rather than iron deficiency. Only when concentrations of both serum iron and serum ferritin increase and decrease together can the patient s iron status be assessed accurately. Hence, in enabling accurate measurement of the iron content of serum ferritin, the present method can improve the diagnosis of the patient s iron status. The prior method of measuring the concentration of iron involves the use of an atomic-absorption spectrophotometer with a graphite furnace. The present method incorporates a modified version of the sample- preparation process of the prior method. First, ferritin is isolated; more specifically, it is immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose beads. The ferritin is then separated from other iron-containing proteins and free iron by a series of centrifugation and wash steps. Next, the ferritin is digested with nitric acid to extract its iron content. Finally, a micronebulizer is used to inject the sample of the product of the digestion into the ICPMS for analysis of its iron content. The sensitivity of the ICP-MS is high enough to enable it to characterize samples smaller than those required in the prior method (samples can be 0.15 to 0.60 mL).

Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice.

PubMed

Tajima, Soichiro; Ikeda, Yasumasa; Enomoto, Hideaki; Imao, Mizuki; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Miyamoto, Licht; Ishizawa, Keisuke; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-08-01

Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.

C-reactive protein, waist circumference, and family history of heart attack are independent predictors of body iron stores in apparently healthy premenopausal women.

PubMed

Suárez-Ortegón, M F; Arbeláez, A; Mosquera, M; Méndez, F; Aguilar-de Plata, C

2012-08-01

Ferritin levels have been associated with metabolic syndrome and insulin resistance. The aim of the present study was to evaluate the prediction of ferritin levels by variables related to cardiometabolic disease risk in a multivariate analysis. For this aim, 123 healthy women (72 premenopausal and 51 posmenopausal) were recruited. Data were collected through procedures of anthropometric measurements, questionnaires for personal/familial antecedents, and dietary intake (24-h recall), and biochemical determinations (ferritin, C reactive protein (CRP), glucose, insulin, and lipid profile) in blood serum samples obtained. Multiple linear regression analysis was used and variables with no normal distribution were log-transformed for this analysis. In premenopausal women, a model to explain log-ferritin levels was found with log-CRP levels, heart attack familial history, and waist circumference as independent predictors. Ferritin behaves as other cardiovascular markers in terms of prediction of its levels by documented predictors of cardiometabolic disease and related disorders. This is the first report of a relationship between heart attack familial history and ferritin levels. Further research is required to evaluate the mechanism to explain the relationship of central body fat and heart attack familial history with body iron stores values.

Improved preoperative iron status assessment by soluble transferrin receptor in elderly patients undergoing knee and hip replacement.

PubMed

Basora, M; Deulofeu, R; Salazar, F; Quinto, L; Gomar, C

2006-12-01

A poor preoperative haemoglobin (Hb) status is frequently encountered among adult patients scheduled for corrective surgery of the locomotive system, representing the main risk factor for blood transfusion. The soluble transferrin receptor (sTfR) has become a highly specific parameter for the detection of iron deficits as it can differentiate between iron deficiency anaemia and anaemia of chronic disease, because of the lack of effect by associated inflammation, unlike ferritin. The objectives of this study were to evaluate patients with the prevalence of risk for transfusion, the effect of inflammation on ferritin (F) values and functional iron deficiency in elderly patients with advanced degenerative arthropathy scheduled for hip or knee replacement. This observational, prospective study included patients over 50 years, operated for hip or knee replacements between April and June 2004. Of 218 patients studied, 87 (39%) presented with Hb levels between 10 and 13 g/dl. The prevalence of functional iron deficit was 27% (sTfR > 1.76 mg/l), while only 8.6% of patients displayed F levels below normal. As expected, C-reactive protein levels were elevated in 24.8% of patients and erythrocyte sedimentation rate was elevated in 50%. These inflammatory markers did not correlate with levels of either F or sTfR. Multiple factors can affect F levels, such as the inflammatory status of osteoarthritis in the elderly, obesity, nonsteroidal anti-inflammatory drugs therapy and low physical performance. As sTfR is not affected by inflammation, it has emerged as a primary parameter for the evaluation of iron status during preoperative assessment among patients scheduled for arthroplasty surgery. Our data strongly suggest that sTfR measurement contributes to improve patient management.

Abscisic acid is involved in the iron-induced synthesis of maize ferritin.

PubMed Central

Lobréaux, S; Hardy, T; Briat, J F

1993-01-01

The ubiquitous iron storage protein ferritin has a highly conserved structure in plants and animals, but a distinct cytological location and a different level of control in response to iron excess. Plant ferritins are plastid-localized and transcriptionally regulated in response to iron, while animal ferritins are found in the cytoplasm and have their expression mainly controlled at the translational level. In order to understand the basis of these differences, we developed hydroponic cultures of maize plantlets which allowed an increase in the intracellular iron concentration, leading to a transient accumulation of ferritin mRNA and protein (Lobréaux,S., Massenet,O. and Briat,J.F., 1992, Plant Mol. Biol., 19, 563-575). Here, it is shown that iron induces ferritin and RAB (Responsive to Abscisic Acid) mRNA accumulation relatively with abscisic acid (ABA) accumulation. Ferritin mRNA also accumulates in response to exogenous ABA. Synergistic experiments demonstrate that the ABA and iron responses are linked, although full expression of the ferritin genes cannot be entirely explained by an increase in ABA concentration. Inducibility of ferritin mRNA accumulation by iron is dramatically decreased in the maize ABA-deficient mutant vp2 and can be rescued by addition of exogenous ABA, confirming the involvement of ABA in the iron response in plants. Therefore, it is concluded that a major part of the iron-induced biosynthesis of ferritin is achieved through a pathway involving an increase in the level of the plant hormone ABA. The general conclusion of this work is that the synthesis of the same protein in response to the same environmental signal can be controlled by separate and distinct mechanisms in plants and animals. Images PMID:8440255

Relationship between T2* magnetic resonance imaging-derived liver and heart iron content and serum ferritin levels in transfusion-dependent thalassemic children

PubMed Central

Suthar, Kiran; Goyal, Vishnu Kumar; Sharma, Pramod; Deopa, Bindu; Rathore, Pradeep Singh; Bishnoi, Rama Krishan

2018-01-01

CONTEXT: T2* magnetic resonance imaging (MRI) is being increasingly used for the assessment of organ iron content in thalassemics, but cost is a major prohibitive factor for repeated measurements. If serum ferritin correlates well with the T2* MRI liver and heart, it will be economical and more simple tool to assess organ iron deposition. AIMS: The aim of this study was to find out the relationship between serum ferritin level and T2* MRI-derived liver and heart iron content in transfusion-dependent thalassemic children SETTINGS: Thalassemia day-care center of a teaching hospital DESIGN: This was a cross-sectional study SUBJECTS AND METHODS: Seventy-three transfusion-dependent beta thalassemic children belonging to 2–18 years of age were subjected to T2* MRI of heart and liver to assess their iron content. Values obtained here were related to serum ferritin. STATISTICAL ANALYSIS USED: Keeping the correlation between serum ferritin and T2* MRI as primary outcome, spearman's correlation coefficient was calculated. RESULTS: We found poor (negative) correlation between serum ferritin level and T2* MRI liver (r = -0.448, P = 0.000) but no correlation between serum ferritin and T2*MRI heart (r = -0.221, P = 0.060). Conclusions: Serum ferritin cannot reliably predict the liver and heart iron content in Indian children with β thalassemia. PMID:29563679

Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells.

PubMed

Mehta, Kosha J; Coombes, Jason D; Briones-Orta, Marco; Manka, Paul P; Williams, Roger; Patel, Vinood B; Syn, Wing-Kin

2018-02-01

Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC). We evaluated the effects of excess iron on fibrogenesis and transforming growth factor beta (TGF-β) signaling in murine HSC. Cells were treated with holotransferrin (0.005-5g/L) for 24 hours, with or without the iron chelator deferoxamine (10µM). Gene expressions (α-SMA, Col1-α1, Serpine-1, TGF-β, Hif1-α, Tfrc and Slc40a1) were analyzed by quantitative real time-polymerase chain reaction, whereas TfR1, ferroportin, ferritin, vimentin, collagen, TGF-β RII and phospho-Smad2 proteins were evaluated by immunofluorescence, Western blot and enzyme-linked immunosorbent assay. HSC expressed the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-export protein ferroportin. Holotransferrin upregulated TfR1 expression by 1.8-fold (P < 0.03) and ferritin accumulation (iron storage) by 2-fold (P < 0.01), and activated HSC with 2-fold elevations (P < 0.03) in α-SMA messenger RNA and collagen secretion, and a 1.6-fold increase (P < 0.01) in vimentin protein. Moreover, holotransferrin activated the TGF-β pathway with TGF-β messenger RNA elevated 1.6-fold (P = 0.05), and protein levels of TGF-β RII and phospho-Smad2 increased by 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01), respectively. In contrast, iron chelation decreased ferritin levels by 30% (P < 0.03), inhibited collagen secretion by 60% (P < 0.01), repressed fibrogenic genes α-SMA (0.2-fold; P < 0.05) and TGF-β (0.4-fold; P < 0.01) and reduced levels of TGF-β RII and phospho-Smad2 proteins. HSC express iron-transport proteins. Holotransferrin (iron) activates HSC fibrogenesis and the TGF-β pathway, whereas iron depletion by chelation reverses this, suggesting that this could be a useful adjunct therapy for patients with fibrosis. Further studies in primary human HSC and animal models are necessary to confirm this. Published by Elsevier Inc.

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents

PubMed Central

Jung, Dong-Wook; Park, Joo-Hyun; Kim, Do-Hoon; Choi, Moonyoung; Kim, Shinhye; Kim, Hyonchong; Seul, Da-eun; Park, Soo Gyeong; Jung, Jin-Hyung; Han, Kyungdo; Park, Young-Gyu

2017-01-01

Abstract It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents. This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined. In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls. This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys. PMID:29390554

Presence of Serum Ferritin before and after Bariatric Surgery: Analysis in Dentate and Edentulous Patients

PubMed Central

Mosquim, Victor; Sales Peres, Matheus de Carvalho; Ceneviva, Reginaldo; Chaim, Elinton Adami

2016-01-01

Society has changed its own lifestyle, specially its eating habits and physical activities, leading to excessive weight and a sedentary behavior, which has contributed to obesity increase. Bariatric surgery is the most effective treatment to obesity, allowing weight loss and its maintenance. However, it has been related high levels of iron deficiency after surgery. A person’s nutritional status might be affected by total or partial tooth loss. The aim of this longitudinal prospective cohort study was to evaluate the levels of serum ferritin before and after bariatric surgery and to identify if there is a relation with tooth loss. The sample was composed of 50 patients selected and assisted at Amaral Carvalho Hospital, located in Jaú city, Brazil. The use and necessity of prosthesis, dental absence or presence, and serum ferritin dosage were evaluated. Student’s t test, Univariate analysis, Chi-square and Odds Ratio were adopted (p<0.05). There was no significant difference regarding the serum ferritin levels between dentate and edentulous patients prior to surgery (p = 0.436). After surgery, the serum ferritin levels were higher in edentulous patients (prosthesis users) when compared to the pre-surgical levels, and the post-surgical levels presented significant difference regarding the dentate patients (p = 0.024). It can be concluded that rehabilitated patients in postoperative period showed better levels of serum ferritin after surgical intervention. PMID:27695053

Presence of Serum Ferritin before and after Bariatric Surgery: Analysis in Dentate and Edentulous Patients.

PubMed

Foratori, Gerson Aparecido; Andrade, Francisco Juliherme Pires de; Mosquim, Victor; Sales Peres, Matheus de Carvalho; Ceneviva, Reginaldo; Chaim, Elinton Adami; Sales Peres, Silvia Helena de Carvalho

2016-01-01

Society has changed its own lifestyle, specially its eating habits and physical activities, leading to excessive weight and a sedentary behavior, which has contributed to obesity increase. Bariatric surgery is the most effective treatment to obesity, allowing weight loss and its maintenance. However, it has been related high levels of iron deficiency after surgery. A person's nutritional status might be affected by total or partial tooth loss. The aim of this longitudinal prospective cohort study was to evaluate the levels of serum ferritin before and after bariatric surgery and to identify if there is a relation with tooth loss. The sample was composed of 50 patients selected and assisted at Amaral Carvalho Hospital, located in Jaú city, Brazil. The use and necessity of prosthesis, dental absence or presence, and serum ferritin dosage were evaluated. Student's t test, Univariate analysis, Chi-square and Odds Ratio were adopted (p<0.05). There was no significant difference regarding the serum ferritin levels between dentate and edentulous patients prior to surgery (p = 0.436). After surgery, the serum ferritin levels were higher in edentulous patients (prosthesis users) when compared to the pre-surgical levels, and the post-surgical levels presented significant difference regarding the dentate patients (p = 0.024). It can be concluded that rehabilitated patients in postoperative period showed better levels of serum ferritin after surgical intervention.

Postmenopausal vegetarians' low serum ferritin level may reduce the risk for metabolic syndrome.

PubMed

Kim, Mi-Hyun; Bae, Yun Jung

2012-10-01

The present study was conducted to compare the serum ferritin status between the postmenopausal vegetarians and non-vegetarians and to identify the relation of serum ferritin with metabolic syndrome (MetS) risk factors in postmenopausal women. The two study groups consisted of postmenopausal vegetarians (n=59) who maintained a vegetarian diet for over 20 years and age-matched non-vegetarian controls (n=48). Anthropometric measurements, dietary intakes, serum metabolic syndrome-related parameters, and serum ferritin level between the two groups were compared. The vegetarians exhibited significantly lower weight (p<0.01), body mass index (BMI) (p<0.001), percentage of body fat (p<0.001), waist circumference (p<0.01), SBP (p<0.001), DBP (p<0.001), and fasting glucose (p<0.05). According to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III criteria for MetS applying Korean guidelines for waist circumference, the prevalence of MetS was lower in vegetarians (33.9 %) than in non-vegetarians (47.9 %). Vegetarians had significantly lower serum level of ferritin (p<0.01) than non-vegetarians. In the correlation analysis, serum ferritin was positively related to fasting glucose (r=0.264, p<0.01), triglycerides (r=0.232, p<0.05), and the NCEP score (r=0.214, p<0.05) and negatively related to high-density lipoprotein-cholesterol (r=-0.225, p<0.05) after adjusting for BMI, lifestyle, and dietary factors (animal protein, animal fat, and dietary fiber intake). In conclusion, postmenopausal vegetarians had lower MetS presence and a lower serum ferritin level compared to non-vegetarians. Furthermore, vegetarians' low serum ferritin level may reduce the risk of MetS in postmenopausal women.

Calcium in drinking water: effect on iron stores in Danish blood donors-results from the Danish Blood Donor Study.

PubMed

Rigas, Andreas S; Ejsing, Benedikte H; Sørensen, Erik; Pedersen, Ole B; Hjalgrim, Henrik; Erikstrup, Christian; Ullum, Henrik

2018-06-01

Studies confirm that calcium inhibits iron absorption. Danish tap water comes from groundwater, which contains varying amounts of calcium depending on the subsoil. We investigated the association of calcium in drinking water with iron levels in Danish blood donors. We used data on Danish blood donors including dietary and lifestyle habits, blood donation history, and physiologic characteristics including measures of ferritin levels along with information on area of residence from The Danish Blood Donor Study. Data on calcium levels in groundwater ("water hardness") were obtained through the Geological Survey of Denmark and Greenland. We performed multiple linear and logistic regression analyses to evaluate the effect of water hardness on ferritin levels and risk of having iron deficiency (defined as ferritin levels <15 ng/mL), stratified by sex. There was a significant negative association between water hardness and ferritin levels in both men and women. Risk of iron deficiency was correspondingly increased in both men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.14-2.12) and women (OR, 1.20; 95% CI, 1.03-1.40) with increasing water hardness. In analyses restricted to individuals who received supplemental iron tablets no significant association between groundwater hardness and ferritin levels was observed. As measured by ferritin levels, residential drinking water calcium content is associated with blood donors- iron levels and risk of iron deficiency. However, effect sizes are small. © 2018 AABB.

Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 μg/L at diagnosis.

PubMed

Barton, James C; Barton, J Clayborn; Acton, Ronald T; So, Jeffrey; Chan, Susanne; Adams, Paul C

2012-04-01

We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 μg/L at diagnosis. We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 μg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 μg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 μg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 μg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 μg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with serum levels of ferritin greater than 1000 μg/L. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Does Iron Supplementation Improve Performance in Iron-Deficient Nonanemic Athletes?

PubMed

Rubeor, Amity; Goojha, Carmen; Manning, Jeffrey; White, Jordan

2018-05-01

Supplementing iron-deficient nonanemic (IDNA) athletes with iron to improve performance is a trend in endurance sports. To investigate the benefits of iron on performance, identify a ferritin level cutoff in IDNA athletes, and determine which iron supplementation regimens are most effective. A search of the PubMed, CINAHL, Embase, ERIC, and Cochrane databases was performed in 2014 including all articles. Citations of pertinent review articles were also searched. In 2017, the search was repeated. Inclusion criteria comprised studies of level 1 to 3 evidence, written in the English language, that researched iron supplementation in nonanemic athletes and reported performance outcomes. Systematic review. Level 3. The search terms used included athletic performance, resistance training, athletes, physical endurance, iron, iron deficiency, supplement, non-anemic, low ferritin, ferritin, ferritin blood level, athletes, and sports. A total of 1884 studies were identified through the initial database search, and 13 were identified through searching references of relevant review articles. A subsequent database search identified 46 studies. Following exclusions, 12 studies with a total of 283 participants were included. Supplementing IDNA athletes with iron improved performance in 6 studies (146 participants) and did not improve performance in the other 6 studies (137 participants). In the 6 studies that showed improved performance with iron supplementation, all used a ferritin level cutoff of ≤20 μg/L for treatment. Additionally, all studies that showed improved performance used oral iron as a supplement. The evidence is equivocal as to whether iron supplementation in IDNA athletes improves athletic performance. Supplementing athletes with ferritin levels <20 μg/L may be more beneficial than supplementing athletes with higher baseline ferritin levels.

Haematinic Deficiency and Macrocytosis in Middle-Aged and Older Adults

PubMed Central

Harrington, Janas; Cadogan, Sharon; Honari, Bahman; Perera, Kanthi; Fitzgerald, Anthony P.; Perry, Ivan J.; Cahill, Mary R.

2013-01-01

Objective To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults. Methods A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT). Results The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). Conclusions Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency. PMID:24244281

Association between serum ferritin and hemoglobin levels and bone health in Korean adolescents: A nationwide population-based study.

PubMed

Jung, Dong-Wook; Park, Joo-Hyun; Kim, Do-Hoon; Choi, Moonyoung; Kim, Shinhye; Kim, Hyonchong; Seul, Da-Eun; Park, Soo Gyeong; Jung, Jin-Hyung; Han, Kyungdo; Park, Young-Gyu

2017-12-01

It is important to identify risk factors for low bone mass at a young age. An influence of iron store on bone health in the general population has been reported but has not been studied in adolescents. This study aimed to investigate the relationship between hemoglobin and serum ferritin levels and bone mineral content (BMC) in South Korean adolescents.This study was based on data collected during the 2009to 2010 Korea National Health and Nutrition Examination Survey. We included 1321 participants aged 10 to 18 years. BMC was measured at the femur and lumbar spine using dual-energy x-ray absorptiometry, and hemoglobin and serum ferritin levels were examined.In boys, hemoglobin and serum ferritin levels were positively associated with BMC of the total femur and lumbar spine after adjusting for confounders, and hemoglobin levels significantly increased as BMC increased at all sites (P for trend = .001 for total femur, .01 for femur neck, and <.001 for lumbar spine). Likewise, serum ferritin levels showed increasing trends according to increasing BMC of the total femur and lumbar spine in boys (P for trend = .04 for total femur; and <.001 for lumbar spine). However, these associations were not observed in girls.This study suggests a positive relationship between serum ferritin and hemoglobin levels and BMC in South Korean adolescent boys. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women

PubMed Central

Ali, M. Aktar; Akhmedkhanov, Arslan; Zeleniuch-Jaquotte, Anne; Toniolo, Paolo; Frenkel, Krystyna; Huang, Xi

2010-01-01

Reliability of serum levels of iron, ferritin and nitrite (NO2−) over a 2-year period were evaluated in 40 healthy women (20 pre-menopausal and 20 post-menopausal), ages 39–65 years, from the New York University Women’s Health Study (NYUWHS). Three blood samples per woman collected at yearly intervals were analyzed. Reliability coefficients (RCs) of serum iron, ferritin, and nitrite were 0.03 (95% confidence interval (CI), 0–0.33), 0.90 (95% CI, 0.79–0.95), and 0.72 (95% CI, 0.50–0.86), respectively, for pre-menopausal women, and 0.26 (95% CI, 0–0.56), 0.77 (95% CI, 0.59–0.89), and 0.55 (95% CI, 0.30–0.77), respectively, for post-menopausal women. In a case–control study nested within NYUWHS cohort, serum levels of nitrite, ferritin, and iron were measured in women apparently healthy at the time of blood donation but diagnosed with renal cancer 1.8–12.2 years later (n = 24) and in individually matched controls (two per case). The results suggest that high serum levels of ferritin and nitrite may be associated with a decreased risk of renal cancer (odds ratio (OR), 0.55, 95% CI, 0.15–2.01 for ferritin, and OR, 0.52, 95% CI, 0.17–1.60 for nitrite in women with above median level as compared to women with below median level). The possible role of ferritin and nitrite in renal cancer is discussed. PMID:12670522

Soluble transferrin receptor, Ferritin index in Pakistani population.

PubMed

Alam, Faiza; Ashraf, Nabeel; Kashif, Ramsha; Arshad, Hashaam; Fatima, Syeda Sadia

2017-03-01

Inflammation affects the reliability of ferritin. The serum level of transferrin receptor protein (sTfR) represents true demand of iron in the body. This study attempts to identify levels of sTfR and correlate the trends of sTfR/ferritin index with BMI in the population of Karachi. 132 gender matched volunteers between the ages of 20-60 years were recruited for this cross-sectional study. BMI was calculated using the formula: (weight in kg / height in m2). Following groups were made according to South Asian criteria of BMI; Group A: normal weight (18.0-22.9 kg/m 2 ), Group B: overweight (23.0-24.9 kg/m2), Group C: obese (>25.0 kg/m 2 ). Serum ferritin, sTfR and CRP levels were determined using ELISA kits. Statistical comparisons were performed using Mann Whitney U and Spearman's rank correlation, where p<0.05 was considered significant. The results identified increased in TIBC, sTfR, ferritin and CRP in obese as compared to normal weight individuals (p<0.001). sTfR/ferritin ratio was 0.822 which signifies increased risk of acute myocardial infarction in group C. Serum iron (r=-0.359,p=0.004) showed negative correlation with BMI while serum ferritin (r=0.237,p< 0.001) and sTfR (r=0.263,p= 0.036) levels were positively associated to BMI. This study highlights a novel finding that sTfR is most likely a better clinical measure of iron status in inflammatory conditions as its expression is effected by erythropoiesis and not by inflammation. Risk of Acute myocardial infarction can also be predicted by increased sTfR/ferritin ratio.

Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

PubMed

Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

2015-09-01

The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=<0.001), glucose (p=<0.001), insulin (p=<0.001) and HOMA IR score (p=<0.0001) in cases of metabolic syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

Characterization of mitochondrial ferritin in Drosophila.

PubMed

Missirlis, Fanis; Holmberg, Sara; Georgieva, Teodora; Dunkov, Boris C; Rouault, Tracey A; Law, John H

2006-04-11

Mitochondrial function depends on iron-containing enzymes and proteins, whose maturation requires available iron for biosynthesis of iron-sulfur clusters and heme. Little is known about how mitochondrial iron homeostasis is maintained, although the recent discovery of a mitochondrial ferritin in mammals and plants has uncovered a potential key player in the process. Here, we show that Drosophila melanogaster expresses mitochondrial ferritin from an intron-containing gene. It has high similarity to the mouse and human mitochondrial ferritin sequences and, as in mammals, is expressed mainly in testis. This ferritin contains a putative mitochondrial targeting sequence and an epitope-tagged version localizes to mitochondria in transfected cells. Overexpression of mitochondrial ferritin fails to alter both total-body iron levels and iron that is bound to secretory ferritins. However, the viability of iron-deficient flies is compromised by overexpression of mitochondrial ferritin, suggesting that it may sequester iron at the expense of other important cellular functions. The conservation of mitochondrial ferritin in an insect species underscores the importance of this iron-storage molecule.

Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

PubMed

Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

2012-01-01

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Sequence analysis of dolphin ferritin H and L subunits and possible iron-dependent translational control of dolphin ferritin gene

PubMed Central

Takaesu, Azusa; Watanabe, Kiyotaka; Takai, Shinji; Sasaki, Yukako; Orino, Koichi

2008-01-01

Background Iron-storage protein, ferritin plays a central role in iron metabolism. Ferritin has dual function to store iron and segregate iron for protection of iron-catalyzed reactive oxygen species. Tissue ferritin is composed of two kinds of subunits (H: heavy chain or heart-type subunit; L: light chain or liver-type subunit). Ferritin gene expression is controlled at translational level in iron-dependent manner or at transcriptional level in iron-independent manner. However, sequencing analysis of marine mammalian ferritin subunits has not yet been performed fully. The purpose of this study is to reveal cDNA-derived amino acid sequences of cetacean ferritin H and L subunits, and demonstrate the possibility of expression of these subunits, especially H subunit, by iron. Methods Sequence analyses of cetacean ferritin H and L subunits were performed by direct sequencing of polymerase chain reaction (PCR) fragments from cDNAs generated via reverse transcription-PCR of leukocyte total RNA prepared from blood samples of six different dolphin species (Pseudorca crassidens, Lagenorhynchus obliquidens, Grampus griseus, Globicephala macrorhynchus, Tursiops truncatus, and Delphinapterus leucas). The putative iron-responsive element sequence in the 5'-untranslated region of the six different dolphin species was revealed by direct sequencing of PCR fragments obtained using leukocyte genomic DNA. Results Dolphin H and L subunits consist of 182 and 174 amino acids, respectively, and amino acid sequence identities of ferritin subunits among these dolphins are highly conserved (H: 99–100%, (99→98) ; L: 98–100%). The conserved 28 bp IRE sequence was located -144 bp upstream from the initiation codon in the six different dolphin species. Conclusion These results indicate that six different dolphin species have conserved ferritin sequences, and suggest that these genes are iron-dependently expressed. PMID:18954429

Is serum ferritin within the reference range a risk predictor of cardiovascular disease? A population-based, long-term study comprising 2874 subjects.

PubMed

Friedrich, Nele; Milman, Nils; Völzke, Henry; Linneberg, Allan; Jørgensen, Torben

2009-08-01

The 'iron hypothesis' claims that Fe depletion protects against IHD. The objective of the present study was to investigate the associations between serum ferritin levels and the risk of CVD and IHD in a population-based sample. A total of 2874 subjects with serum ferritin levels between 15 and 300 microg/l from the Danish part of the 'Monitoring of Trends and Determinants in Cardiovascular Disease' (DAN-MONICA) I study and the 1914 Cohort survey were followed for 10 years. Information on behavioural and socio-demographic characteristics were collected and serum ferritin levels measured. Non-fatal and fatal CVD and IHD were identified by the International Classification of Diseases diagnoses numbers. Multivariable Cox proportional hazard regression models with restricted cubic splines were performed. During the follow-up period, 310 subjects (201 men; 109 women) and 161 subjects (117 men; forty-four women) experienced CVD and IHD, respectively. Our analyses revealed no statistically significant associations between serum ferritin levels and the risk of CVD or IHD in both sexes. However, in women, the results argue for a U-shaped relationship between serum ferritin levels and CVD as well as IHD. In concordance with former prospective studies, the present results do not support the hypothesis that normal body Fe stores should play a significant role in the development of CVD.

Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.

PubMed

Depalma, Ralph G; Hayes, Virginia W; Chow, Bruce K; Shamayeva, Galina; May, Patricia E; Zacharski, Leo R

2010-06-01

This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death. Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with significantly lower ferritin levels (-29.78 ng/mL; Cohen effect size, -0.47 [t(df, 134) = 2.33, P = .02]). Mean follow-up average ferritin levels were higher in 23 participants who died (132.5 ng/mL; 95% CI, 79.36-185.66) vs 77 survivors (83.6 ng/mL; 95% CI, 70.34-96.90; Wilcoxon P = .05). Mean follow-up IL-6 levels were higher in dead participants (21.68 ng/mL; 95% CI, 13.71-29.66) vs survivors (12.61 ng/mL; 95% CI, 10.72-14.50; Wilcoxon P = .018). Ferritin levels correlated (Pearson) with average IL-6 levels (r = 0.1845; P = .002) and hsCRP levels (r = .1175; P = .04) during the study. These data demonstrate statistical correlations between levels of ferritin, inflammatory biomarkers, and mortality in this subset of patients with PAD. Published by Mosby, Inc.

Association of low ferritin with PLM in the Wisconsin Sleep Cohort.

PubMed

Li, Jason; Moore, Hyatt; Lin, Ling; Young, Terry; Finn, Laurel; Peppard, Paul E; Mignot, Emmanuel

2015-11-01

The origins of periodic leg movements (PLMs), a strong correlate of restless legs syndrome (RLS), are uncertain. This study was performed to assess the relationship between PLMs and peripheral iron deficiency, as measured with ferritin levels corrected for inflammation. We included a cross-sectional sample of a cohort study of 801 randomly selected people (n = 1008 assays, mean age 58.6 ± 0.3 years) from Wisconsin state employee agencies. A previously validated automatic detector was used to measure PLMs during sleep. The patients were categorized into RLS symptoms-positive and RLS symptoms-negative based on a mailed survey response and prior analysis. Analyses were performed using a linear model with PLM category above and below 15 PLM/h (periodic leg movement index, PLMI) as the dependent variable, and adjusting for known covariates, including previously associated single-nucleotide polymorphisms (SNPs) within BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Ferritin and C-reactive protein (CRP) levels were measured in serum, and ferritin levels corrected for inflammation using CRP levels. After controlling for cofactors, PLMI ≥ 15 was associated with low (≤50 ng/mL) ferritin levels (OR = 1.55, p = 0.020). The best model was found using quasi-least squares regression of ferritin as a function of PLMI, with an increase of 0.0034 PLM/h predicted by a decrease of 1 ng/mL ferritin (p = 0.00447). An association was found between low ferritin and greater PLMs in a general population of older adults, independent of genetic polymorphisms, suggesting a role of low iron stores in the expression of these phenotypes. Patients with high PLMI may require to be checked for iron deficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

Oral Iron Supplementation After Blood Donation

PubMed Central

Kiss, Joseph E.; Brambilla, Donald; Glynn, Simone A.; Mast, Alan E.; Spencer, Bryan R.; Stone, Mars; Kleinman, Steven H.; Cable, Ritchard G.

2016-01-01

IMPORTANCE Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard (12.5 g/dL) is frequently delayed, and some donors become anemic. OBJECTIVE To determine the effect of oral iron supplementation on hemoglobin recovery time (days to recovery of 80% of hemoglobin removed) and recovery of iron stores in iron-depleted (“low ferritin,” ≤26 ng/mL) and iron-replete (“higher ferritin,” >26 ng/mL) blood donors. DESIGN, SETTING, AND PARTICIPANTS Randomized, nonblinded clinical trial of blood donors stratified by ferritin level, sex, and age conducted in 4 regional blood centers in the United States in 2012. Included were 215 eligible participants aged 18 to 79 years who had not donated whole blood or red blood cells within 4 months. INTERVENTIONS One tablet of ferrous gluconate (37.5 mg of elemental iron) daily or no iron for 24 weeks (168 days) after donating a unit of whole blood (500 mL). MAIN OUTCOMES AND MEASURES Time to recovery of 80% of the postdonation decrease in hemoglobin and recovery of ferritin level to baseline as a measure of iron stores. RESULTS The mean baseline hemoglobin levels were comparable in the iron and no-iron groups and declined from a mean (SD) of 13.4 (1.1) g/dL to 12.0 (1.2) g/dL after donation in the low-ferritin group and from 14.2 (1.1) g/dL to 12.9 (1.2) g/dL in the higher-ferritin group. Compared with participants who did not receive iron supplementation, those who received iron supplementation had shortened time to 80% hemoglobin recovery in both the low-ferritin and higher-ferritin groups. Recovery of iron stores in all participants who received supplements took a median of 76 days (IQR, 20–126); for participants not taking iron, median recovery time was longer than 168 days (IQR, 147->168 days; P < .001). Without iron supplements, 67% of participants did not recover iron stores by 168 days. Low-Ferritin Group (≤26 ng/mL) Higher-Ferritin Group (>26 ng/mL) IronNo IronIronNo Iron Time to 80% hemoglobin recovery, mean (IQR), d32 (30–34)158 (126–>168)31 (29–33)78 (66–95) Time to recovery of baseline ferritin levels, median (IQR), d21 (12–84)>168 (128–>168)107 (75–141)>168 (>168–>168) CONCLUSIONS AND RELEVANCE Among blood donors with normal hemoglobin levels, low-dose iron supplementation, compared with no supplementation, reduced time to 80% recovery of the postdonation decrease in hemoglobin concentration in donors with low ferritin (≤26 ng/mL) or higher ferritin (>26 ng/mL). TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01555060 PMID:25668261

Ferritins and iron storage in plants.

PubMed

Briat, Jean-François; Duc, Céline; Ravet, Karl; Gaymard, Frédéric

2010-08-01

Iron is essential for both plant productivity and nutritional quality. Improving plant iron content was attempted through genetic engineering of plants overexpressing ferritins. However, both the roles of these proteins in the plant physiology, and the mechanisms involved in the regulation of their expression are largely unknown. Although the structure of ferritins is highly conserved between plants and animals, their cellular localization differ. Furthermore, regulation of ferritin gene expression in response to iron excess occurs at the transcriptional level in plants, in contrast to animals which regulate ferritin expression at the translational level. In this review, our knowledge of the specific features of plant ferritins is presented, at the level of their (i) structure/function relationships, (ii) cellular localization, and (iii) synthesis regulation during development and in response to various environmental cues. A special emphasis is given to their function in plant physiology, in particular concerning their respective roles in iron storage and in protection against oxidative stress. Indeed, the use of reverse genetics in Arabidopsis recently enabled to produce various knock-out ferritin mutants, revealing strong links between these proteins and protection against oxidative stress. In contrast, their putative iron storage function to furnish iron during various development processes is unlikely to be essential. Ferritins, by buffering iron, exert a fine tuning of the quantity of metal required for metabolic purposes, and help plants to cope with adverse situations, the deleterious effects of which would be amplified if no system had evolved to take care of free reactive iron. Copyright 2009 Elsevier B.V. All rights reserved.

New insights into ferritin synthesis and function highlight a link between iron homeostasis and oxidative stress in plants.

PubMed

Briat, Jean-Francois; Ravet, Karl; Arnaud, Nicolas; Duc, Céline; Boucherez, Jossia; Touraine, Brigitte; Cellier, Francoise; Gaymard, Frederic

2010-05-01

Iron is an essential element for both plant productivity and nutritional quality. Improving plant iron content was attempted through genetic engineering of plants overexpressing ferritins. However, both the roles of these proteins in plant physiology, and the mechanisms involved in the regulation of their expression are largely unknown. Although the structure of ferritins is highly conserved between plants and animals, their cellular localization differs. Furthermore, regulation of ferritin gene expression in response to iron excess occurs at the transcriptional level in plants, in contrast to animals which regulate ferritin expression at the translational level. In this review, an overview of our knowledge of bacterial and mammalian ferritin synthesis and functions is presented. Then the following will be reviewed: (a) the specific features of plant ferritins; (b) the regulation of their synthesis during development and in response to various environmental cues; and (c) their function in plant physiology, with special emphasis on the role that both bacterial and plant ferritins play during plant-bacteria interactions. Arabidopsis ferritins are encoded by a small nuclear gene family of four members which are differentially expressed. Recent results obtained by using this model plant enabled progress to be made in our understanding of the regulation of the synthesis and the in planta function of these various ferritins. Studies on plant ferritin functions and regulation of their synthesis revealed strong links between these proteins and protection against oxidative stress. In contrast, their putative iron-storage function to furnish iron during various development processes is unlikely to be essential. Ferritins, by buffering iron, exert a fine tuning of the quantity of metal required for metabolic purposes, and help plants to cope with adverse situations, the deleterious effects of which would be amplified if no system had evolved to take care of free reactive iron.

Transcriptional response of Pasteurella multocida to defined iron sources.

PubMed

Paustian, Michael L; May, Barbara J; Cao, Dongwei; Boley, Daniel; Kapur, Vivek

2002-12-01

Pasteurella multocida was grown in iron-free chemically defined medium supplemented with hemoglobin, transferrin, ferritin, and ferric citrate as iron sources. Whole-genome DNA microarrays were used to monitor global gene expression over seven time points after the addition of the defined iron source to the medium. This resulted in a set of data containing over 338,000 gene expression observations. On average, 12% of P. multocida genes were differentially expressed under any single condition. A majority of these genes encoded P. multocida proteins that were involved in either transport and binding or were annotated as hypothetical proteins. Several trends are evident when the data from different iron sources are compared. In general, only two genes (ptsN and sapD) were expressed at elevated levels under all of the conditions tested. The results also show that genes with increased expression in the presence of hemoglobin did not respond to transferrin or ferritin as an iron source. Correspondingly, genes with increased expression in the transferrin and ferritin experiments were expressed at reduced levels when hemoglobin was supplied as the sole iron source. Finally, the data show that genes that were most responsive to the presence of ferric citrate did not follow a trend similar to that of the other iron sources, suggesting that different pathways respond to inorganic or organic sources of iron in P. multocida. Taken together, our results demonstrate that unique subsets of P. multocida genes are expressed in response to different iron sources and that many of these genes have yet to be functionally characterized.

Controlled Aggregation of Ferritin to Modulate MRI Relaxivity

PubMed Central

Bennett, Kevin M.; Shapiro, Erik M.; Sotak, Christopher H.; Koretsky, Alan P.

2008-01-01

Ferritin is an iron storage protein expressed in varying concentrations in mammalian cells. The deposition of ferric iron in the core of ferritin makes it a magnetic resonance imaging contrast agent, and ferritin has recently been proposed as a gene expression reporter protein for magnetic resonance imaging. To date, ferritin has been overexpressed in vivo and has been coexpressed with transferrin receptor to increase iron loading in cells. However, ferritin has a relatively low T2 relaxivity (R2 ≈ 1 mM−1s−1) at typical magnetic field strengths and so requires high levels of expression to be detected. One way to modulate the transverse relaxivity of a superparamagnetic agent is to cause it to aggregate, thereby manipulating the magnetic field gradients through which water diffuses. In this work, it is demonstrated by computer simulation and in vitro that aggregation of ferritin can alter relaxivity. The effects of aggregate size and intraaggregate perturber spacing on R2 are studied. Computer modeling indicates that the optimal spacing of the ferritin molecules in aggregate for increasing R2 is 100–200 nm for a typical range of water diffusion rates. Chemical cross-linking of ferritin at 12 Å spacing led to a 70% increase in R2 compared to uncross-linked ferritin controls. To modulate ferritin aggregation in a potentially biologically relevant manner, ferritin was attached to actin and polymerized in vitro. The polymerization of ferritin-F-actin caused a 20% increase in R2 compared to unpolymerized ferritin-G-actin. The R2-value was increased by another 10% by spacing the ferritin farther apart on the actin filaments. The modulation of ferritin aggregation by binding to cytoskeletal elements may be a useful strategy to make a functional reporter gene for magnetic resonance imaging. PMID:18326661

Significance of clinical and biologic features in Stage 3 neuroblastoma: a report from the International Neuroblastoma Risk Group project.

PubMed

Meany, Holly J; London, Wendy B; Ambros, Peter F; Matthay, Katherine K; Monclair, Tom; Simon, Thorsten; Garaventa, Alberto; Berthold, Frank; Nakagawara, Akira; Cohn, Susan L; Pearson, Andrew D J; Park, Julie R

2014-11-01

International Neuroblastoma Staging System (INSS) Stage 3 neuroblastoma is a heterogeneous disease. Data from the International Neuroblastoma Risk Group (INRG) database were analyzed to define patient and tumor characteristics predictive of outcome. Of 8,800 patients in the INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN-non-amplified (NA) tumors. Significant prognostic factors were identified via log-rank test comparisons of survival curves. Multivariable Cox proportional hazards regression model was used to identify factors independently predictive of event-free survival (EFS). Age at diagnosis (P < 0.0001), tumor MYCN status (P < 0.0001), and poorly differentiating/undifferentiated histology (P = 0.03) were independent predictors of EFS. Compared to other Stage 3 subgroups, outcome was inferior for patients ≥ 547 days with MYCN-NA neuroblastoma (P < 0.0001), and within this cohort, serum ferritin ≥ 96 ng/ml was associated with inferior EFS (P = 0.02). For patients <547 days of age with MYCN-NA tumors, serum ferritin levels were prognostic of overall survival (OS) (P = 0.04) and chromosome 11q aberration was prognostic of EFS (P = 0.03). Among patients with INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology predict outcome. Patients <547 days of age with MYCN-NA tumors that lack chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent prognosis and should be considered for therapy reduction. Prospective clinical trials are needed to identify optimal therapy for those patients ≥ 547 days of age with undifferentiated histology or elevated serum ferritin. © 2014 Wiley Periodicals, Inc.

Ferritin: a zinc detoxicant and a zinc ion donor.

PubMed Central

Price, D; Joshi, J G

1982-01-01

Rats were injected with 1 mg of Zn2+ as zinc sulfate or 2 mg of Cd2+ as cadmium sulfate per kg of body weight on a daily basis. After seven injections, ferritin and metallothionein were isolated from the livers of the rats. Significant amounts of zinc were associated with ferritin. Incubation of such ferritin with apoenzymes of calf intestinal alkaline phosphatase, yeast phosphoglucomutase, and yeast aldolase restored their enzymic activity. The amount of zinc injected was insufficient to stimulate significant synthesis of metallothionein, but similar experiments with injection of cadmium did stimulate the synthesis of metallothionein. The amount of Zn2+ in ferritin of Cd-injected rats was greater than that in ferritin in Zn-injected rats, which was greater than that in ferritin of normal rats. Thus at comparable protein concentration ferritin from Cd-injected rats was a better Zn2+ donor than was ferritin from Zn-injected or normal animals. Ferritin is a normal constituent of several tissues, whereas metallothionein is synthesized under metabolic stress. Thus ferritin may function as a "metal storage and transferring agent" for iron and for zinc. It is suggested that ferritin probably serves as the initial chelator for Zn2+ and perhaps other metal ions as well and that under very high toxic levels of metal ions the synthesis of metallothionein is initiated as the second line of defense. PMID:6212927

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

PubMed Central

DePalma, Ralph G.; Shamayeva, Galina; Chow, Bruce K.

2013-01-01

Objectives. We postulated the existence of a statin–iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores. Methods. Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins. Results. Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status. Conclusions. There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins. PMID:23409890

Clinical outcomes of transfusion-associated iron overload in patients with refractory chronic anemia.

PubMed

Gao, Chong; Li, Li; Chen, Baoan; Song, Huihui; Cheng, Jian; Zhang, Xiaoping; Sun, Yunyu

2014-01-01

The purpose of this study was to evaluate the clinical outcomes of transfusion-associated iron overload in patients with chronic refractory anemia. Clinical manifestations, main organ function, results of computed tomography (CT), endocrine evaluation, and serum ferritin levels were analyzed retrospectively in 13 patients who were transfusion-dependent for more than 1 year (receiving >50 units of red blood cells) to determine the degree of iron overload and efficacy of iron-chelating therapy. Serum ferritin levels increased to 1,830-5,740 ng/mL in all patients. Ten patients had abnormal liver function. The CT Hounsfield units in the liver increased significantly in eleven patients, and were proportional to their serum ferritin levels. Skin pigmentation, liver dysfunction, and endocrine dysfunction were observed in nine patients with serum ferritin >3,500 ng/mL, eight of whom have since died. Interestingly, serum ferritin levels did not decrease significantly in nine transfusion-dependent patients who had received 15-60 days of iron-chelating therapy. Transfusion-dependent patients may progress to secondary iron overload with organ impairment, which may be fatal in those who are heavily iron-overloaded. The CT Hounsfield unit is a sensitive indicator of iron overload in the liver. Iron chelation therapy should be initiated when serum ferritin is >1,000 ng/mL and continued until it is <1,000 ng/mL in transfusional iron-overloaded patients.

Serum ferritin and vitamin d in female hair loss: do they play a role?

PubMed

Rasheed, H; Mahgoub, D; Hegazy, R; El-Komy, M; Abdel Hay, R; Hamid, M A; Hamdy, E

2013-01-01

Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D2 levels were determined for each participant. Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D2 levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. Low serum ferritin and vitamin D2 are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease. Copyright © 2013 S. Karger AG, Basel.

Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome.

PubMed

McElroy, Anita K; Erickson, Bobbie R; Flietstra, Timothy D; Rollin, Pierre E; Nichol, Stuart T; Towner, Jonathan S; Spiropoulou, Christina F

2014-08-15

Ebola hemorrhagic fever (EHF) outbreaks occur sporadically in Africa and result in high rates of death. The 2000-2001 outbreak of Sudan virus-associated EHF in the Gulu district of Uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest EHF outbreak on record. Serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis. Available samples were tested using a series of multiplex assays to measure the concentrations of 55 biomarkers. The data were analyzed to identify statistically significant associations between the tested biomarkers and hemorrhagic manifestations, viremia, and/or death. Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of sCD40L. These novel associations provide a better understanding of EHF pathophysiology and a starting point for researching new potential targets for therapeutic interventions. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Iron overload in patients receiving allogeneic hematopoietic stem cell transplantation: quantification of iron burden by a superconducting quantum interference device (SQUID) and therapeutic effectiveness of phlebotomy.

PubMed

Busca, Alessandro; Falda, Michele; Manzini, Paola; D'Antico, Sergio; Valfrè, Adriano; Locatelli, Franco; Calabrese, Roberto; Chiappella, Annalisa; D'Ardia, Stefano; Longo, Filomena; Piga, Antonio

2010-01-01

Iron overload (IO) is a known adverse prognostic factor in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia and appears to play a similar role in patients with other hematologic disorders. The estimation of IO is based primarily on serum ferritin level; however, many confounding factors can result in ferritin overestimation, especially in HSCT recipients. The aim of the present study was to quantify IO after HSCT using a superconducting quantum interference device (SQUID), and to evaluate the impact of IO on hepatic function and infections. In addition, the feasibility of iron depletion was investigated. A total of 102 consecutive allogeneic HSCT recipients admitted to our outpatient department between December 2005, and December 2007, were analyzed. Primary diagnosis included acute leukemia/myelodysplastic syndrome in 61% of cases. Assessment of IO after HSCT included serum ferritin; in those with hyperferritinemia (ferritin>1000 ng/mL), liver iron concentration (LIC) was evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to patients with moderate IO (LIC 1000-2000 microg Fe/g wet weight [ww]) or severe IO (LIC >2,000 microg Fe/g ww). Fifty-seven patients had a ferritin level <1000 ng/mL: the median time between HSCT and assessment of ferritin level was 1006 days (range, 93-5239 days), significantly different from the median time of 183 days (range, 78-2957 days) in the 45 patients with a ferritin level >1000 ng/mL. Out of 42 patients evaluated by SQUID, 29 had moderate to severe IO (median LIC value, 1493 microg Fe/g ww [range, 1030-3253]). In a multivariate analysis, a significant correlation was found between a ferritin level >1000 ng/mL and the presence of at least one abnormal liver function test (LFT) ORo=6.8; 95% CI=2.2-20.6). In addition, the rate of proven/probable invasive fungal disease was significantly higher in the patients with hyperferritinemia (13% vs 0%; P=.006). Nineteen of the 24 patients considered eligible for iron-depletion therapy underwent regular phlebotomy; 13 completed the program in a median of 287 days (range, 92-779 days), reaching the target of a ferritin level<500 ng/mL; LIC was significantly reduced (median, 1419 microg Fe/g ww to 625 microg Fe/g ww; P < .001) in 8 of the 9 patients who were revaluated by SQUID at the end of the iron-depletion program. In conclusion, the measurement of LIC obtained by SQUID documented the presence of moderate/severe IO in 69% of the patients with a high ferritin level. Our data showed that in HSCT recipients, high ferritin level is an independent risk factor for abnormal LFTs, and IO may be considered a potential risk factor for fungal infections. A phlebotomy program may be feasible in two-thirds of the patients who might benefit from iron depletion. Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Serum iron parameters in liver cirrhosis

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Maail, W.

2018-03-01

The liver plays a fundamental role in iron homeostasis. Iron parameters change, especially ferritin, need to be evaluated in patients with liver cirrhosis. Serum ferritin could predict the prognosis of patients with decompensated cirrhosis since it reflects immunemediated and infectious stimuli. Ferritin could express the severity of liver disease and possible subsequent complications. Finally, it might reflect an iron overload condition resulting in significant morbidity and early mortality. 70 patients with decompensated liver cirrhosis divided into three Child-Pugh subgroups. Serum iron parameters include serum iron (SI), total iron binding capacity (TIBC) and ferritin was measured in these groups. From these 70 patients, 30 (42.9%) with HbsAg positive, 26 (37.1%) with anti-HCV positive and 14 (20%) with both HbsAg and anti-HCV positive. Of the 70 patients, 14 (20%) had CTP Class A cirrhosis, 17 (24.3%) had CTP Class B cirrhosis, and 39 (55.7%) had CTP C cirrhosis. The median (range) value of serum iron was 36 (10-345) μg/dl, TIBC was 160 (59-520) μg/dl, Ferritin was 253.5 (8-6078) ng/ml and the transferrin saturation was 22.9 (3.65-216.98) %.We found a significant difference in serum ferritin level with CTP score. Ferritin levels increased as Child-Pugh class progressed (p<0.001).

Different protein of Echinococcus granulosus stimulates dendritic induced immune response.

PubMed

Wang, Yana; Wang, Qiang; Lv, Shiyu; Zhang, Shengxiang

2015-06-01

Cystic echinococcosis is a chronic infectious disease that results from a host/parasite interaction. Vaccination with ferritin derived from Echinococcus granulosus is a potential preventative treatment. To understand whether ferritin is capable of inducing a host immune response, we investigated the response of dendritic cells (DCs) to both recombinant ferritin protein and the hydatid fluid (HF) of E. granulosus. We evaluated the immunomodulatory potential of these antigens by performing, immunocytochemistry, electron microscopy and in vivo imaging of monocyte-derived murine DCs. During antigen stimulation of DCs, ferritin cause DCs maturation and induced higher levels of surface marker expression and activated T-cell proliferation and migration. On contrary, HF failed to induce surface marker expression and to stimulate T-cell proliferation. In response to HF, DCs produced interleukin-6 (IL-6), but no IL-12 and IL-10. DCs stimulated with ferritin produced high levels of cytokines. Overall, HF appears to induce host immunosuppression in order to ensure parasite survival via inhibits DC maturation and promotes Th2-dependent secretion of cytokines. Although ferritin also promoted DC maturation and cytokine release, it also activates CD4+T-cell proliferation, but regard of the mechanism of the Eg.ferritin induce host to eradicate E. granulosus were not clear.

A High Serum Iron Level Causes Mouse Retinal Iron Accumulation Despite an Intact Blood-Retinal Barrier

PubMed Central

Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L.

2015-01-01

The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms. PMID:25174877

Role of androgen-mediated enhancement of erythropoiesis in the increased body iron stores of patients with polycystic ovary syndrome.

PubMed

Escobar-Morreale, Héctor F; Luque-Ramírez, Manuel

2011-04-01

To determine whether androgen excess contributes to the increased body iron stores of polycystic ovary syndrome (PCOS) by stimulating erythropoietic activity, by measuring serum soluble transferrin receptor (sTfR) concentrations and its ratio to ferritin levels in patients with PCOS, as surrogate markers of erythropoietic activity and of the appropriateness of cellular iron demands for the total body iron contents, respectively. Case-control study. Academic hospital. One hundred-four patients with PCOS and 100 controls without androgen excess. Blood sampling and oral glucose tolerance test. Serum sTfR and ferritin concentrations, as well as indexes of androgen excess, inflammation, obesity, and insulin and glucose metabolism. Serum ferritin levels increased in women presenting with PCOS, obesity, and/or abnormal glucose tolerance, but these disorders did not influence sTfR concentrations. The sTfR/ferritin ratio decreased with obesity and abnormal glucose tolerance, and its logarithm correlated inversely with body mass index, free T, and C-reactive protein levels and directly with the insulin sensitivity and disposition indexes. A stepwise multiple regression analysis indicated that the changes in the insulin sensitivity index explained 7% of the variability of the logarithm of sTfR/ferritin ratio. Increased serum ferritin levels in patients with PCOS are associated with a reduction in insulin sensitivity but do not result from a putative enhancement of erythropoiesis by androgen excess. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hyperferritinemia in Dogs with Splenic Hemangiosarcoma

PubMed Central

CHIKAZAWA, Seishiro; HORI, Yasutomo; HOSHI, Fumio; KANAI, Kazutaka; ITO, Naoyuki; HIGUCHI, Seiichi

2013-01-01

ABSTRACT Serum ferritin concentration increases in dogs in association with various diseases. In this study, we measured serum ferritin levels in dogs with splenic masses, using a sandwich ELISA assay. Eleven dogs with hemangiosarcoma (HSA), six with hematoma, 1 with hemangioma and 3 with lymphoma were enrolled. All dogs with HSA had serum ferritin concentrations above the normal limit (1,357 ng/ml, mean + 2× standard deviation of normal). Increased serum ferritin concentrations have also been observed in few cases of hematoma, hemangioma and lymphoma. Therefore, hyperferritinemia is not specific for splenic HSA, but may have clinical usefulness as a sensitive test for the disease. Further evaluation of serum ferritin concentrations in dogs with splenic HSA is needed. PMID:23803459

Hyperferritinemia in dogs with splenic hemangiosarcoma.

PubMed

Chikazawa, Seishiro; Hori, Yasutomo; Hoshi, Fumio; Kanai, Kazutaka; Ito, Naoyuki; Higuchi, Seiichi

2013-11-01

Serum ferritin concentration increases in dogs in association with various diseases. In this study, we measured serum ferritin levels in dogs with splenic masses, using a sandwich ELISA assay. Eleven dogs with hemangiosarcoma (HSA), six with hematoma, 1 with hemangioma and 3 with lymphoma were enrolled. All dogs with HSA had serum ferritin concentrations above the normal limit (1,357 ng/ml, mean + 2× standard deviation of normal). Increased serum ferritin concentrations have also been observed in few cases of hematoma, hemangioma and lymphoma. Therefore, hyperferritinemia is not specific for splenic HSA, but may have clinical usefulness as a sensitive test for the disease. Further evaluation of serum ferritin concentrations in dogs with splenic HSA is needed.

Abnormal troponin I levels in a thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-01-21

Thalassemia is a congenital hemoglobinopathy leading to anemia because of impaired erythropoiesis and peripheral hemolysis. Thalassemia major patients are transfusion dependent and it results in iron accumulation. The heart is one of the major organs affected with iron overload and iron induced cardiac dysfunction (pump and conduction abnormalities) remains the number one cause of death among thalassemia major patients. It has been reported that a high ferritin concentration is related to high troponin levels in hemodialysis patients receiving more intravenous iron sucrose. Abnormal troponin I levels have also been reported without acute coronary syndrome. We present a case of abnormal troponin I levels in Thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome. To our knowledge, this is the first report of abnormal troponin I levels in a Thalassemia major patient with high ferritin concentration and without acute coronary syndrome and also this case focuses attention on the importance of the correct evaluation of abnormal troponin I levels. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry

PubMed Central

Maruyama, Yukio; Yokoyama, Keitaro; Yokoo, Takashi; Shigematsu, Takashi; Iseki, Kunitoshi; Tsubakihara, Yoshiharu

2015-01-01

Background/Aims Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD). Methods Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008. Results Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31–1.81 and HR, 1.44; 95% CI, 1.13–1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79–1.65). Conclusions Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients. PMID:26599216

Evidence that iron accelerates Alzheimer's pathology: a CSF biomarker study.

PubMed

Ayton, Scott; Diouf, Ibrahima; Bush, Ashley Ian

2018-05-01

To investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau. Mixed-effects models of CSF Aβ 1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ 1-42 for up to 5 years. In subjects with biomarker-confirmed Alzheimer's pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aβ 1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aβ 1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aβ deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aβ from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aβ over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aβ levels to the average level of Alzheimer's subjects from 18.8 to 10.8 years. Iron might facilitate Aβ deposition in Alzheimer's and accelerate the disease process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload.

PubMed

Puliyel, Mammen; Sposto, Richard; Berdoukas, Vasilios A; Hofstra, Thomas C; Nord, Anne; Carson, Susan; Wood, John; Coates, Thomas D

2014-04-01

Ferritin levels and trends are widely used to manage iron overload and assess the efficacy of prescribed iron chelation in patients with transfusional iron loading. A retrospective cohort study was conducted in 134 patients with transfusion-dependent anemia, over a period of up to 9 years. To determine whether the trends in ferritin adequately reflect the changes in total body iron, changes in ferritin between consecutive liver iron measurements by magnetic resonance imaging (MRI) were compared to changes in liver iron concentrations (LIC), a measure of total body iron. The time period between two consecutive LIC measurements was defined as a segment. Trends in ferritin were considered to predict the change in LIC within a segment if the change in one parameter was less than twofold that of the other, and was in the same direction. Using the exclusion criteria detailed in methods, the trends in ferritin were compared to changes in LIC in 358 segments. An agreement between ferritin trends and LIC changes was found in only 38% of the 358 segments examined. Furthermore, the change in ferritin was in opposite direction to that of LIC in 26% of the segments. Trends in ferritin were a worse predictor of changes in LIC in sickle cell disease than in thalassemia (P < 0.01). While ferritin is a convenient measure of iron status; ferritin trends were unable to predict changes in LIC in individual patients. Ferritin trends need to be interpreted with caution and confirmed by direct measurement of LIC. Copyright © 2013 Wiley Periodicals, Inc.

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

PubMed

Payne, Krista A; Rofail, Diana; Baladi, Jean-François; Viala, Muriel; Abetz, Linda; Desrosiers, Marie-Pierre; Lordan, Noreen; Ishak, Khajak; Proskorovsky, Irina

2008-08-01

This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

Modifying effects of 5-azacytidine on metal-containing proteins profile in Guerin carcinoma with different sensitivity to cytostatics.

PubMed

Chekhun, V F; Lozovska, Y V; Naleskina, L A; Borikun, T V; Burlaka, A P; Todor, I N; Demash, D V; Yalovenko, T M; Zadvornyi, T V; Pavlova, A O; Storchay, D M; Lukianova, N Yu

2016-12-01

To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo. The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment. 5-Aza was injected by i.v. route (1 injection in 4 days at a dose of 2 mg/kg starting from the 4 th day after tumor transplantation, 4 injections in total). Ferritin levels in blood serum and tumor tissue were measured by ELISA, transferrin and free iron complexes - by low-temperature EPR, miRNA-200b, -133a and -320a levels and promoter methylation - by real-time quantitative reverse transcription polymerase chain reaction. The study has shown that 5-aza treatment caused demethylation of promoter regions of fth1 and tfr1 genes in all studied Guerin carcinoma strains. 5-Aza treatment resulted in a significant decrease of ferritin levels in tumor tissue (by 32.1% in Guerin/WT strain, by 29.8% in Guerin/Dox and by 69.1% in Guerin/CP). These events were accompanied by 3.5-fold and 2-fold increase of free iron complexes levels in tumor tissue of doxorubicin and cisplatin resistant strains, respectively. Also, 5-aza treatment resulted in significantly elevated levels of miR-200b, -133a, 320a expression in tumor tissue. After 5-aza treatment, ferritin levels in blood serum of animals with Guerin/Dox were increased by 23.9%, while in Guerin/Wt and Guerin/CP they were decreased by 17 and 16%, respectively. Alterations of epigenetic regulation upon in vivo treatment with 5-aza change the levels of metal-containing proteins due to DNA demethylation and altered miRNA expression profiles in Guerin carcinoma cells.

Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent.

PubMed

Hughes, Elizabeth A; Patel, Jeetesh V; Bredow, Zosia; Gill, Paramjit S; Chackathayil, Julia; Agaoglu, Elif S; Flinders, Paul; Mirrielees, Rebecca

2015-01-01

Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P = 0.005), irrespective of site, gender, and central obesity (P ≤ 0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P < 0.001). Diabetes was less in those with low ferritin (<20 mg/mL), P < 0.008, and risk estimate = 0.35 (95% CI 0.15-0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P = 0.001) and age (P < 0.001). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors.

Iron induction of ferritin synthesis in soybean cell suspensions.

PubMed

Proudhon, D; Briat, J F; Lescure, A M

1989-06-01

In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes.

[Polyglobulia and bronchopneumopathies: correlations of ferritin and other ferric parameters with various erythrocytic indexes].

PubMed

Sánchez Sánchez, M L; Ciriza de los Ríos, C; Arroyo Vicente, M; Ortega de Heredia, D; Arroyo Ordóñez, M J; Rubio Pérez, P

1993-08-01

In 15 patients with chronic bronchopneumopathy (7 with polyglobulia and 8 without it), we observed that polyglobulic patients had higher average levels of sideremia and basal saturation of transferrin and lower levels of HCM, CHCM and VCM. No significant differences were observed in the average levels of ferritin between both groups. Overall, in this series of 15 patients, a significant inverse correlation was observed between sideremia and HCM (r = -0.52; p < 0.05) and between sideremia and CHCM (r = -0.55, p < 0.5), as well as a trend towards a direct correlation between sideremia and the red blood cells count (r = 0.45, N.S.). There was also a direct correlation between serum ferritin and the sedimentation rate (r = 0.72, p < 0.01) and trends towards inverse correlations although not significant, between ferritin and sideremia (r = -0.25, N.S.). These data reflect a hyperconsumption of iron in the respiratory polyglobulia, with some relative deficit, suggesting as well that serum ferritin is not a good enough criteria in these cases for the evaluation of iron deposits, because it behaves like the sedimentation rate with respect to acute phase reactants when there is inflammation.

Serum ferritin values in Nigerian pregnant women.

PubMed

Nnatu, S N; Oluboyede, O A

1986-04-01

Serum ferritin values have been studied in 28 indigenous Nigerian pregnant women during the second and third trimesters of pregnancy. The mean serum ferritin value in the second trimester is higher than that in the third trimester, however, the difference is not statistically significant. When our results are related to those of Fenton and co-workers in 1977 (Fenton V, Cavill I, Fisher J: Iron stores in pregnancy. Br J Haem 37: 145, 1977) it appears that serum ferritin decreases in early pregnancy and that this decrease is maintained through the second and third trimesters and towards term, irrespective of adequate iron supplementation. It also seems that the pre-pregnancy serum ferritin level is achieved 5-8 weeks post-delivery. Our results also underline the sensitivity of serum ferritin evaluation in pregnancy, and reinforce the concept that fetal requirement for iron occurs significantly during the later half of pregnancy.

Short repeats in the heme oxygenase 1 gene promoter is associated with increased levels of inflammation, ferritin and higher risk of type-2 diabetes mellitus.

PubMed

Andrews, Mónica; Leiva, Elba; Arredondo-Olguín, Miguel

2016-09-01

We evaluated the relationship between the HO1 genotype, ferritin levels and the risk of type-2 diabetes and inflammation. Eight hundred thirty-five individuals were evaluated and classified according to their nutritional status and the presence of type-2 diabetes: 153 overweight (OW); 62 obese (OB); 55 type-2 diabetes mellitus (DM); 202 OWDM; 239 OBDM and 124 controls (C). We studied biochemical (glycemia, insulin, lipid profile, liver enzyme, creatinine, hsCRP), hematological (hemoglobin, free erythrocyte protoporphyrin, transferrin receptor and serum Fe and ferritin) and oxidative stress (SOD, GHS and TBARS) parameters. We determined heme oxygenase activity and the (GT)n polymorphism in its gene promoter. Individuals with diabetes, independent of nutritional status, showed high levels of ferritin and HO activity compared to control subjects. Allelic frequency was not different between the groups (Chi(2), NS) however, genotypes were different (Chi(2), P<0.001). The SS (short-short) genotype was higher in all DM individuals compared to controls and MM was higher in controls. SM (short-medium) genotype was an independent risk factor for DM in logistic regression analysis. We observed high risk for type-2 diabetes mellitus in the presence of SM genotype and high levels of ferritin (OR adjusted: 2.7; 1.9-3.6; p<0.001; compared to control group). It was also significantly related to inflammation. The SM genotype in HO1 gene promoter and ferritin levels were associated with higher risk for type-2 diabetes and for having a higher marker of inflammation, which is the main risk factor for the development of chronic diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

Hepatic iron content is independently associated with serum hepcidin levels in subjects with obesity.

PubMed

Moreno-Navarrete, José María; Moreno, María; Puig, Josep; Blasco, Gerard; Ortega, Francisco; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel

2017-10-01

Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed. Serum hepcidin, ferritin and hepatic iron content (HIC) were significantly increased in participants with obesity. Age- and gender-adjusted serum hepcidin was positively correlated with BMI, hsCRP, ferritin and HIC. In addition, age- and gender-adjusted serum hepcidin was positively correlated with ferritin and HIC in both non-obese and obese participants. In multivariate regression analysis, hepatic iron content (p < 0.01) and serum ferritin (p < 0.001) contributed independently to circulating hepcidin concentration variation after controlling for age, gender, BMI and hsCRP. Diet intervention-induced weight loss led to decreased serum hepcidin (p = 0.01), serum ferritin concentration (p = 0.01) and HIC (p = 0.002). Of note, the percent change of serum hepcidin strongly correlated with the percent change of serum ferritin (r = 0.69, p = 0.01) and HIC (r = 0.61, p = 0.03) even after controlling for age and gender. Serum hepcidin is a reliable marker of the hepatic iron content in subjects with obesity. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Comparative analysis of proteomic changes in contrasting flax cultivars upon cadmium exposure.

PubMed

Hradilová, Jana; Rehulka, Pavel; Rehulková, Helena; Vrbová, Miroslava; Griga, Miroslav; Brzobohatý, Bretislav

2010-01-01

Cadmium (Cd) is classified as a serious pollutant due to its high toxicity, high carcinogenicity, and widespread presence in the environment. Phytoremediation represents an effective low-cost approach for removing pollutants from contaminated soils, and a crop with significant phytoremediation potential is flax. However, significant differences in Cd accumulation and tolerance were previously found among commercial flax cultivars. Notably, cv. Jitka showed substantially higher tolerance to elevated Cd levels in soil and plant tissues than cv. Tábor. Here, significant changes in the expression of 14 proteins (related to disease/defense, metabolism, protein destination and storage, signal transduction, energy and cell structure) were detected by image and mass spectrometric analysis of two-dimensionally separated proteins extracted from Cd-treated cell suspension cultures derived from these contrasting cultivars. Further, two proteins, ferritin and glutamine synthetase (a key enzyme in glutathione biosynthesis), were only up-regulated by Cd in cv. Jitka, indicating that Cd tolerance mechanisms in this cultivar may include maintenance of low Cd levels at sensitive sites by ferritin and low-molecular weight thiol peptides binding Cd. The identified changes could facilitate marker-assisted breeding for Cd tolerance and the development of transgenic flax lines with enhanced Cd tolerance and accumulation capacities for phytoremediating Cd-contaminated soils.

Successful pregnancy outcome following maternal intravenous immunoglobulin treatment in a woman with recurrent perinatal haemochromatosis.

PubMed

Venkat-Raman, Narayanaswamy; Venkata-Krishnan, Radha V; Howarth, Edmund S

2006-12-01

We report a case of successful pregnancy outcome following maternal intravenous immunoglobulin treatment in a woman with previous history of recurrent fetal hydrops secondary to perinatal haemochromatosis. A 32-year old woman had two successive pregnancies complicated by fetal hydrops and perinatal deaths. Pathological examination of the fetus showed severe liver destruction with siderosis of hepatocytes at extrahepatic sites, but sparing of the reticulo-endothelial elements, consistent with the diagnosis of perinatal haemochromatosis. In the subsequent pregnancy, maternal intravenous immunoglobulin was administered weekly from the 18th week of gestation until delivery by elective caesarean section at 38 weeks. The infant was treated with desferrioxamine, N-acetylcysteine, vitamins K and E. The infant was born in good health, but had high serum ferritin levels, markedly elevated percent transferrin saturation, and mild transient derangement of liver and coagulation function. The infant made an excellent recovery and the treatment was stopped at 7 weeks of age. The liver and coagulation parameters and the serum ferritin levels returned to normal values. Haemochromatosis should be considered in the differential diagnosis of hydrops fetalis. The recurrence risk is high, and immunomodulation with intravenous immunoglobulin treatment appears to alter the course of the disease with better infant survival. Copyright (c) 2006 John Wiley & Sons, Ltd.

Relationship between high serum ferritin level and glaucoma in a South Korean population: the Kangbuk Samsung health study.

PubMed

Gye, Hyo Jung; Kim, Joon Mo; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Sung, Ki Chul; Lee, Mi Yeon; Park, Ki Ho

2016-12-01

To investigate the association between serum ferritin levels and glaucoma in a South Korean population. This retrospective cross-sectional study included 164 029 subjects who underwent screening at Kangbuk Samsung Hospital Health Screening Center between August 2012 and July 2013. All subjects underwent a physical examination, answered sociodemographic and behavioural questions, and provided samples for laboratory analyses. A digital fundus photograph of both eyes was taken, and all photographs were reviewed by ophthalmologists. The ophthalmologists determined if an eye had glaucoma based on criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and the appearance of the retinal nerve fibre layer and optic disc. The mean serum ferritin level was 56.98 ng/mL in women and 223.82 ng/mL in men. After adjusting for age, serum iron, total iron-binding capacity (TIBC), transferrin saturation, white blood cell (WBC) count, high-sensitivity C-reactive protein (HsCRP) and total vitamin D level, males in the highest quartile for serum ferritin level had a higher OR for glaucoma than males in the lowest quartile (OR=1.176, 95% CI 1.030 to 1.342, p=0.016); we did not observe this relationship among women. Other markers of iron metabolism, such as iron level, transferrin saturation and TIBC, and inflammation measures, including WBC, HsCRP and total vitamin D, were not associated with glaucoma. High serum ferritin level was associated with a high risk of glaucoma in men, but not in women. Because serum ferritin is related to oxidative stress and inflammation, it might play a role in glaucoma development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease.

PubMed

Baldwin, E J; Harrington, D J; Sampson, B; Feher, M D; Wierzbicki, A S

2016-03-01

Adult Refsum's Disease (ARD) is caused by defects in the pathway for alpha-oxidation of phytanic acid (PA). Treatment involves restricting the dietary intake of phytanic acid by reducing the intake of dairy-derived fat. The adequacy of micronutrient intake in patients with ARD is unknown. Patients established on the Chelsea low-PA diet had general diet macronutrients, vitamins and trace elements assessed using 7-day-weighed intakes and serial 24-h recalls. Intakes were compared with biochemical assessments of nutritional status for haematinics (ferritin), trace elements (copper, zinc, iron, selenium), water- (vitamin B6 , B12 and folate) and fat-soluble vitamins (A, D, E and K). Eleven subjects (four women, seven men) were studied. Body mass index was 27 ± 5 kg/m(2) (range 19-38). All subjects had high sodium intakes (range 1873-4828 mg). Fat-soluble vitamin insufficiencies occurred in some individuals (vitamin A, n = 2; vitamin D, n = 6; vitamin E, n = 3; vitamin K, n = 10) but were not coincident. Vitamin B6 levels were normal or elevated (n = 6). Folate and 5-methyltetrahydrofolate concentrations were normal. Metabolic vitamin B12 insufficiency was suspected in four subjects based on elevated methylmalonic acid concentrations. Low copper and selenium intakes were noted in some subjects (n = 7, n = 2) but plasma levels were adequate. Iron, ferritin and zinc intakes and concentrations were normal. Subjects with ARD can be safely managed on the Chelsea low PA without routine micronutrient supplementation. Sodium intake should be monitored and reduced. Periodic nutritional screening may be necessary for fat-soluble vitamins, vitamin B12 , copper or selenium. © 2016 John Wiley & Sons Ltd.

Describing and expanding the clinical phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease: case series of nine Canadian patients and literature review.

PubMed

Hoa, S; Troyanov, Y; Fritzler, M J; Targoff, I N; Chartrand, S; Mansour, A M; Rich, E; Boudabbouz, H; Bourré-Tessier, J; Albert, M; Goulet, J R; Landry, M; Senécal, J L

2018-05-01

To describe and expand the phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease (MDA5-RPILD) in Canadian patients. All proven cases of MDA5-RPILD hospitalized in the University of Montreal's affiliated centres from 2004 to 2015 were selected for inclusion. Of nine consecutive patients, RPILD was the presenting manifestation in seven, whereas two patients developed RPILD 2 years after the onset of arthritis and of chronic interstitial lung disease. In the case with arthritis, RPILD was probably triggered by initiation of tumour necrosis factor-α-inhibitor therapy. In most patients (89%), RPILD was accompanied by concomitant onset of palmar/lateral finger papules, skin ulcerations, and/or mechanic's hands. All patients experienced profound weight loss over 1-2 months (mean ± SD 10.2 ± 4.8 kg). All had arthralgias and/or arthritis. Six patients were clinically amyopathic; only one patient had creatine kinase (CK) levels > 500 U/L. Initial ferritin and transaminase levels were elevated in 86% and 67% of patients, respectively. The antinuclear antibody (ANA) test was negative for nuclear and cytoplasmic staining; antisynthetase autoantibodies were negative. Three patients died; time from initial symptoms to death ranged from 7 to 15 weeks. All six survivors received mycophenolate mofetil and/or tacrolimus as part of induction and/or maintenance therapy. In an inpatient setting, RPILD associated with characteristic skin rashes, profound weight loss, articular symptoms, normal or low CK with elevated ferritin, and absent fluorescence on ANA testing should alert the clinician to the possibility of MDA5-RPILD. T-cell-mediated therapies may play a role in this highly lethal condition.

Iron chelation monotherapy in transfusion-dependent beta-thalassemia major patients: a comparative study of deferasirox and deferoxamine

PubMed Central

Hassan, Mohamed Abdel Malik; Tolba, Omar Atef

2016-01-01

Introduction Iron overload is the primary cause of mortality and morbidity in thalassemia major (TM) despite advances in chelation therapy. The aim of this study was to compare the effectiveness and safety of deferasirox (DFX) and deferoxamine (DFO) as iron-chelating agents in patients with transfusion-dependent β-thalassemia major. Methods This prospective randomized study included 60 patients with transfusion-dependent β-TM during the period from September 2014 to September 2015. Their ages were ≥ 6 years, and they had serum ferritin above 1500 μg/L and were on irregular DFO therapy. Patients had regular packed red cell transfusion in a dose of 10 mL/kg/session. They were randomized to receive DFX (single oral daily dose of 20–40 mg/kg/day) or DFO (20–50 mg/kg/day via subcutaneous infusion over 8–10 hours, 5 days a week). Iron overload was determined by serum ferritin level. The primary endpoint was decrease of serum ferritin level below 1500 μg/L. The secondary endpoint was drug safety. Results Both drugs significantly reduced serum ferritin (p < 0.001). At the end of follow-up, there were no significant differences between the two groups in serum ferritin levels (p = 0.673) and in percent reduction of ferritin (p = 0.315). There were no significant differences between the two groups in the total amount of blood transfusion (p = 0.166) and average iron intake (p = 0.227). There were no mortalities or any serious adverse effects, neutropenia, arthropathy, or pulmonary toxicity. Gastrointestinal upset and skin rash occurred more frequently with DFX than with DFO (p = 0.254 and 0.095, respectively). Conclusion With appropriate dosing and compliance with drugs, both DFX and DFO are generally well tolerated, safe, and effective in reducing serum ferritin levels in iron-overloaded, regularly-transfused thalassemia major patients. Therefore, oral DFX is recommended for more convenience and adherence to the treatment regimen. PMID:27382454

Iron chelation monotherapy in transfusion-dependent beta-thalassemia major patients: a comparative study of deferasirox and deferoxamine.

PubMed

Hassan, Mohamed Abdel Malik; Tolba, Omar Atef

2016-05-01

Iron overload is the primary cause of mortality and morbidity in thalassemia major (TM) despite advances in chelation therapy. The aim of this study was to compare the effectiveness and safety of deferasirox (DFX) and deferoxamine (DFO) as iron-chelating agents in patients with transfusion-dependent β-thalassemia major. This prospective randomized study included 60 patients with transfusion-dependent β-TM during the period from September 2014 to September 2015. Their ages were ≥ 6 years, and they had serum ferritin above 1500 μg/L and were on irregular DFO therapy. Patients had regular packed red cell transfusion in a dose of 10 mL/kg/session. They were randomized to receive DFX (single oral daily dose of 20-40 mg/kg/day) or DFO (20-50 mg/kg/day via subcutaneous infusion over 8-10 hours, 5 days a week). Iron overload was determined by serum ferritin level. The primary endpoint was decrease of serum ferritin level below 1500 μg/L. The secondary endpoint was drug safety. Both drugs significantly reduced serum ferritin (p < 0.001). At the end of follow-up, there were no significant differences between the two groups in serum ferritin levels (p = 0.673) and in percent reduction of ferritin (p = 0.315). There were no significant differences between the two groups in the total amount of blood transfusion (p = 0.166) and average iron intake (p = 0.227). There were no mortalities or any serious adverse effects, neutropenia, arthropathy, or pulmonary toxicity. Gastrointestinal upset and skin rash occurred more frequently with DFX than with DFO (p = 0.254 and 0.095, respectively). With appropriate dosing and compliance with drugs, both DFX and DFO are generally well tolerated, safe, and effective in reducing serum ferritin levels in iron-overloaded, regularly-transfused thalassemia major patients. Therefore, oral DFX is recommended for more convenience and adherence to the treatment regimen.

Ferritin and iron levels in children with autistic disorder.

PubMed

Hergüner, Sabri; Keleşoğlu, Fatih Mehmet; Tanıdır, Cansaran; Cöpür, Mazlum

2012-01-01

Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.

Construction of a cDNA library for sea cucumber Acaudina leucoprocta and differential expression of ferritin peptide

NASA Astrophysics Data System (ADS)

Zhou, Jun; Hou, Fujing; Li, Ye; Su, Xiurong; Li, Taiwu; Jin, Chunhua

2016-07-01

Acaudina leucoprocta is an edible sea cucumber of economic interest that is widely distributed in China. Little information is available concerning the molecular genetics of this species although such knowledge would contribute to a better understanding of the optimal conditions for its aquaculture and its mechanisms of defense against disease. Therefore, we constructed a cDNA library and, based on bioinformatics analysis of the sequences, the functions of 75% of the cDNAs were identified, including those involved in cell structure, energy metabolism, mitochondrial function, and signal transduction pathways. Approximately 25% of genes in the library were unmatched. The gene for A. leucoprocta ferritin was also cloned. The predicted amino-acid sequence of ferritin displayed significant homology with other sea-cucumber counterparts but indicated that it was a new member of the ferritin family. Semiquantitative real-time RT-PCR indicated the highest levels of ferritin mRNA expression in the intestine. A polyclonal antibody of ferritin was also produced. These data provide a set of molecular tools essential for further studies of the functions of ferritin protein in A. leucoprocta.

Diagnostic dilemma: Epstein-Barr virus (EBV) infectious mononucleosis with lung involvement or co-infection with Legionnaire's disease?

PubMed

Cunha, Burke A; Gian, John

Hospitalized adults with fever and "pneumonia" can be a difficult diagnostic challenge particularly when the clinical findings may be due to different infectious diseases. We recently had an elderly female who presented with fever, fatigue and dry cough with elevated serum transaminases and lung infiltrates. The diagnosis of Epstein-Barr virus (EBV) infectious mononucleosis (IM) was made based on a positive Monospot test, elevated EBV VCA IgM titer, and highly elevated EBV viral load. Her chest infiltrates were not accompanied by hilar adenopathy which may occur with EBV IM. Her dry cough persisted and she developed abdominal pain. Legionnaire's disease was considered because she had extra-pulmonary findings characteristic of Legionnaire's disease, e.g., relative bradycardia, abdominal pain, hyponatremia, hypophosphatemia, elevated ferritin levels, microscopic hematuria. Legionella titers were negative, but Legionella (serogroup 1) urinary antigen was positive. We present a diagnostic dilemma in an elderly female with both Legionnaire's disease and Epstein-Barr virus infectious mononucleosis with pulmonary involvement. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

PubMed

Han, Jae Ho; Suh, Chang-Hee; Jung, Ju-Yang; Ahn, Mi-Hyun; Kwon, Ji Eun; Yim, Hyunee; Kim, Hyoun-Ah

2017-06-01

Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

Correlation Between C-reactive Protein and Non-enzymatic Antioxidants (Albumin, Ferritin, Uric Acid and Bilirubin) in Hemodialysis Patients.

PubMed

Beciragic, Amela; Resic, Halima; Prohic, Nejra; Karamehic, Jasenko; Smajlovic, Ajdin; Masnic, Fahrudin; Ajanovic, Selma; Coric, Aida

2015-04-01

Increased levels of C-Reactive Protein are found in 30-60% on hemodialysis patients and it is closely associated with the progression of atherosclerosis, cardiovascular morbidity and mortality. Non enzymatic antioxidants are antioxidants which primarily retain potentially dangerous ions of iron and copper in their inactive form and thereby prevent its participation in the production of free radicals. The aim of the study was to examine the relationship of CRP and non enzymatic antioxidants (albumin, ferritin, uric acid and bilirubin) i.e. examine the importance of CRP as a serum biomarker in assessing the condition of inflammation and its relationship to antioxidant protection in patients on hemodialysis. The study was cross-sectional, clinical, comparative and descriptive. The study involved 100 patients (non diabetic) on chronic hemodialysis. The control group consisted of 50 subjects without subjective and objective indicators of chronic renal disease. In all patients, the concentration of CRP as well as concentrations of non enzymatic antioxidants were determined. In the group of hemodialysis patients 60% were men and 40% women. The average age of hemodialysis patients was 54.13 ± 11.8 years and the average age of the control group 41.72 ± 9.8 years. The average duration of hemodialysis treatment was 91.42 ± 76.2 months. In the group of hemodialysis patients statistically significant, negative linear correlation was determined between the concentration of CRP in and albumin concentration (rho = -0.251, p = 0.012) as well as negative, statistics insignificant, linear correlation between serum CRP and the concentration of uric acid (r = -0.077, p = 0.448). Furthermore, the positive, linear correlation was determined between serum CRP and ferritin (r = 0.159, p = 0.114) and positive linear correlation between CRP and total serum bilirubin (r = 0.121, p = 0.230). In the control group was determined a statistically significant, positive, linear correlation between serum CRP and uric acid concentration (rho = 0.438, p = 0.001) and statistically significant, positive, linear correlation between serum CRP and total serum bilirubin (rho = 0.510, p = 0.0001) A statistically significant, negative linear correlation was determined between CRP and albumin concentration (rho= -0.393, p = 0.005) as well as statistically significant, negative linear correlation between serum CRP and ferritin control group (rho = -0.391, p = 0.005). Elevated CRP level is a strong and independent predictor of low levels of serum albumin, which indicates that the hypoalbuminemia in hemodialysis patients could be more due to inflammation than malnutrition. There was no statistically significant correlation between CRP and other non enzymatic antioxidants (uric acid, ferritin, bilirubin), which shows that indicators of antioxidant defense in hemodialysis patients must be individually measured to determine their actual stocks and activity.

Iron Induction of Ferritin Synthesis in Soybean Cell Suspensions

PubMed Central

Proudhon, Dominique; Briat, Jean-François; Lescure, Anne-Marie

1989-01-01

In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes. Images Figure 2 Figure 3 Figure 5 PMID:16666812

The hepcidin gene promoter nc.-1010C > T; -582A > G haplotype modulates serum ferritin in individuals carrying the common H63D mutation in HFE gene.

PubMed

Silva, Bruno; Pita, Lina; Gomes, Susana; Gonçalves, João; Faustino, Paula

2014-12-01

Hereditary hemochromatosis is an autosomal recessive disorder characterized by severe iron overload. It is usually associated with homozygosity for the HFE gene mutation c.845G > A; p.C282Y. However, in some cases, another HFE mutation (c.187C > G; p.H63D) seems to be associated with the disease. Its penetrance is very low, suggesting the possibility of other iron genetic modulators being involved. In this work, we have screened for HAMP promoter polymorphisms in 409 individuals presenting normal or increased serum ferritin levels together with normal or H63D-mutated HFE genotypes. Our results show that the hepcidin gene promoter TG haplotype, originated by linkage of the nc.-1010C > T and nc.-582A > G polymorphisms, is more frequent in the HFE_H63D individuals presenting serum ferritin levels higher than 300 μg/L than in those presenting the HFE_H63D mutation but with normal serum ferritin levels or in the normal control group.Moreover, it was observed that the TG haplotype was associated to increased serum ferritin levels in the overall pool of HFE_H63D individuals. Thus, our data suggest that screening for these polymorphisms could be of interest in order to explain the phenotype. However, this genetic condition seems to have no clinical significance.

Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: Analysis of 2008-2009 Korean National Health and Nutrition Examination Survey data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Byung-Kook; Kim, Yangho, E-mail: yanghokm@nuri.net

Introduction: We present data from the Korean National Health and Nutrition Examination Survey 2008-2009 on the distribution of blood cadmium levels and their association with iron deficiency in a representative sample of the adult Korean population. Methods: Serum ferritin was categorized into three levels: low (serum ferritin <15.0 {mu}g/L), low normal (15.0-30.0 {mu}g/L for women and 15.0-50.0 for men), and normal ({>=}30.0 {mu}g/L for women and {>=}50.0 for men), and its association with blood cadmium level was assessed after adjustment for various demographic and lifestyle factors. Results: Geometric means of blood cadmium in the low serum ferritin group in women,more » men, and all participants were significantly higher than in the normal group. Additionally, multiple regression analysis after adjusting for various covariates showed that blood cadmium was significantly higher in the low-ferritin group in women, men, and all participants compared with the normal group. We also found an association between serum ferritin and blood cadmium among never-smoking participants. Discussion: We found, similar to other recent population-based studies, an association between iron deficiency and increased blood cadmium in men and women, independent of smoking status. The results of the present study show that iron deficiency is associated with increased levels of blood cadmium in the general population.« less

The effect of iron balance on platelet counts in blood donors.

PubMed

Eder, Anne F; Yau, Yu Ying; West, Kamille

2017-02-01

Thrombocytosis (or, less commonly, thrombocytopenia) is associated with iron-deficiency anemia and resolves with iron therapy. Many volunteer blood donors have low iron stores, with or without anemia. Iron balance could affect platelet counts in blood donors. Whole blood donors deferred for finger-stick hemoglobin levels less than 12.5 g/dL were evaluated by complete blood count and serum iron panel before and after oral iron treatment. Group assignment for iron depletion was based on serum ferritin cutoffs of less than 20 µg/L for women and less than 30 µg/L for men or was based on changes in serum ferritin levels after iron replacement. Among 1273 Hb-deferred whole blood donors, 55% (619 of 1128) of the women and 70% (102 of 145) of the men were iron depleted. Iron-depleted donors had higher platelet counts compared with donors who had normal ferritin levels (women: 286 vs. 268 × 10 3 /µL; p < 0.0001; men: 246 vs. 222 × 10 3 /µL; p = 0.0454). Only 4.4% of iron-depleted donors had thrombocytosis (> 400 × 10 3 /µL) compared with 2.0% of donors who had normal ferritin levels (p = 0.017). Iron replacement decreased platelet counts in iron-depleted female donors (mean, -19,800/µL; interquartile range, 8000 to -45,000/μL), but not in donors who had normal or stable ferritin levels. The same trends were observed in male donors. Iron-depleted donors had higher platelet counts than donors who had adequate iron stores. Oral iron replacement decreased platelet counts on average by about 20,000/µL in iron-depleted donors but had no effect on platelet counts in donors who had normal or stable ferritin levels. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.

PubMed

Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Bansal, Sukhvinder S; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Roger, Simon D; Macdougall, Iain C

2016-01-01

Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.

Behavioral decline and premature lethality upon pan-neuronal ferritin overexpression in Drosophila infected with a virulent form of Wolbachia

PubMed Central

Kosmidis, Stylianos; Missirlis, Fanis; Botella, Jose A.; Schneuwly, Stephan; Rouault, Tracey A.; Skoulakis, Efthimios M. C.

2014-01-01

Iron is required for organismal growth. Therefore, limiting iron availability may be a key part of the host’s innate immune response to various pathogens, for example, in Drosophila infected with Zygomycetes. One way the host can transiently reduce iron bioavailability is by ferritin overexpression. To study the effects of neuronal-specific ferritin overexpression on survival and neurodegeneration we generated flies simultaneously over-expressing transgenes for both ferritin subunits in all neurons. We used two independent recombinant chromosomes bearing UAS-Fer1HCH, UAS-Fer2LCH transgenes and obtained qualitatively different levels of late-onset behavioral and lifespan declines. We subsequently discovered that one parental strain had been infected with a virulent form of the bacterial endosymbiont Wolbachia, causing widespread neuronal apoptosis and premature death. This phenotype was exacerbated by ferritin overexpression and was curable by antibiotic treatment. Neuronal ferritin overexpression in uninfected flies did not cause evident neurodegeneration but resulted in a late-onset behavioral decline, as previously reported for ferritin overexpression in glia. The results suggest that ferritin overexpression in the central nervous system of flies is tolerated well in young individuals with adverse manifestations appearing only late in life or under unrelated pathophysiological conditions. PMID:24772084

Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes.

PubMed

Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna

2014-01-01

The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

PubMed Central

Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

Nanoscale On-Silico Electron Transport via Ferritins.

PubMed

Bera, Sudipta; Kolay, Jayeeta; Banerjee, Siddhartha; Mukhopadhyay, Rupa

2017-02-28

Silicon is a solid-state semiconducting material that has long been recognized as a technologically useful one, especially in electronics industry. However, its application in the next-generation metalloprotein-based electronics approaches has been limited. In this work, the applicability of silicon as a solid support for anchoring the iron-storage protein ferritin, which has a semiconducting iron nanocore, and probing electron transport via the ferritin molecules trapped between silicon substrate and a conductive scanning probe has been investigated. Ferritin protein is an attractive bioelectronic material because its size (X-ray crystallographic diameter ∼12 nm) should allow it to fit well in the larger tunnel gaps (>5 nm), fabrication of which is relatively more established, than the smaller ones. The electron transport events occurring through the ferritin molecules that are covalently anchored onto the MPTMS-modified silicon surface could be detected at the molecular level by current-sensing atomic force spectroscopy (CSAFS). Importantly, the distinct electronic signatures of the metal types (i.e., Fe, Mn, Ni, and Au) within the ferritin nanocore could be distinguished from each other using the transport band gap analyses. The CSAFS measurements on holoferritin, apoferritin, and the metal core reconstituted ferritins reveal that some of these ferritins behave like n-type semiconductors, while the others behave as p-type semiconductors. The band gaps for the different ferritins are found to be within 0.8 to 2.6 eV, a range that is valid for the standard semiconductor technology (e.g., diodes based on p-n junction). The present work indicates effective on-silico integration of the ferritin protein, as it remains functionally viable after silicon binding and its electron transport activities can be detected. Potential use of the ferritin-silicon nanohybrids may therefore be envisaged in applications other than bioelectronics, too, as ferritin is a versatile nanocore-containing biomaterial (for storage/transport of metals and drugs) and silicon can be a versatile nanoscale solid support (for its biocompatible nature).

The effect of charge on the renal distribution of ferritin.

PubMed

Cohen, S; Vernier, R L; Michael, A F

1983-02-01

The effect of charge on the tissue distribution of ferritin was evaluated in rats following intravenous administration of 3 monomeric species preparatively separated by molecular sieve chromatography from aggregated ferritin and having the same molecular weight but differing only in electrostatic charge: native ferritin, with a isoelectric point (pI) of 4.5 (NF); cationized ferritin, with a pI of 6.4-7.4 (CF 7.0); and cationized ferritin, with a pI of 8.25-8.75 (CF 8.5). At varying time intervals (30 minutes to 72 hours) after the administration of these ferritins in a dose of 10 mg/100 g, the levels in the blood were determined, the tissue (kidney, liver, spleen) distribution semiquantitatively evaluated by immunofluorescence (IF), and electron microscopic examination (EM) of the kidney carried out. The following results were obtained: 1) The plasma levels of CF (8.5) and CF (7.0) were significantly higher than NF after 6 hours. NF was not detected after 24 hours, whereas CF continued to circulate at 72 hours. 2) There was a striking decrease in the uptake of CF (7.0) and CF (8.5), when compared with NF, by Kupffer cells and splenic phagocytes in the red pulp at all time periods. 3) In the glomerulus, NF was found primarily in the mesangium and gradually disappeared over a period of 72 hours, whereas CF was present in greater amounts and persisted for longer periods of time in the mesangium and in the peripheral capillary wall. By electron microscopy, CF (8.5) could be seen in th lamina rara and within the mesangium in small aggregates aligned parallel to mesangial cell processes, whereas NF and CF (7.0) were distributed homogeneously throughout the mesangial matrix. 4) NF, but not CF, was also observed surrounding blood vessels and in interstitial phagocytes. These in vivo studies demonstrate that the electrostatic charge of ferritin affects its uptake in vivo by components of the mononuclear phagocytic system (MPS). The persistence and distribution of CF in glomeruli is a consequence of higher blood levels associated with impaired phagocytic uptake as well as charge-related binding to sites within the glomeruli.

Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

PubMed Central

Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

2010-01-01

Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

Credibility of the measurement of serum ferritin and transferrin receptor as indicators of iron deficiency anemia in hemodialysis patients.

PubMed

Mahdavi, M R; Makhlough, A; Kosaryan, M; Roshan, P

2011-10-01

Anemia is a common complication in uremic patients. Erythropoietin therapy is prescribed in these cases; however, this treatment is not successful in iron deficient patients. Ferritin-based diagnosis of iron deficiency in these patients is a challenging task, as serum ferritin level may be high due to chronic inflammation and mask iron deficiency. In the current study we evaluated the credibility of another indicator of body iron supply, serum transferrin receptor, in hemodialysis patients in two University-based Hospitals in North of Iran. In a cross-sectional study, 53 hemodialysis patients with a mean age of 56 +/- 18.7 years and 30 persons with iron deficiency and normal renal function with a mean age of 20.1 +/- 14.4 years were examined. All hemodialysis patients were on hemodialysis 2-3 times per week for 3-4 hours. All cases were examined for blood hemoglobin content, serum iron, CRP, serum ferritin and serum transferrin receptor levels. The reference ranges introduced by manufacturers were considered as standard ranges for analysis of the results. Using one sample T-test and Fisher's exact test, data were analyzed. p<0.05 was considered as significant. Hemodialysis patients had blood hemoglobin content below normal range (p<0.05 for men, p<0.001 for women) and CRP levels above normal range (p<0.001). In hemodialysis patients, serum ferritin level was significantly higher than control group (p<0.001), whilst serum transferrin receptor levels in the two groups were not significantly different (p=0.69), and both were above defined normal upper limit (p<0.001 for iron deficient patients; p<0.05 for hemodialysis patients). This study showed measurement of serum ferritin in the presence of chronic inflammation induced by renal failure cannot be a credible indicator of body iron supply, while under this certain condition serum transferrin receptor can more appropriately reflect the amount of body iron supply.

Serum ferritin is a different predictor from transfusion history for allogeneic transplantation outcome in patients with severe aplastic anemia.

PubMed

Zhang, Xiaoyu; Shi, Yuanyuan; Huang, Yong; Zhang, Guixin; He, Yi; Jiang, Erlie; Wei, Jialin; Yang, Donglin; Ma, Qiaoling; Zhang, Rongli; Zhai, Weihua; Feng, Sizhou; Han, Mingzhe

2018-06-01

Severe aplastic anemia (SAA) patients receive more red blood cell (RBC) transfusions as supportive management. We aim to clarify the associations between transfusion history or pre-transplantation serum ferritin (SF) and the overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) among SAA patients. We retrospectively investigated 96 SAA patients undergoing allo-HSCT, and grouped them according to pre-transplantation duration. Pre-transplantation SF, transfused units and other iron-related parameters were collected. Comparisons in transplantation outcomes and complications were made in groups with different SF levels and different transfusion histories. Among the 96 SAA patients, 45 patients received transplantation within 2 months after diagnosis (short-term pre-transplantation period), and the rest of the patients had long-term pre-transplantation treatment. Among the patients with short-term pre-transplantation treatment, a higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF also predicted a trend in incidence of higher bloodstream infection (p = 0.108). Significant correlations were observed between pre-transplantation SF and infection incidence, as well as transfusion history. However, for patients with longer pre-transplantation duration, transfusion history was associated with worse outcome (p = 0.026), in terms of higher incidence of acute graft versus host disease (p = 0.048). High SF was only significantly associated with prolonged RBC transfusion dependence post-transplantation (p = 0.044). Transfusion history was a stronger predictor of outcome than SF in patients undergoing transplantation more than 2 months after diagnosis.

Nitric oxide-mediated modulation of iron regulatory proteins: implication for cellular iron homeostasis.

PubMed

Kim, Sangwon; Ponka, Prem

2002-01-01

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) that are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO(.), a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels and a decrease in ferritin synthesis. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels and a dramatic increase in ferritin synthesis. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels and an increase in ferritin synthesis in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO(+)-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study

PubMed Central

2012-01-01

Background Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation. Study design and methodology Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate. The children were from a rural Gambian population where rates of iron deficiency and infection/inflammation are high. This study identified cross-sectional and longitudinal relationships between FGF23, inflammation (C-reactive protein (CRP)) and iron status (ferritin, haemoglobin, and zinc protoporphyrin). CRP ≥ 5 mg/dL was used to indicate inflammation and FGF23 ≥ 125 RU/mL was considered elevated. Results FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=−0.57 (0.12), R2=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=−0.89 (0.14), R2=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =−0.41 (0.11), R2=14.1%, P=0.0004; haemoglobin=−2.22 (0.64), R2=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R2=18.6%, P≤0.0001) and multivariate analysis (R2=33.1%; ferritin=−0.36 (0.10), P=0.0007, haemoglobin = −1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02). Conclusions Iron status rather than inflammation is a negative predictor of plasma FGF23 concentration. Improvements in iron status following iron supplementation are associated with a significant decrease in FGF23 concentration. PMID:23098062

Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence

PubMed Central

Arcanjo, C. P. C.; Santos, P. R.

2016-01-01

Background. In developing countries there is high prevalence of iron deficiency anemia, which reduces cognitive performance, work performance, and endurance; it also causes learning difficulties and negative impact on development for infant population. Methods. The study concerns a case-control study; data was collected from an appropriate sample consisting of schoolchildren aged 8 years. The sample was divided into two subgroups: those with deficient initial reading skills (DIRS) (case) and those without (control). Blood samples were taken to analyze hemoglobin and serum ferritin levels. These results were then used to compare the two groups with Student's t-test. Association between DIRS and anemia was analyzed using odds ratio (OR). Results. Hemoglobin and serum ferritin levels of schoolchildren with DIRS were statistically lower when compared to those without, hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically associated with a risk of anemia with a weighted OR of 1.62. Conclusions. In this study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels when compared to those without. PMID:27703806

Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence.

PubMed

Arcanjo, F P N; Arcanjo, C P C; Santos, P R

2016-01-01

Background . In developing countries there is high prevalence of iron deficiency anemia, which reduces cognitive performance, work performance, and endurance; it also causes learning difficulties and negative impact on development for infant population. Methods . The study concerns a case-control study; data was collected from an appropriate sample consisting of schoolchildren aged 8 years. The sample was divided into two subgroups: those with deficient initial reading skills (DIRS) (case) and those without (control). Blood samples were taken to analyze hemoglobin and serum ferritin levels. These results were then used to compare the two groups with Student's t -test. Association between DIRS and anemia was analyzed using odds ratio (OR). Results . Hemoglobin and serum ferritin levels of schoolchildren with DIRS were statistically lower when compared to those without, hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically associated with a risk of anemia with a weighted OR of 1.62. Conclusions . In this study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels when compared to those without.

Estimation of cardiac left ventricular ejection fraction in transfusional cardiac iron overload by R2* magnetic resonance.

PubMed

Sakuta, Juri; Ito, Yoshikazu; Kimura, Yukihiko; Park, Jinho; Tokuuye, Koichi; Ohyashiki, Kazuma

2010-12-01

Cardiac dysfunction due to transfusional iron overload is one of the most critical complications for patients with transfusion-dependent hematological disorders. Clinical parameters such as total red blood cell (RBC) transfusion units and serum ferritin level are usually considered as indicators for initiation of iron chelation therapy. We used MRI-T2*, MRI-R2* values, and left ventricular ejection fraction in 19 adult patients with blood transfusion-dependent hematological disorders without consecutive oral iron chelation therapy, and propose possible formulae of cardiac function using known parameters, such as total RBC transfusion units and serum ferritin levels. We found a positive correlation in all patients between both R2* values (reciprocal values of T2*) and serum ferritin levels (r = 0.81) and also total RBC transfusion volume (r = 0.90), but not when we analyzed subgroups of patients whose T2* values were over 30 ms (0.52). From the formulae of the R2*, we concluded that approximately 50 Japanese units or 2,900 pmol/L ferritin might be the cutoff value indicating possible future cardiac dysfunction.

Predictors of preterm birth in patients with mild systemic lupus erythematosus.

PubMed

Clowse, Megan E B; Wallace, Daniel J; Weisman, Michael; James, Andra; Criscione-Schreiber, Lisa G; Pisetsky, David S

2013-09-01

While increased disease activity is the best predictor of preterm birth in women with systemic lupus erythematosus (SLE), even women with low disease activity are at increased risk of this complication. Biomarkers that would identify at-risk pregnancies could allow interventions to prevent preterm birth. Measures of SLE activity, inflammation, placental health and renal function between 20 and 28 weeks gestation (mid-gestation) were correlated to preterm birth and gestational age at delivery in a prospective cohort of pregnant women with SLE. Of the 40 pregnancies in 39 women, all with mild-moderate SLE disease, 9 (23.7%) of the 38 live births were delivered preterm. Low C4 was the only marker of SLE activity associated with younger gestational age at delivery. Elevated ferritin and lower oestradiol correlated with younger gestational age at delivery. Renal function remained normal during all pregnancies at mid-gestation and did not correlate with preterm birth. Higher serum uric acid, however, correlated with younger gestational age at delivery. In women with SLE with mild-moderate disease activity, ferritin, oestradiol and uric acid levels at mid-gestation may predict preterm birth. These markers may prove to be clinically useful in identifying pregnancies at particularly high risk for adverse outcomes.

Diabetes in HFE Hemochromatosis

PubMed Central

Acton, Ronald T.

2017-01-01

Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis. PMID:28331855

Still's Disease in a Pediatric Patient after Liver Transplantation.

PubMed

Meza, Juan-Carlos; Muñoz-Buitrón, Evelyn; Bonilla-Abadía, Fabio; Cañas, Carlos Alberto; Tobón, Gabriel J

2013-01-01

Still's disease (SD) is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

Efficacy of Deferasirox as an Oral Iron Chelator in Paediatric Thalassaemia Patients

PubMed Central

Hishikar, Rajesh; Khandwal, Onkar; Agarwal, Manju; Joshi, Usha; Halwai, Ajay; Maheshwari, Basant; Sheohare, Raka

2017-01-01

Introduction Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. Aim To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level. Materials and Methods This is a prospective; observational study done in 45 multitransfused Thalassaemia Major Children receiving DFX therapy at registered Thalassaemia society Raipur Chhattisgarh. DFX was given in an initial dose of 20 mg/kg/day and according to response increased to a maximum of 40 mg/kg/day. Serum ferritin level was estimated at time of registration and at every three monthly intervals (four times during study period). The primary end point of the study was change in serum ferritin level after 12 months of DFX therapy. Results The mean serum ferritin before DFX therapy of all cases was 3727.02 ng/mL. After 12 months of mean dose of 38 mg/kg/day of DFX, the mean decline in serum ferritin was 1207.11 ng/mL (drop by 32.38%, p-value <0.001). Conclusion DFX monotherapy has a good safety profile and effectively chelates total body iron in Thalassaemia major patients. PMID:28384880

Efficacy of Deferasirox as an Oral Iron Chelator in Paediatric Thalassaemia Patients.

PubMed

Jaiswal, Shikha; Hishikar, Rajesh; Khandwal, Onkar; Agarwal, Manju; Joshi, Usha; Halwai, Ajay; Maheshwari, Basant; Sheohare, Raka

2017-02-01

Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level. This is a prospective; observational study done in 45 multitransfused Thalassaemia Major Children receiving DFX therapy at registered Thalassaemia society Raipur Chhattisgarh. DFX was given in an initial dose of 20 mg/kg/day and according to response increased to a maximum of 40 mg/kg/day. Serum ferritin level was estimated at time of registration and at every three monthly intervals (four times during study period). The primary end point of the study was change in serum ferritin level after 12 months of DFX therapy. The mean serum ferritin before DFX therapy of all cases was 3727.02 ng/mL. After 12 months of mean dose of 38 mg/kg/day of DFX, the mean decline in serum ferritin was 1207.11 ng/mL (drop by 32.38%, p-value <0.001). DFX monotherapy has a good safety profile and effectively chelates total body iron in Thalassaemia major patients.

Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-03-01

tech- jects prior to their participation included standard radio- ques , using- radioisotopes ("SFe and S"Tcm-- diphospho- graphic surveys for evidence of... es were apparent by the third dive day for iron and the iv than ABN. It is of interest that no VGE were heard ajt seventh dive day for ferrtin. No...source of the increased amounts of ferritin levels in acute bepatocellular damage from serum ferritin and iron found during these dives ap.- paracetamol

Reassessment of Iron Biomarkers for Prediction of Dialysis Iron Overload: An MRI Study

PubMed Central

Rostoker, Guy; Griuncelli, Mireille; Loridon, Christelle; Magna, Théophile; Machado, Gabrielle; Drahi, Gilles; Dahan, Hervé; Janklewicz, Philippe; Cohen, Yves

2015-01-01

Background and Objectives Iron overload among hemodialysis patients was previously considered rare but is now an increasingly recognized clinical situation. We analyzed correlations between iron biomarkers and the liver iron concentration (LIC) measured by magnetic resonance imaging (MRI), and examined their diagnostic accuracy for iron overload. Design, Setting, Participants and Measurements We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 212 hemodialysis patients free of overt inflammation or malnutrition, were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent, in keeping with current clinical guidelines. Blinded measurements of hepatic iron stores were performed by T1 and T2* contrast MRI, and relationships were analysed using Spearman’s coefficient, logistic regression and receiver-operator characteristic (ROC) curves. Results Among the biological markers, only serum ferritin showed a strong correlation with LIC (rho= 0.52, 95% CI: 0.41-0.61, p< 0.0001, Spearman test). In logistic analysis, only serum ferritin correctly classified the overall cohort into patients with normal liver iron stores (LIC ≤ 50 μmol/g) and those with elevated liver iron stores (LIC > 50 μmol/g) (odds ratio 1.007; 95% CI: 1.004-1.010). Serum ferritin was the iron biomarker with the best discriminatory capacity in ROC curves analysis (area under the curve (AUC) = 0.767; 95% CI: 0.698-0.835). The optimal serum ferritin cutoffs were 160 μg/L for LIC > 50 μmol/g (mild iron overload) and 290 μg/L for LIC > 200 μmol/g (severe iron overload). Conclusions For clinical purposes, serum ferritin correctly reflects liver iron stores, as assessed by MRI, in hemodialysis patients without overt inflammation or malnutrition. These results strongly suggest that current ferritin target values should be lowered to avoid iron overload. Trial Registration ISRCTN Registry 80100088 PMID:26182077

Iron binding to human heavy-chain ferritin.

PubMed

Pozzi, Cecilia; Di Pisa, Flavio; Bernacchioni, Caterina; Ciambellotti, Silvia; Turano, Paola; Mangani, Stefano

2015-09-01

Maxi-ferritins are ubiquitous iron-storage proteins with a common cage architecture made up of 24 identical subunits of five α-helices that drive iron biomineralization through catalytic iron(II) oxidation occurring at oxidoreductase sites (OS). Structures of iron-bound human H ferritin were solved at high resolution by freezing ferritin crystals at different time intervals after exposure to a ferrous salt. Multiple binding sites were identified that define the iron path from the entry ion channels to the oxidoreductase sites. Similar data are available for another vertebrate ferritin: the M protein from Rana catesbeiana. A comparative analysis of the iron sites in the two proteins identifies new reaction intermediates and underlines clear differences in the pattern of ligands that define the additional iron sites that precede the oxidoreductase binding sites along this path. Stopped-flow kinetics assays revealed that human H ferritin has different levels of activity compared with its R. catesbeiana counterpart. The role of the different pattern of transient iron-binding sites in the OS is discussed with respect to the observed differences in activity across the species.

Relationship of serum ferritin level and tic severity in children with Tourette syndrome.

PubMed

Ghosh, Debabrata; Burkman, Elizabeth

2017-08-01

Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS. Children <18 years, diagnosed with TS during 2009-2015, were reviewed. Only those with serum ferritin testing were included. The following data were collected: tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up. In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron. Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

Characterization of iron metabolism and erythropoiesis in erythrocyte membrane defects and thalassemia traits.

PubMed

Sulovska, Lucie; Holub, Dusan; Zidova, Zuzana; Divoka, Martina; Hajduch, Marian; Mihal, Vladimir; Vrbkova, Jana; Horvathova, Monika; Pospisilova, Dagmar

2016-06-01

Erythropoiesis is closely related to iron metabolism in a balanced homeostasis. Analyses of diverse erythroid and iron metabolism disorders have shown that disrupted erythropoiesis negatively affects iron homeostasis and vice versa. The aim of this study was to characterize the relationship between erythropoietic activity and iron homeostasis in pediatric patients with erythrocyte membrane defects and thalassemia traits. Selected markers of erythropoietic activity (erythropoietin, soluble transferrin receptor - sTfR and growth differentiation factor 15) and iron status parameters (serum iron, ferritin and hepcidin) were evaluated in pediatric patients with erythrocyte membrane defects and thalassemia traits. The patients with erythrocyte membrane defects and thalassemia traits had altered iron homeostasis due to disturbed erythropoiesis. In comparison with healthy controls, they had a normal to low hepcidin/ferritin ratio and concomitantly elevated sTfR. The findings suggest that pediatric patients with erythrocyte membrane defects and thalassemia traits are more susceptible to iron overload than the general population and that the (hepcidin/ferritin)/sTfR ratio can be used to monitor any worsening of the disease.

Quantification of ferritin bound iron in human serum using species-specific isotope dilution mass spectrometry.

PubMed

Ren, Yao; Walczyk, Thomas

2014-09-01

Ferritin is a hollow sphere protein composed of 24 subunits that can store up to 4500 iron atoms in its inner cavity. It is mainly found in the liver and spleen but also in serum at trace levels. Serum ferritin is considered as the best single indicator in assessing body iron stores except liver or bone marrow biopsy. However, it is confounded by other disease conditions. Ferritin bound iron (FBI) and ferritin saturation have been suggested as more robust biomarkers. The current techniques for FBI determination are limited by low antibody specificity, low instrument sensitivity and possible analyte losses during sample preparation. The need for a highly sensitive and reliable method is widely recognized. Here we describe a novel technique to detect serum FBI using species-specific isotope dilution mass spectrometry (SS-IDMS). [(57)Fe]-ferritin was produced by biosynthesis and in vitro labeling with the (57)Fe spike in the form of [(57)Fe]-citrate after cell lysis and heat treatment. [(57)Fe]-ferritin for sample spiking was further purified by fast liquid protein chromatography. Serum ferritin and added [(57)Fe]-ferritin were separated from other iron species by ultrafiltration followed by isotopic analysis of FBI using negative thermal ionization mass spectrometry. Repeatability of our assay is 8% with an absolute detection limit of 18 ng FBI in the sample. As compared to other speciation techniques, SS-IDMS offers maximum control over sample losses and species conversion during analysis. The described technique may therefore serve as a reference technique for clinical applications of FBI as a new biomarker for assessing body iron status.

Triumph and tragedy: anemia management in chronic kidney disease.

PubMed

Novak, James E; Szczech, Lynda A

2008-11-01

Recent trial data have resulted in a reevaluation of the management of anemia in chronic kidney disease, including the use of erythropoiesis-stimulating agents, intravenous iron, and novel pharmaceuticals. In this review, we evaluate the latest research on anemia management in chronic kidney disease. Clinical trials of erythropoiesis-stimulating agents indicate that targeting the complete correction of anemia in patients with chronic kidney disease results in a greater risk of morbidity and mortality despite improved hemoglobin and quality of life. Conversely, intravenous iron has been found effective and relatively well tolerated in treating anemia in chronic kidney disease, even in patients with elevated ferritin. New agents to manage anemia, including long-acting erythropoietin derivatives, are also in active development. Erythropoiesis-stimulating agents should be used to target hemoglobin 11-12 g/dl in patients with chronic kidney disease. Intravenous iron may be beneficial for patients with hemoglobin less than 11 g/dl and transferrin saturation less than 25% despite elevated ferritin (500-1200 ng/ml). An upcoming placebo-controlled trial of darbepoetin should help to define the role of erythropoiesis-stimulating agents in chronic kidney disease.

Inadequate hepcidin serum concentrations predict incident type 2 diabetes mellitus.

PubMed

Pechlaner, Raimund; Weiss, Günter; Bansal, Sukhvinder; Mayr, Manuel; Santer, Peter; Pallhuber, Barbara; Notdurfter, Marlene; Bonora, Enzo; Willeit, Johann; Kiechl, Stefan

2016-02-01

Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions. This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010. The baseline hepcidin-to-ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p = 0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p = 0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66-0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n = 76). Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of changes in periodic limb movements under cpap on adherence and long term compliance in obstructive sleep apnea.

PubMed

Mwenge, Gimbada B; Rougui, Ihsan; Rodenstein, Daniel

2017-11-20

Purpose of the study Periodic leg movements (PLMs) are found in 30% of patients suffering from OSA. Under CPAP, we observed that PLMs can increase, decrease, or remain unchanged. The predictors of these changes are not well established. Objective To determine the predictors of PLMs change under CPAP and its impact on long-term adherence. Materials and method The patients were referred to the sleep laboratory for snoring or sleepiness. A single PSG night has been performed before and after CPAP treatment. Data on medication used, comorbidities and ferritin level were collected. Results A total of 160 patients were recruited with a severe OSA. About 32.5% (52/160) patients had emerging PLM i.e. that appeared after the disappearance of respiratory events. By comparing patients with emerging-PLMs to others, we found that only the blood ferritin level was significantly different between groups. Moreover, after one-year follow-up, a significant difference in adherence and long-term compliance was observed between patients without PLM at both screening and CPAP polysomnographies or emerging PLM at the second study (56%) vs. patients with baseline PLM, whether PLM remained stable or decreased under CPAP treatment (75%) (p-value 0.028). Serum ferritin and presence of diabetes mellitus predicted the evolution of PLM observed. Patients with low ferritin levels demonstrated an increase of PLM after initiation of nasal CPAP treatment. Conclusion The emergence of PLM negatively impacts long-term adherence to nasal CPAP treatment in OSA. Blood ferritin level is a predictor of the evolution of PLM under CPAP therapy.

Effect of iron supplementation during lactation on maternal iron status and oxidative stress: A randomized controlled trial.

PubMed

Jorgensen, Josh M; Yang, Zhenyu; Lönnerdal, Bo; Chantry, Caroline J; Dewey, Kathryn G

2017-10-01

We examined the effect of iron-containing prenatal vitamin-mineral supplements taken postpartum on biomarkers of iron status and oxidative stress. Lactating women (n = 114) were randomly assigned to consume daily one iron-free prenatal vitamin-mineral supplement plus either 27 mg of iron or placebo for approximately 3.5 months. The placebo group took the tablets between meals, while those given iron took the tablets either with (Fe-W) or between meals (Fe-B). Blood and urine samples were collected before and after the supplementation period to analyze hemoglobin (Hb), ferritin, hepcidin, transferrin saturation (TfSat), total plasma iron, and biomarkers of oxidative stress (isoprostane and 8-hydroxy-2-deoxyguanosine (8-OHdG)) and inflammation (C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP)). There was a trend toward a greater change in Hb among women in the Fe-B group compared to placebo (+2.5 vs. -3.7 g/L, respectively, p = 0.063). When the iron groups were combined, there was a greater change in Hb (+1.4 g/L) compared to placebo (p = 0.010). There were trends toward greater changes in TfSat (p = 0.087) and total plasma iron (p = 0.065) in the iron groups compared to placebo, yet no significant differences between the three groups in change in hepcidin (p = 0.291), isoprostane (p = 0.319), or 8-OHdG (p = 0.659), nor in change in ferritin among those with elevated CRP at baseline (60% of women; p = 0.946); among those without elevated CRP (40% of women), ferritin increased more in the iron groups compared to placebo (p = 0.001). Iron consumption during lactation moderately increased iron status, particularly among women without elevated CRP, and increased Hb, but did not significantly increase oxidative stress. © 2016 John Wiley & Sons Ltd.

Is His54 a gating residue for the ferritin ferroxidase site?

PubMed

Bernacchioni, Caterina; Ciambellotti, Silvia; Theil, Elizabeth C; Turano, Paola

2015-09-01

Ferritin is a ubiquitous iron concentrating nanocage protein that functions through the enzymatic oxidation of ferrous iron and the reversible synthesis of a caged ferric-oxo biomineral. Among vertebrate ferritins, the bullfrog M homopolymer ferritin is a frequent model for analyzing the role of specific amino acids in the enzymatic reaction and translocation of iron species within the protein cage. X-ray crystal structures of ferritin in the presence of metal ions have revealed His54 binding to iron(II) and other divalent cations, with its imidazole ring proposed as "gate" that influences iron movement to/from the active site. To investigate its role, His54 was mutated to Ala. The H54A ferritin variant was expressed and its reactivity studied via UV-vis stopped-flow kinetics. The H54A variant exhibited a 20% increase in the initial reaction rate of formation of ferric products with 2 or 4 Fe²⁺/subunit and higher than 200% with 20 Fe²⁺/subunit. The possible meaning of the increased efficiency of the ferritin reaction induced by this mutation is proposed taking advantage of the comparative sequence analysis of other ferritins. The data here reported are consistent with a role for His54 as a metal ion trap that maintains the correct levels of access of iron to the active site. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma?

PubMed

Cunha, Burke A; Sivarajah, Thulashie; Jimada, Ismail

We present a case of an adult female with a past history of pulmonary sarcoidosis who presented with fever, night sweats, profound fatigue, and LUQ abdominal pain. Sarcoidosis is an afebrile disorder (excluding Lofgren's syndrome, Heerfordt's syndrome or neurosarcoidosis). Therefore, the presence of fever with sarcoidosis should suggest infection, usually viral, or lymphoma. Sarcoidosis-lymphoma syndrome describes the evolution of a lymphoma in long standing sarcoidosis. Fever aside, possible lymphoma is suggested by otherwise unexplained fever, pleural unilateral effusion, highly elevated ESR or ferritin levels. In this case, a viral etiology was suggested because of atypical lymphocytosis and mildly elevated transaminases. In this patient, CMV IgM titers and elevated CMV PCR viral load confirmed the diagnosis of CMV infectious mononucleosis with lung and liver involvement. In this case CMV infectious mononucleosis was accompanied by procoagulant activity which resulted a DVT, pulmonary emboli and splenic infarct. We believe this to be the first reported case of CMV infectious mononucleosis splenic infarct in a patient with a history of sarcoidosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation between PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients.

PubMed

Dragović, Gordana; Sumarac-Dumanovic, Mirjana; Khawla, Al Musalhi; Soldatović, Ivan; Andjić, Mladen; Jevtović, Djordje; Nair, Devaki

2018-06-22

Data about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients' age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = -0.282; p = 0.025). PAI-1 (Rho = 0.334; p = 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10, adiponectin, MCP-1, resistin, TNF-α, CRP and VEGF did not significantly correlate with HOMA. Further, multiple logistic regression showed that there is a statistically significant correlation between PAI, leptin and ferritin with HOMA levels (p = 0.042; p < 0.001, p = 0.009). We showed significant correlation between PAI-1, leptin and ferritin, independently of each other with HOMA, in HIV/AIDS patients on cART. Copyright © 2018. Published by Elsevier Inc.

Investigation of the Iron(II) Release Mechanism of Human H-Ferritin as a Function of pH.

PubMed

Sala, Davide; Ciambellotti, Silvia; Giachetti, Andrea; Turano, Paola; Rosato, Antonio

2017-09-25

We investigated the kinetics of the release of iron(II) ions from the internal cavity of human H-ferritin as a function of pH. Extensive molecular dynamics simulations of the entire 24-mer ferritin provided atomic-level information on the release mechanism. Double protonation of His residues at pH 4 facilitates the removal of the iron ligands within the C3 channel through the formation of salt bridges, resulting in a significantly lower release energy barrier than pH 9.

Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.

PubMed

Jacobs, Esther M G; Hendriks, Jan C M; van Deursen, Cees Th B M; Kreeftenberg, Herman G; de Vries, Richard A; Marx, Joannes J M; Stalenhoef, Anton F H; Verbeek, André L M; Swinkels, Dorine W

2009-01-01

In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH. Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS). The best predictive multivariable model forecasted 45% of variation of the serum ferritin levels. In this model severity of iron overload in the proband significantly predicted serum ferritin levels in FDFM. Other significant determinants in this model consisted of C282Y homozygosity, compound heterozygosity, age at testing for serum ferritin and supplemental iron intake, whereas a low body mass index showed a protective effect. This study provides a model to assess the risk of development of iron overload for relatives of probands with HH. These results might be instrumental in the development of an optimal strategy for future family screening programs.

Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral?

PubMed Central

Taddesse, A.; Woldie, I.L.; Khana, P.; Swerdlow, P.S.; Chu, J.-W.; Abrams, J.; Abou-Samra, A.-B.

2013-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. PMID:22678347

Hypogonadism in patients with sickle cell disease: central or peripheral?

PubMed

Taddesse, A; Woldie, I L; Khana, P; Swerdlow, P S; Chu, J-W; Abrams, J; Abou-Samra, A-B

2012-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. Copyright © 2012 S. Karger AG, Basel.

A case of acute infectious mononucleosis presenting with very high ferritin

PubMed Central

Thoufeeq, Muhammed Hameed; Ali Khan, Shahul Leyakath; Jain, Sanjiv Kumar; Al-Shakerchi, Hasanain; Hussain, Munem

2007-01-01

Hepatitis is an important but uncommon manifestation of acute Epstein Barr infection. Infectious mononucleosis is usually a disease of young adults. We report a case of infectious mononucleosis in a 72-year old jaundiced gentleman with ferritin level of 2438 that normalised on clinical improvement. PMID:17278235

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton

PubMed Central

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-01-01

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID:26553998

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton.

PubMed

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-11-24

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation.

Immunocytochemical analysis of the subcellular distribution of ferritin in Imperata cylindrica (L.) Raeuschel, an iron hyperaccumulator plant.

PubMed

de la Fuente, Vicenta; Rodríguez, Nuria; Amils, Ricardo

2012-05-01

Ferritin is of interest at the structural and functional level not only as storage for iron, a critical element, but also as a means to prevent cell damage produced by oxidative stress. The main objective of this work was to confirm by immunocytochemistry the presence and the subcellular distribution of the ferritin detected by Mösbauer spectroscopy in Imperata cylindrica, a plant which accumulates large amounts of iron. The localization of ferritin was performed in epidermal, parenchymal and vascular tissues of shoots and leaves of I. cylindrica. The highest density of immunolabeling in shoots appeared in the intracellular space of cell tissues, near the cell walls and in the cytoplasm. In leaves, ferritin was detected in the proximity of the dense network of the middle lamella of cell walls, following a similar path to that observed in shoots. Immunolabeling was also localized in chloroplasts. The abundance of immunogold labelling in mitochondria for I. cylindrica was rather low, probably because the study dealt with tissues from old plants. These results further expand the localization of ferritin in cell components other than chloroplasts and mitochondria in plants. Copyright © 2011 Elsevier GmbH. All rights reserved.

Determinants of anemia among young children in rural India.

PubMed

Pasricha, Sant-Rayn; Black, James; Muthayya, Sumithra; Shet, Anita; Bhat, Vijay; Nagaraj, Savitha; Prashanth, N S; Sudarshan, H; Biggs, Beverley-Ann; Shet, Arun S

2010-07-01

More than 75% of Indian toddlers are anemic. Data on factors associated with anemia in India are limited. The objective of this study was to determine biological, nutritional, and socioeconomic risk factors for anemia in this vulnerable age group. We conducted a cross-sectional study of children aged 12 to 23 months in 2 rural districts of Karnataka, India. Children were excluded if they were unwell or had received a blood transfusion. Hemoglobin, ferritin, folate, vitamin B(12), retinol-binding protein, and C-reactive protein (CRP) levels were determined. Children were also tested for hemoglobinopathy, malaria infection, and hookworm infestation. Anthropometric measurements, nutritional intake, family wealth, and food security were recorded. In addition, maternal hemoglobin level was measured. Anemia (hemoglobin level < 11.0 g/dL) was detected in 75.3% of the 401 children sampled. Anemia was associated with iron deficiency (low ferritin level), maternal anemia, and food insecurity. Children's ferritin levels were directly associated with their iron intake and CRP levels and with maternal hemoglobin level and inversely associated with continued breastfeeding and the child's energy intake. A multivariate model for the child's hemoglobin level revealed associations with log(ferritin level) (coefficient: 1.20; P < .001), folate level (0.05; P < .01), maternal hemoglobin level (0.16; P < .001), family wealth index (0.02; P < .05), child's age (0.05 per month; P < .005), hemoglobinopathy (-1.51; P < .001), CRP level (-0.18; P < .001), and male gender (-0.38; P < .05). Wealth index and food insecurity could be interchanged in this model. Hemoglobin level was primarily associated with iron status in these Indian toddlers; however, maternal hemoglobin level, family wealth, and food insecurity were also important factors. Strategies for minimizing childhood anemia must include optimized iron intake but should simultaneously address maternal anemia, poverty, and food insecurity.

Associations of dietary, lifestyle, and sociodemographic factors with iron status in Chinese adults: a cross-sectional study in the China Health and Nutrition Survey.

PubMed

Hu, Peter J; Ley, Sylvia H; Bhupathiraju, Shilpa N; Li, Yanping; Wang, Dong D

2017-02-01

Although a high prevalence of anemia and related disease burden have been documented in China, limited evidence is available on the current population-level iron status and risk factors for iron imbalance. We explored the associations of dietary, lifestyle, and sociodemographic factors with iron status in Chinese adults. Our study population consisted of 7672 adults aged 18-65 y from the 2009 China Health and Nutrition Survey. Diet was assessed with the use of 3 consecutive 24-h dietary recalls. Serum ferritin, serum transferrin receptor, and hemoglobin concentrations were measured. The geometric means ± SDs for ferritin concentrations were 135.9 ± 2.7 ng/mL in men and 42.7 ± 3.1 ng/mL in women. After adjustment for potential risk factors, including high-sensitivity C-reactive protein concentration, the association between age and ferritin concentration was inverse in men (P-trend < 0.001) and positive in women (P-trend < 0.001). We observed a positive association between body mass index (in kg/m 2 ) and ferritin concentration in both men and women (both P-trends < 0.001). Dietary phytate intake was inversely associated with ferritin concentration in men (P-trend = 0.002) but not in women. Red meat consumption was positively associated with ferritin concentration both in men (P-trend = 0.002) and in older women (P-trend = 0.009). Lower intakes of grains and higher intakes of pork and poultry were associated with higher ferritin concentrations (all P-trends ≤ 0.05) in men but not in women. We observed variations in ferritin concentrations across different geographic regions (both P ≤ 0.01). Serum ferritin concentrations varied across different sociodemographic, lifestyle, and dietary factors in this Chinese population. A higher intake of red meat was associated with higher ferritin concentrations in men and older women. © 2017 American Society for Nutrition.

Immune Status 'in Children with Beta Thalassemia' in Correlation 'with Iron Overload': Single Center Egyptian Study.

PubMed

Hagag, Adel A; Elgamsy, Mohamed A; El-Asy, Hassan M; Gamal, Rasha M; Elshahaby, Walid N; Abd Elbar, Enaam S

2016-01-01

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ferritin in hypertensive and diabetic women before and after bariatric surgery.

PubMed

Marin, Flávia Andréia; Rasera Junior, Irineu; Leite, Celso Vieira De Souza; Oliveira, Maria Rita Marques de

2014-10-16

In addition to its important role as marker of iron stores, serum ferritin is a marker of systemic inflammation, and obesity has been associated with chronic inflammation. To verify, six months after surgery, the effect of bariatric surgery on the serum ferritin of women who were hypertensive, diabetic, or comorbidity free before surgery. This retrospective study included 200 women aged 20 to 45 years, with a body mass index (BMI) equal to or greater than 35 kg/m2, submitted to Roux-en-Y gastric bypass (RYGB). Seventy of these women were hypertensive, forty had type 2 diabetes (T2D), and ninety were comorbidity free (CF). They were assessed before and six months after surgery. Anthropometric, laboratory (serum ferritin and hemoglobin), and comorbidity- related data were collected from their medical records. Before surgery, women with comorbidities were older, the hypertensives had higher BMI, and the diabetics had higher serum ferritin levels than the CF women. The study comorbidities had resolved in 68% of the hypertensive women and 86% of the diabetic women six months after RYGB. Also at this time, the serum ferritin of hypertensive women decreased from 110.1±86.3 to 88.7±80.5 ng/dL and of diabetic women, from 164.8±133.4 to 101.2±97.7 ng/dL (p0.05). High ferritin in premenopausal obese women was associated with the main obesity-related comorbidities, and these comorbidities determined the reduction of serum ferritin after bariatric surgery. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Efficacy and safety of deferasirox estimated by serum ferritin and labile plasma iron levels in patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia with transfusional iron overload.

PubMed

Kim, Il-Hwan; Moon, Joon-Ho; Lim, Sung-Nam; Sohn, Sang-Kyun; Kim, Hoon-Gu; Lee, Gyeong-Won; Kim, Yang-Soo; Lee, Ho-Sup; Kwon, Ki-Young; Kim, Sung-Hyun; Park, Kyung-Tae; Chung, Joo-Seop; Lee, Won-Sik; Lee, Sang-Min; Hyun, Myung-Soo; Kim, Hawk; Ryoo, Hun-Mo; Bae, Sung-Hwa; Joo, Young-Don

2015-07-01

Patients receiving red blood cell (RBC) transfusions are at risk of iron overload, which can cause significant organ damage and is an important cause of morbidity and mortality. This study was an open-label, single-arm, prospective clinical study to evaluate the efficacy and safety of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled. DFX was administered for up to 1 year. A total of 100 patients were enrolled. Serum ferritin levels decreased significantly following treatment (from 2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin levels was -65 ng/mL in AA (p = 0.037), -647 ng/mL in lower-risk MDS (MDS-LR; p = 0.007), and -552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile plasma iron (LPI) levels decreased from 0.24 μmol/L at baseline to 0.03 μmol/L at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was -0.17 μmol/L in AA, -0.21 μmol/L in MDS-LR, and -0.30 μmol/L in MDS-HR/AML. Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was temporarily skipped for adverse events in seven patients (7.0%) and was permanently discontinued in 11 patients (11.0%). DFX reduced serum ferritin and LPI levels in patients with transfusional iron overload. Despite the relatively high percentage of gastrointestinal side effects, DFX was tolerable in all subgroups. © 2015 AABB.

Relationship of Iron Deficiency and Serum Ferritin Levels with Pulmonary Hypertension: The Jackson Heart Study.

PubMed

Jankowich, Matthew; Elston, Beth; Evans, Samuel K; Wu, Wen-Chih; Choudhary, Gaurav

2016-01-01

Iron deficiency is prevalent in idiopathic pulmonary arterial hypertension (IPAH), but whether iron deficiency or ferritin levels are associated with pulmonary hypertension (PH) in the general population is unknown. We performed a cross-sectional analysis of data on iron deficiency (exposure), and PH (pulmonary artery systolic pressure>40mmHg on echocardiogram) (outcome) on subjects with complete data on exposures and outcomes as well as covariates (n = 2,800) enrolled in the Jackson Heart Study, a longitudinal prospective observational cohort study of heart disease in African-Americans from Jackson, Mississippi. Iron deficiency was defined as a serum ferritin level < 15ng/mL (females); < 30ng/mL (males). We determined crude prevalence ratios (PRs) for PH in iron deficient versus non-iron deficient groups using modified Poisson regression modeling. We also analyzed the prevalence of PH by sex-specific quartiles of ferritin (Females ≤ 47ng/mL; > 47ng/mL- 95ng/mL; > 95ng/mL- 171ng/mL; > 171ng/mL; Males ≤ 110ng/mL; > 110ng/mL- 182ng/mL; > 182ng/mL- 294ng/mL; > 294ng/mL), using the same modeling technique with the lowest quartile as the referent. Median pulmonary artery systolic pressure was 27mmHg (interquartile range 23-31mmHg) in the study cohort. 147 subjects (5.2%) had PH and 140 (5.0%) had iron deficiency. However, of the 147 subjects with PH, only 4 were also iron deficient. The crude PH PR was 0.5 (95% CI 0.2-1.4) in iron-deficiency compared to non-deficient. In analysis by quartiles of ferritin, adjusting for age and sex, there was no evidence of association with PH in quartiles 2 (PR 1.1, 95% CI 0.7-1.6), 3 (PR 0.8, 95% CI 0.5-1.3), or 4 (PR 0.8, 95% CI 0.5-1.2) compared with quartile 1 (referent group, PR 1). Further analyses of the relationship between PH and ferritin as a log-transformed continuous variable or by quartiles of serum iron showed similar results. In the Jackson Heart Study, the prevalence of PH was similar in iron-deficient and non-iron deficient subjects. There was no evidence of association between ferritin (or serum iron) levels and PH. Iron deficiency has been associated with IPAH, a rare disorder. However, in a large community-based sample of African-Americans, there was no evidence that iron deficiency or low iron levels were associated with PH.

Blood Metal Concentrations of Manganese, Lead, and Cadmium in Relation to Serum Ferritin Levels in Ohio Residents

EPA Science Inventory

The objectives of this study were to assess fcrritin-specific profiles of blood metal concentrations such as manganese, lead, and cadmium and to evaluate whether ferritin may affect the behavior of the blood metals in relation to menstruation, menopause, or sex in Ohio residents....

Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants.

PubMed

Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

2016-01-01

Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the high prevalence of elevated BLL, health interventions should look forward to minimize the exposure to lead to better protect the population in West Africa.

Hormonal and echocardiographic abnormalities in adult patients with sickle-cell anemia in Bahrain

PubMed Central

Garadah, Taysir S; Jaradat, Ahmed A; Alalawi, Mohammed E; Hassan, Adla B

2016-01-01

Background Adrenal, thyroid, and parathyroid gland hormonal changes are recognized in children with homozygous (HbSS) sickle-cell anemia (SCA), but are not clear in adult patients with SCA. Aim To assess the metabolic and endocrine abnormalities in adult patients with SCA and evaluate left ventricular (LV) systolic and diastolic functions compared with patients with no SCA and further study the relationship between serum levels of cortisol, free thyroxine (T4), and testosterone with serum ferritin. Materials and methods The study was conducted on 82 patients with adult HbSS SCA compared with a sex- and age-matched control group. The serum levels of cortisol, parathyroid hormone (PTH), testosterone, thyroid-stimulating hormone (TSH), and free T4 were compared. Blood levels of hemoglobin, reticulocyte count, lactate dehydrogenase (LDH), calcium, alkaline phosphatase (ALP), vitamin D3, and ferritin were also compared. Pulsed Doppler echo was performed to evaluate the LV mass, wall thickness, and cavity dimensions with diastolic filling velocities of early (E) and atria (A) waves. Biometric data were analyzed as mean ± standard deviation between the two groups. Multiple regression analysis was performed between serum levels of ferritin as independent variable and testosterone, cortisol, and thyroid hormones. Results A total of 82 adult patients with HbSS SCA were enrolled who had a mean age of 21±5.7 years, with 51 males (62%). Patients with SCA compared with the control group had significantly lower hemoglobin, body mass index, cortisol, vitamin D3, testosterone, and T4. Furthermore, there were significantly high levels of reticulocyte count, PTH, TSH, ferritin, LDH, ALP, and uric acid. The incidence of subclinical hypothyroidism and adrenal insufficiency was 7% and 4.8%, respectively, with hypogonadism 9.8% and vitamin D3 deficiency 61%. There were inverse relationships between ferritin as independent variable and serum levels of testosterone, T4, and cortisol, with regression coefficients of −0.49 (P<0.001), −0.33 (P<0.001), and −0.11 (P<0.92), respectively. Conclusion Patients with adult SCA had a high prevalence of in vivo hypoadrenialism (4.8%), hypogonadism (9.8%), and hypothyroidism (7%). There were significant inverse relationships between serum ferritin as independent variable and cortisol, testosterone, and T4. Pulsed Doppler echocardiography showed increased LV mass, with a restrictive LV diastolic pattern suggestive of diastolic dysfunction. PMID:28008293

[The efficacy of phlebotomy with a low iron diet in the management of pulmonary iron overload].

PubMed

Fukuda, Tomoko; Kimura, Fumiaki; Watanabe, Yoichi; Yoshino, Tadasi; Kimura, Ikuro

2003-05-01

Numerous studies have shown that workers in ferriferous industries have an elevated risk of respiratory tract neoplasia and other airway diseases. Evidence is presented that iron is a carcinogenic and tissue toxic hazard as regarding the inhalation of ferriferous substances. Elimination of the inhaled iron and prevention from accumulation of iron in the lung seems to be very important. A 26-year-old man was admitted to our hospital complaining of right chest pain. He had worked as an arc welder for two years without a mask. A chest CT showed diffuse ground glass opacity in the bilateral lung fields. A transbronchial lung biopsy specimen showed numerous alveolar and interstitial iron-laden macrophages. A 200 ml phlebotomy was carried out biweekly in combination with a low iron diet (8 mg/day). When serum ferritin reached 20 ng/ml, phlebotomy was stopped. After that, serum ferritin level was kept at around 20 ng/ml with the low iron diet alone. A transbronchial lung biopsy was carried out again 7 months later and the specimen showed remarkable reduction in the number of iron-laden alveolar and interstitial macrophages. Phlebotomy in combination with a low iron diet might become a useful strategy in the management of pulmonary conditions associated with iron loading.

Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging.

PubMed

Wahidiyat, Pustika Amalia; Liauw, Felix; Sekarsari, Damayanti; Putriasih, Siti Ayu; Berdoukas, Vasili; Pennell, Dudley J

2017-09-01

Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy. This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy. The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r = -0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r = 0.37) was found between liver iron concentration (LIC) and serum ferritin. The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels. This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.

Oxidation-Induced Degradable Nanogels for Iron Chelation

NASA Astrophysics Data System (ADS)

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-02-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.

Oxidation-Induced Degradable Nanogels for Iron Chelation

PubMed Central

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-01-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners

PubMed Central

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-01-01

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT (p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW (p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW (p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron. PMID:28335426

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners.

PubMed

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-03-14

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT ( p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW ( p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW ( p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron.

Treatment of pediatric restless legs syndrome.

PubMed

Amos, Louella B; Grekowicz, Megan L; Kuhn, Evelyn M; Olstad, Jenna D; Collins, Maureen M; Norins, Nan A; D'Andrea, Lynn A

2014-04-01

The primary aim was to determine if iron supplementation effectively treats children with restless legs syndrome (RLS), the time to improvement or resolution of symptoms, and patient characteristics (family history of RLS, secondary sleep disorders, medical diagnoses, and/or mental health diagnoses) that may affect outcome. METHODS.: This was a retrospective chart review of children between 5 and 18 years old who were diagnosed with RLS at the pediatric sleep disorders clinic at Children's Hospital of Wisconsin in Milwaukee, Wisconsin. Documented RLS treatment approaches included supplemental iron, nonpharmacologic interventions, melatonin, gabapentin, clonidine, and dopamine agonists (pramipexole and ropinirole). Ninety-seven children were diagnosed with RLS; 60.8% of children were between 5 and 11 years old. Most children (65%) received iron either as monotherapy or in combination with other treatments. Approximately 80% of the children who received iron and had follow-up had improvement or resolution of their symptoms. The median baseline ferritin level was 22.7 ng/mL, and 71% of children had a ferritin level less than 30 ng/mL. The median time to improvement or resolution of symptoms was 3.8 months. Supplemental iron as monotherapy or in combination with other treatments is effective in treating pediatric RLS. A prospective study could help determine if the initial ferritin level and degree of change in the ferritin level impact response to iron treatment. It is also important to study the long-term outcomes in these patients.

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.

PubMed

Fiorito, Veronica; Geninatti Crich, Simonetta; Silengo, Lorenzo; Aime, Silvio; Altruda, Fiorella; Tolosano, Emanuela

2013-01-01

The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.

Secreted ferritin arises from the entry of newly translated ferritin chains into the secretory apparatus in response to a deficiency in free cytosolic iron

PubMed Central

De Domenico, Ivana; Vaughn, Michael B; Paradkar, Prasad N; Lo, Eric; Ward, Diane M.; Kaplan, Jerry

2010-01-01

Summary Ferritin is a multisubunit protein that is responsible for storing and detoxifying cytosolic iron. Ferritin can be found in serum but is relatively iron poor. Serum ferritin occurs in iron overload disorders, inflammation and in the genetic disorder hyperferritinemia with cataracts. We show that ferritin secretion results when cellular ferritin synthesis occurs in the relative absence of free cytosolic iron. In yeast and mammalian cells, newly synthesized ferritin monomers can be translocated into the endoplasmic reticulum and transits through the secretory apparatus. Ferritin chains can be translocated into the endoplasmic reticulum in an in vitro translation and membrane insertion system. The insertion of ferritin monomers into the ER occurs under low free iron conditions, as iron will induce the assembly of ferritin. Secretion of ferritin chains provides a mechanism that limits ferritin nanocage assembly and ferritin mediated-iron sequestration in the absence of the translational inhibition of ferritin synthesis. PMID:21195349

Cross sectional, comparative study of serum erythropoietin, transferrin receptor, ferritin levels and other hematological indices in normal pregnancies and iron deficiency anemia during pregnancy.

PubMed

Sharma, Jai B; Bumma, Sirisha D; Saxena, Renu; Kumar, Sunesh; Roy, Kallol K; Singh, Neeta; Vanamail, P

2016-08-01

To test the correlation of the serum erythropoietin levels, serum transferrrin receptor levels and serum ferritin levels along with other hematological parameters in normal pregnant and anemic pregnant patients. In a prospective study, 120 pregnant women were recruited between 18 and 36 weeks of gestation; 53 normal pregnant patients, 67 anemic pregnant patients, in which, 17 had mild, 30 had moderate anemia, 20 had severe anemia. A blood sample was taken. The various hematological parameters, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), total iron binding capacity (TIBC), serum ferritin, percentage saturation of iron, serum erythropoietin (SEPO) levels, serum transferrin receptors (STfRS) were performed. For statistics, Student's 't' test, Pearson's Chi test, Mann Whitney test and Bartlett test were used as per data. MCV was significantly reduced in anemic pregnancies as compared to non-anemic pregnancies (80.2±9.6 vs 94.12±9.8fl, p=0.001), MCHC was also reduced in them (30.2±3.38% vs 34.2±2.33%, p=0.176), TIBC was significantly increased in anemic pregnancies (343.31±28.54% vs 322.88±23.84%, p=0.001), serum ferritin was significantly reduced (24.9±10.48μg/L vs 31.03±9.98μg/L, p=0.001), percentage saturation of iron was also reduced (53.85±13.21% vs 62.04±15.79%, p=0.0024), serum erythropoietin levels were significantly higher in anemic women (26.24±26.61mU/ml vs 18.12±19.08mU/ml, p=0.064). The levels were significantly higher in severe anemia (46.5±46.8mU/ml than in moderate anemia 27.4±28.1mU/ml and mild anemia 22.8±22.8mU/ml. Serum transferrin receptors were significantly higher in anemic pregnancies than in non-anemic pregnancies (1.40±0.0802μg/ml vs 1.08±0.641μg/ml, p=0.019) with rise being higher in severe anemia (2.28±0.986μg/ml) than in moderate (1.4±0.816μg/ml) and mild anemia (1.16±0.702μg/ml). Various hematological parameters especially sTfR, serum erythropoietin, serum ferritin and sTfR/log ferritin levels correlate with the severity of anemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation.

PubMed

Papillard-Marechal, Solesne; Sznajder, Marc; Hurtado-Nedelec, Margarita; Alibay, Yasmin; Martin-Schmitt, Caroline; Dehoux, Monique; Westerman, Mark; Beaumont, Carole; Chevallier, Bertrand; Puy, Herve; Stheneur, Chantal

2012-03-01

Only a few studies based on small cohorts have been carried out on iron status in anorexia nervosa (AN) patients. The aim of this study was to evaluate the role of hepcidin in hyperferritinemia in AN adolescents. Twenty-seven adolescents hospitalized for AN in the pediatric inpatient unit of Ambroise Paré Academic Hospital were enrolled in the study. The control group comprised 11 patients. Hematologic variables and markers of iron status, including serum hepcidin, were measured before and after nutritional rehabilitation. The mean age of patients was 14.4 y. Except for 2 AN patients and 1 control patient, all patients presented normal hemoglobin, vitamin B-12, and folate concentrations. Markers of inflammation and cytokines were normal throughout the study. None of the muscular lysis markers were elevated. Most AN patients had normal serum iron concentrations on admission. Serum ferritin concentrations were significantly higher in patients than in control subjects (198 compared with 49 μg/L, respectively; P < 0.001). The median hepcidin concentration was significantly higher in AN patients than in the control group (186.5 compared with 39.5 μg/L, respectively; P = 0.002). There was a highly significant correlation between ferritinemia and serum hepcidin concentrations (P < 0.0001). After nutritional rehabilitation, a significant reduction was observed (P = 0.004) in serum ferritin. Serum hepcidin analyzed in a smaller number of patients also returned to within the normal range. Hepcidin and ferritin concentrations were higher in the serum of AN patients, without any evidence of iron overload or inflammation. These concentrations returned to normal after nutritional rehabilitation. These results suggest that nutritional stress induced by malnourishment in the hepatocyte could be yet another mechanism that regulates hepcidin.

Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

PubMed

Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

2014-03-01

Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

METABOLISM OF IRON STORES

PubMed Central

SAITO, HIROSHI

2014-01-01

ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since the pioneering research by Shoden in 1953. However, we recently developed a new method for determining ferritin iron and hemosiderin iron by computer-assisted serum ferritin kinetics. Serum ferritin increase or decrease curves were measured in patients with normal storage iron levels (chronic hepatitis C and iron deficiency anemia treated by intravenous iron injection), and iron overload (hereditary hemochromatosis and transfusion dependent anemia). We thereby confirmed the existence of two iron pathways where iron flows followed the numbered order (1) labile iron, (2) ferritin and (3) hemosiderin in iron deposition and mobilization among many previously proposed but mostly unproven routes. We also demonstrated the increasing and decreasing phases of ferritin iron and hemosiderin iron in iron deposition and mobilization. The author first demonstrated here the change in proportion between pre-existing ferritin iron and new ferritin iron synthesized by removing iron from hemosiderin in the course of iron removal. In addition, the author disclosed the cause of underestimation of storage iron turnover rate which had been reported by previous investigators in estimating storage iron turnover rate of normal subjects. PMID:25741033

Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients.

PubMed

Thomas, C; Kobold, U; Balan, S; Roeddiger, R; Thomas, L

2011-04-01

Biochemical markers of iron deficiency do not distinguish iron-deficient anemia (IDA) from the anemia of chronic disease (ACD) and the combined state of ACD/IDA. Serum hepcidin-25 might be a marker resolving this problem. We investigated the extent to which serum hepcidin-25 enables the differentiation of the states above in comparison with the ferritin index plot, the so-called Thomas plot [soluble transferrin receptor (sTfR)/log ferritin and the reticulocyte hemoglobin content (CHr)]. Serum hepcidin-25 was determined in 155 anemic patients who were classified as having latent iron deficiency (latent ID), IDA, ACD, or ACD/IDA using the ferritin index plot (Thomas plot). Hepcidin-25 was determined using an isotope-dilution micro-HPLC-tandem mass spectrometry method. The ability to discriminate among these states based on serum hepcidin-25 alone or in combination with the CHr was evaluated in a receiver operating characteristic curve analysis and a comparison with the recently established ferritin index plot. Serum hepcidin-25 correlated with ferritin and the ferritin index. Use of a hepcidin-25 cutoff level of ≤4 nmol/l allowed the differentiation of IDA from ACD and ACD/IDA. Furthermore, the discrimination of ACD/IDA from ACD required combination with CHr in a new plot (hepcidin-25 and the CHr). The hepcidin-25 plot and the ferritin index plot showed a good correspondence in the differentiation of iron states in patients with anemia. Patients with IDA can be differentiated from ACD and ACD/IDA but not ACD from ACD/IDA based on hepcidin-25 alone. The combination of hepcidin-25 with CHr in the hepcidin-25 plot was useful for the differentiation of the states above. © 2010 Blackwell Publishing Ltd.

Molecular characterization of two ferritins of the scallop Argopecten purpuratus and gene expressions in association with early development, immune response and growth rate.

PubMed

Coba de la Peña, Teodoro; Cárcamo, Claudia B; Díaz, María I; Brokordt, Katherina B; Winkler, Federico M

2016-08-01

Ferritin is involved in several iron homoeostasis processes in molluscs. We characterized two ferritin homologues and their expression patterns in association with early development, growth rate and immune response in the scallop Argopecten purpuratus, a species of economic importance for Chile and Peru. Two ferritin subunits (Apfer1 and Apfer2) were cloned. Apfer1 cDNA is a 792bp clone containing a 516bp open reading frame (ORF) that corresponds to a novel ferritin subunit in A. purpuratus. Apfer2 cDNA is a 681bp clone containing a 522bp ORF that corresponds to a previously sequenced EST. A putative iron responsive element (IRE) was identified in the 5'-untranslated region of both genes. The deduced protein sequences of both cDNAs possessed the motifs and domains characteristic of functional ferritin subunits. Both genes showed differential expression patterns at tissue-specific and early development stage levels. Apfer1 expression level increased 40-fold along larval developmental stages, decreasing markedly after larval settlement. Apfer1 expression in mantle tissue was 2.8-fold higher in fast-growing than in slow-growing scallops. Apfer1 increased 8-fold in haemocytes 24h post-challenge with the bacterium Vibrio splendidus. Apfer2 expression did not differ between fast- and slow-growing scallops or in response to bacterial challenge. These results suggest that Apfer1 and Apfer2 may be involved in iron storage, larval development and shell formation. Apfer1 expression may additionally be involved in immune response against bacterial infections and also in growth; and thus would be a potential marker for immune capacity and for fast growth in A. purpuratus. Copyright © 2016 Elsevier Inc. All rights reserved.

Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome

PubMed Central

Petroni, Roberta Cardoso; da Rosa, Susana Elaine Alves; de Carvalho, Flavia Pereira; Santana, Rúbia Anita Ferraz; Hyppolito, Joyce Esteves; Nascimento, Claudia Mac Donald Bley; Hamerschlak, Nelson; Campregher, Paulo Vidal

2017-01-01

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5’UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5’UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice. PMID:28746593

Characteristics of trapping various organophosphorus pesticides with a ferritin reactor of shark liver (Sphyrna zygaena).

PubMed

Huang, He-Qing; Xiao, Zhi-Qun; Lin, Qing-Mei; Chen, Ping

2005-03-15

A reactor is composed of liver ferritin of Sphyrna zygaena (SZLF) and an oscillating bag. A reactive procedure for trapping various organphosphorus pesticides (OPs) with the SZLF reactor in the flowing water is described in detail, showing the maximal trapping numbers of 28 +/-1.0 dichlorovos/SZLF, 42 +/- 1.0 dimethoate/SZLF, and 55 +/- 1.0 methamido-phos/SZLF determined by a improved spectrophotometric method in 12 h. In addition, it is found that the OP numbers trapped by the reactor increase along with the incubation time and its concentration increment in the flowing water (or seawater), respectively. This trapping capacity is considered to depend on the composition of amino acids on the surface of the ferritin shell interior rather than the available volume within the shell. A novel pathway for trapping various OPs with the ferritin is suggested in reference to unstable characteristics of the protein subunits. We claim that the ferritin reactor will be employed to monitor the contamination level of various OPs in the flowing water continuously.

Variation in intravenous iron use internationally and over time: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

PubMed

Bailie, George R; Larkina, Maria; Goodkin, David A; Li, Yun; Pisoni, Ronald L; Bieber, Brian; Mason, Nancy; Tong, Lin; Locatelli, Francesco; Marshall, Mark R; Inaba, Masaki; Robinson, Bruce M

2013-10-01

To examine patterns of intravenous (IV) iron use across 12 countries from 1999 to 2011. Trends in iron use are described among 32 192 hemodialysis (HD) patients in the Dialysis Outcomes and Practice Patterns Study. Adjusted associations of IV iron dose with serum ferritin and transferrin saturation (TSAT) values were also studied. IV iron was administered to 50% of patients over 4 months in 1999, increasing to 71% during 2009-11, with increasing use in most countries. Among patients receiving IV iron, the mean monthly dose increased from 232 ± 167 to 281 ± 211 mg. Most countries used 3 to 4 doses/month, but Canada used about 2 doses/month, Italy increased from 3 to almost 6 doses/month and Germany used 5 to 6 doses/month. The USA and most European countries predominantly used iron sucrose and sodium ferric gluconate. A significant use of iron dextran was limited to Canada and France; iron polymaltose was used in Australia and New Zealand; and Japan used ferric oxide saccharate, chondroitin polysulfate iron complex and cideferron. Ferritin values rose in most countries: 22% of patients had ≥ 800 ng/mL in the recent years of study. TSAT levels increased to a lesser degree over time. Japan had much lower IV iron dosing and ferritin levels, but similar TSAT levels. In adjusted analyses, serum ferritin and TSAT levels increased signifcantly by 14 ng/mL and 0.16%, respectively, for every 100 mg/month higher mean monthly iron dose. IV iron prescription patterns varied between countries and changed over time from 1999 to 2011. IV iron use and dose increased in most countries, with notable increases in ferritin but not TSAT levels. With rising cumulative IV iron doses, studies of the effects of changing IV iron dosing and other anemia management practices on clinical outcomes should be a high priority.

Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

PubMed

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Feucht, Judith; Queudeville, Manon; Teltschik, Heiko-Manuel; Lang, Peter; Feuchtinger, Tobias; Handgretinger, Rupert; Müller, Ingo

2016-01-01

Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers.

Relationship between Serum Iron Profile and Blood Groups among the Voluntary Blood Donors of Bangladesh.

PubMed

Hoque, M M; Adnan, S D; Karim, S; Al-Mamun, M A; Faruki, M A; Islam, K; Nandy, S

2016-04-01

Blood donation results in a substantial iron loss and subsequent mobilization from body stores. Chronic iron deficiency is a well-recognized complication of regular blood donation. The present study conducted to compare the level of serum ferritin, serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation in different ABO and Rhesus type blood groups among the voluntary blood donors of Bangladesh. The present prospective study included 100 healthy voluntary donors attending at Department of Blood Transfusion, Dhaka Medical College, Dhaka between the periods of July 2013 to Jun 2014. From each donor 10mL venous blood sample was taken and divided into heparinized and non-heparinized tubes for determination of hemoglobin (Hb), hematocrit (Hct), serum iron (SI), total iron binding capacity (TIBC) and serum ferritin by standard laboratory methods. Percentage of transferrin saturation (TS) calculated from serum iron and TIBC. Data were analyzed with SPSS (version 16) software and comparisons between groups were made using student's t-test and one way ANOVA. In the present study mean±SD of age of the respondents was 27.2±6.5 years with a range of 18 to 49 years and 81.0% were male and 19.0% were female. Among the donors 18.0% had blood group A, 35.0% had blood group B, 14.0% had blood group AB and 33.0% had blood group O. Among the donors 91.0% had rhesus positive and 9.0% had rhesus negative. Donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels. Donors with blood group A had highest TIBC level. Donors with blood group B had lowest serum ferritin level. An independent samples 't' test showed statistically significant difference in serum ferritin and percentage transferrin saturation between blood group AB and blood group O and in percentage transferrin saturation between blood group B and blood group O. One way ANOVA showed that there is no significant difference in haemoglobin, serum iron, serum ferritin and percentage transferring saturation in different ABO and Rh blood grouping categories. Blood donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels and donors with blood group A had highest TIBC level. Blood donors with blood group B had lowest serum ferritin level. The understanding of the different blood groups ability to retain iron in their system can give an insight into their ability to handle the disease iron deficiency anaemia.

Increased lectin binding capacity of trophoblastic cells of late day 5 rat blastocysts.

PubMed Central

Stein, B A; Shaw, T J; Turner, V F; Murphy, C R

1994-01-01

The binding of lectins to the trophoblast of rat blastocysts has been studied using quantitative ultrastructural cytochemistry. Rat blastocysts from early, mid and late d 5 of gestation were stained using biotinylated lectins (Phytolacca americana [Phy am], fucose binding protein [FBP] and soybean agglutinin [SBA]) and a sensitive avidin-ferritin cytochemical method. Electron micrographs of ferritin particles along the membrane were processed to produce images for which grey scale levels could be established and the ferritin particles automatically counted. The ferritin:membrane ratio was then calculated. Increased binding with Phy am (which detects short chain oligosaccharides) was found after midday of d 5, i.e. after hatching. Binding of FBP and SBA did not alter during the period studied. The increased concentration of oligosaccharides on the blastocyst surface membrane after hatching may have important implications for blastocyst attachment to the endometrium. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7649802

Siderosomal ferritin. The missing link between ferritin and haemosiderin?

PubMed Central

Andrews, S C; Treffry, A; Harrison, P M

1987-01-01

A minor electrophoretically fast component was found in ferritin from iron-loaded rat liver in addition to a major electrophoretically slow ferritin similar to that observed in control rats. The electrophoretically fast ferritin showed immunological identity with the slow component, but on electrophoresis in SDS it gave a peptide of 17.3 kDa, in contrast with the electrophoretically slow ferritin, which gave a major band corresponding to the L-subunit (20.7 kDa). Thus the electrophoretically fast ferritin resembles that reported by Massover [(1985) Biochim. Biophys. Acta 829, 377-386] in livers of mice with short-term parenteral iron overload. The electrophoretically fast ferritin had a lower iron content (2000 Fe atoms/molecule) than the electrophoretically slow ferritin (3000 Fe atoms/molecule). Removal and re-incorporation of iron was possible without effect on the electrophoretic mobility of either ferritin species. On subcellular fractionation the electrophoretically fast ferritin was enriched in pellet fractions and was the sole soluble ferritin isolated from iron-laden secondary lysosomes (siderosomes). The amount and relative proportion of the electrophoretically fast species increased with iron loading. Haemosiderin isolated from siderosomes was found to contain a peptide reactive to anti-ferritin serum and corresponding to the 17.3 kDa peptide of the electrophoretically fast ferritin species. Unlike the electrophoretically slow ferritin, the electrophoretically fast ferritin did not become significantly radioactive in a 1 h biosynthetic labelling experiment. We conclude that the minor ferritin is not, as has been suggested for mouse liver ferritin, 'a completely new species of smaller holoferritin that represents a shift in the ferritin phenotype' in response to siderosis, but a precursor of haemosiderin, in agreement with the proposal by Richter [(1984) Lab. Invest. 50, 26-35] concerning siderosomal ferritin. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. PMID:3663170

Iron loading, alcohol and mortality: A prospective study.

PubMed

Schutte, Rudolph; Huisman, Hugo; Mels, Catharina M C; Botha, Shani; Kruger, Ruan; Smith, Wayne; Kruger, Iolanthé M; Hawkins, Michelle; Smith, Lee; Breet, Yolandi; Schutte, Aletta E

2018-05-16

The relationship between total body iron and cardiovascular disease remains controversial and information absent in black sub-Saharan Africans in whom alcohol consumption tends to be high. The level of total body iron is tightly regulated, however this regulation is compromised by high alcohol intake causing iron loading. The aim of this study is to investigate total body iron, as represented by serum ferritin, and its interaction with measures of alcohol intake in predicting all-cause and cardiovascular mortality. We followed health outcomes for a median of 9.22 years in 877 randomly selected HIV negative African women (mean age: 50.4 years). One hundred and five deaths occurred of which 40 were cardiovascular related. Ferritin averaged 84.0 (5th to 95th percentile interval, 7.5-533.3) ng/ml and due to the augmenting effect of inflammation, lowered to 75.3 (6.9-523.2) ng/ml after excluding 271 participants with high-sensitivity C-reactive protein (CRP) levels (above 8 mg/l). CRP increased by quartiles of ferritin in the total group (P trend = 0.002), but this relationship was absent after excluding the 271 participants with high CRP values (P trend = 0.10). Ferritin, gamma-glutamyl transferase and carbohydrate deficient transferrin (all P < 0.0001) were higher in drinkers compared to non-drinkers, but CRP was similar (P = 0.77). In multivariable-adjusted analyses, ferritin predicted both all-cause (hazard ratio, 2.08; 95% confidence interval, 1.62-2.68; P < 0.0001) and cardiovascular (1.94; 1.29-2.92; P = 0.002) mortality. In participants with CRP levels below or equal to 8 mg/l, the significant relationship remained between ferritin and all-cause (2.51; 1.81-3.49; P < 0.0001) and cardiovascular mortality (2.34; 1.45-3.76; P = 0.0005). In fully adjusted models, interactions existed between ferritin and gamma-glutamyl transferase, self-reported alcohol use and carbohydrate deficient transferrin in predicting all-cause (P ≤ 0.012) and cardiovascular mortality (P ≤ 0.003). Iron loading in African women predicted all-cause and cardiovascular mortality and the intake of alcohol seems mechanistically implicated. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Genome-wide comparison of ferritin family from Archaea, Bacteria, Eukarya, and Viruses: its distribution, characteristic motif, and phylogenetic relationship

NASA Astrophysics Data System (ADS)

Bai, Lina; Xie, Ting; Hu, Qingqing; Deng, Changyan; Zheng, Rong; Chen, Wanping

2015-10-01

Ferritins are highly conserved proteins that are widely distributed in various species from archaea to humans. The ubiquitous characteristic of these proteins reflects the pivotal contribution of ferritins to the safe storage and timely delivery of iron to achieve iron homeostasis. This study investigated the ferritin genes in 248 genomes from various species, including viruses, archaea, bacteria, and eukarya. The distribution comparison suggests that mammals and eudicots possess abundant ferritin genes, whereas fungi contain very few ferritin genes. Archaea and bacteria show considerable numbers of ferritin genes. Generally, prokaryotes possess three types of ferritin (the typical ferritin, bacterioferritin, and DNA-binding protein from starved cell), whereas eukaryotes have various subunit types of ferritin, thereby indicating the individuation of the ferritin family during evolution. The characteristic motif analysis of ferritins suggested that all key residues specifying the unique structural motifs of ferritin are highly conserved across three domains of life. Meanwhile, the characteristic motifs were also distinguishable between ferritin groups, especially phytoferritins, which show a plant-specific motif. The phylogenetic analyses show that ferritins within the same subfamily or subunits are generally clustered together. The phylogenetic relationships among ferritin members suggest that both gene duplication and horizontal transfer contribute to the wide variety of ferritins, and their possible evolutionary scenario was also proposed. The results contribute to a better understanding of the distribution, characteristic motif, and evolutionary relationship of the ferritin family.

Ferritin gene transcription is regulated by iron in soybean cell cultures.

PubMed

Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

1991-09-15

Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron.

Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit.

PubMed

Zhang, Yinghui; Mikhael, Marc; Xu, Dongxue; Li, Yiye; Soe-Lin, Shan; Ning, Bo; Li, Wei; Nie, Guangjun; Zhao, Yuliang; Ponka, Prem

2010-10-01

Cytosolic ferritins sequester and store iron, consequently protecting cells against iron-mediated free radical damage. However, the mechanisms of iron exit from the ferritin cage and reutilization are largely unknown. In a previous study, we found that mitochondrial ferritin (MtFt) expression led to a decrease in cytosolic ferritin. Here we showed that treatment with inhibitors of lysosomal proteases largely blocked cytosolic ferritin loss in both MtFt-expressing and wild-type cells. Moreover, cytosolic ferritin in cells treated with inhibitors of lysosomal proteases was found to store more iron than did cytosolic ferritins in untreated cells. The prevention of cytosolic ferritin degradation in MtFt-expressing cells significantly blocked iron mobilization from the protein cage induced by MtFt expression. These studies also showed that blockage of cytosolic ferritin loss by leupeptin resulted in decreased cytosolic ferritin synthesis and prolonged cytosolic ferritin stability, potentially resulting in diminished iron availability. Lastly, we found that proteasomes were responsible for cytosolic ferritin degradation in cells pretreated with ferric ammonium citrate. Thus, the current studies suggest that cytosolic ferritin degradation precedes the release of iron in MtFt-expressing cells; that MtFt-induced cytosolic ferritin decrease is partially preventable by lysosomal protease inhibitors; and that both lysosomal and proteasomal pathways may be involved in cytosolic ferritin degradation.

Term babies with delayed cord clamping: an approach in preventing anemia (.).

PubMed

Ertekin, Arif Aktug; Nihan Ozdemir, Nilufer; Sahinoglu, Zeki; Gursoy, Tugba; Erbil, Nazan; Kaya, Erdal

2016-09-01

We investigated the effects of delayed and early clamping of the cord on the hematologic status of the baby at birth and at the end of second month. Umbilical cord of 74 babies were clamped in the first 30 s (Group 1) and 76 were clamped at 90-120 s (Group 2). Levels of hemoglobin, hematocrit, iron and ferritin were analyzed from the umbilical cord blood at birth and from the venous samples at the end of second month. Hemoglobin, hematocrit, iron and ferritin levels of cord blood were similar in both groups. However, their levels other than ferritin were higher in Group 2 at the end of second month. Two babies had respiratory distress and twelve neonates received phototherapy in Group 2 whereas only five neonates received phototherapy in Group 1. Term babies to whom delayed cord clamping was performed had improved hematological parameters at the end of second month. Therefore, delaying cord clamping in these babies may be a favorible approach in preventing anemia.

Ferritin iron minerals are chelator targets, antioxidants, and coated, dietary iron.

PubMed

Theil, Elizabeth C

2010-08-01

Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley's Anemia and other iron overload conditions are faster removal of ferritin iron with chelators guided to ferritin gated pores by peptides; more ferritin protein synthesis using ferritin mRNA activators, by metal complexes that target mRNA 3D structures; and determining if endocytotic absorption of iron from legumes, which is mostly ferritin, is regulated during iron overload to prevent excess iron entry while providing protein. More of a focus on ferritin features, including protein cage structure, iron mineral, regulatable mRNA, and specific gut absorption properties, will achieve the three novel experimental goals for managing iron homeostasis with transfusion therapies.

Reference values for serum ferritin and percentage of transferrin saturation in Korean children and adolescents.

PubMed

Oh, Hea Lin; Lee, Jun Ah; Kim, Dong Ho; Lim, Jung Sub

2018-03-01

Ferritin reference values vary by age, gender, and ethnicity. We aimed to determine reference values of serum ferritin (SF) and the percentage of transferrin saturation (TSAT) for Korean children and adolescents. We analyzed data from 2,487 participants (1,311 males and 1,176 females) aged 10-20 years from the Korea National Health and Nutrition Examination Survey (2010-2012). We calculated age- and gender-stratified means and percentile values for SF and TSAT. We first plotted mean SF and TSAT by gender and according to age. In males, mean SF tended to be relatively constant among participants aged 10 to 14 years, with an upward trend thereafter. Mean SF trended downward among female participants until the age of 15 years and remained constant thereafter. Thus, significant gender differences in ferritin exist from the age of 14 years. High levels of SF were associated with obesity, and lower SF levels were associated with anemia and menarche status. We established reference values of SF and TSAT according to age and gender. The reference values for SF calculated in this study can be used to test the association between SF values and other defined diseases in Korean children and adolescents.

Ferritin gene transcription is regulated by iron in soybean cell cultures.

PubMed Central

Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

1991-01-01

Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron. Images PMID:1896472

The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes

PubMed Central

Berenshtein, Eduard; Eliashar, Ron; Chevion, Mordechai

2016-01-01

Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders. PMID:27458721

Treatment of Iron Deficiency in Women

PubMed Central

Breymann, C.; Römer, T.; Dudenhausen, J. W.

2013-01-01

Iron deficiency with and without anaemia is a common cause of morbidity, particularly in women. Iron deficiency is generally the result of an imbalance between iron loss and iron absorption. In women with symptoms suspicious for iron deficiency, it is important to confirm or exclude the suspicion using proper tests. The use of serum ferritin levels is considered the gold standard for diagnosis. Although the ideal ferritin levels are not unknown the current consent is that levels < 40 ng/ml indicate iron deficiency, which needs to be treated in symptomatic patients. However, symptoms can already occur at ferritin levels of < 100 ng/ml and treatment must be adapted to the individual patient. Iron supplementation is only indicated in symptomatic patients diagnosed with iron deficiency whose quality of life is affected. It is important to treat iron deficiency together with its causes or risk factors. For example, blood loss from hypermenorrhea should be reduced. Women also need to receive information about the benefits of an iron-rich diet. If oral treatment with iron supplements is ineffective, parenteral iron administration is recommended. PMID:26633902

A longitudinal study of serum ferritin in 319 adolescent Danish boys and girls examined in 1986 and 1992.

PubMed

Milman, N; Byg, K E; Backer, V; Ulrik, C; Graudal, N

1999-10-01

This study examined trends in iron status in adolescents. Serum ferritin was measured in 1986 and 1992 in 319 Danes (161 males) stratified into 5 groups: I. median age 9 yr in 1986 vs. 15 yr in 1992; II. 11 vs. 17 yr; III. 13 vs. 19 yr; IV. 15 vs. 21 yr; V. 17 vs. 23 yr. Males in group I demonstrated no change in ferritin or estimated iron stores in mg/kg; groups II-V displayed an increase in iron status parameters. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in group III, and positively correlated with height velocity in group V. Females in age groups I and II demonstrated a fall in ferritin and estimated iron stores in mg/kg in association with menarche; values were unchanged in groups III and IV, and increased in group V. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in groups I and II. In conclusion, ferritin levels in adolescents display great variation during growth spurt and at menarche. Changes in ferritin showed no consistent association with growth velocity. In both genders, estimated total iron stores increased with age.

Nuclear ferritin: A new role for ferritin in cell biology.

PubMed

Alkhateeb, Ahmed A; Connor, James R

2010-08-01

Ferritin has been traditionally considered a cytoplasmic iron storage protein. However, several studies over the last two decades have reported the nuclear localization of ferritin, specifically H-ferritin, in developing neurons, hepatocytes, corneal epithelial cells, and some cancer cells. These observations encouraged a new perspective on ferritin beyond iron storage, such as a role in the regulation of iron accessibility to nuclear components, DNA protection from iron-induced oxidative damage, and transcriptional regulation. This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease. The nuclear translocation of ferritin is a selective energy-dependent process that does not seem to require a consensus nuclear localization signal. It is still unclear what regulates the nuclear import/export of ferritin. Some reports have implicated the phosphorylation and O-glycosylation of the ferritin protein in nuclear transport; others suggested the existence of a specific nuclear chaperone for ferritin. The data argue strongly for nuclear ferritin as a factor in human development and disease. Ferritin can bind and protect DNA from oxidative damage. It also has the potential of playing a regulatory role in transcription. Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule. Copyright 2010 Elsevier B.V. All rights reserved.

Absolute and functional iron deficiency in professional athletes during training and recovery.

PubMed

Reinke, Simon; Taylor, William R; Duda, Georg N; von Haehling, Stephan; Reinke, Petra; Volk, Hans-Dieter; Anker, Stefan D; Doehner, Wolfram

2012-04-19

Iron deficiency (ID) is one of the most important metabolic dysfunctions. Athletic performance depends on oxygen transport and mitochondrial efficiency, thus on optimal iron balance. We hypothesised that physical extremes result in ID in elite athletes and that the short recovery period may be insufficient to allow a lasting replenishment of iron reserves. Iron metabolism was examined in 20 elite rowing athletes and 10 professional soccer players at the end of a competitive season, after recuperation and during pre-season training. Absolute ID values were defined as ferritin <30 μg/L, functional ID as ferritin 30-99 μg/L or 100-299 μg/L+transferrin saturation <20%. At the end of season, 27% of all athletes had absolute ID and 70% showed functional ID. Absolute iron depletion was not generally restored after recuperation and observed at all time points in 14% of the athletes. Although athletes with initially low ferritin levels showed a slight increase during recuperation (p<0.09), these increases remained within borderline levels. Furthermore, 10% showed borderline haemoglobin levels, suggestive of mild anaemia, as defined by the World Health Organisation. A significant proportion of professional athletes have ID, independent of the training mode. Although recuperation seems to allow a certain recovery of iron storage, particularly in athletes with initially low ferritin levels, this retrieval was insufficient to fully normalise reduced iron levels. Therefore, iron status should be carefully monitored during the various training and competitive periods in elite athletes. An adequate iron supplementation may be needed to maintain balanced iron stores. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Solving Biology's Iron Chemistry Problem with Ferritin Protein Nanocages.

PubMed

Theil, Elizabeth C; Tosha, Takehiko; Behera, Rabindra K

2016-05-17

Ferritins reversibly synthesize iron-oxy(ferrihydrite) biominerals inside large, hollow protein nanocages (10-12 nm, ∼480 000 g/mol); the iron biominerals are metabolic iron concentrates for iron protein biosyntheses. Protein cages of 12- or 24-folded ferritin subunits (4-α-helix polypeptide bundles) self-assemble, experimentally. Ferritin biomineral structures differ among animals and plants or bacteria. The basic ferritin mineral structure is ferrihydrite (Fe2O3·H2O) with either low phosphate in the highly ordered animal ferritin biominerals, Fe/PO4 ∼ 8:1, or Fe/PO4 ∼ 1:1 in the more amorphous ferritin biominerals of plants and bacteria. While different ferritin environments, plant bacterial-like plastid organelles and animal cytoplasm, might explain ferritin biomineral differences, investigation is required. Currently, the physiological significance of plant-specific and animal-specific ferritin iron minerals is unknown. The iron content of ferritin in living tissues ranges from zero in "apoferritin" to as high as ∼4500 iron atoms. Ferritin biomineralization begins with the reaction of Fe(2+) with O2 at ferritin enzyme (Fe(2+)/O oxidoreductase) sites. The product of ferritin enzyme activity, diferric oxy complexes, is also the precursor of ferritin biomineral. Concentrations of Fe(3+) equivalent to 2.0 × 10(-1) M are maintained in ferritin solutions, contrasting with the Fe(3+) Ks ∼ 10(-18) M. Iron ions move into, through, and out of ferritin protein cages in structural subdomains containing conserved amino acids. Cage subdomains include (1) ion channels for Fe(2+) entry/exit, (2) enzyme (oxidoreductase) site for coupling Fe(2+) and O yielding diferric oxy biomineral precursors, and (3) ferric oxy nucleation channels, where diferric oxy products from up to three enzyme sites interact while moving toward the central, biomineral growth cavity (12 nm diameter) where ferric oxy species, now 48-mers, grow in ferric oxy biomineral. High ferritin protein cage symmetry (3-fold and 4-fold axes) and amino acid conservation coincide with function, shown by amino acid substitution effects. 3-Fold symmetry axes control Fe(2+) entry (enzyme catalysis of Fe(2+)/O2 oxidoreduction) and Fe(2+) exit (reductive ferritin mineral dissolution); 3-fold symmetry axes influence Fe(2+)exit from dissolved mineral; bacterial ferritins diverge slightly in Fe/O2 reaction mechanisms and intracage paths of iron-oxy complexes. Biosynthesis rates of ferritin protein change with Fe(2+) and O2 concentrations, dependent on DNA-binding, and heme binding protein, Bach 1. Increased cellular O2 indirectly stabilizes ferritin DNA/Bach 1 interactions. Heme, Fe-protoporphyrin IX, decreases ferritin DNA-Bach 1 binding, causing increased ferritin mRNA biosynthesis (transcription). Direct Fe(2+) binding to ferritin mRNA decreases binding of an inhibitory protein, IRP, causing increased ferritin mRNA translation (protein biosynthesis). Newly synthesized ferritin protein consumes Fe(2+) in biomineral, decreasing Fe(2)(+) and creating a regulatory feedback loop. Ferritin without iron is "apoferritin". Iron removal from ferritin, experimentally, uses biological reductants, for example, NADH + FMN, or chemical reductants, for example, thioglycolic acid, with Fe(2+) chelators; physiological mechanism(s) are murky. Clear, however, is the necessity of ferritin for terrestrial life by conferring oxidant protection (plants, animals, and bacteria), virulence (bacteria), and embryonic survival (mammals). Future studies of ferritin structure/function and Fe(2+)/O2 chemistry will lead to new ferritin uses in medicine, nutrition, and nanochemistry.

Purification and cDNA cloning of ferritin from the hepatopancreas of the freshwater crayfish Pacifastacus leniusculus.

PubMed

Huang, T S; Law, J H; Söderhäll, K

1996-03-01

Ferritin was purified from the hepatopancreas of the freshwater crayfish Pacifastacus leniusculus after injection of iron. It has the same size as horse spleen ferritin (440 kDa) and migrates as two bands, 19 kDa and 20 kDa, respectively, in SDS/PAGE under reducing conditions. Crayfish ferritin (20 kDa) was cloned from a hepatopancreas cDNA library. The deduced amino acid sequence of the crayfish ferritin shows a closer relationship to vertebrate ferritin heavy chains than to insect ferritin and contains the conserved H-specific residues for the ferroxidase centre found in vertebrate ferritin heavy chain. An IRE(iron-responsive element)-like sequence with a predicted stem-loop structure was present in the 5' untranslated region of the crayfish ferritin mRNA. Crayfish ferritin does not share the atypical properties of insect ferritins, such as high molecular mass of intact protein, abundance in hemolymph, and export into vacuoles. We suggest that there are two different types of ferritins distributed in different species: insect-type or secretory ferritins which are predominant in the snail oocyte and insects, and vertebrate (crustacean)-type or cytosolic ferritins which are predominant in vertebrates and crustacea.

[Iron nutritional status in pregnant adolescents at the beginning of gestation].

PubMed

Hertrampf, E; Olivares, M; Letelier, A; Castillo, C

1994-12-01

The frequency of anemia and iron nutrition deficiency was assessed in 342 low socioeconomic level pregnant teenagers at entry to prenatal care in 5 outpatient clinics from a South Orient area of Santiago Chile. According to the Center for Disease Control Criteria, 1.2% of women had iron deficiency anemia. Iron stores were insufficient (defined as a serum ferritin lower than 20 g/L) in 55% for women and depleted (serum ferritin lower than 10 g/L) in 21%. Women with more than 14 weeks of gestation had lower packed red cell volumes, hemoglobin, mean corpuscular volumes and ferritin levels than women with less than 14 of gestation. It is concluded that the prevalence of iron deficiency anemia is lower than that predicted for a highly vulnerable group but the high frequency of low iron stores should encourage the use of iron supplementation in these teenagers.

New insights into iron deficiency and iron deficiency anemia.

PubMed

Camaschella, Clara

2017-07-01

Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vitamin D and iron deficiencies in children and adolescents with cerebral palsy.

PubMed

Le Roy, C; Barja, S; Sepúlveda, C; Guzmán, M L; Olivarez, M; Figueroa, M J; Alvarez, M

2018-01-13

Children and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitaminD (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. To describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. We performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. Patients' mean age was 11.1±4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3±8.8ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P=.03), being male (P=.006), and feeding tube use (P=.006). The patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

PubMed Central

Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

2009-01-01

Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias

PubMed Central

Porter, John B; Lin, Kai-Hsin; Beris, Photis; Forni, Gian Luca; Taher, Ali; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Thein, Swee Lay

2011-01-01

Objectives It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. Methods The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10–30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Results Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (−26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (<0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). Conclusions At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism. PMID:21649735

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias.

PubMed

Porter, John B; Lin, Kai-Hsin; Beris, Photis; Forni, Gian Luca; Taher, Ali; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Thein, Swee Lay

2011-10-01

It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10-30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (-26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (< 0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism. © 2011 John Wiley & Sons A/S.

Absorption of Iron from Ferritin Is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments123

PubMed Central

Chen, Huijun; Miranda, Constanza; Janser, Heinz; Elsenhans, Bernd; Núñez, Marco T.; Pizarro, Fernando; Schümann, Klaus

2012-01-01

Ferritin iron from food is readily bioavailable to humans and has the potential for treating iron deficiency. Whether ferritin iron absorption is mechanistically different from iron absorption from small iron complexes/salts remains controversial. Here, we studied iron absorption (RBC 59Fe) from radiolabeled ferritin iron (0.5 mg) in healthy women with or without non-ferritin iron competitors, ferrous sulfate, or hemoglobin. A 9-fold excess of non-ferritin iron competitor had no significant effect on ferritin iron absorption. Larger amounts of iron (50 mg and a 99-fold excess of either competitor) inhibited iron absorption. To measure transport rates of iron that was absorbed inside ferritin, rat intestinal segments ex vivo were perfused with radiolabeled ferritin and compared to perfusion with ferric nitrilotriacetic (Fe-NTA), a well-studied form of chelated iron. Intestinal transport of iron absorbed inside exogenous ferritin was 14.8% of the rate measured for iron absorbed from chelated iron. In the steady state, endogenous enterocyte ferritin contained >90% of the iron absorbed from Fe-NTA or ferritin. We found that ferritin is a slow release source of iron, readily available to humans or animals, based on RBC iron incorporation. Ferritin iron is absorbed by a different mechanism than iron salts/chelates or heme iron. Recognition of a second, nonheme iron absorption process, ferritin endocytosis, emphasizes the need for more mechanistic studies on ferritin iron absorption and highlights the potential of ferritin present in foods such as legumes to contribute to solutions for global iron deficiency. PMID:22259191

Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

PubMed

Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

2015-09-01

Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably responsible for iron donation in neurodegeneration. This is accompanied by only a slight increase in neuronal ferritin and not ferroportin, which suggests that the iron-containing debris of dying inflammatory cells and degenerating neurons gets scavenged by invading macrophages and activated microglia to prevent an increase in neuronal iron. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins

PubMed Central

Venn-Watson, Stephanie K.; Parry, Celeste; Baird, Mark; Stevenson, Sacha; Carlin, Kevin; Daniels, Risa; Smith, Cynthia R.; Jones, Richard; Wells, Randall S.; Ridgway, Sam; Jensen, Eric D.

2015-01-01

Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0) compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001). Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome. PMID:26200116

Moving Fe2+ from ferritin ion channels to catalytic OH centers depends on conserved protein cage carboxylates.

PubMed

Behera, Rabindra K; Theil, Elizabeth C

2014-06-03

Ferritin biominerals are protein-caged metabolic iron concentrates used for iron-protein cofactors and oxidant protection (Fe(2+) and O2 sequestration). Fe(2+) passage through ion channels in the protein cages, like membrane ion channels, required for ferritin biomineral synthesis, is followed by Fe(2+) substrate movement to ferritin enzyme (Fox) sites. Fe(2+) and O2 substrates are coupled via a diferric peroxo (DFP) intermediate, λmax 650 nm, which decays to [Fe(3+)-O-Fe(3+)] precursors of caged ferritin biominerals. Structural studies show multiple conformations for conserved, carboxylate residues E136 and E57, which are between ferritin ion channel exits and enzymatic sites, suggesting functional connections. Here we show that E136 and E57 are required for ferritin enzyme activity and thus are functional links between ferritin ion channels and enzymatic sites. DFP formation (Kcat and kcat/Km), DFP decay, and protein-caged hydrated ferric oxide accumulation decreased in ferritin E57A and E136A; saturation required higher Fe(2+) concentrations. Divalent cations (both ion channel and intracage binding) selectively inhibit ferritin enzyme activity (block Fe(2+) access), Mn(2+) < Co(2+) < Cu(2+) < Zn(2+), reflecting metal ion-protein binding stabilities. Fe(2+)-Cys126 binding in ferritin ion channels, observed as Cu(2+)-S-Cys126 charge-transfer bands in ferritin E130D UV-vis spectra and resistance to Cu(2+) inhibition in ferritin C126S, was unpredicted. Identifying E57 and E136 links in Fe(2+) movement from ferritin ion channels to ferritin enzyme sites completes a bucket brigade that moves external Fe(2+) into ferritin enzymatic sites. The results clarify Fe(2+) transport within ferritin and model molecular links between membrane ion channels and cytoplasmic destinations.

Observational study comparing long-term safety and efficacy of Deferasirox with Desferrioxamine therapy in chelation-naïve children with transfusional iron overload.

PubMed

Aydinok, Yesim; Unal, Sule; Oymak, Yesim; Vergin, Canan; Türker, Zeynep D; Yildiz, Dilek; Yesilipek, Akif

2012-05-01

An observational study was conducted to explore postmarketing safety and efficacy of Deferasirox (DFX) in comparison with conventional Desferrioxamine (DFO) in chelation-naïve children with transfusional iron overload. Transfusion-dependent children (aged ≤ 5 yr) who had serum ferritin above 1000 μg/L and had been prescribed either first-line DFX or DFO for at least 12 months to maintain serum ferritin between 500 and 1000 μg/L were included. Initial DFX dose was 20 mg/kg/d for 7 d a week, and DFO dose was 25-35 mg/kg/d subcutaneously, given for 5 d a week. Dose adjustments were based on serum ferritin changes and safety markers. The primary efficacy endpoint was change in serum ferritin from baseline. The effect of transfusional iron loading rate (ILR) and different doses of chelators on serum ferritin was also assessed. A total of 111 patients were observed for a median of 2.29 yr on DFX (n = 71) and 2.75 yr on DFO (n = 40). Absolute change in serum ferritin from baseline to the last available observation was not significant with DFX (91 μg/L, P = 0.5) but significantly higher with DFO (385 μg/L, P < 0.005). ILR and DFX doses had a major impact on serum ferritin changes in DFX cohort. The height- and weight-standard deviation scores did not differ significantly in both cohorts during the study. Fluctuations in liver enzymes and non-progressive increase in serum creatinine were the most common adverse events (DFX; 9.8%, 18.0% and DFO; 5.0%, 7.5%, respectively). DFX is well tolerable and at least as effective as DFO to maintain safe serum ferritin levels and normal growth progression in chelation-naïve children. © 2012 John Wiley & Sons A/S.

Iron Oxidation and Core Formation in Recombinant Heteropolymeric Human Ferritins.

PubMed

Mehlenbacher, Matthew; Poli, Maura; Arosio, Paolo; Santambrogio, Paolo; Levi, Sonia; Chasteen, N Dennis; Bou-Abdallah, Fadi

2017-08-01

In animals, the iron storage and detoxification protein, ferritin, is composed of two functionally and genetically distinct subunit types, H (heavy) and L (light), which co-assemble in various ratios with tissue specific distributions to form shell-like protein structures of 24 subunits within which a mineralized iron core is stored. The H-subunit possesses a ferroxidase center (FC) that catalyzes Fe(II) oxidation, whereas the L-subunit does not. To assess the role of the L-subunit in iron oxidation and core formation, two human recombinant heteropolymeric ferritins, designated H-rich and L-rich with ratios of ∼20H:4L and ∼22L:2H, respectively, were employed and compared to the human homopolymeric H-subunit ferritin (HuHF). These heteropolymeric ferritins have a composition similar to the composition of those found in hearts and brains (i.e., H-rich) and in livers and spleens (i.e., L-rich). As for HuHF, iron oxidation in H-rich ferritin was found to proceed with a 2:1 Fe(II):O 2 stoichiometry at an iron level of 2 Fe(II) atoms/H-subunit with the generation of H 2 O 2 . The H 2 O 2 reacted with additional Fe(II) in a 2:1 Fe(II):H 2 O 2 ratio, thus avoiding the production of hydroxyl radical. A μ-1,2-peroxo-diFe(III) intermediate was observed at the FC of H-rich ferritin as for HuHF. Importantly, the H-rich protein regenerated full ferroxidase activity more rapidly than HuHF did and additionally formed larger iron cores, indicating dual roles for the L-subunit in facilitating iron turnover at the FC and in mineralization of the core. The L-rich ferritin, while also facilitating iron oxidation at the FC, additionally promoted oxidation at the mineral surface once the iron binding capacity of the FC was exceeded.

Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded by mutation.

PubMed

Hasan, Mohammad R; Tosha, Takehiko; Theil, Elizabeth C

2008-11-14

Ferric minerals in ferritins are protected from cytoplasmic reductants and Fe2+ release by the protein nanocage until iron need is signaled. Deletion of ferritin genes is lethal; two critical ferritin functions are concentrating iron and oxidant protection (consuming cytoplasmic iron and oxygen in the mineral). In solution, opening/closing (gating) of eight ferritin protein pores controls reactions between external reductant and the ferritin mineral; pore gating is altered by mutation, low heat, and physiological urea (1 mm) and monitored by CD spectroscopy, protein crystallography, and Fe2+ release rates. To study the effects of a ferritin pore gating mutation in living cells, we cloned/expressed human ferritin H and H L138P, homologous to the frog open pore model that was unexpressable in human cells. Human ferritin H L138P behaved like the open pore ferritin model in vitro as follows: (i) normal protein cage assembly and mineralization, (ii) increased iron release (t1/2) decreased 17-fold), and (iii) decreased alpha-helix (8%). Overexpression (> 4-fold), in HeLa cells, showed for ferritin H L138P equal protein expression and total cell 59Fe but increased chelatable iron, 16%, p < 0.01 (59Fe in the deferoxamine-containing medium), and decreased 59Fe in ferritin, 28%, p < 0.01, compared with wild type. The coincidence of decreased 59Fe in open pore ferritin with increased chelatable 59Fe in cells expressing the ferritin open pore mutation suggests that ferritin pore gating influences to the amount of iron (59Fe) in ferritin in vivo.

Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, A.G.; Carthew, P.; Francis, J.E.

1990-12-01

After a single subcutaneous dose of iron-dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67-, 42- and 21-fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron-positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of themore » study, the size of the inclusions (which were not membrane-limited) increased to greater than 3 microns in diameter, occupying greater than 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x-ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope. These findings are consistent with the hypothesis that in iron-loaded mouse hepatocytes there is a slow passage of ferritin-molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes.« less

Identification and characterization of a receptor for tissue ferritin on activated rat lipocytes.

PubMed Central

Ramm, G A; Britton, R S; O'Neill, R; Bacon, B R

1994-01-01

Hepatic iron overload causes lipocyte activation with resultant fibrogenesis. This study examines whether rat lipocytes express ferritin receptors, which could be involved in paracellular iron movement and in cellular regulation. Lipocytes from normal rat liver were cultured on plastic and incubated with 125I-labeled rat liver ferritin (RLF) +/- a 100-fold excess of either unlabeled RLF or human heart ferritin, human liver ferritin, human recombinant H-ferritin, a mutant human recombinant L-ferritin, or a variety of nonspecific proteins. Specific binding sites for ferritin were demonstrated by displacement of 125I-RLF by RLF (64.5 +/- 4.3%) and by other ferritins (55-60%), but not by recombinant L-ferritin. Scatchard analysis demonstrated a single class of binding sites with a Kd of 5.1 +/- 2.9 x 10(-10) M, maximum binding capacity of 4.7 +/- 1.3 x 10(-12) M, and 5,000-10,000 receptor sites/cell. Ferritin receptor expression was observed only in activated lipocytes. Internalization of RLF was observed within 15 min using FITC-RLF and confocal microscopy. This study demonstrates that (a) activated lipocytes express a specific high affinity ferritin receptor; (b) the binding appears to be dependent on the H-ferritin subunit; and (c) lipocytes internalize ferritin. Expression of ferritin receptors in activated lipocytes suggests that the receptor may either be involved in the activation cascade or may be a marker of activation. Images PMID:8040296

Systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza pneumonia during the swine influenza (H1N1) pandemic.

PubMed

Cunha, Burke A; Syed, Uzma; Mickail, Nardeen

2011-01-01

We present a young woman with a negative medical history who presented with acute systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza (H1N1) pneumonia. Because this case occurred during the H1N1 pandemic, the initial diagnostic impression was of H1N1 pneumonia. Although her clinical and laboratory findings were consistent with the diagnosis of H1N1 pneumonia, e.g., fever, sore throat, dry cough, arthralgias, myalgias, thrombocytopenia, relative lymphopenia, and elevated serum transaminases, some findings suggested an alternate diagnosis, e.g., leukopenia, a highly elevated erythrocyte sedimentation rate, highly elevated serum ferritin levels, elevated antinuclear antibody (ANA) levels, and double-stranded (DS) DNA titers. Her chest x-ray showed an accentuation of basilar lung markings, with a small pleural effusion similar to the chest x-ray findings of early H1N1 pneumonia. Initially, her headaches were thought to be related to central nervous system manifestations of H1N1. After laboratory test results demonstrated elevated ANA and anti-DS DNA titers, she was diagnosed with acute SLE pneumonitis. The take-home lesson for clinicians is that other infectious diseases, e.g., human parainfluenza virus or Legionnaires' disease, can mimic H1N1 pneumonia during an influenza pandemic. Excluding asthma, congestive heart failure, exacerbations of acute bronchitis, chronic obstructive pulmonary disorder, and pulmonary interstitial disease, noninfectious mimics of H1N1 are extremely rare. To the best of our knowledge, this is the first reported case of de novo SLE pneumonitis mimicking H1N1 pneumonia during the swine influenza pandemic. Copyright © 2011 Elsevier Inc. All rights reserved.

Ferritin and bile acid levels during the intrauterine pre-treatment of gastroschisis by serial amnioexchange

PubMed Central

Demir, Namık; Canda, Mehmet Tunç; Kuday, Şamil; Öztürk, Cengiz; Sezer, Orçun; Danaoğlu, Nihal

2013-01-01

We present a case of gastroschisis managed with serial amnioex-changes. Marked decreases were detected in both ferritin and bile acid levels following the procedure. The bowels were not severely affected, as expected. After delivery, single primary closure of the defect was performed. Early enteral feeding and shorter hospital stay were the main outcome measures. Intrauterine pre-treatment of gastroschisis by serial amnioexchange may provide benefits by decreasing the levels of inflammatory products in the amniotic fluid in order to lower the possible risk of bowel damage, and this may help to achieve better surgical and postnatal outcomes. PMID:24592073

Ferritin gene organization: differences between plants and animals suggest possible kingdom-specific selective constraints.

PubMed

Proudhon, D; Wei, J; Briat, J; Theil, E C

1996-03-01

Ferritin, a protein widespread in nature, concentrates iron approximately 10(11)-10(12)-fold above the solubility within a spherical shell of 24 subunits; it derives in plants and animals from a common ancestor (based on sequence) but displays a cytoplasmic location in animals compared to the plastid in contemporary plants. Ferritin gene regulation in plants and animals is altered by development, hormones, and excess iron; iron signals target DNA in plants but mRNA in animals. Evolution has thus conserved the two end points of ferritin gene expression, the physiological signals and the protein structure, while allowing some divergence of the genetic mechanisms. Comparison of ferritin gene organization in plants and animals, made possible by the cloning of a dicot (soybean) ferritin gene presented here and the recent cloning of two monocot (maize) ferritin genes, shows evolutionary divergence in ferritin gene organization between plants and animals but conservation among plants or among animals; divergence in the genetic mechanism for iron regulation is reflected by the absence in all three plant genes of the IRE, a highly conserved, noncoding sequence in vertebrate animal ferritin mRNA. In plant ferritin genes, the number of introns (n = 7) is higher than in animals (n = 3). Second, no intron positions are conserved when ferritin genes of plants and animals are compared, although all ferritin gene introns are in the coding region; within kingdoms, the intron positions in ferritin genes are conserved. Finally, secondary protein structure has no apparent relationship to intron/exon boundaries in plant ferritin genes, whereas in animal ferritin genes the correspondence is high. The structural differences in introns/exons among phylogenetically related ferritin coding sequences and the high conservation of the gene structure within plant or animal kingdoms of the gene structure within plant or animal kingdoms suggest that kingdom-specific functional constraints may exist to maintain a particular intron/exon pattern within ferritin genes. In the case of plants, where ferritin gene intron placement is unrelated to triplet codons or protein structure, and where ferritin is targeted to the plastid, the selection pressure on gene organization may relate to RNA function and plastid/nuclear signaling.

Molecular Characterization and Functional Analysis of a Ferritin Heavy Chain Subunit from the Eri-Silkworm, Samia cynthia ricini

PubMed Central

Yu, Hai-Zhong; Zhang, Shang-Zhi; Ma, Yan; Fei, Dong-Qiong; Li, Bing; Yang, Li-Ang; Wang, Jie; Li, Zhen; Muhammad, Azharuddin; Xu, Jia-Ping

2017-01-01

Ferritins are conserved iron-binding proteins that are primarily involved in iron storage, detoxification and the immune response. Despite the importance of ferritin in organisms, little is known about their roles in the eri-silkworm (Samia cynthia ricini). We previously identified a ferritin heavy chain subunit named ScFerHCH in the S. c. ricini transcriptome database. The full-length S. c. ricini ferritin heavy chain subunit (ScFerHCH) was 1863 bp and encoded a protein of 231 amino acids with a deduced molecular weight of 25.89 kDa. Phylogenetic analysis revealed that ScFerHCH shared a high amino acid identity with the Bombyx mori and Danaus plexippus heavy chain subunits. Higher ScFerHCH expression levels were found in the silk gland, fat body and midgut of S. c. ricini by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Injection of Staphylococcus aureus and Pseudomonas aeruginosa was associated with an upregulation of ScFerHCH in the midgut, fat body and hemolymph, indicating that ScFerHCH may contribute to the host’s defense against invading pathogens. In addition, the anti-oxidation activity and iron-binding capacity of recombinant ScFerHCH protein were examined. Taken together, our results suggest that the ferritin heavy chain subunit from eri-silkworm may play critical roles not only in innate immune defense, but also in organismic iron homeostasis. PMID:29036914

Distinct Mechanisms of Ferritin Delivery to Lysosomes in Iron-Depleted and Iron-Replete Cells ▿

PubMed Central

Asano, Takeshi; Komatsu, Masaaki; Yamaguchi-Iwai, Yuko; Ishikawa, Fuyuki; Mizushima, Noboru; Iwai, Kazuhiro

2011-01-01

Ferritin is a cytosolic protein that stores excess iron, thereby protecting cells from iron toxicity. Ferritin-stored iron is believed to be utilized when cells become iron deficient; however, the mechanisms underlying the extraction of iron from ferritin have yet to be fully elucidated. Here, we demonstrate that ferritin is degraded in the lysosome under iron-depleted conditions and that the acidic environment of the lysosome is crucial for iron extraction from ferritin and utilization by cells. Ferritin was targeted for degradation in the lysosome even under iron-replete conditions in primary cells; however, the mechanisms underlying lysosomal targeting of ferritin were distinct under depleted and replete conditions. In iron-depleted cells, ferritin was targeted to the lysosome via a mechanism that involved autophagy. In contrast, lysosomal targeting of ferritin in iron-replete cells did not involve autophagy. The autophagy-independent pathway of ferritin delivery to lysosomes was deficient in several cancer-derived cells, and cancer-derived cell lines are more resistant to iron toxicity than primary cells. Collectively, these results suggest that ferritin trafficking may be differentially regulated by cell type and that loss of ferritin delivery to the lysosome under iron-replete conditions may be related to oncogenic cellular transformation. PMID:21444722

Serum levels of iron in Sør-Varanger, Northern Norway--an iron mining municipality.

PubMed

Broderstad, Ann R; Smith-Sivertsen, Tone; Dahl, Inger Marie S; Ingebretsen, Ole Christian; Lund, Eiliv

2006-12-01

The purpose of this study was to investigate iron status in a population with a high proportion of miners in the northernmost part of Norway. Cross-sectional, population-based study performed in order to investigate possible health effects of pollution in the population living on both sides of the Norwegian-Russian border. All individuals living in the community of Sør-Varanger were invited for screening in 1994. In 2000, blood samples from 2949 participants (response rate 66.8 %), age range 30-69 years, were defrosted. S-ferritin and transferrin saturation were analysed in samples from 1548 women and 1401 men. About 30 % (n = 893) were employed in the iron mining industry, 476 of whom were miners and 417 had other tasks in the company. Type and duration of employment and time since last day of work at the company were used as indicators of exposure. Both s-ferritin levels and transferrin saturation were higher in men than in women. S-ferritin increased with increasing age in women, while the opposite was true for men. Iron deficiency occurred with higher frequencies in women (16 %) than in men (4 %). Iron overload was uncommon in both sexes. Adjustment for smoking and self-reported pulmonary diseases did not show any effect on iron levels. Miners had non-significant higher mean s-ferritin and transferrin saturation than non-miners. Neither duration, nor time since employment in the mine, had any impact on iron status. Our analyses did not show any associations between being a miner in the iron mining industry and serum iron levels compared to the general population.

Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study

PubMed Central

Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2015-01-01

Objective To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Study design Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Results Mean length-for-age z score was −0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m2; 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (−41.5 g per twofold increase in ferritin; 95% CI −78 to −5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of −0.06 per 20 nmol/L; 95% CI −0.11 to −0.01) was observed. Conclusions Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. PMID:25246090

Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study.

PubMed

Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2015-02-01

To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Mean length-for-age z score was -0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m(2); 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (-41.5 g per twofold increase in ferritin; 95% CI -78 to -5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of -0.06 per 20 nmol/L; 95% CI -0.11 to -0.01) was observed. Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Serum Ferritin Levels Are Lower in Children With Tic Disorders Compared with Children Without Tics: A Cross-Sectional Study.

PubMed

Avrahami, Matan; Barzilay, Ran; HarGil, Miki; Weizman, Abraham; Watemberg, Nathan

2017-03-01

Alteration in peripheral iron indices has been reported in a number of movement disorders, particularly Parkinson's disease. We hypothesized that iron stores may be diminished in children at an early stage of tic disorder. Using data retrieved from electronic medical records, we compared serum ferritin levels, an indicator of body iron store balance, in drug-naive children diagnosed for the first time with tic disorder (study group; N = 47, 32 boys/15 girls, aged 8.66 ± 3.17 years) compared to age- and sex-matched children with headaches (comparison group, n = 100, 62 boys/38 girls, aged 9.51 ± 3.15 years) treated in the same pediatric neurological clinic. Mean serum ferritin levels were significantly lower (-32%, p = 0.01) in the tic disorder group compared to the headache group. No significant differences were detected in circulatory hemoglobin, iron, transferrin, and platelet count between the two groups. Our findings suggest that body iron stores may be reduced in children with recent-onset tic disorder.

Deferiprone attenuates inflammation and myocardial fibrosis in diabetic cardiomyopathy rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, Chunbo; Liu, Xiaogang; Xie, Rujuan

We attempted to investigate the therapeutic effects of deferiprone on DC rats and explore the underlying mechanism. Total 24 6-week-old male Wistar rats (weighing from 180 g to 220 g) were subjected to DC model construction and then randomly divided to three groups (8 rats per group): DC group, DC + 50 mg, and DC + 100 mg deferiprone treatment group. The 8 normal rats were considered as controls. After deferiprone treatment for 20 weeks, the blood samples were collected for the biochemical parameters test, including fasting glucose, HOMA-IR (homeostasis model assessment of the insulin resistance), serum iron, ferritin and transferrin saturation (TS). The oxidative stress was assessedmore » by detecting the level of malondialdehyde (MDA) and superoxide dismutase (SOD). Histopathologic changes were determined by Masson's trichrome staining and electron microscopy imaging. The expression levels of NF-κB (nuclear factor kappa B), COX2 (cytochrome c oxidase), tenascin C, collagen IV were measured by RT-PCR and western blotting. The expression of nitrotyrosine and MCP-1 (monocyte chemotactic protein 1) were determined by immunohistochemistry. Deferiprone treatment reduced iron deposition and IR in DC rats except for blood glucose. After deferiprone treatment, MDA level was significantly decreased and SOD level was increased significantly. The level of NF-κB, cyclooxygenase-2, tenascin C, collagen IV MCP-1 and nitrotyrosine were significantly reduced. There was no significant difference in the effect of deferiprone at 50 and 100 mg doses. Deferiprone showed therapeutic effects on DC by regulating the pro-inflammatory and pro-fibrotic factors. - Highlights: • The expression of serum iron, ferritin and TS were elevated in DC rats. • Oxidative stress related MDA and SOD were upregulated in DC rats. • NF-κB, COX2, tenascin C, collagen IV were accumulated in DC rats. • All the changes were reversed by deferiprone treatment.« less

Moving Fe2+ from ferritin ion channels to catalytic OH centers depends on conserved protein cage carboxylates

PubMed Central

Behera, Rabindra K.; Theil, Elizabeth C.

2014-01-01

Ferritin biominerals are protein-caged metabolic iron concentrates used for iron–protein cofactors and oxidant protection (Fe2+ and O2 sequestration). Fe2+ passage through ion channels in the protein cages, like membrane ion channels, required for ferritin biomineral synthesis, is followed by Fe2+ substrate movement to ferritin enzyme (Fox) sites. Fe2+ and O2 substrates are coupled via a diferric peroxo (DFP) intermediate, λmax 650 nm, which decays to [Fe3+–O–Fe3+] precursors of caged ferritin biominerals. Structural studies show multiple conformations for conserved, carboxylate residues E136 and E57, which are between ferritin ion channel exits and enzymatic sites, suggesting functional connections. Here we show that E136 and E57 are required for ferritin enzyme activity and thus are functional links between ferritin ion channels and enzymatic sites. DFP formation (Kcat and kcat/Km), DFP decay, and protein-caged hydrated ferric oxide accumulation decreased in ferritin E57A and E136A; saturation required higher Fe2+ concentrations. Divalent cations (both ion channel and intracage binding) selectively inhibit ferritin enzyme activity (block Fe2+ access), Mn2+ << Co2+ < Cu2+ < Zn2+, reflecting metal ion–protein binding stabilities. Fe2+–Cys126 binding in ferritin ion channels, observed as Cu2+–S–Cys126 charge-transfer bands in ferritin E130D UV-vis spectra and resistance to Cu2+ inhibition in ferritin C126S, was unpredicted. Identifying E57 and E136 links in Fe2+ movement from ferritin ion channels to ferritin enzyme sites completes a bucket brigade that moves external Fe2+ into ferritin enzymatic sites. The results clarify Fe2+ transport within ferritin and model molecular links between membrane ion channels and cytoplasmic destinations. PMID:24843174

CONIFER - Non-Interventional Study to Evaluate Therapy Monitoring During Deferasirox Treatment of Iron Toxicity in Myelodysplastic Syndrome Patients with Transfusional Iron Overload.

PubMed

Bruch, Harald-Robert; Dencausse, Yves; Heßling, Jörg; Michl, Gerlinde; Schlag, Rudolf; Skorupa, Alexandra; Schneider-Schranz, Cornelia; Wolf, Sebastian; Schulte, Clemens; Tesch, Hans

2016-01-01

The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (< 15 mg/kg vs. ≥ 15 mg/kg and < 20 mg/kg vs. ≥ 20 mg/kg). The majority of patients (81%) were affected by at least 1 adverse event, with decreased renal creatinine clearance being the most frequent. Higher doses (≥ 15 mg/kg) of deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload. © 2016 S. Karger GmbH, Freiburg.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Infante, Anthony A.; Infante, Dzintra; Chan, M.-C.

We characterized chicken erythrocyte and human platelet ferritin by biochemical studies and immunofluorescence. Erythrocyte ferritin was found to be a homopolymer of H-ferritin subunits, resistant to proteinase K digestion, heat stable, and contained iron. In mature chicken erythrocytes and human platelets, ferritin was localized at the marginal band, a ring-shaped peripheral microtubule bundle, and displayed properties of bona fide microtubule-associated proteins such as tau. Red blood cell ferritin association with the marginal band was confirmed by temperature-induced disassembly-reassembly of microtubules. During erythrocyte differentiation, ferritin co-localized with coalescing microtubules during marginal band formation. In addition, ferritin was found in the nucleimore » of mature erythrocytes, but was not detectable in those of bone marrow erythrocyte precursors. These results suggest that ferritin has a function in marginal band formation and possibly in protection of the marginal band from damaging effects of reactive oxygen species by sequestering iron in the mature erythrocyte. Moreover, our data suggest that ferritin and syncolin, a previously identified erythrocyte microtubule-associated protein, are identical. Nuclear ferritin might contribute to transcriptional silencing or, alternatively, constitute a ferritin reservoir.« less

Genetic manipulation of iron biomineralization enhances MR relaxivity in a ferritin-M6A chimeric complex.

PubMed

Radoul, Marina; Lewin, Limor; Cohen, Batya; Oren, Roni; Popov, Stanislav; Davidov, Geula; Vandsburger, Moriel H; Harmelin, Alon; Bitton, Ronit; Greneche, Jean-Marc; Neeman, Michal; Zarivach, Raz

2016-05-23

Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene - ferritin-M6A - in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies.

Association of Colecalciferol, Ferritin, and Anemia among Pregnant Women: Result from Cohort Study on Vitamin D Status and Its Impact during Pregnancy and Childhood in Indonesia

PubMed Central

Gumilang, Lani; Irianti, Setyorini; Wirhana, Deni; Permana, Irman; Sofjan, Liza; Duhita, Hesty; Tambunan, Lies Ani; Gurnadi, Jeffry Iman; Seno, Umar; Ghrahani, Reni; Indrati, Agnes Rengga; Sribudiani, Yunia; Yuniati, Tetty; Setiabudiawan, Budi

2018-01-01

Studies had shown that iron-cycling was disturbed by inflammatory process through the role of hepcidin. Pregnancy is characterized by shifts of interleukin. Our objective was to determine if 25(OH) vitamin D (colecalciferol) status was associated with ferritin, anemia, and its changes during pregnancy. Method. A cohort study was done in 4 cities in West Java, Indonesia, beginning in July 2016. Subjects were followed up until third trimester. Examinations included were maternal ferritin, colecalciferol, and haemoglobin level. Result. 191 (95.5%) subjects had low colecalciferol, and 151 (75.5%) among them were at deficient state. Anemia is found in 15 (7.5%) subjects, much lower than previous report. Proportion of anemia increased by trimester among women with colecalciferol deficiency. Ferritin status and prepregnancy body mass index in the first trimester were correlated with anemia (r = 0.147, p = 0.038 and r = −0.56, p = 0.03). Anemia in the second trimester was strongly correlated with anemia in the third trimester (r = 0.676, p < 0.01). Conclusion. Our study showed that the state of colecalciferol was not associated with either ferritin state or anemia, but proportion of anemia tends to increase by trimester in the colecalciferol deficient subjects. PMID:29888000

Ferritins: dynamic management of biological iron and oxygen chemistry.

PubMed

Liu, Xiaofeng; Theil, Elizabeth C

2005-03-01

Ferritins are spherical, cage-like proteins with nanocavities formed by multiple polypeptide subunits (four-helix bundles) that manage iron/oxygen chemistry. Catalytic coupling yields diferric oxo/hydroxo complexes at ferroxidase sites in maxi-ferritin subunits (24 subunits, 480 kDa; plants, animals, microorganisms). Oxidation occurs at the cavity surface of mini-ferritins/Dps proteins (12 subunits, 240 kDa; bacteria). Oxidation products are concentrated as minerals in the nanocavity for iron-protein cofactor synthesis (maxi-ferritins) or DNA protection (mini-ferritins). The protein cage and nanocavity characterize all ferritins, although amino acid sequences diverge, especially in bacteria. Catalytic oxidation/di-iron coupling in the protein cage (maxi-ferritins, 480 kDa; plants, bacteria and animal cell-specific isoforms) or on the cavity surface (mini-ferritins/Dps proteins, 280 kDa; bacteria) initiates mineralization. Gated pores (eight or four), symmetrically arranged, control iron flow. The multiple ferritin functions combine pore, channel, and catalytic functions in compact protein structures required for life and disease response.

Timing of clamping and factors associated with iron stores in full-term newborns

PubMed Central

Oliveira, Fabiana de Cássia Carvalho; Assis, Karine Franklin; Martins, Mariana Campos; do Prado, Mara Rúbia Maciel Cardoso; Ribeiro, Andréia Queiroz; Sant’Ana, Luciana Ferreira da Rocha; Priore, Silvia Eloiza; Franceschini, Sylvia do Carmo Castro

2014-01-01

OBJECTIVE To analyze the impact of timing of clamping and obstetric, biological and socioeconomic factors on the iron stores of full-term newborns. METHODS Cross-sectional study between October 2011 and July 2012 in which hematological parameters were evaluated for newborns in Viçosa, MG, Southeastern Brazil. It involved collecting 7 mL of umbilical cord blood from 144 full-term not underweight newborns. The parameters investigated were complete blood count, serum iron, ferritin and C-reactive protein. The time of umbilical cord clamping was measured using a digital timer without interfering in the procedures of childbirth. The birth data were collected from Live Birth Certificates and other information was obtained from the mother through a questionnaire applied in the first month postpartum. Analysis of multiple linear regression was then used to estimate the influence of biological, obstetrics and socioeconomic factors on the ferritin levels at birth. RESULTS The median ferritin was 130.3 µg/L (n = 129, minimum = 16.4; maximum = 420.5 µg/L), the mean serum iron was 137.9 μg/dL (n = 144, SD = 39.29) and mean hemoglobin was 14.7 g/dL (n = 144, SD = 1.47). The median time of cord clamping was 36 seconds, ranging between 7 and 100. The bivariate analysis detected an association between ferritin levels and color of the child, timing clamping of 60 seconds, type of delivery, the presence of gestational diabetes and per capita family income. In multivariate analysis, the variables per capita income, number of antenatal visits and length at birth accounted for 22.0% of variation in ferritin levels. CONCLUSIONS Iron stores at birth were influenced by biological, obstetric and social characteristics. Tackling anemia should involve creating policies aimed at reducing social inequalities, improving the quality of antenatal care, as well as implementing a criterion of delayed clamping of the umbilical cord within the guidelines of labor. PMID:24789632

Menopause increases the iron storage protein ferritin in skin.

PubMed

Pelle, Edward; Jian, Jinlong; Zhang, Qi; Muizzuddin, Neelam; Yang, Qing; Dai, Jisen; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna; Huang, Xi

2013-01-01

Menstruation and desquamation are important routes for humans to excrete iron. Because menstruation is no longer available in postmenopausal women, in the present study, we examined whether iron accumulates more in postmenopausal skin than in premenopausal skin. Skin biopsy samples were obtained from six pre- and six postmenopausal Caucasian women. Iron levels in the form of ferritin were 42% higher, but vascular endothelial growth factor and total antioxidant capacity were 45% and 34% lower in postmenopausal skin (58.8 ± 1.3 years old) than in premenopausal skin (41.6 ± 1.7 years old), respectively. Moreover, in vitro cultured normal human epidermal keratinocytes had surprisingly high levels of ferritin when compared to immortalized human breast epithelial MCF-10A cells or human liver HepG2 cancer cells. Our results indicate that skin is a cellular repository of iron and that menopause increases iron in skin and, thus, may contribute to the manifestation of accelerated skin aging and photo aging after menopause.

The role of myoglobin degradation in nephrotoxicity after rhabdomyolysis.

PubMed

Zorova, Ljubava D; Pevzner, Irina B; Chupyrkina, Anastasia A; Zorov, Savva D; Silachev, Denis N; Plotnikov, Egor Y; Zorov, Dmitry B

2016-08-25

The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Regulatory effects of ferritin on angiogenesis

PubMed Central

Coffman, Lan G.; Parsonage, Derek; D'Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2009-01-01

Angiogenesis, the synthesis of new blood vessels from preexisting vessels, plays a critical role in normal wound healing and tumor growth. HKa (cleaved high molecular weight kininogen) is an endogenous inhibitor of angiogenesis formed by the cleavage of kininogen on endothelial cells. Ferritin is a protein principally known for its central role in iron storage. Here, we demonstrate that ferritin binds to HKa with high affinity (Kd 13 nM). Further, ferritin antagonizes the antiangiogenic effects of HKa, enhancing the migration, assembly, and survival of HKa-treated endothelial cells. Effects of ferritin were independent of its iron content. Peptide mapping revealed that ferritin binds to a 22-aa subdomain of HKa that is critical to its antiangiogenic activity. In vivo, ferritin opposed HKa's antiangiogenic effects in a human prostate cancer xenograft, restoring tumor-dependent vessel growth. Ferritin-mediated regulation of angiogenesis represents a new angiogenic regulatory pathway, and identifies a new role for ferritin in cell biology. PMID:19126685

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis.

PubMed

Farinati, F; Cardin, R; De Maria, N; Della Libera, G; Marafin, C; Lecis, E; Burra, P; Floreani, A; Cecchetto, A; Naccarato, R

1995-04-01

Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation. We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded. Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends. These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis.

PubMed

Gurrin, Lyle C; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Laurie W; Allen, Katrina J

2008-12-01

There are few longitudinal studies of serum ferritin (SF) and transferrin saturation (TS) levels in individuals homozygous for the C282Y mutation. We characterized the development of elevated iron measures in C282Y homozygotes followed for 12 years. From 31,192 people aged 40-69 years at baseline, we identified 203 C282Y homozygotes (95 males), of whom 116 had SF and fasting TS levels measured at baseline (mean age, 55 years) and 86 were untreated and had iron measures at follow-up (mean, 12 years later). The probabilities of SF at follow-up exceeding clinical thresholds were predicted from baseline SF and TS under a multivariate normal model. For C282Y homozygotes, at baseline, 84% of males and 65% of females had elevated SF and 37% of males and 3% of females had SF >1000 microg/L. For males with SF 300-1000 microg/L at baseline, the predicted probability of progressing to SF >1000 microg/L at follow-up was between 13% and 35% and, for females, between 16% and 22%. For C282Y homozygotes with normal baseline SF, <15% were predicted to develop SF >1000 microg/L if left untreated. The majority of C282Y homozygotes who are likely to develop SF levels sufficient to place them at risk of iron overload-related disease will have done so by mean age 55 years. TS >95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation.

Characterization of a New Ferritin Protein from the Polychaete Chaetopterus Sp.

NASA Astrophysics Data System (ADS)

Hamlish, N.; Deheyn, D.; De Meulenaere, E.

2016-02-01

The marine polychaete worm Chaetopterus sp. secretes a sticky mucus that exhibits a soft blue long-lasting bioluminescence. Iron (both ferrous and ferric) and riboflavin have been found abundant in the mucus and identified as potential cofactors involved in the control of the light production. The Deheyn lab has recently identified a novel ferritin protein (ChF) from fractions of the worm mucus still able to produce bioluminescence after purification by chromatography. Ferritin proteins are ubiquitous across the animal kingdom and exhibit ferroxidase activity, converting ferrous iron into a ferric form that is stably stored and soluble in the ferritin. Here, ferritin may serve as a source of biological iron for the worm through a process of iron acquisition, storage, and release during the light production process. This study addresses these options by assessing foundational data that characterize the ferroxidase activity of recombinant ChF with respect to human heavy-chain ferritin (HuHF). ChF exhibits faster initial rates of iron oxidation than HuHF, but reaches an equilibrium state with detectable levels of ferrous iron still in solution; in contrast this was was not observed for HuHF that oxidizes all available iron in solution. This may support the hypothesis that ChF has a reducing activity. This could involve the release of ferric iron, which may be reduced by flavin molecules found in the mucus; the resulting ferrous iron could then subsequently undergo a Fenton reaction, acting as a source of electrons for long-lasting mucus bioluminescence. Word Count: 240

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorodetsky, R.; Goldfarb, A.; Dagan, I.

Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r .more » 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents.« less

Ferritin Assembly in Enterocytes of Drosophila melanogaster

PubMed Central

Rosas-Arellano, Abraham; Vásquez-Procopio, Johana; Gambis, Alexis; Blowes, Liisa M.; Steller, Hermann; Mollereau, Bertrand; Missirlis, Fanis

2016-01-01

Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH) and Ferritin 2 Light Chain Homolog (Fer2LCH) are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated. PMID:26861293

Iron Oxide Biominerals in Protein Nanocages, the Ferritins: Easing Into Life With Oxygen?

NASA Astrophysics Data System (ADS)

Theil, E. C.

2008-12-01

Organisms with ferritins could represent the progenitors of organisms that successfully made the transition to aerobic life. Ferritins are protein nanocages (8 or 12 nm diameter) that catalyze reactions between Fe(II) and O2 or H2O2 to synthesize ferrihydrite-like biominerals of Fe2O3(H2 O)n; phosphate is sometimes incorporated during mineralization. All groups of organisms, archea, bacteria, plants and animals have ferritins. Catalytic reactions between Fe and O occur in the protein cage with the products moving into the central protein cavity (5 or 8 nm diameter) where mineralization occurs; mineral sizes reach 4500 Fe with more than 7000 O atoms in the large cavities of maxi-ferritins and 500 Fe with more than 800 O atoms in the smaller, mini-ferritins, also called Dps proteins. H2O2 is preferentially used by mini-ferritins in archea and bacteria, contrasting with O2, preferentially used by maxi-ferritins in bacteria plants and animals, and some bacterial mini-ferritins that use either H2O2 or O2, to oxidize Fe(II) during biomineralization. The study of ferritins in contemporary organisms can illuminate mechanisms for oxygen and oxidant responses in changing environments now and in the past. Multiple genes encoding ferritins are often regulated by different environmental stimuli and in multi-cellular organisms, by tissue-specific, differentiation programs. The single celled E.coli has four ferritin genes, encoding three maxi-ferritins, one with a heme cofactor (bacterioferritin), and one mini-ferritin (Dps), expressed at different points in the culture cycle and/or in response to different stresses. Environmental iron, oxygen and peroxide all change the amounts of ferritin. When iron is plentiful, mineralized ferritin accumulates. Ferritin iron is recovered during periods of iron deficiency, apparently by selective unfolding of gated pores in ferritin protein nanocage that expose the mineral to reductants. Gene (DNA) transcription is the genetic target for iron or oxidant. Vertebrates use an additional genetic target, ferritin mRNA translation, to increase the range of sensitivity to iron and oxidant signals. The response of ancient organisms to increased peroxide or oxygen in the evolving terrestrial atmosphere may be recapitulated by the responses of contemporary, pathogenic microorganisms to human defense mechanisms. For example, human hosts sequester iron in ferritin to restrict pathogen growth, while releasing hydrogen peroxide to kill the invading cells. Successful pathogens resist the host by synthesizing iron chelators (siderophores) to compete effectively for iron and synthesizing ferritins that consume H2O2 with Fe(II) during biomineralization. New data on Fe (II) binding stoichiometry, iron biomineralization and recovering iron from ferritin minerals will be presented. The data will be related to environmental/cellular iron deficiency and iron repletion and to the evolution of ferritins that consume O2 during iron biomineralization. References: 1. Liu, X. and Theil, E.C. (2005). Acc. Chem. Res. 38:167-175. 2. Theil, E.C., Liu, X.S., Tosha, T. (2008) Inorg. Chim. Acta. 361: 868-874.

Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity.

PubMed

Bader, D; Blondheim, O; Jonas, R; Admoni, O; Abend-Winger, M; Reich, D; Lanir, A; Tamir, A; Eldar, I; Attias, D

1996-04-01

Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.

Determinants of iron status in Malaysian adolescents from a rural community.

PubMed

Foo, Leng Huat; Khor, Geok Lin; Tee, E-Siong; Dhanaraj, Prabakaran

2004-09-01

Iron deficiency anaemia is the most common micronutrient deficiency worldwide. The prevalence of anaemia in the developing countries is three to four times higher than that in the developed countries. The iron status was assessed in 199 apparently healthy male and female adolescents aged 12-19 years living in a fishing community in Sabah, Malaysia. Data on socio-economic characteristics, lifestyles, anthropometry measurements, iron status, and dietary intake were gathered. Dietary intake of energy, iron, and most nutrients (with the exception of protein and vitamin C) were below the recommended levels for Malaysian adolescents. Three-quarters of the iron was derived from plant foods. The mean haemoglobin value for the male was 13.9 +/- 1.3 g/dl with 9.5% having less than 12 g/dl, while the respective figures for the female were 12.4 +/- 1.6 g/dl and 28.6%. The mean serum ferritin concentrations for male and female adolescents were 21.5 and 15.4 microg/l, respectively; with 25.7% of the males and 49.5% of the females having deficient levels of ferritin. Dietary intake of total energy and iron, and gender were found to be independent determinants of serum ferritin and haemoglobin levels, accounting for over 40% of the variations for each of these iron indicators. In males, but not in females, the intake of dietary protein and iron, and physical activity were also found to be significant determinants of serum ferritin. The age of subjects and household size were significant determinants of haemoglobin levels for male subjects, but not for female subjects. The findings indicate the importance of adequate intake of energy and dietary iron for improving the iron status of adolescents.

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD).

PubMed

Patel, Dhruvan; Trivedi, Chinmay; Khan, Nabeel

2018-03-01

Anemia is the most common complication as well as an extra intestinal manifestation of inflammatory bowel disease (IBD). It is associated with a significant impact on patient's quality of life (QoL); as well it represents a common cause of frequent hospitalization, delay of hospital inpatient discharge and overall increased healthcare burden. In spite of all these, anemia is still often underdiagnosed and undertreated. Our aim in this review is to provide a pathway for physicians to help them achieve early diagnosis as well as timely and appropriate treatment of anemia which in turn would hopefully reduce the prevalence and subsequent complications of this condition among IBD patients. The etiology of anemia among IBD patients is most commonly due to iron deficiency anemia (IDA) followed by anemia of chronic disease. Despite this, more than a third of anemic ulcerative colitis (UC) patients are not tested for IDA and among those tested and diagnosed with IDA, a quarter are not treated with iron replacement therapy. A new algorithm has been validated to predict who will develop moderate to severe anemia at the time of UC diagnosis. While oral iron is effective for the treatment of mild iron deficiency-related anemia, the absorption of iron is influenced by chronic inflammatory states as a consequence of the presence of elevated levels of hepcidin. Also, it is important to recognize that ferritin is elevated in chronic inflammatory states and among patients with active IBD, ferritin levels less than 100 are considered to be diagnostic of iron deficiency. Newer formulations of intra-venous (IV) iron have a good safety profile and can be used for replenishment of iron stores and prevention of iron deficiency in the future. Routine screening for anemia is important among patients with IBD. The cornerstone for the accurate management of anemia in IBD patients lies in accurately diagnosing the type of anemia. All IBD patients with IDA should be considered appropriate for therapy with iron supplementation whereas IV administration of iron is recommended in patients with clinically active IBD, or for patients who are previously intolerant to oral iron, with hemoglobin levels below 10 g/dL, and in patients who need erythropoiesis-stimulating agents (ESAs). As the recurrence of anemia is common after resolution, the monitoring for recurrent anemia is equally important during the course of therapy.

Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening.

PubMed

McLaren, Gordon D; McLaren, Christine E; Adams, Paul C; Barton, James C; Reboussin, David M; Gordeuk, Victor R; Acton, Ronald T; Harris, Emily L; Speechley, Mark R; Sholinsky, Phyliss; Dawkins, Fitzroy W; Snively, Beverly M; Vogt, Thomas M; Eckfeldt, John H

2008-11-01

Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.

Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening

PubMed Central

McLaren, Gordon D; McLaren, Christine E; Adams, Paul C; Barton, James C; Reboussin, David M; Gordeuk, Victor R; Acton, Ronald T; Harris, Emily L; Speechley, Mark R; Sholinsky, Phyliss; Dawkins, Fitzroy W; Snively, Beverly M; Vogt, Thomas M; Eckfeldt, John H

2008-01-01

BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study. PMID:19018338

Metal Sulfide Nanocrystals inside Ferritin with Photovoltaic Applications

NASA Astrophysics Data System (ADS)

Hansen, Kameron; Peterson, J. Ryan; Olsen, Cameron; Hogg, Heather; Colton, John; Watt, Richard; Colton Team

Ferritin is a spherical protein shell used universally by organisms to store iron. Due to a number of ferritin's properties (a conductive shell, ability to be arranged in ordered arrays, and high stability), recent theoretical work has proposed that non-native semiconductor nanocrystals inside ferritin can be used for high-efficiency solar energy conversion. We present research on the synthesis of a variety of these nanocrystals (PbS, CuS, Mo2S, ZnS, and PbSe) inside ferritin's hollow interior and band gap energies of the resulting ferritin-nanocrystal constructs. We also report preliminary solar cell results for dye sensitized solar cells with PbS-ferritin as the dye.

Amino-acid sequence and predicted three-dimensional structure of pea seed (Pisum sativum) ferritin.

PubMed Central

Lobreaux, S; Yewdall, S J; Briat, J F; Harrison, P M

1992-01-01

The iron storage protein, ferritin, is widely distributed in the living kingdom. Here the complete cDNA and derived amino-acid sequence of pea seed ferritin are described, together with its predicted secondary structure, namely a four-helix-bundle fold similar to those of mammalian ferritins, with a fifth short helix at the C-terminus. An N-terminal extension of 71 residues contains a transit peptide (first 47 residues) responsible for plastid targetting as in other plant ferritins, and this is cleaved before assembly. The second part of the extension (24 residues) belongs to the mature subunit; it is cleaved during germination. The amino-acid sequence of pea seed ferritin is aligned with those of other ferritins (49% amino-acid identity with H-chains and 40% with L-chains of human liver ferritin in the aligned region). A three-dimensional model has been constructed by fitting the aligned sequence to the coordinates of human H-chains, with appropriate modifications. A folded conformation with an 11-residue helix is predicted for the N-terminal extension. As in mammalian ferritins, 24 subunits assemble into a hollow shell. In pea seed ferritin, its N-terminal extension is exposed on the outside surface of the shell. Within each pea subunit is a ferroxidase centre resembling those of human ferritin H-chains except for a replacement of Glu-62 by His. The channel at the 4-fold-symmetry axes defined by E-helices, is predicted to be hydrophilic in plant ferritins, whereas it is hydrophobic in mammalian ferritins. Images Fig. 3. Fig. 5. Fig. 6. PMID:1472006

Distinguishing ferritin from apoferritin using magnetic force microscopy

NASA Astrophysics Data System (ADS)

Nocera, Tanya M.; Zeng, Yuzhi; Agarwal, Gunjan

2014-11-01

Estimating the amount of iron-replete ferritin versus iron-deficient apoferritin proteins is important in biomedical and nanotechnology applications. This work introduces a simple and novel approach to quantify ferritin by using magnetic force microscopy (MFM). We demonstrate how high magnetic moment probes enhance the magnitude of MFM signal, thus enabling accurate quantitative estimation of ferritin content in ferritin/apoferritin mixtures in vitro. We envisage MFM could be adapted to accurately determine ferritin content in protein mixtures or in small aliquots of clinical samples.

Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study.

PubMed

Maldonado-Araque, Cristina; Valdés, Sergio; Lago-Sampedro, Ana; Lillo-Muñoz, Juan Antonio; Garcia-Fuentes, Eduardo; Perez-Valero, Vidal; Gutierrez-Repiso, Carolina; Goday, Albert; Urrutia, Ines; Peláez, Laura; Calle-Pascual, Alfonso; Castaño, Luis; Castell, Contxa; Delgado, Elias; Menendez, Edelmiro; Franch-Nadal, Josep; Gaztambide, Sonia; Girbés, Joan; Ortega, Emilio; Vendrell, Joan; Chacón, Matilde R; Chaves, Felipe J; Soriguer, Federico; Rojo-Martínez, Gemma

2018-04-26

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.

Biologically Derived Nanoparticle Arrays via a Site-Specific Reconstitution of Ferritin and their Electrochemistry

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; King, Glen C.; Elliott, James R.; Chu, Sang-Hyon; Park, Yeonjoon; Watt, Gerald D.

2004-01-01

Nanoparticle arrays biologically derived from an electrochemically-controlled site-specific biomineralization were fabricated on a gold substrate through the immobilization process of biomolecules. The work reported herein includes the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritins with different inorganic cores, the fabrication of self-assembled arrays with the immobilized ferritin, and the electrochemical characterization of various core materials. Protein immobilization on the substrate is achieved by anchoring ferritins with dithiobis-N-succinimidyl propionate (DTSP). A reconstitution process of electrochemical site-specific biomineralization with a protein cage loads ferritins with different core materials such as Pt, Co, Mn, and Ni. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. The nano-sized metalcored ferritins on a gold substrate displayed a good electrochemical activity for the electron transport and storage, which is suitable for bioelectronics applications such as biofuel cell, bionanobattery, biosensors, etc. Keywords: Ferritin, immobilization, site-specific reconstitution, biomineralization, and bioelectronics

FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia.

PubMed

Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Nolen, Jacqueline G; Roger, Simon D

2014-11-01

The optimal iron therapy regimen in patients with non-dialysis-dependent chronic kidney disease (CKD) is unknown. Ferinject® assessment in patients with Iron deficiency anaemia and Non-Dialysis-dependent Chronic Kidney Disease (FIND-CKD) was a 56-week, open-label, multicentre, prospective and randomized study of 626 patients with non-dialysis-dependent CKD, anaemia and iron deficiency not receiving erythropoiesis-stimulating agents (ESAs). Patients were randomized (1:1:2) to intravenous (IV) ferric carboxymaltose (FCM), targeting a higher (400-600 µg/L) or lower (100-200 µg/L) ferritin or oral iron therapy. The primary end point was time to initiation of other anaemia management (ESA, other iron therapy or blood transfusion) or haemoglobin (Hb) trigger of two consecutive values <10 g/dL during Weeks 8-52. The primary end point occurred in 36 patients (23.5%), 49 patients (32.2%) and 98 patients (31.8%) in the high-ferritin FCM, low-ferritin FCM and oral iron groups, respectively [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.44-0.95; P = 0.026 for high-ferritin FCM versus oral iron]. The increase in Hb was greater with high-ferritin FCM versus oral iron (P = 0.014) and a greater proportion of patients achieved an Hb increase ≥1 g/dL with high-ferritin FCM versus oral iron (HR: 2.04; 95% CI: 1.52-2.72; P < 0.001). Rates of adverse events and serious adverse events were similar in all groups. Compared with oral iron, IV FCM targeting a ferritin of 400-600 µg/L quickly reached and maintained Hb level, and delayed and/or reduced the need for other anaemia management including ESAs. Within the limitations of this trial, no renal toxicity was observed, with no difference in cardiovascular or infectious events. NCT00994318. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

Electrochemical studies of biocatalytic anode of sulfonated graphene/ferritin/glucose oxidase layer-by-layer biocomposite films for mediated electron transfer.

PubMed

Inamuddin; Haque, Sufia Ul; Naushad, Mu

2016-06-01

In this study, a bioanode was developed by using layer-by-layer (LBL) assembly of sulfonated graphene (SG)/ferritin (Frt)/glucose oxidase (GOx). The SG/Frt biocomposite was used as an electron transfer elevator and mediator, respectively. Glucose oxidase (GOx) from Aspergillus niger was applied as a glucose oxidation biocatalyst. The electrocatalytic oxidation of glucose using GOx modified electrode increases with an increase in the concentration of glucose in the range of 10-50mM. The electrochemical measurements of the electrode was carried out by using cyclic voltammetry (CV) at different scan rates (20-100mVs(-1)) in 30mM of glucose solution prepared in 0.3M potassium ferrocyanide (K4Fe(CN)6) and linear sweep voltammetry (LSV). A saturation current density of 50±2mAcm(-2) at a scan rate of 100mVs(-1) for the oxidation of 30Mm glucose is achieved. Copyright © 2016 Elsevier Inc. All rights reserved.

A long-term high-fat diet changes iron distribution in the body, increasing iron accumulation specifically in the mouse spleen.

PubMed

Yamano, Noriko; Ikeda, Yasumasa; Sakama, Minoru; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Miyamoto, Licht; Tomita, Shuhei; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-01-01

Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD.

Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey.

PubMed

Li, Jiang; Xiao, Cheng; Yang, Hui; Zhou, Yun; Wang, Rui; Cao, Yongtong

2017-12-09

Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor (sTfR)/log ferritin index were significant in different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes

PubMed Central

Artz, Andrew S.; Logan, Brent; Zhu, Xiaochun; Akpek, Gorgun; Bufarull, Rodrigo Martino; Gupta, Vikas; Lazarus, Hillard M.; Litzow, Mark; Loren, Alison; Majhail, Navneet S.; Maziarz, Richard T.; McCarthy, Philip; Popat, Uday; Saber, Wael; Spellman, Stephen; Ringden, Olle; Wickrema, Amittha; Pasquini, Marcelo C.; Cooke, Kenneth R.

2016-01-01

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. PMID:27662010

CHANGES IN FERRITIN H- AND L-CHAINS IN CANINE LENSES WITH AGE-RELATED NUCLEAR CATARACT

PubMed Central

Goralska, Małgorzata; Nagar, Steven; Colitz, Carmen M.H.; Fleisher, Lloyd N.; McGahan, M. Christine

2014-01-01

PURPOSE To determine potential differences in the characteristics of the iron storage protein, ferritin and its heavy (H) and light (L) subunits in fiber cells from cataractous and normal lenses of older dogs. METHODS Lens fiber cell homogenates were analyzed by SDS-PAGE and ferritin chains were immunodetected with ferritin chain-specific antibodies. Ferritin concentration was measured by ELISA. Immunohistochemistry was used to localize ferritin chains in lens sections. RESULTS The concentration of assembled ferritin was comparable in normal and cataractous lenses of similarly aged dogs. The ferritin L-chain detected in both lens types was modified and was about 11 kDa larger (30 kDa) than standard L-chain (19 kDa) purified from canine liver. The H-chain identified in cataractous fiber cells (29 kDa) differed from 21 kDa standard canine H-chain and from 12 kDa modified H-chain present in fiber cells of normal lenses. Histologic analysis revealed that the H-chain was distributed differently throughout cataractous lenses when compared to normal lenses. There was also a difference in subunit makeup of assembled ferritin between the two lens types. Ferritin from cataractous lenses contained more H-chain and bound 11-fold more iron than ferritin from normal lenses. CONCLUSIONS There are significant differences in the characteristics of ferritin H-chain and its distribution in canine cataractous lenses as compared to normal lenses. The higher content of H-chain in assembled ferritin allows this molecule to sequester more iron. In addition the accumulation of H-chain in deeper fiber layers of the lens may be part of a defense mechanism by which the cataractous lens limits iron-catalyzed oxidative damage. PMID:18708625

The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cornell, Thomas A.; Srivastava, Yogesh; Jauch, Ralf

Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understandmore » the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.« less

Electrostatic placement of single ferritin molecules

NASA Astrophysics Data System (ADS)

Kumagai, Shinya; Yoshii, Shigeo; Yamada, Kiyohito; Matsukawa, Nozomu; Fujiwara, Isamu; Iwahori, Kenji; Yamashita, Ichiro

2006-04-01

We electrostatically placed a single ferritin molecule on a nanometric 3-aminopropyltriethoxysilane (APTES) pattern that was on an oxidized Si substrate. The numerical analysis of the total interaction free energy for ferritin predicted that a quadrilateral array of 15nm diameter APTES nanodisks placed at intervals of 100nm would accommodate a single molecule of ferritin in each disk under a Debye length of 14nm. The experiments we conducted conformed to theoretical predictions and we successfully placed a single ferritin molecule on each ATPES disk without ferritin adsorbing on the SiO2 substrate surface.

Surface charge dependent separation of modified and hybrid ferritin in native PAGE: Impact of lysine 104.

PubMed

Subhadarshanee, Biswamaitree; Mohanty, Abhinav; Jagdev, Manas Kumar; Vasudevan, Dileep; Behera, Rabindra K

2017-10-01

Preparation of modified and hybrid ferritin provides a great opportunity to understand the mechanisms of iron loading/unloading, protein self-assembly, size constrained nanomaterial synthesis and targeted drug delivery. However, the large size (M.W.=490kDa) has been limiting the separation of different modified and/or hybrid ferritin nanocages from each other in their intact assembled form and further characterization. Native polyacrylamide gel electrophoresis (PAGE) separates proteins on the basis of both charge and mass, while maintaining their overall native structure and activity. Altering surface charge distribution by substitution of amino acid residues located at the external surface of ferritin (K104E & D40A) affected the migration rate in native PAGE while internal modification had little effect. Crystal structures confirmed that ferritin nanocages made up of subunits with single amino acid substitutions retain the overall structure of ferritin nanocage. Taking advantage of K104E migration behavior, formation of hybrid ferritins with subunits of wild type (WT) and K104E were confirmed and separated in native PAGE. Cage integrity and iron loading ability (ferritin activity) were also tested. The migration pattern of hybrid ferritins in native PAGE depends on the subunit ratio (WT: K104E) in the ferritin cage. Our work shows that native PAGE can be exploited in nanobiotechnology, by analyzing modifications of large proteins like ferritin. Native PAGE, a simple, straight-forward technique, can be used to analyze small modification (by altering external surface charge) in large proteins like ferritin, without disintegrating its self-assembled nanocage structure. In doing so, native PAGE can complement the information obtained from mass spectrometry. The confirmation and separation of modified and hybrid ferritin protein nanocages in native PAGE, opens up various prospects of bio-conjugation, which can be useful in targeted drug delivery, nanobiotechnology and in understanding nature's idea of synthesizing hybrid ferritins in different human tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in erythropoietin levels during space flight or space flight simulation

NASA Technical Reports Server (NTRS)

Dunn, C. D. R.; Hen, J. P.

1980-01-01

Two hundred and seventy samples from 24 subjects involved in 3 bedrest studies and from 3 subjects involved in Spacelab Mission Development Test 3 were assayed for erythropoietin (Ep), in an in vitro fetal mouse liver cell assay, and for ferritin using a commercially available immunoradiometric assay kit. No trends or significant changes in serum Ep were observed. Serum ferritin concentrations tended to increases slightly during the 'missions', reflecting a redirection of iron from the suppressed erythron into iron stores.

The Relationship Between Iron and Nitrogen Fixation in Trichodesmium spp.

DTIC Science & Technology

2009-06-01

in the individual Fe stress responses in the two clades, overall we observed similar trends in the Fe level associated with a significant increase in...bacterioferritin protein (Andrews et al., 1993; Keren et al., 2004) and a ferritin -like DPS protein (Michel et al., 2003; Castruita et al., 2006...A B A 21384 112/143 7120 x B A B 75639 111/143 11 - Ferritin -like D PS protein 180 Y P_723752 8501 ZP_00514985 115/169 7120 B A B 75507

Electrochemical Reconstitution of Biomolecules for Applications as Electrocatalysts for the Bionanofuel Cell

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; King, Glen C.; Watt, Gerald D.; Chu, Sang-Hyon; Park, Yeonjoon; Thibeault, Sheila

2004-01-01

Platinum-cored ferritins were synthesized as electrocatalysts by electrochemical biomineralization of immobilized apoferritin with platinum. The platinum cored ferritin was fabricated by exposing the immobilized apoferritin to platinum ions at a reduction potential. On the platinum-cored ferritin, oxygen is reduced to water with four protons and four electrons generated from the anode. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. This results in a smaller catalyst loading of the electrodes for fuel cells or other electrochemical devices. In addition, the catalytic activity of the ferritin-stabilized platinum nanoparticles is enhanced by the large surface area and particle size phenomena. The work presented herein details the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritin with different inorganic cores, and the fabrication of self-assembled 2-D arrays with thiolated ferritin.

Two Kinds of Ferritin Protect Ixodid Ticks from Iron Overload and Consequent Oxidative Stress

PubMed Central

Galay, Remil Linggatong; Umemiya-Shirafuji, Rika; Bacolod, Eugene T.; Maeda, Hiroki; Kusakisako, Kodai; Koyama, Jiro; Tsuji, Naotoshi; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2014-01-01

Ticks are obligate hematophagous parasites that have successfully developed counteractive means against their hosts' immune and hemostatic mechanisms, but their ability to cope with potentially toxic molecules in the blood remains unclear. Iron is important in various physiological processes but can be toxic to living cells when in excess. We previously reported that the hard tick Haemaphysalis longicornis has an intracellular (HlFER1) and a secretory (HlFER2) ferritin, and both are crucial in successful blood feeding and reproduction. Ferritin gene silencing by RNA interference caused reduced feeding capacity, low body weight and high mortality after blood meal, decreased fecundity and morphological abnormalities in the midgut cells. Similar findings were also previously reported after silencing of ferritin genes in another hard tick, Ixodes ricinus. Here we demonstrated the role of ferritin in protecting the hard ticks from oxidative stress. Evaluation of oxidative stress in Hlfer-silenced ticks was performed after blood feeding or injection of ferric ammonium citrate (FAC) through detection of the lipid peroxidation product, malondialdehyde (MDA) and protein oxidation product, protein carbonyl. FAC injection in Hlfer-silenced ticks resulted in high mortality. Higher levels of MDA and protein carbonyl were detected in Hlfer-silenced ticks compared to Luciferase-injected (control) ticks both after blood feeding and FAC injection. Ferric iron accumulation demonstrated by increased staining on native HlFER was observed from 72 h after iron injection in both the whole tick and the midgut. Furthermore, weak iron staining was observed after Hlfer knockdown. Taken together, these results show that tick ferritins are crucial antioxidant molecules that protect the hard tick from iron-mediated oxidative stress during blood feeding. PMID:24594832

Serum ferritin: Past, present and future.

PubMed

Wang, Wei; Knovich, Mary Ann; Coffman, Lan G; Torti, Frank M; Torti, Suzy V

2010-08-01

Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. Copyright 2010 Elsevier B.V. All rights reserved.

The clearance of /sup 131/I-human plasma ferritin in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Worwood, M.; Cragg, S.J.; Williams, A.M.

1982-10-01

Ferritin was purified 33,000-fold from the plasma of patients with idiopathic hemochromatosis. The plasma ferritin was labeled with /sup 131/I and injected into 2 normal men. Clearance was found to be relatively slow, with 50% /sup 131/I-ferritin remaining in the plasma at 27-30 hr. The fraction of plasma ferritin that bound to concanavalin-A was found to be cleared more slowly than the nonbinding fraction. These findings confirm our previous suggestion that glycosylation is a major factor prolonging the survival of ferritin in the plasma, but differ from the results of earlier studies in experimental animals and preterm infants, which indicatedmore » very rapid plasma ferritin turnover.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thiruselvam, Viswanathan; Sivaraman, Padavattan; Kumarevel, Thirumananseri, E-mail: kumarevel.thirumananseri@riken.jp

Highlights: • Crystal structure of ferritin was determined. • Endogenously expressed iron’s were identified. • Binuclear iron sites were observed at A and B active sites. - Abstract: Ferritin is an iron regulatory protein. It is responsible for storage and detoxification of excess iron thereby it regulates iron level in the body. Here we report the crystal structure of ferritin with two endogenously expressed Fe atoms binding in both the sites. The protein was purified and characterized by MALDI-TOF and N-terminal amino acid sequencing. The crystal belongs to I4 space group and it diffracted up to 2.5 Å. The structuralmore » analysis suggested that it crystallizes as hexamer and confirmed that it happened to be the first report of endogenously expressed Fe ions incorporated in both the A and B sites, situated in between the helices.« less

Zinc transport by respiratory epithelial cells and interaction with iron homeostasis.

PubMed

Deng, Zhongping; Dailey, Lisa A; Soukup, Joleen; Stonehuerner, Jacqueline; Richards, Judy D; Callaghan, Kimberly D; Yang, Funmei; Ghio, Andrew J

2009-10-01

Despite recurrent exposure to zinc through inhalation of ambient air pollution particles, relatively little information is known about the homeostasis of this metal in respiratory epithelial cells. We describe zinc uptake and release by respiratory epithelial cells and test the postulate that Zn(2+) transport interacts with iron homeostasis in these same cells. Zn(2+) uptake after 4 and 8 h of exposure to zinc sulfate was concentration- and time-dependent. A majority of Zn(2+) release occurred in the 4 h immediately following cell exposure to ZnSO(4). Regarding metal importers, mRNA for Zip1 and Zip2 showed no change after respiratory epithelial cell exposure to zinc while mRNA for divalent metal transporter (DMT)1 increased. Western blot assay for DMT1 protein supported an elevated expression of this transport protein following zinc exposure. RT-PCR confirmed mRNA for the metal exporters ZnT1 and ZnT4 with the former increasing after ZnSO(4). Cell concentrations of ferritin increased with zinc exposure while oxidative stress, measured as lipid peroxides, was decreased supporting an anti-oxidant function for Zn(2+). Increased DMT1 expression, following pre-incubations of respiratory epithelial cells with TNF-alpha, IFN-gamma, and endotoxin, was associated with significantly decreased intracellular zinc transport. Finally, incubations of respiratory epithelial cells with both zinc sulfate and ferric ammonium citrate resulted in elevated intracellular concentrations of both metals. We conclude that exposure to zinc increases iron uptake by respiratory epithelial cells. Elevations in cell iron can possibly affect an increased expression of DMT1 and ferritin which function to diminish oxidative stress. Comparable to other metal exposures, changes in iron homeostasis may contribute to the biological effects of zinc in specific cells and tissues.

Malignancy and chemotherapy induced haemophagocytic lymphohistiocytosis in children and adolescents-a single centre experience of 20 years.

PubMed

Strenger, Volker; Merth, Gerald; Lackner, Herwig; Aberle, Stephan W; Kessler, Harald H; Seidel, Markus G; Schwinger, Wolfgang; Sperl, Daniela; Sovinz, Petra; Karastaneva, Anna; Benesch, Martin; Urban, Christian

2018-06-01

Haemophagocytic lymphohistiocytosis (HLH) is a possibly life-threatening syndrome of immune dysregulation and can be divided into primary (hereditary) and secondary forms (including malignancy-associated HLH (M-HLH)). We retrospectively analysed epidemiological, clinical, virological and laboratory data from patients with M-HLH treated at our department between 1995 and 2014. Out of 1.706 haemato-/oncologic patients treated at our department between 1995 and 2014, we identified 22 (1.29%) patients with secondary HLH (1.3-18.0, median 10.1 years; malignancy induced n = 2; chemotherapy induced n = 20). Patients with acute myeloblastic leukaemia (AML) developed HLH significantly more often than patients with acute lymphoblastic leukaemia (ALL) (10/55, 18.2% vs. 6/148, 4.1%, p = 0.0021). As possible viral triggers, we detected BKV (53.8% of the tested patients), HHV-6 (33.3%), EBV (27.8%), CMV (23.5%), ADV (16.7%) and PVB19 (16.7%) significantly more frequently than in haemato-/oncologic patients without HLH. Despite lacking evidence of concurrent bacterial infection, C-reactive protein (CRP) and procalcitotnin (PCT) were elevated in 94.7 and 77.7% of the patients, respectively. Ferritin and sIL2R were markedly elevated in all patients. HLH-associated mortality significantly (p = 0.0276) decreased from 66.6% (1995-2004) to 6.25% (2005-2014), suggesting improved diagnostic and therapeutic management. Awareness of HLH is important, and fever refractory to antibiotics should prompt to consider this diagnosis. Elevated ferritin and sIL2R seem to be good markers, while inflammatory markers like CRP and PCT are not useful to discriminate viral triggered HLH from severe bacterial infection. Re-/activation of several viruses may play a role as possible trigger.

Ferritin accumulation and degradation in different organs of pea (Pisum sativum) during development.

PubMed Central

Lobreaux, S; Briat, J F

1991-01-01

Iron concentration and ferritin distribution have been determined in different organs of pea (Pisum sativum) during development under conditions of continuous iron supply from hydroponic cultures. No ferritin was detected in total protein extracts from roots or leaves. However, a transient iron accumulation in the roots, which corresponds to an increase in iron uptake, was observed when young fruits started to develop. Ferritin was detectable in total protein extracts of flowers and pods, and it accumulated in seeds. In seeds, the same relative amount of ferritin was detected in cotyledons and in the embryo axis. In cotyledons, ferritin and iron concentration decrease progressively during the first week of germination. Ferritin in the embryo axis was processed, and disappeared, during germination, within the first 4 days of radicle and epicotyl growth. This degradation of ferritin in vivo was marked by a shortening of a 28 kDa subunit, giving 26.5 and 25 kDa polypeptides, reminiscent of the radical damage occurring in pea seed ferritin during iron exchange in vitro [Laulhere, Laboure & Briat (1989) J. Biol. Chem. 264, 3629-3635]. Developmental control of iron concentration and ferritin distribution in different organs of pea is discussed. Images Fig. 4. Fig. 6. Fig. 7. PMID:2006922

Ferritin: the protein nanocage and iron biomineral in health and in disease.

PubMed

Theil, Elizabeth C

2013-11-04

At the center of iron and oxidant metabolism is the ferritin superfamily: protein cages with Fe(2+) ion channels and two catalytic Fe/O redox centers that initiate the formation of caged Fe2O3·H2O. Ferritin nanominerals, initiated within the protein cage, grow inside the cage cavity (5 or 8 nm in diameter). Ferritins contribute to normal iron flow, maintenance of iron concentrates for iron cofactor syntheses, sequestration of iron from invading pathogens, oxidant protection, oxidative stress recovery, and, in diseases where iron accumulates excessively, iron chelation strategies. In eukaryotic ferritins, biomineral order/crystallinity is influenced by nucleation channels between active sites and the mineral growth cavity. Animal ferritin cages contain, uniquely, mixtures of catalytically active (H) and inactive (L) polypeptide subunits with varied rates of Fe(2+)/O2 catalysis and mineral crystallinity. The relatively low mineral order in liver ferritin, for example, coincides with a high percentage of L subunits and, thus, a low percentage of catalytic sites and nucleation channels. Low mineral order facilitates rapid iron turnover and the physiological role of liver ferritin as a general iron source for other tissues. Here, current concepts of ferritin structure/function/genetic regulation are discussed and related to possible therapeutic targets such as mini-ferritin/Dps protein active sites (selective pathogen inhibition in infection), nanocage pores (iron chelation in therapeutic hypertransfusion), mRNA noncoding, IRE riboregulator (normalizing the ferritin iron content after therapeutic hypertransfusion), and protein nanovessels to deliver medicinal or sensor cargo.

Serum Ferritin: Past, Present and Future

PubMed Central

Wang, Wei; Knovich, Mary Ann; Coffman, Lan G.; Torti, Frank M.; Torti, Suzy V.

2010-01-01

Background Serum ferritin was discovered in the 1930’s, and was developed as a clinical test in the 1970’s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. Scope of Review In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Major Conclusions Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. General Significance Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. PMID:20304033

Coordinating subdomains of ferritin protein cages with catalysis and biomineralization viewed from the C4 cage axes.

PubMed

Theil, Elizabeth C; Turano, Paola; Ghini, Veronica; Allegrozzi, Marco; Bernacchioni, Caterina

2014-06-01

Integrated ferritin protein cage function is the reversible synthesis of protein-caged, solid Fe2O3·H2O minerals from Fe(2+) for metabolic iron concentrates and oxidant protection; biomineral order differs in different ferritin proteins. The conserved 432 geometric symmetry of ferritin protein cages parallels the subunit dimer, trimer, and tetramer interfaces, and coincides with function at several cage axes. Multiple subdomains distributed in the self-assembling ferritin nanocages have functional relationships to cage symmetry such as Fe(2+) transport though ion channels (threefold symmetry), biomineral nucleation/order (fourfold symmetry), and mineral dissolution (threefold symmetry) studied in ferritin variants. On the basis of the effects of natural or synthetic subunit dimer cross-links, cage subunit dimers (twofold symmetry) influence iron oxidation and mineral dissolution. 2Fe(2+)/O2 catalysis in ferritin occurs in single subunits, but with cooperativity (n = 3) that is possibly related to the structure/function of the ion channels, which are constructed from segments of three subunits. Here, we study 2Fe(2+) + O2 protein catalysis (diferric peroxo formation) and dissolution of ferritin Fe2O3·H2O biominerals in variants with altered subunit interfaces for trimers (ion channels), E130I, and external dimer surfaces (E88A) as controls, and altered tetramer subunit interfaces (L165I and H169F). The results extend observations on the functional importance of structure at ferritin protein twofold and threefold cage axes to show function at ferritin fourfold cage axes. Here, conserved amino acids facilitate dissolution of ferritin-protein-caged iron biominerals. Biological and nanotechnological uses of ferritin protein cage fourfold symmetry and solid-state mineral properties remain largely unexplored.

Coordinating Subdomains of Ferritin Protein Cages with Catalysis and Biomineralization viewed from the C4 Cage Axes

PubMed Central

Theil, Elizabeth C.; Turano, Paola; Ghini, Veronica; Allegrozzi, Marco; Bernacchioni, Caterina

2014-01-01

Integrated ferritin protein cage function is the reversible synthesis of protein-caged, solid Fe2O3•H2O minerals from Fe2+, for metabolic iron concentrates and oxidant protection; biomineral order varies in different ferritin proteins. The conserved 4, 3, 2 geometric symmetry of ferritin protein cages, parallels subunit dimer, trimer and tetramer interfaces, and coincides with function at several cage axes. Multiple subdomains distributed in the self- assembling ferritin nanocages have functional relationships to cage symmetry such as Fe2+ transport though ion channels (3-fold symmetry), biomineral nucleation/order (4-fold symmetry) and mineral dissolution (3-fold symmetry) studied in ferritin variants. Cage subunit dimers (2-fold symmetry) influence iron oxidation and mineral dissolution, based on effects of natural or synthetic subunit dimer crosslinks. 2Fe2+/O2 catalysis in ferritin occurs in single subunits, but with cooperativity (n=3) that is possibly related to the structure/function of the ion channels, which are constructed from segments of 3 subunits. Here, we study 2Fe2+ + O2 protein catalysis (diferric peroxo formation) and dissolution of ferritin Fe2O3•H2O biominerals in variants with altered subunit interfaces for trimers (ion channels), E130I, and external dimer surfaces (E88A) as controls, and altered tetramer subunit interfaces (L165I and H169F). The results extend observations on the functional importance of structure at ferritin protein 2-fold and 3-fold cage axes to show function at ferritin 4-fold cage axes. Here, conserved amino acids facilitate dissolution of ferritin protein-caged iron biominerals. Biological and nanotechnological uses of ferritin protein cage 4-fold symmetry and solid state mineral properties remain largely unexplored. PMID:24504941

Endosperm-specific co-expression of recombinant soybean ferritin and Aspergillus phytase in maize results in significant increases in the levels of bioavailable iron.

PubMed

Drakakaki, Georgia; Marcel, Sylvain; Glahn, Raymond P; Lund, Elizabeth K; Pariagh, Sandra; Fischer, Rainer; Christou, Paul; Stoger, Eva

2005-12-01

We have generated transgenic maize plants expressing Aspergillus phytase either alone or in combination with the iron-binding protein ferritin. Our aim was to produce grains with increased amounts of bioavailable iron in the endosperm. Maize seeds expressing recombinant phytase showed enzymatic activities of up to 3 IU per gram of seed. In flour paste prepared from these seeds, up to 95% of the endogenous phytic acid was degraded, with a concomitant increase in the amount of available phosphate. In seeds expressing ferritin in addition to phytase, the total iron content was significantly increased. To evaluate the impact of the recombinant proteins on iron absorption in the human gut, we used an in vitro digestion/Caco-2 cell model. We found that phytase in the maize seeds was associated with increased cellular iron uptake, and that the rate of iron uptake correlated with the level of phytase expression regardless of the total iron content of the seeds. We also investigated iron bioavailability under more complex meal conditions by adding ascorbic acid, which promotes iron uptake, to all samples. This resulted in a further increase in iron absorption, but the effects of phytase and ascorbic acid were not additive. We conclude that the expression of recombinant ferritin and phytase could help to increase iron availability and enhance the absorption of iron, particularly in cereal-based diets that lack other nutritional components.

First comparative characterization of three distinct ferritin subunits from a teleost: Evidence for immune-responsive mRNA expression and iron depriving activity of seahorse (Hippocampus abdominalis) ferritins.

PubMed

Oh, Minyoung; Umasuthan, Navaneethaiyer; Elvitigala, Don Anushka Sandaruwan; Wan, Qiang; Jo, Eunyoung; Ko, Jiyeon; Noh, Gyeong Eon; Shin, Sangok; Rho, Sum; Lee, Jehee

2016-02-01

Ferritins play an indispensable role in iron homeostasis through their iron-withholding function in living beings. In the current study, cDNA sequences of three distinct ferritin subunits, including a ferritin H, a ferritin M, and a ferritin L, were identified from big belly seahorse, Hippocampus abdominalis, and molecularly characterized. Complete coding sequences (CDS) of seahorse ferritin H (HaFerH), ferritin M (HaFerM), and ferritin L (HaFerL) subunits were comprised of 531, 528, and 522 base pairs (bp), respectively, which encode polypeptides of 177, 176, and 174 amino acids, respectively, with molecular masses of ∼20-21 kDa. Our in silico analyses demonstrate that these three ferritin subunits exhibit the typical characteristics of ferritin superfamily members including iron regulatory elements, domain signatures, and reactive centers. The coding sequences of HaFerH, M, and L were cloned and the corresponding proteins were overexpressed in a bacterial system. Recombinantly expressed HaFer proteins demonstrated detectable in vivo iron sequestrating (ferroxidase) activity, consistent with their putative iron binding capability. Quantification of the basal expression of these three HaFer sequences in selected tissues demonstrated a gene-specific ubiquitous spatial distribution pattern, with abundance of mRNA in HaFerM in the liver and predominant expression of HaFerH and HaFerL in blood. Interestingly, the basal expression of all three ferritin genes was found to be significantly modulated against pathogenic stress mounted by lipopolysaccharides (LPS), poly I:C, Streptococcus iniae, and Edwardsiella tarda. Collectively, our findings suggest that the three HaFer subunits may be involved in iron (II) homeostasis in big belly seahorse and that they are important in its host defense mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5340 Ferritin immunological test system. (a) Identification. A ferritin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340...

Electrochemically Controlled Reconstitution of Immobilized Ferritins for Bioelectronic Applications

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; Chu, Sang-Hong; King, Glen C.; Watt, Gerald D.

2007-01-01

Site-specific reconstituted nanoparticles were fabricated via electrochemically-controlled biomineralization through the immobilization of biomolecules. The work reported herein includes the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritins with different inorganic cores, and the electrocatalytic reduction of oxygen on the reconstituted Pt-cored ferritins. Protein immobilization on the substrate is achieved by anchoring ferritins with dithiobis-N-succinimidyl propionate (DTSP). A reconstitution process of site-specific electrochemical biomineralization with a protein cage loads ferritins with different core materials. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. This first demonstration of electrochemically controlled site-specific reconstitution of biomolecules provides a new tool for biomineralization and opens the way to produce the bio-templated nanoparticles by electrochemical control. The nanosized platinum-cored ferritins on gold displayed good catalytic activity for the electrochemical reduction of oxygen, which is applicable to biofuel cell applications. This results in a smaller catalyst loading on the electrodes for fuel cells or other bioelectronic devices.

Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass

NASA Technical Reports Server (NTRS)

Rice, L.; Ruiz, W.; Driscoll, T.; Whitley, C. E.; Tapia, R.; Hachey, D. L.; Gonzales, G. F.; Alfrey, C. P.

2001-01-01

BACKGROUND: Studies of space-flight anemia have uncovered a physiologic process, neocytolysis, by which young red blood cells are selectively hemolyzed, allowing rapid adaptation when red cell mass is excessive for a new environment. OBJECTIVES: 1) To confirm that neocytolysis occurs in another situation of acute plethora-when high-altitude dwellers with polycythemia descend to sea level; and 2) to clarify the role of erythropoietin suppression. DESIGN: Prospective observational and interventional study. SETTING: Cerro de Pasco (4380 m) and Lima (sea level), Peru. PARTICIPANTS: Nine volunteers with polycythemia. INTERVENTIONS: Volunteers were transported to sea level; three received low-dose erythropoietin. MEASUREMENTS: Changes in red cell mass, hematocrit, hemoglobin concentration, reticulocyte count, ferritin level, serum erythropoietin, and enrichment of administered(13)C in heme. RESULTS: In six participants, red cell mass decreased by 7% to 10% within a few days of descent; this decrease was mirrored by a rapid increase in serum ferritin level. Reticulocyte production did not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in circulating heme were consistent with hemolysis of young cells. Erythropoietin was suppressed, and administration of exogenous erythropoietin prevented the changes in red cell mass, serum ferritin level, and(13)C-heme. CONCLUSIONS: Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.

Multilayer Ferritin Array for Bionanobattery

NASA Technical Reports Server (NTRS)

Chu, Sang-Hyon (Inventor); Choi, Sang H. (Inventor); Kim, Jae-Woo (Inventor); Lillehei, Peter T. (Inventor); Park, Yeonjoon (Inventor); King, Glen C. (Inventor); Elliott, James R., Jr. (Inventor)

2009-01-01

A thin-film electrode for a bio-nanobattery is produced by consecutively depositing arrays of a ferritin protein on a substrate, employing a spin self-assembly procedure. By this procedure, a first ferritin layer is first formed on the substrate, followed by building a second, oppositely-charged ferritin layer on the top of the first ferritin layer to form a bilayer structure. Oppositely-charged ferritin layers are subsequently deposited on top of each other until a desired number of bilayer structures is produced. An ordered, uniform, stable and robust, thin-film electrode material of enhanced packing density is presented, which provides optimal charge density for the bio-nanobattery.

Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation after Traumatic Brain Injury in Children

PubMed Central

Newell, Elizabeth; Shellington, David K.; Simon, Dennis W.; Bell, Michael J.; Kochanek, Patrick M.; Feldman, Keri; Bayır, Hülya; Aneja, Rajesh K.; Carcillo, Joseph A.; Clark, Robert S. B.

2015-01-01

Objective The magnitude and role of the cellular immune response following pediatric traumatic brain injury (TBI) remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric TBI by measuring cerebrospinal fluid (CSF) levels of sCD163 and ferritin, and sIL-2Rα, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome. Design Retrospective analysis of samples from an established, single-center CSF bank. Setting Pediatric Intensive Care Unit (PICU) in a tertiary Children’s Hospital Patients Sixty-six pediatric patients after severe TBI (Glasgow coma scale score [GCS]<8) age 1 mo-16 y and 17 control patients age 1 mo-14 y. Measurements and Main Results CSF levels of sCD163, ferritin, and sIL-2Rα were determined by ELISA at 2 time points (t1=17±10, t2=72±15 h) for each TBI patient. CSF sCD163, ferritin, and sIL2Rα levels after TBI were compared with controls and analyzed for associations with age, patient sex, initial GCS, diagnosis of abusive head trauma (AHT), the presence of hemorrhage on computerized tomography scan, and Glasgow outcome scale score (GOS). CSF sCD163 was increased in TBI patients at t2 vs. t1 and controls (95.4[21.8–134.0] vs. 31.0[5.7–77.7] and 27.8[19.1–43.1] ng/ml, respectively; median[IQ]; P<0.05). CSF ferritin was increased in TBI patients at t2 and t1 vs. controls (8.3[7.5–19.8] and 8.9[7.5–26.7] vs. [7.5[0.0–0.0] ng/ml, respectively; P<0.05). CSF sIL-2Rα in TBI patients at t2 and t1 were not different vs. controls. Multivariate regression revealed associations between high ferritin and age ≤ 4 y, lower GCS, AHT, and unfavorable GOS. Conclusions Children with TBI demonstrate evidence for macrophage activation after TBI, and in terms of CSF ferritin, this appears more prominent with young age, initial injury severity, AHT, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses, and whether inflammation represents a therapeutic target after TBI. PMID:25850867

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes.

PubMed

Artz, Andrew S; Logan, Brent; Zhu, Xiaochun; Akpek, Gorgun; Bufarull, Rodrigo Martino; Gupta, Vikas; Lazarus, Hillard M; Litzow, Mark; Loren, Alison; Majhail, Navneet S; Maziarz, Richard T; McCarthy, Philip; Popat, Uday; Saber, Wael; Spellman, Stephen; Ringden, Olle; Wickrema, Amittha; Pasquini, Marcelo C; Cooke, Kenneth R

2016-11-01

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. Copyright© Ferrata Storti Foundation.

Toxicological responses of the hard clam Meretrix meretrix exposed to excess dissolved iron or challenged by Vibrio parahaemolyticus.

PubMed

Zhou, Qing; Zhang, Yong; Peng, Hui-Fang; Ke, Cai-Huan; Huang, He-Qing

2014-11-01

The responses of genes encoding defense components such as ferritin, the lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), the inhibitor of nuclear factor-κB (IκB), metallothionein, and glutathione peroxidase were assessed at the transcriptional level in order to investigate the toxicological and immune mechanism of the hard clam Meretrix meretrix (HCMM) following challenge with iron or a bacterium (Vibrio parahaemolyticus). Fe dissolved in natural seawater led to an increase of Fe content in both the hepatopancreas and gill tissue of HCMM between 4 and 15 days of exposure. The ferritin gene responded both transcriptionally as indicated by real-time quantitative PCR and translationally as shown by western blotting results to iron exposure and both transcriptional and translational ferritin expression in the hepatopancreas had a positive correlation with the concentration of dissolved iron in seawater. Both iron and V. parahaemolyticus exposure triggered immune responses with similar trends in clam tissues. There was a significant post-challenge mRNA expression of LITAF and IκB at 3h, ferritin at 24h, and metallothionein and glutathione peroxidase at 48h. This behavior might be linked to their specific functions in physiological processes. These results suggested that similar signaling pathways were triggered during both iron and V. parahaemolyticus challenges. Here, we indicated that the ferritin of Meretrix meretrix was an intermediate in the pathway of iron homeostasis and in its innate immune defense mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

On the mineral core of ferritin-like proteins: structural and magnetic characterization

NASA Astrophysics Data System (ADS)

García-Prieto, A.; Alonso, J.; Muñoz, D.; Marcano, L.; Abad Díaz de Cerio, A.; Fernández de Luis, R.; Orue, I.; Mathon, O.; Muela, A.; Fdez-Gubieda, M. L.

2015-12-01

It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K-edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction.It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K-edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04446d

Iron homeostasis: a new job for macrophages in adipose tissue?

PubMed Central

Hubler, Merla J.; Peterson, Kristin R.; Hasty, Alyssa H.

2015-01-01

Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity. PMID:25600948

Ferritin and ferrihydrite nanoparticles as iron sources for Pseudomonas aeruginosa

PubMed Central

Dehner, Carolyn; Morales-Soto, Nydia; Behera, Rabindra K.; Shrout, Joshua; Theil, Elizabeth C.; Maurice, Patricia A.

2013-01-01

Metabolism of iron derived from insoluble and/ or scarce sources is essential for pathogenic and environmental microbes. The ability of Pseudomonas aeruginosa to acquire iron from exogenous ferritin was assessed; ferritin is an iron-concentrating and antioxidant protein complex composed of a catalytic protein and caged ferrihydrite nanomineral synthesized from Fe(II) and O2 or H2O2. Ferritin and free ferrihydrite supported growth of P. aeruginosa with indistinguishable kinetics and final culture densities. The P. aeruginosa PAO1 mutant (ΔpvdDΔpchEF), which is incapable of siderophore production, grew as well as the wild type when ferritin was the iron source. Such data suggest that P. aeruginosa can acquire iron by siderophore-independent mechanisms, including secretion of small-molecule reductant(s). Protease inhibitors abolished the growth of the siderophore-free strain on ferritins, with only a small effect on growth of the wild type; predictably, protease inhibitors had no effect on growth with free ferrihydrite as the iron source. Proteolytic activity was higher with the siderophore-free strain, suggesting that the role of proteases in the degradation of ferritin is particularly important for iron acquisition in the absence of siderophores. The combined results demonstrate the importance of both free ferrihydrite, a natural environmental form of iron and a model for an insoluble form of partly denatured ferritin called hemosiderin, and caged ferritin iron minerals as bacterial iron sources. Ferritin is also revealed as a growth promoter of opportunistic, pathogenic bacteria such a P. aeruginosa in diseased tissues such as the cystic fibrotic lung, where ferritin concentrations are abnormally high. PMID:23417538

Maxi- and mini-ferritins: minerals and protein nanocages.

PubMed

Bevers, Loes E; Theil, Elizabeth C

2011-01-01

Ferritins synthesize ferric oxide biominerals and are central to all life for concentrating iron and protection against oxidative stress from the ferrous and oxidant chemistry. The ferritin protein nanocages and biomineral synthesis are discussed in terms of wide biological distribution of the maxi-ferritins (24 subunit ± heme) and mini-ferritins (Dps) (12 subunit), conservations of the iron/oxygen catalytic sites in the protein cages, mineral formation (step i. Fe(II) entry and binding, step ii. O(2) or H(2)O(2) binding and formation of transition intermediates, step iii. release of differric oxo mineral precursors from active sites, step iv. nucleation and mineralization) properties of the minerals, and protein control of mineral dissolution and release of Fe(II). Pores in ferritin protein cages control iron entry for mineralization and iron exit after mineral dissolution. The relationship between phosphate or the presence of catalytically inactive subunits (animal L subunits) and ferritin iron mineral disorder is developed based on new information about contributions of ferritin protein cage structure to nucleation in protein cage subunit channels that exit close enough to those of other subunits and exiting mineral nuclei to facilitate bulk mineral formation. How and where protons move in and out of the protein during mineral synthesis and dissolution, how ferritin cage assembly with 12 or 24 subunits is encoded in the widely divergent ferritin amino acid sequences, and what is the role of the protein in synthesis of the bulk mineral are all described as problems requiring new approaches in future investigations of ferritin biominerals.

Hyperexpandable, self-healing macromolecular crystals with integrated polymer networks.

PubMed

Zhang, Ling; Bailey, Jake B; Subramanian, Rohit H; Tezcan, F Akif

2018-05-01

The formation of condensed matter typically involves a trade-off between structural order and flexibility. As the extent and directionality of interactions between atomic or molecular components increase, materials generally become more ordered but less compliant, and vice versa. Nevertheless, high levels of structural order and flexibility are not necessarily mutually exclusive; there are many biological (such as microtubules 1,2 , flagella 3 , viruses 4,5 ) and synthetic assemblies (for example, dynamic molecular crystals 6-9 and frameworks 10-13 ) that can undergo considerable structural transformations without losing their crystalline order and that have remarkable mechanical properties 8,14,15 that are useful in diverse applications, such as selective sorption 16 , separation 17 , sensing 18 and mechanoactuation 19 . However, the extent of structural changes and the elasticity of such flexible crystals are constrained by the necessity to maintain a continuous network of bonding interactions between the constituents of the lattice. Consequently, even the most dynamic porous materials tend to be brittle and isolated as microcrystalline powders 14 , whereas flexible organic or inorganic molecular crystals cannot expand without fracturing. Owing to their rigidity, crystalline materials rarely display self-healing behaviour 20 . Here we report that macromolecular ferritin crystals with integrated hydrogel polymers can isotropically expand to 180 per cent of their original dimensions and more than 500 per cent of their original volume while retaining periodic order and faceted Wulff morphologies. Even after the separation of neighbouring ferritin molecules by 50 ångströms upon lattice expansion, specific molecular contacts between them can be reformed upon lattice contraction, resulting in the recovery of atomic-level periodicity and the highest-resolution ferritin structure reported so far. Dynamic bonding interactions between the hydrogel network and the ferritin molecules endow the crystals with the ability to resist fragmentation and self-heal efficiently, whereas the chemical tailorability of the ferritin molecules enables the creation of chemically and mechanically differentiated domains within single crystals.

HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.

PubMed

Kaczorowska-Hac, Barbara; Luszczyk, Marcin; Antosiewicz, Jedrzej; Ziolkowski, Wieslaw; Adamkiewicz-Drozynska, Elzbieta; Mysliwiec, Malgorzata; Milosz, Ewa; Kaczor, Jan J

2017-07-01

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

Fe(II) formation after interaction of the amyloid β-peptide with iron-storage protein ferritin.

PubMed

Balejcikova, Lucia; Siposova, Katarina; Kopcansky, Peter; Safarik, Ivo

2018-05-09

The interaction of amyloid β-peptide (Aβ) with the iron-storage protein ferritin was studied in vitro. We have shown that Aβ during fibril formation process is able to reduce Fe(III) from the ferritin core (ferrihydrite) to Fe(II). The Aβ-mediated Fe(III) reduction yielded a two-times-higher concentration of free Fe(II) than the spontaneous formation of Fe(II) by the ferritin itself. We suggest that Aβ can also act as a ferritin-specific metallochaperone-like molecule capturing Fe(III) from the ferritin ferrihydrite core. Our observation may partially explain the formation of Fe(II)-containing minerals in human brains suffering by neurodegenerative diseases.

Enrichment and characterization of ferritin for nanomaterial applications

NASA Astrophysics Data System (ADS)

Ghirlando, Rodolfo; Mutskova, Radina; Schwartz, Chad

2016-01-01

Ferritin is a ubiquitous iron storage protein utilized as a nanomaterial for labeling biomolecules and nanoparticle construction. Commercially available preparations of horse spleen ferritin, widely used as a starting material, contain a distribution of ferritins with different iron loads. We describe a detailed approach to the enrichment of differentially loaded ferritin molecules by common biophysical techniques such as size exclusion chromatography and preparative ultracentrifugation, and characterize these preparations by dynamic light scattering, and analytical ultracentrifugation. We demonstrate a combination of methods to standardize an approach for determining the chemical load of nearly any particle, including nanoparticles and metal colloids. Purification and characterization of iron content in monodisperse ferritin species is particularly critical for several applications in nanomaterial science.

Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose: an analysis of the randomized FIND-CKD trial.

PubMed

Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Meier, Yvonne; Larroque, Sylvain; Roger, Simon D

2017-01-17

Preclinical studies demonstrate renal proximal tubular injury after administration of some intravenous iron preparations but clinical data on renal effects of intravenous iron are sparse. FIND-CKD was a 56-week, randomized, open-label, multicenter study in which patients with non-dialysis dependent chronic kidney disease (ND-CKD), anemia and iron deficiency without erythropoiesis-stimulating agent therapy received intravenous ferric carboxymaltose (FCM), targeting either higher (400-600 μg/L) or lower (100-200 μg/L) ferritin values, or oral iron. Mean (SD) eGFR at baseline was 34.9 (11.3), 32.8 (10.8) and 34.2 (12.3) mL/min/1.73 m 2 in the high ferritin FCM (n = 97), low ferritin FCM (n = 89) and oral iron (n = 167) groups, respectively. Corresponding values at month 12 were 35.6 (13.8), 32.1 (12.7) and 33.4 (14.5) mL/min/1.73 m 2 . The pre-specified endpoint of mean (SE) change in eGFR from baseline to month 12 was +0.7 (0.9) mL/min/1.73 m 2 with high ferritin FCM (p = 0.15 versus oral iron), -0.9 (0.9) mL/min/1.73 m 2 with low ferritin FCM (p = 0.99 versus oral iron) and -0.9 (0.7) mL/min/1.73 m 2 with oral iron. No significant association was detected between quartiles of FCM dose, change in ferritin or change in TSAT versus change in eGFR. Dialysis initiation was similar between groups. Renal adverse events were rare, with no indication of between-group differences. Intravenous FCM at doses that maintained ferritin levels of 100-200 μg/L or 400-600 μg/L did not negatively impact renal function (eGFR) in patients with ND-CKD over 12 months versus oral iron, and eGFR remained stable. These findings show no evidence of renal toxicity following intravenous FCM over a 1-year period. ClinicalTrials.gov NCT00994318 (first registration 12 October 2009).

[Liver and heart T2* measurement in secondary haemochromatosis].

PubMed

Barrera Portillo, M C; Uranga Uranga, M; Sánchez González, J; Alústiza Echeverría, J M; Gervás Wells, C; Guisasola Íñiguez, A

2013-01-01

To determine whether there is iron overload by calculating the T2* value in the liver and myocardium in patients with secondary haemochromatosis. To analyse the correlation of the values obtained with the iron levels in blood, with the liver iron concentration (LIC) calculated using magnetic resonance (MR) imaging, and the correlation between them. A total of 16 patients (13 males, 3 females), with a mean age of 61 years, were included and evaluated in the years 2008 and 2009. Fifteen of them had received multiple transfusions, and one was diagnosed with hereditary sideroblastic anaemia. The measurements included, blood ferritin, LIC by MRI, cardiac function using MRI and the T2* value by means of multi-echo sequences in the liver (TR/TE1/ΔTE/No of echos/α: 21/1,18/1.0/20/35°) and myocardium (26/1.04/0.8/30/60°). A correlation-regression analysis was performed by comparing the cardiac and liver T2* values with the ferritin, LIC and between each of them. A total of 13 patients had ferritin values greater than 1000ng/ml (median/minimum/maximum: 1762/294/3785ng/ml). An increased LIC greater than 80μmol/g (median/minimum/maximum: 125.4/41.2/241.5μmol/g) was observed in 13 patients. In all cases cardiac function was conserved, and in 15 cases the liver T2* value was less than 6.3ms. The myocardium T2* value was less than 20ms. in only one case. A high correlation was observed between the liver T2* values and the LIC (r:-0.912). The correlation was statistically significant between the liver T2* value and ferritin (r:-0.541). The correlations between myocardium T2* and ferritin, myocardium T2* and LIC, and myocardium T2* and liver T2* were not statistically significant. The liver T2* showed a high correlation with LIC and a statistically significant correlation with ferritin. No association was observed between the myocardium T2* values and ferritin in blood, the LIC or the liver T2* value. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

Nanophase iron phosphate, iron arsenate, iron vanadate, and iron molybdate minerals synthesized within the protein cage of ferritin.

PubMed

Polanams, Jup; Ray, Alisha D; Watt, Richard K

2005-05-02

Nanoparticles of iron phosphate, iron arsenate, iron molybdate, and iron vanadate were synthesized within the 8 nm interior of ferritin. The synthesis involved reacting Fe(II) with ferritin in a buffered solution at pH 7.4 in the presence of phosphate, arsenate, vanadate, or molybdate. O2 was used as the oxidant to deposit the Fe(III) mineral inside ferritin. The rate of iron incorporation into ferritin was stimulated when oxo-anions were present. The simultaneous deposition of both iron and the oxo-anion was confirmed by elemental analysis and energy-dispersive X-ray analysis. The ferritin samples containing iron and one of the oxo-anions possessed different UV/vis spectra depending on the anion used during mineral formation. TEM analysis showed mineral cores with approximately 8 nm mineral particles consistent with the formation of mineral phases inside ferritin.

METALLOPROTEINS DURING DEVELOPMENT OF WALKER-256 CARCINOSARCOMA RESISTANT PHENOTYPE.

PubMed

Chekhun, V F; Lozovska, Yu V; Burlaka, A P; Ganusevich, I I; Shvets, Yu V; Lukianova, N Yu; Todor, I M; Demash, D V; Pavlova, A A; Naleskina, L A

2015-01-01

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development ofdoxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carc'inosarcoma tissue. We observed decreased serumferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases withfully developed resistance phenotype. Transferrin content showed changes opposite to that offerritin. During the development of resistance phenotype the tumor tissue also exhibited increased 'free iron' concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

Energetics of surface confined ferritin during iron loading.

PubMed

Federici, Stefania; Padovani, Francesco; Poli, Maura; Rodriguez, Fernando Carmona; Arosio, Paolo; Depero, Laura E; Bergese, Paolo

2016-09-01

We report on the first quantitative picture on how iron loading inside ferritin molecules occurs when they are self-assembled onto solid surfaces. Recombinant human ferritin H-chain with ferroxidase activity was adsorbed onto microcantilever beams to form a stable close-packed thin film. The obtained nanomechanical system was used to track in real time the energetics of inter-ferritin surface interactions during incubation with Fe(II) for iron loading. We observed that iron loading is accompanied by increasing attractive in-plane inter-ferritin interactions able to perform a maximum surface work of 6.0±1.5mJ/m(2), corresponding to a surface energy variation per ferritin of about 40kbT. Unique to this protein surface transformation, part of the surface work is exerted by the attractive electrostatic forces arising among the new born nanosized iron cores inside the ferritin shells. The remaining work comes from subtle action of steric, bridging and depletion forces. These findings are of fundamental interest and add important information for the rational development of ferritin nanotechnology. Copyright © 2016 Elsevier B.V. All rights reserved.

A prospective study of Willis-Ekbom disease/restless legs syndrome during and after pregnancy.

PubMed

Neyal, Abdurrahman; Senel, Gulcin Benbir; Aslan, Rahime; Nalbantoglu, Mecbure; Acikgoz, Serdar; Yilmaz, Nevin; Tumay, Feray Bolukbasi; Neyal, Munife; Karadeniz, Derya

2015-09-01

Willis-Ekbom disease/restless legs syndrome (WED/RLS) is the most common sleep-related movement disorder in pregnancy. We designed a prospective longitudinal study to investigate the correlates of WED/RLS during and after pregnancy. A total of 138 pregnant women with WED/RLS and a control group of 251 age-matched pregnant women were enrolled prospectively. A questionnaire was administered during a face-to-face interview at first evaluation during pregnancy and three months after delivery. Among all women in the first trimester, 15.6% were diagnosed with WED/RLS, whereas 32.8% of those in the second trimester and 38.8% of those in the third trimester were diagnosed with WED/RLS (p = 0.032). In regression analysis, later gestational age [p < 0.001; odds ratio (OR) 1.054] and previous history of WED/RLS (p = 0.001; OR 2.795) were positively correlated with the presence of WED/RLS, while ferritin levels (p = 0.001; OR 0.956) were negatively correlated with the presence of WED/RLS. Ferritin levels were also negatively correlated with the International RLS Study Group severity index (p = 0.041). Forty-eight patients (34.8%) experienced WED/RLS symptomatology after delivery. The ferritin levels were lower, and the mean number of pregnancies was higher, in women with residual WED/RLS (p = 0.008). Our survey showed that WED/RLS was more common in the second and third trimesters. Emergence of WED/RLS during the second trimester was strongly associated with residual WED/RLS. Lower ferritin levels were associated with both WED/RLS in pregnancy and residual WED/RLS after delivery. A higher number of pregnancies were also associated with a greater likelihood of having residual WED/RLS after delivery. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Iron Deficiency Parameters in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

PubMed

Percinel, Ipek; Yazici, Kemal Utku; Ustundag, Bilal

2016-04-01

The aim of this study is to compare iron deficiency parameters in patients with stimulant-naive attention-deficit/hyperactivity disorder (ADHD) and healthy controls, to investigate whether there are differences among the ADHD presentations, and to evaluate the relationship between ADHD symptom severity and serum ferritin levels. In addition, ADHD-Predominantly Inattentive (ADHD-PI) patients with restrictive hyperactivity/impulsivity symptoms were evaluated as a separate group with "restrictive inattention presentation" (ADHD-Rest) and were compared with other groups. Patients with ADHD-Rest are typically defined as having six or more symptoms of inattention and fewer than three symptoms of hyperactivity/impulsivity. A total of 200 ADHD cases consisting of 100 ADHD-Combine (ADHD-C) and 100 ADHD-PI and a total of 100 healthy control cases were included in the study. The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version was performed in a semi-structured interview during the diagnosis. The Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale, the Conners' Rating Scale-Revised: Long Form (Parent-Teacher) (CPRSR:L, CTRS-R:L) were used for clinical evaluation. Hemogram, serum iron, iron binding capacity and serum ferritin levels were assessed. There were no significant differences between the ADHD patients and the healthy control cases in terms of iron deficiency parameters. Further, there were no significant differences among the ADHD presentations in terms of the same parameters, nor were there any significant differences when the groups were examined after the identification of the ADHD-Rest. The CPRS-R:L Hyperactivity and the CTRS-R:L Hyperactivity scores were negatively correlated with serum ferritin level in the ADHD group. To our knowledge, our current study is the first to compare serum ferritin levels in ADHD-Rest with other presentations of ADHD, and included the largest number of patients that were classified by ADHD presentations. Elucidation of these findings is important for both the etiology and treatment of ADHD.

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

PubMed

Jalalzadeh, M; Shekari, E; Mirzamohammadi, F; Ghadiani, M H

2012-05-01

Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

The nutritional status of iron, folate, and vitamin B-12 of Buddhist vegetarians.

PubMed

Lee, Yujin; Krawinkel, Michael

2011-01-01

Nutritional status of iron, folate, and vitamin B-12 in vegetarians were assessed and compared with those of non- vegetarians in Korea. The vegetarian subjects were 54 Buddhist nuns who ate no animal source food except for dairy products. The non-vegetarians were divided into two groups: 31 Catholic nuns and 31 female college students. Three-day dietary records were completed, and the blood samples were collected for analyzing a complete blood count, and serum levels of ferritin, folate, and vitamin B-12. There was no difference in hemoglobin among the diet groups. The serum ferritin and hematocrit levels of vegetarians did not differ from that of non- vegetarian students with a high intake of animal source food but low intake of vitamin C, and the levels were lower than that of non-vegetarian Catholic nuns with a modest consumption of animal source food and a high intake of vitamin C. The serum vitamin B-12 levels of all subjects except one vegetarian and the serum folate levels of all subjects except one non-vegetarian student fell within a normal range. In vegetarians, there was a positive correlation between the vitamin C intake and serum ferritin levels as well as between the laver intake and serum vitamin B-12 levels. In order to achieve an optimal iron status, both an adequate amount of iron intake and its bioavailability should be considered. Sufficient intake of vegetables and fruits was reflected in adequate serum folate status. Korean laver can be a good source of vitamin B-12 for vegetarians.

Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization

PubMed Central

Buisson, Christophe; Daou, Nadine; Kallassy, Mireille; Lereclus, Didier; Arosio, Paolo; Bou-Abdallah, Fadi; Nielsen Le Roux, Christina

2014-01-01

In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis. PMID:24550730

Ferritin-Templated Quantum-Dots for Quantum Logic Gates

NASA Technical Reports Server (NTRS)

Choi, Sang H.; Kim, Jae-Woo; Chu, Sang-Hyon; Park, Yeonjoon; King, Glen C.; Lillehei, Peter T.; Kim, Seon-Jeong; Elliott, James R.

2005-01-01

Quantum logic gates (QLGs) or other logic systems are based on quantum-dots (QD) with a stringent requirement of size uniformity. The QD are widely known building units for QLGs. The size control of QD is a critical issue in quantum-dot fabrication. The work presented here offers a new method to develop quantum-dots using a bio-template, called ferritin, that ensures QD production in uniform size of nano-scale proportion. The bio-template for uniform yield of QD is based on a ferritin protein that allows reconstitution of core material through the reduction and chelation processes. One of the biggest challenges for developing QLG is the requirement of ordered and uniform size of QD for arrays on a substrate with nanometer precision. The QD development by bio-template includes the electrochemical/chemical reconsitution of ferritins with different core materials, such as iron, cobalt, manganese, platinum, and nickel. The other bio-template method used in our laboratory is dendrimers, precisely defined chemical structures. With ferritin-templated QD, we fabricated the heptagonshaped patterned array via direct nano manipulation of the ferritin molecules with a tip of atomic force microscope (AFM). We also designed various nanofabrication methods of QD arrays using a wide range manipulation techniques. The precise control of the ferritin-templated QD for a patterned arrangement are offered by various methods, such as a site-specific immobilization of thiolated ferritins through local oxidation using the AFM tip, ferritin arrays induced by gold nanoparticle manipulation, thiolated ferritin positioning by shaving method, etc. In the signal measurements, the current-voltage curve is obtained by measuring the current through the ferritin, between the tip and the substrate for potential sweeping or at constant potential. The measured resistance near zero bias was 1.8 teraohm for single holoferritin and 5.7 teraohm for single apoferritin, respectively.

Specific repression of β-globin promoter activity by nuclear ferritin

PubMed Central

Broyles, Robert H.; Belegu, Visar; DeWitt, Christina R.; Shah, Sandeep N.; Stewart, Charles A.; Pye, Quentin N.; Floyd, Robert A.

2001-01-01

Developmental hemoglobin switching involves sequential globin gene activations and repressions that are incompletely understood. Earlier observations, described herein, led us to hypothesize that nuclear ferritin is a repressor of the adult β-globin gene in embryonic erythroid cells. Our data show that a ferritin-family protein in K562 cell nuclear extracts binds specifically to a highly conserved CAGTGC motif in the β-globin promoter at −153 to −148 bp from the cap site, and mutation of the CAGTGC motif reduces binding 20-fold in competition gel-shift assays. Purified human ferritin that is enriched in ferritin-H chains also binds the CAGTGC promoter segment. Expression clones of ferritin-H markedly repress β-globin promoter-driven reporter gene expression in cotransfected CV-1 cells in which the β-promoter has been stimulated with the transcription activator erythroid Krüppel-like factor (EKLF). We have constructed chloramphenicol acetyltransferase reporter plasmids containing either a wild-type or mutant β-globin promoter for the −150 CAGTGC motif and have compared the constructs for susceptibility to repression by ferritin-H in cotransfection assays. We find that stimulation by cotransfected EKLF is retained with the mutant promoter, whereas repression by ferritin-H is lost. Thus, mutation of the −150 CAGTGC motif not only markedly reduces in vitro binding of nuclear ferritin but also abrogates the ability of expressed ferritin-H to repress this promoter in our cell transfection assay, providing a strong link between DNA binding and function, and strong support for our proposal that nuclear ferritin-H is a repressor of the human β-globin gene. Such a repressor could be helpful in treating sickle cell and other genetic diseases. PMID:11481480

Fe(2+) substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization.

PubMed

Behera, Rabindra K; Torres, Rodrigo; Tosha, Takehiko; Bradley, Justin M; Goulding, Celia W; Theil, Elizabeth C

2015-09-01

Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3·H2O), by moving cytoplasmic Fe(2+) through intracage ion channels to cage-embedded enzyme (2Fe(2+)/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe(2+) movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one -CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650 nm (DFP λ max). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe(3+)-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: (1) narrower interior ion channel openings/pores; (2) increased numbers of ion channel protein-metal binding sites, and (3) a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells.

Fe2+ Substrate Transport through Ferritin Protein Cage Ion Channels Influences Enzyme Activity and Biomineralization

PubMed Central

Behera, Rabindra K.; Torres, Rodrigo; Tosha, Takehiko; Bradley, Justin M.; Goulding, Celia W.; Theil, Elizabeth C.

2015-01-01

Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3.H2O), by moving cytoplasmic Fe2+ through intracage ion channels to cage-embedded enzyme (2Fe2+/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe2+ movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one – CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650nm (DFP λmax). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe3+-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: 1. narrower interior ion channel openings/pores, 2. increased numbers of ion channel protein-metal binding sites, and 3. a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells. PMID:26202907

Ferritin ion channel disorder inhibits Fe(II)/O2 reactivity at distant sites.

PubMed

Tosha, Takehiko; Behera, Rabindra K; Theil, Elizabeth C

2012-11-05

Ferritins, a complex, mineralized, protein nanocage family essential for life, provide iron concentrates and oxidant protection. Protein-based ion channels and Fe(II)/O(2) catalysis initiate conversion of thousands of Fe atoms to caged, ferritin Fe(2)O(3)·H(2)O minerals. The ion channels consist of six helical segments, contributed by 3 of 12 or 24 polypeptide subunits, around the 3-fold cage axes. The channel structure guides entering Fe(II) ions toward multiple, catalytic, diiron sites buried inside ferritin protein helices, ~20 Å away from channel internal exits. The catalytic product, Fe(III)-O(H)-Fe(III), is a mineral precursor; mineral nucleation begins inside the protein cage with mineral growth in the central protein cavity (5-8 nm diameter). Amino acid substitutions that changed ionic or hydrophobic channel interactions R72D, D122R, and L134P increased ion channel structural disorder (protein crystallographic analyses) and increased Fe(II) exit [chelated Fe(II) after ferric mineral reduction/dissolution]. Since substitutions of some channel carboxylate residues diminished ferritin catalysis with no effect on Fe(II) exit, such as E130A and D127A, we investigated catalysis in ferritins with altered Fe(II) exit, R72D, D122R and L134P. The results indicate that simply changing the ionic properties of the channels, as in the R72D variant, need not change the forward catalytic rate. However, both D122R and L134P, which had dramatic effects on ferritin catalysis, also caused larger effects on channel structure and order, contrasting with R72D. All three amino acid substitutions, however, decreased the stability of the catalytic intermediate, diferric peroxo, even though overall ferritin cage structure is very stable, resisting 80 °C and 6 M urea. The localized structural changes in ferritin subdomains that affect ferritin function over long distances illustrate new properties of the protein cage in natural ferritin function and for applied ferritin uses.

Ferritin nanocontainers that self-direct in synthetic polymer systems

NASA Astrophysics Data System (ADS)

Sengonul, Merih C.

Currently, there are many approaches to introduce functionality into synthetic polymers. Among these, for example, are copolymerization, grafting, and blending methods. However, modifications made by such methods also change the thermodynamics and rheological properties of the polymer system of interest, and each new modification often requires a costly reoptimization of polymer processing. Such a reoptimalization would not be necessary if new functionality could be introduced via a container whose external surface is chemically and physically tuned to interact with the parent polymer. The contents of the container could then be changed without changing other important properties of the parent polymer. In this context this thesis project explores an innovative nanocontainer platform which can be introduced into phase-separating homopolymer blends. Ferritin is a naturally existing nanocontainer that can be used synthetically to package and selectively transport functional moieties to a particular phase that is either in the bulk or on the surface of a homopolymer blend system. The principal focus of this work centers on modifying the surface of wild ferritin to: (1) render modified ferritin soluble in a non-aqueous solvent; and (2) impart it with self-directing properties when exposed to a homopolymer blend surface or incorporated into the bulk of a homopolymer blend. Wild ferritin is water soluble, and this research project successfully modified wild ferritin by grafting either amine-functional poly(ethylene glycol) (PEG) or short-chain alkanes to carbodiimide activated carboxylate groups on ferritin's surface. Such modified ferritin is soluble in dichloromethane (DCM). Modification was confirmed by ion-exchange chromatography, zeta-potential measurements, and electrospray mass spectroscopy. FT-IR was used to quantify the extent of PEGylation of the reaction products through area ratios of the -C-O-C asymmetric stretching vibration of the grafted PEG chains to the carbonyl stretching vibration (amide I band) of the protein. The dimensionless grafting density after PEGylation was found to be 0.13 with 120 average grafted PEG chains per ferritin nanocontainer. Modified ferritin was used for bulk modification of a phase-separated polymer blend of poly(desaminotyrosyl tyrosine dodecyl ester carbonate) [PDTD] and PEG. TEM micrographs showed remarkable selectivity of PEGylated ferritin to PEG domains, while alkylated ferritin self-directs to the PDTD matrix. We explain this strong selectivity by the favourable interaction energies between the grafted and free matrix chains. In addition, both modified and wild ferritin were used for surface modification of the phase-separated homopolymer blend of PDTD and poly(ε-caprolactone) (PCL). At physiological pH wild ferritin selectively adsorbed onto the PDTD phase, while alkylated ferritin showed a striking selectivity to PCL phase. We attribute this behavior to the increase in protein's pI point above physiological pH after modification, which changes the electrostatic interactions between the ferritin and the polymer surface. Collectively, these results demonstrate the versatile use of ferritin as a model nanocontainer for the selective modification of surface and bulk properties of polymers.

Ferritin light-chain subunits: key elements for the electron transfer across the protein cage.

PubMed

Carmona, Unai; Li, Le; Zhang, Lianbing; Knez, Mato

2014-12-18

The first specific functionality of the light-chain (L-chain) subunit of the universal iron storage protein ferritin was identified. The electrons released during iron-oxidation were transported across the ferritin cage specifically through the L-chains and the inverted electron transport through the L-chains also accelerated the demineralization of ferritin.

Serum iron level and kidney function: a Mendelian randomization study.

PubMed

Del Greco M, Fabiola; Foco, Luisa; Pichler, Irene; Eller, Philipp; Eller, Kathrin; Benyamin, Beben; Whitfield, John B; Pramstaller, Peter P; Thompson, John R; Pattaro, Cristian; Minelli, Cosetta

2017-02-01

Iron depletion is a known consequence of chronic kidney disease (CKD), but there is contradicting epidemiological evidence on whether iron itself affects kidney function and whether its effect is protective or detrimental in the general population. While epidemiological studies tend to be affected by confounding and reverse causation, Mendelian randomization (MR) can provide unconfounded estimates of causal effects by using genes as instruments. We performed an MR study of the effect of serum iron levels on estimated glomerular filtration rate (eGFR), using genetic variants known to be associated with iron. MR estimates of the effect of iron on eGFR were derived based on the association of each variant with iron and eGFR from two large genome-wide meta-analyses on 48 978 and 74 354 individuals. We performed a similar MR analysis for ferritin, which measures iron stored in the body, using variants associated with ferritin. A combined MR estimate across all variants showed a 1.3% increase in eGFR per standard deviation increase in iron (95% confidence interval 0.4–2.1%; P = 0.004). The results for ferritin were consistent with those for iron. Secondary MR analyses of the effects of iron and ferritin on CKD did not show significant associations but had very low statistical power. Our study suggests a protective effect of iron on kidney function in the general population. Further research is required to confirm this causal association, investigate it in study populations at higher risk of CKD and explore its underlying mechanism of action.

Iron regulatory protein 1 is not required for the modulation of ferritin and transferrin receptor expression by iron in a murine pro-B lymphocyte cell line

PubMed Central

Schalinske, Kevin L.; Blemings, Kenneth P.; Steffen, Daniel W.; Chen, Opal S.; Eisenstein, Richard S.

1997-01-01

Iron regulatory proteins (IRPs) are cytoplasmic RNA binding proteins that are central components of a sensory and regulatory network that modulates vertebrate iron homeostasis. IRPs regulate iron metabolism by binding to iron responsive element(s) (IREs) in the 5′ or 3′ untranslated region of ferritin or transferrin receptor (TfR) mRNAs. Two IRPs, IRP1 and IRP2, have been identified previously. IRP1 exhibits two mutually exclusive functions as an RNA binding protein or as the cytosolic isoform of aconitase. We demonstrate that the Ba/F3 family of murine pro-B lymphocytes represents the first example of a mammalian cell line that fails to express IRP1 protein or mRNA. First, all of the IRE binding activity in Ba/F3-gp55 cells is attributable to IRP2. Second, synthesis of IRP2, but not of IRP1, is detectable in Ba/F3-gp55 cells. Third, the Ba/F3 family of cells express IRP2 mRNA at a level similar to other murine cell lines, but IRP1 mRNA is not detectable. In the Ba/F3 family of cells, alterations in iron status modulated ferritin biosynthesis and TfR mRNA level over as much as a 20- and 14-fold range, respectively. We conclude that IRP1 is not essential for regulation of ferritin or TfR expression by iron and that IRP2 can act as the sole IRE-dependent mediator of cellular iron homeostasis. PMID:9380695

High ferritin levels have major effects on the morphology of erythrocytes in Alzheimer's disease.

PubMed

Bester, Janette; Buys, Antoinette V; Lipinski, Boguslaw; Kell, Douglas B; Pretorius, Etheresia

2013-01-01

Unliganded iron both contributes to the pathology of Alzheimer's disease (AD) and also changes the morphology of erythrocytes (RBCs). We tested the hypothesis that these two facts might be linked, i.e., that the RBCs of AD individuals have a variant morphology, that might have diagnostic or prognostic value. We included a literature survey of AD and its relationships to the vascular system, followed by a laboratory study. Four different microscopy techniques were used and results statistically compared to analyze trends between high and normal serum ferritin (SF) AD individuals. Light and scanning electron microscopies showed little difference between the morphologies of RBCs taken from healthy individuals and from normal SF AD individuals. By contrast, there were substantial changes in the morphology of RBCs taken from high SF AD individuals. These differences were also observed using confocal microscopy and as a significantly greater membrane stiffness (measured using force-distance curves). We argue that high ferritin levels may contribute to an accelerated pathology in AD. Our findings reinforce the importance of (unliganded) iron in AD, and suggest the possibility both of an early diagnosis and some means of treating or slowing down the progress of this disease.

Upfront dilution of ferritin samples to reduce hook effect, improve turnaround time and reduce costs.

PubMed

Wu, Shu Juan; Hayden, Joshua A

2018-02-15

Sandwich immunoassays offer advantages in the clinical laboratory but can yield erroneously low results due to hook (prozone) effect, especially with analytes whose concentrations span several orders of magnitude such as ferritin. This study investigated a new approach to reduce the likelihood of hook effect in ferritin immunoassays by performing upfront, five-fold dilutions of all samples for ferritin analysis. The impact of this change on turnaround time and costs were also investigated. Ferritin concentrations were analysed in routine clinical practice with and without upfront dilutions on Siemens Centaur® XP (Siemens Healthineers, Erlang, Germany) immunoanalysers. In addition, one month of baseline data (1026 results) were collected prior to implementing upfront dilutions and one month of data (1033 results) were collected after implementation. Without upfront dilutions, hook effect was observed in samples with ferritin concentrations as low as 86,028 µg/L. With upfront dilutions, samples with ferritin concentrations as high as 126,050 µg/L yielded values greater than the measurement interval and would have been diluted until an accurate value was obtained. The implementation of upfront dilution of ferritin samples led to a decrease in turnaround time from a median of 2 hours and 3 minutes to 1 hour and 18 minutes (P = 0.002). Implementation of upfront dilutions of all ferritin samples reduced the possibility of hook effect, improved turnaround time and saved the cost of performing additional dilutions.

MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

NASA Astrophysics Data System (ADS)

Walsh, Edward G.; Mills, David R.; Lim, Sierin; Sana, Barindra; Brilliant, Kate E.; Park, William K. C.

2013-01-01

A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r 1 and r 2. The r 1 and r 2 values of the uniformly distributed modified ferritin were significantly higher ( r 1 = 1,290 mM-1 s-1 and r 2 = 5,740 mM-1 s-1) than values observed for wild-type ferritin (e.g., horse spleen, r 1 = 0.674 mM-1 s-1, r 2 = 95.54 mM-1 s-1). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T2 contrast with negligible T1 effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

Screening of female family members of von Willebrand disease patients: utility of a modified screening tool in a high-risk population.

PubMed

Faiz, A S; Kaveney, A; Guo, S; Murphy, S; Philipp, C S

2017-09-01

Family members of Von Willebrand disease (VWD) patients may have low levels of VWF without major bleeding episodes and often remain undiagnosed. The purpose of this study was to assess the utility of a modified Screening Tool in identifying previously untested reproductive age female family members of VWD patients for haemostatic evaluation. Ninety-four reproductive age women including 41 previously untested family members of VWD patients, 26 previously diagnosed VWD patients and 27 healthy controls were administered a modified Screening Tool and had blood drawn for CBC, ferritin, and VWF testing. Participants completed a pictorial blood assessment chart (PBAC) with menses. The modified Screening Tool was positive in 32% family members, 77% VWD patients, and 19% controls (P < 0.001). Combined with low ferritin, the modified Screening Tool was positive in 66% family members, 92% VWD patients, and 44% controls (P = 0.001). In family members, incorporating low ferritin with the modified Screening Tool resulted in a sensitivity of 86% (95% CI, 42-100) and negative predictive value of 93% (95% CI, 66-100). In the control group, NPV was between 92% and 95% for the modified Screening Tool and also for the modified Screening Tool combined with low ferritin or a positive PBAC. These data in a racially diverse population suggest the usefulness of a simple, easy to administer modified Screening Tool. In conjunction with ferritin it could be used in a primary care setting to stratify reproductive age women with a family history of VWD for haemostatic evaluation. © 2017 John Wiley & Sons Ltd.

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

PubMed

Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

2011-11-01

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

PubMed

Roger, Simon D; Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Macdougall, Iain C

2017-09-01

The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Serum ferritin concentration in sickle cell crisis.

PubMed Central

Brownell, A; Lowson, S; Brozović, M

1986-01-01

Serum ferritin, aspartate aminotransferase (AST), alkaline phosphatase and hydroxybutyrate dehydrogenase (HBD) were studied during 21 vaso-occlusive crises in 12 adults with sickle cell disease (11 SS, 1 S beta degrees). The patients comprised three groups: those who had been untransfused (4), those who had received occasional exchange transfusion in crisis (3), and those who had been multiply transfused (5). Serum ferritin concentrations in crisis were compared with those of the steady state value. Rises in serum ferritin concentrations occurred in all crises in all groups. Although AST, alkaline phosphatase, and HBD rose, there was no correlation between these and log ferritin concentrations. The clinical impression was that the degree of rise in ferritin related to the severity of the particular crisis, and the above results showed that haemolysis and liver damage were not causally related to this rise. An estimate of serum ferritin cannot be used to assess the state of iron balance in sickle cell disease unless the patient is in the steady state. The considerable rise in serum ferritin concentration found in crisis, however, may be a useful marker of the extent of vaso-occlusion and tissue damage. PMID:3958215

Photoreduction and incorporation of iron into ferritins.

PubMed Central

Laulhère, J P; Labouré, A M; Briat, J F

1990-01-01

Pea seed ferritin is able to incorporate ferrous iron into the mineral core. Fe2+ may be formed by reduction of exogenous Fe3+ with ascorbate or by photoreduction by ferritin and by ferric citrate. In our experimental conditions the bulk of the photoreduction is carried out by ferritin, which is able to photoreduce its endogenous iron. Citrate does not enhance the photoreduction capacity of ferritin, and exogenous ferric citrate improves the yield of the reaction by about 30%. The mineral core of the ferritin is shown to photoreduce actively, and the protein shell does not participate directly in the photoreduction. Low light intensities and low concentration of reducing agents do not allow a release of iron from ferritins, but induce a 'redox mill' of photoreduction and simultaneous ferroxidase-mediated incorporation. High ascorbate concentrations induce the release of ferritin iron. These reactions are accompanied by the correlated occurrence of damage caused by radicals arising from Fenton reactions, leading to specific cleavages in the 28 kDa phytoferritin subunit. This damage caused by radicals occurs during the oxidative incorporation into the mineral core and is prevented by o-phenanthroline or by keeping the samples in the dark. Images Fig. 1. Fig. 2. Fig. 3. Fig. 5. PMID:2375759

Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain

PubMed Central

Iordanova, B; Goins, WF; Clawson, DS; Hitchens, TK; Ahrens, ET

2017-01-01

The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications. PMID:22996196

Self-assembly in the ferritin nano-cage protein superfamily.

PubMed

Zhang, Yu; Orner, Brendan P

2011-01-01

Protein self-assembly, through specific, high affinity, and geometrically constraining protein-protein interactions, can control and lead to complex cellular nano-structures. Establishing an understanding of the underlying principles that govern protein self-assembly is not only essential to appreciate the fundamental biological functions of these structures, but could also provide a basis for their enhancement for nano-material applications. The ferritins are a superfamily of well studied proteins that self-assemble into hollow cage-like structures which are ubiquitously found in both prokaryotes and eukaryotes. Structural studies have revealed that many members of the ferritin family can self-assemble into nano-cages of two types. Maxi-ferritins form hollow spheres with octahedral symmetry composed of twenty-four monomers. Mini-ferritins, on the other hand, are tetrahedrally symmetric, hollow assemblies composed of twelve monomers. This review will focus on the structure of members of the ferritin superfamily, the mechanism of ferritin self-assembly and the structure-function relations of these proteins.

Permanganate-based synthesis of manganese oxide nanoparticles in ferritin

NASA Astrophysics Data System (ADS)

Olsen, Cameron R.; Smith, Trevor J.; Embley, Jacob S.; Maxfield, Jake H.; Hansen, Kameron R.; Peterson, J. Ryan; Henrichsen, Andrew M.; Erickson, Stephen D.; Buck, David C.; Colton, John S.; Watt, Richard K.

2017-05-01

This paper investigates the comproportionation reaction of MnII with {{{{MnO}}}4}- as a route for manganese oxide nanoparticle synthesis in the protein ferritin. We report that {{{{MnO}}}4}- serves as the electron acceptor and reacts with MnII in the presence of apoferritin to form manganese oxide cores inside the protein shell. Manganese loading into ferritin was studied under acidic, neutral, and basic conditions and the ratios of MnII and permanganate were varied at each pH. The manganese-containing ferritin samples were characterized by transmission electron microscopy, UV/Vis absorption, and by measuring the band gap energies for each sample. Manganese cores were deposited inside ferritin under both the acidic and basic conditions. All resulting manganese ferritin samples were found to be indirect band gap materials with band gap energies ranging from 1.01 to 1.34 eV. An increased UV/Vis absorption around 370 nm was observed for samples formed under acidic conditions, suggestive of MnO2 formation inside ferritin.

Plant Ferritin—A Source of Iron to Prevent Its Deficiency

PubMed Central

Zielińska-Dawidziak, Magdalena

2015-01-01

Iron deficiency anemia affects a significant part of the human population. Due to the unique properties of plant ferritin, food enrichment with ferritin iron seems to be a promising strategy to prevent this malnutrition problem. This protein captures huge amounts of iron ions inside the apoferritin shell and isolates them from the environment. Thus, this iron form does not induce oxidative change in food and reduces the risk of gastric problems in consumers. Bioavailability of ferritin in human and animal studies is high and the mechanism of absorption via endocytosis has been confirmed in cultured cells. Legume seeds are a traditional source of plant ferritin. However, even if the percentage of ferritin iron in these seeds is high, its concentration is not sufficient for food fortification. Thus, edible plants have been biofortified in iron for many years. Plants overexpressing ferritin may find applications in the development of bioactive food. A crucial achievement would be to develop technologies warranting stability of ferritin in food and the digestive tract. PMID:25685985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Zhiwen; Wu, Hong J.; Zhang, Youyu

Ferritins are nano-scale globular protein cages encapsulating a ferric core. They widely exist in animals, plants, and microbes, playing indispensable roles in iron homeostasis. Interestingly, our study clearly demonstrates that ferritin has an enzyme-mimic activity derived from its ferric nano-core, but not the protein cage. Further study revealed that the mimic-enzyme activity of ferritin is more thermally stable and pH-tolerant compared with horseradish peroxidase. Considering the abundance of ferritin in numerous organisms, this finding may indicate a new role of ferritin in antioxidant and detoxification metabolisms. In addition, as a natural protein-caged nanoparticle with an enzyme-mimic activity, ferritin is readilymore » conjugated with biomolecules to construct nano-biosensors, thus holds promising potential for facile and biocompatible labeling for sensitive and robust bioassays in biomedical applications.« less

Ferritin family proteins and their use in bionanotechnology

PubMed Central

He, Didi; Marles-Wright, Jon

2015-01-01

Ferritin family proteins are found in all kingdoms of life and act to store iron within a protein cage and to protect the cell from oxidative damage caused by the Fenton reaction. The structural and biochemical features of the ferritins have been widely exploited in bionanotechnology applications: from the production of metal nanoparticles; as templates for semi-conductor production; and as scaffolds for vaccine design and drug delivery. In this review we first discuss the structural properties of the main ferritin family proteins, and describe how their organisation specifies their functions. Second, we describe materials science applications of ferritins that rely on their ability to sequester metal within their cavities. Finally, we explore the use of ferritin as a container for drug delivery and as a scaffold for the production of vaccines. PMID:25573765

Antioxidant capacity of parsley cells (Petroselinum crispum L.) in relation to iron-induced ferritin levels and static magnetic field.

PubMed

Rajabbeigi, Elham; Ghanati, Faezeh; Abdolmaleki, Parviz; Payez, Atefeh

2013-12-01

This study was aimed to evaluate antioxidant response of parsley cells to 21 ppm iron and static magnetic field (SMF; 30 mT). The activity of catalase (CAT) and ascorbate peroxidase (APX) and the contents of malonyldialdehyde, iron and ferritin were measured at 6 and 12 h after treatments. Exposure to SMF increased the activity of CAT in treated cells, while combination of iron and SMF treatments as well as iron supply alone decreased CAT activity, compared to that of control cells. Combination of SMF with iron treatment reduced iron content of the cells and ameliorated mal effect of iron on CAT activity. All treatments reduced APX activity; however, the content of total ascorbate increased in response to iron and SMF+iron. The results showed that among the components of antioxidant system of parsley cells, enhanced activity of CAT in SMF-treated cells and increase of ascorbate in SMF+Fe-treated ones were responsible for the maintenance of membranes integrity. Ferritin contents of SMF- and SMF+Fe-treated cells also decreased significantly 12 h after treatments, compared to those of the control cells. These results cast doubt on the proposed functions of ferritin as a putative reactive oxygen species detoxifying molecule.

Anti-inflammatory and antioxidant effect of ginger in tuberculosis.

PubMed

Kulkarni, Rashmi Anant; Deshpande, Ajit Ramesh

2016-06-01

Tuberculosis (TB) has reemerged to become the world's leading cause of death from a single infectious agent. Inflammatory cytokines play an important role during the course of the disease and may be responsible for tissue damage by lipid peroxidation. The study was aimed to explore the anti-inflammatory and antioxidant effect of ginger in pulmonary TB patients. A total of 69 pulmonary TB patients participated in a randomized and placebo-controlled study. The intervention group received 3 g of ginger extract daily for 1 month and placebo group was supplemented with starch capsule. Participants of both groups were taking standard antitubercular treatment during the study. The concentrations of tumor necrosis factor (TNF) alpha, ferritin and malondialdehyde (MDA) in blood samples were analyzed before and after the intervention by using enzyme-linked immunosorbent assay for TNF alpha and ferritin and spectrophotometry for MDA. Ginger supplementation significantly reduced the levels of TNF alpha, ferritin and MDA in ginger supplemented group in comparison to baseline. Ginger supplementation with antitubercular treatment significantly lowered TNF alpha, ferritin and MDA concentrations in comparison to control group. Ginger was found to be effective as an anti-inflammatory and antioxidant supplement along with anti-TB therapy as it possesses strong free radical scavenging property.

Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eid, Rawan; Department of Biology, Queen's University, Kingston, Ontario; Boucher, Eric

Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomycesmore » cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast. • Rgi1p is a pro-survival protein that is not a ferritin but that may play a role in iron metabolism of yeast.« less

Coxiella burnetii Infection With Severe Hyperferritinemia in an Asplenic Patient

PubMed Central

Paine, Allison; Miya, Tadashi; Webb, Brandon J.

2015-01-01

Q fever is an uncommon but likely underreported zoonotic infection. Severe hyperferritinemia has been associated with hemophagocytic lymphohistiocytosis and other infectious diseases. In this study, we report a case of Coxiella burnetii infection in an asplenic patient complicated by severe hyperferritinemia and bone marrow infiltration. In this case, the marked ferritin elevation may have been an indicator of profound systemic macrophage activation due to preferential intracellular infection of this cell type by C burnetii, perhaps exacerbated by altered mononuclear phagocyte system function in the setting of asplenia. PMID:26430699

Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism.

PubMed

Mousa, Amany A; Ghonem, Mohamed; Elhadidy, El Hadidy M; Azmy, Emad; Elbackry, Magda; Elbaiomy, Azza A; Elzehery, Rasha R; Shaker, Gehan A; Saleh, Omyma

2016-05-01

to assess the growth and pubertal development among a group of patients with β-Thalassemia Major (β-TM) and to evaluate the role of the pituitary gland and liver MRI signal intensity (SI) reduction in assessing and predicting the clinical severity of growth and pubertal dysfunctions. Thirty-eight patients with β-TM were examined and divided into two groups: Group I patients were of normal height and puberty and Group II patients had short statures and hypogonadism. Laboratory investigations included serum ferritin, LH, FSH, prolactin, TSH, and basal and dynamic growth hormones. Pituitary and liver MRIs were performed to assess the pituitary to fat (P/F) and liver to muscle (L/M) signal intensities (SI), respectively. Fifteen healthy and sex- and age-matched subjects were included as controls. Both patient groups had significantly elevated serum ferritin and significantly decreased prolactin and IGF1 compared to control subjects. Group II showed a significant reduction in LH, FSH, and IGF1 and a significant increase in ferritin in comparison with Group I and the control group, and it had a highly significant reduction in both P/F and L/M SI in comparison with Group I (p<0.001 and 0.008, respectively). The reduced P/F ratio was significantly correlated with FSH and LH, and a cutoff for a P/F ratio ≥0.94 was obtained to differentiate between Group I and II. MRI in conjunction with the P/F signal intensity ratio is a useful and noninvasive tool for the early diagnosis of pituitary iron overload.

First biochemical and crystallographic characterization of a fast-performing ferritin from a marine invertebrate.

PubMed

De Meulenaere, Evelien; Bailey, Jake Brian; Tezcan, Faik Akif; Deheyn, Dimitri Dominique

2017-12-11

Ferritin, a multimeric cage-like enzyme, is integral to iron metabolism across all phyla through the sequestration and storage of iron through efficient ferroxidase activity. While ferritin sequences from ∼900 species have been identified, crystal structures from only 50 species have been reported, the majority from bacterial origin. We recently isolated a secreted ferritin from the marine invertebrate Chaetopterus sp. (parchment tube worm), which resides in muddy coastal seafloors. Here, we present the first ferritin from a marine invertebrate to be crystallized and its biochemical characterization. The initial ferroxidase reaction rate of recombinant Chaetopterus ferritin (ChF) is 8-fold faster than that of recombinant human heavy-chain ferritin (HuHF). To our knowledge, this protein exhibits the fastest catalytic performance ever described for a ferritin variant. In addition to the high-velocity ferroxidase activity, ChF is unique in that it is secreted by Chaetopterus in a bioluminescent mucus. Previous work has linked the availability of Fe 2+ to this long-lived bioluminescence, suggesting a potential function for the secreted ferritin. Comparative biochemical analyses indicated that both ChF and HuHF showed similar behavior toward changes in pH, temperature, and salt concentration. Comparison of their crystal structures shows no significant differences in the catalytic sites. Notable differences were found in the residues that line both 3-fold and 4-fold pores, potentially leading to increased flexibility, reduced steric hindrance, or a more efficient pathway for Fe 2+ transportation to the ferroxidase site. These suggested residues could contribute to the understanding of iron translocation through the ferritin shell to the ferroxidase site. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Hybrid magnetic materials formed by ferritin intercalated into a layered double hydroxide

NASA Astrophysics Data System (ADS)

Clemente-León, Miguel; Coronado, Eugenio; Primo, Vicent; Ribera, Antonio; Soriano-Portillo, Alejandra

2008-12-01

A hybrid magnetic material formed by ferritin intercalated into a layered double hydroxide (LDH) of Mg and Al (Mg/Al molar ratio 2) is prepared and characterized through powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, electron probe microanalysis (EPMA) and high resolution transmission electron microscopy (HRTEM). One observes an enhancement in the thermal stability of the ferritin molecules when they are inserted in the layered material. Magnetic measurements of the hybrid material exhibit the typical superparamagnetic behaviour of the ferritin molecule. On the other hand, the intercalation of ferritin into the LDH guarantees a homogeneous dispersion of the ferritin molecules, which do not aggregate even after calcination of the sample. This feature allows obtaining well-dispersed magnetic metal oxide nanoparticles upon calcination of the hybrid material.

Ferritin-Triggered Redox Cycling for Highly Sensitive Electrochemical Immunosensing of Protein.

PubMed

Akanda, Md Rajibul; Ju, Huangxian

2018-06-04

Electrochemical immunoassay amplified with redox cycling has become a challenging topic in highly sensitive analysis of biomarkers. Here a ferritin-triggered redox cycling is reported by using a highly outersphere reaction-philic (OSR-philic) redox mediator ruthenium hexamine (Ru(NH3)63+) to perform the OSR-philic/innersphere reaction-philic (ISR-philic) controlled signal amplification. The screened mediator can meet the needs of lower E0 than ferritin, low reactivity with ISR-philic species, and quick electron exchange with ferritin redox couple. The ferritin-labeled antibody is firstly bounded to immunosensor surface by recognizing the target antigen capured by the immobilized primary antibody. The ferritin then mediates OSR-philic/ISR-philic transfer from Ru(NH3)63+/2+/immunosensor to ferritin-H2O2 redox system. The fast mediation and excellent resistant of highly OSR-philic Ru(NH3)63+ against radical oxygen species lead to highly sensitive electrochemical readout and high signal-to-background ratio. The proposed redox cycling greatly enhances the readout signal and the sensitivity of traditional ferritin-labelled sandwich immunoassay. Using Enteropathogenic Coli (E. Coli) antigen as a model analyte, the developed method shows excellent linearity over the concentration range from 10.0 pg/mL to 0.1 µg/mL and a detection limit of 10.0 fg/mL. The acceptable accuracy, good reproducibility and selectivity of the proposed immunoassay method in real samples indicate the superior practicability of the ferritin-triggered redox cycling.

Solution and solid state NMR approaches to draw iron pathways in the ferritin nanocage.

PubMed

Lalli, Daniela; Turano, Paola

2013-11-19

Ferritins are intracellular proteins that can store thousands of iron(III) ions as a solid mineral. These structures autoassemble from four-helix bundle subunits to form a hollow sphere and are a prototypical example of protein nanocages. The protein acts as a reservoir, encapsulating iron as ferric oxide in its central cavity in a nontoxic and bioavailable form. Scientists have long known the structural details of the protein shell, owing to very high resolution X-ray structures of the apoform. However, the atomic level mechanism governing the multistep biomineralization process remained largely elusive. Through analysis of the chemical behavior of ferritin mutants, chemists have found the role of some residues in key reaction steps. Using Mössbauer and XAS, they have identified some di-iron intermediates of the catalytic reaction trapped by rapid freeze quench. However, structural information about the iron interaction sites remains scarce. The entire process is governed by a number of specific, but weak, interactions between the protein shell and the iron species moving across the cage. While this situation may constitute a major problem for crystallography, NMR spectroscopy represents an optimal tool to detect and characterize transient species involving soluble proteins. Regardless, NMR analysis of the 480 kDa ferritin represents a real challenge. Our interest in ferritin chemistry inspired us to use an original combination of solution and solid state approaches. While the highly symmetric structure of the homo-24-mer frog ferritin greatly simplifies the spectra, the large protein size hinders the efficient coherence transfer in solution, thus preventing the sequence specific assignments. In contrast, extensive (13)C-spin diffusion makes the solution (13)C-(13)C NOESY experiment our gold standard to monitor protein side chains both in the apoprotein alone and in its interaction with paramagnetic iron species, inducing line broadening on the resonances of nearby residues. We could retrieve the structural information embedded in the (13)C-(13)C NOESY due to a partial sequence specific assignment of protein backbone and side chains we obtained from solid state MAS NMR of ferritin microcrystals. We used the 59 assigned amino acids (∼33% of the total) as probes to locate paramagnetic ferric species in the protein cage. Through this approach, we could identify ferric dimers at the ferroxidase site and on their pathway towards the nanocage. Comparison with existing data on bacterioferritins and bacterial ferritins, as well as with eukaryotic ferritins loaded with various nonfunctional divalent ions, allowed us to reinterpret the available information. The resulting picture of the ferroxidase site is slightly different with various ferritins but is designed to provide multiple and generally weak iron ligands. The latter assist binding of two incoming iron(II) ions in two proximal positions to facilitate coupling with oxygen. Subsequent oxidation is accompanied by a decrease in the metal-metal distance (consistent with XAS/Mössbauer) and in the number of protein residues involved in metal coordination, facilitating the release of products as di-iron clusters under the effect of new incoming iron(II) ions.

Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

PubMed

Toki, Yasumichi; Ikuta, Katsuya; Kawahara, Yoshie; Niizeki, Noriyasu; Kon, Masayuki; Enomoto, Motoki; Tada, Yuko; Hatayama, Mayumi; Yamamoto, Masayo; Ito, Satoshi; Shindo, Motohiro; Kikuchi, Yoko; Inoue, Mitsutaka; Sato, Kazuya; Fujiya, Mikihiro; Okumura, Toshikatsu

2017-07-01

Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

Increase in type II collagen turnover after iron depletion in patients with hereditary haemochromatosis.

PubMed

Richette, Pascal; Eymard, Claire; Deberg, Michelle; Vidaud, Dominique; de Kerguenec, Caroline; Valla, Dominique; Vicaut, Eric; Bardin, Thomas; Henrotin, Yves

2010-04-01

To determine the effects of iron depletion on serum levels of joint biomarkers and on joint symptoms in patients with hereditary haemochromatosis (HH). Levels of biomarkers were measured in 18 patients with HH at the time of diagnosis and after iron depletion. The markers were type II collagen degradation (Coll2-1) and its nitrated form (Coll2-1NO(2)), type II procollagen synthesis (CPII), MPO, COMP and HA. For each patient, demographic data were collected and the global joint pain (visual analogue scale) was assessed before and after iron depletion by phlebotomy. A total of 18 patients [10 males; mean (s.d.) age 48 (11) years] were homozygous for the C282Y mutation. No patient had liver dysfunction. Ferritin level before iron removal was 627.5 (range 133-3276) microg/l, and duration of the iron depletion phase was 295 (70-670) days. Serum levels of both Coll2-1 and CPII were significantly increased from diagnosis after iron depletion: 80.1 (55.6-113.5) vs 96.0 (48.8-136.3) nM (P = 0.004) and 731.4 (374.2-1012.3) vs 812.8 (535.8-1165.6) ng/ml (P = 0.03), respectively. Levels of other biomarkers were not modified by iron depletion. Ferritin level, which at baseline was correlated with body iron store (r = 0.63; P = 0.008), was significantly correlated with HA level measured before iron depletion (r = 0.60; P = 0.01). Global joint pain was not correlated with ferritin concentration and did not significantly decrease after iron depletion: 43 (19-73) vs 36 (16-67) mm (P = 0.07). In patients with HH, cartilage homoeostasis is modified by iron excess and an increase in type II collagen turnover occurs after excess iron removal.

Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions.

PubMed Central

Lescure, A M; Massenet, O; Briat, J F

1990-01-01

Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron. Images Fig. 2. Fig. 3. PMID:2264818

Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions.

PubMed

Lescure, A M; Massenet, O; Briat, J F

1990-11-15

Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron.

Cerebrospinal fluid ferritin and albumin index: potential candidates for scoring system to differentiate between bacterial and viral meningitis in children.

PubMed

Jebamalar, Angelin A; Prabhat; Balakrishnapillai, Agiesh K; Parmeswaran, Narayanan; Dhiman, Pooja; Rajendiran, Soundravally

2016-07-01

To evaluate the diagnostic role of cerebrospinal fluid (CSF) ferritin and albumin index (AI = CSF albumin/serum albumin × 1000) in differentiating acute bacterial meningitis (ABM) from acute viral meningitis (AVM) in children. The study included 42 cases each of ABM and AVM in pediatric age group. Receiver operating characteristic (ROC) analysis was carried out for CSF ferritin and AI. Binary logistic regression was also done. CSF ferritin and AI were found significantly higher in ABM compared to AVM. Model obtained using AI and CSF ferritin along with conventional criteria is better than existing models.

Tracking Temperature-Dependent Relaxation Times of Ferritin Nanomagnets with a Wideband Quantum Spectrometer

NASA Astrophysics Data System (ADS)

Schäfer-Nolte, Eike; Schlipf, Lukas; Ternes, Markus; Reinhard, Friedemann; Kern, Klaus; Wrachtrup, Jörg

2014-11-01

We demonstrate the tracking of the spin dynamics of ensemble and individual magnetic ferritin proteins from cryogenic up to room temperature using the nitrogen-vacancy color center in diamond as a magnetic sensor. We employ different detection protocols to probe the influence of the ferritin nanomagnets on the longitudinal and transverse relaxation of the nitrogen-vacancy center, which enables magnetic sensing over a wide frequency range from Hz to GHz. The temperature dependence of the observed spectral features can be well understood by the thermally induced magnetization reversals of the ferritin and enables the determination of the anisotropy barrier of single ferritin molecules.

Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

PubMed

Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

2018-01-01

Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

Functionalization and Characterization of Magnetic Nanoparticles for the Detection of Ferritin Accumulation in Alzheimer's Disease.

PubMed

Fernández, Tamara; Martínez-Serrano, Alberto; Cussó, Lorena; Desco, Manuel; Ramos-Gómez, Milagros

2018-05-16

Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the presence of some of the pathological signs of AD. In the present study, we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an antiferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations. Both in vitro and after intravenous injection, functionalized magnetic nanoparticles were able to recognize and bind specifically to the ferritin protein accumulated in the subiculum area of the AD transgenic mice.

Iron-induced nitric oxide leads to an increase in the expression of ferritin during the senescence of Lotus japonicus nodules.

PubMed

Chungopast, Sirinapa; Duangkhet, Mallika; Tajima, Shigeyuki; Ma, Jian Feng; Nomura, Mika

2017-01-01

Iron is an essential nutrient for legume-rhizobium symbiosis and accumulates abundantly in the nodules. However, the concentration of free iron in the cells is strictly controlled to avoid toxicity. It is known that ferritin accumulates in the cells as an iron storage protein. During nodule senescence, the expression of the ferritin gene, Ljfer1, was induced in Lotus japonicus. We investigated a signal transduction pathway leading to the increase of Ljfer1 in the nodule. The Ljfer1 promoter of L. japonicus contains a conserved Iron-Dependent Regulatory Sequence (IDRS). The expression of Ljfer1 was induced by the application of iron or sodium nitroprusside, which is a nitric oxide (NO) donor. The application of iron to the nodule increased the level of NO. These data strongly suggest that iron-induced NO leads to increased expression of Ljfer1 during the senescence of L. japonicus nodules. Copyright © 2016 Elsevier GmbH. All rights reserved.

Making bread with sourdough improves iron bioavailability from reconstituted fortified wheat flour in mice.

PubMed

Chaoui, Asmaa; Faid, Mohamed; Belahsen, Rekia

2006-01-01

This study aimed to evaluate the effect of a diet prepared with traditional sourdough (TS) on iron status. Levels of blood hemoglobin (Hb), Hematocrite (Ht), serum ferritin and serum iron as well as excreted iron were determined in three groups of mice fed with: TS bread (TS group), baking yeast bread (BY group) or bread with no starters (control group), respectively. The results show that the levels of Hb, Ht, ferritin and iron were significantly higher in the TS compared to the BY and control groups. Also a significant decrease in the excreted iron levels was observed in the mice fed with TS compared to the others dietary groups. In conclusion, the study results indicate an improvement of iron status indicators in mice when they were fed sourdough bread as compared to baking yeast bread and bread with no starters.

Use of Iron Chelating Agents in Transfusion Dependent Thalassaemia Major Patients.

PubMed

Santra, S; Bhattacharya, A; Mukhopadhyay, T; Agrawal, D; Kumar, S; Das, P; Chakrabarty, P

2015-10-01

This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.

Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2013-12-01

targeted liposomes containing H- ferritin caused a 9.5 day extension of lifespan as compared to No Surgery; this effect is trending strongly towards... Ferritin 2.0 mg/ml groups, respectively. There is a trend towards significance in overall survival, p =0.09. 20 Figure 3 Figure 3...in the No Surgery, aCSF, and H- Ferritin groups, respectively. There is a trend towards significance, p =0.11. 24 Figure 7 Figure 7

Repletion of Zinc and Iron Deficiencies Improves Cognition of Premenopausal Women.

DTIC Science & Technology

1997-10-01

to our earlier observations in premenopausal women (1, 13) and are consistent with the fact that many premenopausal women select diets that are low...women: associations of diet with serum ferritin and plasma zinc disappearance, and of serum ferritin with plasma zinc and plasma zinc disappearance...women: Associations of diet with serum ferritin and plasma zinc disappearance and of serum ferritin with plasma zinc and plasma zinc disappearance. J

Study of the rhizobacterium Azospirillum brasilense Sp245 using Mössbauer spectroscopy with a high velocity resolution: Implication for the analysis of ferritin-like iron cores

NASA Astrophysics Data System (ADS)

Alenkina, I. V.; Oshtrakh, M. I.; Tugarova, A. V.; Biró, B.; Semionkin, V. A.; Kamnev, A. A.

2014-09-01

The results of a comparative study of two samples of the rhizobacterium Azospirillum brasilense (strain Sp245) prepared in different conditions and of human liver ferritin using Mössbauer spectroscopy with a high velocity resolution demonstrated the presence of ferritin-like iron (i.e. iron similar to that found in ferritin-like proteins) in the bacterium. Mössbauer spectra of these samples were fitted in two ways: as a rough approximation using a one quadrupole doublet fit (the homogeneous iron core model) and using a superposition of quadrupole doublets (the heterogeneous iron core model). Both results demonstrated differences in the Mössbauer parameters for mammalian ferritin and for bacterial ferritin-like iron. Moreover, some differences in the Mössbauer parameters were observed between the two samples of A. brasilense Sp245 related to the differences in their preparation conditions.

Ferritin family proteins and their use in bionanotechnology.

PubMed

He, Didi; Marles-Wright, Jon

2015-12-25

Ferritin family proteins are found in all kingdoms of life and act to store iron within a protein cage and to protect the cell from oxidative damage caused by the Fenton reaction. The structural and biochemical features of the ferritins have been widely exploited in bionanotechnology applications: from the production of metal nanoparticles; as templates for semi-conductor production; and as scaffolds for vaccine design and drug delivery. In this review we first discuss the structural properties of the main ferritin family proteins, and describe how their organisation specifies their functions. Second, we describe materials science applications of ferritins that rely on their ability to sequester metal within their cavities. Finally, we explore the use of ferritin as a container for drug delivery and as a scaffold for the production of vaccines. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

The usage of phage mini-antibodies as a means of detecting ferritin concentration in animal blood serum.

PubMed

Staroverov, Sergey A; Volkov, Alexei A; Fomin, Alexander S; Laskavuy, Vladislav N; Mezhennyy, Pavel V; Kozlov, Sergey V; Larionov, Sergey V; Fedorov, Michael V; Dykman, Lev A; Guliy, Olga I

2015-01-01

Mini-antibodies that have specific ferritin response have been produced for the first time using sheep's phage libraries (Griffin.1, Medical Research Council, Cambridge, UK). Produced phage antibodies were used for the first time for the development of diagnostic test kits for ferritin detection in the blood of cattle. The immunodot assay with secondary biospecific labeling is suggested as means of ferritin detection in cow blood serum (antiferritin phage antibodies and rabbit antiphage antibodies conjugated with different labels). Сolloidal gold, gold nanoshells, and horse reddish peroxidase used as labels have shown a similar response while detecting concentration of ferritin (0.2 mg/mL). It is shown that the method of solid-phase immunoassay with a visual view of the results allows determination of the minimum concentration of ferritin in the blood of cows at 0.225 g/mL.

Restless legs syndrome, sleep impairment, and fatigue in chronic obstructive pulmonary disease.

PubMed

Cavalcante, Antonio George Matos; de Bruin, Pedro Felipe Carvalhedo; de Bruin, Veralice Meireles Sales; Pereira, Eanes Delgado Barros; Cavalcante, Marina Medeiros; Nunes, Deuzilane Muniz; Viana, Cynthia Sampaio

2012-08-01

To investigate the frequency of factors associated with restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD). RLS diagnosis was investigated (International RLS Study Group, IRLSSG) and severity was assessed (IRLS rating scale) in 104 consecutive COPD patients (age 69.1±8). Other measures were dyspnea severity (Modified Medical Research Council, MMRC), sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime somnolence (Epworth Sleepiness Scale, ESS), depressive symptoms (Beck Depression Inventory, BDI-II), and fatigue (Fatigue Severity Scale, FSS). Laboratory values included hemoglobin, ferritin, creatinine, and fibrinogen. Thirty-two patients (30.8%) were diagnosed with RLS (65.6% women), which was moderate/severe (IRLS >11) in 26 (81.3%). RLS symptoms started after age 40 in most patients (93.3%). RLS patients had poorer sleep quality (PSQI >5=59.6%; p=0.002), worse fatigue (FSS >27=51%; p=0.005), and more depressive symptoms (BDI-II >10=14.4%; p=0.005). Patients with RLS also presented more severe dyspnea (p=0.009) and lower creatinine levels (p=0.005). Overall, fatigue severity was correlated with older age (p=0.001); level of dyspnea was positively correlated with PSQI and FSS (p<0.005) and negatively correlated with ferritin (p=0.03) and creatinine (p=0.005), and PSQI scores correlated positively with FSS (p<0.005) and negatively with ferritin (p=0.005) and creatinine (p=0.02). Quality of sleep was independently predicted by dyspnea severity and creatinine and fatigue by age and depression. RLS is common in COPD. Patients with RLS have low creatinine, poorer quality of sleep, and more fatigue and depressive symptoms. RLS symptom severity is correlated to lower ferritin and severity of dyspnea. Copyright © 2012 Elsevier B.V. All rights reserved.

Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.

1984-01-01

Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, ..beta..-HCG, and ..beta../sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serummore » the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and ..beta../sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum ..beta..-HCG was normal in all patients. According to these results serum ferritin, TPA, and ..beta../sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum ..beta../sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and ..beta../sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases.« less

mRNA Regulation of Cardiac Iron Transporters and Ferritin Subunits in a Mouse Model of Iron Overload

PubMed Central

Brewer, Casey J.; Wood, Ruth I.; Wood, John C.

2014-01-01

Iron cardiomyopathy is the leading cause of death in iron overload. Men have twice the mortality rate of women, though the cause is unknown. In hemojuvelin-knockout mice, a model of the disease, males load more cardiac iron than females. We postulated that sex differences in cardiac iron import cause differences in cardiac iron concentration. RT-PCR was used to measure mRNA of cardiac iron transporters in hemojuvelin-knockout mice. No sex differences were discovered among putative importers of non-transferrin bound iron (L-type and T-type calcium channels, ZRT/IRT-like protein 14 zinc channels). Transferrin-bound iron transporters were also analyzed; these are controlled by the iron regulatory element/iron regulatory protein (IRE/IRP) system. There was a positive relationship between cardiac iron and ferroportin mRNA in both sexes, but it was significantly steeper in females (p<0.05). Transferrin receptor 1 and divalent metal transporter 1 were more highly expressed in females than males (p<0.01 and p<0.0001, respectively), consistent with their lower cardiac iron levels, as predicted by IRE/IRP regulatory pathways. Light-chain (L) ferritin showed a positive correlation with cardiac iron that was nearly identical in males and females (R2=0.41, p<0.01 and R2=0.56, p<0.05, respectively), while heavy-chain (H) ferritin was constitutively expressed in both sexes. This represents the first report of IRE/IRP regulatory pathways in the heart. Transcriptional regulation of ferroportin was suggested in both sexes, creating a potential mechanism for differential set points for iron export. Constitutive H-ferritin expression suggests a logical limit to cardiac iron buffering capacity at levels known to produce heart failure in humans. PMID:25220979

Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants.

PubMed

Sturza, Julie; Silver, Monica K; Xu, Lin; Li, Mingyan; Mai, Xiaoqin; Xia, Yankai; Shao, Jie; Lozoff, Betsy; Meeker, John

2016-01-01

Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning. Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split). Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant's cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group. ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9 months in a cohort study of Chinese infants

PubMed Central

Sturza, Julie; Silver, Monica K.; Xu, Lin; Li, Mingyan; Mai, Xiaoqin; Xia, Yankai; Shao, Jie; Lozoff, Betsy; Meeker, John

2016-01-01

Background Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning. Methods Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split). Results Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant’s cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group. Conclusions ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect. PMID:27166702

Multiple ferritins are vital to successful blood feeding and reproduction of the hard tick Haemaphysalis longicornis.

PubMed

Galay, Remil Linggatong; Aung, Kyaw Min; Umemiya-Shirafuji, Rika; Maeda, Hiroki; Matsuo, Tomohide; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Suzuki, Hiroshi; Xuan, Xuenan; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2013-05-15

Ticks are obligate hematophagous parasites and important vectors of diseases. The large amount of blood they consume contains great quantities of iron, an essential but also toxic element. The function of ferritin, an iron storage protein, and iron metabolism in ticks need to be further elucidated. Here, we investigated the function a newly identified secreted ferritin from the hard tick Haemaphysalis longicornis (HlFER2), together with the previously identified intracellular ferritin (HlFER1). Recombinant ferritins, expressed in Escherichia coli, were used for anti-serum preparation and were also assayed for iron-binding activity. RT-PCR and western blot analyses of different organs and developmental stages of the tick during blood feeding were performed. The localization of ferritins in different organs was demonstrated through an indirect immunofluorescent antibody test. RNA interference (RNAi) was performed to evaluate the importance of ferritin in blood feeding and reproduction of ticks. The midgut was also examined after RNAi using light and transmission electron microscopy. RT-PCR showed differences in gene expression in some organs and developmental stages. Interestingly, only HlFER2 was detected in the ovary during oviposition and in the egg despite the low mRNA transcript. RNAi induced a reduction in post-blood meal body weight, high mortality and decreased fecundity. The expression of vitellogenin genes was affected by silencing of ferritin. Abnormalities in digestive cells, including disrupted microvilli, and alteration of digestive activity were also observed. Taken altogether, our results show that the iron storage and protective functions of ferritin are crucial to successful blood feeding and reproduction of H. longicornis.

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels*

PubMed Central

Chandramouli, Balasubramanian; Bernacchioni, Caterina; Di Maio, Danilo; Turano, Paola; Brancato, Giuseppe

2016-01-01

Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe2+-loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe2+ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe2+ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H′ protein and some of its variants as case studies. We describe the structural features that determine Fe2+ translocation with atomistic detail, and we propose a putative mechanism for Fe2+ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin. PMID:27756844

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels.

PubMed

Chandramouli, Balasubramanian; Bernacchioni, Caterina; Di Maio, Danilo; Turano, Paola; Brancato, Giuseppe

2016-12-02

Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe 2+ -loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe 2+ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe 2+ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H' protein and some of its variants as case studies. We describe the structural features that determine Fe 2+ translocation with atomistic detail, and we propose a putative mechanism for Fe 2+ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Human-brain ferritin studied by muon spin rotation: a pilot study

NASA Astrophysics Data System (ADS)

Bossoni, Lucia; Grand Moursel, Laure; Bulk, Marjolein; Simon, Brecht G.; Webb, Andrew; van der Weerd, Louise; Huber, Martina; Carretta, Pietro; Lascialfari, Alessandro; Oosterkamp, Tjerk H.

2017-10-01

Muon spin rotation is employed to investigate the spin dynamics of ferritin proteins isolated from the brain of an Alzheimer’s disease (AD) patient and of a healthy control, using a sample of horse-spleen ferritin as a reference. A model based on the Néel theory of superparamagnetism is developed in order to interpret the spin relaxation rate of the muons stopped by the core of the protein. Using this model, our preliminary observations show that ferritins from the healthy control are filled with a mineral compatible with ferrihydrite, while ferritins from the AD patient contain a crystalline phase with a larger magnetocrystalline anisotropy, possibly compatible with magnetite or maghemite.

Insect Ferritins: typical or atypical?

PubMed Central

Pham, Daphne Q. D.; Winzerling, Joy J.

2010-01-01

Insects transmit millions of cases of disease each year, and cost millions of dollars in agricultural losses. The control of insect-borne diseases is vital for numerous developing countries, and the management of agricultural insect pests is a very serious business for developed countries. Control methods should target insect-specific traits in order to avoid non-target effects, especially in mammals. Since insect cells have had a billion years of evolutionary divergence from those of vertebrates, they differ in many ways that might be promising for the insect control field—especially, in iron metabolism because current studies have indicated that significant differences exist between insect and mammalian systems. Insect iron metabolism differs from that of vertebrates in the following respects. Insect ferritins have a heavier mass than mammalian ferritins. Unlike their mammalian counterparts, the insect ferritin subunits are often glycosylated and are synthesized with a signal peptide. The crystal structure of insect ferritin also shows a tetrahedral symmetry consisting of 12 heavy chain and 12 light chain subunits in contrast to that of mammalian ferritin that exhibits an octahedral symmetry made of 24 heavy chain and 24 light chain subunits. Insect ferritins associate primarily with the vacuolar system and serve as iron transporters—quite the opposite of the mammalian ferritins, which are mainly cytoplasmic and serve as iron storage proteins. This review will discuss these differences. PMID:20230873

PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis

PubMed Central

Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo

2017-01-01

Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC–binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin. PMID:28375153

METAL-DEPENDENT EXPRESSION OF FERRITIN AND LACTOFERRIN BY RESPIRATORY EPITHELIAL CELLS

EPA Science Inventory

Increased availability of catalytically active metal has been associated with an oxidative injury. The sequestration of transition metals within intracellular ferritin confers an antioxidant function to this protein. Such storage by ferritin requires that the metal be transported...

Effect of nutrition education and diet modification in iron depleted preschool children in nurseries in Tehran: a pilot study.

PubMed

Khoshnevisan, Farnaz; Kimiagar, Masood; Kalantaree, Nasser; Valaee, Nasser; Shaheedee, Nooshin

2004-07-01

In view of the high prevalence of iron deficiency in preschool children and its consequences, this study was carried out to examine the effect of nutrition education and dietary modification on 438 two- to six-year-old nursery school children in Tehran in 1999. Sixty-two children who were judged anemic, iron-depleted, or having low iron stores were randomly allocated to "control," "dietary modification" (consuming one additional citrus fruit after lunch), and "nutrition education" (teaching the mothers proper eating patterns based on the food pyramid) groups. Food habits were surveyed, including 24-hour dietary recall and food frequency, as well as timing of consumption of special items; this survey was carried out for each child before and after intervention. After three months, blood samples were taken from the subjects. The prevalence of anemia, iron depletion, and low iron stores was 11.4, 62.8, and 15.1% respectively, with no significant differences observed in hemoglobin and percent transferrin saturation (%TS) between the groups. Mean+/-SD serum ferritin concentrations in "control," "diet modification," and "nutrition education" groups were 8.9+/-3.1, 9.5+/-3.7, and 6.9+/-2.3 microg/dL. The same figures at the end of intervention were 6.9+/-3.5, 11.2+/-5, and 10.7+/-5.9 microg/dL, respectively. Analysis of variance showed ferritin concentrations to be significantly different, in that there was a reduction in the control and elevation in the nutrition education groups. There was no significant difference in %TS before and after the intervention. During three months of intervention, changes in frequency of fruit and fruit juice intake after the meals in nutrition education and diet modification groups were significantly correlated to serum ferritin alteration. Frequency of fruit juice intake (rich in vitamin C) after meals (at least five times a week) can significantly increase serum ferritin within three months. Therefore, educating mothers of iron-deficient children while increasing the iron stores in children can prevent the recurrence of iron deficiency and result in general child well-being.

Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

PubMed Central

Zarjou, Abolfazl; Bolisetty, Subhashini; Joseph, Reny; Traylor, Amie; Apostolov, Eugene O.; Arosio, Paolo; Balla, Jozsef; Verlander, Jill; Darshan, Deepak; Kuhn, Lukas C.; Agarwal, Anupam

2013-01-01

Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule–specific FtH-knockout mice (FtHPT–/– mice). FtHPT–/– mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtHPT–/– mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase–associated lipocalin, hemopexin, and transferrin were increased in FtHPT–/– mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI. PMID:24018561

Study of Insulin Resistance in Patients With β Thalassemia Major and Validity of Triglyceride Glucose (TYG) Index.

PubMed

Ansari, Arif M; Bhat, Kamalakshi G; Dsa, Smitha S; Mahalingam, Soundarya; Joseph, Nitin

2018-03-01

Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin >1500 ng/mL were studied. Serum ferritin, fasting blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG index calculated and analyzed. Mean fasting glucose, triglyceride, and serum insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of thalassemia patients and showed increase with age and serum ferritin. Insulin resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of 4.3. Using receiver operating charecteristic curve analysis, it was found that, by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from 39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value of 4.0215 for TYG index for better sensitivity and specificity in identifying insulin resistance.

Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer.

PubMed

Truffi, Marta; Fiandra, Luisa; Sorrentino, Luca; Monieri, Matteo; Corsi, Fabio; Mazzucchelli, Serena

2016-05-01

Nowadays cancer represents a prominent challenge in clinics. Main achievements in cancer management would be the development of highly accurate and specific diagnostic tools for early detection of cancer onset, and the generation of smart drug delivery systems for targeted chemotherapy release in cancer cells. In this context, protein-based nanocages hold a tremendous potential as devices for theranostics purposes. In particular, ferritin has emerged as an excellent and promising protein-based nanocage thanks to its unique architecture, surface properties and high biocompatibility. By exploiting natural recognition of the Transferrin Receptor 1, which is overexpressed on tumor cells, ferritin nanocages may ensure a proper drug delivery and release. Moreover, researchers have applied surface functionalities on ferritin cages for further providing active tumor targeting. Encapsulation strategies of non metal-containing drugs within ferritin cages have been explored and successfully performed with encouraging results. Various preclinical studies have demonstrated that nanoformulation within ferritin nanocages significantly improved targeted therapy and accurate imaging of cancer cells. Aims of this review are to describe structure and functions of ferritin nanocages, and to provide an overview about the nanotechnological approaches implemented for applying them to cancer diagnosis and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemistry at the protein–mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster

PubMed Central

Pozzi, Cecilia; Di Pisa, Flavio; Mangani, Stefano; Turano, Paola

2017-01-01

X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (μ3-oxo)Tris[(μ2-peroxo)(μ2-glutamato-κO:κO′)](glutamato-κO)(diaquo)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin. PMID:28202724

Differents aspects du fer dans l'organisme

PubMed Central

Bessis, Marcel; Breton-Gorius, Janine

1959-01-01

On voit des molécules de ferritine apparaitre dans le cytoplasme des cellules réticulaires au cours de la digestion des érythrocytes, autour des stromas phagocytés. Cette ferritine s'accumule en amas dans lesquels entrent d'autres substances, en particulier des lipides, provenant aussi des stromas globulaires et qui apparaissent sous forme myélinique. Souvent la ferritine se dispose d'une manière cristalline. Parfois la ferritine et l'apoferritine alternent dans ces cristaux. Parfois l'hémosidérine contient des cristaux qui semblent bien être de l'apoferritine pure. L'injection de sels de fer donne lieu à l'apparition de ferritine dans les cellules réticulaires. Dans les conditions de nos expériences, la plus grande partie du fer injecté était sous forme de ferritine dans un délai de 3 jours. Un aspect intermédiaire entre celui du fer injecté et celui de la ferritine a été trouvé. Dans le cas des injections de saccharate de fer ce sont de fines aiguilles; dans le cas des injections de lactate de fer, il s'agit de masses fibreuses. PMID:13800106

Development of a Bio-nanobattery for Distributed Power Storage Systems

NASA Technical Reports Server (NTRS)

King, Glen C.; Choi, Sang H.; Chu, Sang-Hyon; Kim, Jae-Woo; Park, Yeonjoon; Lillehei, Peter; Watt, Gerald D.; Davis, Robert; Harb, John N.

2004-01-01

Currently available power storage systems, such as those used to supply power to microelectronic devices, typically consist of a single centralized canister and a series of wires to supply electrical power to where it is needed in a circuit. As the size of electrical circuits and components become smaller, there exists a need for a distributed power system to reduce Joule heating, wiring, and to allow autonomous operation of the various functions performed by the circuit. Our research is being conducted to develop a bio-nanobattery using ferritins reconstituted with both an iron core (Fe-ferritin) and a cobalt core (Co-ferritin). Both Co-ferritin and Fe-ferritin were synthesized and characterized as candidates for the bio-nanobattery. The reducing capability was determined as well as the half-cell electrical potentials, indicating an electrical output of nearly 0.5 V for the battery cell. Ferritins having other metallic cores are also being investigated, in order to increase the overall electrical output. Two dimensional ferritin arrays were also produced on various substrates, demonstrating the necessary building blocks for the bio-nanobattery. The bio-nanobattery will play a key role in moving to a distributed power storage system for electronic applications.

Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster.

PubMed

Pozzi, Cecilia; Ciambellotti, Silvia; Bernacchioni, Caterina; Di Pisa, Flavio; Mangani, Stefano; Turano, Paola

2017-03-07

X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (μ 3 -oxo)Tris[(μ 2 -peroxo)(μ 2 -glutamato-κ O :κ O ')](glutamato-κ O )(diaquo)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin.

Direct evidence of spatially selective iron mineralization using an immobilized ferritin protein cage.

PubMed

Uto, Koichiro; Yamamoto, Kazuya; Kishimoto, Naoko; Muraoka, Masahiro; Aoyagi, Takao; Yamashita, Ichiro

2014-04-01

(Apo)ferritins are cage-shaped proteins which have recently received a great deal of attention because the inner cavity of the protein shell can be used as a size-restricted reaction field for the synthesis of nanomaterials. The biomineralization behavior and inorganic nanoparticle (NP) synthesis mechanism of (apo)ferritin in solution systems have been studied but the mineralization behavior of (apo)ferritin on the substrates has not yet been well studied. Here, we conducted quantitative and kinetic analyses of the mineralization behavior of immobilized (apo)ferritin on a polyelectrolyte multilayer (PEM) using quartz crystal microbalance (QCM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) techniques. We demonstrated that the (apo)ferritin immobilized on a substrate synthesizes a ferrihydrite core within the confines of the protein cage; similar to a solution dispersed system. In addition, we applied a ferritin/apoferritin blended monolayer to the study of iron mineralization and revealed that biomineralization in this system is spatially selective. It is important to understand the mineralization mechanisms for the synthesis of other functional NPs as this approach has potential for a broad range of magnetic, catalytic, and biomedical sensing applications.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Y.; Chen, D; Park, S

High-density arrays of highly ordered ferritin nanocages are fabricated through the guided assembly of thiol-modified ferritin on prepatterned gold nanodots, which are prepared by block copolymer micelle lithography. One and only one ferritin nanocage is anchored to each gold nanodot, as confirmed by scanning electron and scanning force microscopy.

Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2013-09-01

and 129 days in the No Surgery, aCSF, and H- Ferritin 2.0 mg/ml groups, respectively. There is a trend towards significance in overall survival, p...H- Ferritin 4.0 mg/ml groups, respectively. There is a trend towards a significant extension of lifespan with aCSF, p =0.09. 21 Figure 5...125.75 days, 131 days, and 128 days in the No Surgery, aCSF, and H- Ferritin groups, respectively. There is a trend towards significance, p =0.11

Hierarchical Biosilicates by the 3-D Replication of Block Copolymer Templates in Supercritical Fluids

DTIC Science & Technology

2009-12-30

Iron Oxide Nanoparticles through Supercritical CO2 Infusion of TEOS into Ferritin Doped Block Copolymers…………………………………………………...4 4.2 Simple...which is doped with ferritin (yellow spheres). The blue PPO domains are removed during calcination as is the apoferritin shell, leaving magnetic...iron oxide particles (black) embedded in the mesoporous silica film. 5 2 TEM images of ferritin -containing samples at the specified ferritin

Incorporation of organometallic Ru complexes into apo-ferritin cage.

PubMed

Takezawa, Yusuke; Böckmann, Philipp; Sugi, Naoki; Wang, Ziyue; Abe, Satoshi; Murakami, Tatsuya; Hikage, Tatsuo; Erker, Gerhard; Watanabe, Yoshihito; Kitagawa, Susumu; Ueno, Takafumi

2011-03-14

Spherical protein cages such as an iron storage protein, ferritin, have great potential as nanometer-scale capsules to assemble and store metal ions and complexes. We report herein the synthesis of a composite of an apo-ferritin cage and Ru(p-cymene) complexes. Ru complexes were efficiently incorporated into the ferritin cavity without degradation of its cage structure. X-Ray crystallography revealed that the Ru complexes were immobilized on the interior surface of the cage mainly by the coordination of histidine residues.

Large G protein α-subunit XLαs limits clathrin-mediated endocytosis and regulates tissue iron levels in vivo.

PubMed

He, Qing; Bouley, Richard; Liu, Zun; Wein, Marc N; Zhu, Yan; Spatz, Jordan M; Wang, Chia-Yu; Divieti Pajevic, Paola; Plagge, Antonius; Babitt, Jodie L; Bastepe, Murat

2017-11-07

Alterations in the activity/levels of the extralarge G protein α-subunit (XLαs) are implicated in various human disorders, such as perinatal growth retardation. Encoded by GNAS , XLαs is partly identical to the α-subunit of the stimulatory G protein (Gsα), but the cellular actions of XLαs remain poorly defined. Following an initial proteomic screen, we identified sorting nexin-9 (SNX9) and dynamins, key components of clathrin-mediated endocytosis, as binding partners of XLαs. Overexpression of XLαs in HEK293 cells inhibited internalization of transferrin, a process that depends on clathrin-mediated endocytosis, while its ablation by CRISPR/Cas9 in an osteocyte-like cell line (Ocy454) enhanced it. Similarly, primary cardiomyocytes derived from XLαs knockout (XLKO) pups showed enhanced transferrin internalization. Early postnatal XLKO mice showed a significantly higher degree of cardiac iron uptake than wild-type littermates following iron dextran injection. In XLKO neonates, iron and ferritin levels were elevated in heart and skeletal muscle, where XLαs is normally expressed abundantly. XLKO heart and skeletal muscle, as well as XLKO Ocy454 cells, showed elevated SNX9 protein levels, and siRNA-mediated knockdown of SNX9 in XLKO Ocy454 cells prevented enhanced transferrin internalization. In transfected cells, XLαs also inhibited internalization of the parathyroid hormone and type 2 vasopressin receptors. Internalization of transferrin and these G protein-coupled receptors was also inhibited in cells expressing an XLαs mutant missing the Gα portion, but not Gsα or an N-terminally truncated XLαs mutant unable to interact with SNX9 or dynamin. Thus, XLαs restricts clathrin-mediated endocytosis and plays a critical role in iron/transferrin uptake in vivo. Published under the PNAS license.

Comparative proteomic analysis of fibrotic liver of rats fed high fat diet contained lard versus corn oil.

PubMed

Wang, Hualin; Sit, Wat-Hung; Tipoe, George Lim; Liu, Zhiguo; Wan, Jennifer Man-Fan

2017-02-01

The influences of dietary fatty acids on the progress of chronic liver diseases have attracted lots of attentions, but the mechanisms of the effects of lipids rich in saturated fatty acids or PUFAs on hepatic fibrogenesis remain unclear. Female Fischer 344 rats were fed normal chow or chow plus 20% (w/w) of corn oil or lard, respectively, and injected CCl 4 twice a week for 4 weeks to induce liver fibrosis. Masson's staining was adopted to illustrate the fibrosis level. The mRNA expression level of α-SMA and the DNA methylation level of its promoter region were analyzed. A 2-DE gel based proteomic approach was constructed to investigate the differential expression level of hepatic proteome between three diet groups. Histological evaluations and α-SMA expression analysis illustrated the high corn oil intake has no effects on hepatic fibrogenesis, but lard intake aggravated liver fibrosis, partly attributed to DNA demethylation of α-SMA promoter region. 2-DE Gel based proteomic study demonstrated excessive lard consumption elevated the expression of fibrosis related alpha-1-antitrypsin precursor, and endoplasmic reticulum stress related proteins such as heat shock cognate 71 kDa, eukaryotic translation initiation factor 4A1 and protein disulfide isomerase associated 3. Moreover, unlike corn oil rich in PUFAs, lard had no effects to elevate the expression of glutathione S-transferases, but decreased the expression of iron store related proteins heme binding protein 1 and ferritin. Lard intake aggravates CCl 4 induced liver fibrosis via enhancing the expression of fibrogenesis and ER stress related proteins, and disturbing the hepatic transmethylation reaction. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Spectroscopic evidence for the role of a site of the di-iron catalytic center of ferritins in tuning the kinetics of Fe(ii) oxidation.

PubMed

Ebrahimi, Kourosh Honarmand; Bill, Eckhard; Hagedoorn, Peter-Leon; Hagen, Wilfred R

2016-11-15

Ferritin is a nanocage protein made of 24 subunits. Its major role is to manage intracellular concentrations of free Fe(ii) and Fe(iii) ions, which is pivotal for iron homeostasis across all domains of life. This function of the protein is regulated by a conserved di-iron catalytic center and has been the subject of extensive studies over the past 50 years. Yet, it has not been fully understood how Fe(ii) is oxidized in the di-iron catalytic center and it is not known why eukaryotic and microbial ferritins oxidize Fe(ii) with different kinetics. In an attempt to obtain a new insight into the mechanism of Fe(ii) oxidation and understand the origin of the observed differences in the catalysis of Fe(ii) oxidation among ferritins we studied and compared the mechanism of Fe(ii) oxidation in the eukaryotic human H-type ferritin (HuHF) and the archaeal ferritin from Pyrococcus furiosus (PfFtn). The results show that the spectroscopic characteristics of the intermediate of Fe(ii) oxidation and the Fe(iii)-products are the same in these two ferritins supporting the proposal of unity in the mechanism of Fe(ii) oxidation among eukaryotic and microbial ferritins. Moreover, we observed that a site in the di-iron catalytic center controls the distribution of Fe(ii) among subunits of HuHF and PfFtn differently. This observation explains the reported differences between HuHF and PfFtn in the kinetics of Fe(ii) oxidation and the amount of O 2 consumed per Fe(ii) oxidized. These results provide a fresh understanding of the mechanism of Fe(ii) oxidation by ferritins.

Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells

NASA Astrophysics Data System (ADS)

Li, Ke; Zhang, Zhi-Ping; Luo, Ming; Yu, Xiang; Han, Yu; Wei, Hong-Ping; Cui, Zong-Qiang; Zhang, Xian-En

2011-12-01

Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging αvβ3 integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging.Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging αvβ3 integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c1nr11132a

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Hu; D Samanta; S Parelkar

Controlled free radical polymerization chemistry is used to graft polymer chains to the corona of horse spleen ferritin (HSF) nanocages. Specifically, poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) and poly(PEG methacrylate) (polyPEGMA) chains are grafted onto the nanocages by atom transfer radical polymerization (ATRP), in which the molecular weight of the polymer grafts is controlled by the monomer-to-initiator feed ratio. PolyMPC and polyPEGMA-grafted ferritin show a generally suppressed inclusion into diblock copolymer films relative to native ferritin, and the polymer coating is seen to mask the ferritin nanocages from antibody recognition. The solubility of polyPEGMA-coated ferritin in organic solvents enables its processing with polystyrene-block-poly(ethylenemore » oxide) copolymers, and selective integration into the PEO domains of microphase-separated copolymer structures.« less

Comparison of deferiprone and deferrioxamine for the treatment of transfusional iron overload in children with beta thalassemia major.

PubMed

Waheed, Nadia; Ali, Shafqut; Butt, Muhammad Asghar

2014-01-01

Thalassemia major is the most common genetic disorder in Pakistan. The study was done to compare the efficacy and safety of the deferiprone with deferrioxamine for the treatment of iron overload in children with thalassemia major. This randomized controlled trail was conducted at thalassemia blood transfusion unit of Allied Hospital, Faisalabad (AHF)/District Headquarter Hospital (DHQ), Faisalabad. Thalassemia-Unit Hilal-e-Ahmar, Alizeb Foundation and Blood Bank Services Faisalabad from November 2010 to December 2011.Children with beta thalassemia major of age more than 2 years and less than 16 years with transfusion iron over load were randomly allocated to one of the two groups each comprising of 67 patients. One group received deferiprone given at a daily dose of 75mg/kg in three divided doses orally while the other group received deferrioxamine at dose 50 mg/kg/24hrs for 5 days/week as parental infusion. Changes in the serum ferritin level were assessed. Cardiac function and toxicity were also examined. Serum ferritin was significantly reduced after 1 year in both treatment arms (p=0.01). Neutropenia observed in 13 (19.40%) non-splenectomized patients taking deferiprone. Transient elevations in ALT were observed in 3 (4.47%) children taking deferiprone. Left ventricular ejection fraction (LVEF) remained in normal range in both treatment arm but has decreased significantly in Deferrioxamine group compliance. Compliance was better in deferiprone as compared to deferrioxamine. Discontinuing percentage 2 (3%) vs 9 (13.43%). Deferiprone is a highly efficacious and safe chelation therapy for patients with thalassemia major who are non-compliant to Deferrioxamine. Deferiprone have an efficacy profile comparable to standard Deferrioxamine.

[Old and new iron parameters in iron metabolism and diagnostics].

PubMed

Graf, Lukas; Herklotz, Roberto; Huber, Andreas R; Korte, Wolfgang

2008-09-01

Iron is an element which is essential to life but also potentially toxic. Therefore, clever mechanisms exist in the human body for uptake, transport and storage of iron. Hepcidin, which seems to be the master protein for regulation of intestinal iron absorption, is known for a short time. The expression of hepcidin is not only influenced by iron levels but also by mediators of inflammation and growth factors of erythropoiesis. Hence hepcidin plays also a crucial role in the development of anemia of chronic disease and iron overload due to ineffective erythropoiesis. Serum ferritin is a reliable parameter to estimate the storage iron. It is an acute phase protein which is elevated during infections and inflammations, though. In these situations, measurement of soluble transferrin receptors is a useful tool to differentiate between iron deficiency and anemia of chronic disease. Newer parameters as erythrocyte zink protoporphyrin or percentage of hypochromic erythrocytes (%HYPO) are suited to detect a functional iron deficiency. Early diagnosis of iron overload is essential to prevent organ damage. Serum ferritin and transferrin are useful parameters to screen for iron overload. If no clear reason for a secondary iron overload can be found, the search for a hereditary haemochromatosis is recommended. Most of these hereditary haemochromatoses are a result of mutations in the HFE gene (homozygous state for Cys282Tyr or compound heterozygosity for Cys282Tyr/ His63Asp) which can be detected by PCR technique. Liver biopsy is still the gold standard for quantification of storage iron. However, a method of increasing importance for quantification of iron overload is magnetic resonance imaging with new approaches as for example T2*.

Ferroportin (Q248H) mutations in African families with dietary iron overload.

PubMed

McNamara, Lynne; Gordeuk, Victor R; MacPhail, A Patrick

2005-12-01

Dietary iron overload found in sub-Saharan Africa might be caused by an interaction between dietary iron and an iron-loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of iron overload and inflammation. We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. The present study of 19 families with African iron overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations. Copyright 2005 Blackwell Publishing Asia Pty Ltd.

Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123

PubMed Central

Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M

2011-01-01

Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. PMID:21653798

Identification and characterization of a ferritin gene and its product from the multicellular green alga Ulva pertusa.

PubMed

Morimoto, Shin-Ichiro; Masuda, Taro; Sugihara, Itaru; Toyohara, Haruhiko

2012-01-01

Iron is an essential element for virtually all kingdoms of life, and especially for primary producers in ocean ecosystems. To date, the molecular mechanism of iron utilization by macroalgae remains largely unknown. To elucidate the strategy of iron acquisition and storage in macroalgae, we focused on the function of the iron storage protein ferritin in the sea lettuce, Ulva pertusa, which has abundant iron content. Judging from the primary structure, U. pertusa ferritin (UpFer) can be classified as a land-plant-type ferritin, which is usually found in plastids. The gene of UpFer was expressed in the peripheral, central and rhizoid parts. Western blot analysis showed that UpFER was present and functioned in processed 26- and 22-kDa forms. Furthermore, recombinant UpFER had iron incorporation activity comparable to other ferritins. These results suggest that ferritin also functions as an iron storage protein as in unicellular algae and land plants.

The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement.

PubMed

Honarmand Ebrahimi, Kourosh; Bill, Eckhard; Hagedoorn, Peter-Leon; Hagen, Wilfred R

2012-11-01

A conserved iron-binding site, the ferroxidase center, regulates the vital iron storage role of the ubiquitous protein ferritin in iron metabolism. It is commonly thought that two Fe(II) simultaneously bind the ferroxidase center and that the oxidized Fe(III)-O(H)-Fe(III) product spontaneously enters the cavity of ferritin as a unit. In contrast, in some bacterioferritins and in archaeal ferritins a persistent di-iron prosthetic group in this center is believed to mediate catalysis of core formation. Using a combination of binding experiments and isotopically labeled (57)Fe(II), we studied two systems in comparison: the ferritin from the hyperthermophilic archaeal anaerobe Pyrococcus furiosus (PfFtn) and the eukaryotic human H ferritin (HuHF). The results do not support either of the two paradigmatic models; instead they suggest a unifying mechanism in which the Fe(III)-O-Fe(III) unit resides in the ferroxidase center until it is sequentially displaced by Fe(II).

Ferromagnetic resonance in the ethmoid bones of salmon and silver carp

NASA Astrophysics Data System (ADS)

Gorobets, Svitlana; Gorobets, Oksana; Golub, Volodymyr; Gromnadska, Marina

2017-10-01

The detection of biogenic magnetic nanoparticles (BMN) with different magnetic properties in biological material was done using magnetic resonance (MR) spectroscopy. MR spectra of biological material of ethmoid bone of salmon (containing ferritin and BMN), bacteria E. coli K13 (containing ferritin and without BMN), yeast S. cerevisiae (without ferritin or BMN) and ethmoid bone of silver carp (containing ferritin and not investigated for the presence of BMN) were investigated. The analysis of MR spectra shows that S. cerevisiae cells produce much lower signal MR than samples of ethmoid bones of salmon and silver carp which is confirming conclusions about the presence of BMN and ferritin in the ethmoid bones of fishes. The narrow MR linewidth indicates that the magnetic particles in the ethmoid bones of salmon and silver carp are in monodisperse state. The presence of a broad line and the absence of a narrow peak in MR spectrum of E. coli K13 cells are typical for ferritin.

Clinical outcomes of Torque teno virus-infected thalassemic patients with and without hepatitis C virus infection

PubMed Central

Alavi, Samin; Sharifi, Zohreh; Nourbakhsh, Kazem; Shamsian, Bibi Shahin; Arzanian, Mohammad Taghi; Safarisharari, Alieh; Navidinia, Masoumeh

2011-01-01

Background Although a marked proportion of thalassemic patients acquire Torque teno virus (TTV) through blood transfusion, its clinical importance is unclear. This study was designed to investigate the clinical importance of TTV infection in thalassemic patients with and without hepatitis C virus (HCV) co-infection in Iran. Methods In this case-control study, 107 thalassemic patients on chronic transfusion and 107 healthy individuals were selected. According to HCV and TTV infection status (detected by semi-nested PCR), patients were categorized into 4 groups: TTV and HCV negative, TTV positive, HCV positive, and TTV and HCV positive. Blood ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in these 4 groups were assessed. Results Approximately half of the thalassemic patients (50.5%) and 27.1% of controls had TTV infection. Thalassemic patients had a greater chance of TTV infection compared to the control group with a sex-adjusted OR of 4.13 (95% CI=2.28-8.13). The increased levels of ALT, AST, and ferritin in the TTV and HCV-infected group were not significantly different from those in the TTV and HCV negative group. Co-infection with TTV and HCV did not significantly increase ALT, AST, and ferritin levels compared to infection with TTV alone. Conclusion Although common in thalassemic patients, TTV infection appears to have a negligible role in increasing the severity of liver disease, even when co-infection with HCV occurs. PMID:21747885

Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress.

PubMed

Fonseca, Ana Mafalda; Pereira, Carlos F; Porto, Graça; Arosa, Fernando A

2003-12-01

We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified proteins, suggesting that RBC efficiently counteracted ROS production on the activated T cells. Flow cytometry and immunodetection demonstrated that T cells dividing in the presence of RBC had increased levels of intracellular ferritin rich in L-subunits and HO-1 along with a downmodulation in CD71 expression. Finally, using the fluorescent iron indicator calcein and flow cytometry analysis, we were able to show that a relative amount of the labile iron pool (LIP) was upregulated in T cells growing in the presence of RBC. These findings are consistent with a typical response to iron overload. However, neither heme compounds nor ferric iron reproduced the levels of expansion and survival of T cells induced by intact RBC. Altogether, these data suggest that RBC inhibit apoptosis of activated T cells by a combination of ROS scavenging and upregulation of cytoprotective proteins such as ferritin and HO-1, which may counteract a possible toxic effect of the increased intracellular free iron.

Anemia and deficiencies of folate and vitamin B-6 are common and vary with season in Chinese women of childbearing age.

PubMed

Ronnenberg, A G; Goldman, M B; Aitken, I W; Xu, X

2000-11-01

Little is known about the micronutrient status of Chinese women of childbearing age. We assessed nonfasting plasma concentrations of folic acid, vitamin B-12, vitamin B-6 (as pyridoxal-5'-phosphate), hemoglobin (Hb), ferritin and transferrin receptor (TfR) in 563 nonpregnant textile workers aged 21-34 y from Anqing, China. All women had obtained permission to become pregnant and were participating in a prospective study of pregnancy outcomes. Mean (SD) plasma concentrations were 9.7 (4.1) nmol/L folic acid, 367 (128) pmol/L vitamin B-12, 40.2 (15.8) nmol/L vitamin B-6, 108 (12. 9) g/L Hb, 42.6 (34.2) microgram/L ferritin and 5.2 (2.7) mg/L TfR. Twenty-three percent of women had biochemical evidence of folic acid deficiency, 26% were deficient in vitamin B-6 and 10% had low vitamin B-12. Overall, 44% of women were deficient in at least one B vitamin. Although anemia (Hb < 120 g/L) was detected in 80% of women, only 17% had depleted iron stores (ferritin < 12 microgram/L); 11% had elevated TfR concentrations. Distinct seasonal trends were observed in the prevalence of moderate anemia (Hb < 100 g/L) and deficiencies of folic acid and vitamin B-6, with significantly lower concentrations of folate and Hb occurring in summer and lower concentrations of vitamin B-6 occurring in winter and spring than in other seasons. We conclude that deficiencies of folic acid, vitamin B-6 and iron were relatively common in this sample of Chinese women of childbearing age and were contributing to the high prevalence of anemia. Without appropriate supplementation, these deficiencies could jeopardize the women's health and increase their risk of adverse pregnancy outcomes.

Effects of interferon-gamma and lipopolysaccharide on macrophage iron metabolism are mediated by nitric oxide-induced degradation of iron regulatory protein 2.

PubMed

Kim, S; Ponka, P

2000-03-03

Iron regulatory proteins (IRP-1 and IRP-2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements, which are located in the 3'-untranslated region and the 5'-untranslated region of their respective mRNAs. Cellular iron levels affect binding of IRPs to iron-responsive elements and consequently expression of TfR and ferritin. Moreover, NO(*), a redox species of nitric oxide that interacts primarily with iron, can activate IRP-1 RNA binding activity resulting in an increase in TfR mRNA levels. Recently we found that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA binding of IRP-2 followed by IRP-2 degradation, and these changes were associated with a decrease in TfR mRNA levels (Kim, S., and Ponka, P. (1999) J. Biol. Chem. 274, 33035-33042). In this study, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP-1 binding activity, whereas RNA binding of IRP-2 decreased and was followed by a degradation of this protein. Moreover, the decrease of IRP-2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. Furthermore, LPS/IFN-gamma-stimulated RAW 264.7 cells showed increased rates of ferritin synthesis. These results suggest that NO(+)-mediated degradation of IRP-2 plays a major role in iron metabolism during inflammation.

Effects of a 7-day military training exercise on inflammatory biomarkers, serum hepcidin, and iron status.

PubMed

McClung, James P; Martini, Svein; Murphy, Nancy E; Montain, Scott J; Margolis, Lee M; Thrane, Ingjerd; Spitz, Marissa G; Blatny, Janet-Martha; Young, Andrew J; Gundersen, Yngvar; Pasiakos, Stefan M

2013-11-04

Hepcidin, a peptide that is released into the blood in response to inflammation, prevents cellular iron export and results in declines in iron status. Elevated serum and urinary levels of hepcidin have been observed in athletes following exercise, and declines in iron status have been reported following prolonged periods of training. The objective of this observational study was to characterize the effects of an occupational task, military training, on iron status, inflammation, and serum hepcidin. Volunteers (n = 21 males) included Norwegian Soldiers participating in a 7-day winter training exercise that culminated in a 3-day, 54 km ski march. Fasted blood samples were collected at baseline, on day 4 (PRE, prior to the ski march), and again on day 7 (POST, following the ski march). Samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), interleukin-6 (IL-6), and serum hepcidin. Military training affected inflammation and serum hepcidin levels, as IL-6 and hepcidin concentrations increased (P < 0.05) from the baseline to POST (mean ± SD, 9.1 ± 4.9 vs. 14.5 ± 8.4 pg/mL and 6.5 ± 3.5 vs. 10.2 ± 6.9 ng/mL, respectively). Iron status was not affected by the training exercise, as sTfR levels did not change over the course of the 7-day study. Military training resulted in significant elevations in IL-6 and serum hepcidin. Future studies should strive to identify the role of hepcidin in the adaptive response to exercise, as well as countermeasures for the prevention of chronic or repeated elevations in serum hepcidin due to exercise or sustained occupational tasks which may result in longer term decrements in iron status.

Heme Iron Concentrate and Iron Sulfate Added to Chocolate Biscuits: Effects on Hematological Indices of Mexican Schoolchildren.

PubMed

Quintero-Gutiérrez, Adrián Guillermo; González-Rosendo, Guillermina; Pozo, Javier Polo; Villanueva-Sánchez, Javier

2016-08-01

Food fortification is one of the most effective strategies for increasing iron intake in the population. A simple blind trial was conducted to compare the effect of 2 forms of iron fortification and assess the changes in hemoglobin and iron status indices among preschool children from rural communities. Hemoglobin was evaluated in 47 children aged 3-6 years old. For 72 days (10-week period), children ate Nito biscuits. Thirteen pupils with elevated hemoglobin levels were assigned to the biscuit control group, and pupils with hemoglobin equal to 13.5 mg/dL or less were randomly allocated to consume fortified biscuits with a heme iron concentrate (n = 15) or iron sulfate (n = 19). Changes in hemoglobin, plasma ferritin, and other hematological indices were evaluated with analysis of variance (ANOVA) for repeated measurements. Except mean corpuscular hemoglobin concentrations (+1.27 ± 2.25 g/dL), hematological indices increased significantly across the study: Mean corpuscular volume (+2.2 ± 1.0 f/dL), red blood cells (+0.30 ± 0.37 M/μL), mean corpuscular hemoglobin (+1.8 ± 1.74 pg), hemoglobin (+1.68 ± 0.91 g/dL), hematocrit (+3.43% ± 3.03%), and plasma ferritin (+18.38 ± 22.1 μg/L) were all p < 0.05. After 10 weeks, the adjusted effect of the iron-fortified chocolate biscuits in the hemoglobin levels was higher than the control group (+1.1 ± 0.2 g/dL) but no difference was found between consumers of fortified biscuits with heme iron concentrate or iron sulfate (+1.9 ± 0.2 g/dL and +2.0 ± 0.2 g/dL, respectively). Heme iron concentrate and iron sulfate were equally effective in increasing Hb levels and hematological indices. Processed foods were shown to be an effective, valuable, and admissible intervention to prevent anemia in preschool children.

PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

EPA Science Inventory

PLASMID DNA DAMAGE CAOUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

ABSTRACT

Both dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) release iron from human liver ferritin (HLF) with or without the presence of ascorbic acid. ...

Iron Storage Capacity and its Ecological Role within Phylogenetically Distinct Marine Diatoms

NASA Astrophysics Data System (ADS)

Cohen, N.; Jacquot, J. E.; Stemple, B.; Sunda, W. G.; Twining, B. S.; Marchetti, A.

2016-02-01

Natural and artificial iron fertilization occurring in iron-limited regions of the ocean often results in large blooms of pennate diatoms. The ability of these pennate diatoms to quickly respond to bioavailable iron and proliferate has been attributed in part to their use of the iron storage protein ferritin. Recent concerted efforts to sequence the transcriptomes of eukaryotic protists have made it apparent that some, but not all, centric diatoms also possess a ferritin gene homolog. Using a combination of physiological and molecular biological techniques, we determined the cellular iron quotas and associated ferritin gene expression within both ferritin-containing and non-containing centric and pennate diatoms grown under a range of iron concentrations. Our results show that under steady-state conditions there are no clear differences between the maximum iron cellular quotas of ferritin-containing versus non-ferritin containing centric and pennate diatoms. However, based on differences in gene expression patterns, ferritin appears to play fundamentally different functional roles between centric and pennate diatoms. We propose the success of oceanic pennate diatoms such as Pseudo-nitzschia following iron addition is not only a function of achieving a high iron storage capacity, but also due to their unique ability to drastically reduce intracellular iron requirements while still maintaining rapid growth rates, and depends on iron bioavailability in the environment.

Ferritin, an iron source in meat for Staphylococcus xylosus?

PubMed

Vermassen, Aurore; Talon, Régine; Leroy, Sabine

2016-05-16

Staphylococcus xylosus is frequently isolated from food of animal origin. Moreover, this species is one of the major starter cultures used for meat fermentation. Iron is a key element for growth and survival of bacteria. Meat is particularly rich in haemic (myoglobin and haemoglobin) and non-haemic (ferritin and transferrin) iron sources. Ferritin is a storage protein able to capture large quantities of iron. It is highly resistant to microbial attack and few microorganisms can use it as an iron source. Surprisingly, we found that the S. xylosus C2a strain grows in the presence of ferritin as a sole iron source. A three-cistron operon was highly overexpressed under ferritin iron growth conditions. We generated a deletion-insertion in the first gene of the operon and evaluated the phenotype of the mutant. The mutant showed decreased growth because it was less able to acquire iron from ferritin. Transcriptional analysis of the mutant revealed downregulation of several genes involved in the response to oxidative stress. This study characterized for the first time the capacity of a Staphylococcus to use iron from ferritin and revealed that a potential reductive pathway was involved in this acquisition. We hypothesize that this ability could give an advantage to S. xylosus in meat products. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron Release from Soybean Seed Ferritin Induced by Cinnamic Acid Derivatives.

PubMed

Sha, Xuejiao; Chen, Hai; Zhang, Jingsheng; Zhao, Guanghua

2018-05-04

Plant ferritin represents a novel class of iron supplement, which widely co-exists with phenolic acids in a plant diet. However, there are few reports on the effect of these phenolic acids on function of ferritin. In this study, we demonstrated that cinnamic acid derivatives, as widely occurring phenolic acids, can induce iron release from holo soybean seed ferritin (SSF) in a structure-dependent manner. The ability of the iron release from SSF by five cinnamic acids follows the sequence of Cinnamic acid > Chlorogenic acid > Ferulic acid > p -Coumaric acid > Trans -Cinnamic acid. Fluorescence titration in conjunction with dialysis results showed that all of these five compounds have a similar, weak ability to bind with protein, suggesting that their protein-binding ability is not related to their iron release activity. In contrast, both Fe 2+ -chelating activity and reducibility of these cinnamic acid derivatives are in good agreement with their ability to induce iron release from ferritin. These studies indicate that cinnamic acid and its derivatives could have a negative effect on iron stability of holo soybean seed ferritin in diet, and the Fe 2+ -chelating activity and reducibility of cinnamic acid and its derivatives have strong relations to the iron release of soybean seed ferritin.

The treatment of iron deficiency without anaemia (in otherwise healthy persons).

PubMed

Clénin, German E

2017-06-21

Iron deficiency is the most widespread and frequent nutritional disorder in the world. It affects a high proportion of children and women in developing countries and is also significantly prevalent in the industrialised world, with a clear predominance in adolescents and menstruating females. Iron is essential for optimal cognitive function and physical performance, not only as a binding site of oxygen but also as a critical constituent of many enzymes. Therefore iron deficiency at all its levels - nonanaemic iron deficiency, iron deficiency with microcytosis or hypochromia and iron deficiency anaemia - should be treated. In the presence of normal stores, however, preventative iron administration is inefficient, has side effects and seems to be harmful. In symptomatic patients with fatigue or in a population at risk for iron deficiency (adolescence, heavy or prolonged menstruation, high performance sport, vegetarian or vegan diet, eating disorder, underweight), a baseline set of blood tests including haemoglobin concentration, haematocrit, mean cellular volume, mean cellular haemoglobin, percentage of hypochromic erythrocytes and serum ferritin levels are important to monitor iron deficiency. To avoid false negative results (high ferritin levels in spite of iron deficiency), an acute phase reaction should be excluded by history and measurement of C-reactive protein. An algorithm leads through this diagnostic process and the decision making for a possible treatment. For healthy males and females aged >15 years, a ferritin cut-off of 30 µg/l is appropriate. For children from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 µg/l, respectively, are recommended. As a first step in treatment, counselling and oral iron therapy are usually combined. Integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial. In order to prevent reduced compliance, mainly as a result of gastrointestinal side effects of oral treatment, the use of preparations with reasonable but not excessive elemental iron content (28-50 mg) seems appropriate. Only in exceptional cases will an intravenous injection be necessary (e.g., concomitant disease needing urgent treatment, repeated failure of first-step therapy).To measure the success of treatment, the basic blood tests should be repeated after 8 to 10 weeks. Patients with repeatedly low ferritin will benefit from intermittent oral substitution to preserve iron stores and from long term follow-up, with the basic blood tests repeated every 6 or 12 months to monitor iron stores. Long-term daily oral or intravenous iron supplementation in the presence of normal or even high ferritin values is, however, not recommended and is potentially harmful.

Alteration of serum concentrations of manganese, iron, ferritin, and transferrin receptor following exposure to welding fumes among career welders.

PubMed

Lu, Ling; Zhang, Long-Lian; Li, G Jane; Guo, Wenrui; Liang, Wannian; Zheng, Wei

2005-03-01

This study was performed to determine airborne manganese levels during welding practice and to establish the relationship between long-term, low-level exposure to manganese and altered serum concentrations of manganese, iron, and proteins associated with iron metabolism in career welders. Ninety-seven welders (average age of 36 years) who have engaged in electric arc weld in a vehicle manufacturer were recruited as the exposed group. Welders worked 7-8h per day with employment duration of 1-33 years. Control subjects consisted of 91 employees (average age of 35 years) in the same factory but not in the welding profession. Ambient manganese levels in welders' breathing zone were the highest inside the vehicle (1.5 +/- 0.7 mg/m3), and the lowest in the center of the workshop (0.2 +/- 0.05 mg/m3). Since the filter size was 0.8 microm, it is possible that these values may be likely an underestimation of the true manganese levels. Serum levels of manganese and iron in welders were about three-fold (p < 0.01) and 1.2-fold (p < 0.01), respectively, higher than those of controls. Serum concentrations of ferritin and transferrin were increased among welders, while serum transferrin receptor levels were significantly decreased in comparison to controls. Linear regression analyses revealed a lack of association between serum levels of manganese and iron. However, serum concentrations of iron and ferritin were positively associated with years of welder experience (p < 0.05). Moreover, serum transferrin receptor levels were inversely associated with serum manganese concentrations (p < 0.05). These findings suggest that exposure to welding fume among welders disturbs serum homeostasis of manganese, iron, and the proteins associated with iron metabolism. Serum manganese may serve as a reasonable biomarker for assessment of recent exposure to airborne manganese.

Anaemia, folate and vitamin B12 deficiency among pregnant women in an area of unstable malaria transmission in eastern Sudan.

PubMed

Abdelrahim, Ishraga I; Adam, Gamal K; Mohmmed, Ahmed A; Salih, Magdi M; Ali, Naji I; Elbashier, Mustafa I; Adam, Ishag

2009-05-01

A cross-sectional study was carried out between October 2007 and January 2008 to investigate the prevalence and types of anaemia among pregnant women of eastern Sudan. Socio-demographic and obstetrical data were collected using a questionnaire. Haemoglobin (Hb), serum ferritin, serum folate and vitamin B(12) were assessed using standard laboratory methods. Two hundred and seventy-nine pregnant Sudanese women were recruited. Anaemia (Hb <11 gdl) and iron deficiency (ferritin <15 microg/l) were prevalent in 80.3 and 14.3% of the study sample, respectively. Of the total sample, 11.1% had iron-deficiency anaemia. Serum folate (<6.6 ng/ml) and vitamin B(12) (<150 pg/ml) deficiency was reported in 57.7 and 1%, respectively, and none of the women had both folate and vitamin B(12) deficiencies. Univariate and multivariate analyses showed that ferritin, serum folate and vitamin B(12) levels were not significantly associated with anaemia. Thus, there was a high prevalence of anaemia and folate deficiency. Measures to control these should be considered.

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

PubMed Central

Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

2014-01-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin “halos.” Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2–3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6–15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin “halos,” with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that “halo” labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin “halo” labeling should not be used to demonstrate physiological bone interstitial fluid flow. PMID:15964255

Mapping bone interstitial fluid movement: displacement of ferritin tracer during histological processing.

PubMed

Ciani, Cesare; Doty, Stephen B; Fritton, Susannah P

2005-09-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that "halo" labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin "halo" labeling should not be used to demonstrate physiological bone interstitial fluid flow.

Loop electrostatics modulates the intersubunit interactions in ferritin.

PubMed

Bernacchioni, Caterina; Ghini, Veronica; Pozzi, Cecilia; Di Pisa, Flavio; Theil, Elizabeth C; Turano, Paola

2014-11-21

Functional ferritins are 24-mer nanocages that self-assemble with extended contacts between pairs of 4-helix bundle subunits coupled in an antiparallel fashion along the C2 axes. The largest intersubunit interaction surface in the ferritin nanocage involves helices, but contacts also occur between groups of three residues midway in the long, solvent-exposed L-loops of facing subunits. The anchor points between intersubunit L-loop pairs are the salt bridges between the symmetry-related, conserved residues Asp80 and Lys82. The resulting quaternary structure of the cage is highly soluble and thermostable. Substitution of negatively charged Asp80 with a positively charged Lys in homopolymeric M ferritin introduces electrostatic repulsions that inhibit the oligomerization of the ferritin subunits. D80K ferritin was present in inclusion bodies under standard overexpressing conditions in E. coli, contrasting with the wild type protein. Small amounts of fully functional D80K nanocages formed when expression was slowed. The more positively charged surface results in a different solubility profile and D80K crystallized in a crystal form with a low density packing. The 3D structure of D80K variant is the same as wild type except for the side chain orientations of Lys80 and facing Lys82. When three contiguous Lys groups are introduced in D80KI81K ferritin variant the nanocage assembly is further inhibited leading to lower solubility and reduced thermal stability. Here, we demonstrate that the electrostatic pairing at the center of the L-loops has a specific kinetic role in the self-assembly of ferritin nanocages.

Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2012-09-01

infusions with or without H- ferritin shows a significant extension of lifespan and a clear trend of increased survival (Figures 7 and 8). Given that the......August 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Apo- Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis 5b. GRANT NUMBER

Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin

NASA Astrophysics Data System (ADS)

Volatron, Jeanne; Kolosnjaj-Tabi, Jelena; Javed, Yasir; Vuong, Quoc Lam; Gossuin, Yves; Neveu, Sophie; Luciani, Nathalie; Hémadi, Miryana; Carn, Florent; Alloyeau, Damien; Gazeau, Florence

2017-01-01

Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein - namely the ferritin - in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products.

Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin

PubMed Central

Volatron, Jeanne; Kolosnjaj-Tabi, Jelena; Javed, Yasir; Vuong, Quoc Lam; Gossuin, Yves; Neveu, Sophie; Luciani, Nathalie; Hémadi, Miryana; Carn, Florent; Alloyeau, Damien; Gazeau, Florence

2017-01-01

Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein – namely the ferritin – in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products. PMID:28067263

[Iron deficiency: A diagnostic and therapeutic perspective in psychiatry].

PubMed

Kassir, A

2017-02-01

Iron plays an essential role in balancing the various metabolism in the body. It is also involved in the synthesis of several neurotransmitters. Nutritional iron deficiency is one of the most widespread worldwide; it poses a great health challenge due to the consequences it entails. The aim of this research study is to explore the percentage of psychiatric patients who have a deficiency in iron. In addition, the study investigates the efficacy of iron administered by oral treatment on psychiatric symptomatology among iron deficient patients. The research study utilized the martial biological results, which involved the observation of the level of iron deficiency among the outpatients of a local psychiatrist and assessor from the period of January 2012 until December 2013. Out of 412 patients, 295 were women and 117 men. The age of the participants ranged from 16 to 89years, with an average age of 45years. The only exclusion criterion was a patient's refusal or inability to take the prescribed iron assessment test. We considered a transferrin saturation coefficient (TSC)<30% and/or a serum ferritin level≤50ng/mL to be "indicative" of obvious iron deficiency, and a ferritin level between 51 and 100ng/mL to be "suggestive" of iron deficiency. A plasma ferritin assay was performed at least once on all of the participants prior to any proposed iron treatment. A calculation of the TSC in 138 patients was requested due to suspected iron deficiency despite a blood ferritin level of>100ng/ml. A single method was utilized in the various laboratories to analyse the blood samples to determine whether there was a deficiency in iron. Only those patients with blood ferritin levels ≤100ng/mL and/or a TSC of<30% (335 patients) were subsequently given exclusively an oral iron treatment prescribed on its own or as a supplement or simultaneously with psychotropic treatment. The daily administered dose of elemental iron varied between 50 and 200mg a day. About half of the women - 145 (35.19% of the subjects) - and 15 men (3.64% of the subjects) certainly had a deficiency in iron (blood ferritin level≤50ng/mL). Ninety women and 24 men (27.6% of the subjects) had blood ferritin levels between 51 and 100ng/mL indicating iron deficiency, and 28 women and 33 men (14.8% of the subjects) had a TSC of<30% despite a blood ferritin level of>100ng/mL. Overall, 335 patients (81.3% of the subjects) showed an iron deficiency based on the criteria we set. In the remaining 77 patients (18.7% of the subjects), all of them had blood ferritin levels>100ng/mL and some had TSC≤30%, while the remaining patients' TSC was unknown because it was not measured. The results indicated that there is an iron deficiency in 198 out of 240 patients suffering mostly from mood and behavioural disorders, in 101 out of 126 patients suffering mostly from anxiety disorders, in 18 out of 27 patients suffering mostly from sleep disorders, in 14 out of 15 patients suffering mostly from delusions of persecution, and in the 4 patients suffering mostly from burn out. There was evidence of regression/remission of psychiatric symptoms in 193 responsive patients whereas the remaining 142 patients were considered non-responsive. In the responsive patient category, 37 participants were treated with just iron, 52 received iron supplemented to the initial psychotropic treatment which was not fully effective, and 104 patients were treated with iron and prescribed psychotropic drugs simultaneously. The iron treatment seems to bring about a reduction - particularly through its mono-aminergic neurotransmitter synthesis-promoting action - in hyperemotivity, anxiety, irritability, aggressiveness, sadness, anhedonia, apathy, asthenia, sleep disorders, dysautonomia symptoms, eating disorders, restless-leg syndrome, cognitive performance and the likelihood of resorting to psychiatric admission. A daily elemental iron dose intake between 50 and 200mg/day by deficient patients appears to likely enhance the effects of the psychotropic drugs and even to act as an actual antidepressant. Many patients who received a prescription for iron and antidepressants showed few side effects related to antidepressants and a small number required psychiatric hospitalization. Patients considered unresponsive to iron therapy were those who left the study, were not assessed because the study's timeframe ended, still had an iron deficiency because they did not continuously take the medication, or suffered from somatic diseases which explains their resistance to treat the low iron level (nutritional imbalance, digestive or urinary or gynecological or iatrogenic diseases, sleep apnea). Our clinical observation of two years in a local psychiatrist's clinic revealed that over 80% of patients had iron deficiency. Although the low iron level cannot explain all physical and psychiatric symptoms in patients, it is useful to note that more than half of the iron deficient patients responded favorably after an oral treatment of iron. This result leads to further investigation of the level of iron in psychiatric patients and to reconsider the iron range placed by the laboratories. In addition, it is crucial not to eliminate the possibility of iron deficiency in psychiatric patients. Further research studies are needed to set more specific and detailed criteria to determine the range of iron deficiency in order to support the findings of this study and optimize the care given to patients suffering from various disorders and psychiatric syndromes. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Enzyme Encapsulation by a Ferritin Cage.

PubMed

Tetter, Stephan; Hilvert, Donald

2017-11-20

Ferritins, conserved across all kingdoms of life, are protein nanocages that evolved to mineralize iron. The last several decades have shown that these cages have considerable technological and medical potential owing to their stability and tolerance to modification, as well as their ability to template nanoparticle synthesis and incorporate small molecules. Here we show that it is possible to encapsulate proteins in a ferritin cage by exploiting electrostatic interactions with its negatively charged interior. Positively supercharged green fluorescent protein is efficiently taken up by Archaeoglobus fulgidus ferritin in a tunable fashion. Moreover, several enzymes were readily incorporated when genetically tethered to this fluorescent protein. These fusion proteins retained high catalytic activity and showed increased tolerance to proteolysis and heat. Equipping ferritins with enzymatic activity paves the way for many new nanotechnological and pharmacological applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells.

PubMed

Li, Ke; Zhang, Zhi-Ping; Luo, Ming; Yu, Xiang; Han, Yu; Wei, Hong-Ping; Cui, Zong-Qiang; Zhang, Xian-En

2012-01-07

Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging α(v)β(3) integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging.

Long-Term Trends in Hematological and Nutritional Status After Gastrectomy for Gastric Cancer.

PubMed

Kim, Ji-Hyun; Bae, You-Jin; Jun, Kyong-Hwa; Chin, Hyung-Min

2017-08-01

This study investigated long-term trends in hematological and nutritional parameters after gastrectomy for gastric cancer and evaluated the influence of the reconstruction type on these trends. The medical records of 558 patients who underwent curative gastrectomy with standard lymph node dissection for stage I gastric cancer between January 2006 and December 2013 were reviewed. The hematological and nutritional parameters evaluated included hemoglobin, ferritin, vitamin B 12 , total protein, albumin, total cholesterol, triglyceride, and calcium. The patients were followed up for 6 months postoperatively and then annually until death, cancer recurrence, or follow-up loss. In the long term, ferritin and triglyceride gradually decreased after gastrectomy, while the other parameters decreased slightly or were stable. In the comparisons according to reconstruction type, the Roux-en-Y group had the lowest levels of hemoglobin, ferritin, vitamin B12, total protein, albumin, and total cholesterol beginning 6 months postoperatively compared with the Billroth I and II groups. However, only ferritin and vitamin B 12 had significant differences in the 5-year cumulative incidences of deficiency/reduction according to the reconstruction type, whereas albumin, triglyceride, total cholesterol, and calcium did not. Although malabsorption and malnutrition are common in patients after a gastrectomy, most nutritional parameters were stable or decreased slightly in the long-term and were not markedly influenced by the reconstruction type or extent of gastrectomy. Therefore, for more accurate nutritional assessment after gastrectomy, multidirectional monitoring should be considered rather than simply measuring biochemical parameters.

Diet and iron status of nonpregnant women in rural Central Mexico.

PubMed

Backstrand, Jeffrey R; Allen, Lindsay H; Black, Anne K; de Mata, Margarita; Pelto, Gretel H

2002-07-01

Few studies have examined the relation of iron status to diet in populations from developing countries with high levels of iron deficiency and diets of poor quality. The objective was to identify nutrients, dietary constituents, and foods that are associated with better iron status in a rural Mexican population. A prospective cohort study was conducted in rural central Mexico. The subjects were 125 nonpregnant women aged 16-44 y. During the 12 mo before blood collection, food intakes were assessed repeatedly by a combination of dietary recalls, food weighing, and food diaries [mean (+/-SD) days of food intake data: 18.8 +/- 5.9 d]. Hemoglobin, hematocrit, and plasma ferritin were measured at the end of the study. Higher plasma ferritin concentrations were associated with greater intakes of nonheme iron and ascorbic acid after control for age, BMI, breast-feeding, season, and the time since the birth of the last child. Higher ascorbic acid intakes, but not higher intakes of heme and nonheme iron, predicted a lower risk of low hemoglobin and hematocrit values after control for the background variables. Consumption of the alcoholic beverage pulque predicted a lower risk of low ferritin and low hemoglobin values. Seasonal variation in ferritin, hemoglobin, and hematocrit values was observed. Better iron status was associated with greater intakes of foods containing nonheme iron and ascorbic acid. PULQUE:a beverage containing iron, ascorbic acid, and alcohol-may influence the iron status of women in rural central Mexico.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Margrete Meltzer, Helle, E-mail: helle.margrete.meltzer@fhi.no; Lise Brantsaeter, Anne; Borch-Iohnsen, Berit

Low iron (Fe) stores may influence absorption or transport of divalent metals in blood. To obtain more knowledge about such associations, the divalent metal ions cadmium (Cd), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) and lead (Pb) and parameters of Fe metabolism (serum ferritin, haemoglobin (Hb) and transferrin) were investigated in 448 healthy, menstruating non-smoking women, age 20-55 years (mean 38 years), participating in the Norwegian HUNT 2 study. The study population was stratified for serum ferritin: 257 were iron-depleted (serum ferritin <12 {mu}g/L) and 84 had iron deficiency anaemia (serum ferritin <12 {mu}g/L and Hb<120 g/L). The lowmore » ferritin group had increased blood concentrations of Mn, Co and Cd but normal concentrations of Cu, Zn and Pb. In multiple regression models, ferritin emerged as the main determinant of Mn, Co and Cd (p<0.001), while no significant associations with Cu, Zn and Pb were found. Adjusted r{sup 2} for the models were 0.28, 0.48 and 0.34, respectively. Strong positive associations between blood concentrations of Mn, Co and Cd were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the six divalent metals studied. Very mild anaemia (110{<=}Hb<120 g/L) did not seem to have any effect independent of low ferritin. Approximately 26% of the women with iron deficiency anaemia had high concentrations of all of Mn, Co and Cd as opposed to 2.3% of iron-replete subjects. The results confirm that low serum ferritin may have an impact on body kinetics of certain divalent metal ions, but not all. Only a fraction of women with low iron status exhibited an increased blood concentration of divalent metals, providing indication of complexities in the body's handling of these metals.« less

A pilot iron substitution programme in female blood donors with iron deficiency without anaemia.

PubMed

Pittori, C; Buser, A; Gasser, U E; Sigle, J; Job, S; Rüesch, M; Tichelli, A; Infanti, L

2011-04-01

Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non-anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain. Women aged≤50 with haemoglobin levels adequate for donation and serum ferritin≤10 ng/ml were offered iron supplementation. Substitution lasted 16 weeks and the donation interval was extended. History collection including iron deficiency-related symptoms, whole blood count and serum ferritin determination was performed at baseline and after 2 and 6 months. Data were recorded prospectively and compared with those of 108 female controls with iron deficiency not receiving iron substitution (retrospective data). Of the 116 participating subjects, 60% completed the programme. Significant results were serum ferritin increase (from a mean value of 7.12 to 25.2 ng/ml), resolution of prostration, fatigue, sleep disturbances, tension in the neck, hair loss and nail breakage. No case of anaemia occurred. Sixty per cent of the women completed the programme and donated blood again. Targeted iron substitution prevents the development of anaemia and enhances donation return in premenopausal female blood donors with iron deficiency. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Thyroid Status in Children with Transfusion Dependent Hb-E β-Thalassaemia.

PubMed

Sharmin, T; Mollah, A H; Morshed, A A; Chowdhury, M K

2018-04-01

Despite improved haematological care, multi-endocrine dysfunction is a common complication in thalassemia. Iron overload is thought to be the most likely mechanism in thyroid dysfunction in these patients. Moreover, chronic tissue hypoxia might havedirect toxic effect on thyroid gland resulting in hypothyroidism. This study was designed to evaluate the thyroid status of children with Hb-E β-thalassemia. This cross sectional analytic study was conducted among thepatients with Hb-E β-thalassemia attending both in-patient & out-patient department of Paediatrics, Dhaka Medical College & Hospital, Dhaka, Bangladesh from April 2012 to March 2013. The children who attended inpatient and outpatient department of Paediatrics for some other illness were screened out for thalassaemia and were recruited as comparison group. Thyroid function tests (TSH & FT₄ level) were performed in both thalassaemic patients and comparison group. Serum ferritin level was also measured for assessing iron status of thalassaemic patients and their pre-transfusion Hb levels were recorded in the pre-formed data collection form. Of the 50 thalassaemia patients, 13(26%) had subclinical hypothyroidism. This proportion of subclinical hypothyroidism was significantly high, compared to that (2.5%) of non thalassaemia comparison group. Among the subclinically hypothyroid thalassaemia subjects, 8 were males and 5 were females and their mean age was 102.38±33.29 months. The mean serum ferritin levels in hypothyroid and euthyroid thalassaemia cases were 2387.87±1642.85ng/ml and 1822.95±1345.33ng/ml respectively (normal level upto 300ng/ml). This difference was not statistically significant (p=0.279); but the pre-transfusion Hb level wasfound significantly different (p=0.02) among the two groups. It was 5.57±0.98g/dl in hypothyroid & 6.37±0.09g/dl in euthyroid thalassaemic cases. Subclinical hypothyroidism was quite high among the children with transfusion dependent Hb-E β-thalassaemia. Their hypothyroid status had no significant correlation with their serum ferritin level but had significant correlation with low haemoglobin status.

Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

PubMed Central

Darton, Thomas C.; Blohmke, Christoph J.; Giannoulatou, Eleni; Waddington, Claire S.; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J.; Armitage, Andrew E.

2015-01-01

Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi. PMID:26394303

Clinical expression of haemochromatosis in Irish C282Y homozygotes identified through family screening.

PubMed

Gleeson, F; Ryan, E; Barrett, S; Crowe, J

2004-09-01

In Ireland, the homozygote frequency of the C282Y mutation in the HFE gene is 1/83. The biochemical expression of this mutation is high in haemochromatosis (HH) individuals identified through family screening, but the clinical expression of the mutation in Irish HH subjects to date has not been investigated fully. To determine the clinical, biochemical and histological penetrance of the C282Y mutation in Irish C282Y homozygotes identified through family screening. Two hundred and nine C282Y homozygous individuals comprising of 172 first-degree relatives, 31 second-degree relatives and four unrelated individuals were identified following HFE mutation analysis of 167 families. The following variables were analysed: age at identification, gender, fasting transferrin saturation, fasting serum ferritin, liver enzymes, clinical symptomatology, liver histopathology and histochemical iron staining. An elevated transferrin saturation in combination with an elevated ferritin was present in 43.4% of males and 23.3% of females. Abnormal liver enzymes were found in 32.3% of males. Diabetes, a haemochromatosis-specific association, was noted in 2.8% of males. Of those individuals requiring liver histopathology evaluation, 38% had moderate-to-severe iron staining, and 42% had fibrosis; 2.8% of the biopsied cohort had cirrhosis. Thus, HH cirrhotics were identified in less than 1% of the screened population. Although the homozygote frequency in Ireland is very high, the prevalence of advanced liver disease was less than 1% of the family members screened. Nevertheless, 42% of biopsied patients had histological evidence of iron overload-related architectural change and 2.8% had cirrhosis. This cohort of young people had previously unrecognized biochemical iron overload and histopathological change. This emphasizes the importance and value of both genetic and biochemical screening in first-degree relatives of identified homozygotes.

The Association of Serum Iron-Binding Proteins and the Antioxidant Parameter Levels in Age-Related Macular Degeneration.

PubMed

Čolak, Emina; Žorić, Lepša; Radosavljević, Aleksandra; Ignjatović, Svetlana

2018-05-01

Age-related macular degeneration (AMD) is the leading cause of the irreversible central visual loss among the elderly in the developed countries. Iron is considered a potent generator of the oxidative damage whose levels increase with age, potentially exacerbating the age-related diseases. The aim of this study was to assess the serum values of iron, and iron-binding proteins (transferrin, ferritin, and haptoglobin) in patients with AMD along with the parameters of the antioxidant defense: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase, and total antioxidant status (TAS), in order to analyze the possible impact of iron and iron-binding proteins to the development of oxidative stress in AMD patients, and the association of the selected parameters with the AMD. In addition, the aim was to examine the gender differences and calculate the cutoff points of tested parameters that could be associated with AMD. A cross-sectional study included 55 AMD patients aged 71.7 ± 7.36 years and 65 aged-matched control subjects aged 70.25 ± 6.46 years. Significantly lower ferritin (P = 0.025), SOD (P = 0.026), GPx (P = 0.019), and TAS (P < 0.004) values were found in patients with AMD compared to the controls (P < 0.05). Significant association of GPx < 27 U/gHb (odds ratio [OR]: 1.13; 95% confidence interval [CI] 0.78-2.10; P = 0.049), TAS < 1.25 mmol/L (OR: 5.77; 95% CI 0.98-367.0; P < 0.000), ferritin < 84.8 pg/mL (OR: 2.52; 95% CI 1.37-4.62; P = 0.002), and haptoglobin<1.51 g/L (OR: 1.94; 95% CI 1.05-3.56; P = 0.031) was found with the AMD. According to receiver operating characteristic curve analysis, ferritin concentration <84.8 pg/L, GPx < 27 U/gHb, and TAS < 1.25 mmol/L have sufficient predictive ability for AMD. Significantly reduced capacity of the antioxidant defense system and iron-binding storage proteins (ferritin) found in AMD could have an important role in the development of increase oxidative stress in AMD patients.

Enhanced Iron Uptake of Saccharomyces cerevisiae by Heterologous Expression of a Tadpole Ferritin Gene

PubMed Central

Shin, Young-Mi; Kwon, Tae-Ho; Kim, Kyung-Suk; Chae, Keon-Sang; Kim, Dae-Hyuk; Kim, Jae-Ho; Yang, Moon-Sik

2001-01-01

We genetically engineered Saccharomyces cerevisiae to express ferritin, a ubiquitous iron storage protein, with the major heavy-chain subunit of tadpole ferritin. A 450-kDa ferritin complex can store up to 4,500 iron atoms in its central cavity. We cloned the tadpole ferritin heavy-chain gene (TFH) into the yeast shuttle vector YEp352 under the control of a hybrid alcohol dehydrogenase II and glyceraldehyde-3-phosphate dehydrogenase promoter. We confirmed transformation and expression by Northern blot analysis of the recombinant yeast, by Western blot analysis using an antibody against Escherichia coli-expressed TFH, and with Prussian blue staining that indicated that the yeast-expressed tadpole ferritin was assembled into a complex that could bind iron. The recombinant yeast was more iron tolerant in that 95% of transformed cells, but none of the recipient strain cells, could form colonies on plates containing 30 mM ferric citrate. The cell-associated concentration of iron was 500 μg per gram (dry cell weight) of the recombinant yeast but was 210 μg per gram (dry cell weight) in the wild type. These findings indicate that the iron-carrying capacity of yeast is improved by heterologous expression of tadpole ferritin and suggests that this approach may help relieve dietary iron deficiencies in domesticated animals by the use of the engineered yeast as a feed and food supplement. PMID:11229922

Ferritin-based nanocrystals for solar energy harvesting

NASA Astrophysics Data System (ADS)

Colton, John; Erickson, Stephen; Olsen, Cameron; Embley, Jacob; Smith, Trevor; Watt, Richard

2015-03-01

Ferritin is a 12 nm diameter hollow protein with an 8 nm cavity that can be filled with a variety of nanocrystals (ferrihydrite being native). We report on several experiments with ferritin-based nanocrystals designed to utilize ferritin for solar energy harvesting. First, we have shown that the native band gap can be altered by controlling nanocrystal size, by replacing the native iron oxide core with other metal oxides, and by depositing halides and oxo-anions with the iron oxide core. This gives available band gaps of 1.6 to 2.3 eV. Theoretical efficiency calculations based on these band gaps show that the efficiency of a multi-junction solar cell based on layered structures of ferritin can be as high as 44.9 %, and up to 63.1 % if a ferritin-based material with band gap of 1.1 eV can be developed. For the latter case, the efficiencies remain quite high even in a current-matched configuration, namely 50.0 %. We have also demonstrated that photo-excitation of these materials can produce charge separation and give rise to usable electrons; we have used photo-excited electrons to reduce gold in solution and thereby produce gold nanoparticles on the surface of the ferritin. This technique can potentially be extended to platinum, whose nanoparticles catalyze water splitting. This research was partially supported by the Utah Office of Energy Development, Governor's Energy Leadership Scholars Program.

Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development.

PubMed

González-Morales, Nicanor; Mendoza-Ortíz, Miguel Ángel; Blowes, Liisa M; Missirlis, Fanis; Riesgo-Escovar, Juan R

2015-01-01

In Drosophila melanogaster, iron is stored in the cellular endomembrane system inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. In larvae, ferritin accumulates in the midgut, hemolymph, garland, pericardial cells and in the nervous system. Here we present analyses of embryonic phenotypes for mutations in Fer1HCH, Fer2LCH and in both genes simultaneously. Mutations in either gene or deletion of both genes results in a similar set of cuticular embryonic phenotypes, ranging from non-deposition of cuticle to defects associated with germ band retraction, dorsal closure and head involution. A fraction of ferritin mutants have embryonic nervous systems with ventral nerve cord disruptions, misguided axonal projections and brain malformations. Ferritin mutants die with ectopic apoptotic events. Furthermore, we show that ferritin maternal contribution, which varies reflecting the mother's iron stores, is used in early development. We also evaluated phenotypes arising from the blockage of COPII transport from the endoplasmic reticulum to the Golgi apparatus, feeding the secretory pathway, plus analysis of ectopically expressed and fluorescently marked Fer1HCH and Fer2LCH. Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. These functions are required in multiple tissues during Drosophila embryonic development.

Urea-Driven Epigallocatechin Gallate (EGCG) Permeation into the Ferritin Cage, an Innovative Method for Fabrication of Protein-Polyphenol Co-assemblies.

PubMed

Yang, Rui; Liu, Yuqian; Meng, Demei; Chen, Zhiyu; Blanchard, Christopher L; Zhou, Zhongkai

2017-02-22

The 8 nm diameter cavity endows the ferritin cage with a natural space to encapsulate food components. In this work, urea was explored as a novel medium to facilitate the formation of ferritin-polyphenol co-assemblies. Results indicated that urea (20 mM) could expand the 4-fold channel size of apo-red bean ferritin (apoRBF) with an increased initial iron release rate υ 0 (0.22 ± 0.02 μM min -1 ) and decreased α-helix content (5.6%). Moreover, urea (20 mM) could facilitate the permeation of EGCG into the apoRBF without destroying the ferritin structure and thus form ferritin-EGCG co-assemblies (FECs) with an encapsulation ratio and loading capacity of 17.6 and 2.1% (w/w), respectively. TEM exhibited that FECs maintained a spherical morphology with a 12 nm diameter in size. Fluorescence analysis showed that urea intervention could improve the binding constant K [(1.22 ± 0.8) × 10 4 M -1 ] of EGCG to apoRBF. Furthermore, the EGCG thermal stability was significantly improved (20-60 °C) compared with free EGCG. Additionally, this urea-involved method was applicable for chlorogenic acid and anthocyanin encapsulation by the apoRBF cage. Thus, urea shows potential as a novel potential medium to encapsulate and stabilize bioactive polyphenols for food usage based on the ferritin protein cage structure.

Anaemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

PubMed Central

Weng, Ting-Chia; Chang, Chia-Hsuin; Dong, Yaa-Hui; Chang, Yi-Cheng; Chuang, Lee-Ming

2015-01-01

Objective To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. Eligibility criteria Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B12 and folate levels. Data collection and analysis Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively. Results Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B12 deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency. Conclusions RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range. PMID:26185175

Haptoglobin Phenotype Modifies Serum Iron Levels and the Effect of Smoking on Parkinson Disease Risk

PubMed Central

Costa-Mallen, Paola; Zabetian, Cyrus P.; Agarwal, Pinky; Hu, Shu-Ching; Yearout, Dora; Samii, Ali; Leverenz, James B.; Roberts, John W.; Checkoway, Harvey

2015-01-01

Introduction Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk. Methods The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk. Results PD cases had lower serum iron than controls (83.28 ug/100ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity. Conclusions Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated. PMID:26228081

Effect of short-term food restriction on iron metabolism, relative well-being and depression symptoms in healthy women.

PubMed

Wojciak, Rafal W

2014-01-01

The idea that iron deficiency anemia can be recognized in depressive patients has been around for a few years, as well as negative association between ferritin levels and depression. Iron deficiency anemia, associated with low iron intake, has been observed in women using restriction diets, for example in vegetarians or anorexics. There are no data on the influence of the short-term food restrictions, observed for example in slimming women, on iron management and its connection with behavior expressed via changes in the subject's emotional state. This study describes the effect of one- and two-day food restrictions (every 8 days for a period of 48 days) on selected iron management parameters in the serum and blood of 46 healthy volunteer women (23 in each group), aged 25.5 ± 3.0 years, in association with the subjects' self-described emotional status and depression symptoms. The association between iron parameters and depression was also analyzed. Results show that short-term (2 days) fasting significantly decreases iron concentrations in serum and hair, as well as levels of ferritin, hemoglobin, hematocrit, red blood cells, and total iron binding capacity, but the short-term fasting did not influence the other iron management parameters. Each model of food restrictions also increased negative feelings towards depression. A significant negative correlation between serum ferritin levels and depression was found in women who starved for 2 days. The study shows that, through an impact on mineral levels, even short-term food restrictions, as observed in many slimming women and girls, can be a reason for iron deficiency and also can alter the emotional status of healthy women. Maybe depression symptoms in anorexia or other eating disorders patients can be associated with iron deficiencies.

Macroscopic quantum coherence in ferritin

NASA Astrophysics Data System (ADS)

Garg, Anupam

1996-04-01

In a breakthrough experiment, Awschalom et al. [ Phys. Rev. Lett. 68, 3092 (1992)] have demonstrated that the antiferromagnetic core in ferritin resonates between two states with oppositely directed Néel vectors, making it the first observation of MQC. A theory has been developed for this resonance including the effect of the 100 or so57Fe nuclear spins expected in each ferritin core. Since the hyperfine coupling is known to be ˜68 MHz and the MQC frequency is ˜1 MHz, the degeneracy of the Néel states, and with it, the MQC resonance, is destroyed in all ferritin particles except those with zero total staggered nuclear spin. From the measured size of λ″(ω), the energy being absorbed by the ferritin is at least 4000 times larger than the maximum permissible. Hence, the true importance of these experiments lies not in the narrow issue of MQC, but in the disproof of long cherished theoretical conservation laws.

Iron, ferritin, and nutrition.

PubMed

Theil, Elizabeth C

2004-01-01

Ferritin, a major form of endogenous iron in food legumes such as soybeans, is a novel and natural alternative for iron supplementation strategies where effectiveness is limited by acceptability, cost, or undesirable side effects. A member of the nonheme iron group of dietary iron sources, ferritin is a complex with Fe3+ iron in a mineral (thousands of iron atoms inside a protein cage) protected from complexation. Ferritin illustrates the wide range of chemical and biological properties among nonheme iron sources. The wide range of nonheme iron receptors matched to the structure of the iron complexes that occurs in microorganisms may, by analogy, exist in humans. An understanding of the chemistry and biology of each type of dietary iron source (ferritin, heme, Fe2+ ion, etc.), and of the interactions dependent on food sources, genes, and gender, is required to design diets that will eradicate global iron deficiency in the twenty-first century.

Octopus microvasculature: permeability to ferritin and carbon.

PubMed

Browning, J

1979-01-01

The permeability of Octopus microvasculature was investigated by intravascular injection of carbon and ferritin. Vessels were tight to carbon while ferritin penetrated the pericyte junction, and was found extravascularly 1-2 min after its introduction. Vesicles occurred rarely in pericytes; fenestrae were absent. The discontinuous endothelial layer did not consitute a permeability barrier. The basement membrane, although retarding the movement of ferritin, was permeable to it; carbon did not penetrate the basement membrane. Evidence indicated that ferritin, and thus similarly sized and smaller water soluble materials, traverse the pericyte junction as a result of bulk fluid flow. Comparisons are made with the convective (or junctional) and slower, diffusive (or vesicular) passage of materials known to occur across the endothelium of continuous capillaries in mammals. Previous macrophysiological determinations concerning the permeability of Octopus vessels are questioned in view of these findings. Possible reasons for some major structural differences in the microcirculatory systems of cephalopods and vertebrates are briefly discussed.

Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

PubMed Central

Hardy, S.; Vandemergel, X.

2015-01-01

Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed. PMID:26000018

Evaluation of the children with beta-thalassemia in terms of their self-concept, behavioral, and parental attitudes.

PubMed

Yalçn, Siddika Songül; Durmuşoğlu-Sendoğdu, Mine; Gümrük, Fatma; Unal, Selma; Karg, Eda; Tuğrul, Belma

2007-08-01

This study was planned to explore the self-concept, behavioral, and parental attitudes of the children with beta-thalassemia major, and the factors that affect them. The study was undertaken between January and June 2004 at the Hacettepe University Ihsan Doğramaci Children's Hospital, Pediatric Hematology Unit, Ankara and 43 voluntary children with beta-thalassemia major on regular blood transfusion and iron chelation treatment between the ages of 5.0 and 18.0 years were included into the study. Age, sex, birth order, school performance, hemoglobin value, serum ferritin levels, associated illness, splenectomy status, presence of thalassemic sibling or relatives, death of thalassemic relatives, place of residence, maternal and paternal education were recorded. Parental Attitude Research Instrument, Piers-Harris Self-Concept Scale, and Child Behavior Checklist were applied. Higher educated mothers have lower overprotection (P=0.009), parental discordance (P=0.044), and discipline scores (P=0.002) than lower educated mothers. In cases with death of thalassemic relatives, democratic/equality attitude scores were decreased (P=0.034). With stepwise multiple linear regression analysis, splenectomy, good school achievement, absence of death of thalassemic relatives, and serum ferritin levels were found to increase Piers-Harris Self-Concept Scale; however, total behavior problem score was found to decrease with increasing age, splenectomy and decreasing overprotection subscale of Parental Attitude Research Instrument scores. The self-esteem and behavior problems of children with thalassemia depended not only on the variables related exclusively to the child (age, school achievement) and the illness-associated conditions (splenectomy, serum ferritin levels) but also on the parental attitude (overprotection).

Association between chilli food habits with iron status and insulin resistance in a Chinese population.

PubMed

Li, Jiang; Wang, Rui; Xiao, Cheng

2014-04-01

Some studies have indicated that the consumption of chilli-containing foods can influence iron absorption and affect serum insulin and glucose concentrations, which may help to alleviate diabetes or prediabetes. The objective of this study was to explore the relationship between chilli food habits with iron status and insulin resistance in the Chinese population. Fasting blood samples, anthropometric data, and chilli food habit data collected from 8433 adults (aged 18 to 99), in 2009, as part of the China Health and Nutrition Survey, a large-scale longitudinal, household-based survey in China. Chilli food habits were assessed using chilli food eating frequencies (no eating, sometimes eating, often eating, and usually eating) and chilli food types (a little bit hot, moderately hot, and very hot). Fasting serum ferritin, insulin, and fasting plasma glucose were also measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin resistance. Compared with the chilli-eating group, the no eating group had higher HOMA-IR levels for both men and women (P<.05). There were significant differences in HOMA-IR (P<.05) for both men and women and in ferritin (P<.001) for women according to different chilli food types. However, there was no significant difference in the ferritin level and HOMA-IR components for different chilli food eating frequencies in both sex groups. Chilli food habits, especially the different hotness levels of chilli food, were associated with iron status and insulin resistance in the Chinese population. Additional studies are needed to elucidate mechanisms of action and to establish causal inference.

Dietary iron intake and iron status of German female vegans: results of the German vegan study.

PubMed

Waldmann, Annika; Koschizke, Jochen W; Leitzmann, Claus; Hahn, Andreas

2004-01-01

As shown in previous studies vegetarians and especially vegans are at risk for iron deficiency. Our study evaluated the iron status of German female vegans. In this cross-sectional study, the dietary intakes of 75 vegan women were assessed by two 9-day food frequency questionnaires. The iron status was analyzed on the basis of blood parameters. Mean daily iron intake was higher than recommended by the German Nutrition Society. Still 42% of the female vegans < 50 years (young women, YW) had a daily iron intake of < 18 mg/day, which is the recommended allowance by the US Food and Nutrition Board. The main dietary sources of iron were vegetables, fruits, cereals and cereal products. Median serum ferritin concentrations were 14 ng/ml for YW and 28 ng/ml for women > or = 50 years (old women, OW). In all, 40% (tri-index model (TIM) 20%) of the YW and 12% (TIM 12%) of the OW were considered iron-deficient based on either serum ferritin levels of < 12 ng/ml or a TIM. Only 3 women had blood parameters which are defined as iron deficiency anemia. Correlations between serum ferritin levels and dietary factors were not found. Although the mean iron intake was above the recommended level, 40% (TIM 20%) of the YW were considered iron-deficient. It is suggested that especially YM on a vegan diet should have their iron status monitored and should consider taking iron supplements in case of a marginal status. Copyright 2004 S. Karger AG, Basel

Iron regulatory proteins and their role in controlling iron metabolism.

PubMed

Kühn, Lukas C

2015-02-01

Cellular iron homeostasis is regulated by post-transcriptional feedback mechanisms, which control the expression of proteins involved in iron uptake, release and storage. Two cytoplasmic proteins with mRNA-binding properties, iron regulatory proteins 1 and 2 (IRP1 and IRP2) play a central role in this regulation. Foremost, IRPs regulate ferritin H and ferritin L translation and thus iron storage, as well as transferrin receptor 1 (TfR1) mRNA stability, thereby adjusting receptor expression and iron uptake via receptor-mediated endocytosis of iron-loaded transferrin. In addition splice variants of iron transporters for import and export at the plasma-membrane, divalent metal transporter 1 (DMT1) and ferroportin are regulated by IRPs. These mechanisms have probably evolved to maintain the cytoplasmic labile iron pool (LIP) at an appropriate level. In certain tissues, the regulation exerted by IRPs influences iron homeostasis and utilization of the entire organism. In intestine, the control of ferritin expression limits intestinal iron absorption and, thus, whole body iron levels. In bone marrow, erythroid heme biosynthesis is coordinated with iron availability through IRP-mediated translational control of erythroid 5-aminolevulinate synthase mRNA. Moreover, the translational control of HIF2α mRNA in kidney by IRP1 coordinates erythropoietin synthesis with iron and oxygen supply. Besides IRPs, body iron absorption is negatively regulated by hepcidin. This peptide hormone, synthesized and secreted by the liver in response to high serum iron, downregulates ferroportin at the protein level and thereby limits iron absorption from the diet. Hepcidin will not be discussed in further detail here.

Daily supplementation with iron increases lipid peroxidation in young women with low iron stores.

PubMed

King, Sarah M; Donangelo, Carmen M; Knutson, Mitchell D; Walter, Patrick B; Ames, Bruce N; Viteri, Fernando E; King, Janet C

2008-06-01

The aim of this study was to determine whether women with low iron stores (plasma ferritin

Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial.

PubMed

Chua, Seng; Gupta, Sarika; Curnow, Jennifer; Gidaszewski, Beata; Khajehei, Marjan; Diplock, Hayley

2017-12-19

Acute post-partum anaemia can be associated with significant morbidity including a predisposition for postnatal depression. Lack of clear practice guidelines means a number of women are treated with multiple blood transfusions. Intravenous iron has the potential to limit the need for multiple blood transfusions but its role in the post-partum setting is unclear. IIBAPPA is a multi-centre randomised non-inferiority trial. Women with a primary post-partum haemorrhage (PPH) >1000 mL and resultant haemoglobin (Hb) 5.5-8.0 g/dL after resuscitation with ongoing symptomatic anaemia who are otherwise stable (no active bleeding) are eligible to participate. Patients with sepsis or conditions necessitating rapid Hb restoration are excluded. Eligible participants are randomised to receive a blood transfusion or a single dose of intravenous iron polymaltose calculated using the Ganzoni formula. Primary outcome measures include Hb, Ferritin and C-Reactive Protein levels on Day 7. Secondary outcomes evaluate (i) Hb, Ferritin and CRP levels on Day 14, 28, (ii) anaemia symptoms on Day 0, 7, 14 and 28 using structured health related quality of life questionnaires, (iii) treatment safety by assessing adverse reactions and infection endpoints and (iv) the quantitative impact of anaemia on breast feeding quality using a hospital designed questionnaire. If equivalence in Hb and ferritin levels, symptom scores and safety endpoints is demonstrated, intravenous iron may become the preferred treatment for women with acute post-partum anaemia to minimise transfusion reactions and costs. Australian and New Zealand Clinical Trials Registry: ACTRN12615001370594 on 16th December, 2015 (prospective approval).

Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

PubMed

DeVita, M V; Frumkin, D; Mittal, S; Kamran, A; Fishbane, S; Michelis, M F

2003-11-01

Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33% were enrolled. Subjects were divided as follows: Group 1: target SFer of 200 ng/ml, Group 2: target SFer of 400 ng/ml. Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target. HCT was maintained between 32.5% and 36% by adjusting rHuEPO dosage. Mean SFer concentration at the study conclusion in Group 1: 261 ng/ml; Group 2: 387 ng/ml. The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week (250 - 219 U/kg bw/wk) while in Group 2 it was 154 U/kg body weight/week (312 - 158 U/kg bw/wk) (p < 0.001). There was no difference in HCT between groups. Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements.

A distance-controlled nanoparticle array using PEGylated ferritin

NASA Astrophysics Data System (ADS)

He, Chao; Uenuma, Mutsunori; Okamoto, Naofumi; Kamitake, Hiroki; Ishikawa, Yasuaki; Yamashita, Ichiro; Uraoka, Yukiharu

2014-12-01

A distance-controlled nanoparticle (NP) array was investigated using a simple spin coating process. It was found that the separation distance of NPs was controlled at the nanoscale by using polyethylene glycols (PEGs). Ferritin was used to synthesize NPs and carry them to a substrate by using the different molecular weight of PEGs. In order to control the distance of the NPs, PEGs with molecular weights of 2k, 5k, 10k and 20k were modified on ferritin with 10 mM ion strength and 0.01 mg ml-1 ferritin concentration. The separated distances of NPs increased along with increase in PEG molecular weight.

Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

NASA Astrophysics Data System (ADS)

Balejcikova, Lucia; Strbak, Oliver; Baciak, Ladislav; Kovac, Jozef; Masarova, Marta; Krafcik, Andrej; Frollo, Ivan; Dobrota, Dusan; Kopcansky, Peter

2017-04-01

Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation.

Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption

PubMed Central

Felipe, Avila; Guadalupe, Echeverría; Druso, Pérez; Carlos, Martinez; Pablo, Strobel; Oscar, Castillo; Luis, Villaroel; Diego, Mezzano; Jaime, Rozowski; Inés, Urquiaga; Federico, Leighton

2015-01-01

Background and Aims. Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. Methods and Results. Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose) as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin), hepatic damage markers (GGT, SGOT), and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose) correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. Conclusion. Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men. PMID:26451235

Serum Ferritin Is Associated with Metabolic Syndrome and Red Meat Consumption.

PubMed

Avila, Felipe; Echeverría, Guadalupe; Pérez, Druso; Martinez, Carlos; Strobel, Pablo; Castillo, Oscar; Villaroel, Luis; Mezzano, Diego; Rozowski, Jaime; Urquiaga, Inés; Leighton, Federico

2015-01-01

Hyperferritinemia has been related with a wide spectrum of pathologies, including diabetes, cardiovascular disease, neurodegenerative disorders, and metabolic syndrome. The aim of this study was to investigate the association between hyperferritinemia and iron consumption. Serum ferritin concentration was evaluated in 66 presumed healthy men, along with other clinical and biochemical markers of chronic diseases. A three-day food questionnaire was applied for nutrition information. Hyperferritinemia was a condition found in 13.4% of the volunteers analyzed. Significant correlations were found between serum ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose) as well as an increase of the serum ferritin mean value with the number of risk factors of metabolic syndrome. Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin), hepatic damage markers (GGT, SGOT), and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose) correlate significantly with serum ferritin. Volunteers had an excessive iron intake, principally by bread consumption. Analyses of food intake showed that red meat consumption correlates significantly with serum ferritin. Red meat consumption, metabolic syndrome, and chronic disease markers are associated with hyperferritinemia in a population of Chilean men.

Iron status in obese women.

PubMed

Stankowiak-Kulpa, Hanna; Kargulewicz, Angelika; Styszyński, Arkadiusz; Swora-Cwynar, Ewelina; Grzymisławski, Marian

2017-12-23

A decreased concentration of iron, and consecutively haemoglobin, ferritin and decreased level of saturated transferrin, were observed in obese individuals more often than in healthy subjects. The purpose of this study was to determine whether iron, ferritin, transferrin saturation are significantly diminished in obese female patients compared to non-obese counterparts, and whether excess adiposity and inflammation were associated with depleted iron. Female patients (n=48) diagnosed with obesity (BMI > 30 kg/m²), aged 18-40 were accepted for the study. A control group (n=30) encompassed normal weight women, aged 18-30. All obese women obtained an individually adjusted dietary plan with an energy content of 1,500 kcal. Blood glucose, insulin, lipids, ferritin, TIBC and iron concentrations were assayed in serum twice, initially and after 8 weeks of dieting. The obese women at the initial evaluation, in comparison to non-obese control women, were characterized by a significantly lower mean red blood cell volume (MCV; 84.2±12.4 vs. 91.3±9.3 fL; p<0.0001), serum iron level (92.6±42.4 vs. 119.8±44.0 μg/dL; p<0.01), and transferrin saturation (TSAT; 25.9±12.7 vs. 38.8±15.7%; p<0.01), but by higher plasma level of the C-reactive protein (CRP; 7.0±6.7 vs. 1.2±1.3 mg/L; p<0.01). The obese women after 8 weeks of diet decreased their mean total body weight from 104.1±21.3 to 99.2±20.7 kg (p<0.0001). CRP level decreased slightly but significantly from 6.9±7.1 to 6.2±7.5 (p<0.05). Obese women exhibit an increased level of CRP which may affect iron homeostasis. Weight loss leads to decrease in the CRP level, but it does not change haematologic parameters in the period of 8 weeks.

HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

PubMed Central

Evangelista, Andreia Silva; de Araújo, Thiago Ferreira; Abrantes-Lemos, Clarice Pires; Deguti, Marta Mitiko; Cançado, Eduardo Luiz Rachid

2015-01-01

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population. PMID:25654085

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

PubMed

Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

2008-08-01

Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

Government-industry partnership in weekly iron-folic acid supplementation for women of reproductive age in the Philippines: impact on iron status.

PubMed

Angeles-Agdeppa, Imelda; Paulino, Lourdes S; Ramos, Adelisa C; Etorma, Unita Marie; Cavalli-Sforza, Tommaso; Milani, Silvano

2005-12-01

The effectiveness of weekly iron-folic acid supplements promoted through a government-industry partnership was assessed in pregnant and non-pregnant women in the Philippines. Compliance to both weekly and daily supplementation increased during the year-long study period, but was highest with weekly supplementation. Serum ferritin and hematocrit increased significantly, whereas the hemoglobin level showed minimal change, probably because of lack of other heme-forming nutrients such as vitamin A. Serum ferritin increments were significantly higher in women taking the iron-folic acid supplements for more than 6 weeks. Weekly iron-folic acid supplementation should be recommended as a preventive strategy to control iron deficiency among reproductive-age women in the Philippines.

Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells

NASA Astrophysics Data System (ADS)

Geninatti Crich, S.; Cadenazzi, M.; Lanzardo, S.; Conti, L.; Ruiu, R.; Alberti, D.; Cavallo, F.; Cutrin, J. C.; Aime, S.

2015-04-01

In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation. Electronic supplementary information (ESI) available: Competition studies with free apoferritin, Fig. S1; APO-FITC intracellular distribution by immunofluorescence, Fig. S2. See DOI: 10.1039/c5nr00352k

Transfusional iron overload in children with sickle cell anemia on chronic transfusion therapy for secondary stroke prevention.

PubMed

Kwiatkowski, Janet L; Cohen, Alan R; Garro, Julian; Alvarez, Ofelia; Nagasubramanian, Ramamorrthy; Sarnaik, Sharada; Thompson, Alexis; Woods, Gerald M; Schultz, William; Mortier, Nicole; Lane, Peter; Mueller, Brigitta; Yovetich, Nancy; Ware, Russell E

2012-02-01

Chronic transfusion reduces the risk of recurrent stroke in children with sickle cell anemia (SCA) but leads to iron loading. Management of transfusional iron overload in SCA has been reported as suboptimal [1], but studies characterizing monitoring and treatment practices for iron overload in children with SCA, particularly in recent years with the expansion of chelator options, are lacking. We investigated the degree of iron loading and treatment practices of 161 children with SCA receiving transfusions for a history of stroke who participated in the Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) trial. Data obtained during screening, including past and entry liver iron concentration (LIC) measurements, ferritin values, and chelation were analyzed. The mean age at enrollment was 12.9 ± 4 years and the mean duration of transfusion was 7 ± 3.8 years. Baseline LIC (median 12.94 mg/g dw) and serum ferritin (median 3,164 ng/mL) were elevated. Chelation therapy was initiated after a mean of 2.6 years of transfusions. At study entry, 137 were receiving chelation, most of whom (90%) were receiving deferasirox. This study underscores the need for better monitoring of iron burden with timely treatment adjustments in chronically transfused children with SCA.

Systemic and Cerebral Iron Homeostasis in Ferritin Knock-Out Mice

PubMed Central

Li, Wei; Garringer, Holly J.; Goodwin, Charles B.; Richine, Briana; Acton, Anthony; VanDuyn, Natalia; Muhoberac, Barry B.; Irimia-Dominguez, Jose; Chan, Rebecca J.; Peacock, Munro; Nass, Richard; Ghetti, Bernardino; Vidal, Ruben

2015-01-01

Ferritin, a 24-mer heteropolymer of heavy (H) and light (L) subunits, is the main cellular iron storage protein and plays a pivotal role in iron homeostasis by modulating free iron levels thus reducing radical-mediated damage. The H subunit has ferroxidase activity (converting Fe(II) to Fe(III)), while the L subunit promotes iron nucleation and increases ferritin stability. Previous studies on the H gene (Fth) in mice have shown that complete inactivation of Fth is lethal during embryonic development, without ability to compensate by the L subunit. In humans, homozygous loss of the L gene (FTL) is associated with generalized seizure and atypical restless leg syndrome, while mutations in FTL cause a form of neurodegeneration with brain iron accumulation. Here we generated mice with genetic ablation of the Fth and Ftl genes. As previously reported, homozygous loss of the Fth allele on a wild-type Ftl background was embryonic lethal, whereas knock-out of the Ftl allele (Ftl-/-) led to a significant decrease in the percentage of Ftl-/- newborn mice. Analysis of Ftl-/- mice revealed systemic and brain iron dyshomeostasis, without any noticeable signs of neurodegeneration. Our findings indicate that expression of the H subunit can rescue the loss of the L subunit and that H ferritin homopolymers have the capacity to sequester iron in vivo. We also observed that a single allele expressing the H subunit is not sufficient for survival when both alleles encoding the L subunit are absent, suggesting the need of some degree of complementation between the subunits as well as a dosage effect. PMID:25629408

Efficacy and Safety of Combined Oral Chelation With Deferiprone and Deferasirox in Children With β-Thalassemia Major: An Experience From North India.

PubMed

Parakh, Nupur; Chandra, Jagdish; Sharma, Sunita; Dhingra, Bhavna; Jain, Rajesh; Mahto, DeoNath

2017-04-01

A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years. Patients on either DFP or DFX who were not improving on monotherapy over a long period and persistently maintaining serum ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum ferritin levels assessed at 12 months and 2 years. Complete blood counts and liver and kidney function tests were monitored to assess the safety of the combination of drugs. In total, 33 patients with a mean age of 12.67 years (7.5 to 17.5 y) and a mean ferritin of 4835.2394±1443.85 µg/L formed the study cohort.In total, 28 patients completed the 1-year study period; and 12 patients completed 2 years. Mean serum ferritin reduction at 1 and 2 years was 34.99%±18.13% (range, -34.36% to 56.17%) and 44.67%±13.78% (range, 22.17% to 62.74%), respectively. The combination therapy was well tolerated. Combined oral chelation with DFP and DFX has better efficacy than either drug used alone. The combination of drugs was well tolerated and no new adverse effects were observed.

Biomolecule nanoparticle-induced nanocomposites with resistive switching nonvolatile memory properties

NASA Astrophysics Data System (ADS)

Ko, Yongmin; Ryu, Sook Won; Cho, Jinhan

2016-04-01

Resistive switching behavior-based memory devices are considered promising candidates for next-generation data storage because of their simple structure configuration, low power consumption, and rapid operating speed. Here, the resistive switching nonvolatile memory properties of Fe2O3 nanocomposite (NC) films prepared from the thermal calcination of layer-by-layer (LbL) assembled ferritin multilayers were successfully investigated. For this study, negatively charged ferritin nanoparticles were alternately deposited onto the Pt-coated Si substrate with positively charged poly(allylamine hydrochloride) (PAH) by solution-based electrostatic LbL assembly, and the formed multilayers were thermally calcinated to obtain a homogeneous transition metal oxide NC film through the elimination of organic components, including the protein shell of ferritin. The formed memory device exhibits a stable ON/OFF current ratio of approximately 103, with nanosecond switching times under an applied external bias. In addition, these reversible switching properties were kept stable during the repeated cycling tests of above 200 cycles and a test period of approximately 105 s under atmosphere. These solution-based approaches can provide a basis for large-area inorganic nanoparticle-based electric devices through the design of bio-nanomaterials at the molecular level.