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Sample records for pre-transplant serum ferritin

  1. Serum ferritin.

    PubMed

    Worwood, M

    1979-01-01

    (1) Brief introduction to iron metabolism and the biochemistry of ferritin. (2) Early studies of circulating ferritin. (3) Methods for measuring serum ferritin concentrations -- immunoradiometric, radioimmuno- and enzyme-linked immuno assays based on liver or spleen ferritin -- an evaluation of these techniques. (4) Serum ferritin concentrations in normal subjects -- definition of normality -- relationship between storage iron and serum ferritin concentrations -- changes during development from birth to old age -- iron deficiency -- variability of serum ferritin concentration -- evaluation of use of ferritin assay for assessment of storage iron levels. (5) Serum ferritin concentrations in disease -- hemochromatosis -- secondary iron overload -- liver damage -- infection and chronic disease -- cancer. (6) Assay of serum ferritin with antibodies to ferritins other than liver or spleen -- ferritinemia and cancer. (7) Properties of serum ferritin -- molecular weight -- iron content -- isoelectric focusing patterns -- carbohydrate content -- immunological properties. (8) Physiology of circulating ferritin -- release of ferritin from tissues -- origin of circulating ferritin -- clearance from the plasma -- iron and protein turnover. (9) Summary -- factors influencing serum ferritin concentrations and clinical use of ferritin estimations.

  2. Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pre-transplant Ferritin, Albumin and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation

    PubMed Central

    Vaughn, Jennifer E.; Storer, Barry; Armand, Philippe; Raimondi, Roberto; Gibson, Christopher; Rambaldi, Alessandro; Ciceri, Fabio; Oneto, Rosi; Bruno, Benedetto; Martin, Paul J.; Sandmaier, Brenda M.; Storb, Rainer; Sorror, Mohamed L.

    2015-01-01

    Purpose Pre-transplant values of serum ferritin, albumin and peripheral blood counts were previously suggested to provide prognostic information about hematopoietic cell transplantation (HCT) outcomes. Whether these “biomarkers” have prognostic value independent of each other and the HCT-comorbidity index (HCT-CI) is unknown. Patients and Methods We analyzed data from 3917 allogeneic HCT recipients at multiple sites in the US and Italy using multivariate models including each biomarker and the HCT-CI. Data from all sites were then randomly divided into a training set (n=2352) to develop weights for the relevant biomarkers to be added to the HCT-CI scores and a validation set (n=1407) to validate an augmented HCT-CI compared to the original index. Results Multivariate analysis with data from one site showed that ferritin, albumin and platelets-- not neutrophils or hemoglobin--were independently associated with increased non-relapse mortality (NRM) and decreased overall survival. Findings were validated in data from the other sites. Subsequently, in a training set from all sites, ferritin >2500 mg/dL (HR:1.69); albumin 3–3.5 g/dL (HR:1.61) and <3.0 g/dL (HR:2.27); and platelets 50–<100,000 (HR:1.28), 20–<50,000 (HR:1.29) and <20,000 (HR:1.55) were statistically significantly associated with NRM. Weights were assigned to these laboratory values following the same equation used to design the original index. In the validation set, The addition of the biomarkers to the original index to develop an augmented HCT-CI resulted in a statistically significant increase in higher c-statistic estimate for prediction of NRM. (p=0.0007). Conclusion Ferritin, albumin, and platelet counts are important prognostic markers that further refine the discriminative power of the HCT-CI for transplant outcomes. PMID:25862589

  3. Serum selenium assay following serum ferritin assay

    SciTech Connect

    Stevens, R.G.; Morris, J.S.; Hann, H.L.; Pulsipher, B.; Stahlhut, M.W.

    1986-08-01

    Stored serum samples can be an important research resource into the etiology of cancer. These sera cannot be replaced and should therefore be used to best advantage. In previous epidemiologic studies, only single serum constituents have been assayed in individual serum samples. For example, serum ferritin has been examined in samples stored for as long as 10 years at -20C for a possible relation with general mortality (1) and cancer death (2). Ferritin is the tissue iron-storage protein and is therefore subject to denaturation. Serum selenium has also been examined in relation to cancer risk in a prospective manner by using stored frozen serum samples (3, 4). The interactions of a variety of serum factors in relation to cancer risk would be a desirable research goal, except that the amounts of serum typically available in frozen serum banks are less than 1 ml. It was the purpose of this investigation to determine if a radioimmunoassay for ferritin affected a subsequent neutron activation assay for selenium on the same 0.1 ml serum sample.

  4. Elevated serum ferritin - what should GPs know?

    PubMed

    Goot, Katie; Hazeldine, Simon; Bentley, Peter; Olynyk, John; Crawford, Darrell

    2012-12-01

    Elevated serum ferritin is commonly encountered in general practice. Ninety percent of elevated serum ferritin is due to noniron overload conditions, where venesection therapy is not the treatment of choice. This article aims to outline the role of the Australian Red Cross Blood Service Therapeutic Venesection program, to clarify the interpretation of the HFE gene test and iron studies, and to describe the steps in evaluating a patient with elevated serum ferritin. After exclusion of hereditary haemochromatosis, investigation of elevated serum ferritin involves identifying alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection or inflammation as causative factors. Referral to a gastroenterologist, haematologist or physician with an interest in iron overload is appropriate if serum ferritin is >1000 µg/L or if the cause of elevated serum ferritin is still unclear.

  5. Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

    PubMed

    Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

    2014-09-01

    Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Prognostic Value of Pre-transplantation Serum Alpha-Fetoprotein Levels in Hepatocellular Carcinoma Recurrence.

    PubMed

    Montalvá, E M; Cantos, M; Boscà, A; Rubín, A; Vinaixa, C; Granero, P; Maupoey, J; López-Andújar, R

    2016-11-01

    Serum alpha-fetoprotein (AFP) value is still not included in the consensus guidelines to make decisions referring to liver transplantation (LT) for hepatocellular carcinoma (HCC). Many studies demonstrated the influence of high AFP level in poor prognosis after LT for HCC. We studied 301 consecutive recipients transplanted for HCC from January 2002 to December 2011. The median follow-up was 64.3 months (interquartile range, 41.6-90.8). HCC recurrence was 31.6% when AFP was >400 ng/mL and 50% when AFP was >1,000 ng/mL. Specificity to predict HCC recurrence was 95.1% (95% confidence interval [CI], 91.9-97.1) when AFP was >400 ng/mL and 98.9% (95% CI, 96.8-99.6) when AFP was >1,000 ng/mL. The overall survival (P = .008) and disease-free survival (P = .004) differed between patients groups when an AFP cutoff level of 1,000 ng/mL was used. The predictive accuracy of high pre-transplantation serum AFP level for HCC post-transplantation recurrence should be used in decision algorithms for LT. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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…

  8. 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…

  9. Serum ferritin levels in hemoglobin H disease.

    PubMed

    Galanello, R; Melis, M A; Paglietti, E; Cornacchia, G; de Virgiliis, S; Cao, A

    1983-01-01

    This study shows that hemoglobin H disease patients aged between 0.5 and 44 years, usually (27 out of 30) have normal serum ferritin levels according to age. This reconfirms that in this disease there are usually normal iron stores. However, in a few patients (3 out of 30) increased levels were found. This may be due to inappropriate iron medication, transfusions or associated idiopathic hereditary hemocromatosis gene.

  10. Serum & cerebrospinal fluid ferritin levels in children with acute leukaemia.

    PubMed

    Srinivasan, A; Rusia, U; Anand, N K; Sood, S K

    1989-06-01

    Serum and CSF ferritin were estimated in 35 consecutive patients of acute leukaemia at the time of admission and on induction of remission. Serum ferritin levels were significantly raised in 94 per cent patients of acute leukaemia. The mean (+/- SD) serum ferritin (314.36 +/- 158.4 micrograms/1) was significantly higher when compared with control values (P less than 0.001). Remission induction resulted in significant fall in serum ferritin values to a mean of 149 (+/- 98.7) micrograms/l (P less than 0.05). Serum ferritin is thus of value in assessing the state of remission and is a sensitive indicator of the leukaemic cell mass and the state of activity of the disease. CSF ferritin levels in acute leukaemia were comparable to normal control values. CSF ferritin did not reflect CNS involvement in acute leukaemia and therefore its value as a tumour marker of CNS infiltration is doubtful.

  11. Serum ferritin concentration in patients receiving maintenance hemodialysis.

    PubMed

    Lynn, K L; Mitchell, T R; Shepperd, J

    1980-09-01

    Studies in 144 patients on maintenace hemodialysis have shown that serum ferritin concentration is influenced by the period the patient has been on dialysis, the presence of liver disease and to some extent the underlying diagnosis. It was observed that parenteral iron therapy could still produce an increase in hemoglobin concentration when the serum ferritin was as high as 60--55 micrograms/l. This suggests that the target serum ferritin, whatever the route of iron replacement, should be at least 55 micrograms/l. The higher levels of ferritin at which an increase in hemoglobin concentration can occur, together with the variable increment in serum ferritin after parenteral iron, indicates that the simple relationship between serum ferritin and marrow iron stores may be distrubed in some patients.

  12. Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Abreu-González, Pedro; Díaz, Dácil; Moreno, Antonia M.; Borja, Elisa; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

    2016-01-01

    Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT. PMID:27058525

  13. [Serum ferritin in donors with regular plateletpheresis].

    PubMed

    Ma, Chun-Hui; Guo, Ru-Hua; Wu, Wei-Jian; Yan, Jun-Xiong; Yu, Jin-Lin; Zhu, Ye-Hua; He, Qi-Tong; Luo, Yi-Hong; Huang, Lu; Ye, Rui-Yun

    2011-04-01

    This study was aimed to evaluate the impact of regular donating platelets on serum ferritin (SF) of donors. A total of 93 male blood donors including 24 initial plateletpheresis donors and 69 regular plateletpheresis donors were selected randomly. Their SF level was measured by ELISA. The results showed that the SF level of initial plateletpheresis donors and regular plateletpheresis donors were 91.08 ± 23.38 µg/L and 57.16 ± 35.48 µg/L respectively, and all were in normal levels, but there was significant difference between the 2 groups (p < 0.05). The SF level decreased when the donation frequency increased, there were no significant differences between the groups with different donation frequency. Correlation with lifetime donations of platelets was not found. It is concluded that regular plateletpheresis donors may have lower SF level.

  14. The association between serum ferritin with colorectal cancer.

    PubMed

    Feng, Zhe; Chen, Ji-Wei; Feng, Jian-Hua; Shen, Fei; Cai, Wen-Song; Cao, Jie; Xu, Bo

    2015-01-01

    There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum level of ferritin than the healthy controls (SMD=-1.569, 95% CI=[-2.718, -0.420], P= 0.007). Further subgroup analysis found lower serum level of ferritin among patients with colorectal cancer in eastern country (SMD=-1.956, 95% CI=[-3.750, -0.162], P=0.033), but not in western country (SMD=-1.285, 95% CI=[-2.778, 0.207], P=0.091). In conclusion, this meta-analysis supports a significant association between serum ferritin with colorectal cancer. However, the subgroup analysis found that there was significant effect modification of ferritin level by ethnic. Thus this finding needs further confirmation by trans-regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between serum ferrintin levels and colorectal cancer, through measuring ferritin at baseline to investigate whether the highest ferritin category versus lowest is associated with colorectal cancer risk.

  15. The purification and properties of ferritin from human serum.

    PubMed Central

    Worwood, M; Dawkins, S; Wagstaff, M; Jacobs, A

    1976-01-01

    1. Ferritin has been isolated from the serum of four patients with iron overload by using two methods. 2. In method A, the serum was adjusted to pH 4.8 and heated to 70 degrees C. After removal of denatured protein, ferritin was concentrated and further purified by ion-exchange chromatography and gel filtration. In most cases, only a partial purification was achieved. 3. In method B, ferritin was extracted from the serum with a column of immuno-adsorbent [anti-(human ferritin)] and released from the column with 3M-KSCN. Further purification was achieved by anion-exchange chromatography followed by the removal of remaining contaminating serum proteins by means of a second immunoadsorbent. Purifications of up to 31 000-fold were achieved, and the homogeneity of the final preparations was demonstrated by polyacrylamide-gel electrophoresis. 4. Serum ferritin purified by either method has the same elution volume as human spleen ferritin on gel filtration on Sephadex G-200. Serum ferritin has a relatively low iron content and iron/protein ratios of 0.023 and 0.067 (mug of Fe/mug of protein) were found in two pure preparations. On anion-exchange chromatography serum ferritin has a low affinity for the column when compared with various tissue ferritins. Isoelectric focusing has demonstrated the presence of a high proportion of isoferritins of relatively high pI. 5. Possible mechanisms for the release of ferritin into the circulation are briefly discussed. Images PLATE 2 PLATE 1 PMID:962866

  16. Abnormally high serum ferritin levels among professional road cyclists

    PubMed Central

    Zotter, H; Robinson, N; Zorzoli, M; Schattenberg, L; Saugy, M; Mangin, P

    2004-01-01

    Background: An international, longitudinal medical follow up examination of male professional road cyclists revealed excessively elevated serum ferritin levels. Objective: To evaluate the importance of elevated ferritin values among professional cyclists, their relationship with age and nationality, and their evolution over 3 years. Methods: Over 1000 serum ferritin values were collected. Other parameters were included in order to exclude conditions which might have increased ferritin levels without changing body iron stores. Results: In 1999, over 45% of riders displayed ferritin values above 300 ng/ml and one fourth levels over 500 ng/ml. These percentages had decreased to 27% and 9%, respectively, 3 years later, while the overall average, which was above the normal limits in 1999, had decreased by 33% in 3 years. Older cyclists had higher ferritin values than younger cyclists. There was also a relationship between ferritin levels and the nationality of the cyclists. Analysis of 714 riders in 2000 and 2002 showed only a slight and insignificant decrease in the mean ferritin value although those with initially elevated iron stores had a much greater decrease. Conclusion: Professional road cyclists used excessive iron supplementation leading to high serum ferritin levels correlating with increased body iron stores. Although the situation progressively improved over 3 years, it remains worrying as increased body iron stores are related to health complications. Therefore, prevention in addition to the fight against doping should be a main goal of the UCI. Aggressive therapy for athletes with excessive ferritin values should be carried out at or before the end of their careers. PMID:15562163

  17. 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

  18. Measurement of ferritin and anti-ferritin autoantibodies in serum and colostrum of Holstein and Japanese Black cows.

    PubMed

    Kanno, Yoshiya; Ohtsuka, Hiromichi; Yoshikawa, Yasunaga; Watanabe, Kiyotaka; Orino, Koichi

    2013-07-01

    Anti-ferritin autoantibody is a ferritin-binding protein commonly found in mammals; it is thought to form an immune complex with ferritin and thereby mediate the rapid clearance of circulating ferritin. The aim of this study is to determine concentrations of ferritin and anti-ferritin autoantibodies (immunoglobulin (Ig)M, IgG and IgA) in serum and colostrum of Holstein (H) and Japanese Black (JB) cows within 24 h of normal calving. Blood and colostrum samples were collected from cows of various ages (2-11 years) and calving number (1-8 live births). Mean ferritin concentrations were higher in colostrum than in serum for both breeds, and higher colostrum ferritin concentrations were found in H than JB cows. IgA antibodies in serum and colostrum from both breeds had negligible ferritin-binding activity. For both breeds, IgM and IgG antibodies had higher ferritin-binding activity in colostrum than in serum. There was a significant correlation between IgM and IgG ferritin-binding activities in serum and colostrum of H and JB cows. These results suggest that ferritin and IgM and IgG autoantibodies are actively transferred from the blood stream to the colostrum at prepartum or early lactation.

  19. Serum iron and ferritin level in idiopathic Parkinson.

    PubMed

    Farhoudi, Mehdi; Taheraghdam, Aliakbar; Farid, Gholnar Abbasi; Talebi, Mahnaz; Pashapou, Ali; Majidi, Jafar; Goldust, Mohamad

    2012-11-15

    Parkinson disease is a prevalent progressive neurodegenerative disorder, especially in western countries and among the elderly. This study aimed at evaluating serum iron and ferritin in patients with idiopathic Parkinson disease. In this case-control study, 50 patients with clinical diagnosis of idiopathic Parkinson disease (case group) were evaluated during a 12 month period. Fifty healthy persons (control group) recruited as well. Serum iron and ferritin levels were measured by biochemical and quantitative luminance methods, respectively in the case and control group. Fifty patients, 28 males and 22 females with the mean age of 64.53 +/- 10.18 (40-84) years and 50 controls were enrolled. Serum iron levels were 70.22 +/- 25.18 mg dL(-1) and 67.62 +/- 39.53 mg dL(-1) in case and control group, respectively. Serum ferritin levels were 129.79 +/- 137.67 ng dL(-1) and 109.87 +/- 154.71 ng dL(-1) in case and control group, respectively. There was no significant difference between different grades of Parkinson disease considering the serum level of iron or ferritin. The current study showed that generally there is no significant difference between the patients with the idiopathic Parkinson disease and healthy controls in terms of serum iron and ferritin levels. The same results were attributable to different grades of the disease.

  20. Evaluation of iron stores in blood donors by serum ferritin.

    PubMed

    Mittal, Romilla; Marwaha, Neelam; Basu, Sabita; Mohan, Harsh; Ravi Kumar, A

    2006-12-01

    Regular blood donation can lead to pre-clinical iron deficiency as well as iron deficiency anaemia. There is a need to increase the national voluntary blood donation for safe blood supply. However, there is paucity of data in the country regarding impact of regular voluntary blood donation on iron status of donors. Hence, iron stores were evaluated by serum ferritin estimation in the voluntary blood donors at Chandigarh. 400 voluntary blood donors included in the study were divided into four groups depending upon their periodicity of blood donations. Pre-donation haemoglobin assessment was done by copper sulphate method. Serum ferritin was estimated by indirect ELISA. The number of female donors with deficient iron stores was more as compared to male donors. First time donors had higher mean serum ferritin levels than that in repeat donors. The frequency of donations per year was more predictive of decreased iron stores rather than the number of lifetime donations. An increase in donation frequency was accompanied by a significant decrease in serum ferritin; values <15 microg/l were found in 21 and 46 per cent of male and female donors respectively who donated once per year, in 29 and 27 per cent in those who donated twice per year and in 49 and 100 per cent in those who donated thrice per year. Haemoglobin estimation alone in regular blood donors may not be adequate; serum ferritin estimations may need to be done to detect pre-clinical iron deficiency states. Also, iron supplementation needs to be considered in regular, repeat voluntary blood donors.

  1. Relationship between serum ferritin level and amikacin ototoxicity.

    PubMed

    Shayaninasab, Mohammad; Fatololoomi, Mohammadreza; Behnood, Fatollah; Alizamir, Azam

    2012-07-01

    Aminoglycosides are highly effective against bacteria but have serious side-effects including ototoxicity and nephrotoxicity. One of the theories in aminoglycosides ototoxicity is that Iron-aminoglycoside complex causes ototoxicity by creating free radicals. Based on this theory, the relationship between serum iron level and amikacin ototoxicity was studied to determine whether more iron results in more ototoxcity. This prospective cohort study was conducted from August 2005 to October 2008. Patients with amikacin prescription and different serum-ferritin levels were examined. Burned patients with amikacin prescription were divided into Group1 (89 patients; serum-ferritin >150) and Group2 (92 patients, serum-ferritin <150). Their hearing thresholds and red-blood-cells indices were compared using t- and paired t-test. In comparing the two groups, thresholds of Group1 were higher than Group2 at all frequencies, and the difference was statistically significant (p<0.001). The maximum threshold shift in Group1 was greater than 20 dB and in Group2, it was less than 10 dB, at 8000Hz. Again, this result was statistically and clinically significant (p<0.001). Finally, the mean corpuscular volume (MCV)was higher in Group1 than Group2, and (p=0.001). The results suggest that the level of iron is related to aminoglycoside ototoxicity. More iron can create more ototoxicity, and iron deficiency may inhibit aminoglycoside ototoxicity. An increase in MCV may be due to higher serum ferritin and an indication of more ototoxicity.

  2. Enzyme-linked immunosorbent assay to measure serum ferritin and the relationship between serum ferritin and nonheme iron stores in cats.

    PubMed

    Andrews, G A; Chavey, P S; Smith, J E

    1994-11-01

    Serum ferritin concentration correlates with tissue iron stores in humans, horses, calves, dogs, and pigs but not in rats. Because serum iron and total iron-binding capacity can be affected by disorders unrelated to iron adequacy (such as hypoproteinemia, chronic infection, hemolytic anemia, hypothyroidism, and renal disease), serum ferritin is probably the most reliable indicator of total body iron stores in larger species. To test the hypothesis that serum ferritin might be correlated with tissue iron levels in cats, we developed a quantitative enzyme-linked immunosorbent assay that uses two monoclonal antibodies in a sandwich arrangement to measure feline serum ferritin. The recovery of purified ferritin added to feline sera ranged from 94% to 104%; the within-assay coefficient of variability was 8.4%, and the assay-to-assay variability was 13.2%. Mean serum ferritin from 40 apparently healthy cats was 76 ng/ml (SD = 24 ng/ml). Serum ferritin concentration was significantly correlated (P < 0.001, n = 101, r = 0.365) with the nonheme iron in the liver and spleen (expressed as milligrams of iron per kilogram of body weight), as determined by Pearson product-moment correlation analysis. Because serum iron can decrease in diseases other than iron deficiency, the combination of serum iron and serum ferritin should provide sufficient evidence to differentiate anemia of chronic inflammation from anemia of iron deficiency in the cat.

  3. Relationship between serum ferritin, alcohol intake, and social status in 2235 Danish men and women.

    PubMed

    Milman, N; Kirchhoff, M

    1996-03-01

    The objective was to examine the relationships between serum ferritin, alcohol intake, and socioeconomic factors (school education, occupational education, occupation, income, marital status, cohabitation status, housing, social class) in a population survey performed in Copenhagen County during 1982-1984. The participants were selected at random from the census register and comprised 2235 healthy Danish individuals, non-blood donors (1044 men, 1191 women) in cohorts being 30, 40, 50, and 60 years old. The participants gave a detailed social and medical history and had a clinical examination including blood samples. In all age-groups, men had significantly higher serum ferritin and alcohol intake than women. In men, there was no relationship between serum ferritin and social class. Significant relationships were observed between ferritin and occupation (unemployed and self-employed men had higher ferritin than those with other occupations) and ferritin and income (in younger men, ferritin displayed a steady increase with income). None of the social variables were related to the prevalence of iron deficiency or iron overload. Alcohol intake was related to occupation and income, but not to social class. In women, none of the social variables showed any significant relationship to ferritin levels or iron overload. The prevalence of small iron stores (serum ferritin < or = 30 micrograms/l) was lower and the intake of alcohol was higher in women from high social classes. In both men and women, serum ferritin displayed highly significant positive correlations with alcohol intake. Likewise, the prevalence of iron overload (serum ferritin > 90th percentile) was closely correlated to alcohol intake. In conclusion, socioeconomic factors per se had a minor influence on serum ferritin levels and iron status in Danes. The distinct association between alcohol intake and serum ferritin levels should be considered in future iron status surveys.

  4. [Evaluation of Basic Performance of "Point Strip ferritin-3000" for Simple and Rapid Quantification of Serum Ferritin].

    PubMed

    Shibusa, Kotoe; Hatayama, Mayumi; Toki, Yasumichi; Yamamoto, Masayo; Ito, Satoshi; Shindo, Motohiro; Fujiya, Mikihiro; Niizeki, Noriyasu; Tomoda, Yutaka; Kawai, Yuichi; Addo, Lynda; Ikuta, Katsuya

    2015-12-01

    Serum ferritin is an excellent marker for total iron content in the body and is essential for the diagnosis of iron deficiency or iron overload. Recently, a simple and rapid method, which utilizes immunochromatography for the quantification of serum ferritin, was developed. However, the range of measurement in previous reagents was limited (10-500 ng/mL). This range is rather narrow and is not fully helpful for the diagnosis of iron overload which sometimes occurs as a result of prolonged transfusions, or for monitoring iron contents during iron chelation therapy against iron overload. In the present study we evaluated the basic performance of the newly developed "Point Strip ferritin-3000", which can measure serum ferritin in the range of 300-3,000 ng/mL. Coefficient of variation (CV) s of within and inter-day assays were in the ranges of 7.3-11.1% and 2.1-5.2%, respectively. Using 87 serum samples obtained from the patients with written informed consents, the correlation coefficient was calculated to be 0.93 compared to the control method. In addition, the quantification of serum ferritin by "Point Strip ferritin-3000" was not influenced by bilirubin, hemoglobin, chyle, rheumatoid factor, or ascorbic acid. From our data, "Point Strip ferritin-3000" is reliable reagent in the range of 300-3,000 ng/mL, and is therefore considered to be useful for the diagnosis of iron overload, as well as for monitoring iron contents during iron chelation therapy. In addition, this quantification method can be easily performed using a small desktop equipment without any special technique, making this system applicable for epidemiological surveys and clinical studies.

  5. Serum ferritin and total iron-binding capacity to estimate iron storage in pigs.

    PubMed

    Smith, J E; Moore, K; Boyington, D; Pollmann, D S; Schoneweis, D

    1984-11-01

    The inability to accurately determine storage iron in baby pigs limits the development of new treatment programs. In pigs treated neonatally with iron dextran, serum ferritin had increased dramatically at ten days of age and then returned to near preinjection levels by 50 days of age. In contrast, serum ferritin in untreated pigs declined until they were offered creep feed at 21 days of age. When serum ferritin, serum iron, serum total iron-binding capacity, erythrocyte number, packed cell volume, and blood hemoglobin were measured in three-week-old pigs, serum ferritin combined with serum total iron-binding capacity correlated significantly with the total nonheme iron in the liver and spleen. The nonheme iron (in mg) could be predicted (r2 = 0.71) by the following expression: 8.7 + 0.6 (ferritin in ng/ml).

  6. Transformation rate between ferritin and hemosiderin assayed by serum ferritin kinetics in patients with normal iron stores and iron overload.

    PubMed

    Saito, Hiroshi; Hayashi, Hisao

    2015-11-01

    Ferritin iron, hemosiderin iron, total iron stores and transformation rate were determined by serum ferritin kinetics. The transformation rate between ferritin and hemosiderin is motivated by the potential difference between them. The transformer determines transformation rate according to the potential difference in iron mobilization and deposition. The correlations between transformation rate and iron stores were studied in 11 patients with chronic hepatitis C (CHC), 1 patent with treated iron deficiency anemia (TIDA), 9 patients with hereditary hemochromatosis (HH) and 4 patients with transfusion-dependent anemia (TD). The power regression curve of approximation showed an inverse correlation between transformation rate and ferritin iron, hemosiderin iron in part and total iron stores in HH. Such an inverse correlation between transformation rate and iron stores implies that the larger the amount of iron stores, the smaller the transformation of iron stores. On the other hand, a minimal inverse correlation between transformation rate and ferritin iron and no correlation between transformation rate and hemosiderin iron or total iron stores in CHC indicate the derangement of storage iron metabolism in the cells with CHC. Radio-iron fixation on the iron storing tissue in iron overload was larger than that in normal subjects by ferrokinetics. This is consistent with the inverse correlation between transformation rate and total iron stores in HH. The characteristics of iron turnover between ferritin and hemosiderin were disclosed from the correlation between transformation rate and ferritin iron, hemosiderin iron or total iron stores.

  7. Serum ferritin and the iron status of Canadians.

    PubMed Central

    Valberg, L. S.; Sorbie, J.; Ludwig, J.; Pelletier, O.

    1976-01-01

    Serum ferritin concentration was determined in 1105 Canadians aged 1 to 90 years. Geometric mean values (ng/ml) were as follows: children 1 to 4 years old, 12; children 5 to 9 years old, 15; adolescent girls, 17; adolescent boys, 18; women 20 to 39 years, 23; women 65 years and older, 52; men 20 to 39 years, 93; and men 40 and older, 92. Ranges were side in all age groups, reflecting variations in size of body iron stores. From analysis of the ferritin values it is highly probably that iron stores were greatly reduced in approximately 25% of children, 30% of adolescents, 30% of menstruating women, 60% of pregnant women and 3% of men. Iron-deficiency anemia was noted in only 2% of subjects. If "normality" requires more than small amounts of storage iron to meet physiologic demands, the study results suggest a high probability of iron deficiency in 60% of the pregnant women and in 19% of the other subjects; but if normality is defined as maintenance of adequate iron stores for erythropoiesis, the prevalence of iron deficiency was zero in the pregnant women and 2% in the other subjects. PMID:1253085

  8. Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis

    PubMed Central

    Lawton, Paul D.; Barzi, Federica; Cass, Alan; Hughes, Jaquelyne T.

    2017-01-01

    Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT) as measures of iron status and ferritin and C-reactive protein (CRP) as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years) on maintenance haemodialysis (>3 months) from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9) years. 1244 (79.3%) were Indigenous. 44.2% (n = 693) were male. Indigenous patients were younger (mean age [52.3 (11.1) versus 57.4 (15.2), p < 0.001]) and had higher CRP [14.7 mg/l (7–35) versus 5.9 mg/l (1.9–17.5), p < 0.001], higher median serum ferritin [1069 µg/l (668–1522) versus 794.9 µg/l (558.5–1252.0), p < 0.001], but similar transferrin saturation [26% (19–37) versus 28% (20–38), p = 0.516]. We observed a small positive correlation between ferritin and TSAT (r2 = 0.11, p < 0.001), no correlation between ferritin and CRP (r2 = 0.001, p < 0.001), and positive association between high serum ferritin and TSAT (p < 0.001), Indigenous ethnicity (p < 0.001), urea reduction ratio (p = 0.001), and gender (p < 0.001) after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation. PMID:28243472

  9. Serum ferritin as an indicator of the development of encephalopathy in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome.

    PubMed

    Shimizu, Masaki; Inoue, Natsumi; Kuroda, Mondo; Irabu, Hitoshi; Takakura, Maiko; Kaneda, Hisashi; Sugimoto, Naotoshi; Ohta, Kazuhide; Yachie, Akihiro

    2017-03-10

    To investigate the diagnostic value of serum ferritin levels as a marker of disease activity and the development of encephalopathy in hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli. Twenty patients with HUS were studied. Serum ferritin levels were compared with clinical features and serum soluble tumor necrosis factor receptor (sTNFR) I and sTNFRII levels. Serum sTNFRI and sTNFRII levels were quantified by enzyme-linked immunosorbent assays. Serum ferritin levels were significantly elevated at the time of the diagnosis of HUS. Serum ferritin levels were significantly elevated in patients with encephalopathy compared to patients without encephalopathy. HUS patients with serum ferritin levels of >687.5 ng/ml were at high risk of encephalopathy. Serum ferritin levels were significantly positively correlated with serum sTNFRI and sTNFRII levels. Serum ferritin levels are a promising indicator of the development of encephalopathy in HUS.

  10. Serum Ferritin as a Predictor of Host Response to Hepatitis B Virus Infection

    NASA Astrophysics Data System (ADS)

    Lustbader, Edward D.; Hann, Hie-Won L.; Blumberg, Baruch S.

    1983-04-01

    With hemodialysis patients, a high serum ferritin before there was serological evidence of hepatitis B virus infection increased the likelihood that the infection would be persistent. This finding suggested that hepatitis B virus is likely to infect and actively replicate in liver cells with the propensity for increased ferritin synthesis. The virus itself could stimulate the synthesis of ferritin in a cyclic positive feedback mechanism that increases intracellular ferritin concentration and, eventually, intracellular iron. Transformed liver cells have low iron content, do not replicate hepatitis B virus, and require iron for growth. Infected, nonmalignant liver cells could supply iron to the transformed cells and nourish their expansion.

  11. 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.

  12. 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.

  13. 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

  14. Association between serum ferritin and goitre in Iranian school children.

    PubMed

    Hashemipour, Mahin; Soheilipour, Fahimeh; Keshteli, Ammar Hassanzadeh; Siavash, Mansour; Amini, Masoud; Kelishadi, Roya

    2010-04-01

    Despite long-standing supplementation of iodine in Iran, the prevalence of goitre among general people remains high in some regions. The study investigated the role of iron status in the aetiology of goitre in school children in Isfahan, Iran. Two thousand three hundred and thirty-one school children were selected by multi-stage random sampling. Thyroid size was estimated by inspection and palpation. Urinary iodine concentration (UIC) and serum ferritin (SF) were measured. Overall, 32.9% of the children had goitre. The median UIC was 195.5 microg/L. The mean +/- SD of SF in the goitrous and non-goitrous children was 47.65 +/- 42.51 and 44.55 +/- 37.07 microg/L respectively (p=0.52). The prevalence of iron deficiency in goitrous and non-goitrous children was 9.6% and 3.1% respectively (p=0.007). Goitre is still prevalent in school children of Isfahan. However, their median UIC was well in the accepted range. Iron deficiency is associated with goitre in a small group of goitrous children. The role of goitrogens should also be investigated in this region.

  15. Association between Serum Ferritin and Goitre in Iranian School Children

    PubMed Central

    Hashemipour, Mahin; Soheilipour, Fahimeh; Siavash, Mansour; Amini, Masoud; Kelishadi, Roya

    2010-01-01

    Despite long-standing supplementation of iodine in Iran, the prevalence of goitre among general people remains high in some regions. The study investigated the role of iron status in the aetiology of goitre in school children in Isfahan, Iran. Two thousand three hundred and thirty-one school children were selected by multi-stage random sampling. Thyroid size was estimated by inspection and palpation. Urinary iodine concentration (UIC) and serum ferritin (SF) were measured. Overall, 32.9% of the children had goitre. The median UIC was 195.5 μg/L. The mean±SD of SF in the goitrous and non-goitrous children was 47.65±42.51 and 44.55±37.07 μg/L respectively (p=0.52). The prevalence of iron deficiency in goitrous and non-goitrous children was 9.6% and 3.1% respectively (p=0.007). Goitre is still prevalent in school children of Isfahan. However, their median UIC was well in the accepted range. Iron deficiency is associated with goitre in a small group of goitrous children. The role of goitrogens should also be investigated in this region. PMID:20411676

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

    DTIC Science & Technology

    1979-03-01

    N. Cooley. 1974. Bone scane withcomplex. Damageo fluorine-18 in diagnosing osteonecrosis in divers. In: :ould result in release of stored reserves...STRESS-GILMAN ET AL. Related Osteonecrosis . Proceedings of a symposium on in patients with iron overload and with acute and Dysbaric Osteonecrosis ...N. Walder. 1975. Serum ferritin, cobalt excretion, and body iron 19ඕ. Serum ferritin and dysbaric osteonecrosis . Under- status. C.M.A. J., 112

  17. 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

  18. Association between serum ferritin level and diastolic cardiac function in patients with major β-thalassemia.

    PubMed

    Eghbali, A; Taherahmadi, H; Bagheri, B; Nikanjam, S; Ebrahimi, L

    2015-01-01

    Prevention of myocardial siderosis is a key step to reduce rate of mortality in thalassemic patients. Our objective was to study association between echocardiography parameters and serum ferritin level in patients with major thalassemia. Sixty-six patients with major thalassemia were studied in Amir Kabir hospital, Arak, Iran. Serum ferritin levels were measured during 3 months in patients with no symptoms of infection. It was measured by enzyme-linked immunosorbent assay (ELISA). Ejection Fraction (EF), Fractional Shortening (FS) and Early/Late ratio (E/A) were studied by echocardiography. Fifty two percent were female and 48% were male. Mean age was 16 ± 9 years and the age range was3-26years. Mean serum ferritin level was1912 ± 1748 ng/dl and its range was from 303 to 8333 ng/dl. There were significant correlations between serum ferritin level and EF(r=0.3 and P=0.05) and also between serum ferritin level and FS. Due to significant association between serum ferritin level and echo parameters, it is beneficial that all patients with major thalassemia undergo echocardiography to gain better understating about cardiac function.

  19. Relation between serum ferritin and liver and heart MRI T2* in beta thalassaemia major patients.

    PubMed

    Azarkeivan, A; Hashemieh, M; Akhlaghpoor, S; Shirkavand, A; Yaseri, M; Sheibani, K

    2013-08-01

    There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2*. Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2* relaxation time (r = -0.535) and a weak negative correlation between serum ferritin and heart MRI T2* relaxation time (r = -0.361). Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2*. Liver and heart MRI T2* readings were poorly correlated (r = 0.281). Routine evaluation of liver and heart iron content using MRI T2* is suggested to better evaluate the haemosiderosis status in thalassemia patients.

  20. The Association of Serum Vascular Endothelial Growth Factor and Ferritin in Diabetic Microvascular Disease

    PubMed Central

    Guo, Li; Jiang, Fang; Tang, Yue-Ting; Si, Meng-Ya

    2014-01-01

    Abstract Background: Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic microvascular disease. Most diabetes patients have higher serum levels of ferritin that may participate in diabetic vascular complications through high oxidative stress induced by iron. However, the mechanistic link between ferritin and VEGF is obscure. The study investigated the association of VEGF and ferritin in patients with diabetic microvascular disease. Patients and Methods: Sixty patients with type 2 diabetes mellitus (T2DM) and 26 healthy individuals were selected in this study. Serum ferritin, VEGF, hematological parameters, and clinical data were assessed in this cohort. The Spearman rank method was used to evaluate the associations among them. Results: Serum levels of VEGF and ferritin were significantly higher in diabetes patients compared with the controls; levels of both were elevated with development of the disease. There were positive correlations between VEGF and glucose levels and between VEGF and ferritin in diabetes groups, especially in patients with diabetic retinopathy. Positive correlations were also found between VEGF level and the parameters of age, hemoglobin, and albumin in patients with diabetes hypertension. Conclusions: Our data suggest that high ferritin levels in T2DM are closely related to the development of diabetic vascular complications through interaction with VEGF. PMID:24279470

  1. 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.

  2. 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.

  3. Silybin treatment is associated with reduction in serum ferritin in patients with chronic hepatitis C.

    PubMed

    Bares, Julie M; Berger, Jose; Nelson, James E; Messner, Donald J; Schildt, Sandra; Standish, Leanna J; Kowdley, Kris V

    2008-09-01

    The goal of this study was to examine the effect of a standardized silybin and soy phosphatidylcholine complex (IdB 1016) on serum markers of iron status. Milk thistle and its components are widely used as an alternative therapy for liver disease because of purported antioxidant, anti-inflammatory, and iron chelating properties. Thirty-seven patients with chronic hepatitis C and Batts-Ludwig fibrosis stage II, III, or IV were randomized to 1 of 3 doses of IdB 1016 for 12 weeks. Serum ferritin, serum iron, total iron binding capacity, and transferrin-iron saturation were measured at baseline, during treatment, and 4 weeks thereafter. Wilcoxon signed rank tests were used to compare baseline and posttreatment values. There was a significant decrease in serum ferritin from baseline to end of treatment (mean, 244 vs. 215 mug/L; median, 178 vs. 148 mug/L; P=0.0005); 78% of subjects had a decrease in serum ferritin level. There was no significant change in serum iron or transferrin-iron saturation. Multivariate logistic regression analysis in a model that included dose, age, sex, HFE genotype, history of alcohol use, and elevated baseline ferritin levels demonstrated that stage III or IV fibrosis was independently associated with decreased posttreatment serum ferritin level. Treatment with IdB 1016 is associated with reduced body iron stores, especially among patients with advanced fibrosis stage.

  4. High serum ferritin is associated with worse outcome of patients with decompensated cirrhosis

    PubMed Central

    Oikonomou, Theodora; Goulis, Ioannis; Soulaidopoulos, Stergios; Karasmani, Areti; Doumtsis, Petros; Tsioni, Konstantina; Mandala, Eudokia; Akriviadis, Evangelos; Cholongitas, Evangelos

    2017-01-01

    Background Studies in patients with decompensated cirrhosis showed a correlation between serum ferritin levels and patients’ prognosis. Besides, red blood cell distribution width (RDW) and mean platelet volume (MPV) have been associated with the severity of hepatic function. The aim of this study was to evaluate the prognostic impact of serum ferritin and RDW/MPV in the outcome [survival, death, or liver transplantation (LT)] of patients with stable decompensated cirrhosis. Methods Consecutive adult patients with stable decompensated cirrhosis admitted to our department between September 2010 and February 2016 were included. Serum ferritin, RDW and MPV were recorded in every patient. They were followed up and their outcome (alive, death, or LT) was evaluated. Results 192 consecutive patients with stable decompensated cirrhosis (142 men, age 54.2±12 years); at the end of follow up [12 (range: 1-64) months] 62 patients remained alive and 130 died or underwent LT. In multivariate analysis, serum ferritin (HR 1.001, 95%CI 1.00-1.002, P=0.005) and GFR (HR 0.96, 95%CI 0.92-0.99, P=0.035) were the only independent factors significantly associated with the outcome. Ferritin had low discriminative ability (AUC: 0.61) to the outcome yielding a sensitivity and specificity of 85.3% and 44.2%, respectively, at the best cut-off point (>55 ng/mL), while patients with ferritin >55 ng/mL (n=145) had a worse outcome compared to those with ferritin ≤55 ng/mL (n=47) (log rank P=0.001). RDW and MPV were not associated with the outcome. Conclusion High serum ferritin, but not RDW/MPV, is associated with worse outcome in patients with established decompensated cirrhosis. However, further studies are needed to elucidate better this issue. PMID:28243043

  5. Serum ferritin levels and transferrin saturation in men with prostate cancer.

    PubMed Central

    Kuvibidila, Solo R.; Gauthier, Tony; Rayford, Walter

    2004-01-01

    Elevated body iron stores (serum ferritin >300 microg/L, transferrin saturation TS >50%) are associated with increased risk of liver and lung cancers. To determine whether such association also exists for prostate cancer (PC), we measured serum ferritin, serum iron, total iron-binding capacity (TIBC), and TS in serum samples from 34 men with newly diagnosed, untreated PC and 84 healthy men, ranging in age from 49-78 years. In contrast with other malignancies, men with PC had significantly lower mean concentrations of serum ferritin (156 microg/L) and TS (24.35%) than those without PC (ferritin, 245 microg/L; TS, 31.98%) (p<0.05). The 95% confidence intervals for ferritin were 109-203 microg/L and 205-286 microg/L, and those for TS were 20.29-28.4% and 28.35-35.61% for men with and without PC, respectively. Significant differences were observed between both groups in the distribution of serum ferritin (<100, 101-300, >300 microg/L) and TS (<16, 16-50, >50%) (p<0.05). A lower percentage of cases than of controls had serum ferritin (17.6% versus 29.8%) and TS (5.9% versus 14.7%) above normal. These differences persisted when the analysis was limited to African-American men (31 cases and 52 controls). Data suggest that elevated body iron stores are less common in men with PC compared to those without PC. PMID:15160979

  6. Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients.

    PubMed

    Kuragano, Takahiro; Matsumura, Osamu; Matsuda, Akihiko; Hara, Taiga; Kiyomoto, Hideyasu; Murata, Toshiaki; Kitamura, Kenichiro; Fujimoto, Shouichi; Hase, Hiroki; Joki, Nobuhiko; Fukatsu, Atushi; Inoue, Toru; Itakura, Ikuhiro; Nakanishi, Takeshi

    2014-10-01

    In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.

  7. 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.

  8. The relationship between Willis-Ekbom disease and serum ferritin levels among children in Northwestern Turkey

    PubMed Central

    Halac, Gulistan; Sezer, Gulsen M.; Saglam, Neslihan O.; Tekturk, Pinar; Demir, Aysegul D.; Demir, Saliha; Akcay, Faruk; Uslu, Aysegul; Yapıcı, Zuhal; Asil, Talip

    2015-01-01

    Objective: To examine the incidence of restless legs syndrome (RLS) among children with iron deficiency, or iron deficiency anemia, or both, and the relationship between RLS prevalence and serum ferritin levels. Methods: This prospective, cross-sectional, case controlled study was carried out between January and June 2013, and included 98 iron deficiency and/or iron deficiency anemia, and 102 healthy children referred to the Neurology and Pediatric Departments of the Medical Faculty of Bezmialem Vakif University, Istanbul, Turkey. Both groups were evaluated according to the International Restless Legs Syndrome Study Group diagnostic criteria. Results: The range of ferritin levels was 0.01-12 mg/ml in patients while it was 12.3-91.8 mg/mL in the control group. Restless legs syndrome was detected in 61.2% of children with iron deficiency anemia, and in 37.3% of children with normal biochemistry values. A statistically significant correlation was found between serum ferritin levels and frequency of RLS. In patients with serum ferritin levels higher than 50 ng/ml, 92.3% had no RLS, while 55.2% of patients with serum ferritin levels lower than 50ng/ml had RLS. The patients with serum ferritin levels of >50ng/ml had a significantly higher incidence of RLS. Serum ferritin levels were significantly different between the 2 groups. Conclusion: The incidence of RLS, also known as Willis-Ekbom Disease, is high in children aged between 8-18 years with iron deficiency, or iron deficiency anemia, or both. This finding supports the importance of iron replacement therapy especially during the growth and development of children. PMID:26492111

  9. The relationship between Willis-Ekbom disease and serum ferritin levels among children in Northwestern Turkey.

    PubMed

    Halac, Gulistan; Sezer, Gulsen M; Saglam, Neslihan O; Tekturk, Pinar; Demir, Aysegul D; Demir, Saliha; Akcay, Faruk; Uslu, Aysegul; Yapıcı, Zuhal; Asil, Talip

    2015-10-01

    To examine the incidence of restless legs syndrome (RLS) among children with iron deficiency, or iron deficiency anemia, or both, and the relationship between RLS prevalence and serum ferritin levels. This prospective, cross-sectional, case controlled study was carried out between January and June 2013, and included 98 iron deficiency and/or iron deficiency anemia, and 102 healthy children referred to the Neurology and Pediatric Departments of the Medical Faculty of Bezmialem Vakif University, Istanbul, Turkey. Both groups were evaluated according to the International Restless Legs Syndrome Study Group diagnostic criteria. The range of ferritin levels was 0.01-12 mg/ml in patients while it was 12.3-91.8 mg/mL in the control group. Restless legs syndrome was detected in 61.2% of children with iron deficiency anemia, and in 37.3% of children with normal biochemistry values. A statistically significant correlation was found between serum ferritin levels and frequency of RLS. In patients with serum ferritin levels higher than 50 ng/ml, 92.3% had no RLS, while 55.2% of patients with serum ferritin levels lower than 50 ng/ml had RLS. The patients with serum ferritin levels of > 50 ng/ml had a significantly higher incidence of RLS. Serum ferritin levels were significantly different between the 2 groups. The incidence of RLS, also known as Willis-Ekbom Disease, is high in children aged between 8-18 years with iron deficiency, or iron deficiency anemia, or both. This finding supports the importance of iron replacement therapy especially during the growth and development of children.

  10. Evaluation of Iron Store by Serum Ferritin in Healthy Blood Donors of Bangladesh.

    PubMed

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

    2016-07-01

    Iron stores in the body exist primarily in the form of ferritin. Small amounts of ferritin secreted into the plasma and plasma ferritin is positively correlated with the size of the total body iron stores. The present study conducted to determine the iron status using the serum ferritin level among healthy Bangladeshi blood donors. The present cross sectional study was conducted in the Department of Transfusion Medicine, Dhaka Medical College, Dhaka, Bangladesh from July 2011 to June 2012. Blood donor signed informed consent and has satisfactory pre-donation health assessment and satisfactory post-donation blood test results were included in the study. Full blood counts were performed within 4 hours of collection using an automated haematology analyzer. Serum ferritin was measured using a validated enzyme immunoassay. Data were analyzed using SPSS version 16 (SPPS Incorporation, Chicago, IL, USA). P value <0.05 was considered as statistically significant. Total 100 blood donors were included in the study, among them 88 were male and 12 were female. Mean±SD of the age of the respondents was 26.8±5.9 years with a range of 19 to 45 years. Mean±SD of heamoglobin level (gm/dl) and total count of Red Blood Cell (million/cmm) were 14.1±1.4 and 5.1±0.4 respectively. Mean±SD of serum ferritin level (ng/ml) was 96.4±69.0ng/ml with a range of 4.1ng/ml to 298.7ng/ml. Among the respondents 9.0% had depleted iron store, 7.0 reduced iron store and 84.0% had normal iron store. Among the respondents 5.0% had iron deficiency anaemia in term of serum ferritin level. Statistically significant difference of serum ferritin level observed between male and female and donors with and without history of previous blood donation. Among the healthy blood donors of Bangladesh abnormal serum ferritin is highly prevalent among blood donors specially among female. Monitoring of iron stores by serum ferritin seems justified in order to identify those with depleted iron stores who will

  11. Serum Ferritin and Metal Levels as Risk Factors for Amyotrophic Lateral Sclerosis

    PubMed Central

    Qureshi, Muddasir; Brown Jr, Robert H; Rogers, Jack T; Cudkowicz, Merit E

    2008-01-01

    Metal toxicity has been identified as a possible risk factor for amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. We conducted a retrospective chart review of urinary, hair and blood metal levels and serum ferritin in 321 people with ALS seen over a ten-year period at the Massachusetts General Hospital (MGH). We found that hair lead levels and serum ferritin levels were elevated in ALS patients compared to published normal values. Metal levels of arsenic, lead, mercury, cadmium, thallium, cobalt and aluminum in 24-hour urine specimens and lead, mercury and arsenic in serum were within the normal range. We conclude that twenty-four hour urine or blood testing for metals is not warranted as part of the evaluation of ALS. Elevated levels of serum ferritin in ALS population could reflect an underlying perturbation in iron metabolism. PMID:19452011

  12. 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

  13. 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

  14. Association between serum ferritin levels and metabolic syndrome: an updated meta-analysis

    PubMed Central

    Jin, Yuelong; He, Lianping; Chen, Yi; Fang, Yun; Yao, Yingshui

    2015-01-01

    It is definite that the serum iron level has a positive correlation with the risk of obesity. However, the association between increased serum ferritin levels and the metabolic syndrome still remains controversial. The purpose of this meta-analysis is to confirm the association between serum ferritin levels and metabolic syndrome. We searched PubMed and the China National Knowledge Infrastructure (CNKI) for relevant articles that assessed the association between serum ferritin levels and metabolic syndrome and were published between 2006 and 2014. Review Manage 5.3 software was used to collect and analysis the data cited in the ultimately selected papers. The variance was exhibited using the forest plot and the heterogeneity among studies was examined using the I2 index. We use the funnel plot to evaluate the publication bias. Cross-sectional study, case-control study and prospective cohort study met our inclusion criteria including data from a total of 4,797 participants. The pooled odds ratio (OR) for the metabolic syndrome comparing the highest and lowest category of ferritin levels was 1.20 (95% CI: 0.69, 1.71; I2=96%). The meta-analysis demonstrates that elevated ferritin levels are positive aassociated with metabolic syndrome. PMID:26550259

  15. Association of Serum Gamma-Glutamyl Transferase and Ferritin with the Metabolic Syndrome.

    PubMed

    Wei, Dong; Chen, Tao; Li, Jie; Gao, Yun; Ren, Yan; Zhang, Xiangxun; Yu, Hongling; Tian, Haoming

    2015-01-01

    Aim. To investigate the relationship among GGT, ferritin, and the risk of metabolic syndrome. Methods. A total of 1024 eligible individuals of the Chinese Yi ethnic group were enrolled in this cross-sectional study. The presence of metabolic syndrome was determined using the revised NCEP-ATP III and CDS criteria. Odds ratios for the metabolic syndrome and its components for different groups based on the levels of GGT and ferritin were calculated using multiple logistic regressions. Results. Serum GGT and ferritin concentrations were significantly higher in subjects with metabolic syndrome compared to those without metabolic syndrome in both genders (p < 0.05). Serum GGT was positively correlated with ferritin (p < 0.05). The risk of the metabolic syndrome was significantly higher in female subjects who had elevated GGT and ferritin levels (p < 0.05). Furthermore, the increased risk of having each of the metabolic syndrome components (overweight or obesity, hypertriglyceridemia, hypertension, hyperglycemia, and insulin resistance) was also observed in those subjects after adjustment for possible confounders (p < 0.05). Conclusions. These data indicate that GGT and ferritin synergistically correlate with the risk of the metabolic syndrome, suggesting that they could potentially be used as predictive biomarkers for the metabolic syndrome.

  16. High maternal serum ferritin in early pregnancy and risk of spontaneous preterm birth.

    PubMed

    Khambalia, Amina Z; Collins, Clare E; Roberts, Christine L; Morris, Jonathan M; Powell, Katie L; Tasevski, Vitomir; Nassar, Natasha

    2015-08-14

    Previous studies have reported inconsistent associations between maternal serum ferritin concentrations and the risk of spontaneous preterm birth (sPTB). The aim of the present study was to examine the association between Fe biomarkers, including serum ferritin concentrations, and the risk of total ( 75th percentile ( ≥ 43 μg/l) (OR 1.49, 95% CI 1.06, 2.10) and >90th percentile ( ≥ 68 μg/l) (OR 1.92, 95% CI 1.25, 2.96). Increased odds of early and moderate-to-late sPTB were associated with ferritin levels >90th percentile (OR 2.50, 95% CI 1.32, 4.73) and >75th percentile (OR 1.56, 95% CI 1.03, 2.37), respectively. No association was found between the risk of sPTB and elevated sTfR levels or Fe deficiency. In conclusion, elevated maternal serum ferritin levels in early pregnancy are associated with an increased risk of sPTB from 34 weeks of gestation. The usefulness of early pregnancy ferritin levels in identifying women at risk of sPTB warrants further investigation.

  17. 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.

  18. 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

  19. 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.

  20. Serum iron, Folate, Ferritin and CD4 Count in HIV Seropositive Women.

    PubMed

    Kharb, Simmi; Kumawat, Manjulata; Lallar, Meenakshi; Ghalaut, P S; Nanda, Smiti

    2017-03-01

    HIV infects cluster of differentiation 4 (CD4) T-lymphocytes, monocytes and macrophages resulting in decreased number and function of CD4 cells, changes that affect both cell mediated and humoral immunity. Hematological abnormalities are a common complication of human immune virus (HIV) infection and these abnormalities increase as the disease advances. Anemia is the most common haematological abnormality in HIV seropositive patients and its incidence is strongly associated with the progression of the disease. The aim of present study was to assess the haematological profile of HIV seropositive women and compare them with CD4 count. Two hundred seropositive females (age 18-25 years) attending antiretroviral therapy clinic were selected. Routine gynaecological and haematological investigations were carried out, study samples were drawn and serum iron, folate and ferritin were analysed by chemiluminiscence and CD4 count was determined by using flow-cytometry. Anemia was prevalent in seropositive women especially in those with low CD4 levels. Serum folate and ferritin levels were significantly lower in females with lower CD4 levels. Serum iron levels were higher at low CD4 levels. The mean CD4 count in HIV seropositive anaemic women were lower as compared to non anaemics suggesting that anaemia improves with higher CD4 cell counts. Plasma folate and ferritin levels are sensitive predictor of anaemia in early HIV infections and these patients should have a regular monitoring of their folate and ferritin levels especially with lower CD4 levels.

  1. Associations between serum hepcidin, ferritin and Hb concentrations and type 2 diabetes risks in a Han Chinese population.

    PubMed

    Guo, Xin; Zhou, Daizhan; An, Peng; Wu, Qian; Wang, Hao; Wu, Aimin; Mu, Mingdao; Zhang, Di; Zhang, Zhou; Wang, Hui; He, Lin; Liu, Yun; Wang, Fudi

    2013-12-01

    Systemic Fe overload can contribute to abnormal glucose metabolism and the onset of type 2 diabetes (T2D). Although hepcidin is the master regulator of systemic Fe homeostasis, few studies have systematically evaluated the associations of serum hepcidin concentrations with Fe metabolism parameters and risks for the development of T2D. In this regard, whether hepcidin concentrations are associated with T2D remains controversial. We measured serum hepcidin and ferritin concentrations in a case-control study of 1259 Han Chinese participants to evaluate the possible associations of serum hepcidin concentrations with Fe metabolism parameters and risks of T2D. Individuals with diabetes (n 555) and control participants (n 704) were recruited and serum hepcidin and ferritin concentrations were quantified. Additionally, selected biochemical and anthropometric variables were determined. A logistic regression analysis was performed to evaluate the association of serum hepcidin and ferritin concentrations with T2D. A linear regression analysis was used to test for associations between serum hepcidin and ferritin concentrations and a number of clinical, demographic and diabetes-associated variables. We found that serum hepcidin concentrations correlated with Hb and serum ferritin concentrations. No differences in hepcidin concentrations were found between the group with diabetes and the control group. Hepcidin concentrations were not significantly correlated with T2D risk factors. We also found that serum ferritin concentrations were elevated in individuals with diabetes and were positively correlated with both Hb concentrations and T2D risk factors. The present findings suggest that serum ferritin concentrations correlate with T2D risk factors, while serum hepcidin concentrations are positively associated with Hb and serum ferritin concentrations, but do not correlate with T2D.

  2. The challenges of using serum ferritin to guide i.v. iron treatment practices in patients on hemodialysis with anemia.

    PubMed

    Easom, Andrea

    2006-01-01

    Expert guidelines recommend routine administration of intravenous iron therapy and frequent monitoring of iron status for patients on hemodialysis who are being treated for anemia with erythropoiesis-stimulating agents. However, monitoring iron status using conventional markers, such as serum ferritin, may be complicated by acute and chronic inflammation and malnutrition, which are common in this patient population. Therefore, nephrology nurses must be knowledgeable of the limitations of using serum ferritin to assess iron status and how to interpret high serum ferritin values to effectively treat patients on hemodialysis with anemia.

  3. Premarital screening of 466 Mediterranean women for serum ferritin, vitamin B12, and folate concentrations.

    PubMed

    Karabulut, Aysun; Güler, Ömer Tolga; Karahan, Hatice Tuba; Özkan, Sevgi; Koyuncu, Hasan; Demirciler, Ibrahim

    2015-01-01

    Iron, folate, and vitamin B12 serum levels are closely related with dietary habits and have an essential role in the healthy development of a fetus. We aimed to investigate hemoglobin, ferritin, folate, and vitamin B12 levels in preconceptional women in an area where a plant-based diet referred to as Mediterranean cuisine is commonly used. The study population included 466 women between the ages of 18 and 45 years admitted for thalassemia screening. Sociodemographic variables and history of menometrorrhagia, pica, and dietary habits were collected. Serum vitamin B12, folate, ferritin, and hemoglobin levels were measured. Ferritin of <12µg/L, vitamin B12 of <200 pg/mL, and folate of <4 ng/mL were accepted as deficiencies. Hemoglobin level of <12 g/dL was classified as anemia. Polymenorrhea was present in 11.7% and hypermenorrhea in 24.8% of women. Anemia was detected in 24.9% and thalassemia trait in 3.0% of women. Low ferritin levels were observed in 46.1%, vitamin B12 in 21.6%, and folate in 3.4% of women. In the group with low vitamin B12, decreased meat consumption was more prevalent (27.5% vs. 16.9%; P = 0.019). Vitamin B12 and iron are the main micronutrients depleted in our community. This necessitates implementing a public health program for women consuming a Mediterranean diet.

  4. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration.

    PubMed

    Krayenbuehl, Pierre-Alexandre; Battegay, Edouard; Breymann, Christian; Furrer, Joerg; Schulthess, Georg

    2011-09-22

    This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin ≤ 50 ng/mL, and hemoglobin ≥ 120 g/L were randomized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P = .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin ≤ 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P = .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P = .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P = .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International Standard Randomized Controlled Trial Number Register (www.isrctn.org) as ISRCTN78430425.

  5. Serum ferritin and risk of the metabolic syndrome: a population-based study.

    PubMed

    Chang, Jung-Su; Lin, Shiue-Ming; Huang, Tzu-Chieh; Chao, Jane C-J; Chen, Yi-Chun; Pan, Wen-Harn; Bai, Chyi-Huey

    2013-01-01

    Ferritin concentrations in circulation reflect iron stores in healthy individuals. However, elevated serum ferritin (SF) concentrations have recently been implicated in the pathogenesis of the metabolic syndrome (MetS). We aim to investigate factors associated with elevated SF and to evaluate the association between SF and risk of MetS in Taiwanese adults. Data was collected from 2654 healthy individuals aged >=19 years old, who participated in the Nutrition and Health Survey in Taiwan (NAHSIT Adults 2005-2008). Mean concentrations of SF were 173±282 ng/mL (men 229±349 ng/mL and women 119±180 ng/mL). Prevalence proportion of MetS was 34.6% (men 43.1% and women 26.5%). Prevalence proportion of iron overload was 18.6% (men 21.5% and women 15.8%) and iron deficiency anemia was 5.2% (2.0% for men and 8.3% for women). Individuals with the highest SF tertile (T3) were more likely to consume higher amount of animal protein (p=0.001), betel nuts (p=0.004), and lower amounts of carbohydrates (p<0.0001), compared with the lowest SF group (T1). After adjustments, individuals with the highest SF tertile were associated with risk of MetS compared with those with the lowest (OR=1.724, 95% CI: 1.21-2.45). Serum ferritin concentrations showed a gradient relationship with individual components of MetS (all p<0.0001). Individuals with the highest SF tertile were significantly associated with fasting serum glucose (OR=2.16, 95% CI: 1.75-2.65) and serum triglyceride (OR=2.58, 95% CI: 1.07-3.22) than those with the lowest. In conclusions, our results highlight the crucial role of serum ferritin in the pathogenesis of the MetS in healthy Taiwanese adults.

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

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:27007895

  7. 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.

  8. EVALUATION OF SERUM FERRITIN AND SERUM IRON IN FREE-RANGING BLACK RHINOCEROS (DICEROS BICORNIS) AS A TOOL TO UNDERSTAND FACTORS AFFECTING IRON-OVERLOAD DISORDER.

    PubMed

    Miller, Michele; Chavey, Patricia Sue; Hofmeyr, Jennifer; Mathebula, Nomkhosi; Doering, Alyssa; Buss, Peter; Olea-Popelka, Francisco

    2016-09-01

    Iron overload disorder (IOD) is a significant health issue for captive black rhinoceros ( Diceros bicornis ). Measurement of serum ferritin with a validated rhinoceros ferritin ELISA has been used extensively to detect animals in U.S. zoos that are at risk of developing IOD. However, there is limited information on serum ferritin levels in free-ranging black rhinoceros using this same assay. Serum ferritin, iron, and gamma-glutamyl transpeptidase (GGT) were determined in 194 black rhinoceros from southern Africa. Mean ferritin in free-ranging black rhinoceros (290.54 ±247.4 ng/ml) was significantly higher than in free-ranging white rhinoceros (64.0 ± 102.4 ng/ml) sampled in this study from Kruger National Park, South Africa. However, there were no significant differences between genders or age groups. Ferritin values varied with geographical location of the black rhinoceros, although this was not clinically significant. Serum iron values were also higher in black rhinoceros (40.4 ± 19.1 μmol/L) compared to white rhinoceros (29.7 ± 10.7 μmol/L). There was no association between ferritin and GGT. This study provides serum ferritin, iron, and GGT values from free-ranging black rhinoceros that can be used for as comparative target values for captive animals.

  9. Ferritin in the Serum of Normal Subjects and Patients with Iron Deficiency and Iron Overload

    PubMed Central

    Jacobs, A.; Miller, F.; Worwood, M.; Beamish, M. R.; Wardrop, C. A.

    1972-01-01

    The concentration of ferritin in serum gives a quantitative measure of the amount of storage iron in normal subjects and those with iron deficiency or overload. The mean level in normal men is 69 ng/ml, compared with 35 ng/ml in normal women. A concentration below 10 ng/ml is associated with a low transferrin saturation and iron-deficient erythropoiesis. PMID:5082548

  10. The Association between the Levels of Serum Ferritin and Sex Hormones in a Large Scale of Chinese Male Population

    PubMed Central

    Zhang, Haiying; Gao, Yong; Tan, Aihua; Zhang, Shijun; Xiao, Qiang; Zhang, Bing; Huang, Lulu; Ye, Bingbing; Qin, Xue; Wu, Chunlei; Lu, Zheng; Zhang, Youjie; Liao, Ming; Yang, Xiaobo; Mo, Zengnan

    2013-01-01

    Background The ferritin is an important participant of iron-storage but its regulation and related factors were not well defined. The present objective was to explore the potential association between serum ferritin levels and sex hormones. Methods 1999 Chinese men in the Fangchenggang Area Male Health and Examination Survey (FAMHES) were recruited in this cross-sectional study. Levels of serum ferritin, total testosterone (free testosterone was calculated from the total one), estradiol and sex hormone-binding protein were detected in venous blood samples. The effects of age, BMI, smoking as well as alcohol consumption were analyzed on ferritin levels, respectively, and then the Pearson’s correlation analysis was used to evaluate the association between ferritin levels and sex hormones adjusting for the above factors. Results The age, BMI and alcohol consumption significantly affected serum ferritin levels, but there was no significant difference between smokers and nonsmokers. Ferritin levels were significantly and negatively associated with total testosterone (R = −0.205, P< 0.001), sex hormone-binding protein (R = −0.161, P<0.001) and free testosterone (R = −0.097, P<0.001). After age and alcohol consumption were adjusted, the above associations were still significant (R = −0.200, −0.181 and −0.083, respectively, all P<0.001). However, there was only borderline negative association between ferritin levels and estradiol (adjusted R = −0.039, P = 0.083). Conclusion The large scale of epidemic results showed the significantly negative associations between serum ferritin levels and sex hormones, which may provide more clues to explore the potential regulation and biological mechanism of ferritin. PMID:24146788

  11. High serum ferritin levels are associated with insulin resistance but not with impaired glucose tolerance in a healthy people population.

    PubMed

    Aguirre, Luis G; Urrunaga-Pastor, Diego; Moncada-Mapelli, Enrique; Guarnizo-Poma, Mirella; Lazaro-Alcantara, Herbert; Benites-Zapata, Vicente A

    2017-07-20

    To assess the association between elevated serum ferritin levels and the presence of insulin resistance (IR) or impaired glucose tolerance (IGT) in a population of individuals with no endocrine or metabolic disorders background. Analytical cross-sectional study, carried out in adults of both sexes with no medical history of type 2 diabetes mellitus (T2DM) or other metabolic or endocrine disorder, who attended the outpatient service of a private clinic in Lima-Peru during 2012-2014 period. Impaired serum ferritin levels were defined as serum ferritin values >300μg/L in men and >200μg/L in women. IR was defined as a Homeostasis Model Assessment (HOMA-IR) value ≥3.8 and IGT was defined as an oral glucose tolerance test (OGTT) value between 126mg/dL and 199mg/dL. The reported association measure was the prevalence ratio (PR) with their respective 95% confidence intervals (95% CI). We analyzed 213 participants, the average age was 35.8±11.1years and 35.7% were males. The prevalence of impaired serum ferritin levels, IR and IGT in the population was 12.7%, 33.3% and 9.9% respectively. In the adjusted Poisson regression models, the prevalence of IR was higher among the group with impaired serum ferritin levels (PR=1.74; 95%CI:1.18-2.56); however, we found no association between impaired serum ferritin levels and IGT (PR=1.42; 95%CI:0.47-4.30). Impaired levels of serum ferritin are associated with IR, nevertheless, not with IGT in a metabolically healthy population. Serum ferritin could be considered as an early marker of IR prior to the onset of glycaemia disorders. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. The effect of running on serum and red cell ferritin. A longitudinal comparison.

    PubMed

    Balaban, E P; Snell, P; Stray-Gundersen, J; Frenkel, E P

    1995-07-01

    It is unclear whether running can affect iron stores. Results using the serum ferritin assay (SER FER) have been conflicting. Decreased red cell ferritin (RBC FER) values (< or = 4 ag/RBC) occur in iron depleted or inflammatory states. We compared the longitudinal changes of hemoglobin (Hb), SER FER, RBC FER, % saturation of total iron binding capacity (% sat TIBC), and daily dietary intake in 27 runners during a training program. These parameters were measured at days 0, 49 (range 48-52), and 115 (range 85-120). No significant changes occurred in the SER FER, % sat TIBC and Hb determinations throughout the study. Overall the RBC FER values trended down (mean values 11.7 ag/RBC to 7.7 ag/RBC; p = 0.06). Fifteen runners (56%) acquired RBC FER values in the iron deficient range (mean 6.8 ag/RBC to 2.4 ag/RBC; p < 0.05). These values differed significantly from the remaining 12 runners (mean 17.3 ag/RBC to 14.7 ag/RBC). The decline in RBC FER into the iron deficient range was primarily seen in a subset of runners who began with a RBC FER value < or = 10 ag/RBC (positive predictive value 0.79) and was independent of iron intake. We conclude that ferritin can be affected by running as recognized by the red cell ferritin assay. Moreover our results suggest that this decrease in red cell ferritin is likely a function of defective iron utilization rather than total body iron deficiency. A potential consideration is that this fall may occur as a result of repetitive running-associated injury and inflammation.

  13. Genome-Wide Association Study Identifies Variants in PMS1 Associated with Serum Ferritin in a Chinese Population

    PubMed Central

    Gao, Yong; Tan, Aihua; Wu, Chunlei; Lu, Zheng; Yang, Xiaobo; Zhang, Shijun; Hu, Yanlin; Qin, Xue; Li, Jianling; Chen, Gang; Xu, Jianfeng; Mo, Zengnan; Zhang, Haiying

    2014-01-01

    Only a small proportion of genetic variation in serum ferritin has been explained by variant genetic studies, and genome-wide association study (GWAS) for serum ferritin has not been investigated widely in Chinese population. We aimed at exploring the novel genetic susceptibility to serum ferritin, and performed this two stage GWAS in a healthy Chinese population of 3,495 men aged 20–69 y, including 1,999 unrelated subjects in the first stage and 1,496 independent individuals in the second stage. Serum ferritin was measured with electrochemiluminescence immunoassay, and DNA samples were collected for genotyping. A total of 1,940,243 SNPs were tested by using multivariate linear regression analysis. After adjusting for population stratification, age and BMI, the rs5742933 located in the 5′UTR region of PMS1 gene on chromosome 2 was the most significantly associated with ferritin concentrations (P-combined = 2.329×10−10) (β = −0.11, 95% CI: −0.14, −0.07). Moreover, this marker was about 200kb away from the candidate gene SLC40A1 which is responsible for iron export. PMS1 gene was the novel genetic susceptibility to serum ferritin in Chinese males and its relation to SLC40A1 needs further study. PMID:25162662

  14. The diagnostic value of cervicovaginal and serum ferritin levels in midgestation time to predict spontaneous preterm delivery

    PubMed Central

    Broumand, Farzaneh; Saeidkar, Soudabeh; Behrouzlak, Tahereh; Khalkhali, Hamidreza; Sadeghi-Bazargani, Homayoun

    2014-01-01

    Background: The aim of this study was to determine diagnostic value of cervicovaginal ferretin and serum ferretin levels at midgestation time in predicting preterm delivery in singleton pregnancies. Patients and Methods: A diagnostic test study through a prospective cohort design was carried out on 300 singleton pregnant women in 2012. A blood sample was obtained from all the patients within 22-24 gestational weeks for laboratory assessment of serum ferretin, and cervicovaginal sample was also taken to assess cervicovaginal ferritin level. Ferritin levels were compared between term and preterm deliveries at 37, 34 and 32 weeks of gestation. Receiver operating characteristics (ROC) curves were plotted to assess the diagnostic test values. Results: Mean serum ferritin level was 55.38 [standard deviation (SD 23.8)] ng/mL in term deliveries versus a mean of 91.27 (SD 25.2) ng/mL in preterm deliveries, which showed a statistically significant difference (P < 0.001). The ferritin levels in cervicovaginal term delivery group had mean of 11.29 (SD 16.2) ng/mL compared with a mean of 21.95 (SD 10.1) ng/mL among those with preterm delivery before 37 weeks of gestational age(P < 0.001). The cervicovaginal ferritin level had a moderate to good diagnostic value with an area under curve being above 0.8 for all assessments. The serum ferritin level had a moderate to good diagnostic value with an area under curve being above 0.8 for all assessments. In both tests, its diagnostic value was higher for predicting preterm delivery at earlier gestational age. Conclusions: The results of this study indicate that high levels of serum and cervicovaginal ferritin in singleton pregnancies may alert the clinician of the risk of preterm delivery. Serum and cervicovaginal ferritin measurement at midgestation may be used as a predictive scale for preterm delivery in singleton pregnancies. PMID:25114368

  15. Associations between Serum C-reactive Protein and Serum Zinc, Ferritin, and Copper in Guatemalan School Children

    PubMed Central

    Bui, Vinh Q.; Stein, Aryeh D.; DiGirolamo, Ann M.; Ramakrishnan, Usha; Flores-Ayala, Rafael C.; Ramirez-Zea, Manuel; Grant, Frederick K.; Villalpando, Salvador

    2013-01-01

    Inflammation affects trace nutrient concentrations, but research on copper and particularly in children is limited. We assessed associations between serum C-reactive protein (CRP) and zinc, iron, copper, and other biomarkers (alkaline phosphatase, hemoglobin, and albumin), in 634 healthy 6- to 11-year-old Guatemalan schoolchildren. CRP was measured by a standardized, high-sensitive method. For significant associations with CRP, we stratified nutrient concentrations across categories of CRP and compared concentrations above and below several CRP cutoff points (0.5, 1, 3, 5, and 10 mg/L), and then adjusted values using correction factors (ratios of geometric means of the nutrients in the low and high groups). Prevalence of serum zinc (<65 μg/dL0, ferritin (<15 μg/L), and copper (<90 μg/dL) deficiency were 21%, 2.1%, and 23.8%, respectively. Median (25th and 75th percentiles) CRP was 0.56 (0.26 and 1.54) mg/L. CRP concentration was positively associated with ferritin and copper concentrations (r=0.23 and 0.29, respectively; P<0.0001) but not with zinc and other bio-markers (P>0.05). Regardless of CRP cutoffs, high (> cutoff) vs. low (≤ cutoff) CRP levels had higher ferritin and copper concentrations and lower prevalence of copper deficiency of <90 μg/dL (P<0.05). Adjustment for inflammation had the greatest influence on recalculated prevalence for the CRP 0.5 mg/L cutoff. The low ferritin prevalence hardly changed (from 2.1% to 2.5%) while the low copper prevalence changed appreciably (from 23.8% to 31.2%). In conclusion, CRP was positively associated with ferritin and copper but not with zinc concentrations. Adjustment for inflammation had little effect on low ferritin prevalence, low to begin with, and a large impact on low copper prevalence. High-sensitive CRP methods and the use of very low CRP cutoffs may be more accurate than traditional CRP methods in the adjustment of serum copper concentrations for inflammation in healthy school children. PMID:22354676

  16. Associations between serum C-reactive protein and serum zinc, ferritin, and copper in Guatemalan school children.

    PubMed

    Bui, Vinh Q; Stein, Aryeh D; DiGirolamo, Ann M; Ramakrishnan, Usha; Flores-Ayala, Rafael C; Ramirez-Zea, Manuel; Grant, Frederick K; Villalpando, Salvador; Martorell, Reynaldo

    2012-08-01

    Inflammation affects trace nutrient concentrations, but research on copper and particularly in children is limited. We assessed associations between serum C-reactive protein (CRP) and zinc, iron, copper, and other biomarkers (alkaline phosphatase, hemoglobin, and albumin), in 634 healthy 6- to 11-year-old Guatemalan schoolchildren. CRP was measured by a standardized, high-sensitive method. For significant associations with CRP, we stratified nutrient concentrations across categories of CRP and compared concentrations above and below several CRP cutoff points (0.5, 1, 3, 5, and 10 mg/L), and then adjusted values using correction factors (ratios of geometric means of the nutrients in the low and high groups). Prevalence of serum zinc (<65 μg/dL0, ferritin (<15 μg/L), and copper (<90 μg/dL) deficiency were 21%, 2.1%, and 23.8%, respectively. Median (25th and 75th percentiles) CRP was 0.56 (0.26 and 1.54) mg/L. CRP concentration was positively associated with ferritin and copper concentrations (r = 0.23 and 0.29, respectively; P < 0.0001) but not with zinc and other biomarkers (P > 0.05). Regardless of CRP cutoffs, high (> cutoff) vs. low (≤ cutoff) CRP levels had higher ferritin and copper concentrations and lower prevalence of copper deficiency of <90 μg/dL (P < 0.05). Adjustment for inflammation had the greatest influence on recalculated prevalence for the CRP 0.5 mg/L cutoff. The low ferritin prevalence hardly changed (from 2.1% to 2.5%) while the low copper prevalence changed appreciably (from 23.8% to 31.2%). In conclusion, CRP was positively associated with ferritin and copper but not with zinc concentrations. Adjustment for inflammation had little effect on low ferritin prevalence, low to begin with, and a large impact on low copper prevalence. High-sensitive CRP methods and the use of very low CRP cutoffs may be more accurate than traditional CRP methods in the adjustment of serum copper concentrations for inflammation in healthy school children.

  17. 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.

  18. Urinary hepcidin identifies a serum ferritin cut-off for iron supplementation in young athletes: a pilot study.

    PubMed

    Borrione, P; Spaccamiglio, A; Rizzo, M; Termine, A; Chierto, E; Campostrini, N; Quaranta, F; Di Gianfrancesco, A; Pigozzi, F

    2011-01-01

    The use of iron supplements should be a judicious choice, primarily when considering the possible risks deriving from an unjustified treatment. In trained athletes, levels of ferritin between 15 and 30 microg/L are frequently observed. Within this ferritin range, the usefulness of iron supplementation is still controversial. The aim of the present study is to evaluate the clinical usefulness of hepcidin assessment in the analysis of the iron status of young non-anemic athletes. Fifty young athletes were enrolled. The subjects were divided into 4 groups according to their ferritin levels. No statistically significant difference was found regarding hepcidin levels between athletes with ferritin lower than 15 microg/L and those in the 15-30 microg/L range. Similarly, no difference was found between athletes with ferritin higher than 50 microg/L and those in the 30-50 microg/L range. On the contrary, statistically significant differences were found between athletes with ferritin levels ranging from 15 to 30 microg/L and those in the 30-50 microg/L range. The present study suggests that serum ferritin levels below 30 microg/L indicate an asymptomatic iron deficiency status inhibiting hepcidin expression and that 30 microg/L should be considered the ferritin cut-off when considering an iron supplementation in young athletes.

  19. Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis.

    PubMed

    Ferreira, Katerine Panichi Zanin; Oliveira, Sayonara R; Kallaur, Ana Paula; Kaimen-Maciel, Damacio R; Lozovoy, Marcell Alysson B; de Almeida, Elaine Regina Delicato; Morimoto, Helena Kaminami; Mezzaroba, Leda; Dichi, Isaias; Reiche, Edna Maria Vissoci; Simão, Andréa Name Colado

    2017-02-15

    Hyperferritinemia and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS). The aim of the present study was to evaluate the serum levels of ferritin and to verify their association with oxidative stress markers and MS progression. This study included 164 MS patients, which were divided in two groups according to their levels of ferritin (cut off 125.6μg/L). Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), sulfhydryl groups of protein and total radical-trapping antioxidant parameter (TRAP). MS patients with elevated levels of ferritin showed higher disease progression (p=0.030), AOPP (p=0.001), and lower plasma NOx levels (p=0.031) and TRAP (p=0.006) than MS patients with lower ferritin levels. The multivariate binary logistic regression analysis showed that increased AOPP and progression of disease were significantly and positively associated with increase of ferritin. The combination of serum ferritin levels and oxidative stress markers were responsible for 13,9% in the disease progression. In conclusion, our results suggest that ferritin could aggravate oxidative stress in patients with MS and contribute to progression of disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Logarithmic quantitation model using serum ferritin to estimate iron overload in secondary haemochromatosis.

    PubMed

    Güngör, T; Rohrbach, E; Solem, E; Kaltwasser, J P; Kornhuber, B

    1996-04-01

    Nineteen children and adolescents receiving repeated transfusions and subcutaneous desferrioxamine treatment were investigated in an attempt to quantitate iron overload non-invasively. Before patients were started on desferrioxamine individual relationships were correlated for 12 to 36 months between transfused iron, absorbed iron estimated gastrointestinally, and increasing serum ferritin concentrations. Patients with inflammation, increased liver enzymes, or haemolysis were excluded from analysis. The relationship between the variables could be described by a logarithmic regression curve (y = transfused iron [plus eventually gastrointestinally absorbed iron] = iron overload = a+b log [x = serum ferritin]) for each individual patient. All patients showed close correlation (R2) between x and y (median R2 of 0.909, 0.98, and 0.92 in thalassaemia, aplastic anaemia, and sickle cell anaemia patients, respectively). When started on desferrioxamine, current serum ferritin concentrations were used to derive the iron overload from each individual regression curve. The derived estimated iron overload ranged from 0.6 g to 31 g. Left ventricular dilatation was observed in three patients with beta thalassaemia and in one patient with aplastic anaemia with median iron overload of 20.7 (14.1-31.3) g and 24.0 g respectively. Hypothyroidism was found in four patients with beta thalassaemia and one patient with aplastic anaemia with iron overload between 14.7 (6.8 and 26.1) g and 15.1 g respectively. Human growth hormone deficiency was detected in three patients with beta thalassaemia with an iron overload of 4.2 (3.5-6.8) g; all three patients had excellent desferrioxamine compliance.

  1. Serum ferritin level and red blood cell parameters in healthy controls and chronic periodontitis patients.

    PubMed

    Latha, S; Thirugnanamsambandan, S; Arun, R T; Masthan, K M K; Malathi, L; Rajesh, E

    2015-04-01

    Periodontitis, which is a chronic inflammatory disease causes reduction in the number of erythrocytes and hemoglobin. It is found to be caused by specific pathogenic subgingival plaque bacteria. Periodontitis is host mediated through release of pro inflammatory cytokines by local tissues and immune cells in response to bacterial flora and its products, especially lipopolysacharides. Periodontitis is found to have systemic effect and the cytokines produced inhibit proliferation and differentiation of erythrocytes leading to anaemia. This study evaluate level of hemoglobin erythrocytes, hematocrit and serum ferritin levels in healthy subjects and periodontitis patient.

  2. 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

  3. 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.

  4. Blood metal concentrations of manganese, lead, and cadmium in relation to serum ferritin levels in Ohio residents.

    PubMed

    Kim, Yangho; Lobdell, Danelle T; Wright, Chris W; Gocheva, Vihra V; Hudgens, Edward; Bowler, Rosemarie M

    2015-05-01

    The objectives of this study were to assess ferritin-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. Recruited participants included residents from Marietta, East Liverpool, and Mt. Vernon, OH, USA, who were aged 30-75 years and lived at least 10 years in their respective town. The levels of the neurotoxic metals such as manganese, cadmium, and lead were assayed in whole blood. Serum was analyzed for ferritin level [as a biomarker of iron (Fe) status]. An association between blood metal concentrations and independent variables (age, serum ferritin, manganese exposure status, and sex) by multiple regression analysis was assessed, controlling for various covariates such as BMI, educational level, smoking, and alcohol drinking status. Overall, the geometric means of blood manganese, cadmium, and lead levels of all participants (n = 276) were 9.307 μg/L, 0.393 μg/L, and 1.276 μg/dL, respectively. Log serum ferritin concentrations were inversely associated with log blood manganese concentration (β = -0.061 log ferritin and β = 0.146 categorical ferritin) and log blood cadmium concentrations (β = -0.090 log ferritin and β = 0.256 categorical ferritin). Log serum ferritin concentrations were not associated with log blood lead concentrations. Variables of age, sex, and exposure status were not associated with log manganese concentrations; however, log blood cadmium concentrations were higher in older population, women, and smokers. Log blood lead concentrations were higher in older population, men, and postmenopausal women. Our study showed that iron deficiency is associated with increased levels of blood manganese and cadmium, but not blood lead, in Ohio residents. These metals showed different toxicokinetics in relation to age, sex, and menopausal status despite

  5. Serum Ferritin, Weight Gain, Disruptive Behavior, and Extrapyramidal Symptoms in Risperidone-Treated Youth.

    PubMed

    Calarge, Chadi A; Murry, Daryl J; Ziegler, Ekhard E; Arnold, L Eugene

    2016-06-01

    Iron deficiency disrupts dopaminergic signaling in rodents, resulting in cognitive deficits that may be reversed with psychostimulants. In humans, iron deficiency with or without anemia has similarly been found to cause neuropsychological and behavioral impairments. However, the clinical effects of low body iron stores in antipsychotic-treated children have not been examined. Medically healthy, 5- to 17-year-old boys treated with risperidone for at least 1 year were enrolled between February 2009 and November 2013 in a multiphase study, examining the skeletal effects of calcium and vitamin D supplementation in risperidone-induced hyperprolactinemia. Anthropometric measures were collected and medical and pharmacy records were reviewed to obtain treatment history. Psychiatric diagnoses were based on clinical interviews, structured interviews, rating scales, and a review of their medical records. Extrapyramidal symptoms were assessed, and a food frequency questionnaire was completed in a subsample. Laboratory tests, including ferritin concentration (a marker of body iron status), were obtained upon study entry. A total of 114 participants (mean age: 11.0 ± 2.6 years) were included, the vast majority (>90%) having attention-deficit/hyperactivity disorder and/or disruptive behavior disorder. They had taken risperidone for an average 3.1 ± 2.0 years. Their serum ferritin concentration was 37.3 ± 25.6 μg/L with 21% of the sample having a level <20 μg/L, despite appropriate daily dietary iron intake. Ferritin concentration was inversely associated with weight gain following risperidone treatment onset but was not significantly associated with prolactin. After adjusting for the weight-adjusted dose of psychostimulants and risperidone and the daily dose of selective serotonin reuptake inhibitors, ferritin was inversely associated with the severity of disruptive behavior and positively associated (albeit marginally) with prosocial behavior. No association

  6. Serum iron level, ferritin and total iron binding capacity level among nonpregnant women with and without melasma

    PubMed Central

    Behrangi, Elham; Baniasadi, Farzaneh; Esmaeeli, Shooka; Hedayat, Kosar; Goodarzi, Azade; Azizian, Zahra

    2015-01-01

    Background: Melasma is a common acquired disorder characterized by symmetric, hyperpigmented patches with an irregular outline, occurring most commonly on the face. It is most prevalent among young to middle-aged women. Although iron overload affects skin pigmentation, effect of iron deficiency on skin is not clear. So, we evaluated serum iron level, ferritin and total iron binding capacity (TIBC) level among nonpregnant women with and without melasma. Materials and Methods: A cross-sectional case study was conducted in 2012 at university dermatologic department on 33 nonpregnant women with melasma (case) and 33 nonpregnant women without melasma (control). Serum iron level, TIBC and ferritin in the two groups was measured and compared. Results: Serum iron level was lower in the case group (85 ± 11) in comparison with control group (102 ± 9), but the difference was not significant (P: 0.9). Mean TIBC and Ferritin were higher in the case group (TIBC: 329.4 ± 29, ferritin: 6 ± 18) than the control group (TIBC: 329.3 ± 29, ferritin: 33 ± 6) without significant difference. Conclusion: Although the serum iron level was lower in nonpregnant women with mealsma, it was not significant compared with those without melasma. PMID:26109976

  7. Dietary iron intake and serum ferritin concentration in 213 patients homozygous for the HFEC282Y hemochromatosis mutation

    PubMed Central

    Gordeuk, Victor R; Lovato, Laura; Barton, James C; Vitolins, Mara; McLaren, Gordon; Acton, Ronald T; McLaren, Christine; Harris, Emily L; Speechley, Mark; Eckfeldt, John H; Diaz, Sharmin; Sholinsky, Phyliss; Adams, Paul

    2012-01-01

    BACKGROUND: HFEC282Y homozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals. OBJECTIVE: To determine whether dietary iron content influences iron stores in HFEC282Y homozygotes as assessed by serum ferritin concentration. DESIGN: Serum ferritin concentration was measured and a dietary iron questionnaire was completed as part of the evaluation of 213 HFEC282Y homozygotes who were identified through screening of >100,000 primary care patients at five HEmochromatosis and IRon Overload Screening (HEIRS) Study Field Centers in the United States and Canada. RESULTS: No significant relationships between serum ferritin concentration and dietary heme iron content, dietary nonheme iron content or reports of supplemental iron use were found. CONCLUSION: These results do not support recommending dietary heme or nonheme iron restrictions for HFEC282Y homozygotes diagnosed through screening in North America. PMID:22720276

  8. 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

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

    PubMed Central

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

    2016-01-01

    Purpose 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. Methods 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. Results 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. Conclusions In the Jackson Heart Study, the

  10. Relationship Between Serum Hepcidin and Ferritin Levels in Patients With Thalassemia Major and Intermedia in Southern Iran

    PubMed Central

    Haghpanah, Sezaneh; Esmaeilzadeh, Masoomeh; Honar, Naser; Hassani, Fatemeh; Dehbozorgian, Javad; Rezaei, Narges; Abdollahi, Maryam; Bardestani, Marzieh; Safaei, Sanaz; Karimi, Mehran

    2015-01-01

    Background: Hepcidin is a key regulator of iron absorption in humans. It is mainly affected by hypoxia and iron stores. Objectives: The current study aimed to determine the correlation between serum hepcidin and ferritin levels in patients with Thalassemia Major (TM) and Thalassemia Intermedia (TI). Patients and Methods: The current cross-sectional study investigated 88 randomly selected patients with Thalassemia, 48 TM and 40 TI, registered at the Thalassemia Clinic of Shiraz University of Medical Sciences, a referral center for Thalassemia in Southern Iran in 2013. All patients with TI were receiving Hydroxyurea (HU) 10 - 15 mg/kg/day for at least 10 years. The serum hepcidin, ferritin levels, hemoglobin (Hb) and nucleated Red Blood Cell (RBC) of the two groups were measured. Results: No statistically significant correlation was observed between serum hepcidin and ferritin levels in any of the two groups of patients with TM (rs = 0.02, P = 0.892) or TI (rs = 0.055, P = 0.734). The median Interquartile Range (IQR) for serum hepcidin and ferritin levels were significantly higher in TM compared to TI group, (hepcidin: 87.6 (43.9) vs. 51.8 (23.4), P < 0.001; ferritin: 2208 (3761) vs. 465 (632), P < 0.001). Conclusions: There was insignificant correlation between serum hepcidin and ferritin levels in the two groups of patients with TM and TI. It seems that regulation of hepcidin in patients with Thalassemia is more affected by erythropoeitic activity than iron stores. Also, hepcidin levels were significantly higher in patients with TM than TI, possibly due to higher erythropoeitic activity in TI. In TI, it seems that low dose HU increases Hb levels and leads to transfusion-independence, but it is not high enough to suppress bone marrow activity and ineffective erythropoiesis. Consequently, serum hepcidin level decreases. PMID:26421179

  11. Correlation between liver iron concentration determined by magnetic resonance imaging and serum ferritin in adolescents with thalassaemia disease.

    PubMed

    Chuansumrit, Ampaiwan; Laothamathat, Jiraporn; Sirachainan, Nongnuch; Sungkarat, Witaya; Wongwerawattanakoon, Pakawan; Kumkrua, Patrapop

    2016-08-01

    MRI imaging is an alternative to serum ferritin for assessing iron overload in patients with thalassaemia disease. To correlate liver iron concentration (LIC) determined by MRI and clinical and biochemical parameters. An MRI study using cardiovascular magnetic resonance (CMR) tools to determine cardiac and liver iron was undertaken in adolescents with thalassaemia disease. Eighty-nine patients (48 males) with thalassaemia disease were enrolled. Seventy patients had been transfusion-dependent since a mean (SD) age of 3.8 (3.0) years, and 19 patients were not transfusiondependent. Mean (SD) haematocrit was 27.3 (2.9)%. Twenty-eight patients were splenectomized. Mean (SD) serum ferritin was 1673 (1506) μg/L. All transfusion-dependent patients received iron chelation at the mean (SD) age of 8.4 (3.5) years with either monotherapy of desferrioxamine, deferiprone, deferasirox or combined therapy of desferrioxamine and deferiprone, while only 5 of 19 patients who were not transfusion-dependent received oral chelation. The 89 patients underwent an MRI scan at the mean (SD) age of 14.8 (3.2) years. No patients had myocardial iron overload, but nine had severe liver iron overload, 27 had moderate liver iron overload, and 36 had mild liver iron overload. A significant correlation between liver T2* and serum ferritin was expressed as the equation: T2* (ms) = 28.080-7.629 log ferritin (μg/L) (r(2) 0.424, P = 0.0001). Patients with serum ferritin of >1000 to >2500 μg/L risked moderate and severe liver iron loading with the odds ratio ranging from 6.8 to 13.3 (95% CI 2.5-50.8). In thalassaemia, MRI is an alternative means of assessing iron stores, but when it is not available serum ferritin can be used to estimate liver T2*.

  12. Predictors of serum ferritin and haemoglobin during pregnancy, in a malaria-endemic area of western Kenya.

    PubMed

    Alusala, D N; Estambale, B B A; Magnussen, P; Friis, H; Luoba, A I; Mwaniki, D

    2008-06-01

    Between 2000 and 2004, a cross-sectional survey was conducted, as part of a prospective cohort study, among the women attending antenatal-care clinics in Bondo district, a malaria-endemic area of western Kenya. The aim was to assess the prevalence of iron deficiency and determine the predictors of haemoglobin and serum ferritin concentrations in the women who had a gestational age between 14 and 24 weeks. A standardized questionnaire was used to collect and store the relevant bio-data for the study. Haemoglobin and ferritin concentrations were evaluated, sickle-cell status was determined, and malarial parasitaemias were detected and evaluated, using blood samples collected at enrollment. Multiple regression analysis was then used to test for significant predictors of the haemoglobin and serum ferritin concentrations. Although 842 women were enrolled in the prospective cohort study, haemoglobin concentrations were evaluated for only 828 of them, serum ferritin levels for 621, and levels of parasitaemia for 812. The mean haemoglobin concentration recorded was 10.9 g/dl. Although 37.9% of the subjects had mild-moderate anaemia (7.0-10.5 g haemoglobin/dl), only 0.5% were severely anaemic (<7.0 g haemoglobin/dl). The geometric mean serum ferritin concentration recorded was 18.9 microg/litre, and 32.3% of the subjects evaluated had low serum concentrations of ferritin (<12 microg/litre). Among the parasitaemic primigravidae (but not the parasitaemic multigravidae), those found positive for sickle-cell trait had significantly lower haemoglobin concentrations than those found negative in a sickling test (P=0.01). Among the pregnant women of Bondo district, gravidity, malarial infection and sickle cell appear to be key predictors of haemoglobin concentration.

  13. ["Free" iron, transferrin and ferritin levels in serum and their relation with severe malnutrition].

    PubMed

    Velásquez Rodríguez, C Ma; Parra Sosa, B; Morales Mira, G; Agudelo Ochoa, G; Cardona Henao, O; Bernal Parra, C; Burgos Herrera, L; Betancur Acosta, M

    2007-01-01

    "Free" serum iron has been associated with the development of edema in Kwashiorkor-type severe acute malnutrition. A descriptive, cross sectional study was performed. Twenty-four children with edematous malnutrition, 22 with marasmus and 20 without malnutrition were compared. "Free" iron, transferrin, saturation index and attachment capacity of iron, ferritin, total protein, albumin, total iron, and C-reactive protein (CRP) were determined in serum. A significant difference was found between malnourished children with "free" serum iron and the control group in which "free" iron was not found. However, no significant differences were found in "free" serum iron levels between marasmatic and edematous children. Transferrin was negatively correlated with "free" iron (r=-0.519; p=0.000). Total proteins, albumin and transferrin were all significantly lower in children with edema than in those with marasmus. A low transferrin level and a high saturation index could be used to estimate the probability of edema in 67.5% of cases (p=0.001). Severe acute malnutrition was associated with the presence of "free" serum iron both in children with marasmus and in those with edema. "Free" iron does not explain the presence of edema but, as with severe hypoalbuminemia, the concurrence of a low transferrin level and a high saturation index may contribute to the etiology of edema.

  14. SERUM FERRITIN CONCENTRATION IS NOT A RELIABLE BIOMARKER OF IRON OVERLOAD DISORDER PROGRESSION OR HEMOCHROMATOSIS IN THE SUMATRAN RHINOCEROS (DICERORHINUS SUMATRENSIS).

    PubMed

    Roth, Terri L; Reinhart, Paul R; Kroll, Jennifer L

    2017-09-01

    The aim of this study was to determine if ferritin is a reliable biomarker of iron overload disorder (IOD) progression and hemochromatosis in the Sumatran rhinoceros (Dicerorhinus sumatrensis) by developing a species-specific ferritin assay and testing historically banked samples collected from rhinos that did and did not die of hemochromatosis. Ferritin extracted from Sumatran rhino liver tissue was used to generate antibodies for the Enzyme Immunoassay. Historically banked Sumatran rhino serum samples (n = 298) obtained from six rhinos in US zoos (n = 290); five rhinos at the Sumatran Rhino Conservation Centre in Sungai Dusun, Malaysia (n = 5); and two rhinos in Sabah, Malaysia (n = 3) were analyzed for ferritin concentrations. Across all US zoo samples, serum ferritin concentrations ranged from 348 to 7,071 ng/ml, with individual means ranging from 1,267 (n = 25) to 2,604 ng/ml (n = 36). The ferritin profiles were dynamic, and all rhinos exhibited spikes in ferritin above baseline during the sampling period. The rhino with the highest mean ferritin concentration did not die of hemochromatosis and exhibited only mild hemosiderosis postmortem. A reproductive female exhibited decreases and increases in serum ferritin concurrent with pregnant and nonpregnant states, respectively. Mean (±SD) serum ferritin concentration for Sumatran rhinos in Malaysia was high (4,904 ± 4,828 ng/ml) compared to that for US zoo rhinos (1,835 ± 495 ng/ml). However, those in Sabah had lower ferritin concentrations (1,025 ± 52.7 ng/ml) compared to those in Sungai Dusun (6,456 ± 4,941 ng/ml). In conclusion, Sumatran rhino serum ferritin concentrations are dynamic, and increases often are not associated with illness or hemochromatosis. Neither a specific pattern nor the individual's overall mean ferritin concentration can be used to accurately assess IOD progression or diagnose hemochromatosis in this rhino species.

  15. Association between Serum Ferritin and Osteocalcin as a Potential Mechanism Explaining the Iron-Induced Insulin Resistance

    PubMed Central

    Juanola-Falgarona, Martí; Cándido-Fernández, José; Salas-Salvadó, Jordi; Martínez-González, Miguel A.; Estruch, Ramón; Fiol, Miquel; Arija-Val, Victoria

    2013-01-01

    Background Increased iron stores are associated with increased risk of type 2 diabetes, however, the mechanisms underlying these associations are poorly understood. Because a reduction of circulating osteocalcin levels after iron overload have been demonstrated in cell cultures, and osteocalcin is related to glucose and insulin metabolism, the iron-induced osteocalcin reductions could contribute to explain the role of iron metabolism in the development of type 2 diabetes mellitus. Objective To analyzed the associations between serum total and uncarboxylated osteocalcin and adiponectin concentrations with serum ferritin and soluble transferrin receptor (sTfR) in elderly subjects. Design We evaluated a total of 423 subjects from the PREDIMED cohort in a population-based cross-sectional analysis. Extensive clinical, nutritional and laboratory measurements, including total and uncarboxylated osteocalcin, adiponectin, ferritin and sTfR were recorded. Results Serum ferritin was positively correlated with increased glucose and insulin circulating levels but also with HOMA-IR, and was inversely associated with total osteocalcin and adiponectin. A regression analysis revealed that serum ferritin and transferrin receptor levels were significantly associated with a decrease in total and uncarboxylated osteocalcin. Serum sTfR levels were associated with lower uncarboxylated osteocalcin levels in the whole-study subjects and remained significant only in the IFG (impaired fasting glucose) individuals. Conclusions We described, for the first time, an inverse association between serum ferritin and sTfR with osteocalcin and extend previous results on adiponectin, thus supporting that factors related to iron metabolism could contribute to the insulin resistance and the development of type 2 diabetes mellitus. Trial Registration Controlled-Trials.com ISRCTN35739639 . PMID:24167545

  16. 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/.

  17. Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation

    PubMed Central

    Hu, Xiaohui; Yang, Yan; Su, Junfeng; Yao, Changjiang

    2016-01-01

    Objective: To study the possible relationship between amyotrophic lateral sclerosis (ALS) patients and their susceptibility to serum ferritin level elevation. Methods: We searched the PubMed, Springer, Medline, and OVID databases for any-language original research articles relating to serum ferritin levels in ALS patients published between June 2005 and June 2015. The search term used with ‘amyotrophic lateral sclerosis’, ‘ferritins’, ‘ferritin’, ‘iron’, ‘iron stores, ‘iron status, ‘iron intake’, and ‘iron consumption’. The meta-analysis software RevMan 5.0 was used for the heterogeneity test, and to test for the overall effect. Results: Six case-control studies met our inclusion criteria including data from a total of 1813 participants. The mean difference of serum ferritin levels comparing ALS to healthy controls was 69.05 (95% confidence interval: 52.56-85.54; p<0.00001); heterogeneity: p=0.03; I2=50%. The findings indicate homology in the sensitivity analysis. Funnel plot assessment indicated publication bias. Conclusion: Our results suggest that ALS is positively associated with susceptibility to the elevation of serum ferritin levels; however, further evidence is required to support this. PMID:27094521

  18. Serum ferritin in normal individuals and in patients with malignant lymphoma and chronic renal failure measured with seven different commercial immunoassay techniques.

    PubMed Central

    Grail, A; Hancock, B W; Harrison, P M

    1982-01-01

    A comparison of serum ferritin determination by seven different commercial immunoassay techniques gave mean coefficients of variation of 57% for normal individuals, 41 . 4% for patients with malignant lymphoma and 43 . 1% for patients with chronic renal failure. One of the immunoradiometric assays gave consistently higher serum ferritin values in both normal and patient groups; mean values were increased (greater than 100% for normal males, greater than 50% for normal females) with respect to the other assays. Underestimation of serum ferritin by an enzyme-linked immunosorbent assay was also evident. Results were affected by storage conditions, but not by dilution of samples, in two kits. Solutions of ferritin purified from normal and malignant human and mouse tissues, and lymphoma isoferritins, were used for reference. There were overestimations of normal human liver ferritin and the most basic isoferritin. Mouse ferritin displayed minimal reactivity in all kits, and human lymphoma ferritin was often underestimated. Variability in serum ferritin determination chiefly reflects the lack of a universal standard for ferritin measurement. Images PMID:7142429

  19. Role of Serum Uric Acid and Ferritin in the Development and Progression of NAFLD

    PubMed Central

    Lombardi, Rosa; Pisano, Giuseppina; Fargion, Silvia

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), tightly linked to the metabolic syndrome (MS), has emerged as a leading cause of chronic liver disease worldwide. Since it is potentially progressive towards non-alcoholic steatohepatitis (NASH) and hepatic fibrosis, up to cirrhosis and its associated complications, the need for predictive factors of NAFLD and of its advanced forms is mandatory. Despite the current “gold standard” for the assessment of liver damage in NAFLD being liver biopsy, in recent years, several non-invasive tools have been designed as alternatives to histology, of which fibroscan seems the most promising. Among the different serum markers considered, serum uric acid (SUA) and ferritin have emerged as possible predictors of severity of liver damage in NAFLD. In fact, as widely described in this review, they share common pathogenetic pathways and are both associated with hepatic steatosis and MS, thus suggesting a likely synergistic action. Nevertheless, the power of these serum markers seems to be too low if considered alone, suggesting that they should be included in a wider perspective together with other metabolic and biochemical parameters in order to predict liver damage. PMID:27077854

  20. Catha Edulis (Khat) Chewing Decreases Serum Levels of Iron, Ferritin and Vitamin B12 and Increases Folic Acid.

    PubMed

    Al-Dubai, Waled; Al-Ghazaly, Jameel; Al-Habori, Molham; Saif-Ali, Riyadh; Mohammed, Ahmed

    2014-01-01

    Catha edulis (Khat) is customarily chewed to attain a state of stimulation and reduce physical fatigue. In view of the reported common adverse effects of Khat, the aim of this study was to evaluate the levels of iron, ferritin, folic acid, vitamin B(12) and body mass index (BMI) as nutritive indicators in Yemeni Khat chewers. This study was a prospective cohort study, carried out on 90 male workers aged 19 - 23 years old; 45 were healthy non-Khat chewers serving as control group and 45 were regular Khat chewers. Serum iron, ferritin, folic acid, vitamin B(12) and body mass index were measured at baseline and after a year of follow up. Serum iron and BMI were significantly (p < 0.01) lower at baseline in Khat chewers by 9 % and 6 %, respectively; whereas ferritin, folic acid and vitamin B(12) were non-significantly different from non-Khat chewers. In the follow-up one year later, serum iron, ferritin, vitamin B(12) and BMI were significantly (p < 0.001) lower in Khat chewers by 19.0, 31.4, 20.6 and 10.7 %; whereas folic acid was significantly (p = 0.007) higher by 26.7 %. Comparison within groups showed serum iron, ferritin, and BMI to be significantly (p < 0.01) decreased after one year in the Khat chewers with respect to its baseline; whereas folic acid significantly (p < 0.001) increased. This study shows Khat chewers to be more susceptible to malnutrition, which should be considered by the general population and the public health authorities.

  1. Initial Serum Ferritin Predicts Number of Therapeutic Phlebotomies to Iron Depletion in Secondary Iron Overload

    PubMed Central

    Panch, Sandhya R.; Yau, Yu Ying; West, Kamille; Diggs, Karen; Sweigart, Tamsen; Leitman, Susan F.

    2014-01-01

    Background Therapeutic phlebotomy is increasingly used in patients with transfusional siderosis to mitigate organ injury associated with iron overload (IO). Laboratory response parameters and therapy duration are not well characterized in such patients. Methods We retrospectively evaluated 99 consecutive patients undergoing therapeutic phlebotomy for either transfusional IO (TIO, n=88; 76% had undergone hematopoietic transplantation) or non-transfusional indications (hyperferritinemia or erythrocytosis) (n=11). CBC, serum ferritin (SF), transferrin saturation, and transaminases were measured serially. Phlebotomy goal was an SF< 300 mcg/L. Results Mean SF prior to phlebotomy among TIO and nontransfusional subjects was 3,093 and 396 mcg/L, respectively. Transfusion burden in the TIO group was 94 ± 108 (mean ± SD) RBC units; about half completed therapy with 24 ± 23 phlebotomies (range 1–103). One-third was lost to follow-up. Overall, 15% had mild adverse effects, including headache, nausea, and dizziness, mainly during first phlebotomy. Prior transfusion burden correlated poorly with initial ferritin and total number of phlebotomies to target (NPT) in the TIO group. However, NPT was strongly correlated with initial SF (R2=0.8; p<0.0001) in both TIO and nontransfusional groups. ALT decreased significantly with serial phlebotomy in all groups (mean initial and final values, 61 and 39 U/L; p = 0.03). Conclusions Initial SF but not transfusion burden predicted number of phlebotomies to target in patients with TIO. Despite good treatment tolerance, significant losses to follow-up were noted. Providing patients with an estimated phlebotomy number and follow-up duration, and thus a finite endpoint, may improve compliance. Hepatic function improved with iron off-loading. PMID:25209879

  2. Preliminary evaluation of the performance of a new, highly sensitive commercial immunoassay for serum ferritin determination.

    PubMed

    Signò, Paolo; Barassi, Alessandra; Novario, Raffaele; Melzi d'Eril, Gian Vico

    2005-01-01

    We evaluated the analytical performance of a new, commercial, fully automated immunoturbidimetric assay for the determination of ferritin [FER-Latex(X2)CN SEIKEN, Denka Seiken, Japan] in serum on the Olympus AU2700 analyzer. The new assay is a latex-enhanced turbidimetric immunoassay with an analysis time of 10 min. The linearity of the assay was confirmed up to 2505 pmol/L (R2=0.999). The detection limit and the functional sensitivity were both 4.5 pmol/L. The intra- and inter-assay imprecision (CV) at 67, 506, 2186 pmol/L was < 1.8% and < 2.5%, respectively. Verification of the traceability to a WHO standard (80/578) showed a recovery of 102.6% (target value 449 pmol/L). No hook effect was observed in samples containing up to 33,705 pmol/L. The assay showed good correlation with the Beckman Immage nephelometric system (r=0.999). Hemoglobin (< or = 9.8 g/L), total bilirubin (< or = 113 micromol/L), conjugated bilirubin (< or = 109 micromol/L) and rheumatoid factor (< or = 5.2x10(5) IU/L) did not interfere with the assay. The reference interval (2.5-97.5 percentile) was 72-521 pmol/L for men and 27-267 pmol/L for women. The reference interval in patients with anemia, malignant tumors and hemochromatosis was 5.6-52, 130-2436 and 1465-2903 pmol/L, respectively. On the basis of the receiver operating characteristic curve, the 90% sensitivity cut-off value to distinguish between patients with and without iron deficiency was 40 pmol/L. The new latex turbidimetric procedure for ferritin assay is an attractive alternative that avoids the need for dedicated instrumentation.

  3. Serum ferritin as prognostic marker in classical Hodgkin lymphoma treated with ABVD-based therapy.

    PubMed

    Fernandez-Alvarez, Ruben; Gonzalez-Rodriguez, Ana P; Gonzalez, M Esther; Rubio-Castro, Arturo; Dominguez-Iglesias, Francisco; Solano, Jackeline; Alonso-Nogues, Eva; Fernandez-Alvarez, Carmen; Zanabili, Yahya; Alonso, Jose Manuel; Payer, Angel Ramirez; Vicente, Jose Maria; Medina, Jesus; Sancho, Juan M

    2015-01-01

    Ferritin levels might correlate with disease activity in classical Hodgkin lymphoma (cHL). We analyzed the prognostic significance of the ferritin value at diagnosis in 173 cHL patients treated with ABVD between 2003 and 2013. The 5-year overall survival (OS) and progression-free survival (PFS) probabilities were 80% and 64%, respectively. Patients with ferritin ≥ 350 μg/l [high ferritin group (HF), n = 62] were more likely to have advanced stage disease, B-symptoms and higher International Prognostic Score (IPS) compared with patients with ferritin < 350 μg/l [low ferritin group (LF), n = 111]. The complete remission (CR) rate and 5-year PFS and OS probabilities were lower in HF vs. LF patients (69% vs. 89%, p = 0.025; 40% vs. 78%, p < 0.001; 61% vs. 90%, p = 0.001; respectively). Multivariate analysis revealed that advanced stage (p = 0.001) and ferritin levels ≥ 350 μg/l (p = 0.002) were independent predictors for PFS. In conclusion, the ferritin level at diagnosis is a useful prognostic marker for cHL.

  4. Diagnostic use of serum ferritin levels to differentiate infectious and noninfectious diseases in patients with fever of unknown origin.

    PubMed

    Kim, Seong Eun; Kim, Uh Jin; Jang, Mi Ok; Kang, Seung Ji; Jang, Hee Chang; Jung, Sook In; Lee, Shin Seok; Park, Kyung Hwa

    2013-01-01

    In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases. FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed. Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0-951.8) ng/mL for the infectious disease group, 1818.2 (485.4-4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6-1927.2) ng/mL for the noninfectious inflammatory disease group, p=0.048, Kruskal-Wallis test). By comparison using the Mann-Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p=0.049) and between the infectious disease and groups (p=0.04). An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

  5. 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

  6. Alteration of Serum Concentrations of Manganese, Iron, Ferritin, and Transferrin Receptor Following Exposure to Welding Fumes Among Career Welders

    PubMed Central

    Lu, Ling; Zhang, Long-lian; Li, G. Jane; Guo, Wenrui; Liang, Wannian; Zheng, Wei

    2014-01-01

    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 7–8 h 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 μm, 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. PMID:15713346

  7. Serum ferritin contributes to racial or geographic disparities in metabolic syndrome in Taiwan.

    PubMed

    Chang, Jung-Su; Lin, Shiue-Ming; Chao, Jane C-J; Chen, Yi-Chun; Wang, Chi-Mei; Chou, Ni-Hsin; Pan, Wen-Harn; Bai, Chyi-Huey

    2014-07-01

    Asians and Pacific Islanders have higher circulating serum ferritin (SF) compared with Caucasians but the clinical significance of this is unclear. There is a higher prevalence of metabolic syndrome (MetS) in Taiwanese Indigenous than Han Chinese. Genetically, Indigenous are related to Austronesians and account for 2 % of Taiwan's population. We tested the hypothesis that accumulation of Fe in the body contributes to the ethnic/racial disparities in MetS in Taiwan. A population-based, cross-sectional study. National Nutrition and Health Survey in Taiwan and Penghu Island. A total of 2638 healthy adults aged ≥19 years. Three ethnic groups were included. Han Chinese and Indigenous people had comparable levels of SF. Austronesia origin was independently associated with MetS (OR = 2·61, 95 % CI 2·02, 3·36). After multiple adjustments, the odds for MetS (OR = 2·49, 95 % CI 1·15, 5·28) was significantly higher among Indigenous people in the highest SF tertile compared with those in the lowest tertile. Hakka and Penghu Islanders yielded the lowest risks (OR = 1·08, 95 % CI 0·44, 2·65 and OR = 1·21, 95 % CI 0·52, 2·78, respectively). Indigenous people in the highest SF tertile had increased risk for abnormal levels of fasting glucose (OR = 2·34, 95 % CI 1·27, 4·29), TAG (OR = 1·94, 95 % CI 1·11, 3·39) and HDL-cholesterol (OR = 2·10, 95 % CI 1·18, 3·73) than those in the lowest SF tertile. Our results raise the possibility that ethnic/racial differences in body Fe store susceptibility may contribute to racial and geographic disparities in MetS.

  8. Evaluation of serum ferritin in screening for iron deficiency in tuberculosis.

    PubMed

    Kotru, M; Rusia, U; Sikka, M; Chaturvedi, S; Jain, A K

    2004-02-01

    Serum ferritin (SF) values

  9. Serum magnesium, iron and ferritin levels in patients with diabetic retinopathy attending Makkah Eye Complex, Khartoum, Sudan.

    PubMed

    Hamdan, Hamdan Z; Nasser, Nasser M; Adam, Ammar M; Saleem, Mahgoub A; Elamin, Maha I

    2015-05-01

    Diabetic retinopathy is the most common complications of diabetes mellitus that, in most occasions, lead to blindness. Multiple evidences linked the serum magnesium, iron and ferritin disturbance with diabetes and its complications. A case-control study was conducted at Makkah Eye Complex, Khartoum, Sudan, to compare the levels of serum magnesium, iron and ferritin in patients with diabetic retinopathy with diabetic patients without diabetic retinopathy (controls). Findings indicate that all patients had type 2 diabetes. The two groups (50 in each arm) were well matched in their basic characteristics. Median (25th-75th interquartile) of serum magnesium in patients with diabetic retinopathy were significantly lower than patients without diabetic retinopathy [1.48 (0.75-1.64) vs. 1.92 (1.4-2.3)mg/dl, P = 0.022]. The median of serum iron and ferritin were lower in cases than control group but did not reach a statistical significance [20.5 (17.2-48.0) vs. 27.0 (16.0-54.0) μg/dl, P = 0.568; 98.0 (45.0-134.75) vs. 101.0 (47.0-161.0) μg/l, P = 0.818]. The duration of diabetes [16.5 (9.3) vs. 11.2 (6.6) years; P = 0.014] and haemoglobin level [13.7 (0.9) vs. 12.5 (2.0) g/dl; P = 0.039] were significantly higher in cases group than control group. A significant inverse correlation was observed between serum magnesium and iron levels. Twenty (40 %) patients had severe non-proliferative diabetic retinopathy with mild macular edema, which is the most prevalent type among the cases group. Hypomagnesaemia among diabetic patients was associated with diabetic retinopathy, while serum iron and ferritin have no significant effect in this setting. Severe non-proliferative diabetic retinopathy with mild macular edema is the prevalent type in this study.

  10. Association of serum ferritin with insulin resistance, abdominal obesity, and metabolic syndrome in Korean adolescent and adults: The Korean National Health and Nutrition Examination Survey, 2008 to 2011.

    PubMed

    Shim, Young Suk; Kang, Min Jae; Oh, Yeon Jeong; Baek, Joon Woo; Yang, Seung; Hwang, Il Tae

    2017-02-01

    This study aimed to evaluate the associations of serum ferritin with insulin resistance indices, body fat mass/percentage, and all the components of metabolic syndrome (MetS), as well as the risk for MetS according to serum ferritin levels in Korean adolescents and adults.A total of 15,963 Korean males and females aged 16 to 80 years were analyzed using data from the Korean National Health and Nutrition Examination Survey, 2005 to 2011.The median serum ferritin concentration was 98.82 ng/mL for males and 38.60 ng/mL for females (P < 0.001). Increased risks of greater waist circumference and elevated glucose levels, elevated triglyceride levels, and reduced high-density lipoprotein cholesterol levels were noted across the serum ferritin quartiles after adjustment for confounders in both genders (P ≤ 0.012 for trend). Insulin resistance indices and abdominal obesity (trunk fat mass/percent) increased across the ferritin concentration quartiles after adjustment for confounders in males and females (P ≤ 0.011 for trend), and the risk of MetS increased across the ferritin quartiles in males (P < 0.001 for trend) and females (P = 0.001 for trend). The highest serum ferritin quartile exhibited a 1.62-fold increased risk of MetS (95% CI, 1.28-2.12) in males and a 1.36-fold increased risk of MetS (95% CI, 1.09-1.69) in females compared with the lowest quartile after adjustment for confounders.Our results suggest that ferritin is associated with insulin resistance and abdominal obesity.

  11. Comparison of four immunoassays to measure serum ferritin concentrations and iron deficiency prevalence among non-pregnant Cambodian women and Congolese children.

    PubMed

    Karakochuk, Crystal D; Whitfield, Kyly C; Rappaport, Aviva I; Barr, Susan I; Vercauteren, Suzanne M; McLean, Judy; Hou, Kroeun; Talukder, Aminuzzaman; Houghton, Lisa A; Bailey, Karl B; Boy, Erick; Green, Timothy J

    2017-01-01

    Global standardization of ferritin assays is lacking, which could have direct implications on the accurate measurement and comparability of ferritin concentration and iron deficiency (ID) prevalence rates in at-risk populations. We measured serum ferritin concentrations using four immunoassays: the s-ELISA and the AxSYM™ analyzer were compared among 420 non-pregnant Cambodian women; the Centaur® XP analyzer, s-ELISA, and AxSYM™ analyzer were compared among a subset of 100 Cambodian women; and the s-ELISA and the Elecsys® 2010 analyzer were compared among 226 Congolese children aged 6-59 months. Median ferritin concentrations (adjusted for inflammation) ranged between 48 and 91 μg/L among Cambodian women and between 54 and 55 μg/L among Congolese children. ID prevalence ranged from 2% to 10% among Cambodian women and 5% to 7% among Congolese children. Bias between methods varied widely (-9 to 45 μg/L) among women, and was 43 μg/L among children. Bias was lower when ferritin values outside of the s-ELISA measurement range (>250 μg/L) were excluded. The observed differences in ferritin concentrations likely reflect different ferritin isoforms, antibodies, and calibrators used across assays and by different laboratories. However, despite differences in ferritin concentrations, ID prevalence was relatively similar and low across all methods.

  12. Evaluation of serum ferritin and some metal elements in type 2 diabetes mellitus patients: comparative cross-sectional study

    PubMed Central

    Wolide, Amare Desalegn; Zawdie, Belay; Alemayehu, Tilahun; Tadesse, Samuel

    2016-01-01

    Background The chronic hyperglycemia of diabetes has been associated with an imbalance of some trace metal elements in the blood sample of type 2 diabetes patients. Aim To evaluate the status of serum ferritin and some selected metal elements among type 2 diabetes mellitus (T2DM) patients. Methods Facility-based comparative cross-sectional study was conducted from February 15, 2015 to October 30, 2015, at Jimma University Specialized Hospital, Ethiopia. A total of 428 type 2 diabetes and nondiabetes study subjects were recruited to the study. After overnight fasting, 10 mL of venous blood samples were taken for biochemical and trace metal element analysis. Data were entered into EpiData version 3.5.1 and exported to SPSS version 20 for Windows for analysis. Results Serum concentration of Zn+2, Mg+2, Cr+3, ferritin, and Fe+3 in patients with type 2 diabetes was significantly lower (p<0.0001) than nondiabetes patients. In contrast, serum Cu+2 was significantly higher (p<0.0001) in type 2 diabetes patients than nondiabetics. In addition, significant differences were not seen in both groups with regard to serum Mn+2, Ca+2, and Po4−3. Waist-to-hip ratio (WHR), serum Fe+3, ferritin, and Mn+2 were significantly higher among oral hypoglycemic agent users of type 2 diabetes patients than the injectable insulin users. Serum Zn+2 had significant positive correlation with serum Mg+2 (r=0.738), Cr+3 (r=0.233), Ca+2 (r=0.238), and Po4−3 (r=0.222). In addition, serum Zn+2 had shown significant and negative correlation with body mass index (BMI, r=−0.331), WHR (r=−0.340), and fasting blood glucose (FBG, r=−0.186). Likewise, serum Mg+2 and Po4−3 are significantly and negatively correlated with BMI, WHR, and FBG. Conclusion The imbalance of trace metal elements in the blood sample of diabetes is uncertain. Thus, we recommend a prospective cohort study to find out the principal factors behind the problem. PMID:27980430

  13. Evaluation of serum ferritin and some metal elements in type 2 diabetes mellitus patients: comparative cross-sectional study.

    PubMed

    Wolide, Amare Desalegn; Zawdie, Belay; Alemayehu, Tilahun; Tadesse, Samuel

    2016-01-01

    The chronic hyperglycemia of diabetes has been associated with an imbalance of some trace metal elements in the blood sample of type 2 diabetes patients. To evaluate the status of serum ferritin and some selected metal elements among type 2 diabetes mellitus (T2DM) patients. Facility-based comparative cross-sectional study was conducted from February 15, 2015 to October 30, 2015, at Jimma University Specialized Hospital, Ethiopia. A total of 428 type 2 diabetes and nondiabetes study subjects were recruited to the study. After overnight fasting, 10 mL of venous blood samples were taken for biochemical and trace metal element analysis. Data were entered into EpiData version 3.5.1 and exported to SPSS version 20 for Windows for analysis. Serum concentration of Zn(+2), Mg(+2), Cr(+3), ferritin, and Fe(+3) in patients with type 2 diabetes was significantly lower (p<0.0001) than nondiabetes patients. In contrast, serum Cu(+2) was significantly higher (p<0.0001) in type 2 diabetes patients than nondiabetics. In addition, significant differences were not seen in both groups with regard to serum Mn(+2), Ca(+2), and Po4(-3). Waist-to-hip ratio (WHR), serum Fe(+3), ferritin, and Mn(+2) were significantly higher among oral hypoglycemic agent users of type 2 diabetes patients than the injectable insulin users. Serum Zn(+2) had significant positive correlation with serum Mg(+2) (r=0.738), Cr(+3) (r=0.233), Ca(+2) (r=0.238), and Po4(-3) (r=0.222). In addition, serum Zn(+2) had shown significant and negative correlation with body mass index (BMI, r=-0.331), WHR (r=-0.340), and fasting blood glucose (FBG, r=-0.186). Likewise, serum Mg(+2) and Po4(-3) are significantly and negatively correlated with BMI, WHR, and FBG. The imbalance of trace metal elements in the blood sample of diabetes is uncertain. Thus, we recommend a prospective cohort study to find out the principal factors behind the problem.

  14. Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis.

    PubMed

    Nielsen, Peter; Engelhardt, Rainer; Düllmann, Jochen; Fischer, Roland

    2002-01-01

    In the HFE-gene era, precise diagnostic parameters remain important to characterize individual iron stores, because the indication for therapy and prognosis are mainly related to the extent of iron loading. The frequently used serum ferritin interferes with non-iron related factors such as inflammation and may produce falsely positive values. We used a SQUID-biosusceptometer in a large series of patients (n = 679) to measure liver iron concentration in the differential diagnosis and therapy control of hereditary hemochromatosis (SQUID = superconducting quantum interference device). This truly non-invasive technique is sensitive, reliable, fast (online results), and also cost-effective when compared to invasive liver biopsy. Recently, ferritin iron content was propagated as a better parameter than ferritin protein. However, we found a poor correlation between ferritin iron and individual liver iron concentrations in patients with iron overload. Ferritin iron saturation varied in a range between 3 and 10%, independent from liver iron concentration. No differences were found between patients with hemochromatosis and secondary iron overload disease. Only patients with liver cell damage had increased ferritin iron saturations. In conclusion the diagnostic values of serum ferritin protein and iron to assess iron overload are limited.

  15. Endocrine involvement in children with beta-thalassaemia major. Transverse and longitudinal studies. I. Pituitary-thyroidal axis function and its correlation with serum ferritin levels.

    PubMed

    Cavallo, L; Licci, D; Acquafredda, A; Marranzini, M; Beccasio, R; Scardino, M L; Altomare, M; Mastro, F; Sisto, L; Schettini, F

    1984-09-01

    Thyroid function was investigated by a TRH test in 24 clinically prepubertal children, 3-15 years old with beta-thalassaemia major; in 7 of them the test was repeated once and in 2 twice at intervals of at least 12 months. Basal T4, T3, TBG and TSH levels and the TSH levels during a TRH test were determined and correlated with age and serum ferritin levels. Basal serum T4, T3 and TBG levels were lower and serum TSH levels were higher during the test and in the basal state in thalassaemia major children than in control children. These results show a compensated sub-clinical primary hypothyroidism. The transversal study did not show any significant correlation between the hormonal parameters studied and chronological age or serum ferritin levels. In contrast, the longitudinal study showed a significant correlation between pituitary-thyroidal axis function and siderosis (positive correlations between the variations of TSH levels as delta, peak, 30 and 45 min values and the variations of serum ferritin levels). The thyroid impairment seems not to be correlated with serum ferritin levels in the transversal study because of the presence of an individual different sensitivity of the gland to the iron overload. The ferritin dependence of this impairment is shown only by longitudinal studies where individual differences in sensitivity of the gland are absent.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L.

    PubMed

    Patel, Sheetal; Monemian, Seyed; Khalid, Ayesha; Dosik, Harvey

    2011-01-01

    Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  17. Evaluation of Iron Overload in the Heart and Liver Tissue by Magnetic Resonance Imaging and its Relation to Serum Ferritin and Hepcidin Concentrations in Patients with Thalassemia Syndromes.

    PubMed

    Karakus, Volkan; Kurtoğlu, Ayşegül; Soysal, Dilek Ersil; Dere, Yelda; Bozkurt, Selen; Kurtoğlu, Erdal

    2017-09-01

    Iron overload is one of the major prognostic factor in thallassemia patients. We aimed to evaluate iron accumulation in the heart and liver by MRI in thalassemia major, thalassemia intermedia, and S-ß thalassemia patients and to examine its association with ferritin and hepcidin levels. Serum ferritin and hepcidin levels were recorded. Iron overload (IOL) in the heart and liver parenchyma was determined based on the standardized T2* and R2 values measured by MRI. The results were evaluated considering the tissue iron overload, serum ferritin and hepcidin levels. Comparing the 109 patients with the 30 healthy controls revealed the mean age: 24.4 ± 11 versus 31.2 ± 5 years, median levels of serum ferritin: 1693 versus 40 ng/mL, and hepcidin: 1.94 versus 0.355 ng/mL; p < 0.001, respectively. Comparison of age, serum ferritin and hepcidin levels and MRI findings of the patients with or without IOL revealed that, ferritin and T2* were significantly different in the patients with IOL in cardiac tissue (p = 0.004 and p < 0.001), and, age, ferritin and R2 were significantly different in the patients with IOL in liver tissue (p = 0.036, p < 0.001 and p < 0.001). The MRI-based T2* and R2 values were moderately and inversely correlated with serum ferritin (r = -0.37; p < 0.001 and r = -0.46; p < 0.001). No correlations were found between the MRI-based T2*, R2 values and serum hepcidin. A moderate and positive correlation existed between serum ferritin and hepcidin (r = 0.45; p < 0.001). We considered that, enhanced intestinal iron absorption characterized by decreased serum hepcidin levels in the intervals between successive transfusions were resulted in iron accumulation in our patients.

  18. Association of serum ferritin levels with smoking and lung function in the Korean adult population: analysis of the fourth and fifth Korean National Health and Nutrition Examination Survey

    PubMed Central

    Lee, Chan Ho; Goag, Eun Kyung; Lee, Su Hwan; Chung, Kyung Soo; Jung, Ji Ye; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Song, Joo Han

    2016-01-01

    Background Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. Materials and methods Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study. Results The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. Conclusion Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher

  19. Maternal Serum Ferritin Concentration Is Positively Associated with Newborn Iron Stores in Women with Low Ferritin Status in Late Pregnancy123

    PubMed Central

    Shao, Jie; Lou, Jingan; Rao, Raghavendra; Georgieff, Michael K.; Kaciroti, Niko; Felt, Barbara T.; Zhao, Zheng-Yan; Lozoff, Betsy

    2012-01-01

    Iron deficiency (ID) is common in pregnant women and infants, particularly in developing countries. The relation between maternal and neonatal iron status remains unclear. This study considered the issue in a large sample of mother-newborn pairs in rural southeastern China. Hemoglobin (Hb) and serum ferritin (SF) were measured in 3702 pregnant women at ≥37 wk gestation and in cord blood of their infants born at term (37–42 wk gestation). Maternal anemia (Hb <110 g/L) was present in 27.5% and associated with maternal SF <20 μg/L in 86.9%. Only 5.6% of neonates were anemic (Hb <130 g/L) and 9.5% had cord-blood SF <75 μg/L. There were low-order correlations between maternal and newborn iron measures (r = 0.07–0.10 for both Hb and SF; P ≤ 0.0001 due to the large number). We excluded 430 neonates with suggestion of inflammation [cord SF >370 μg/L, n = 208 and/or C-reactive protein (CRP) >5 mg/L, n = 233]. Piecewise linear regression analyses identified a threshold for maternal SF at which cord-blood SF was affected. For maternal SF below the threshold of 13.6 μg/L (β = 2.4; P = 0.001), cord SF was 0.17 SD lower than in neonates whose mothers had SF above the threshold (167 ± 75 vs. 179 ± 80 μg/L). The study confirmed that ID anemia remains common during pregnancy in rural southeastern China. Despite widespread maternal ID, however, iron nutrition seemed to meet fetal needs except when mothers were very iron deficient. The impact of somewhat lower cord SF on iron status later in infancy warrants further study. PMID:23014493

  20. Raised serum ferritin concentration in hereditary hyperferritinemia cataract syndrome is not a marker for iron overload.

    PubMed

    Yin, Dan; Kulhalli, Vasu; Walker, Ann P

    2014-03-01

    Hyperferritinemia and bilateral cataracts are features of the rare hereditary hyperferritinemia cataract syndrome (HHCS; OMIM #600886). HHCS is an autosomal dominant condition caused by mutations which increase expression of the ferritin light polypeptide (FTL) gene. We report a patient with HHCS who was misdiagnosed and treated as having hemochromatosis, in whom a heterozygous c.-160A>G mutation was identified in the iron responsive element (IRE) of FTL, causing ferritin synthesis in the absence of iron overload. This report demonstrates the need for clinical awareness of HHCS as a cause of hyperferritinemia in the absence of iron overload and provides a possible diagnostic schema. © 2014 The Authors. HEPATOLOGY published by Wiley on behalf of the American Association for the Study of Liver Diseases.

  1. Hemoglobin and serum ferritin levels in women using copper-releasing or levonorgestrel-releasing intrauterine devices: a systematic review.

    PubMed

    Lowe, Richard F; Prata, Ndola

    2013-04-01

    The use of intrauterine devices as a contraceptive method has been steadily growing in developing countries. Anemia in reproductive-age women is a growing concern in those settings. A systematic review of studies with measured hemoglobin and serum ferritin at baseline and after 1 year of use of copper intrauterine devices (IUDs) or a levonorgestrel-releasing intrauterine system (LNG IUS) was performed. Fourteen studies involving copper IUDs in nonanemic women and 4 studies in anemic women and 6 involving the LNG IUS met the criteria for the systematic review. Meta-analyses for hemoglobin changes showed significant decreases for users of copper IUDs and an increase for the LNG IUS, but with limited data. In general, ferritin levels followed the same pattern. Decreases in hemoglobin mean values in copper IUD users were not sufficient to induce anemia in previously nonanemic women. Women who are borderline anemic would likely benefit from using the LNG IUS. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma.

    PubMed

    Yuan, Chuanshu; Yang, Kai; Tang, Hong; Chen, Dan

    2016-01-01

    At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1), squamous cell carcinoma antigen (SCCAg), ferritin, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and α-fetoprotein (AFP) for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC). One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (P<0.05). The levels of CA19-9 and AFP showed no significant difference between patients with OSCC/OPSCC, benign tumor, and healthy group (P>0.05). The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II) was significantly higher than that of benign tumor and healthy control group (P<0.05). However, the levels of serum SCCAg, ferritin, CEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05). The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV) were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (P<0.05). The diagnostic cutoff levels of Cyfra21-1, SCCAg, ferritin, and CEA were 2.17, 0.72, 109.95, and 1.99 ng/mL, respectively. The sensitivities were 60.36%, 73.37%, 81.66%, and 66.27%, respectively. The specificities were 81.03%, 68.10%, 40.52%, and 61.21%, respectively

  3. Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study

    PubMed Central

    Alessandrino, Emilio Paolo; Porta, Matteo Giovanni Della; Bacigalupo, Andrea; Malcovati, Luca; Angelucci, Emanuele; Van Lint, Maria Teresa; Falda, Michele; Onida, Francesco; Bernardi, Massimo; Guidi, Stefano; Lucarelli, Barbarella; Rambaldi, Alessandro; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Pascutto, Cristiana; Oneto, Rosi; Pirolini, Laura; Fanin, Renato; Bosi, Alberto

    2010-01-01

    Background Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified. Design and Methods We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007. Results Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload. Conclusions Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non

  4. The association between serum ferritin levels and the risk of new-onset type 2 diabetes mellitus: A 10-year follow-up of the Chinese Multi-Provincial Cohort Study.

    PubMed

    Gao, Shen; Zhao, Dong; Qi, Yue; Wang, Miao; Zhao, Fan; Sun, Jiayi; Liu, Jing

    2017-08-01

    To investigate the association of serum ferritin levels and ferritin level changes with the 10-year risk of new-onset type 2 diabetes mellitus (T2DM). Among 2359 subjects without T2DM at baseline in 2002, 1956 subjects were re-examined in 2007, and 1660 subjects were invited to be re-examined in 2012. Serum ferritin (ng/ml) levels were measured by latex-enhanced turbidimetric immunoassay. Five-year serum ferritin changes were categorized into four groups using the median as the cut-off point. Multivariate logistic regression was performed to examine the independent association of serum ferritin levels and 5-year ferritin level changes with 10-year new-onset T2DM. At the 10-year follow-up, 205 (12.3%) subjects had developed new-onset T2DM. After adjusting for traditional risk factors and high-sensitivity C-reactive protein, 10-year new-onset T2DM risk was significantly increased in subjects in the highest tertile of baseline serum ferritin levels [odds ratio (OR)=1.80, 95% confidence interval (CI): 1.17-2.79] and in subjects with high serum ferritin levels in both 2002 and 2007 (OR=1.54, 95% CI: 1.01-2.34). After adjusting for baseline fasting blood glucose, the effect was attenuated and became borderline or non-significant. Serum ferritin levels and ferritin level changes were associated with 10-year new-onset T2DM risk in the Chinese population, whereas the independent effect awaits validation from studies with larger sample sizes. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. FERROPORTIN Q248H, DIETARY IRON AND SERUM FERRITIN IN COMMUNITY AFRICAN AMERICANS WITH LOW TO HIGH ALCOHOL CONSUMPTION

    PubMed Central

    Gordeuk, Victor R.; Diaz, Sharmin F.; Onojobi, Gladys O.; Kasvosve, Ishmael; Debebe, Zufan; Edossa, Amanuel; Pantin, Jeremy M.; Xiong, Shigang; Nekhai, Sergei; Nouraie, Mehdi; Tsukamoto, Hidekazu; Taylor, Robert E.

    2012-01-01

    Background Alcohol consumption is associated with increased iron stores. In sub-Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African Americans. Methods Inner-city African Americans (103 men, 40 women) were recruited from the community according to reported ingestion of >4 alcoholic drinks per day or <2 per week. Typical daily heme iron, non-heme iron and alcohol were estimated using University of Hawaii’s multiethnic dietary questionnaire. Based on dietary questionnaire estimates we established categories of < versus ≥56 g alcohol per day, equivalent to 4 alcoholic drinks per day assuming 14 g alcohol per drink. Results Among 143 participants, 77% drank <56 g alcohol/day and 23% ≥56 g/d as estimated by the questionnaire. The prevalence of ferroportin Q248H was 23.3% with alcohol >56 g/d versus 7.5% with lower amounts (P=0.012). Among subjects with no history of HIV disease, serum ferritin concentration had positive relationships with male gender (P=0.041), alcohol consumption (P=0.021) and ALT concentration (P=0.0001) but not with dietary iron intake or ferroportin Q248H. Serum AST and ALT concentrations had significant positive associations with male gender and hepatitis C seropositivity but not with alcohol or dietary iron intake or ferroportin Q248H. Conclusions Our findings suggest a higher prevalence of ferroportin Q248H with greater alcohol consumption, and this higher prevalence raises the possibility that the allele might ameliorate the toxicity of alcohol. Our results suggest that alcohol but not dietary iron contributes to higher body iron stores in African Americans. Studies with larger numbers of participants are needed to further clarify the relationship of ferroportin Q248H with the

  6. A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE Hereditary Haemochromatosis

    PubMed Central

    Constantine, C. C.; Anderson, G. J.; Vulpe, C. D.; McLaren, C. E.; Bahlo, M.; Yeap, H. L.; Gertig, D. M.; Osborne, N. J.; Bertalli, N. A.; Beckman, K. B.; Chen, V.; Matak, P.; McKie, A. T.; Delatycki, M. B.; Olynyk, J. K.; English, D. R.; Southey, M. C.; Giles, G. G.; Hopper, J. L.; Allen, K. J.; Gurrin, L. C.

    2009-01-01

    There is emerging evidence that there are genetic modifiers of iron indices for HFE gene mutation carriers at risk of hereditary hemochromatosis. A random sample stratified by HFE genotype of 863 from a cohort of 31,192 people of northern European descent provided blood samples for genotyping of 476 SNPs in 44 genes involved in iron metabolism. Single SNP association testing using linear regression models adjusted for sex, menopause and HFE genotype was conducted for four continuously distributed outcomes: serum ferritin (log transformed), transferrin saturation, serum transferrin, and serum iron. The SNP rs884409 in CYBRD1 is a novel modifier specific to HFE C282Y homozygotes. Median unadjusted serum ferritin concentration decreased from 1194 µg/L (N=27) to 387 µg/L (N=16) for male C282Y homozygotes and from 357 µg/L (N=42) to 69 µg/L (N=12) for females, comparing those with no copies to those with one copy of rs884409. Functional testing of this CYBRD1 promoter polymorphism using a heterologous expression assay resulted in a 30% decrease in basal promoter activity relative to the common genotype (p=0.004). This putative genetic modifier of iron overload expression accounts for 11% (95% CI 0.4%, 22.6%) of the variance in serum ferritin levels of C282Y homozygotes. PMID:19673882

  7. Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis: A cross-sectional study.

    PubMed

    Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid

    2017-09-01

    There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children.All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated.Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%).The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis.

  8. Assessment of liver iron overload by T2-quantitative magnetic resonance imaging: correlation of T2-QMRI measurements with serum ferritin concentration and histologic grading of siderosis.

    PubMed

    Papakonstantinou, O G; Maris, T G; Kostaridou, V; Gouliamos, A D; Koutoulas, G K; Kalovidouris, A E; Papavassiliou, G B; Kordas, G; Kattamis, C; Vlahos, L J

    1995-01-01

    To correlate hepatic 1/T2 values obtained by means of a T2-Quantitative MRI (T2-QMRI) technique with three widely applied methods for the evaluation of hemosiderosis, i.e., (a) liver iron concentrations (LFeC) (b) serum ferritin (SF), and (c) histologic grading of siderosis. The impact of coexisting hepatitis was also considered. T2-QMRI measurements were compared with signal intensity (SI) ratio measurements on conventional SE images. Liver T2 relaxation times were calculated in 40 thalassemic patients, on a 0.5 T magnetic resonance imaging system using a multiple spin-echo sequence with parameters: TR = 2500 ms, TE = 12 ms in 20 symmetrically repeatable echoes. (a) 1/T2 values were well correlated (r = 0.97) with liver iron concentrations, which ranged from 2.32 to 18.0 mg/g dry weight (normal < 1.6 mg/g). (b) 1/T2 values were also correlated with serum ferritin levels (r = 0.84). At various 1/T2 values, serum ferritin levels were higher for the anti-HCV(+) patients than the anti-HCV(-) ones. (c) T2 values corresponding to successive grades of siderosis presented statistically significant differences. (d) SI ratio measurement assigned less statistically significant results, as compared to T2 values. T2-QMRI measurement of T2 relaxation time is more accurate than SI ratios in evaluating liver iron overload. It is particularly useful for hemosiderotic patients with coexisting hepatitis since, in this case, serum ferritin is not considered a reliable index of hemosiderosis.

  9. Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan.

    PubMed

    Riaz, Haris; Riaz, Talha; Khan, Muhammad Ubaid; Aziz, Sina; Ullah, Faizan; Rehman, Anis; Zafar, Qandeel; Kazi, Abdul Nafey

    2011-08-11

    Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required. The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis.Of the seventy-nine patients included in the study, 46 (58.2%) were males while 33 (41.8%) were females. The mean age was 10.8 (± 4.5) years with the dominant age group (46.2%) being 10 to 14 years. In 62 (78.8%) cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2%) cases with monthly house hold income significant factor to the use of therapy. The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients.Conflicts of Interest: None.

  10. ironPhone: Mobile device-coupled point-of-care diagnostics for assessment of iron status by quantification of serum ferritin.

    PubMed

    Srinivasan, Balaji; O'Dell, Dakota; Finkelstein, Julia L; Lee, Seoho; Erickson, David; Mehta, Saurabh

    2018-01-15

    Iron deficiency (ID) is an urgent public health problem that has devastating effects on maternal and child health. However, due to poor access and affordability, screening and diagnosis for ID is often limited to proxy hemoglobin measurements alone. Here, we report the development and validation of ironPhone, a mobile-device coupled portable diagnostics for quantification of serum ferritin concentrations, an iron status biomarker, within a few minutes, from a drop of fingerprick blood. The ironPhone diagnostic platform comprises of a smartphone accessory, an app, and a disposable lateral flow immunoassay test strip to quantify serum ferritin. For initial validation in the lab, we optimized and evaluated the performance of ironPhone with known ferritin concentrations in spiked buffer and serum samples. Following lab validation, we performed a human validation by collecting fingerprick whole blood samples from 20 participants to assess iron status using ironPhone and compared the results with the laboratory standard IMMULITE 2000 analyzer. Findings from the ironPhone for the buffer and spiked serum samples provided a calibration curve with R(2) values of 0.97 (n=27) and 0.93 (n=12), respectively. On comparison with the laboratory standard IMMULITE analyzer in whole blood samples, a correlation of 0.92 (P<0.0001) was observed with a sensitivity of over 90% for predicting ID (ferritin<15.0µg/L) via the ironPhone, demonstrating its promise for iron status assessment at the point-of-care. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  12. Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia.

    PubMed

    Taher, Ali T; Porter, John B; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Origa, Raffaella; Karakas, Zeynep; Habr, Dany; Zhu, Zewen; Cappellini, Maria Domenica

    2015-01-01

    Liver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non-transfusion-dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade(®) in non-transfusion-dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (<300 μg/l) and dose escalation (>2000 μg/l). (clinicaltrials.gov identifier: NCT00873041). © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  13. Deficiencies of Serum Ferritin and Vitamin B12, but not Folate, are Common in Adolescent Girls Residing in a Slum in Delhi.

    PubMed

    Gupta Bansal, Priyanka; Singh Toteja, Gurudayal; Bhatia, Neena; Kishore Vikram, Naval; Siddhu, Anupa; Kumar Garg, Ashok; Kumar Roy, Ashok

    2015-01-01

    Anemia among adolescent girls is one of the major challenges faced by India. The present study was undertaken to assess the prevalence of anemia and status of other hematological parameters among adolescent girls (11 - 18 years) residing in an urban slum of Delhi. A total of 794 adolescent girls were recruited for the study. The prevalence of anemia was estimated using the cyanmethemoglobin method. Serum levels of ferritin, folic acid and vitamin B12 were estimated for anemic subjects. The prevalence of anemia was reported as 58.7 %, with 31.6 %, 25.7 % and 1.4 % of subjects being mild, moderate and severely anemic. Hemoglobin levels of subjects who had attained menarche were found to be significantly lower than those who had not attained menarche. The prevalence of serum ferritin, folic acid and vitamin B12 deficiency among those who were anemic was reported as 41.1 %, 5.0 % and 63.3 % respectively. A total of 23.5 % anemic subjects had concomitant micronutrient deficiencies of serum vitamin B12 and ferritin. The results indicate that supplemental iron and vitamin B12 may better address the burden of anemia in adolescent girls in Delhi.

  14. Study of the correlation between serum ferritin levels and the aggregation of metabolic disorders in non-diabetic elderly patients.

    PubMed

    Li, Biqiang; Lin, Wei; Lin, Nan; Dong, Xiaowen; Liu, Libin

    2014-06-01

    The present study aimed to explore the correlation between serum ferritin (SF) levels and the aggregation of metabolic disorders in non-diabetic elderly patients. A total of 2,600 patients were enrolled in the study. Various parameters, including blood pressure (BP), height, weight, lipid profiles, blood glucose (BG), body mass index (BMI), fasting insulin (FINS), serum uric acid (SUA), the urinary albumin/creatinine ratio (UACR) and SF levels were measured. A homeostatic model was used to evaluate insulin resistance (HOMA-IR) and β-cell function (HOMA-β). The quantitative insulin sensitivity check index (QUICKI) and disposition index (DI) were calculated. The QUICKI and DI decreased significantly and other parameters increased significantly when the number of metabolic disorders increased. Patients with high triglycerides (TG), high total cholesterol (TC), high SUA and obesity demonstrated higher SF levels than those with normal TG, normal TC, normal SUA and normal weight, respectively (P<0.01). Male patients with metabolic disorders (high TG, high TC, high BP, high SUA and obesity) had higher SF levels than female patients with the corresponding disorders (P<0.01). BG, FINS, BMI, TC, TG, SUA, HOMA-IR and HOMA-β were positively correlated with SF, while DI and QUICKI were negatively correlated with SF (P<0.01). Stepwise regression analysis showed that HOMA-IR, BMI, TC, TG and SUA were risk factors for elevated SF levels. In conclusion, the SF levels in non-diabetic, elderly individuals with metabolic disorders may be significantly related to the clustering of the metabolic disorders. Dyslipidemia, obesity, disorders of purine metabolism and insulin resistance may be important risk factors for higher SF levels in the elderly.

  15. Association between Serum Ferritin Concentrations and Depressive Symptoms among Chinese Adults: A Population Study from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study

    PubMed Central

    Yu, Bin; Yu, Fei; He, Haiyan; Zhang, Qing; Meng, Ge; Wu, Hongmei; Du, Huanmin; Liu, Li; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Bao, Xue; Liu, Fangfang; Fang, Liyun; Yang, Huijun; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Song, Kun; Niu, Kaijun

    2016-01-01

    Depressive symptoms have become the most important global public health issue. Iron plays an important role in brain function, cognition, and behavior, and its impacts on depressive symptoms may be multifactorial with both positive and negative effects. Previous observational studies focusing on the association between iron status and depressive symptoms showed inconsistent results. Ferritin is a ubiquitous intracellular protein that can store and release iron and is widely used as a clinical biomarker to evaluate iron status. We performed a cross-sectional study to examine the relationship between serum ferritin and depressive symptoms among 3,839 subjects who were from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort. Depressive symptoms were assessed using the Chinese version of 20-item self-rating Depression Scale (SDS) with 4 cutoffs (40, 45, 48 and 50) to indicate elevated depressive symptoms (40 was the primary cut-off). The prevalence of depressive symptoms was 36.5%, 17.6%, 11.0% and 7.0% for SDS ≥40, ≥45, ≥48 and ≥50, respectively. With the primary cut-off point of 40, multiple potential confounding factors were adjusted and the odds ratios (95% confidence interval) of having elevated depressive symptoms by quartiles of serum ferritin concentrations were 1.00 (reference), 1.10 (0.91, 1.34), 0.81 (0.66, 1.01) and 1.02 (0.81, 1.28) for the first, second, third and fourth quartile, respectively (P for trend = 0.76). Similar relations were observed with the use of other cut-offs as a definition of depressive symptoms. In conclusion, there is no significant relationship between serum ferritin concentrations and depressive symptoms among Chinese adults. PMID:27611581

  16. Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2* MRI assessment.

    PubMed

    Chirico, Valeria; Rigoli, Luciana; Lacquaniti, Antonio; Salpietro, Vincenzo; Piraino, Basilia; Amorini, Maria; Salpietro, Carmelo; Arrigo, Teresa

    2015-05-01

    Endocrinopathies and metabolic disorders-characterized β thalassemic (βT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in βT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. Seventy-two βT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan-Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. High ferritin levels were observed in patients with hypothyroidism [1500 (872.5-2336.5) μg/L], hypogonadism [878 (334-2010) μg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367-1857) μg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = -0.64; P:0.0006) and liver (r = -0.40; P:0.03) values was observed. Patients with ferritin values above 1800 μg/L experienced a significantly faster evolution to hypothyroidism [log-rank (χ(2) ):7.7; P = 0.005], hypogonadism [log-rank (χ(2) ):10.7; P = 0.001], and multiple endocrinopathies [log-rank (χ(2) ):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P < 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. Ferritin represents a prognostic marker for βT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility

  17. Higher Serum Ferritin Levels Correlate with an Increased Risk of Cutaneous Morbidity in Adult Patients with β-Thalassemia: A Single-Center Retrospective Study.

    PubMed

    Skandalis, Konstantinos; Vlachos, Christoforos; Pliakou, Xanthi; Gaitanis, Georgios; Kapsali, Eleni; Bassukas, Ioannis D

    2016-01-01

    Disturbed iron homeostasis characterizes β-thalassemia and increases its morbidity. Our aim was to retrospectively associate β-thalassemia disease characteristics with treatment-requiring skin conditions. The files of adult β-thalassemia (including sickle β-thalassemia) patients were screened over a 10-year period for treatment-requiring skin disease episodes and their correlation with hematologic diagnoses and epidemiological and serological characteristics. Seventy-eight patients were identified, and 7 (9%) developed at least one relevant episode including cutaneous small-vessel vasculitis (CSVV), urticaria, and leg ulcers. Average ferritin serum level correlated significantly with development of a dermatosis (2,034 ± 799 μg/l in cases vs. 920 ± 907 μg/l in the overall population; p = 0.001, ANOVA). This difference relied exclusively on the high ferritin levels observed in patients with 'generalized' dermatoses (urticaria and CSVV: 3,860 ± 1,220 μg/l) as opposed to values within the normal range in the case of 'localized' ones (leg ulcers: 662 ± 167 μg/l). The employed iron chelation treatment influenced ferritin levels (p = 0.002, Kruskal-Wallis test) since chelation with a single agent seems to increase the risk of a skin disease (p = 0.013, likelihood ratio method). Conclusively, serum ferritin can be evaluated as risk factor for generalized dermatoses, but not for leg ulcers, in patients with the β-thalassemia genotype. This risk can be efficiently controlled with adequate chelation. © 2015 S. Karger AG, Basel.

  18. 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

  19. Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

    PubMed

    Lee, C S; Lee, S D; Kang, S-H; Park, H Y; Yoon, I-Y

    2014-02-01

    It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

  20. Comparison of Tissue Elastography With Magnetic Resonance Imaging T2* and Serum Ferritin Quantification in Detecting Liver Iron Overload in Patients With Thalassemia Major.

    PubMed

    Pipaliya, Nirav; Solanke, Dattatray; Parikh, Pathik; Ingle, Meghraj; Sharma, Ratna; Sharma, Sujata; Sawant, Prabha

    2017-02-01

    We investigated whether tissue elastography (TE) can be used as an alternative to magnetic resonance imaging (MRI) T2* analysis to determine the degree of iron overload in patients with thalassemia major. We conducted a prospective study of 154 patients (99 male; mean age, 12 ± 3.6 years) with thalassemia major requiring chronic blood transfusion and on iron chelator therapy. The study was performed at a tertiary hospital in India from January 2015 through June 2015. We performed routine blood sample analyses, measurements of serum levels of ferritin, and TE within 1 month of MRI T2* analysis of the liver. The Spearman correlation test and linear regression analysis were used to evaluate the correlation between TE liver stiffness measurements and R2* MRI results or serum ferritin levels. The subjects' mean total serum levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, and albumin were 1.4 ± 0.6 mg/dL, 65.0 ± 51.8 IU/L, 62.9 ± 44 IU/L, and 4.2 ± 0.2 g/d, respectively. Mean liver stiffness measurement, MRI T2* (3 T), corresponding MRI R2* (3 T), and ferritin values were 8.2 ± 4.4 kPa, 3.18 ± 2.6 milliseconds, 617.3 ± 549 Hz, and 4712 ± 3301 ng/mL, respectively. On the basis of MRI analysis, 67 patients (43.5%) had mild iron overload, 49 patients (31.8%) had moderate iron overload, and 22 patients (14.3%) had severe iron overload. Fibroscan liver stiffness measurements correlated with MRI R2* values (r = 0.85; P < .001). TE results identified the patients with severe, moderate, and mild iron overload with area under the receiver operating characteristic curve values of 94.8%, 84.5%, and 84.7%, respectively. Liver stiffness measurements greater than 13.5, 7.8, and 5.5 kPa identified patients with severe, moderate, and mild iron overload, respectively; the sensitivity and specificity values were 92% and 93% for severe overload, 82% and 82% for moderate overload, and 73% and 75% for mild overload. No correlation was found between TE

  1. Effect of sodium iron ethylenediaminetetra-acetate (NaFeEDTA) on haemoglobin and serum ferritin in iron-deficient populations: a systematic review and meta-analysis of randomised and quasi-randomised controlled trials.

    PubMed

    Wang, Bo; Zhan, Siyan; Xia, Yinyin; Lee, Liming

    2008-12-01

    We aimed to synthesise evidence to assess the effect and safety of NaFeEDTA on Hb and serum ferritin in Fe-deficient populations. We performed a systematic review, identifying potential studies by searching the electronic databases of Medline, Cochrane Library, Embase, WHO Library and China National Knowledge Infrastructure. We also hand-searched relevant conference proceedings and reference lists. Finally, we contacted experts in the field. The selection criteria included randomised or quasi-randomised controlled trials of NaFeEDTA compared with placebo. Hb, serum ferritin and adverse effects were outcomes of interest. Inclusion decisions, quality assessment and data extraction were performed by two reviewers independently. Seven studies met the inclusion criteria. All included studies assessed the effect of NaFeEDTA on Hb concentration, four studies assessed the effect on serum ferritin concentration, and one study on serum Zn concentration. After the intervention, Hb concentration and serum ferritin concentration were both higher in the NaFeEDTA group compared with the control group. For Hb, data from six studies could be pooled and the pooled estimate (weighted mean difference) was 8.56 (95 % CI 2.21, 14.90) g/l (P = 0.008). For serum ferritin, data from four studies could be pooled and the pooled difference was 1.58 (95 % CI 1.20, 2.09) microg/l (P < 0.001). Subgroup analysis indicated that a lower baseline Hb level was associated with a greater increase in Hb concentration. No significant difference in serum Zn concentration was found. We concluded that NaFeEDTA increased both Hb concentration and serum ferritin concentration substantially in Fe-deficient populations, and could be an effective Fe preparation to combat Fe deficiency.

  2. 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....

  3. 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....

  4. Ferritin, finger clubbing, and lung disease.

    PubMed Central

    Shneerson, J M; Jones, B M

    1981-01-01

    The serum ferritin concentration has been determined by an immunoradiometric assay in 90 subjects with a variety of pulmonary diseases. No association between ferritin concentrations and finger clubbing has been found in any of the diseases studied. Ferritin levels were significantly raised in the subjects with bronchial carcinoma, but were not useful in monitoring recurrence of the tumour. Pulmonary artery and pulmonary vein ferritin concentrations were similar to systemic venous concentrations. It is therefore unlikely that the tumour releases ferritin into the pulmonary circulation. Ferritin levels were raised in patients with acute pneumonias but did not correlate with the total white cell count or erythrocyte sedimentation rate. Serum ferritin concentrations were also increased in a variety of chronic lung diseases but were normal in subjects with asbestosis. PMID:7314044

  5. Relationship between myocardial T2 values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels.

    PubMed

    Liguori, Carlo; Pitocco, Francesca; Di Giampietro, Ilenia; de Vivo, Aldo Eros; Schena, Emiliano; Cianciulli, Paolo; Zobel, Bruno Beomonte

    2013-09-01

    Myocardial T2 cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2 value in myocardium and left-right ventricular volumetric and functional parameters and to evaluate the existing associations between left-right ventricles volumetric and functional parameter, myocardial T2 values and blood ferritin levels. A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2 measurements, and volumetric functions were analyzed using the steady state free precession sequence. A significant correlation was observed between EFLV and T2 (p=0.0001), EFRV and T2 (p=0.0279). An inverse correlation was present between DVLV and T2 (p=0.0468), SVLV and T2 (p=0.0003), SVRV and T2 (p=0.0001). There was no significant correlation between cardiac T2 and LV-RV mass indices. A significant correlation was observed between T2 and serum ferritin levels (p<0.001) and between EFLV and serum ferritin (p<0.05). Myocardial iron load assessed by T2 cardiac magnetic resonance is associated with deterioration in left-right ventricular function; this is more evident when T2 values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. 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

  7. Causes and prognostic value of pre-transplant elevated kynurenine level in kidney allograft recipients.

    PubMed

    Kaden, Jürgen; Abendroth, Dietmar; Völp, Andreas; Marzinzig, Michael; Wesslau, Claus

    2014-01-27

    The activation of the tryptophane catabolizing enzyme Indoleamine 2,3-dioxygenase leads to the formation of kynurenine and other metabolites that counter-regulate immune activation resulting in restoration of immune homeostasis. But in chronic immune activation, as in hemodialysed patients, the immunosuppressive feedback mechanisms continue as indicated by elevated kynurenine concentrations. However, its relevance is still a matter of debate. This retrospective analysis presents the pre-transplant kynurenine levels (quantified photometrically) of 307 kidney graft recipients in connection with some pre- and post-transplant variables and the type of immunosuppression (cyclosporine-based triple drug therapy without/with ATG-Fresenius-induction). Statistical analyses performed were analysis of variance, Scheffé's test for pairwise comparisons, Cox regression, Spearman's rank correlation, and extended segmentation analysis. The pre-transplant kynurenine level was significantly elevated as compared to healthy adults (14.1±5.9 vs. 2.7±0.6 nmol/ml, p<0.0001), significantly higher in PRA positive than in PRA negative patients (16.1 vs. 12.9 nmol/ml, p<0.001) and, supporting this observation, also higher (p<0.0001) in a cohort with predominant (89.7%) pre-sensitized patients (16.4±6.4 nmol/ml) having the longest time on the waiting list (median 39 months) as compared to cohorts with fewer (16.8-22%) pre-sensitized patients (12.7±4.4 resp. 13.4±5.8 nmol/ml) having shorter times on the waiting list (16-24 months). Patients with immediately functioning grafts showed a lower pre-transplant kynurenine level than patients with non-immediately functioning grafts (13.5±6.0 vs. 14.9±5.7 nmol/ml, p=0.053). No associations were found with basic diseases, rejections, or graft survival. The pre-transplant elevated serum kynurenine levels were highly associated with the patient's pre-sensitization status and their longer time on hemodialysis treatments, but did not allow

  8. Low body weight gain, low white blood cell count and high serum ferritin as markers of poor nutrition and increased risk for preterm delivery.

    PubMed

    Hsu, Wen-Yin; Wu, Cheng-Hsuan; Hsieh, Charles Tsung-Che; Lo, Hui-Chen; Lin, Jen-Shiou; Kao, Mei-Ding

    2013-01-01

    This study determined factors of preterm delivery in Taiwan. Healthy women (n=520, age 29.1±4.2 y) at 8-12 weeks of pregnancy were recruited from prenatal clinics. Background information, anthropometrics, biochemical parameters, and dietary intake, collected by 24 h-recall were obtained from the first, second, and third trimesters to delivery. Clinical outcomes of neonates were also collected. The results show that 53.7% of women were primiparous and that the incidence of preterm delivery was 6.2%. Body weight gains in the first trimester and throughout pregnancy were significantly lower in mothers with preterm delivery (preterm group) than in mothers with term delivery (term group, p<0.05). Maternal cholesterol intake, circulating white blood cell counts (WBC) and serum albumin were significantly lower and that serum magnesium and ferritin were significantly higher in the preterm group than in the term group. Maternal weight gain was positively correlated with caloric and nutrient intake (p<0.05). Neonatal birth weight was positively correlated with maternal weight gain and intakes of protein and phosphate during pregnancy; with intakes of calories, vitamin B-1 and B-2 in the first trimester; and with intakes of calcium, magnesium, iron and zinc, as well as circulating WBC in the third trimester. However, neonatal birth weight was negatively correlated with serum iron in the third trimester and with serum iron and ferritin at the time of delivery. In conclusion, maternal weight gain in early pregnancy and WBC, mineral intake and iron status in late pregnancy seem to be major factors affecting delivery and neonatal outcomes.

  9. Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans.

    PubMed

    Li, Jin; Lange, Leslie A; Duan, Qing; Lu, Yurong; Singleton, Andrew B; Zonderman, Alan B; Evans, Michele K; Li, Yun; Taylor, Herman A; Willis, Monte S; Nalls, Mike; Wilson, James G; Lange, Ethan M

    2015-01-15

    Iron is an essential component of many important proteins and enzymes, including hemoglobin, which is responsible for carrying oxygen to the cells. African Americans (AAs) have a greater prevalence of iron deficiency compared with European Americans. We conducted genome-wide admixture-mapping and association studies for serum iron, serum ferritin, transferrin saturation (SAT) and total iron binding capacity (TIBC) in 2347 AAs participating in the Jackson Heart Study (JHS). Follow-up replication analyses for JHS iron-trait associated SNPs were conducted in 329 AA participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS). Higher estimated proportions of global African ancestry were significantly associated with lower levels of iron (P = 2.4 × 10(-5)), SAT (P = 0.0019) and TIBC (P = 0.042). We observed significant associations (P < 5 × 10(-8)) between serum TIBC levels and two independent SNPs around TF on chromosome 3, the first report of a genome-wide significant second independent signal in this region, and SNPs near two novel genes: HDGFL1 on chromosome 6 and MAF on chromosome 16. We also observed significant associations between ferritin levels and SNPs near GAB3 on chromosome X. We replicated our two independent associations at TF and our association at GAB3 in HANDLS. Our study provides evidence for both shared and unique genetic risk factors that are associated with iron-related measures in AAs. The top two variants in TF explain 11.2% of the total variation in TIBC levels in AAs after accounting for age, gender, body mass index and background ancestry.

  10. Accuracy of erythrogram and serum ferritin for the maternal anemia diagnosis (AMA): a phase 3 diagnostic study on prediction of the therapeutic responsiveness to oral iron in pregnancy

    PubMed Central

    2013-01-01

    Background Pregnancy anemia remains as a public health problem, since the official reports in the 70’s. To guide the treatment of iron-deficiency anemia in pregnancy, the haemoglobin concentration is the most used test in spite of its low accuracy, and serum ferritin is the most reliable test, although its cutoff point remains an issue. Methods/design The aim of this protocol is to verify the accuracy of erythrocyte indices and serum ferritin (studied tests) for the diagnosis of functional iron-deficiency in pregnancy using the iron-therapy responsiveness as the gold-standard. This is an ongoing phase III accuracy study initiated in August 2011 and to be concluded in April 2013. The subjects are anemic pregnant women (haemoglobin concentration < 11.0 g/dL) attended at a low-risk prenatal care center in the Northeast of Brazil. The sample size (n 278) was calculated to estimate sensitivity of 90% and 80% of specificity with relative error of 10% and power of 95%. This study has a prospective design with a before-after intervention of 80 mg of daily oral iron during 90 days and will be analyzed as a delayed-type cross-sectional study. Women at the second trimester of pregnancy are being evaluated with clinical and laboratorial examinations at the enrollment and monthly. The ‘responsiveness to therapeutic test with oral iron’ (gold-standard) was defined to an increase of at least 0.55 Z-score in haemoglobin after 4 weeks of treatment and a total dose of 1200 mg of iron. At the study conclusion, sensitivities, specificities, predictive values, likelihood ratios and areas under the ROC (Receiver Operating Characteristic) curves of serum ferritin and erythrocyte indices (red blood cell count, haematocrit, haemoglobin concentration, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, reticulocyte count) will be tested. The compliance and adverse effects are considered

  11. INCIDENCE AND EARLY OUTCOMES ASSOCIATED WITH PRE-TRANSPLANT ANTI-VIMENTIN ANTIBODIES IN THE CARDIAC TRANSPLANTATION POPULATION

    PubMed Central

    Young, Raymond K.; Dale, Bethany; Russell, Stuart D.; Zachary, Andrea A.; Tedford, Ryan J.

    2015-01-01

    Background In cardiac transplant recipients, the development of antibodies to the endothelial intermediate filament protein vimentin (anti-vimentin antibodies, AVA) has been associated with rejection and poor outcomes. However, the incidence of these antibodies prior to transplantation and their association with early rejection has not been investigated. Methods Pre-transplant serum was analyzed from 50 patients who underwent de novo cardiac transplant at Johns Hopkins Hospital from 2004-2012. Demographic, one year rejection, and survival data were obtained from the transplant database. Results The incidence of pre-transplant AVA was 34%. AVA positive patients were younger (p=0.03) and there was an increased incidence in females (p=0.08). Demographic data were similar among both groups. AVA positivity did not predict rejection in the 1st year post-transplant. There was no difference in rejection-free graft survival (53 vs. 52%, p=0.85) at 1 year. Similarly there was no difference in graft survival at 1 year (82 vs. 88%, p=0.56) or graft survival at a median follow up of 23 and 26 months, respectively (76 vs. 85%, p=0.41). Conclusions AVA is common in the cardiac pre-transplant population with a higher incidence in the young. The presence of detectable AVA did not correlate with early post-transplant rejection or graft survival. PMID:25982351

  12. Ferritin Protein Nanocage Ion Channels

    PubMed Central

    Tosha, Takehiko; Behera, Rabindra K.; Ng, Ho-Leung; Bhattasali, Onita; Alber, Tom; Theil, Elizabeth C.

    2012-01-01

    Ferritin protein nanocages, self-assembled from four-α-helix bundle subunits, use Fe2+ and oxygen to synthesize encapsulated, ferric oxide minerals. Ferritin minerals are iron concentrates stored for cell growth. Ferritins are also antioxidants, scavenging Fenton chemistry reactants. Channels for iron entry and exit consist of helical hairpin segments surrounding the 3-fold symmetry axes of the ferritin nanocages. We now report structural differences caused by amino acid substitutions in the Fe2+ ion entry and exit channels and at the cytoplasmic pores, from high resolution (1.3–1.8 Å) protein crystal structures of the eukaryotic model ferritin, frog M. Mutations that eliminate conserved ionic or hydrophobic interactions between Arg-72 and Asp-122 and between Leu-110 and Leu-134 increase flexibility in the ion channels, cytoplasmic pores, and/or the N-terminal extensions of the helix bundles. Decreased ion binding in the channels and changes in ordered water are also observed. Protein structural changes coincide with increased Fe2+ exit from dissolved, ferric minerals inside ferritin protein cages; Fe2+ exit from ferritin cages depends on a complex, surface-limited process to reduce and dissolve the ferric mineral. High concentrations of bovine serum albumin or lysozyme (protein crowders) to mimic the cytoplasm restored Fe2+ exit in the variants to wild type. The data suggest that fluctuations in pore structure control gating. The newly identified role of the ferritin subunit N-terminal extensions in gating Fe2+ exit from the cytoplasmic pores strengthens the structural and functional analogies between ferritin ion channels in the water-soluble protein assembly and membrane protein ion channels gated by cytoplasmic N-terminal peptides. PMID:22362775

  13. Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women.

    PubMed

    Muslimatun, S; Schmidt, M K; Schultink, W; West, C E; Hautvast, J A; Gross, R; Muhilal

    2001-01-01

    We investigated whether weekly iron supplementation was as effective as the national daily iron supplementation program in Indonesia in improving iron status at near term in pregnancy. In addition, we examined whether weekly vitamin A and iron supplementation was more efficacious than weekly supplementation with iron alone. One group of pregnant women (n = 122)was supplemented weekly with iron (120 mg Fe as FeSO4) and folic acid (500 microg); another group (n = 121) received the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. A third ("daily") group (n = 123), participating in the national iron plus folic acid supplementation program, was also recruited. Data on subjects with complete biochemical data are reported (n = 190). At near term, hemoglobin concentrations increased, whereas serum ferritin concentrations decreased significantly in the weekly vitamin A and iron group, suggesting that vitamin A improved utilization of iron for hematopoiesis. Iron status in the weekly iron group was not different from that of the "daily" group. However, iron status decreased with daily supplementation if <50 iron tablets were ingested. Serum transferrin receptor concentrations increased in all groups (P < 0.01). Serum retinol concentrations were maintained in the weekly vitamin A and iron group, but decreased in the other two groups (P < 0.01). Thus, delivery of iron supplements on a weekly basis can be as effective as ona daily basis if compliance can be ensured. Addition of vitamin A to the supplement improved hemoglobin concentration.

  14. Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure

    PubMed Central

    Govus, Andrew D.; Garvican-Lewis, Laura A.; Abbiss, Chris R.; Peeling, Peter; Gore, Christopher J.

    2015-01-01

    Purpose To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass) and iron parameters after 2–4 weeks of moderate altitude exposure. Methods Hematological data collected from 178 athletes (98 males, 80 females) exposed to moderate altitude (1,350–3,000 m) were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII) and blood iron parameters [ferritin and transferrin saturation (TSAT)]. Results Altitude exposure (mean ± s: 21 ± 3 days) increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d) = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d) = -2.87 [-3.88, -1.66]). Conclusion Oral iron supplementation during 2–4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores. PMID:26263553

  15. End-Stage Renal Disease after Liver Transplantation in Patients with Pre-Transplant Chronic Kidney Disease

    PubMed Central

    Bahirwani, Ranjeeta; Forde, Kimberly A.; Mu, Yifei; Lin, Fred; Reese, Peter; Goldberg, David; Abt, Peter; Reddy, K Rajender; Levine, Matthew

    2014-01-01

    Renal dysfunction prior to liver transplantation has a marked impact on post-transplant kidney outcomes. The aim of this study was to assess post-transplant renal function in patients with chronic kidney disease (CKD) receiving orthotopic liver transplantation (OLT) alone. METHODS Retrospective review of 40 OLT recipients with pre-transplant CKD (serum creatinine ≥ 2 mg/dl for at least 3 months) at the University of Pennsylvania from February 2002 to July 2010. Primary outcome was estimated glomerular filtration rate (eGFR) up to 3 years post-transplant. Secondary outcomes included incidence of stage 4 CKD (eGFR < 30 ml/min), need for renal replacement therapy (RRT), meeting criteria for kidney transplant listing (eGFR ≤ 20 ml/min), and mortality. RESULTS Median patient age was 56.5 years and 48% patients had pre-transplant diabetes. Median serum creatinine at transplant was 2.7 mg/dl (eGFR 24 ml/min). Median eGFR at 1, 2, and 3 years post-transplant was 35, 34, and 37 ml/min respectively. Twelve patients (30%) required RRT at a median of 1.21 years posttransplant and 16 (40%) achieved an eGFR ≤ 20 ml/min at 1.09 years post-transplant. Mortality was 35% at a median of 1.60 years post-transplant. CONCLUSIONS OLT recipients with pre-transplant CKD have a substantial burden of post-transplant renal dysfunction and high short-term mortality, questioning the rationale for OLT alone in this population. PMID:24382253

  16. Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in Native Americans and whites in the Hemochromatosis and Iron Overload Screening Study.

    PubMed

    Barton, J C; Acton, R T; Lovato, L; Speechley, M R; McLaren, C E; Harris, E L; Reboussin, D M; Adams, P C; Dawkins, F W; Gordeuk, V R; Walker, A P

    2006-01-01

    We compared initial screening transferrin saturation (TfSat) and serum ferritin (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and 43,453 white Hemochromatosis and Iron Overload Screening Study participants who did not report a previous diagnosis of hemochromatosis or iron overload. Elevated measurements were defined as TfSat >50% in men and >45% in women and SF >300 ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in white women (p < 0.0001). Mean SF was 153 microg/l in Native American and 151 microg/l in white men (p = 0.8256); mean SF was 55 microg/l in Native American women and 63 microg/l in white women (p = 0.0015). The C282Y allele frequency was 0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We conclude that the screening TfSat and SF phenotypes of Native Americans are similar to those of whites. The allele frequencies of HFE C282Y and H63D are significantly lower in Native Americans than in whites.

  17. A prospective randomized wait list control trial of intravenous iron sucrose in older adults with unexplained anemia and serum ferritin 20-200 ng/mL.

    PubMed

    Price, Elizabeth; Artz, Andrew S; Barnhart, Huiman; Sapp, Shelly; Chelune, Gordon; Ershler, William B; Walston, Jeremy D; Gordeuk, Victor R; Berger, Nathan A; Reuben, David; Prchal, Josef; Rao, Sunil V; Roy, Cindy N; Supiano, Mark A; Schrier, Stanley L; Cohen, Harvey Jay

    2014-12-01

    Anemia is common in older persons and is associated with substantial morbidity and mortality. One third of anemic older adults have unexplained anemia of the elderly (UAE). We carried out a randomized, wait list control trial in outpatients with UAE and serum ferritin levels between 20 and 200 ng/mL. Intravenous iron sucrose was given as a 200-mg weekly dose for 5 weeks either immediately after enrollment (immediate intervention group) or following a 12-week wait list period (wait list control group). The primary outcome measure was changed in 6-minute walk test (6MWT) distances from baseline to 12 weeks between the two groups. Hematologic, physical, cognitive, and quality of life parameters were also assessed. The study was terminated early after 19 subjects enrolled. The distance walked in the 6MWT increased a mean 8.05±55.48 m in the immediate intervention group and decreased a mean 11.45±49.46 m in the wait list control group (p=0.443). The hemoglobin increased a mean 0.39±0.46 g/dL in the immediate intervention group and declined a mean 0.39±0.85 g/dL in the wait list control group (p=0.026). Thus, a subgroup of adults with UAE may respond to intravenous iron. Enrollment of subjects into this type of study remains challenging.

  18. 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

  19. Failure of twice-weekly iron supplementation to increase blood haemoglobin and serum ferritin concentrations: results of a randomized controlled trial.

    PubMed

    Olsen, A; Nawiri, J; Magnussen, P; Krarup, H; Friis, H

    2006-04-01

    In order to increase the intestinal absorption of iron whilst simultaneously minimising the side-effects and thus increasing compliance, once- or twice-weekly, instead of daily, iron supplementation has been widely recommended. In a randomized, placebo-controlled, double-blind study in western Kenya, a tablet of ferrous dextran (containing 60 mg elemental iron) or an identical-looking placebo tablet was provided twice-weekly for 12 months to each child or adult investigated. At baseline each subject had a moderately low blood concentration of haemoglobin (Hb). Initial Hb and serum ferritin (SF) concentrations were determined and each subject was tested for malarial and helminth infection and treated, if necessary, with the appropriate anthelminthic drug(s). Overall, 200 children (aged 4-15 years) and 129 adults (aged 16-63 years) completed the 12-month study. At baseline, 47.5% of the children and 58.1% of the adults were anaemic, hookworm (detected in 60.0% of the children and 69.9% of the adults) was the most common helminth infection, and malaria was endemic. The results of bivariate analyses indicated that twice-weekly iron supplementation had no significant effect on blood Hb or SF concentrations, either in the children or the adults investigated. The results were confirmed in multiple linear-regression analyses, which revealed that the predictors of the final Hb concentration in the children investigated were age and infection, after enrollment, with Ascaris lumbricoides. Gender and the serum concentration of alpha-1-antichymotrypsin (ACT) at final follow-up were predictors of the final SF concentration in the children. In adults, the predictors of the final Hb concentration were gender and HIV infection, and the predictors of the final SF concentration were age and the serum concentration of ACT at the final follow-up. Twice-weekly iron supplementation did not increase Hb or iron stores in children or adults. Since compliance appeared to be high, this lack

  20. [Value of combined measurement of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase and serum ferritin in etiological diagnosis of fever of unknown origin in children].

    PubMed

    Xie, Ting; Pan, Jia-Hua; Zhang, Xue

    2015-09-01

    To study the clinical value of combined measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and serum ferritin (SF) in the etiological diagnosis of fever of unknown origin (FUO) in children. The clinical data of 154 hospitalized children who had FUO for at least two weeks were retrospectively analyzed, and they were classified into infection (n=54), rheumatism (n=67), and tumor (n=33) groups according to the diagnosis at discharge. The levels of CRP, ESR, LDH, and SF were compared between the three groups, and the diagnostic values of the four indices alone or together were analyzed using the receiver operating characteristic (ROC) curve. Serum CRP and ESR levels were elevated in all the three groups, and increased most significantly in the rheumatism group. Serum LDH level was increased most significantly in the tumor group. SF level was significantly increased in the rheumatism and tumor groups. The area under the ROC curve (AUC) of LDH for diagnosing rheumatism and the AUC of ESR and CRP for diagnosing tumors were lower than 0.7 (P>0.05). The AUC of CRP for diagnosing infection and rheumatism was 0.861 and 0.782, respectively. The AUC of ESR for diagnosing infection and rheumatism was 0.770 and 0.743, respectively. LDH had relatively low AUC, sensitivity, specificity, and Youden's index in diagnosing infection and tumors. SF had the highest AUC, sensitivity, and Youden's index in diagnosing infection, but had the lowest specificity. SF had relatively high AUC, sensitivity, specificity, and Youden's index in diagnosing rheumatism, but had relatively low AUC in diagnosing tumor. The four indices had higher AUC, sensitivity, and specificity in diagnosing rheumatism and tumors when measured together than when measured alone. In the etiological diagnosis of FUO in children, CRP, ESR, LDH, and SF have certain clinical significance in the preliminary diagnosis of rheumatic diseases, but have limited value in the

  1. Impact of non-transferrin-bound iron (NTBI) in comparison to serum ferritin on outcome after allogeneic stem cell transplantation (ASCT).

    PubMed

    Hilken, Annekathrin; Langebrake, Claudia; Wolschke, Christine; Kersten, Jan Felix; Rohde, Holger; Nielsen, Peter; Kröger, Nicolaus

    2017-08-01

    The optimal parameters and time points for the measurement of iron overload (IO) in allogeneic stem cell transplantation (ASCT) patients are still under discussion. Hyperferritinemia and IO are poor prognostic factors in ASCT. We hypothesize that non-transferrin-bound iron (NBTI) is possibly a better marker to predict the effect of IO on the outcome than serum ferritin (SF), which however is not specific for IO. The aim of this prospective observational trial was to evaluate the influence of NBTI in comparison to SF on the outcome of ASCT patients [overall survival, bloodstream infections (BSIs), and invasive fungal infections (IFIs)]. We analyzed daily transferrin saturation (TSAT), SF, and NTBI (if TSAT exceeded 70%) in 100 patients who received ASCT during conditioning, and on day 0, +7, and +14 post-ASCT. After a median NTBI level of 0 μmol/l at baseline, the median of the area under the curve (AUC) of NTBI between conditioning and ASCT (d0) increased to 17 μmol*d/l, and between ASCT and day +14 to 56.3 μmol*d/l. Higher NTBI-AUC d0 resulted in a higher risk of BSI (HR 1.042, p = 0.009) and IFI (HR 1.070, p = 0.001) and showed a trend of inferior 1-year survival (65 vs. 76%, p = 0.09). Baseline SF did not influence BSI, but higher levels resulted in more IFI (HR 1.26, p < 0.001). In conclusion, NTBI possibly better predict for a higher risk of bloodstream infections than SF and needs further investigation.

  2. Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury

    PubMed Central

    Abboud, Miguel R.; Paley, Carole; Olivieri, Nancy; Kirby-Allen, Melanie; Vichinsky, Elliott; Casella, James F.; Alvarez, Ofelia A.; Barredo, Julio C.; Lee, Margaret T.; Iyer, Rathi V.; Kutlar, Abdullah; McKie, Kathleen M.; McKie, Virgil; Odo, Nadine; Gee, Beatrice; Kwiatkowski, Janet L.; Woods, Gerald M.; Coates, Thomas; Wang, Winfred; Adams, Robert J.

    2009-01-01

    Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% ± 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% ± 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% ± 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% ± 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182. PMID:19721013

  3. Effects of Cardiorespiratory Fitness on Serum Ferritin Concentration and Incidence of Type 2 Diabetes: Evidence from the Aerobics Center Longitudinal Study (ACLS).

    PubMed

    Le, Tuan D; Bae, Sejong; Ed Hsu, Chiehwen; Singh, Karan P; Blair, Steven N; Shang, Ning

    2008-01-01

    Cardiorespiratory fitness (CRF) and physical activity (PA) are inversely related to the occurrence of type 2 diabetes (T2D). Both play an important role in reducing serum ferritin (SF) concentration. Increased SF concentration is considered a contributing factor for developing T2D. The present cohort study investigated 5,512 adult participants enrolled in the Aerobics Center Longitudinal Study (ACLS) between 1995 and 2001. The subjects completed a comprehensive medical examination and a SF evaluation, and had been followed up until either diabetes onset, death, or the cut-off date of November 2007. Three CRF levels were categorized. SF quartile levels were defined by gender and menopausal status. The incidence of T2D was calculated for 10,000 person-years, and hazard ratios (HR) were computed to predict the incidence of T2D based on SF quartiles and CRF levels. SF concentration was significantly higher in males than in females (148.5 +/- 104.7 ng/ml vs. 52.2 +/- 45.9 ng/ml) and was inversely associated with CRF levels. In the high CRF group, 32.7% of participants had a low SF concentration whereas only 16.8% of participants had a high SF concentration level. After adjusting for potential confounders, male participants in the highest SF quartile level had a 1.7 times (HR: 1.67, 95% CI: 1.05, 2.66; p-trend = 0.027) increased risk for developing T2D compared with those in the lowest SF quartile group. Lower SF concentration was associated with lower risk of developing T2D in those regularly participating in CRF. The findings from this study suggest that SF concentration could be used as a diabetic predictor. Based on these results clinicians and public health professionals should promote regular physical activity or fitness to reduce the incidence of T2D.

  4. Effects of Cardiorespiratory Fitness on Serum Ferritin Concentration and Incidence of Type 2 Diabetes: Evidence from the Aerobics Center Longitudinal Study (ACLS)

    PubMed Central

    Le, Tuan D.; Bae, Sejong; Ed Hsu, Chiehwen; Singh, Karan P.; Blair, Steven N.; Shang, Ning

    2008-01-01

    BACKGROUND: Cardiorespiratory fitness (CRF) and physical activity (PA) are inversely related to the occurrence of type 2 diabetes (T2D). Both play an important role in reducing serum ferritin (SF) concentration. Increased SF concentration is considered a contributing factor for developing T2D. METHODS: The present cohort study investigated 5,512 adult participants enrolled in the Aerobics Center Longitudinal Study (ACLS) between 1995 and 2001. The subjects completed a comprehensive medical examination and a SF evaluation, and had been followed up until either diabetes onset, death, or the cut-off date of November 2007. Three CRF levels were categorized. SF quartile levels were defined by gender and menopausal status. The incidence of T2D was calculated for 10,000 person-years, and hazard ratios (HR) were computed to predict the incidence of T2D based on SF quartiles and CRF levels. RESULTS: SF concentration was significantly higher in males than in females (148.5 ± 104.7 ng/ml vs. 52.2 ± 45.9 ng/ml) and was inversely associated with CRF levels. In the high CRF group, 32.7% of participants had a low SF concentration whereas only 16.8% of participants had a high SF concentration level. After adjusting for potential confounders, male participants in the highest SF quartile level had a 1.7 times (HR: 1.67, 95% CI: 1.05, 2.66; p-trend = 0.027) increased risk for developing T2D compared with those in the lowest SF quartile group. CONCLUSION: Lower SF concentration was associated with lower risk of developing T2D in those regularly participating in CRF. The findings from this study suggest that SF concentration could be used as a diabetic predictor. Based on these results clinicians and public health professionals should promote regular physical activity or fitness to reduce the incidence of T2D. PMID:19290385

  5. The Homozygous Hemoglobin EE Genotype and Chronic Inflammation Are Associated with High Serum Ferritin and Soluble Transferrin Receptor Concentrations among Women in Rural Cambodia.

    PubMed

    Karakochuk, Crystal D; Whitfield, Kyly C; Rappaport, Aviva I; Barr, Susan I; Vercauteren, Suzanne M; McLean, Judy; Prak, Sophonneary; Hou, Kroeun; Talukder, Aminuzzaman; Devenish, Robyn; Green, Timothy J

    2015-12-01

    Ferritin and soluble transferrin receptor (sTfR) concentrations are commonly used to assess iron deficiency (ID); however, they are influenced by multiple factors. We assessed associations between numerous variables and both ferritin and sTfR concentrations in Cambodian women and compared ID prevalence through the use of study-generated correction factors (CFs) for ferritin with those from a published meta-analysis. Venous blood from 450 women (aged 18-45 y) was assessed for hemoglobin (Hb), ferritin, sTfR, retinol binding protein, folate, vitamin B-12, C-reactive protein, α-1 acid glycoprotein (AGP), and genetic Hb disorders. Linear regression was used to calculate geometric mean ratios (95% CIs) for ferritin and sTfR concentrations. The variant Hb EE genotype was associated with 50% (14%, 96%) and 51% (37%, 66%) higher geometric mean ferritin and sTfR concentrations, respectively, than was the normal Hb AA genotype; a 1-g/L increase in AGP was associated with 99% (50%, 162%) and 48% (33%, 64%) higher concentrations in the same variables, respectively. ID prevalence in nonpregnant women (n = 420) was 2% (n = 9) with the use of ferritin <15 μg/L and 18% (n = 79) with the use of sTfR >8.3 mg/L as criteria. ID prevalence with the use of sTfR was higher in women with the Hb EE genotype (n = 17; 55%) than in those with the Hb AA genotype (n = 20; 10%); and in women with the Hb AA genotype and chronic inflammation (n = 10; 18%) than in that group of women without chronic inflammation (n = 10; 7%) (P < 0.05). No differences in ID prevalence were found with the use of ferritin between women with Hb EE and AA genotypes (P = 1.0) or by chronic inflammation status (P = 0.32). There were no differences in mean ferritin concentrations among all 450 women when study-generated CFs were compared with those from the meta-analysis (P = 0.87). Compared with sTfR, ferritin concentrations appear to reflect more accurately true ID in rural Cambodian women. The CFs from a published

  6. Bivariate mixture modeling of transferrin saturation and serum ferritin concentration in Asians, African Americans, Hispanics, and whites in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

    PubMed Central

    Mclaren, Christine E.; Gordeuk, Victor R.; Chen, Wen-Pin; Barton, James C.; Acton, Ronald T.; Speechley, Mark; Castro, Oswaldo; Adams, Paul C.; Snively, Beverly M.; Harris, Emily L.; Reboussin, David M.; Mclachlan, Geoffrey J.; Bean, Richard

    2013-01-01

    Bivariate mixture modeling was used to analyze joint population distributions of transferrin saturation (TS) and serum ferritin concentration (SF) measured in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Four components (C1, C2, C3, and C4) with successively age-adjusted increasing means for TS and SF were identified in data from 26,832 African Americans, 12,620 Asians, 12,264 Hispanics, and 43,254 whites. The largest component, C2, had normal mean TS (21% to 26% for women, 29% to 30% for men) and SF (43–82 μg/L for women, 165–242 μg/L for men), which consisted of component proportions greater than 0.59 for women and greater than 0.68 for men. C3 and C4 had progressively greater mean values for TS and SF with progressively lesser component proportions. C1 had mean TS values less than 16% for women (<20% for men) and SF values less than 28 μg/L for women (<47 μg/L for men). Compared with C2, adjusted odds of iron deficiency were significantly greater in C1 (14.9–47.5 for women, 60.6–3530 for men), adjusted odds of liver disease were significantly greater in C3 and C4 for African-American women and all men, and adjusted odds of any HFE mutation were increased in C3 (1.4–1.8 for women, 1.2–1.9 for men) and in C4 for Hispanic and white women (1.5 and 5.2, respectively) and men (2.8 and 4.7, respectively). Joint mixture modeling identifies a component with lesser SF and TS at risk for iron deficiency and 2 components with greater SF and TS at risk for liver disease or HFE mutations. This approach can identify populations in which hereditary or acquired factors influence metabolism measurement. PMID:18201677

  7. Impact of Pre-Transplant Bacterial Infections on Post-Operative Outcomes in Patients after Liver Transplantation.

    PubMed

    Kim, Im-Kyung; Park, Joon Seong; Ju, Man Ki

    In contrast to studies evaluating the negative effect of bacterial infections on clinical outcomes after liver transplantation, there is little evidence with regard to pre-transplant bacterial infections. We aimed to investigate the impact of pre-transplant bacterial infections on post-transplant outcomes in patients after liver transplantation. We retrospectively analyzed clinical data from 33 consecutive patients who underwent primary liver transplantations. Patients were divided into two groups based on the occurrence of a bacterial infection within the 30 days before transplantation. Of the 33 patients, 23 patients did not have pre-transplant bacterial infections, while 10 patients did have pre-transplant bacterial infections. Pre-transplant bacterial infections were urinary tract infections (n = 4), spontaneous bacterial peritonitis (n = 3), and one each of pneumonia, bacteremia, and cellulitis. There were no differences in clinical characteristics between the two groups. Post-operative clinical outcomes, including post-operative bacterial infection, intensive-care unit re-admission, 30-day re-hospitalization, and 90-day mortality rate were not significantly different between the two groups. The two-year overall survival rate was 76.7% in patients with pre-transplant infections and 80.0% in those without pre-transplant infections. Patients with pre-transplant bacterial infections did not have inferior clinical outcomes, compared with those without pre-transplant bacterial infections.

  8. Effect of 40-cm segment umbilical cord milking on hemoglobin and serum ferritin at 6 months of age in full-term infants of anemic and non-anemic mothers.

    PubMed

    Bora, R; Akhtar, S S; Venkatasubramaniam, A; Wolfson, J; Rao, R

    2015-10-01

    To assess the effect of early clamping and milking of a 40-cm umbilical cord LUCM (long umbilical cord and milking) on hemoglobin (Hb) and serum ferritin concentrations at 6 months of age and to evaluate whether the effect is different in infants of anemic and non-anemic mothers. Eligible term-infants of anemic (maternal Hb<11.0 g dl(-1)) and non-anemic mothers (Hb ⩾11.0 g dl(-1)) were randomized to LUCM or control groups (N=100 each). In the LUCM group, the umbilical cord was clamped at 40-cm length and milked. The control group had the cord clamped at 5 cm and not milked. Neonatal morbidities until discharge and Hb and serum ferritin at 6 months of age were compared. Effects in infants of anemic and non-anemic mothers were compared. Compared with infants of non-anemic mothers, cord Hb was similar (14.50±1.90 g dl(-1) vs 14.67±1.73 g dl(-1)), but cord ferritin lower (85.8±55.4 ng ml(-1) vs 119.4±58.5 ng ml(-1), P<0.01) in infants of anemic mothers. Mean Hb concentration at 6 months was 9.60±1.42 g dl(-1) in the LUCM group and 9.07±1.10 g dl(-1) in the control group (P=0.004). Mean serum-ferritin concentration at 6 months was 113.9±43.8 ng ml(-1) in the LUCM group and 70.8±39.5 ng/ml in the control group (P<0.001). The effectiveness of LUCM did not vary with the maternal anemia status. Keeping the umbilical cord long and milking may be an effective method for improving Hb and iron stores at 6 months of age in term-infants.

  9. Ferritin Diversity: Mechanistic Studies, Disease Implications, and Materials Chemistry

    NASA Astrophysics Data System (ADS)

    Hilton, Robert J.

    2011-07-01

    The study of ferritin includes a rich history of discoveries and scientific progress. Initially, the composition of ferritin was determined. Soon, it was shown that ferritin is a spherical, hollow protein. Eventually, over several decades of research, the structure and some function of this interesting protein was elucidated. However, the ferritin field was not completely satisfied. Today, for example, researchers are interested in refining the details of ferritin function, in discovering the role of ferritin in a variety of diseases, and in using ferritin for materials chemistry applications. The work presented in this dissertation highlights the progress that we have made in each of these three areas: (1) Mechanistic studies: The buffer used during horse spleen ferritin iron loading significantly influences the mineralization process and the quantity of iron deposited in ferritin. The ferrihydrite core of ferritin is crystalline and ordered when iron is loaded into ferritin in the presence of imidazole buffer. On the other hand, when iron is loaded into ferritin in the presence of MOPS buffer, the ferrihydrite core is less crystalline and less ordered, and a smaller amount of total iron is loaded in ferritin. We also show that iron can be released from the ferritin core in a non-reductive manner. The rate of Fe3+ release from horse spleen ferritin was measured using the Fe3+-specific chelator desferoxamine. We show that iron release occurs by three kinetic events. (2) Disease studies: In order to better understand iron disruption during disease states, we performed in vitro assays that mimicked chronic kidney disease. We tested the hypothesis that elevated levels of serum phosphate interrupted normal iron binding by transferrin and ferritin. Results show that phosphate competes for iron, forming an iron(III)-phosphate complex that is inaccessible to either transferrin or ferritin. Ferritin samples separated from the iron(III)-phosphate complex shows that as the

  10. Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation.

    PubMed

    Jacobi, Nicole; Herich, Lena

    2016-10-01

    There are conflicting data regarding the role of serum ferritin (SF) as surrogate parameter for iron overload as an independent prognostic factor for outcome after allogeneic stem cell transplantation (SCT). Superconducting quantum interference device (SQUID) biomagnetic liver susceptometry, a noninvasive measurement of iron overload, allows measurement of the interference of an exteriorly applied small but highly constant magnetic field by the paramagnetic liver storage iron. By measuring the true iron load of patients through SQUID, we wanted to assess the effect of iron overload on patients undergoing SCT. We conducted a single-center retrospective analysis (1994-2010), comparing the effect of SF and liver iron content measured by SQUID shortly before transplantation on overall survival (OS), event-free survival (EFS), and transplant-related mortality (TRM) in 142 patients (median age 54.5 yr, range 5.6-75 yr) undergoing SCT (80% reduced intensity regimen). Patients were subdivided into five groups: myelodysplastic syndrome, de novo acute myeloid leukemia (AML), secondary AML, primary myelofibrosis, and others. Correlation between SF and SQUID was significant (r = 0.6; P < 0.001; log function). The chance of infection was increased 2.4-fold (95% CI 1.22-4.71) when SQUID values ranged ≥1000 μg Fe/g liver (P = 0.012). We found similar results for SF >1000 ng/mL (P = 0.003). A significant association between SQUID and fungal infection was also seen (P = 0.004). For patients with SQUID ≥1000, the risk of proven fungal infection was increased 3.08-fold (95% CI 1.43-6.63). A similar association between SF >1000 and fungal infection was shown (P = 0.01). In univariate analysis, age was a prognostic factor for TRM (P = 0.034, HR 1.04, CI 1.00-1.08). SF ≥1000 was associated with OS (P = 0.033, HR 2.09, CI 1.06-4.11) and EFS (P = 0.016, HR 2.15, 95% CI 1.15-4.10). In multivariate analysis on EFS, only age and SF >1000 remained as independent factors (HR 1.027, P

  11. Neuroferritinopathy: From ferritin structure modification to pathogenetic mechanism

    PubMed Central

    Levi, Sonia; Rovida, Ermanna

    2015-01-01

    Neuroferritinopathy is a rare, late-onset, dominantly inherited movement disorder caused by mutations in L-ferritin gene. It is characterized by iron and ferritin aggregate accumulation in brain, normal or low serum ferritin levels and high variable clinical feature. To date, nine causative mutations have been identified and eight of them are frameshift mutations determined by nucleotide(s) insertion in the exon 4 of L-ferritin gene altering the structural conformation of the C-terminus of the L-ferritin subunit. Acting in a dominant negative manner, mutations are responsible for an impairment of the iron storage efficiency of ferritin molecule. Here, we review the main characteristics of neuroferritinopathy and present a computational analysis of some representative recently defined mutations with the purpose to gain new information about the pathogenetic mechanism of the disorder. This is particularly important as neuroferritinopathy can be considered an interesting model to study the relationship between iron, oxidative stress and neurodegeneration. PMID:25772441

  12. Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

    PubMed

    El-Jawahri, Areej; Chen, Yi-Bin; Brazauskas, Ruta; He, Naya; Lee, Stephanie J; Knight, Jennifer M; Majhail, Navneet; Buchbinder, David; Schears, Raquel M; Wirk, Baldeep M; Wood, William A; Ahmed, Ibrahim; Aljurf, Mahmoud; Szer, Jeff; Beattie, Sara M; Battiwalla, Minoo; Dandoy, Christopher; Diaz, Miguel-Angel; D'Souza, Anita; Freytes, Cesar O; Gajewski, James; Gergis, Usama; Hashmi, Shahrukh K; Jakubowski, Ann; Kamble, Rammurti T; Kindwall-Keller, Tamila; Lazarus, Hilard M; Malone, Adriana K; Marks, David I; Meehan, Kenneth; Savani, Bipin N; Olsson, Richard F; Rizzieri, David; Steinberg, Amir; Speckhart, Dawn; Szwajcer, David; Schoemans, Helene; Seo, Sachiko; Ustun, Celalettin; Atsuta, Yoshiko; Dalal, Jignesh; Sales-Bonfim, Carmem; Khera, Nandita; Hahn, Theresa; Saber, Wael

    2017-05-15

    To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant

  13. 21 CFR 866.5340 - Ferritin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia....

  14. Production and Characterization of a Murine Monoclonal Antibody Against Human Ferritin

    PubMed Central

    Bayat, Ali Ahmad; Yeganeh, Omid; Ghods, Roya; Zarnani, Amir Hassan; Ardekani, Reza Bahjati; Mahmoudi, Ahmad Reza; Mahmoudian, Jafar; Haghighat-Noutash, Farzaneh; Jeddi-Tehrani, Mahmood

    2013-01-01

    Background Ferritin is an iron storage protein, which plays a key role in iron metabolism. Measurement of ferritin level in serum is one of the most useful indicators of iron status and also a sensitive measurement of iron deficiency. Monoclonal antibodies may be useful as a tool in various aspects of ferritin investigations. In this paper, the production of a murine monoclonal antibody (mAb) against human ferritin was reported. Methods Balb/c mice were immunized with purified human ferritin and splenocytes of hyper immunized mice were fused with Sp2/0 myeloma cells. After four times of cloning by limiting dilution, a positive hybridoma (clone: 2F9-C9) was selected by ELISA using human ferritin. Anti-ferritin mAb was purified from culture supernatants by affinity chromatography. Results Determination of the antibody affinity for ferritin by ELISA revealed a relatively high affinity (2.34×109 M -1) and the isotype was determined to be IgG2a. The anti-ferritin mAb 2F9-C9 reacted with 79.4% of Hela cells in flow cytometry. The antibody detected a band of 20 kDa in K562 cells, murine and human liver lysates, purified ferritin in Western blot and also ferritin in human serum. Conclusion This mAb can specifically recognize ferritin and may serve as a component of ferritin diagnostic kit if other requirements of the kit are met. PMID:24285995

  15. Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

    PubMed

    Bresani Salvi, Cristiane Campello; Braga, Maria Cynthia; Figueirôa, José Natal; Batista Filho, Malaquias

    2016-08-12

    Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40

  16. Ferritin content in human cancerous and noncancerous colonic tissue.

    PubMed

    Vaughn, C B; Weinstein, R; Bond, B; Rice, R; Vaughn, R W; McKendrick, A; Ayad, G; Rockwell, M A; Rocchio, R

    1987-01-01

    Tumor tissue samples from 25 patients with adenocarcinoma of the colon, twelve related samples of normal colons as well as five serum specimens from the same patients were analyzed for ferritin. The average ferritin content of the tumor tissue was 788 ng/mcp with a range of 47-1,745 ng/mcp. The average ferritin content of normal colon mucosa was 115 ng/mcp with a range of 32-230 ng/mcp. Two specimens of metastatic colon cancer taken from the retroperitoneal space and liver, respectively, contained 3,867 and 2,827 ng/mcp of ferritin. The ferritin content of the tumor tissue was higher than that of the normal colon in 8 of 9 patients who had specimens obtained from both sites. The amount of ferritin found in tumor tissue was independent of sex, age, and the site of the original tumor. This study shows that the ferritin content of colon neoplasms is elevated and indicates that the tumor tissue may be the direct source of elevated serum levels of ferritin previously observed in cancer patients.

  17. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    PubMed Central

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  18. Analytical Bias Exceeding Desirable Quality Goal in 4 out of 5 Common Immunoassays: Results of a Native Single Serum Sample External Quality Assessment Program for Cobalamin, Folate, Ferritin, Thyroid-Stimulating Hormone, and Free T4 Analyses.

    PubMed

    Kristensen, Gunn B B; Rustad, Pål; Berg, Jens P; Aakre, Kristin M

    2016-09-01

    We undertook this study to evaluate method differences for 5 components analyzed by immunoassays, to explore whether the use of method-dependent reference intervals may compensate for method differences, and to investigate commutability of external quality assessment (EQA) materials. Twenty fresh native single serum samples, a fresh native serum pool, Nordic Federation of Clinical Chemistry Reference Serum X (serum X) (serum pool), and 2 EQA materials were sent to 38 laboratories for measurement of cobalamin, folate, ferritin, free T4, and thyroid-stimulating hormone (TSH) by 5 different measurement procedures [Roche Cobas (n = 15), Roche Modular (n = 4), Abbott Architect (n = 8), Beckman Coulter Unicel (n = 2), and Siemens ADVIA Centaur (n = 9)]. The target value for each component was calculated based on the mean of method means or measured by a reference measurement procedure (free T4). Quality specifications were based on biological variation. Local reference intervals were reported from all laboratories. Method differences that exceeded acceptable bias were found for all components except folate. Free T4 differences from the uncommonly used reference measurement procedure were large. Reference intervals differed between measurement procedures but also within 1 measurement procedure. The serum X material was commutable for all components and measurement procedures, whereas the EQA materials were noncommutable in 13 of 50 occasions (5 components, 5 methods, 2 EQA materials). The bias between the measurement procedures was unacceptably large in 4/5 tested components. Traceability to reference materials as claimed by the manufacturers did not lead to acceptable harmonization. Adjustment of reference intervals in accordance with method differences and use of commutable EQA samples are not implemented commonly. © 2016 American Association for Clinical Chemistry.

  19. Biochemical analysis of ferritin subunits in sera from adult Still's disease patients.

    PubMed

    Higashi, S; Ota, T; Eto, S

    1995-01-01

    To determine the origin of the increased serum ferritin that occurs in adult Still's disease (ASD), we analyzed subunits of the serum ferritin as follows. Gel filtration with Sepharose CL-6B demonstrated that the molecular weight of serum ferritin was about 490 kDa. Western blot analysis revealed only L-subunits (molecular weight 19 kDa) in patients with serum ferritin levels higher than 1,000 ng/ml. Patients with serum ferritin levels higher than 1,000 ng/ml, however, showed G-subunits (molecular weight 23 kDa) in addition to the L-subunits. When concanavalin A (Con-A) Sepharose 4B was used in an absorption test, the percentage absorption was extremely low in the patients with serum ferritin levels higher than 1,000 ng/ml. Isoferritin patterns of the patients determined by chromatofocusing revealed traces of acidic ferritin. The findings suggested that glycosylated ferritin does not account for the major portion of the increased serum ferritin.

  20. Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients.

    PubMed

    DeWolfe, David; Gandhi, Jinal; Mackenzie, Matthew R; Broge, Thomas A; Bord, Evelyn; Babwah, Amaara; Mandelbrot, Didier A; Pavlakis, Martha; Cardarelli, Francesca; Viscidi, Raphael; Chandraker, Anil; Tan, Chen S

    2017-01-01

    BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.

  1. Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients

    PubMed Central

    Gandhi, Jinal; Mackenzie, Matthew R.; Broge, Thomas A.; Bord, Evelyn; Babwah, Amaara; Mandelbrot, Didier A.; Pavlakis, Martha; Cardarelli, Francesca; Viscidi, Raphael; Chandraker, Anil

    2017-01-01

    BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation. PMID:28562595

  2. Obesity is an independent risk factor for pre-transplant portal vein thrombosis in liver recipients

    PubMed Central

    2012-01-01

    Background Portal vein thrombosis is a frequent complication in end-stage cirrhosis with a considerable peri-operative risk for liver transplant candidates. We aimed to characterize the pre-transplant portal vein thrombosis in a cohort of liver transplant recipients, and to identify independent risk factors for this complication. Methods 380 consecutive primary orthotopic liver transplants were performed in the Digestive Surgery Department of “12 de Octubre” Hospital (Madrid, Spain), between January 2001 and December 2006. The main risk factors considered were smoking, obesity, metabolic disorders, previous immobility, surgery or trauma, nephrotic syndrome, associated tumor, inflammatory disease, neoplasm myeloprolipherative. Furthermore we have reported genetic thrombophilia results for 271 recipients. Results Sixty-two (16.3%) patients developed pre-transplant portal vein thrombosis and its presence had no impact in the overall survival of liver recipients. Obesity was the only independent risk factor for pre-transplant portal vein thrombosis. Conclusion We recommend close control of cardiovascular factors in patients with liver cirrhosis in order to avoid associated thrombosis. PMID:22909075

  3. Pre-Transplant Depression Is Associated with Length of Hospitalization, Discharge Disposition, and Survival after Liver Transplantation

    PubMed Central

    Rogal, Shari S.; Mankaney, Gautham; Udawatta, Viyan; Chinman, Matthew; Good, Chester B.; Zickmund, Susan; Bielefeldt, Klaus; Chidi, Alexis; Jonassaint, Naudia; Jazwinski, Alison; Shaikh, Obaid; Hughes, Christopher; Fontes, Paulo; Humar, Abhinav; DiMartini, Andrea

    2016-01-01

    Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort. PMID:27820828

  4. Prognostic pre-transplant factors in myelodysplastic syndromes primarily treated by high dose allogeneic hematopoietic stem cell transplantation: a retrospective study of the MDS subcommittee of the CMWP of the EBMT.

    PubMed

    Cremers, E M P; van Biezen, A; de Wreede, L C; Scholten, M; Vitek, A; Finke, J; Platzbecker, U; Beelen, D; Schwerdtfeger, R; Volin, L; Harhalakis, N; Blijlevens, N; Nagler, A; Kröger, N; de Witte, T

    2016-12-01

    Many pre-transplant factors are known to influence the outcome of allogeneic stem cell transplantation (SCT) treatment in myelodysplastic syndromes (MDS). However, patient cohorts are often heterogeneous by disease stage and treatment modalities, which complicates interpretation of the results. This study aimed to obtain a homogeneous patient cohort by including only de novo MDS patients who received upfront allogeneic SCT after standard high dose myelo-ablative conditioning. The effect of pre-transplant factors such as age, disease stage, transfusions, iron parameters and comorbidity on overall survival (OS), non-relapse mortality (NRM), and relapse incidence (RI) was evaluated in 201 patients. In this cohort, characterized by low comorbidity and a short interval between diagnosis and transplantation, NRM was the most determinant factor for survival after SCT (47 % after 2-year follow-up). WHO classification and transfusion burden were the only modalities with a significant impact on overall survival after SCT. Estimated hazard ratios (HR) showed a strongly increased risk of death, NRM and RI, in patients with a high transfusion-burden (HR 1.99; P = 0.006, HR of 1.89; P = 0.03 and HR 2.67; P = 0.03). The HR's for ferritin level and comorbidity were not significantly increased.

  5. Ferritin: isolation of aluminum-ferritin complex from brain.

    PubMed Central

    Fleming, J; Joshi, J G

    1987-01-01

    Ferritin was isolated from the livers and brains of two groups of rats, one of which was fed aluminum chloride (100 microM) for 1 year in the drinking water. Brain tissue contained about one-third of the amount of ferritin found in the liver. While brain ferritin from normal rats contained 42.1 +/- 14.3 mol of aluminum, that from the aluminum-fed group contained 115.4 +/- 48.3 mol of aluminum per mol of ferritin. Liver ferritin from both groups contained similar amounts of both aluminum and iron, and the amounts were less than that found associated with brain ferritin. Ferritin isolated from the brains of patients who died of Alzheimer disease contained more aluminum and more iron than that from age-matched controls. Human brain ferritin is composed of two types of subunits--about 70% heavy chain (Mr, 22,000) and 30% light chain (Mr, 19,500). The isoelectric focusing pattern of human brain ferritin was considerably different from that of human liver. Only 5 of the 20 brain ferritin bands migrated similarly to the acidic isoferritins from the liver, and the major component of brain ferritin, representing 30% of the total ferritin, had a pI of 8.0. Images PMID:3479769

  6. Fever of unknown origin (FUO) due to large B-cell lymphoma: the diagnostic significance of highly elevated alkaline phosphatase and serum ferritin levels.

    PubMed

    Cunha, Burke A; Petelin, Andrew

    2013-01-01

    Determining the cause of fever of unknown origin (FUO) is often a vexing and difficult diagnostic process. In most cases, the signs and symptoms in adult FUOs suggest a malignant, infectious, or rheumatic/inflammatory etiology. The diagnosis of FUO may be narrowed if specific findings are present (eg, hepatosplenomegaly) that limit the diagnostic possibilities. Infectious causes of FUO with hepatosplenomegaly include miliary tuberculosis, typhoid fever, and visceral leishmanosis (kala-azar). However, FUOs with hepatosplenomegaly are most often attributable to malignant neoplasms, ie, Hodgkin lymphoma, non-Hodgkin lymphoma, hepatoma, hypernephroma (renal-cell carcinoma), or preleukemia. We present a middle-aged woman with FUO and hepatosplenomegaly. Inpatient nonspecific laboratory findings included a highly elevated erythrocyte sedimentation rate, and elevated levels of vitamin B12, lactate dehydrogenase, angiotensin-converting enzyme, ferritin, and alkaline phosphatase. These individual findings are nonspecific, but together point to a lymphoma. An important test in differentiating malignant from infectious FUOs is the Naprosyn test, and her Naprosyn test was positive, indicating malignancy. A gallium scan suggested a uterine lymphoma. A computed tomography scan revealed hepatosplenomegaly, but the gallium uptake was not increased in her liver and spleen. Uterine and bone marrow biopsies were negative for lymphoma. We present a case of FUO with hepatosplenomegaly attributable to large B-cell lymphoma as diagnosed via liver biopsy. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Inflammation associated anemia and ferritin as disease markers in SLE

    PubMed Central

    2012-01-01

    Introduction In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. Methods A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. Results Protein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. Conclusion Urine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. PMID:22871034

  8. Spontaneous bacterial peritonitis prevalence in pre-transplant patients and its effect on survival and graft loss post-transplant

    PubMed Central

    Shah, Neeral L; Intagliata, Nicolas M; Henry, Zachary H; Argo, Curtis K; Northup, Patrick G

    2016-01-01

    AIM To investigate the incidence of spontaneous bacterial peritonitis (SBP) in pre-transplant patients and its effect on post transplant mortality and graft failure. METHODS We conducted a retrospective cohort study of patient records from the organ procurement and transplant network data set. Patients were identified by the presence of SBP pre-transplant. Univariate post-transplant survival models were constructed using the Kaplan-Meier technique and multivariate models were constructed using the Cox proportional hazards model. Variables that affected post-transplant graft survival were identified in the SBP population. RESULTS Forty-seven thousand eight hundred and eighty patient records were included in the analysis for both groups, and 1966 (4.11%) patients were identified in the data set as having pre-transplant SBP. Patients that had pre-transplant SBP had higher rates of graft loss from recurrent hepatitis C virus (HCV) (3.6% vs 2.0%, P < 0.0001), infections leading to graft loss (1.9% vs 1.3%, P = 0.02), primary non-function (4.3% vs 3.0%, P < 0.0001) and chronic rejection (1.1% vs 0.7%, P = 0.04). Kaplan-Meier survival analysis showed a statistically significant difference in all-cause survival in patients with a history of SBP vs those without (P < 0.0001). Pre-transplant history of SBP was independently predictive of mortality due to recurrent HCV (HR = 1.11, 95%CI: 1.02-1.21, P < 0.017) after liver transplantation. CONCLUSION HCV patients prior to the advent of directing acting anti-viral agents had a higher incidence of pre-transplant SBP than other patients on the liver transplant wait list. SBP history pre-transplant resulted in a higher rate of graft loss due to recurrent HCV infection and chronic rejection. PMID:28083084

  9. Pre-transplant emotional support is associated with longer survival after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Ehrlich, K B; Miller, G E; Scheide, T; Baveja, S; Weiland, R; Galvin, J; Mehta, J; Penedo, F J

    2016-12-01

    Emerging evidence suggests that psychosocial factors pre-transplant predict survival in cancer patients undergoing hematopoietic stem cell transplantation (HSCT). These studies, however, typically have small sample sizes, short-term follow ups or a limited panel of medical covariates. We extend this research in a large, well-characterized sample of transplant patients, asking whether patients' perceived emotional support and psychological distress predict mortality over 2 years. Prior to transplant, 400 cancer patients (55.5% males; 82.8% White; Mage=50.0 years; 67.0% leukemia, 20.0% lymphoma) were interviewed by a social caseworker, who documented the patients' perceived emotional support and psychological distress. Subsequently, patients received an allogeneic HSCT (51.0% matched-related donor, 42.0% matched-unrelated donor and 7.0% cord blood). HSCT outcomes were obtained from medical records. Controlling for demographic characteristics (age, sex, race/ethnicity and marital status) and medical confounders (disease type, conditioning regimen, remission status, cell dosage, donor and recipient CMV seropositivity, donor sex, comorbidities and disease risk), ratings of good emotional support pre-transplant predicted longer overall survival (hazard ratio (HR)=0.61, 95% confidence interval (CI), 0.42-0.91; P=0.013). Pre-transplant psychological distress was unrelated to survival, however (Ps>0.58). Emotional support was marginally associated with lower rates of treatment-related mortality (HR=0.58, CI, 0.32-1.05; P=0.073). These findings are consistent with the hypothesis that emotional support contributes to better outcomes following HSCT. Future studies should examine whether intervention efforts to optimize emotional resources can improve survival in cancer patients.

  10. Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.

    PubMed

    Lenzhofer, Markus; Schroedl, Falk; Trost, Andrea; Kaser-Eichberger, Alexandra; Wiedemann, Helmut; Strohmaier, Clemens; Hohensinn, Melchior; Strasser, Michael; Muckenthaler, Martina U; Grabner, Guenther; Aigner, Elmar; Reitsamer, Herbert A

    2015-04-01

    Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens. During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed. Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene. In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.

  11. Iron Regulation by Ferritin

    DTIC Science & Technology

    1988-08-15

    block number) FIED GOUP 1 SB.GOUP ’~’RRIINRONSTORAGE, BIOMINERALIZATION , MAGNETITE FERRIHYDRITEMAGNETOTAXIS. 19. ABSTRACT (Continue on reverse if...the mechanisms of iron deposition, storage and mobilization in ferritin proteins, and to study related iron biomineralization processes in...Algae Biophysical Effects of Steady Magnetic Fields, edited by G. Maret ( Springer -Verlag, Berlin, 1986) pp. 173-179. 3. R.B. Frankel and R.P

  12. Risk of end-stage renal disease among liver transplant recipients with pre-transplant renal dysfunction

    PubMed Central

    Ruebner, R; Goldberg, D; Abt, PL; Bahirwani, R; Levine, M; Sawinski, D; Bloom, RD; Reese, PP

    2012-01-01

    Guidelines recommend restricting simultaneous liver-kidney (SLK) transplant to candidates with prolonged dialysis or estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 for 90 days. However, few studies exist to support the latter recommendation. Using SRTR and Medicare dialysis data, we assembled a cohort of 4997 liver transplant recipients from 2/27/2002–1/1/2008. Serial eGFRs were calculated from serum creatinines submitted with MELD reports. We categorized recipients by eGFR patterns in the 90 days pre-transplant: Group 1 (eGFR always >30), Group 2 (eGFR fluctuated), Group 3 (eGFR always <30) and Group 4 (short-term dialysis). For Group 2, we characterized fluctuations in renal function using time-weighted mean eGFR. Among liver-alone recipients in Group 3, the rate of end-stage renal disease (ESRD) by 3 years was 31%, versus <10% for other groups (p<0.001). In multivariable Cox regression, eGFR Group, diabetes (HR 2.65, p<0.001) and black race (HR 1.83, p=0.02) were associated with ESRD. Among liver-alone recipients in Group 2, only diabetics with time-weighted mean eGFR<30 had a substantial ESRD risk (25.6%). In summary, among liver transplant candidates not on prolonged dialysis, SLK should be considered for those whose eGFR is always <30 and diabetic candidates whose weighted mean eGFR is <30 for 90 days. PMID:22759237

  13. Pre-transplant thymic function is associated with the risk of cytomegalovirus disease after solid organ transplantation.

    PubMed

    Gracia-Ahufinger, I; Ferrando-Martínez, S; Montejo, M; Muñoz-Villanueva, M C; Cantisán, S; Rivero, A; Solana, R; Leal, M; Torre-Cisneros, J

    2015-05-01

    Cytomegalovirus (CMV) disease is an important complication in solid organ transplant recipients. Thymic function in adults is associated with specific T-cell immunity. Pre-transplant thymic function was analysed in 75 solid organ transplant patients by the use of nested PCR. The primary outcome was the incidence of CMV disease 12 months after transplantation. Using multivariable logistic regression, we studied whether pre-transplant thymic function is an independent risk factor for CMV disease after transplantation. Thymic function was related to the risk of CMV disease in CMV-seropositive recipients. In these recipients, pre-transplant thymic function of <9.5 (OR 11.27, 95% CI 1.11-114.43, p 0.040) and the use of thymoglobulin (OR 8.21, 95% CI 1.09-61.84, p 0.041) were independent risk factors for CMV disease at 12 months after transplantation. Patients with pre-transplant thymic function values of <9.5 had a higher subsequent incidence of CMV disease (24%) than patients with values of ≥ 9.5 (3%) (log-rank test: 5.727; p 0.017). The positive and negative predictive values of these pre-transplant thymic function cut-offs were 0.24 (95% CI 0.10-0.45) and 0.97 (95% CI 0.82-1.00), respectively. Pre-transplant thymic function in CMV-seropositive candidates could be useful in determining the risk of post-transplant CMV disease in solid organ transplant patients, selecting a group of low-risk candidates.

  14. Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

    PubMed

    Butler, Javed; Stankewicz, Mark A; Wu, Jack; Chomsky, Don B; Howser, Renee L; Khadim, Ghazanfar; Davis, Stacy F; Pierson, Richard N; Wilson, John R

    2005-02-01

    Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.

  15. Impact of Obesity on Heart and Lung Transplantation: Does Pre-Transplant Obesity Affect Outcomes?

    PubMed

    Bozso, S J; Nagendran, Je; Gill, R S; Freed, D H; Nagendran, Ja

    2017-03-01

    Increasing prevalence of obesity has led to a rise in the number of prospective obese heart and lung transplant recipients. The optimal management strategy of obese patients with end-stage heart and lung failure remains controversial. This review article discusses and provides a summary of the literature surrounding the impact of obesity on outcomes in heart and lung transplantation. Studies on transplant obesity demonstrate controversy in terms of morbidity and mortality outcomes and obesity pre-transplantation. However, the impact of obesity on outcomes seems to be more consistently demonstrated in lung rather than heart transplantation. The ultimate goal in heart and lung transplantation in the obese patient is to identify those at highest risk of complication that may warrant therapies to mitigate risk by addressing comorbid conditions.

  16. Demographic Characteristics and Association of Serum Vitamin B12, Ferritin and Thyroid Function with Premature Canities in Indian Patients from an Urban Skin Clinic of North India: A Retrospective Analysis of 71 Cases.

    PubMed

    Sonthalia, Sidharth; Priya, Adity; Tobin, Desmond J

    2017-01-01

    The incidence of self-reported premature hair graying (PHG) seems to be on the rise. PHG has a profound impact on the patient's quality of life. It remains an incompletely understood etiology with limited and modest treatment options. The evaluation of the demographic and clinical profile of patients with premature canities, and exploration of the association of this entity with certain systemic disorders suspected to be related to its etiology. Seventy-one cases of premature canities (onset noticed by patients before 25 years of age) presenting to an urban skin clinic in Gurugram, India, between September 2012 and September 2015 with this complaint were retrospectively analyzed. The patient records were retrieved that provided details of the onset, duration and pattern of involvement, history, and examination findings (scalp, cutis, and general physical). Since all these patients had been screened for anemia, thyroid disorder, fasting blood glucose, and Vitamin B12 levels at the time of presentation, these parameters were also available for analysis. The mean age at onset of graying was 10.2 ± 3.6 years (range: 5-19 years), with an almost equal gender distribution. The earliest age of onset recorded was 5 years. A positive family history of PHG (at least one of the biological parents or siblings) was obtained in 64 (90.1%) of the cases. The temporal regions of the scalp (35.2%) were most commonly involved followed by the frontal region (18.3%). Hypovitaminosis B12 and hypothyroidism showed significant association with the disorder, whereas anemia, serum ferritin, and fasting blood glucose did not. The age of onset of hair graying can be as low as 5 years. Temporal and frontal areas are the most commonly involved sites. A strong family history, Vitamin B12 deficiency, and hypothyroidism are strongly associated with PHG. Larger case-control studies are mandated for discerning the correlation of these and other risk factors with PHG.

  17. Prevalence and predictors of early cardiovascular events after kidney transplantation: evaluation of pre-transplant cardiovascular work-up.

    PubMed

    Delville, Marianne; Sabbah, Laurent; Girard, Delphine; Elie, Caroline; Manceau, Sandra; Piketty, Marie; Martinez, Frank; Méjean, Arnaud; Legendre, Christophe; Sberro-Soussan, Rebecca

    2015-01-01

    Cardiovascular disease is the leading cause of mortality after renal transplantation. The purpose of this study was to analyze cardiovascular risk factors at transplantation, occurrence of cardiovascular events in the first year after transplantation and evaluate pre-transplant work-up. In total, 244 renal transplant recipients older than 50 years were included. The results of pre-transplant work-up, including clinical evaluation, electrocardiogram, echocardiography, myocardial perfusion testing and coronary angiography were analyzed. Patients had multiple risk factors at inclusion on renal transplantation waiting list as high blood pressure (94.7%), dyslipidemia (81.1%), smoking (45.3%), diabetes (23.6%), past history of cardiovascular disease (21.3%) and obesity (12.7%). Following transplantation, 15.5% (n = 38) of patients experienced a cardiovascular event, including 2.8% (n = 7) acute coronary syndrome, 5.8% (n = 14) isolated increase in troponin level and 5.3% (n = 13) new onset atrial fibrillation. The pre-transplant parameters associated with a cardiovascular event were a past medical history of cardiovascular disease (HR = 2.06 [1.06-4.03], p = 0.03), echocardiographic left ventricular hypertrophy (HR = 2.04 [1.04-3.98], p = 0.037) and abnormal myocardial perfusion testing (HR = 2.25 [1.09 -5.96], p = 0.03). Pre-transplantation evaluation allowed the diagnosis of unknown coronary artery lesions in 8.9% of patients.

  18. The Effect of Pre-Transplant Distress on Immune Reconstitution among Adult Autologous Hematopoietic Cell Transplantation Patients

    PubMed Central

    McGregor, Bonnie A.; Syrjala, Karen L.; Dolan, Emily D.; Langer, Shelby L.; Redman, Mary

    2012-01-01

    Myeloablative hematopoietic cell transplantation (HCT) is a common treatment for hematological malignancy. Delayed immune reconstitution following HCT is a major impediment to recovery with patients being most vulnerable during the first month after transplant. HCT is a highly stressful process. Because psychological distress has been associated with down regulation of immune function we examined the effect of pre-transplant distress on white blood cell (WBC) count among 70 adult autologous HCT patients during the first 3 weeks after transplant. The participants were on average 38 years old; 93% Caucasian, non-Hispanic and 55% male. Pre-transplant distress was measured 2–14 days before admission using the Cancer and Treatment Distress (CTXD) scale, and the Symptom Checklist-90-R (SCL-90-R) anxiety and depression subscales. WBC count was measured during initial immune recovery on days 5 through 22 post-transplant. Linear mixed model regression analyses controlling for gender and treatment-related variables revealed a significant effect of the mean pre-transplant SCL Depression-Anxiety score on WBC recovery. We found no significant effect of pre-transplant CTXD on WBC recovery. In general, higher levels of pre-treatment depression and anxiety were associated with slower WBC recovery. Psychological modulation of WBC recovery during HCT suggests a unique mechanism by which psychological distress can exert influence over the immune system. Given that WBC recovery is essential to survival for HCT patients, these data provide a rationale for treating anxiety and depression in HCT patients. PMID:22910186

  19. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome.

    PubMed

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2015-10-27

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p < 0.001) and NRM (p = 0.007). Pre-transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p < 0.001, respectively) and overall survival (p = 0.043 and p < 0.001, respectively). Our retrospective study suggests that MDS patients losing weight prior to alloSCT have an inferior outcome after transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted.

  20. Biliary excretion of iron and ferritin in idiopathic hemochromatosis

    SciTech Connect

    Hultcrantz, R.; Angelin, B.; Bjoern-Rasmussen, E.E.; Ewerth, S.; Einarsson, K.

    1989-06-01

    The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

  1. INVERTEBRATE FERRITIN: OCCURRENCE IN MOLLUSCA.

    PubMed

    TOWE, K M; LOWENSTAM, H A; NESSON, M H

    1963-10-04

    Ferritin, in both crystalline and paracrystalline forms, occurs in the columnar epithelial cells of the dorsal wall of the radula of the marine chiton Cryptochiton stelleri, order, Polyplacophora. The ferritin occurs in association with the magnetite of the radular teeth. It has been isolated and crystallized in the presence of cadmium sulfate.

  2. 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.

  3. [Red cell zinc protoporphyrin and its ratio to serum ferritin (ZPP/logSF index) in the detection of iron deficiency in patients with end-stage renal failure on hemodialysis].

    PubMed

    Matuszkiewicz-Rowińska, Joanna; Ostrowski, Grzegorz; Niemczyk, Stanisław; Przedlacki, Jerzy; Wardyn, Kazimierz; Puka, Janusz; Włodarczyk, Dariusz; Switalski, Marek; Zakrzewska, Teresa; Ostrowski, Kazimierz

    2003-07-01

    Monitoring of iron metabolism has become a major clinical issue in end-stage renal patients undergoing hemodialysis. It can be done at three levels: storage, transport and marrow availability. The objective of that study was to evaluate if a combination of an iron storage marker, serum ferritin (SF) with red cell zinc protoporphyrin (ZPP), a marker of iron availability for erythron, will improve diagnostic value of both tests. In a baseline survey in the population of 186 haemodialysis patients (75% treated with rHuEpo), the following parameters were determined: complete blood count, serum transferrin saturation (TSAT), transferrin, SF, hypochromic red cells % (HRC) and ZPP; the ZPP/logSF ratio was calculated. Iron deficiency was defined as a fernitin saturation--TSAT < 20%. In the second part of the study, 24 pts with SF < 50 ng/ml were given 50 mg of i.v. iron weekly for three months, then the same tests were repeated. During that time the doses of rhuEpo were stable. An increase in hemoglobin of > 1.0 g/dl was considered as a positive response. In 186 studied patients mean SF was 274 +/- 335 ng/ml, and mean ZPP was 68 +/- 44 mumol/mol heme. A ZPP/logSF ratio > or = 40 had the best combination of diagnostic sensitivity and specificity in detecting iron deficiency (76% and 83% vs: 56% and 89% for ZPP > 90 mumol/mol heme, 84% and 34% for HRC > 5%, 68% and 58% for HRC > 10%) and the strong correlations with all other examined parameters were found. The index showed also the highest correlation with the response to the i.v. iron (r = 59; p < 0.01) of the tests evaluated. After three months the values of ZPP/logSF ratio decreased from 80 +/- 105 to 39 +/- 19 (p < 0.01). A significant difference between responders and nonresponders was found for basal ZPP/logSF (p < 0.05) but not for ZPP. Our data suggest that the ZPP/logSF index provides a new valuable parameter for the identification of hemodialysis patients with iron deficiency and the prediction an erythropoietic

  4. Erythrocyte ferritin content in idiopathic haemochromatosis and alcoholic liver disease with iron overload.

    PubMed Central

    Van Der Weyden, M B; Fong, H; Salem, H H; Batey, R G; Dudley, F J

    1983-01-01

    The erythrocyte ferritin content was measured in patients with either idiopathic haemochromatosis or alcoholic liver disease and iron overload to define its value as a marker for an excess of tissue iron. The mean erythrocyte ferritin content in patients with untreated idiopathic haemochromatosis was increased 60-fold and fell with phlebotomy. After phlebotomy many patients had an increased red cell ferritin content despite normal serum ferritin concentrations. That this reflected persistent iron overload with inadequate phlebotomy was suggested by the higher serum iron concentrations, percentage transferrin saturation, and urinary excretion of iron after administration of desferrioxamine, together with a lower annual iron loss by phlebotomy in this group compared with patients with treated disease and normal red cell ferritin content. The mean erythrocyte ferritin content in patients with alcoholic liver disease and iron overload was increased only sevenfold, and the ratio of erythrocyte to serum ferritin clearly discriminated these patients from those with idiopathic haemochromatosis. The determination of erythrocyte ferritin content is a useful non-invasive test for diagnosing idiopathic haemochromatosis, monitoring the effect of phlebotomy in this disorder, and distinguishing patients with this disorder from those with alcoholic liver disease with iron overload. PMID:6402233

  5. Iron loading into ferritin by an intracellular ferroxidase.

    PubMed

    Reilly, C A; Aust, S D

    1998-11-01

    An intracellular, membrane-bound enzyme exhibiting both p-phenylenediamine oxidase activity and ferrous iron oxidase activity was isolated with the plasma membrane fraction of horse heart and studied for its ability to load iron into ferritin. The ferroxidase activity of the tissue oxidase was stimulated approximately twofold by horse spleen apoferritin, and the iron was loaded into ferritin. The loading of iron into ferritin by the tissue oxidase was inhibited by anti-horse serum ceruloplasmin antibody. The stoichiometry of iron oxidation and oxygen consumption during iron loading into ferritin by the tissue-derived oxidase and serum ceruloplasmin were 3.6 +/- 0.2 and 3.9 +/- 0.2, respectively. These data provide evidence that an enzyme analogous to ceruloplasmin is present on the plasma membrane of horse heart and that this ferroxidase is capable of catalyzing the loading of iron into ferritin. The implications of these data on the present models for the uptake and storage of iron by cells are discussed.

  6. Hematological parameters, ferritin and vitamin B12 in vegetarians.

    PubMed

    Pongstaporn, W; Bunyaratavej, A

    1999-03-01

    Hematological parameters and serum ferritin were compared between 179 vegetarians and 58 control subjects using Hematology analyzer H3 and microparticle enzyme immunoassay, respectively. Serum Vitamin B12 was also compared between 68 vegetarians and 30 control subjects using microparticle enzyme immunoassay. It was found that hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white blood cells, neutrophils, serum ferritin and serum vitamin B12 in vegetarian were significantly lower than control subjects (P < 0.05). In addition, red cell distribution width and lymphocytes in vegetarians were significantly higher than control subjects (P < 0.05). There were 34 cases of iron deficiency in 179 vegetarians (19.%) which can be classified to iron depletion (4 cases), iron deficient erythropoiesis (12 cases) and iron deficiency anemia (18 cases). Vitamin B12 deficiency was found in 27 cases of 68 vegetarians (40%).

  7. Pre-transplant depression as a predictor of adherence and morbidities after orthotopic heart transplantation.

    PubMed

    Delibasic, Maja; Mohamedali, Burhan; Dobrilovic, Nikola; Raman, Jaishankar

    2017-07-25

    Psychosocial factors are useful predictors of adverse outcomes after solid organ transplantation. Although depression is a known predictor of poor outcomes in patients who undergo orthotopic heart transplantation (OHT) and is actively screened for during pre-transplant evaluation, the effects of early identification of this entity on post-transplant outcomes are not clearly understood. The purpose of this study was to evaluate the impact of pre-transplant depression on outcomes after OHT. In this retrospective study, 51 patients that underwent psychosocial evaluation performed by a social worker prior to the transplant and followed up in our center post-transplant were enrolled. Patients were stratified by the presence/absence of depression during the initial encounter. Primary end-points were overall survival, 1st-year hospitalizations, overall hospitalizations, rejections, and compliance with medications and outpatient appointments. Depressed patients were 3.5 times more likely to be non-compliant with medications; RR = 3.5, 95% CI (1.2,10.2), p = 0.046 and had higher incidence of first year hospitalizations (4.7 ± 3.1 vs. 2.2 ± 1.9, p = 0.046), shorter time to first hospitalization 25 days (IQR 17-39) vs. 100 days (IQR 37-229), p = 0.001. Patients with depression also had higher overall hospitalizations (8.3 ± 4.4 vs. 4.6 ± 4.2, p = 0.025,) and higher number of admissions for infections (2.8 ± 1.3 vs. 1.5 ± 1.4, p = 0.018) compared to patients without depression. There were no statistically significant differences in total number of rejections or compliance with outpatient appointments. Kaplan-Meier survival analysis did not reveal differences between the two groups (mean 3705 vs. 3764 days, log-rank p = 0.52). Depression was a strong predictor of poor medication compliance and higher rates of hospitalization in transplant recipients. No difference in survival between depressed and non-depressed patients after OHT was noted.

  8. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    PubMed

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  9. Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity.

    PubMed

    Phipps, Colin; Gopal, Ajay K; Storer, Barry E; Cassaday, Ryan D; Press, Oliver W; Till, Brian G; Pagel, John M; Palanca-Wessels, Maria C; Philip, Mary; Bensinger, William I; Holmberg, Leona A; Shustov, Andrei R; Green, Damian J; Chauncey, Thomas; Maloney, David G; Libby, Edward N

    2015-01-01

    Patients with rituximab-refractory follicular lymphoma (FL) have limited options. Before the rituximab era, autologous stem cell transplant (ASCT) was shown to improve outcomes in chemotherapy-sensitive, relapsed FL, but the impact of rituximab-sensitivity on these results is unknown. We analyzed 194 consecutive relapsed patients with FL who underwent ASCT at out center and categorized them as rituximab-sensitive (RS, n = 35), rituximab-refractory (RR, n = 65) or no rituximab (NoR, n = 94) if transplanted before rituximab was used. Progression-free survival at 3 years was 85% in RS and 35% in RR patients (p = 0.0004). Only rituximab-sensitivity was significant on multivariate analysis with improved overall survival (OS) (hazard ratio [HR] 0.24, p = 0.01) and progression-free survival (PFS) (HR 0.35, p = 0.006) in RS patients and increased relapse in RR patients (HR 2.11, p = 0.01). Pre-transplant rituximab-sensitivity is a strong independent predictor of post-transplant outcomes in relapsed FL, although one-third of RR patients achieved a PFS of over 3 years with ASCT.

  10. Ex vivo perfusion of the swine heart as a method for pre-transplant assessment.

    PubMed

    Colah, S; Freed, D H; Mundt, P; Germscheid, S; White, P; Ali, A; Tian, G; Large, S; Falter, F

    2012-09-01

    We describe a cost-effective, reproducible circuit in a porcine, ex vivo, continuous warm-blood, bi-ventricular, working heart model that has future possibilities for pre-transplant assessment of marginal hearts donated from brain stem dead donors and hearts donated after circulatory determination of death (DCDD). In five consecutive experiments over five days, pressure volume loops were performed. During working mode, the left ventricular end systolic pressure volume relationship (LV ESPVR) was 23.1±11.1 mmHg/ml and the LV preload recruitable stroke work (PRSW) was 67.8±7.2. (Standard PVAN analysis software) (Millar Instruments, Houston, TX, USA) All five hearts were perfused for 219±64 minutes and regained normal cardiac function on the perfusion system.They displayed a significant upward and leftward shift of the end systolic pressure volume relationship, a significant increase in preload recruitable stroke work and minimal stiffness. These hearts could potentially be considered for transplantation. The circuit was effective during reperfusion and working modes whilst proving to be successful in maintaining cardiac function in excess of four hours. Using an autologous prime of approximately 20% haematocrit (Hct), electrolytes and blood gases were easy to control within this period using standard perfusion techniques.

  11. 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.

  12. Magneto-Optics of Ferritin

    NASA Astrophysics Data System (ADS)

    Dobek, Andrzej

    2010-01-01

    Ferritins are the metalloproteides present in plant and animal cells. Their micelleous tertiary structure allows iron accumulation in the form of hydratated oxides and phosphates. Thus, ferritin is a large spherical macromolecular protein with iron compounds in the cavity created by a peptide shell. Because of the spherical shape, ferritin macromolecule should not manifest magnetic anisotropy; however, in solution it shows the induced magnetic birefringence (Cotton-Mouton effect) and changes in intensity of the scattered light components. Therefore, the Cotton-Mouton effect, Rayleigh light scattering and nonlinear light scattering in dc magnetic field, were measured at room temperature for 100 mM NaCl solutions of apoferritin/ferritin loaded with different contents of Fe atoms/molecule. Analysis of the results has shown that the deformation of linear optical polarizability induced in the ferritin by a magnetic field and the orientation of the induced and permanent magnetic dipole moment by this field are the main sources of the magneto-optical phenomena observed. The results suggest the simultaneous diamagnetic and superparamagnetic behavior of the ferritin biomacromolecule.

  13. Impact of Pre-transplant Therapy and Depth of Disease Response prior to Autologous Transplantation for Multiple Myeloma

    PubMed Central

    Vij, Ravi; Kumar, Shaji; Zhang, Mei-Jie; Zhong, Xiaobo; Huang, Jiaxing; Dispenzieri, Angela; Abidi, Muneer H.; Bird, Jennifer M.; Freytes, César O.; Gale, Robert Peter; Kindwall-Keller, Tamila L.; Kyle, Robert A.; Landsburg, Daniel J.; Lazarus, Hillard M.; Munker, Reinhold; Roy, Vivek; Sharma, Manish; Vogl, Dan T.; Wirk, Baldeep; Hari, Parameswaran N.

    2014-01-01

    Patients with multiple myeloma (MM), who are eligible for autologous stem cell transplantation (ASCT), typically receive a finite period of initial therapy prior to ASCT. It is not clear if patients with suboptimal (less than a partial) response to initial therapy benefit from additional alternative therapy with intent to maximize pre-transplant response. We identified 539 patients with MM who had an ASCT after having achieved less than a partial response (PR) to first line induction chemotherapy between 1995 and 2010. These patients were then divided into two groups: those who received additional salvage chemotherapy prior to ASCT (n=324) and those who had no additional salvage chemotherapy immediately prior to ASCT (n=215). Additional pre-transplant chemotherapy resulted in deepening responses in 68% (complete response in 8% and PR in 60%). On multivariate analysis there was no impact of pre-transplant salvage chemotherapy on treatment related mortality (TRM), risk for relapse, progression free or overall survival. In conclusion, for patients achieving a less than PR to initial induction therapy including with novel agent combinations, additional pre-ASCT salvage chemotherapy improved the depth of response and pre-ASCT disease status but was not associated with survival benefit. PMID:25445028

  14. Pre-transplant diabetes mellitus is a risk factor for non-relapse mortality, especially infection-related mortality, after allogeneic hematopoietic SCT.

    PubMed

    Takano, K; Fuji, S; Uchida, N; Ogawa, H; Ohashi, K; Eto, T; Sakamaki, H; Morishima, Y; Kato, K; Suzuki, R; Fukuda, T

    2015-04-01

    Diabetes mellitus (DM) is a factor in the hematopoietic cell transplantation-comorbidity index. However, the impact of pre-transplant DM on morbidity and cause-specific non-relapse mortality (NRM) remains unclear. We performed a retrospective study with registry data that included a total of 7626 patients who underwent their first allogeneic hematopoietic SCT (HSCT) between 2007 and 2010. The median age was 44 years (range 0-88). Compared with patients without pre-transplant DM (non-DM group, n=7248), patients with pre-transplant DM (DM group, n=378) were older and were more likely to have high-risk disease, a reduced-intensity conditioning regimen and GVHD prophylaxis using tacrolimus. Multivariate analyses showed that pre-transplant DM was associated with increased risks of NRM (hazard ratio (HR)1.46, 95% confidence interval (CI) 1.21-1.76, P<0.01) and infection-related NRM (HR 2.08, 95% CI 1.58-2.73, P<0.01). The presence of pre-transplant DM was associated with an increased risk of overall mortality in a multivariate analysis (HR 1.55, 95% CI 1.35-1.78, P<0.01). In conclusion, pre-transplant DM was a risk factor for NRM, particularly infection-related mortality, after allogeneic HSCT. To improve the clinical outcome in patients with DM, the benefits of strict infection control and appropriate glycemic control should be explored in future trials.

  15. Pre-transplant dialysis modality does not influence short- or long-term outcome in kidney transplant recipients: analysis of paired kidneys from the same deceased donor.

    PubMed

    Dipalma, Teresa; Fernández-Ruiz, Mario; Praga, Manuel; Polanco, Natalia; González, Esther; Gutiérrez-Solis, Elena; Gutiérrez, Eduardo; Andrés, Amado

    2016-09-01

    Previous studies have reported contradictory results regarding the effect of pre-transplant dialysis modality on the outcomes after kidney transplantation (KT). To minimize the confounding effect of donor-related variables, we performed a donor-matched retrospective comparison of 160 patients that received only one modality of pre-transplant dialysis (peritoneal dialysis [PD] and hemodialysis [HD] in 80 patients each) and that subsequently underwent KT at our center between January 1990 and December 2007. Cox regression models were used to evaluate the association between pre-transplant dialysis modality and primary study outcomes (death-censored graft survival and patient survival). To control for imbalances in recipient-related baseline characteristics, we performed additional adjustments for the propensity score (PS) for receiving pre-transplant PD (versus HD). There were no significant differences according to pre-transplant dialysis modality in death-censored graft survival (PS-adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [95% CI]: 0.25-1.68) or patient survival (aHR: 0.58; 95% CI: 0.13-2.68). There were no differences in 10-year graft function or in the incidence of post-transplant complications either, except for a higher risk of lymphocele in patients undergoing PD (odds ratio: 4.31; 95% CI: 1.15-16.21). In conclusion, pre-transplant dialysis modality in KT recipients does not impact short- or long-term graft outcomes or patient survival.

  16. Soluble transferrin receptor, ferritin and soluble transferrin receptor--Ferritin index in assessment of anaemia in rhaeumatoid arthritis.

    PubMed

    Pavai, S; Jayaranee, S; Sargunan, S

    2007-10-01

    Anaemia of chronic disease (ACD) is a frequent complication of rheumatoid arthritis (RA). A diagnostic difficulty in RA is the distinction between iron deficiency anaemia (IDA) and ACD. The aim of our study was to evaluate the usefulness of serum soluble transferrin receptor (sTfR) and sTfR/log ferritin (TfR-F) index to diagnose iron deficiency in RA patients with anaemia. Routine laboratory indices of anaemia and sTfR were measured in 20 healthy persons to form the control group, 30 patients with iron deficiency anaemia and 28 RA patients with anaemia. Serum sTfR levels were significantly elevated above the cut-off value in patients with IDA and those in the iron depleted RA subgroup (ferritin < 60 microg/L) compared with those in the control and iron repleted RA subgroup (ferritin > 60 microg/L). The same was observed for TfR-F index. However, five patients in the iron repleted RA sub group had an elevated sTfR level, of which two had increased TfR-F index. Serum sTfR correlated well with the markers of anaemia and not with ESR. Ferritin had no correlation with markers of anaemia but correlated well with ESR. Measurement of sTfR and TfR-F index are good indicators of iron deficiency in RA patients with anaemia. To be cost effective, sTfR can be estimated in RA patients with anaemia when the ferritin level is more than 60 microg/L.

  17. Association of ferritin elevation and metabolic syndrome in males. Results from the Aragon Workers' Health Study (AWHS).

    PubMed

    Ledesma, Marta; Hurtado-Roca, Yamilee; Leon, Montserrat; Giraldo, Pilar; Pocovi, Miguel; Civeira, Fernando; Guallar, Eliseo; Ordovas, Jose Maria; Casasnovas, Jose Antonio; Laclaustra, Martin

    2015-05-01

    Ferritin concentration is associated with metabolic syndrome, but the possibility of a nonlinear association has never been explored. This study aimed to examine the relationship between serum ferritin levels and the metabolic syndrome in Spanish adult males. This was a cross-sectional analysis of baseline data from the Aragon Workers' Health Study. Healthy workers from a factory were studied during their annual checkup. Spanish male adults (n = 3386) between the ages of 19 and 65 years participated. We excluded participants with ferritin > 500 μg/L, ferritin < 12 μg/L, or C-reactive protein > 10 mg/L. Metabolic syndrome was defined according to the 2009 consensus definition from the Joint Interim Statement of several international societies. Metabolic syndrome prevalence was 27.1%. We found a positive association between elevated iron stores, measured as serum ferritin concentration, and metabolic syndrome and its criteria. Participants within the highest serum ferritin quintile had a higher risk than those in the lowest quintile for central obesity (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.46-2.42), hypertriglyceridemia (OR, 2.15; 95% CI, 1.69-2.74), and metabolic syndrome (OR, 1.92; 95% CI, 1.48-2.49). The association was nonlinear and occurred at serum ferritin concentrations > 100 μg/L (∼ 33th percentile). Ferritin was also associated with insulin resistance, measured by homeostatic model assessment-insulin resistance (HOMA-IR) (P trend < .001). Our findings suggest that serum ferritin is significantly associated with metabolic syndrome and its criteria (especially central obesity and hypertriglyceridemia), suggesting that ferritin could be an early marker of metabolic damage in the development of metabolic syndrome.

  18. 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

  19. Pre-transplant assessment of CMV-specific immune response by Elispot assay in kidney transplant recipients.

    PubMed

    Rittà, Massimo; Costa, Cristina; Sidoti, Francesca; Ballocco, Cinzia; Ranghino, Andrea; Messina, Maria; Biancone, Luigi; Cavallo, Rossana

    2015-07-01

    Cytomegalovirus (CMV) primary infection or re-activation in solid organ transplant (SOT) recipients is associated with increased morbidity and mortality, with patients with IgG-CMV D+/R- sero-matching at greater risk. The impact of pre-transplant CMV-specific host cellular immunity on the long-term risk of CMV replication in kidney transplants (KT) was prospectively evaluated in eighty patients by CMV-EliSpot assay. The study population included 54 male and 26 female recipients, with CMV-IgG distribution: 60 D+/R+, 11 D-/R+, 7 D+/R-, 2 D-/R-. At pre-transplantation, 49 KT (61.3%) were CMV-responders by EliSpot. At 3-month follow up, 16 (32.7%) out of 49 CMV-responders showed CMV blood infection, compared to 8 (25.8%) out of 31 non-responders. No further episode of CMV viraemia was reported in the responder group, in comparison to 15 out 31 non-responders (48.4%) showing at least one episode of CMV-DNAemia at 12-month follow-up. Baseline CMV-IgG serology showed a strong correlation with EliSpot determinations; KT recipients exhibiting at least one episode of CMV viraemia at 12-month follow-up showed lower baseline CMV-EliSpot values than those without signs of CMV replication. The study suggests that monitoring CMV-specific T-cell responses at pre-transplantation by EliSpot assay may be useful for predicting the post-transplantation risk of CMV infection and reactivation.

  20. The impact of pre-transplant dialysis on simultaneous pancreas-kidney versus living donor kidney transplant outcomes.

    PubMed

    Wiseman, Alexander C; Huang, Edmund; Kamgar, Mandana; Bunnapradist, Suphamai

    2013-04-01

    Pre-transplant dialysis is known to affect kidney graft survival. Here, we report the impact of pre-transplant dialysis on patient and graft survival of type 1 diabetic recipients of either a simultaneous pancreas-kidney (SPK) or living donor kidney (LDK) transplant. Using the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database, 6822 adult type 1 diabetic recipients transplanted through 2000-2011 were identified. Patients were categorized based on pre-transplant dialysis time (DT): preemptive recipients (P-LDK, n = 498; P-SPK, n = 1529), recipients with <1 year of DT (0-1 year DT; LDK n = 582, SPK n = 1700), and those with 1-2 years DT (1-2 year DT; LDK n = 301, SPK n = 2212). Seven-year patient and kidney survival were examined. Compared with the P-SPK group, both 0-1 year DT and 1-2 year DT SPK recipients had lower 7-year patient survival (89, 84 & 84% respectively; log-rank P-value versus P-SPK = 0.01 & <0.001). For LDK groups, DT > 1 year was associated with inferior patient survival (7-year survival 76% versus 87% for P-LDK, P-value versus P-LDK = 0.009). Comparing P-LDK to all other SPK groups, there was no significant difference in 7-year patient or kidney survival. Preemptive transplantation is associated with the highest patient survival in both LDK and SPK. Compared with the P-LDK group, DT > 1 year is associated with lower patient survival among LDK recipients, but there is no difference in survival with dialysis up to 2 years with SPK. These results highlight the differential impact of DT on LDK and SPK transplantation.

  1. Quantification of ferritin from staple food crops.

    PubMed

    Lukac, Rebecca J; Aluru, Maneesha R; Reddy, Manju B

    2009-03-25

    Ferritin-iron has been shown to be as bioavailable as ferrous sulfate in humans. Thus, biofortification to breed crops with high ferritin content is a promising strategy to alleviate the global iron deficiency problem. Although ferritin is present in all food crops, its concentration varies between species and varieties. Therefore, a successful ferritin biofortification strategy requires a method to rapidly measure ferritin concentrations in food crops. The objective of this study was to develop a simple and reliable ELISA using an anti-ferritin polyclonal antibody to detect ferritin in various crops. Crude seed extracts were found to have 10.2 +/- 1.0, 4.38 +/- 0.9, 1.2 +/- 0.3, 0.38 +/- 0.1, and 0.04 +/- 0.01 microg of ferritin/g of dry seed in red beans, white beans, wheat, maize, and brown rice, respectively. Although the measured absolute concentrations of ferritin values were low, the presented method is applicable for rapid screening for the relative ferritin concentrations of large numbers of seeds to identify and breed ferritin-rich crops.

  2. Ferritin Assembly in Enterocytes of Drosophila melanogaster.

    PubMed

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

    2016-02-05

    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.

  3. 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

  4. Ferritin Is a Marker of Inflammation rather than Iron Deficiency in Overweight and Obese People

    PubMed Central

    Khan, Wazir Muhammad; Ayub, Maimoona; Humayun, Mohammad; Haroon, Mohammad

    2016-01-01

    Background. In clinical practice, serum ferritin is used as a screening tool to detect iron deficiency. However, its reliability in obesity has been questioned. Objectives. To investigate the role of ferritin in overweight and obese people, either as a marker of inflammation or iron deficiency. Methods. On the basis of body mass index (BMI), 150 participants were divided into three equal groups: A: BMI 18.5–25 kg/m2, B: BMI 25–30 kg/m2, and C: BMI > 30 kg/m2. Serum iron, total iron binding capacity (TIBC), transferrin saturation, ferritin, C-reactive protein, and hemoglobin (Hb) were measured for each participant and analyzed through SPSS version 16. One-way ANOVA and Pearson's correlation tests were applied. Results. Ferritin was the highest in group C (M = 163.48 ± 2.23, P < 0.001) and the lowest in group A, (M = 152.78 ± 1.81, P < 0.001). Contrarily to ferritin, transferrin was the lowest in group C, (M = 30.65 ± 1.39, P < 0.001) and the highest in group A, (M = 38.66 ± 2.14, P < 0.001). Ferritin had a strong positive correlation with both BMI (r = 0.86, P < 0.001) and CRP (r = 0.87, P < 0.001) and strong negative correlation with Hb, iron, TIBC, and transferrin saturation (P < 0.001). Conclusion. Ferritin is a marker of inflammation rather than iron status in overweight and obese people. Complete iron profile including transferrin, rather than serum ferritin alone, can truly predict iron deficiency in such people. PMID:28116148

  5. Hepcidin-25, mean corpuscular volume, and ferritin as predictors of response to oral iron supplementation in hemodialysis patients.

    PubMed

    Takasawa, Kazuya; Takaeda, Chikako; Maeda, Teiryo; Ueda, Norishi

    2014-12-29

    The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients.

  6. Hepcidin-25, Mean Corpuscular Volume, and Ferritin as Predictors of Response to Oral Iron Supplementation in Hemodialysis Patients

    PubMed Central

    Takasawa, Kazuya; Takaeda, Chikako; Maeda, Teiryo; Ueda, Norishi

    2014-01-01

    The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients. PMID:25551249

  7. A comparative study on iron sources for mitochondrial haem synthesis including ferritin and models of transit pool species.

    PubMed

    Funk, F; Lecrenier, C; Lesuisse, E; Crichton, R R; Schneider, W

    1986-06-02

    The rates of reaction of various exogenic iron(III) complexes with deuteroporphyrin IX in isolated mitochondria to form deuterohaem were measured. Ferritin was shown to supply iron readily for haem synthesis if the ferritin iron was reductively mobilised by the mitochondrial respiratory chain with succinate as substrate and FMN as mediator. In contrast, polynuclear complexes of iron(III) were able to form deuterohaem without added FMN. Rates of haem formation are about five times higher for the lowest polynuclear units than for ferritin. Sorbitol, gluconate, and bovine serum albumin were used as scavengers for polynuclear complexes with restricted size. Strong chelators of iron(II) compete favourably for deuterohaem formation, which supports the multistep mechanism for haem formation suggested by a priori arguments. Rates of deuterohaem formation were measured in homologous and heterologous systems of ferritins and mitochondria. Slightly differing rates of haem formation were shown to originate in different rates of iron mobilisation from the ferritins. The lack of species specificity in the interaction of ferritin with mitochondria also shows up in the linear dependence of ferritin binding on its bulk concentration as measured using 3H-labeled ferritin. Rates of haem formation are virtually the same in mitoplasts and mitochondria which indicates insignificant influences of the outer membrane. The hypothesis of low polynuclears as major components of the intracellular transit iron pool implies that both ferritin and transit iron pool species are largely equivalent sources of iron for mitochondrial haem synthesis.

  8. Evaluation of Usefulness of hs-CRP and Ferritin Assays in Patients with Nasal Polyps

    PubMed Central

    Partyka, Robert; Pałac, Jacek; Paluch, Zbigniew; Szyguła-Jurkiewicz, Bożena; Namysłowski, Grzegorz; Misiołek, Maciej; Jałowiecki, Przemysław; Kokocińska, Danuta

    2014-01-01

    Background. Chronic nature of the nasal polyps, tendency to recurrence, and lack of satisfying treatment need the diagnostic's parameters which show early inflammatory state as ferritin and hs-CRP. The Aim of Study. Assessment of hs-CRP and ferritin blood levels in nasal polyps patients in evaluation of treatment efficacy. Methods. All 38 patients were divided into 2 groups. Group I included 19 patients with anti-inflammatory therapy 2 weeks after surgery. Group II included 19 patients without anti-inflammatory therapy 2 weeks after surgery. The levels of hs-CRP and ferritin have been assessed before and 2 and 6 weeks after surgical treatment. Results. Research showed statistically significant difference of ferritin's concentration between examined groups 6 weeks after surgery (P < 0.05) and statistically significant difference of hs-CRP concentration 2 and 6 weeks after surgery (P < 0.05). Conclusion. (1) The analysis of serum ferritin and hs-CRP concentrations can be useful in early postoperative detection of inflammatory state in patients with nasal polyps and for the effectiveness of therapy. (2) Lack of correlation between mean ferritin and hs-CRP serum levels, at each diagnostic and monitoring stage, shows that they are independent and cannot be determined interchangeably. PMID:24737923

  9. Impact of pre-transplant pulmonary infection developed in horizontal laminar flow unit on the outcome of subsequent allogeneic hematopoietic stem cell transplantation.

    PubMed

    He, Gan-Lin; Chang, Ying-Jun; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-08-01

    So far, there is very little literature on how pre-transplant pulmonary infection developed in horizontal laminar flow unit (HLFU) affects outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was performed on allo-HSCT recipients who were diagnosed with pre-transplant pulmonary infection developed in HLFU between January 2012 and December 2012. Various tests were analyzed to evaluate the overall survival (OS) and pulmonary infection rate after allo-HSCT. Among 317 patients who received allo-HSCT from related donors, 7 cases of human leukocyte antigen (HLA)-haploidentical transplantation reported a fever, cough, and other symptoms before transplantation. Chest radiography findings showed pulmonary infection, and the C-reactive protein (CRP) level was higher than normal, which confirmed pulmonary infection (incidence rate 2.21%). The Breslow test suggested that the early survival rate was lower in the group with pre-transplant pulmonary infection than in the group without pre-transplant pulmonary infection (OS: 28.4 vs. 42.4 months; P=0.023); the early survival rate was lower in patients with a pulmonary infection accompanied by bilateral pleural effusion than in patients without pleural effusion (OS: 1.5 vs. 36.3 months; P=0.010). In the first month after transplantation, the difference in the CD4CD45RO+CD45RA- and CD4CD45RO-CD45RA+ between the groups with and without pre-transplant pulmonary infection was statistically significant (P<0.05). Patients with pre-transplant pulmonary infection who survived >3 years had a higher rate of pulmonary infection in the first 2 months after allo-HSCT than those without pre-transplant pulmonary infection [100% (5/5 patients) vs. 38.1% (118/310); χ(2)=5.542, P=0.019]. Development of pre-transplant pulmonary infection in the HLFU in patients with hematological malignancies who receive HLA-haploidentical HSCT is associated with an increased risk of recurrent pulmonary infection in

  10. Psychological impact of working with patients with cystic fibrosis at end-of-life, pre-transplant stage.

    PubMed

    Clisby, Nicola; Shaw, Samantha; Cormack, Maggie

    2013-04-01

    Multidisciplinary staff who work with end-of-life, pre-transplant patients with cystic fibrosis (CF) have to juggle two seemingly opposing care approaches; active care to maintain their patients' health and condition in anticipation of a transplant, and sensitive palliative care that takes their end-of-life wishes into consideration should they not receive a transplant. Little is known about the psychological impact on staff working within this care dichotomy. The aim of this study is to explore staff's experiences and understand more about the psychological impact of this work on them professionally and personally, and how this affects their ability to provide appropriate care for their patients. A qualitative explorative research design was used. Ten semistructured interviews with multidisciplinary staff working in cystic fibrosis centers and units across the United Kingdom were analyzed using interpretative phenomenological analysis (IPA). Two superordinate themes emerged from the analysis: factors contributing to the "juggle" of active and palliative care, and extent of emotional impact on staff. The study indicates that there is an emotional impact on staff working with patients with CF at end-of-life, pre-transplant stages. Specifically, it reveals the extent of the unpredictability that staff work with, and the range of emotions that staff experience, including uncertainty about professional identity and anxiety about working practices. The depth and intimacy of professional-patient relationships is highlighted, particularly for staff in close contact with and similar in age to their patients. Additionally, the strength of staff's commitment and desire to care for patients within broader humanistic terms that mesh with their own personal values is brought to light. Despite the difficulties with their work, the majority of staff adopted numerous coping strategies to manage their emotions, many of which emphasized the link between their professional and

  11. A photonic crystal biosensor assay for ferritin utilizing iron-oxide nanoparticles.

    PubMed

    Peterson, Ross D; Cunningham, Brian T; Andrade, Juan E

    2014-06-15

    Iron deficiency anemia afflicts 1 in 3 individuals, mostly women and children worldwide. A novel application using iron-oxide nanoparticles (IONPs) and a photonic crystal (PC) optical biosensor as an immunodiagnostic platform for detection of serum ferritin, a biomarker for iron deficiency, is presented. Human liver ferritin (450 kDa), clinical serum controls, and three commercially available ferritin ELISA tests were used to evaluate the PC biosensor assay in terms of inter- and intra-assay variability, spike-recovery (%), limit of detection (LOD), and matrix effects on binding. For the PC biosensor, signal response from label-free, sandwich with secondary antibody (pAb), and pAb functionalized with iron-oxide nanoparticles (FpAb) assays were detected using the Biomolecular Interaction Detection (BIND) system. Bland-Altman analysis was used to evaluate agreement between expected values for ferritin in control sera and each of the detection platforms. Inter- and intra-assay variability of the PC biosensor were both <10%. Percent mean recovery (±%RSD) of ferritin from two control sera samples were 94.3% (13.1%) and 96.9% (7.6%). Use of FpAb in PC biosensor resulted in two orders of magnitude increase in sensitivity compared to label-free assay; capable of measuring serum ferritin as low as 26 ng/mL. In comparison to ELISA tests, the PC biosensor assay had the lowest bias (-1.26; 95% CI [-3.0-5.5]) and narrower limit of agreement (-11.6-9.1 ng/mL) when determining ferritin concentrations from control sera. These proof-of-concept studies support the use of IONPs to enhance detection sensitivity of PC biosensors for determination of biomarkers of nutritional status.

  12. Effects of radiofrequency radiation on human ferritin: an in vitro enzymun assay.

    PubMed

    Fattahi-Asl, Jafar; Baradaran-Ghahfarokhi, Molood; Karbalae, Mojtaba; Baradaran-Ghahfarokhi, Milad; Baradaran-Ghahfarokhi, Hamid Reza

    2012-10-01

    Ferritin is a macromolecule and is responsible for the long term iron storage function in human serum and plasma. Recent studies have highlighted the role of cell phone exposure on central nervous system, immune function and reproduction. The aim of this study was to investigate whether the human serum ferritin level could be interfered by the exposure to the 900 MHz GSM cell phones. Fifty human serum wells from 25 normal healthy donors were labeled with ruthenium to form a sandwich complex based on an immunoassay technique. All of them were placed into two batches, and the well heads in the first batch were exposed to 900 MHz exposure emitted from a speech mode cell phone (Nokia, Model 1202, India) for 30 min. Unexposed batch was served as the control sample under identical conditions and was compared with the exposed one in quantitative determination of ferritin using the Wilcoxon test with criterion level of P = 0.050. Human serum wells in the exposed batch showed a significant decrease in serum ferritin relative to the control batch (P = 0.029). The average ± SD ferritin level in the exposed batch was 84.94 ± 1.04 μg/L while it was 87.25 ± 0.83 μg/L for the unexposed batch. Radiofrequency electromagnetic waves emitted from cell phones may lead to oxidative stress and rapid diffusion of the human ferritin level in an in vitro enzymun assay. Also, the enzyme activity can be affected. Effects of exposure from mobile phones must be considered further.

  13. Effects of Radiofrequency Radiation on Human Ferritin: An In Vitro Enzymun Assay

    PubMed Central

    Fattahi-asl, Jafar; Baradaran-Ghahfarokhi, Molood; Karbalae, Mojtaba; Baradaran-Ghahfarokhi, Milad; Baradaran-Ghahfarokhi, Hamid Reza

    2012-01-01

    Ferritin is a macromolecule and is responsible for the long term iron storage function in human serum and plasma. Recent studies have highlighted the role of cell phone exposure on central nervous system, immune function and reproduction. The aim of this study was to investigate whether the human serum ferritin level could be interfered by the exposure to the 900 MHz GSM cell phones. Fifty human serum wells from 25 normal healthy donors were labeled with ruthenium to form a sandwich complex based on an immunoassay technique. All of them were placed into two batches, and the well heads in the first batch were exposed to 900 MHz exposure emitted from a speech mode cell phone (Nokia, Model 1202, India) for 30 min. Unexposed batch was served as the control sample under identical conditions and was compared with the exposed one in quantitative determination of ferritin using the Wilcoxon test with criterion level of P = 0.050. Human serum wells in the exposed batch showed a significant decrease in serum ferritin relative to the control batch (P = 0.029). The average ± SD ferritin level in the exposed batch was 84.94 ± 1.04 μg/L while it was 87.25 ± 0.83 μg/L for the unexposed batch. Radiofrequency electromagnetic waves emitted from cell phones may lead to oxidative stress and rapid diffusion of the human ferritin level in an in vitro enzymun assay. Also, the enzyme activity can be affected. Effects of exposure from mobile phones must be considered further. PMID:23724375

  14. Ferritin-stimulated lipid peroxidation, lysosomal leak, and macroautophagy promote lysosomal "metastability" in primary hepatocytes determining in vitro cell survival.

    PubMed

    Krenn, Margit A; Schürz, Melanie; Teufl, Bernhard; Uchida, Koji; Eckl, Peter M; Bresgen, Nikolaus

    2015-03-01

    Several pathologies are associated with elevated levels of serum ferritin, for which growth inhibitory properties have been reported; however, the underlying mechanisms are still poorly defined. Previously we have described cytotoxic properties of isoferritins released from primary hepatocytes in vitro, which induce apoptosis in an iron and oxidative stress-dependent mode. Here we show that this ferritin species stimulates endosome clustering and giant endosome formation in primary hepatocytes accompanied by enhanced lysosomal membrane permeability (LMP). In parallel, protein modification by lipid peroxidation-derived 4-hydroxynonenal (HNE) is strongly promoted by ferritin, the HNE-modified proteins (HNE-P) showing remarkable aggregation. Emphasizing the prooxidant context, GSH is rapidly depleted and the GSH/GSSG ratio is substantially declining in ferritin-treated cells. Furthermore, ferritin triggers a transient upregulation of macroautophagy which is abolished by iron chelation and apparently supports HNE-P clearance. Macroautophagy inhibition by 3-methyladenine strongly amplifies ferritin cytotoxicity in a time- and concentration-dependent mode, suggesting an important role of macroautophagy on cellular responses to ferritin endocytosis. Moreover, pointing at an involvement of lysosomal proteolysis, ferritin cytotoxicity and lysosome fragility are aggravated by the protease inhibitor leupeptin. In contrast, EGF which suppresses ferritin-induced cell death attenuates ferritin-mediated LMP. In conclusion, we propose that HNE-P accumulation, lysosome dysfunction, and macroautophagy stimulated by ferritin endocytosis provoke lysosomal "metastability" in primary hepatocytes which permits cell survival as long as in- and extrinsic determinants (e.g., antioxidant availability, damage repair, EGF signaling) keep the degree of lysosomal destabilization below cell death-inducing thresholds.

  15. Prognostic value of pre-transplant PET/CT in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation.

    PubMed

    Winter, Allison; Rybicki, Lisa; Shah, Shetal N; Jagadeesh, Deepa; Gerds, Aaron T; Hamilton, Betty K; Liu, Hien; Dean, Robert; Sobecks, Ronald; Pohlman, Brad; Smith, Mitchell; Kalaycio, Matt; Bolwell, Brian J; Majhail, Navneet S; Hill, Brian T

    2017-08-30

    Pre-transplant PET/CT may be prognostic in diffuse large B-cell lymphoma (DLBCL) patients undergoing autologous stem cell transplantation (ASCT). We reviewed relapsed and pre-transplant PET/CT scans of 32 patients with DLBCL treated with ASCT to determine the Deauville score and the maximum standardized uptake value (SUVmax). Patients with a Deauville score of 4 had a significantly inferior prognosis. The 3-year progression-free survival (PFS) for patients with Deauville 1-3 score was 64%, compared to 0% for Deauville 4, while the 3-year overall survival (OS) was 84% and 25%, respectively (p < .001, p = .002). The change in the SUVmax (>66 versus ≤66%) was not predictive of PFS or OS, but a high pre-transplant SUVmax (>6) demonstrated a trend towards an inferior PFS. Pre-transplant PET/CT is a tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies.

  16. Optimization of Pre-transplantation Conditions to Enhance the Efficacy of Mesenchymal Stem Cells

    PubMed Central

    Haque, Nazmul; Kasim, Noor Hayaty Abu; Rahman, Mohammad Tariqur

    2015-01-01

    Mesenchymal stem cells (MSCs) are considered a potential tool for cell based regenerative therapy due to their immunomodulatory property, differentiation potentials, trophic activity as well as large donor pool. Poor engraftment and short term survival of transplanted MSCs are recognized as major limitations which were linked to early cellular ageing, loss of chemokine markers during ex vivo expansion, and hyper-immunogenicity to xeno-contaminated MSCs. These problems can be minimized by ex vivo expansion of MSCs in hypoxic culture condition using well defined or xeno-free media i.e., media supplemented with growth factors, human serum or platelet lysate. In addition to ex vivo expansion in hypoxic culture condition using well defined media, this review article describes the potentials of transient adaptation of expanded MSCs in autologous serum supplemented medium prior to transplantation for long term regenerative benefits. Such transient adaptation in autologous serum supplemented medium may help to increase chemokine receptor expression and tissue specific differentiation of ex vivo expanded MSCs, thus would provide long term regenerative benefits. PMID:25678851

  17. Impact of Pre-Transplant Anti-T Cell Globulin (ATG) on Immune Recovery after Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation.

    PubMed

    Servais, Sophie; Menten-Dedoyart, Catherine; Beguin, Yves; Seidel, Laurence; Gothot, André; Daulne, Coline; Willems, Evelyne; Delens, Loïc; Humblet-Baron, Stéphanie; Hannon, Muriel; Baron, Frédéric

    2015-01-01

    Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented. In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F). Detailed phenotypes of circulating T, B, natural killer (NK) and invariant NKT (iNKT) cells were analyzed by multicolor flow cytometry at serial time-points from day 40 to day 365 after transplantation. Thymic function was also assessed by sjTREC quantification. Serious infectious events were collected up to 2 years post-transplantation. Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells. Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells. Levels of sjTRECs were similar in both cohorts at 1-year after PBSCT, suggesting that ATG-F unlikely impaired thymopoiesis at long-term after PBSCT. Finally, the incidence and rate of serious infections were similar in both groups, while ATG-F patients had a lower incidence of grade II-IV acute graft-versus-host disease. Pre-transplant ATG-F induces long-lasting modulation of the circulating T-cell pool after myeloablative PBSCT, that may participate in preventing graft-versus-host disease without deeply compromising anti-pathogen defenses.

  18. Isolation and purification of duck liver ferritin.

    PubMed

    Díez, J M; Agapito, M T; Recio, J M

    1985-09-01

    A rapid method of purifying duck liver ferritin using high speed centrifugation and chromatography on Sephadex G-200 and Sepharose 6B is described. Protein and iron concentration for each step of purification is given. This method yields 0.12 mg of pure ferritin per gram of wet tissue.

  19. The role of vesicles in the transport of ferritin through frog endothelium.

    PubMed Central

    Clough, G; Michel, C C

    1981-01-01

    1. The transport of ferritin molecules by endothelial cell vesicles has been quantitatively investigated by electron microscopy. Single mesenteric capillaries of pithed frogs were perfused with solutions containing 6.7 g ferritin 100 ml.-1 for known periods before fixation in situ with osmium tetroxide. 2. Two series of experiments were carried out: in the first series the perfusate contained bovine serum albumin (1.0 g 100 ml.-1); in the second series the perfusate contained no protein other than the ferritin. To assess the molecular radius of ferritin in solution, the free diffusion coefficient of ferritin was measured in the presence and absence of albumin. 3. The free diffusion coefficient of ferritin in saline solution (110 m-mole 1.-1) was found to be 0.35 X 10(-6) cm2 sec-1 at 21 degrees C and was not affected by the presence of bovine serum albumin. This indicates that there is no significant binding of albumin to ferritin in solution and yields a value for the Stokes-Einstein radius of ferritin of 6.1 nm. 4. In all perfusion experiments the percentage of luminal vesicles containing ferritin exceeded the percentage of labelled cytoplasmic vesicles, which in turn exceeded the percentage of labelled abluminal vesicles. 5. Labelling of all vesicle populations was seen after perfusions lasting less than 1 sec. At this time luminal vesicles were more heavily labelled in the absence of albumin. 6. The labelling of luminal vesicles increased with lengthening perfusion times up to 30-40 sec, after which steady levels of labelling were achieved. The rate of rise in luminal labelling and the steady-state levels reached were both greater in the absence of albumin. By contrast cytoplasmic labelling increased above its initial value only after perfusions of longer than 10 sec. 7. In the steady state, labelled cytoplasmic vesicles contained, on average, fewer ferritin molecules than labelled luminal vesicles. This finding is inconsistent with translocation of labelled

  20. Zinc protoporphyrin/haem ratio and plasma ferritin in preterm infants

    PubMed Central

    Griffin, I; Reid, M; McCormick, K; Cooke, R

    2002-01-01

    Objective: To study the utility of the zinc protoporphyrin/haem (ZPP/H) ratio as a measure of iron status in healthy, growing, preterm infants. Method: ZPP/H was measured in 109 well, preterm infants from the time of hospital discharge until 1 year of age (637 determinations). Results: ZPP/H was initially high, but steadily declined. This was opposite to what was expected from the known changes in iron stores during the first year of life and the observed changes in plasma ferritin. Subjects with higher ZPP/H ratios tended to have lower ferritins, but changes in ZPP/H in a given subject were poorly reflected by changes in plasma ferritin. Between 6 and 9 months of age, ZPP/H correlated with other measures of iron status, but serum ferritin concentration did not. Conclusion: Use of the ZPP/H ratio as a measure of iron status during the first year of life appears to be confounded by the developmental changes in ZPP/H, but in the later half of this period it may be a better measure of iron status than serum ferritin. PMID:12091292

  1. Ferritin and iron status in pregnancy: Relationship to fetal alcohol syndrome

    SciTech Connect

    Baumstark, J.S.; Hill, W.C.; Chun, M.A.; Hunter, W.J. )

    1989-02-09

    Ferritin is a water soluble macromolecule of M{sub r} = 450,000 within whose inner core is stored approximately 4,500 atoms of iron (as ferric oxyhydroxide). The protein is the chief source of stored iron and its determination in serum is an excellent indicator of iron status. This laboratory is engaged in a study of iron metabolism and its relationship to fetal alcohol syndrome (FAS). Ferritin and transferrin levels have been determined ion serial maternal sera, as well as cord serum. Patients were identified as high risk for the development of FAS by questionnaire. Transferrin levels for both maternal and cord serum were within normal literature values and increased, in maternal serum, at a rate of 5 mg/dl per week of gestation. Ferritin levels decreased at a rate of 1 ng/ml per gestational week. At term, the ferritin level for maternal serum in ten patients was 17 ng/ml {plus minus} 12 SD with a range of 2-35 ng/ml. The value for ferritin in cord serum was 78 {plus minus} 36 SD which is significantly lower than the normal mean value of 101 {plus minus} 52 ng/ml. Equating 101 ng/ml with 100% efficiency in iron metabolism it can be calculated that the high risk-for-FAS fetus is 23% less efficient in general iron metabolism than is the fetus of the normal patient. A decrease of 23% efficiency in iron metabolism could be associated with intrauterine growth retardation and/or the genesis of birth defects.

  2. Structure of Human Ferritin L Chain

    SciTech Connect

    Wang,Z.; Li, C.; Ellenburg, M.; Soistman, E.; Ruble, J.; Wright, B.; Ho, J.; Carter, D.

    2006-01-01

    Ferritin is the major iron-storage protein present in all cells. It generally contains 24 subunits, with different ratios of heavy chain (H) to light chain (L), in the shape of a hollow sphere hosting up to 4500 ferric Fe atoms inside. H-rich ferritins catalyze the oxidation of iron(II), while L-rich ferritins promote the nucleation and storage of iron(III). Several X-ray structures have been determined, including those of L-chain ferritins from horse spleen (HoSF), recombinant L-chain ferritins from horse (HoLF), mouse (MoLF) and bullfrog (BfLF) as well as recombinant human H-chain ferritin (HuHF). Here, structures have been determined of two crystal forms of recombinant human L-chain ferritin (HuLF) obtained from native and perdeuterated proteins. The structures show a cluster of acidic residues at the ferrihydrite nucleation site and at the iron channel along the threefold axis. An ordered Cd{sup 2+} structure is observed within the iron channel, offering further insight into the route and mechanism of iron transport into the capsid. The loop between helices D and E, which is disordered in many other L-chain structures, is clearly visible in these two structures. The crystals generated from perdeuterated HuLF will be used for neutron diffraction studies.

  3. GATED PORES IN THE FERRITIN PROTEIN NANOCAGE

    PubMed Central

    Theil, Elizabeth C.; Liu, Xiaofeng S.; Tosha, Takehiko

    2008-01-01

    Synopsis and pictogram: Gated pores in the ferritin family of protein nanocages, illustrated in the pictogram, control transfer of ferrous iron into and out of the cages by regulating contact between hydrated ferric oxide mineral inside the protein cage, and reductants such as FMNH2 on the outside. The structural and functional homology between the gated ion channel proteins in inaccessible membranes and gated ferritin pores in the stable, water soluble nanoprotein, make studies of ferritin pores models for gated pores in many ion channel proteins. Properties of ferritin gated pores, which control rates of FMNH2 reduction of ferric iron in hydrated oxide minerals inside the protein nanocage, are discussed in terms of the conserved pore gate residues (arginine 72-apspartate 122 and leucine 110-leucine 134), of pore sensitivity to heat at temperatures 30 °C below that of the nanocage itself, and of pore sensitivity to physiological changes in urea (1–10 mM). Conditions which alter ferritin pore structure/function in solution, coupled with the high evolutionary conservation of the pore gates, suggest the presence of molecular regulators in vivo that recognize the pore gates and hold them either closed or open, depending on biological iron need. The apparent homology between ferrous ion transport through gated pores in the ferritin nanocage and ion transport through gated pores in ion channel proteins embedded in cell membranes, make studies of water soluble ferritin and the pore gating folding/unfolding a useful model for other gated pores. PMID:19262678

  4. Ferritins for Chemistry and for Life

    PubMed Central

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

    2012-01-01

    Ferritins, highly symmetrical protein nanocages, are reactors for Fe2+ and dioxygen or hydrogen peroxide that are found in all kingdoms of life and in many different cells of multicellular organisms. They synthesize iron concentrates required for cells to make cofactors of iron proteins (heme, FeS, mono and diiron). The caged ferritin biominerals, Fe2O3•H2O are also antioxidants, acting as sinks for iron and oxidants scavenged from damaged proteins; genetic regulation of ferritin biosynthesis is sensitive to both iron and oxidants. Here, the emphasis here is ferritin oxidoreductase chemistry, ferritin ion channels for Fe 2+ transit into and out of the protein cage and Fe 3+ O mineral nucleation, and uses of ferritin cages in nanocatalysis and nanomaterial synthesis. The Fe2+ and O ferritin protein reactors, likely critical in the transition from anaerobic to aerobic life on earth, play central, contemporary roles that balance iron and oxygen chemistry in biology and have emerging roles in nanotechnology. PMID:23470857

  5. 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

  6. Pre-transplant risk factors for cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia after hematopoietic cell transplantation.

    PubMed

    Nakasone, H; Onizuka, M; Suzuki, N; Fujii, N; Taniguchi, S; Kakihana, K; Ogawa, H; Miyamura, K; Eto, T; Sakamaki, H; Yabe, H; Morishima, Y; Kato, K; Suzuki, R; Fukuda, T

    2013-10-01

    Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P=0.05), female-to-male HCT (OR 1.53, P=0.023), and PBSC transplant (OR 1.84, P=0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P=0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P=0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P=0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n=19) and 26% (n=12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.

  7. Autophagy promotes ferroptosis by degradation of ferritin.

    PubMed

    Hou, Wen; Xie, Yangchun; Song, Xinxin; Sun, Xiaofang; Lotze, Michael T; Zeh, Herbert J; Kang, Rui; Tang, Daolin

    2016-08-02

    Macroautophagy/autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis, a novel form of regulated cell death, is characterized by a production of reactive oxygen species from accumulated iron and lipid peroxidation. However, the relationship between autophagy and ferroptosis at the genetic level remains unclear. Here, we demonstrated that autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 (nuclear receptor coactivator 4) was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. Consistently, genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis. In contrast, overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis. These findings provide novel insight into the interplay between autophagy and regulated cell death.

  8. Magnetic properties of artificially synthesized ferritins

    NASA Astrophysics Data System (ADS)

    Kim, B. J.; Lee, H. I.; Cho, S.-B.; Yoon, S.; Suh, B. J.; Jang, Z. H.; St. Pierre, T. G.; Kim, S.-W.; Kim, K.-S.

    2005-05-01

    Human ferritin homopolymers with H or L subunits (rHF and rLF) were genetically engineered in E coli. Apoferritins were then reconstituted with 2000 Fe atoms. A big difference was observed in the rates of iron uptake, whereas the mean core size was similar in rHF and rLF. Magnetization of the recombinant human ferritins were measured as functions of temperature and field. The blocking temperature TB(H) at low fields is considerably higher in rLF than in rHF. From the fit of M(H ) data to a modified Langevin function: M(H )=M0L(μpH/kBT)+χaH, the effective magnetic moment μp is found to be much larger in rLF than in rHF. Experimental data demonstrate that the magnetic properties, in particular, the uncompensated spins of ferritin core are related to the biomineralization process in ferritins.

  9. 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.

  10. Intestinal ferritin H is required for an accurate control of iron absorption.

    PubMed

    Vanoaica, Liviu; Darshan, Deepak; Richman, Larry; Schümann, Klaus; Kühn, Lukas C

    2010-09-08

    To maintain appropriate body iron levels, iron absorption by the proximal duodenum is thought to be controlled by hepcidin, a polypeptide secreted by hepatocytes in response to high serum iron. Hepcidin limits basolateral iron efflux from the duodenal epithelium by binding and downregulating the intestinal iron exporter ferroportin. Here, we found that mice with an intestinal ferritin H gene deletion show increased body iron stores and transferrin saturation. As expected for iron-loaded animals, the ferritin H-deleted mice showed induced liver hepcidin mRNA levels and reduced duodenal expression of DMT1 and DcytB mRNA. In spite of these feedback controls, intestinal ferroportin protein and (59)Fe absorption were increased more than 2-fold in the deleted mice. Our results demonstrate that hepcidin-mediated regulation alone is insufficient to restrict iron absorption and that intestinal ferritin H is also required to limit iron efflux from intestinal cells.

  11. Is It Possible to Predict Pulmonary Complications and Mortality in Hematopoietic Stem Cell Transplantation Recipients from Pre-Transplantation Exhaled Nitric Oxide Levels?

    PubMed

    Köktürk, Nurdan; Yıldırım, Fatma; Aydoğdu, Müge; Akı, Şahika Zeynep; Yeğin, Zeynep Arzu; Özkurt, Zübeyde Nur; Suyanı, Elif; Kıvılcım Oğuzülgen, İpek; Türköz Sucak, Gülsan

    2016-03-05

    Chemo/radiotherapy-induced free oxygen radicals and reactive oxygen derivatives contribute to the development of early and late transplantation-related pulmonary and extra-pulmonary complications in hematopoietic stem cell transplantation (HSCT) recipients. It has been proposed that an increase in fractional exhaled nitric oxide (FeNO) level indicates oxidative stress and inflammation in the airways. The aim of this prospective study is to evaluate the pre-transplantation FeNO levels in HSCT patients and to search for its role in predicting post-transplantation pulmonary complications and mortality. HSCT patients were included in the study prospectively between October 2009 and July 2011. Pre-transplantation FeNO levels were measured with a NIOX MINO® device prior to conditioning regimens. All patients were monitored prospectively for post-transplantation pulmonary complications with medical history, physical examination, chest X-ray, and pulmonary function tests. A total of 56 patients (33 autologous, 23 allogeneic) with mean age of 45±13 years were included in the study, among whom 40 (71%) were male. Pre-transplantation FeNO level of the whole study group was found to be 24±13 (mean ± standard deviation) parts per billion (ppb). The FeNO level in allogeneic HSCT recipients was 19±6 ppb while it was 27±15 ppb in autologous HSCT recipients (p=0.042). No significant correlation was found between the pre-transplantation chemotherapy and radiotherapy protocols and baseline FeNO levels (p>0.05). Post-transplantation pulmonary toxicity was identified in 12 (21%) patients and no significant relationship was found between baseline FeNO levels and pulmonary toxicity. The survival rate of the whole study group for 1 year after transplantation was 70%. No significant relationship was identified between baseline FeNO values and survival (FeNO 19±7 ppb in patients who died and 26±15 ppb in the survivors; p=0.114). Pre-transplantation FeNO measurement does not seem to

  12. Relationship between iron and phosphate in mammalian ferritins.

    PubMed

    de Silva, D; Guo, J H; Aust, S D

    1993-06-01

    The core of mammalian ferritin is known to contain varying amounts of phosphate as well as iron. This study examined the variations in phosphate found in ferritins from horse spleen, rat liver, and bovine liver. The amount of phosphate varied inversely with the amount of iron present in the core. Theoretical extrapolation showed that in the absence of phosphate approximately 4400 atoms of iron could be incorporated into ferritin. Reconstitution of ferritin with iron and ceruloplasmin followed by prolonged incubation with phosphate produced cores similar to native ferritin in terms of iron to phosphate ratios and rates of iron release. However, ferritin reconstituted in the presence of phosphate differed markedly from native ferritins. The data suggest that phosphate is an integral part of mammalian ferritin cores and influences both core formation and the ease by which iron is released from ferritin.

  13. Bioavailability of iron from plant and animal ferritins.

    PubMed

    Lv, Chenyan; Zhao, Guanghua; Lönnerdal, Bo

    2015-05-01

    Iron deficiency is a major public health problem in the world. Ferritin is being explored as a novel and natural strategy for iron supplementation. The objective of this study was to evaluate iron bioavailability from ferritin isolated from plant and animal sources. The stability of plant ferritin and animal ferritin was studied by in vitro and in vivo digestion to determine whether these ferritins can pass through the gastrointestinal tract in intact form. Results from sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot indicate that both plant ferritin and animal ferritin can resist digestion (both under acidic and moderately acidic conditions). Furthermore, ferritin was labeled with (59)Fe, and bioavailability of iron from ferritin was assessed by uptake into Caco-2 cells. Our results indicate that iron is taken up from the ferritins and that iron bioavailability from soybean ferritin (rH-1:rH-2=1:1) is the highest. These results may be explained by the binding of ferritin to Caco-2 cells, which can be attributed to the interaction between ferritin and its putative receptor(s) at the surface of Caco-2 cells. In conclusion, ferritin from plant and animal sources may be developed as an iron source.

  14. Vitamin B12, folic acid, ferritin and haematological variables among Thai construction site workers in urban Bangkok.

    PubMed

    Tungtrongchitr, R; Pongpaew, P; Phonrat, B; Chanjanakitskul, S; Paksanont, S; Migasena, P; Schelp, F P

    1995-01-01

    Serum vitamin B12, folic acid, ferritin and haematological variables were investigated in eighty-seven male and nineteen female construction site workers in Bangkok. Haemoglobin concentration, haematocrit and MCHC were found to be higher in male than in female workers. Serum ferritin was slightly higher in males than in females. Serum B12 was found to be higher in male than in female workers and serum folic acid level were significantly higher in female than in male workers. Vitamin B12 deficiency was found in 2.3 per cent and folic acid deficiency in 6.9 per cent of the male workers. Serum vitamin B12 and folic acid levels were normal for female workers. The adequate serum levels of vitamin B12 and folic acid might be the result of the habit of the workers to consume tonic drinks which contain glucose, caffeine, and vitamins especially vitamins B6, and B12.

  15. 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.

  16. Ferritin couples iron and fatty acid metabolism.

    PubMed

    Bu, Weiming; Liu, Renyu; Cheung-Lau, Jasmina C; Dmochowski, Ivan J; Loll, Patrick J; Eckenhoff, Roderic G

    2012-06-01

    A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 μM affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 Å and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.

  17. Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome

    PubMed Central

    2013-01-01

    Background Hereditary Hyperferritinaemia Cataract Syndrome (HHCS) is a rare autosomal dominant disease characterized by increased serum ferritin levels and early onset of bilateral cataract. The disease is caused by mutations in the Iron-Responsive Element (IRE) located in the 5′ untranslated region of L-Ferritin (FTL) mRNA, which post-transcriptionally regulates ferritin expression. Methods We describe two families presenting high serum ferritin levels and juvenile cataract with novel mutations in the L-ferritin IRE. The mutations were further characterized by in vitro functional studies. Results We have identified two novel mutations in the IRE of L-Ferritin causing HHCS: the Badalona +36C > U and the Heidelberg +52 G > C mutation. Both mutations conferred reduced binding affinity on recombinant Iron Regulatory Proteins (IPRs) in EMSA experiments. Interestingly, the Badalona +36C > U mutation was found not only in heterozygosity, as expected for an autosomal dominant disease, but also in the homozygous state in some affected subjects. Additionally we report an update of all mutations identified so far to cause HHCS. Conclusions The Badalona +36C > U and Heidelberg +52 G > C mutations within the L-ferritin IRE only mildly alter the binding capacity of the Iron Regulatory Proteins but are still causative for the disease. PMID:23421845

  18. Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome.

    PubMed

    Luscieti, Sara; Tolle, Gabriele; Aranda, Jessica; Campos, Carmen Benet; Risse, Frank; Morán, Érica; Muckenthaler, Martina U; Sánchez, Mayka

    2013-02-19

    Hereditary Hyperferritinaemia Cataract Syndrome (HHCS) is a rare autosomal dominant disease characterized by increased serum ferritin levels and early onset of bilateral cataract. The disease is caused by mutations in the Iron-Responsive Element (IRE) located in the 5' untranslated region of L-Ferritin (FTL) mRNA, which post-transcriptionally regulates ferritin expression. We describe two families presenting high serum ferritin levels and juvenile cataract with novel mutations in the L-ferritin IRE. The mutations were further characterized by in vitro functional studies. We have identified two novel mutations in the IRE of L-Ferritin causing HHCS: the Badalona +36C > U and the Heidelberg +52 G > C mutation. Both mutations conferred reduced binding affinity on recombinant Iron Regulatory Proteins (IPRs) in EMSA experiments. Interestingly, the Badalona +36C > U mutation was found not only in heterozygosity, as expected for an autosomal dominant disease, but also in the homozygous state in some affected subjects. Additionally we report an update of all mutations identified so far to cause HHCS. The Badalona +36C > U and Heidelberg +52 G > C mutations within the L-ferritin IRE only mildly alter the binding capacity of the Iron Regulatory Proteins but are still causative for the disease.

  19. Ferritin protein imaging and detection by magnetic force microscopy.

    PubMed

    Hsieh, Chiung-Wen; Zheng, Bin; Hsieh, Shuchen

    2010-03-14

    Magnetic force microscopy was used to image and detect ferritin proteins and the strength of the magnetic signal is discussed, revealing a large workable lift height between the magnetic tip and the ferritin sample.

  20. C29G in the iron-responsive element of L-ferritin: a new mutation associated with hyperferritinemia-cataract.

    PubMed

    Bosio, Sandra; Campanella, Alessandro; Gramaglia, Enrico; Porporato, Paolo; Longo, Filomena; Cremonesi, Laura; Levi, Sonia; Camaschella, Clara

    2004-01-01

    Hyperferritinemia-cataract syndrome (HHCS) is a dominant disorder characterized by high serum ferritin and early onset of bilateral cataract. The disorder is caused by mutations in the iron-responsive element (IRE) of l-ferritin, which disrupt the postranscriptional control of l-ferritin synthesis. Here, we report a new (C>G) mutation which affects base 29 in the loop (c.-169C>G), previously unrecognized as essential for the stem loop stability. The mutation was identified in two members of an Italian family. Computer modeling and electrophoretic mobility shift assay (EMSA) confirm a decreased affinity of the C29G IRE for IRPs control proteins.

  1. Single-Center Experience in Pre-transplant Hepatitis C Virus (HCV) Treatment Among Living Donor Liver Transplant Candidates: Bridging the Direct-Acting Antivirals (DAA).

    PubMed

    Niranjan-Azadi, Ashwini M; Kabacam, Gokhan; Durand, Christine M; Anjum, Saad; Saberi, Behnam; Dagher, Nabil N; Philosophe, Benjamin; Gurakar, Ahmet

    2017-09-22

    BACKGROUND Treatment with DAAs before deceased donor liver transplantation has been shown to be an effective strategy to prevent post-transplant HCV recurrence, with a 95% cure-rate among individuals who achieve undetectable HCV VL for ≥30 days pre- transplant. This strategy has not been evaluated in LDLT. MATERIAL AND METHODS We evaluated outcomes in LDLT recipients treated with DAAs pre-transplant and bridged with 4 weeks of post-transplant SOF. All cases of LDLT at Johns Hopkins (1/1/2014-3/1/15) were retrospectively reviewed. RESULTS There were 4 HCV+ LDLT cases treated with DAAs pre- and post-transplant. Pre-transplant DAA regimens included SOF plus SIM in 2 cases of HCC and SOF plus RBV in 2 cases of ESLD. All patients achieved negative VL by week 7 of treatment and all patients had at least 30 days of HCV RNA negativity at the time of LDLT. Patient 4 had a delay in LDLT due to uncontrolled pulmonary hypertension, and experienced viral breakthrough because of treatment interruption. Due to concerns for SOF resistance, a salvage regimen of LDV-SOF and SIM was used. Post-LDLT patients 1-3 received 4 weeks of SOF monotherapy and patient 4 received 14 weeks of LDV-SOF. Three patients achieved SVR12. One died from non-HCV related complications at 4 months post-LDLT. CONCLUSIONS Our preliminary experience suggests that bridging DAAs pre- and post-LDLT is an effective strategy to prevent HCV recurrence. With delays in transplant and prolonged use of SOF/RBV, there is a risk of viral breakthrough, but a salvage strategy of triple DAA therapy can be effective.

  2. Pre-transplant Quantitative Determination of NPM1 Mutation Significantly Predicts Outcome of AIlogeneic Hematopoietic Stem Cell Transplantation in Patients with Normal Karyotype AML in Complete Remission.

    PubMed

    Karas, Michal; Steinerova, Katerina; Lysak, Daniel; Hrabetova, Marcela; Jungova, Alexandra; Sramek, Jiri; Jindra, Pavel; Polivka, Jiri; Holubec, Lubos

    2016-10-01

    Minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) before allogeneic hematopoietic stem cell transplantation (alloHSCT) can influence the results of therapy. With the aim of evaluating the potential role of pre-transplant MRD, we studied the impact of pre-transplant MRD level on the outcome of alloHSCT in patients with AML in complete remission (CR). From 2/2005 to 9/2014, 60 patients with a median age of 54 years (range=30-66 years) with normal karyotype-AML harboring nucleophosmin 1 (NPM1) mutation [53% Fms-related tyrosine kinase receptor 3 internal tandem duplication (FLT3/ITD)-positive] in first (n=45) or second (n=15) CR underwent myeloablative (n=16) or reduced-intensity (n=44) alloHSCT (27% related, 73% unrelated). The MRD level was determined from bone marrow samples using real-time polymerase chain reaction for detection of NPM1 mutations before starting the conditioning regimen. The estimated probabilities of 3-year relapse, event-free survival (EFS) and overall survival (OS) for the whole cohort were 28%, 54%, and 59%, respectively. Statistical analysis showed that only age over 63 years and high MRD level affected alloHSCT outcome. Pre-transplant MRD level of 10 mutant copies of NPM1 per 10,000 Abelson murine leukemia viral oncogene homolog 1 (ABL) copies had the strongest statistical significance, and detection of higher MRD level (>10 NPM1-mutant copies) before alloHSCT was associated with increased overall mortality (hazard ratio=3.71; 95% confidence interval=1.55-9.06; p=0.004). The estimated probabilities of 3-year relapse, EFS, and OS were 6%, 72%, and 75% for patients with a low level of MRD and 48%, 35%, and 40% for patients with a higher level. Our data showed that the pre-transplant level of MRD in patients with normal karyotype AML harboring NPM1 mutation in CR provides important prognostic information, which as an independent prognostic factor predicts transplant results. Copyright© 2016 International Institute of

  3. 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

  4. Structural differences in ferritins from normal and malignant rat tissues.

    PubMed

    Linder, M C; Moor, J R; Munro, H N; Morris, H P

    1975-04-29

    Ferritins purified from several normal and malignant rat tissues were examined for amino acid composition, content of tryptic peptides, available sulfhydryl groups and subunit sizes and proportion. Ferritin extracted from adult kidney, neonatal liver and hepatic and renal tumors differed from the ferritin of adult rat liver in migration on electrophoretic gels and in antibody affinity, but did not differ among themselves. Nevertheless, they showed distinctive differences in amino acid composition and tryptic peptide content. All of them and also adult liver ferritin contained two major species of subunits differing in molecular weight. The proportions of subunits, and the available sulfhydryl groups of the intact ferritin molecules, differed among these tissue ferritins. On the basis of amino acid and peptide content, the ferritins of hepatomas and the renal tumor analyzed showec the greatest similarity but not identity. The ferritin of neonatal liver was next most similar. Kidney ferritin differed considerably in composition from tumor and neonatal ferritins, while adult liver ferritin was the most extremely divergent of the series examined. A similar progressive difference was found on examining the proportions of subunits and sulfhydryl groups in these ferritins. However, changes in subunit proportion cannot explain the amino acid and peptide compositional changes.

  5. Factors Influencing Measurement of Serum Iron Concentration in Dogs: Diurnal Variation and Hyperferritinemia

    PubMed Central

    CHIKAZAWA, Seishiro; HORI, Yasutomo; KANAI, Kazutaka; ITO, Naoyuki; HOSHI, Fumio; ORINO, Koichi; WATANABE, Kiyotaka; HIGUCHI, Seiichi

    2013-01-01

    ABSTRACT We evaluated diurnal variation and hyperferritinemia as factors that influence the values of serum iron concentration in dogs, using the International Committee for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels were significantly higher in the morning than in the evening in 6 clinically healthy beagle dogs, and the maximum decrease in serum iron concentration was 47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine cases with various serum ferritin levels was evaluated by immunoprecipitation of ferritin. The rate of decline in the serum iron concentrations positively correlated with serum ferritin levels (r=0.48, P=0.024). These results show that it is necessary to consider the sampling time and serum ferritin level for accurate interpretation of serum iron concentrations in dogs. PMID:23877842

  6. Magic ferritin: A novel chemotherapeutic encapsulation bullet

    NASA Astrophysics Data System (ADS)

    Simsek, Ece; Akif Kilic, Mehmet

    2005-05-01

    The dissociation of apoferritin into subunits at pH 2 followed by its reformation at pH 7.4 in the presence of doxorubicin-HCl gives rise to a solution containing five doxorubicin-HCl molecules trapped within the apoferritin. This is the first report showing that ferritin can encapsulate an anti-cancer drug into its cavity.

  7. THE CELLULAR TRANSFORMATION OF INJECTED COLLOIDAL IRON COMPLEXES INTO FERRITIN AND HEMOSIDERIN IN EXPERIMENTAL ANIMALS

    PubMed Central

    Richter, Goetz W.

    1959-01-01

    As revealed by electron microscopy and electron diffraction, the physical state of ferric hydroxide micelles contained in iron-dextran, saccharated iron oxide, and hydrous ferric oxide ("ferric hydroxide") differs notably from the state of the ferric hydroxide in ferritin or hemosiderin. By virtue of this difference one can trace the intracellular transformation of colloidal iron, administered parenterally, into ferritin and hemosiderin. One hour after intraperitoneal injection of iron-dextran or saccharated iron oxide into mice, characteristic deposits were present in splenic macrophages, in sinusoidal endothelial cells of spleen and liver, and in vascular endothelial cells of various renal capillaries. Four hours after injection, small numbers of ferritin molecules were identifiable about intracellular aggregates of injected iron compounds; and by the 6th day, ferritin was abundant in close proximity to deposits of injected iron compounds. The latter were frequently situated in cytoplasmic vesicles delimited by single membranes. These vesicles were most frequently found in tissue obtained during the first 6 days after injection; and in certain of the vesicles ferritin molecules surrounded closely packed aggregates of injected material. Much unchanged ferric hydroxide was still present in macrophages and vascular endothelial cells 3 to 4 weeks after injection. While electron microscopy left no doubt about the identity of injected ferric hydroxide on the one hand, and of ferritin or hemosiderin on the other, histochemical tests for iron failed in this respect. Precipitation of ferric hydroxide (hydrous ferric oxide) from stabilized colloidal dispersions of iron-dextran was brought about in vitro by incubation with minced mouse tissue (e.g. liver), but not by incubation with mouse serum or blood. Subcutaneous injections of hydrous gel of ferric oxide into mice initially produced localized extracellular precipitates. Most of the material was still extracellular 16

  8. Ferritins as Nanoplatforms for Imaging and Drug Delivery

    PubMed Central

    Zhen, Zipeng; Tang, Wei; Todd, Trever; Xie, Jin

    2015-01-01

    Introduction Due to unique architecture and surface properties, ferritin has emerged as an important class of biomaterial. Many studies suggest that ferritin and its derivatives hold great potential in a wide range of bio-applications. Areas covered In this review, we summarize recent progress on employing ferritins as a platform to construct functional nanoparticles for applications in magnetic resonance imaging (MRI), optical imaging, cell tracking, and drug delivery. Expert opinion As a natural polymer, ferritins afford advantages such as high biocompatibility, good biodegradability, and a relatively long plasma half-life. These attributes put ferritins ahead of conventional materials in clinical translation for imaging and drug delivery purposes. PMID:25070839

  9. 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.

  10. Distinguishing ferritin from apoferritin using magnetic force microscopy.

    PubMed

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

    2014-11-21

    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.

  11. Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin.

    PubMed

    Kapoian, Toros; O'Mara, Neeta B; Singh, Ajay K; Moran, John; Rizkala, Adel R; Geronemus, Robert; Kopelman, Robert C; Dahl, Naomi V; Coyne, Daniel W

    2008-02-01

    The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.

  12. Axillary versus peripheral blood levels of sialic acid, ferritin, and CEA in patients with breast cancer.

    PubMed

    Monti, M; Catania, S; Locatelli, E; Gandini, R; Reggiani, A; Cunietti, E

    1990-12-01

    Serum levels of total sialic acid, carcinoembryonic antigen (CEA), ferritin, lactate dehydrogenase, and creatine phosphokinase were measured both in tumor drainage blood (axillary vein) and in peripheral blood obtained from 121 breast cancer patients during surgery. No significant differences between mean values in peripheral and tumor draining blood, between cancer patients and healthy controls, or between patients with or without axillary lymph node metastases were found for any of the markers. Both ferritin and CEA levels were higher in axillary and peripheral blood from patients with central breast cancer versus other sites but the difference was significant only for CEA (p less than 0.05). CEA levels were significantly higher (p less than 0.01) in patients with greater than 2 cm diameter carcinomas versus T1 stage patients in axillary but not in peripheral blood. When the cephalic vein was clamped before the axillary sample was taken, ferritin showed a significant increase (p less than 0.05). We conclude that measurement of sialic acid, CEA, and ferritin in axillary venous blood in breast cancer patients is not of clinical benefit, although further data are needed to clarify whether other advantages can be derived.

  13. Children with autism: effect of iron supplementation on sleep and ferritin.

    PubMed

    Dosman, Cara F; Brian, Jessica A; Drmic, Irene E; Senthilselvan, Ambikaipakan; Harford, Mary M; Smith, Ryan W; Sharieff, Waseem; Zlotkin, Stanley H; Moldofsky, Harvey; Roberts, S Wendy

    2007-03-01

    To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency.

  14. Combined use of rituximab and plasmapheresis pre-transplant increases post-transplant infections in renal transplant recipients with basiliximab induction therapy.

    PubMed

    Chung, B H; Yun, J T; Ha, S E; Kim, J I; Moon, I S; Choi, B S; Park, C W; Kim, Y S; Yang, C W

    2013-12-01

    We investigated the effect of combined use of rituximab (RTX) and plasmapheresis (PP) pre-transplant on post-transplant infection. A total of 196 patients undergoing living-donor kidney transplantation at Seoul St. Mary's Hospital, all of whom underwent basiliximab induction therapy, were included in the study. They were divided into 3 groups: RTX/PP/intravenous immune globulin (IVIG) (the RPI group; n = 53), RTX monotherapy (the RTX group; n = 14), and control (the CONT group; n = 129). We compared the post-transplant infections in the 3 groups. The overall prevalence of infection was significantly higher, and the infection-free survival rate was lower, in the RPI group compared with the RTX or CONT groups (P < 0.05). A trend toward more severe bacterial infections was seen in the RPI group compared with the other groups, and fungal infections developed only in the RPI group. After anti-rejection therapy, a significantly higher rate of infection developed in the RPI group than in the other groups (P < 0.05). In addition, the RPI group was an independent risk factor for the development of infection. Our results show that in the setting of basiliximab induction, the use of combined RTX and PP therapy pre-transplant significantly increases the risk for post-transplant infection. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Characterization of nuclear ferritin and mechanism of translocation

    PubMed Central

    2005-01-01

    Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in cell nuclei. It is an established fact that H-ferritin is the major form of nuclear ferritin, but little is known about the roles of ferritin in nuclei or about the mechanisms that control its appearance within the nuclear volume. In the present study, we show that, for human SW1088 astrocytoma cells, the nuclear and cytoplasmic forms of H-ferritin are products of the same mRNA. Histochemical and biochemical evidence is presented showing that ferritin is distributed non-randomly within the nuclear volume and that it preferentially associates with heterochromatin. Both cytoplasmic and nuclear populations of H-ferritin contain mixtures of non- and O-glycosylated forms, but the nuclear population is enriched in O-glycosylated forms. Cells treated with alloxan, a potent inhibitor of O-glycosylation, contained significantly less nuclear ferritin compared with cells grown in control media. Alloxan inhibited the reappearance of H-ferritin in nuclei of cells released from conditions of iron depletion, but did not prevent its disappearance from nuclei of cells undergoing iron depletion. These results suggest that O-glycosylation accompanies the transfer of ferritin from the cytoplasm to the nucleus, but does not influence the reverse process. The picture that emerges is one in which ferritin translocation between the cytoplasm and the nucleus is post-translationally regulated and responds to environmental and nutritional cues. PMID:15675895

  16. THE ASSOCIATION BETWEEN SERUM FERRITIN AND URIC ACID IN HUMANS

    EPA Science Inventory

    OBJECTIVE: Urate forms a coordination complex with Fe(3+) which does not support electron transport. The only enzymatic source of urate is xanthine oxidoreductase. If a major purpose of xanthine oxidoreductase is the production of urate to function as an iron chelator and antioxi...

  17. THE ASSOCIATION BETWEEN SERUM FERRITIN AND URIC ACID IN HUMANS

    EPA Science Inventory

    OBJECTIVE: Urate forms a coordination complex with Fe(3+) which does not support electron transport. The only enzymatic source of urate is xanthine oxidoreductase. If a major purpose of xanthine oxidoreductase is the production of urate to function as an iron chelator and antioxi...

  18. Utility of Access Soluble Transferrin Receptor (sTfR) and sTfR/log Ferritin Index in Diagnosing Iron Deficiency Anemia.

    PubMed

    Shin, Dong Hoon; Kim, Hyun Soo; Park, Min Jeong; Suh, In Bum; Shin, Kyu Sung

    2015-01-01

    The Access(®) soluble transferrin receptor (sTfR) is considered the world's first automated chemiluminescence immunoassay. In this study, the diagnostic utility of this and other tests for serum iron were evaluated by studying their interrelationships with inflammation. A total of 367 patients with anemia (iron deficiency anemia [IDA], 157; anemia of chronic disease [ACD], 210) and 80 normal controls were subjected to a battery of diagnostic tests, including complete blood cell count, serum iron, total iron-binding capacity (TIBC), C-reactive protein (CRP), ferritin, sTfR, and hepcidin. The accuracy of test parameters was determined by the area under the receiver operating characteristic curve (AUC). Patients falling within the ferritin grey zone (10-100 ng/ml) were evaluated separately, given that such individuals are typically difficult to detect and manage in actual clinical practice. CRP was used to assess the correlation between the aforementioned markers of iron and inflammation. The single most accurate diagnostic test used to differentiate IDA from ACD was serum ferritin (AUC 0.989). However, sTfR assay outperformed other tests in the ferritin grey zone (AUC 0.931), and the sTfR/log ferritin index was the most reliable parameter in both scenarios (AUC 0.994 and 0.962, respectively). Ferritin, TIBC, and hepcidin showed the highest correlation with CRP, whereas sTfR displayed the lowest. The Access sTfR and sTfR/log ferritin index enabled highly accurate diagnosis of IDA in the ferritin grey zone. This is an easy-to-use automated chemiluminescence immunoassay, amenable to routine use in hospitals. © 2015 by the Association of Clinical Scientists, Inc.

  19. The effect of UVB irradiation on ferritin subunit synthesis, ferritin assembly and Fe metabolism in cultured canine lens epithelial cells.

    PubMed

    Harned, J; Grimes, A M; McGahan, M C

    2003-04-01

    Ferritin is a multimeric protein consisting of heavy and light chains assembled in different tissue-specific ratios, which can protect cells from oxidative stress by storing reactive iron (Fe). Because the lens is constantly exposed to UV irradiation, we studied its effects on ferritin synthesis and Fe metabolism in cultured lens epithelial cells with and without ascorbic acid (Asc). UVB caused a large increase in accumulation of newly synthesized ferritin chains; this increase was additive to that induced by Asc. In contrast to the Asc-induced increase in Fe storage, Fe storage in ferritin was unaltered by UVB. Although UVB increased accumulation of newly synthesized ferritin chains, total ferritin levels were unaltered. In contrast, Asc, which induced a quantitatively similar increase in accumulation of newly synthesized ferritin chains, doubled the total amount of ferritin. Because UVB did not change Fe storage in ferritin or the size of the labile Fe pool, it was hypothesized and then determined that these newly synthesized chains did not assemble into functional holoferritin. Numerous studies detail the effects of various treatments on de novo ferritin synthesis; however, this study provides a cautionary note regarding the conclusions of such studies in the absence of data indicating assembly of functional ferritin molecules.

  20. Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury.

    PubMed

    Rothman, R J; Serroni, A; Farber, J L

    1992-10-01

    A cellular pool of transient ferric iron that is chelatable by deferoxamine, distinct from ferritin, and required for oxidative cell injury has been identified in cultured rat hepatocytes labeled with 59FeCl3. Pretreatment of hepatocytes with deferoxamine depleted the cellular pool of chelatable iron and protected the cells from an oxidative injury. Incubation of deferoxamine-pretreated hepatocytes in serum-free medium restored both the chelatable iron pool and the susceptibility to oxidative injury. Furthermore, inhibition of protein degradation with chymostatin prevented the restoration of both the chelatable pool and susceptibility to oxidative injury. The deferoxamine-chelatable iron pool was distinguished kinetically and immunochemically from the larger cellular pool of ferritin iron. The labeled iron in the deferoxamine-chelatable pool was transient, unlike either the total cellular uptake of 59Fe or its incorporation into ferritin, both of which increased with time of labeling. With pulse-chase labeling, the percentage of the total uptake of 59Fe that was represented by the deferoxamine-chelatable pool decreased. At the same time, the percentage represented by radioactivity immunoprecipitable as ferritin increased. Furthermore, immunoprecipitation of ferritin from the labeled lysates enriched the resulting immunosupernatants in deferoxamine-chelatable iron. The degree of enrichment for chelatable iron correlated with the percentage of the cellular label that was immunoprecipitable as ferritin. The deferoxamine-chelatable iron appears to represent a metabolically common pool of iron that is rapidly in transit through the cell. Extracellular iron entering the pool can be utilized for heme synthesis or stored in ferritin, whereas protein degradation releases storage iron into this pool.

  1. Ferritin levels and risk of metabolic syndrome: meta-analysis of observational studies

    PubMed Central

    2014-01-01

    Background Elevated ferritin levels have been associated with single cardiovascular risk factors but the relationship to the presence of metabolic syndrome is inconclusive. The aim of this systematic review and meta-analysis of published observational studies was to estimate the association between serum ferritin levels and metabolic syndrome in adults. Methods The Pubmed, SCOPUS and the Cochrane Library databases were searched for epidemiological studies that assessed the association between ferritin levels and metabolic syndrome and were published before September 2013. There were no language restrictions. Two investigators independently selected eligible studies. Measures of association were pooled by using an inverse-variance weighted random-effects model. The heterogeneity among studies was examined using the I2 index. Publication bias was evaluated using the funnel plot. Results Twelve cross-sectional, one case–control and two prospective studies met our inclusion criteria including data from a total of 56,053 participants. The pooled odds ratio (OR) for the metabolic syndrome comparing the highest and lowest category of ferritin levels was 1.73 (95% CI: 1.54, 1.95; I2 = 75,4%). Subgroup analyses indicate that pooled OR was 1.92 (95% CI: 1.61, 2.30; I2 = 78%) for studies adjusting for C-reactive protein (CRP), and 1.52 (95% CI:1. 36, 1.69; I2 = 41%) for studies that did not adjust for CRP (P = 0.044). This finding was remarkably robust in the sensitivity analysis. We did not find publication bias. Conclusions The meta-analysis suggests that increased ferritin levels are independently and positively associated with the presence of the metabolic syndrome with an odds ratio higher than 1.73. PMID:24884526

  2. Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control

    PubMed Central

    Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

    2016-01-01

    Background The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. Patients and Methods 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Results Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33–3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Conclusions Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm

  3. Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

    PubMed

    Schrem, Harald; Schneider, Valentin; Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

    2016-01-01

    The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age <52.3 years (p = 0.007, Hazard ratio (HR): 0.82), age >62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (p<0.001, HR: 1.04), ADPKD (p = 0.008, HR: 1.26) and diabetic nephropathy (p = 0.004, HR = 1.51). G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05). Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root

  4. Ferritin Level Is Positively Associated with Chronic Kidney Disease in Korean Men, Based on the 2010–2012 Korean National Health and Nutrition Examination Survey

    PubMed Central

    Kang, Hee-Taik; Linton, John A.; Kwon, Soon Kil; Park, Byoung-Jin; Lee, Jong Hun

    2016-01-01

    (1) Background: Oxidative stress and inflammation are associated with higher risk of chronic kidney disease (CKD). Serum ferritin concentrations correlate with total iron levels and systemic inflammation. (2) Methods: This study was cross-sectionally designed, based on the 2010–2012 Korean National Health and Nutrition Examination Survey (KNHANES). According to ferritin values, 13,462 participants (6082 men and 7380 women) were categorized into the normal- and high-ferritin groups (cut-off points: 200 ng/mL in men, 150 ng/mL in women). (3) Results: The mean ages of men and women were 44.5 and 48.4 years, respectively. The percentage of participants categorized into the high-ferritin group was 15.1% for men and 3.6% for women. The estimated glomerular filtration rate levels in the normal- and high-ferritin groups were 93.2 and 93.8 mL/min/1.73 m2 for men and 97.1 and 87.7 mL/min/1.73 m2 for women, respectively. The prevalence of CKD in the normal- and high-ferritin groups was 2.6% and 3.9% for men and 3.2% and 8.1% for women, respectively. Compared with the normal-ferritin group, the odds ratios (95% confidence intervals) for CKD of the high-ferritin group were 1.573 (1.014–2.441) in men and 1.061 (0.381–2.955) in women, after adjustments for age and other covariates. (4) Conclusions: High ferritin levels were associated with a higher risk of CKD in men but not in women. PMID:27801876

  5. LOSS OF IRON FROM MOUSE PERITONEAL MACROPHAGES IN VITRO AFTER UPTAKE OF [55FE]FERRITIN AND [55FE]FERRITIN RABBIT ANTIFERRITIN COMPLEXES

    PubMed Central

    Fedorko, Martha E.

    1974-01-01

    Mouse peritoneal macrophages in culture for 24 h were exposed to horse [55Fe]ferritin and rabbit antihorse [55Fe]ferritin antibody complex and the amount of 55Fe in the medium was assayed up to 2 days after the pulse uptake. Cell survival was assayed by photographing the same areas of the tissue culture Petri dish on successive days and by counting cell numbers per unit area. In experiments in which quantitative assay for cell death is negligible, about 10–20% of the iron ingested by pinocytosis or phagocytosis is released to iron-free medium containing either freshly dialyzed or deironized newborn calf serum (10%). Over the 2-day postpulse period, iron loss is linear. This loss of iron to the medium is significantly reduced by adding iron-saturated newborn calf serum in the postpulse recovery period. A significant portion of the iron released to the medium is bound to transferrin. When human serum is used in the tissue culture system, similar quantities (10–25%) of the ingested iron are lost to the medium 2 days after the pulse. PMID:4859401

  6. Serum transferrin receptor.

    PubMed

    Cook, J D; Skikne, B S; Baynes, R D

    1993-01-01

    The transferrin receptor plays a critical role in iron metabolism by precisely controlling the flow of transferrin iron into body cells. A soluble truncated form of the receptor can be detected in human serum using sensitive immunoassays, and the initial clinical experience with this new measurement indicates that it reflects the total body mass of tissue receptor. Serum receptor levels rise significantly with tissue iron deficiency and the heightened demand for iron associated with expansion of the erythroid marrow. The serum receptor provides a quantitative measure of functional iron deficiency and distinguishes the associated anemia from that of chronic disease. If iron deficiency is excluded, the serum receptor provides a quantitative measure of total erythropoiesis that is more sensitive and less invasive than bone marrow examination currently used to assess red cell precursor mass. Performed in conjunction with serum ferritin measurements, the serum receptor will be useful in establishing the true prevalence of iron deficiency anemia in population studies.

  7. Long-Range Tunneling Processes across Ferritin-Based Junctions.

    PubMed

    Kumar, Karuppannan Senthil; Pasula, Rupali Reddy; Lim, Sierin; Nijhuis, Christian A

    2016-03-02

    The mechanism of long-range charge transport across tunneling junctions with monolayers of ferritin is investigated. It is shown that the mechanism can be switched between coherent tunneling, sequential tunneling, and hopping by changing the iron content inside the ferritin. This study shows that ferritins are an interesting class of biomolecules to control charge transport. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. 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.

  9. Other aspects of bariatric surgery: liver steatosis, ferritin and cholesterol metabolism.

    PubMed

    Pontiroli, A E; Benetti, A; Folini, L; Merlotti, C; Frigè, F

    2013-03-01

    Bariatric surgery developed in the late 1970 to treat severe hyperlipidemias in overweight individuals, not necessarily obese. Several techniques have been developed, and the concept has come first of a surgery for morbid obesity, then of a cure for diabetes in morbid obesity. There are other aspects of bariatric surgery that deserve attention, beyond BMI and diabetes, such as hypertension, poor life expectancy, increased prevalence of cancer, congestive heart failure, social inadequacy. The aim of this presentation is to review some recent development in clinical research, in the fields of liver steatosis, ferritin metabolism, and cholesterol metabolism. Liver steatosis, also called fatty liver encompasses a graduation of diseases with different clinical relevance and prognosis. NAFLD correlates with atherosclerosis, insulin resistance and diabetes mellitus. There is now evidence that weight loss, obtained through diet or restrictive surgery, reduces the prevalence (and the severity) of NAFLD. An other issue is represented by serum ferritin concentrations, that are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients, especially in the presence of obesity. Body iron contributes to excess oxidative stress already at non iron overload concentrations. Moreover, serum ferritin is an important and independent predictor of the development of diabetes. Weight loss is accompanied by reduction of ferritin, more after restrictive than malabsorptive surgery. Metabolic changes are greater after malabsorptive or mixed surgery than after purely restrictive surgery, and this has been ascribed to a greater weight loss. Studies comparing the two kinds of surgery indicate that, for the same amount of weight loss, decrease of cholesterol is greater with the former than with the latter techniques, and this difference is mainly due to a greater reduction of intestinal absorption of cholesterol. In the choice of surgery for the single patient, among

  10. A ferritin from Dendrorhynchus zhejiangensis with heavy metals detoxification activity.

    PubMed

    Li, Chenghua; Li, Zhen; Li, Ye; Zhou, Jun; Zhang, Chundan; Su, Xiurong; Li, Taiwu

    2012-01-01

    Ferritin, an iron homeostasis protein, has important functions in transition and storage of toxic metal ions. In this study, the full-length cDNA of ferritin was isolated from Dendrorhynchus zhejiangensis by cDNA library and RACE approaches. The higher similarity and conserved motifs for ferritin were also identified in worm counterparts, indicating that it belonged to a new member of ferritin family. The temporal expression of worm ferritin in haemocytes was analyzed by RT-PCR, and revealed the ferritin could be induced by Cd(2+), Pb(2+) and Fe(2+). The heavy metal binding activity of recombinant ferritin was further elucidated by atomic force microscopy (AFM). It was observed that the ferritin protein could form a chain of beads with different size against three metals exposure, and the largest one with 35~40 nm in height was identified in the Cd(2+) challenge group. Our results indicated that worm ferritin was a promising candidate for heavy metals detoxification.

  11. Electron microscopic localization of cytoplasmic myosin with ferritin- labeled antibodies

    PubMed Central

    1981-01-01

    We localized myosin in vertebrate nonmuscle cells by electron microscopy using purified antibodies coupled with ferritin. Native and formaldehyde-fixed filaments of purified platelet myosin filaments each consisting of approximately 30 myosin molecules bound an equivalent number of ferritin-antimyosin conjugates. In preparations of crude platelet actomyosin, the ferritin-antimyosin bound exclusively to similar short, 10-15 nm wide filaments. In both cases, binding of the ferritin-antimyosin to the myosin filaments was blocked by preincubation with unlabeled antimyosin. With indirect fluorescent antibody staining at the light microscope level, we found that the ferritin-antimyosin and unlabeled antimyosin stained HeLa cells identically, with the antibodies concentrated in 0.5-microns spots along stress fibers. By electron microscopy, we found that the concentration of ferritin-antimyosin in the dense regions of stress fibers was five to six times that in the intervening less dense regions, 20 times that in the cytoplasmic matrix, and 100 times that in the nucleus. These concentration differences may account for the light microscope antibody staining pattern of spread interphase cells. Some, but certainly not all, of the ferritin-antimyosin was associated with 10-15-nm filaments. In mouse intestinal epithelial cells, ferritin- antimyosin was located almost exclusively in the terminal web. In isolated brush borders exposed to 5 mM MgCl2, ferritin-antimyosin was also concentrated in the terminal web associated with 10-15-nm filaments. PMID:7193682

  12. A Ferritin from Dendrorhynchus zhejiangensis with Heavy Metals Detoxification Activity

    PubMed Central

    Li, Chenghua; Li, Zhen; Li, Ye; Zhou, Jun; Zhang, Chundan; Su, Xiurong; Li, Taiwu

    2012-01-01

    Ferritin, an iron homeostasis protein, has important functions in transition and storage of toxic metal ions. In this study, the full-length cDNA of ferritin was isolated from Dendrorhynchus zhejiangensis by cDNA library and RACE approaches. The higher similarity and conserved motifs for ferritin were also identified in worm counterparts, indicating that it belonged to a new member of ferritin family. The temporal expression of worm ferritin in haemocytes was analyzed by RT-PCR, and revealed the ferritin could be induced by Cd2+, Pb2+ and Fe2+. The heavy metal binding activity of recombinant ferritin was further elucidated by atomic force microscopy (AFM). It was observed that the ferritin protein could form a chain of beads with different size against three metals exposure, and the largest one with 35∼40 nm in height was identified in the Cd2+ challenge group. Our results indicated that worm ferritin was a promising candidate for heavy metals detoxification. PMID:23284696

  13. Acute Rejection, Kidney Allograft Function, and Graft Survival in Patients with Circulating Pre-Transplant IgG Antibodies Directed Against Donor HLA-A, -B, or -C Locus Determined Antigens.

    PubMed

    Abuhelaiqa, Essa; Friedlander, Rex; Aull, Meredith; Putheti, Prabhakar; Sharma, Vijay; Suthanthiran, Manikkam; Dadhania, Darshana

    2016-01-01

    The relationship between circulating pre-transplant immunoglobulin G (IgG) antibodies to donor human leukocyte antigen (HLA) -C locus determined antigens alone and acute rejection, kidney allograft function, and graft survival is not fully defined. Also, the impact of circulating pre-transplant IgG antibodies to donor HLA-C locus antigens alone on these outcomes has not been compared with the impact of circulating pre-transplant IgG antibodies to donor HLA-A or -B locus antigens. We conducted a retrospective review of records of 1252 kidney allograft recipients transplanted at our center between January 2010 and January 2016 to identify patients with circulating pre-transplant IgG antibodies directed at kidney donor HLA-A, -B, or -C locus determined antigens. Antibodies were detected and reported using the LABScreen Single Antigen Bead assay with microbeads coated with single HLA class I antigens. Pre-transplant and post-transplant data were collected and the graft outcomes of 16 kidney graft recipients with antibodies to HLA-C locus antigens were compared to the outcomes in 56 recipients with antibodies to HLA-A or -B locus determined antigens. The one-year acute rejection rate was 6% in those with donor-specific antibodies (DSA) to HLA-C locus antigens and 20% in those with DSA to HLA-A or -B locus antigens. The graft survival rate was 100% in those with DSA to HLA-C locus antigens and 95% in those with DSA to HLA-A or -B locus antigens. None of the numerical differences were statistically significant (p>0.05). The presence of circulating pre-transplant IgG antibodies directed at kidney donor HLA-C locus antigens alone may not be associated with an increased risk of acute rejection or a decreased graft survival rate. Our observations support the concept that circulating pre-transplant IgG antibodies directed at kidney donor HLA-C locus antigens alone do not negatively impact kidney allograft outcomes and that the mean fluorescence intensities of the antibodies

  14. Differential degradation of ferritin H- and L-chains: accumulation of L-chain-rich ferritin in lens epithelial cells.

    PubMed

    Goralska, Malgorzata; Nagar, Steven; Fleisher, Lloyd N; McGahan, M Christine

    2005-10-01

    The storage of iron by ferritin is determined by tissue-specific composition of its 24 subunits, which are designated as either heavy (H) or light (L). For a better understanding of how lens epithelial cells regulate their ferritin subunit makeup, the degradation pattern of each subunit type was analyzed. In addition, age-related changes in ferritin concentration and subunit makeup were determined. Ferritin turnover in primary cultures of canine lens epithelial cells was determined by metabolic labeling with [(35)S]-methionine. Transient transfection with vectors containing coding sequences for either H- or L-chains were used to modify ferritin subunit makeup. Ferritin concentration was measured by ELISA. Immunodetection and fluorescence immunocytochemistry were used to study age-related changes in ferritin chain concentration. Inhibition of the proteasomal protein degradation pathway by clastolactacystin-beta-lactone had no effect on ferritin degradation, whereas inhibition of lysosomal degradation markedly increased ferritin levels, confirming that this system is involved in ferritin turnover. H-chain ferritin degraded at a faster rate than the L-chain. L-chain-rich ferritin in L-chain-transfected cells formed inclusion bodies that were localized to the cytosol. Similar inclusion bodies were found in older lens cells kept in cell culture for more than 8 days. Steady degradation of H-chain ferritin contributed to the maintenance of a constant level of this chain within the lens epithelial cells. In contrast, slower turnover of the L-chain resulted in accumulation of L-chain-enriched ferritin associated with cytoplasmic inclusion bodies. These L-chain-containing inclusion bodies were found in the cytosol of cells overexpressing L-ferritin chain and in nontransfected cells maintained in culture for 8 to 35 days. Overexpression of the L-chain has been associated with the formation of premature cataracts in humans with hereditary hyperferritinemia cataract syndrome

  15. Possible relationship between Al/ferritin complex and Alzheimer's disease.

    PubMed

    De Sole, Pasquale; Rossi, Cristina; Chiarpotto, Michela; Ciasca, Gabriele; Bocca, Beatrice; Alimonti, Alessandro; Bizzarro, Alessandra; Rossi, Concetta; Masullo, Carlo

    2013-01-01

    Ferritin is the main iron-storage protein capable of containing thousands of iron atoms. However, ferritin can bind in vitro other atoms such as aluminum and it has been shown that also in vivo atoms other than iron, as aluminum and zinc, are present in large amounts in ferritin. Since aluminum appears to be involved in the development of Alzheimer's disease, in the present study the specific content of aluminum in ferritin of Alzheimer's patients was analyzed and compared with other control groups. The content of Fe, Al and Zn of blood ferritin was measured by mass spectrometry in patients with Alzheimer's disease and compared with other clinical and control groups. The results obtained confirm the hypothesis of a functional role of ferritin as a regulatory protein of toxic metals and clearly indicate that ferritin from Alzheimer's patients has a content of aluminum higher than that of controls. The specific aluminum content of ferritin seems to be related to different disease stages of Alzheimer's disease. This result confirms the hypothesis of aluminum as a possible factor inducing the Alzheimer's disease and opens the ways to possible new diagnostic tests. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Ferritins: iron/oxygen biominerals in protein nanocages.

    PubMed

    Theil, Elizabeth C; Matzapetakis, Manolis; Liu, Xiaofeng

    2006-10-01

    Ferritin protein nanocages that form iron oxy biominerals in the central nanometer cavity are nature's answer to managing iron and oxygen; gene deletions are lethal in mammals and render bacteria more vulnerable to host release of antipathogen oxidants. The multifunctional, multisubunit proteins couple iron with oxygen (maxi-ferritins) or hydrogen peroxide (mini-ferritins) at catalytic sites that are related to di-iron sites oxidases, ribonucleotide reductase, methane monooxygenase and fatty acid desaturases, and synthesize mineral precursors. Gated pores, distributed symmetrically around the ferritin cages, control removal of iron by reductants and chelators. Gene regulation of ferritin, long known to depend on iron and, in animals, on a noncoding messenger RNA (mRNA) structure linked in a combinatorial array to functionally related mRNA of iron transport, has recently been shown to be linked to an array of proteins for antioxidant responses such as thioredoxin and quinone reductases. Ferritin DNA responds more to oxygen signals, and ferritin mRNA responds more to iron signals. Ferritin genes (DNA and RNA) and protein function at the intersection of iron and oxygen chemistry in biology.

  17. 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

  18. Magnetic birefringence of natural and synthetic ferritin

    NASA Astrophysics Data System (ADS)

    Koralewski, M.; Pochylski, M.; Mitróová, Z.; Timko, M.; Kopčanský, P.; Melníková, L.

    2011-10-01

    Magnetically induced optical birefringence (Δn) was measured for magnetoferritin (MFer), horse spleen ferritin (HSF) and nanoscale magnetite aqueous suspensions. The anisotropy of optical polarizability was calculated. The average magnetic dipole moment calculated assuming the Langevin model was about 20,000 and 8500 μB per particle, for magnetite nanoparticle and magnetoferritin, respectively. Poor fitting results and the unphysical value of average magnetic moment per Fe ion for MFer excluded the use of the simple Langevin model for description of Δn for this compound. It was deduced that for MFer the estimated average magnetic moment should be about 1125 μB per molecule. A magnetic contribution from the protein shell was found to be negligible. Results from the low-field region permit the calculation of the Cotton-Mouton (C-M) constants and their comparison for the substances studied. It was shown that magnetic birefringence and C-M constant can be powerful parameters in identification of the magnetic core structure of ferritins, especially useful in biomedicine.

  19. Growth retardation and hair loss in transgenic mice overexpressing human H-ferritin gene.

    PubMed

    Hasegawa, Sumitaka; Harada, Kazutoshi; Morokoshi, Yukie; Tsukamoto, Satoshi; Furukawa, Takako; Saga, Tsuneo

    2013-06-01

    H-ferritin (HF) is a core subunit of the iron storage protein ferritin, and plays a central role in the regulation of cellular iron homeostasis. Recent studies revealed that ferritin and HF are involved in a wide variety of iron-independent functions, including regulating biological processes during physiological and pathological conditions, and can be overexpressed in some human diseases. To investigate the in vivo function of HF, we generated transgenic (tg) mice overexpressing the human HF gene (hHF-tg). We established two independent hHF-tg mouse lines. Although both lines of hHF-tg mice were viable, they showed reduced body size compared to wild-type (WT) mice at 4-12 weeks of age. Serum iron concentration and blood parameters of hHF-tg mice such as hemoglobin and red blood cell counts were comparable to those of WT mice. At 3-5 weeks of age, hHF-tg mice exhibited temporary loss of coat hair on the trunk, but not on the head or face. Histological analyses revealed that although initial hair development was normal, hHF-tg mice had epidermal hyperplasia with hyperkeratosis, dilated hair follicles, bended hair shafts and keratinous debris during the hairless period. In conclusion, we showed that hHF-tg mice exhibited mild growth retardation and temporary hairless phenotype. Our findings highlight the physiological roles of HF and demonstrate that hHF-tg mice are useful for understanding the in vivo functions of HF.

  20. What is the evidence for gender differences in ferritin and haemoglobin?

    PubMed

    Rushton, D Hugh; Barth, Julian H

    2010-01-01

    Reference ranges for haemoglobin and ferritin in women of reproductive age are widely reported showing values that are lower than equivalent aged males. Similar values would be expected in the absence of different biological requirements. While reference ranges have been derived from data on large populations, it is likely that these populations have included significant numbers of women who are iron deficient in view of menstrual blood loss and poor dietary intake. Populations with a daily iron intake in excess of 100mg have shown that iron deficiency in females is rare. Studies reporting bone marrow with iron stains from 50 years ago pointed out that significant numbers of women were iron deficient and more recently serum ferritin studies have confirmed this. However, a large number of women in the Western world spend a significant part of their lives in a negative iron balance due to a combination of poor diet and menstrual blood loss. The presence of haem iron in the diet of humans enhances non-haem iron absorption but dietary surveys consistently report that women's diet is deficient in iron. Furthermore, the typical Western diet contains many common foods that limit iron absorption. It appears that lower haemoglobin and ferritin values in menstruating women have been accepted as normal rather than possibly representing widespread iron deficiency. Reference ranges should be re-evaluated in populations proven to be iron replete.

  1. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation

    PubMed Central

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support

  2. 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

  3. Enrichment and characterization of ferritin for nanomaterial applications.

    PubMed

    Ghirlando, Rodolfo; Mutskova, Radina; Schwartz, Chad

    2016-01-29

    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.

  4. Tuning Ferritin's Band Gap through Mixed Metal Oxide Nanoparticle Formation.

    PubMed

    Olsen, Cameron; Embley, Jacob; Hansen, Kameron; Henrichsen, Andrew; Peterson, J; Colton, John S; Watt, Richard

    2017-03-23

    This study uses the formation of a mixed metal oxide inside ferritin to tune the band gap energy of the ferritin mineral. The mixed metal oxide is composed of both Co and Mn, and is formed by reacting aqueous Co2+ with MnO4- in the presence of apoferritin. Altering the ratio between the two reactants allowed for controlled tuning of the band gap energies. All minerals formed were indirect band gap materials, with indirect band gap energies ranging from 0.52 to 1.30 eV. The direct transitions were also measured, with energy values ranging from 2.71 to 3.11 eV. Tuning the band gap energies of these samples changes the wavelengths absorbed by each mineral, increasing ferritin's potential in solar-energy harvesting. Additionally, the success of using MnO4- in ferritin mineral formation opens the possibility for new mixed metal oxide cores inside ferritin.

  5. 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.

  6. Maxi- and Mini-Ferritins: Minerals and Protein Nanocages

    PubMed Central

    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. O2 or H2O2 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. PMID:21877262

  7. 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.

  8. Sialic acid, ferritin and CEA levels in peripheral blood and blood draining from the tumor in breast cancer.

    PubMed

    Monti, M; Catania, S; Locatelli, E; Scazzoso, A; Calzaferri, G; Cunietti, E

    1988-01-01

    Concentrations of total serum N-acetyl-neuraminic acid, carcinoembryonic antigen, ferritin, lactate dehydrogenase, creatine phosphokinase and total proteins were measured in both tumor drainage blood (axillary vein) and in peripheral blood taken during surgery from 44 breast cancer patients. There were no significant differences in any of the markers between mean values in peripheral and tumor drainage blood, between cancer patients and healthy controls, between patients with or without axillary lymph node metastases, or according to the site of breast mass.

  9. Redox reactions of apo mammalian ferritin.

    PubMed

    Watt, R K; Frankel, R B; Watt, G D

    1992-10-13

    Apo horse spleen ferritin undergoes a 6.3 +/- 0.5 electron redox reaction at -310 mV at pH 6.0-8.5 and 25 degrees C to form reduced apoferritin (apoMFred). Reconstituted ferritin containing up to 50 ferric ions undergoes reduction at the same potential, taking up one electron per ferric ion and six additional electrons by the protein. We propose that apo mammalian ferritin (apoMF) contains six redox centers that can be fully oxidized forming oxidized apoferritin (apoMFox) or fully reduced forming apoMFred. ApoMFred can be prepared conveniently by dithionite or methyl viologen reduction. ApoMFred is slowly oxidized by molecular oxygen but more rapidly by Fe(CN)6(3-) to apoMFox. Fe(III)-cytochrome c readily oxidizes apoMFred to apoMFox with a stoichiometry of 6 Fe(III)-cytochrome c per apoMFred, demonstrating a rapid interprotein electron-transfer reaction. Both redox states of apoMF react with added Fe3+ and Fe2+. Addition of eight Fe2+ to apoMFox under anaerobic conditions produced apoMFred and Fe3+, as evidenced by the presence of a strong g = 4.3 EPR signal. Subsequent addition of bipyridyl produced at least six Fe(bipyd)3(2+) per MF, establishing the reversibility of this internal electron-transfer process between the redox centers of apoMF and bound iron. Incubation of apoMFred with the Fe(3+)-ATP complex under anaerobic conditions resulted in the formation and binding of two Fe2+ and four Fe3+ by the protein. The various redox states formed by the binding of Fe2+ and Fe3+ to apoMFox and apoMFred are proposed and discussed. The yellow color of apoMF appears to be an integral characteristic of the apoMF and is possibly associated with its redox activity.

  10. Clinical value of pre-transplant minimal residual disease in childhood lymphoblastic leukaemia: the results of the French minimal residual disease-guided protocol.

    PubMed

    Gandemer, Virginie; Pochon, Cécile; Oger, Emmanuel; Dalle, Jean-Hugues H; Michel, Gérard; Schmitt, Claudine; de Berranger, Eva; Galambrun, Claire; Cavé, Hélène; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rorhlich, Pierre; Lutz, Patrick; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Bordigoni, Pierre

    2014-05-01

    Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non-ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T-cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high-risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD <10(-3) and the 27 with MRD ≥10(-3) . Multivariate analysis identified sex match and MRD as being significantly associated with 5-year survival. MRD ≥10(-3) compromised the 5-year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre-transplant MRD is still a major predictor of outcome for ALL. The MRD-guided strategy resulted in survival for 72·3% of patients with MRD<10(-3) and 40·4% of those with MRD ≥10(-3). © 2014 John Wiley & Sons Ltd.

  11. Long Term Clinical Outcome of Patients with Severe Combined Immunodeficiency who Received Related Donor Bone Marrow Transplants without Pre-transplant Chemotherapy or Post-transplant GVHD Prophylaxis

    PubMed Central

    Railey, Mary Dell; Lokhnygina, Yuliya; Buckley, Rebecca H.

    2009-01-01

    Objective To determine long term health benefits of non-ablative bone marrow transplantation for severe combined immunodeficiency (SCID), we investigated our cohort of 161 related donor bone marrow transplanted SCID patients. Only 16 (10%) had HLA-identical donors. Study design All 124 survivors were sent questionnaires about their current clinical statuses. Details from clinic visits were also compiled. One hundred eleven patients (90%) were reached. We compared outcomes of patients transplanted before and after 3.5 months of life and by molecular defect. Results The overall survival rate is 77%, but the rate for the 48 infants transplanted in the first 3.5 months of life is 94%, compared with 70% for the 113 transplanted after 3.5 months (p=0.002). Twenty-eight (76%) of the 37 deceased patients died from viral infections present at diagnosis. One or more clinical problems were reported to have been present in the past two years in 71 (64%) of the survivors, although 95 (86%) are considered healthy by their families. Conclusions Most patients with SCID transplanted with related donor marrow without pre-transplant chemotherapy have done well long-term, but those transplanted at <3.5 months of age had a superior survival rate, a lower rate of clinical problems, less need for booster transplants and better nutritional status. PMID:19818451

  12. Iron release analyses from ferritin by visible light irradiation.

    PubMed

    Ohishi, Kentaro; Zhang, Xiao Mei; Moriwaki, Shinichi; Hiramitsu, Tadahisa; Matsugo, Seiichi

    2005-08-01

    We investigated the iron release from ferritin by irradiation from a white fluorescent light in the absence or presence of ADP. Irradiation of a ferritin solution at 17,000 lx in the absence of ADP slightly induces iron release from ferritin but only at acidic pH conditions (pH 5.0 or pH 6.0). Irradiation in the presence of ADP markedly enhances iron release from ferritin under the same conditions. In the absence of irradiation, the iron release from ferritin was low even in the presence of ADP. The induction of the iron release by irradiation in the presence of ADP was also affected by various factors such as irradiation dose and acidity, but not temperature (4-47 degrees C), oxygen concentration, or free radical generations during the irradiation. The iron release during the irradiation ceased to increase by turning off the light and was found to increase again after additional irradiation. These results suggest that visible light directly induces iron release from ferritin via the photoreduction of iron stored inside ferritin.

  13. 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.

  14. 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.

  15. Correlation between maternal and childhood VitB12, folic acid and ferritin levels

    PubMed Central

    Zeeshan, Fatima; Bari, Attia; Farhan, Saima; Jabeen, Uzma; Rathore, Ahsan Waheed

    2017-01-01

    Objective: To determine the correlation between serum folic acid, vitamin B12 and ferritin of mother and child and to study various neonatal risk factors as a cause of anemia in children. Methods: One hundred eighty children two months to two years of age admitted in the department of Pediatric Medicine of The Children’s Hospital and The Institute of Child Health Lahore from January 2013 to January 2015 with common medical conditions having anemia were included. Complete blood count (CBC), serum ferritin level, folic acid and Vitamin (Vit) B12 level were sent of children and their mothers. Data was analyzed using SPSS version 20. Results: Out of 180 children with anemia, 66.7% were males. Mean age of children was 7.3months. Fifty-five percent children were malnourished according to z scoring. The mean Hemoglobin (Hb) of children was 8 g/dl. Only 4% children had low ferritin level while 60% had low folic acid and 45% had decreased VitB12. There was significant correlation between Hb of mother and child (p =0.02), Vit B12 deficiency (p=0.008) and iron deficiency (p<0.001). Premature children had lower folic acid levels (p =0.02), while prematurity, IUGR, previous admission and history of sepsis showed no association with anemia in our study. Both breast-feeding and top feeding showed significant association with anemia with p-value of 0.042 and 0.003 respectively while dilution showed no impact on anemia. Conclusion: Maternal anemia has a significant impact on child’s hemoglobin. As compared to previous concept of increased iron deficiency in children we found increased occurrence of folic acid and VitB12 deficiency in children and their mothers. PMID:28367192

  16. 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

  17. Dual-Functional Carbon Dots Pattern on Paper Chips for Fe(3+) and Ferritin Analysis in Whole Blood.

    PubMed

    Hu, Shan-Wen; Qiao, Shu; Xu, Bi-Yi; Peng, Xiang; Xu, Jing-Juan; Chen, Hong-Yuan

    2017-02-07

    Though microfluidic paper analytical devices (μPADs) have attracted paramounting attentions in recent years as promising devices for low cost point-of-care tests, their real applications for blood analysis are still challenged by integrating sample preparation with different detection modes on a same μPAD. Herein, we developed a novel μPAD, which well coupled automatic serum extraction with reliable dual mode iron health tests: fluorescent analysis for Fe(3+) and colorimetric ELISA for ferritin. All these functions are made available by in situ carbon dots (CDs) and AuNPs sequential patterning techniques. For CDs immobilization, hydrothermal reaction was taken on paper, to which a patterned through-hole polydimethylsiloxane (PDMS) mask was applied. None fluorescence CDs (nF-CDs) were generated on exposed regions, while the fluorescent CDs (F-CDs) were generated simultaneously on covered regions. Sensitive serum iron quantification was realized on the F-CDs modified regions, where Fe(3+) ion can selectively quench the fluorescence of F-CDs. For AuNPs immobilization, electroless plating was taken on nF-CDs modified regions. The resulting AuNPs on nF-CDs layer on one hand triggered the coagulation of blood cells and thus led to the longest ever wicking distance for serum separation, on the other hand facilitated colorimetric enzyme linked immunosorbent assay (ELISA) for detection of serum ferritin. Combining the two readings, the μPAD can provide reliable measurement for serum iron and serum ferritin in whole blood. Furthermore, as CDs and AuNPs modified μPAD has the features of easy handling, low-cost, lightweight, and disposability, it is accounting for a promising prototype for whole blood point-of-care analysis.

  18. Complex I, iron, and ferritin in Parkinson's disease substantia nigra.

    PubMed

    Mann, V M; Cooper, J M; Daniel, S E; Srai, K; Jenner, P; Marsden, C D; Schapira, A H

    1994-12-01

    Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron-ferritin ratio and complex I activity in the substantia nigra samples.

  19. 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

  20. Synergistic effects of ferritin and propolis in modulation of beryllium induced toxicogenic alterations.

    PubMed

    Nirala, Satendra Kumar; Bhadauria, Monika

    2008-09-01

    Synergistic therapeutic potential of ferritin (5mg/kg, i.p.) and propolis (honeybee hive product; 200mg/kg, p.o.) was analyzed to encounter the beryllium induced biochemical and ultra morphological alterations. Female albino rats were exposed to beryllium nitrate (1mg/kg, i.p.) daily for 28 days followed by treatment of above mentioned therapeutic agents either individually or in combination for five consecutive days. Exposure to beryllium increased its concentration in serum, liver and kidney and significantly altered the activities of CYP2E1 and CYP1A2 enzymes, microsomal lipid peroxidation and microsomal proteins. Activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, protein, creatinine and urea in serum as well as hemoglobin and blood glucose level; activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose-6-phosphatase and succinic dehydrogenase, total triglycerides, total cholesterol, total protein contents, glycogen contents, lipid peroxidation and glutathione level in liver and kidney were significantly altered after beryllium administration. Beryllium exposure severely altered ultramorphology of liver and kidney that proved its toxic consequences at cellular level. Ferritin in combination with propolis dramatically reversed the alterations of these variables towards control in a synergistic manner concluding its beneficial effects over monotherapy in attenuating beryllium induced systemic toxicity.

  1. Measurement of ferritin levels: comparison of a commercial IRMA to an in-house ELISA method.

    PubMed

    Zemelka, S; Biesalski, H K

    2001-01-01

    The purpose of this study was a comparison of a commercial IRMA to an in-house ELISA method. Because IRMA methods are considered to be very sensitive and results of these assays are widely accepted, the ferritin levels of 378 school children were determined in parallel with a commercial IRMA kit (Becton Dickinson Co., Orangeburg, NY) and the ELISA. For organizing reasons plasma was used for the ELISA, whereas serum was used for the IRMA. Regression analysis of the pairs of values, taking the IRMA reading as the independent variable, yielded a coefficient of variation r=0,90 (Spearman, two-tailed, p=0,01) and the straight line y=0,99x+3,13. Using this ELISA technique described by DAKO, ferritin levels in plasma were, on average, 13,2% higher than in serum taken at the same time. The ELISA technique described was found to have good accuracy and the speed and ease with which it may be carried out makes it suitable for a large number of samples.

  2. Conceptions and First Results on the Electrocrystallization Behaviour of Ferritin

    SciTech Connect

    Moreno,A.; Rivera, M.

    2005-01-01

    The role of electrochemical processes on Fe and CdSO{sub 4} in the crystallization of horse spleen ferritin has been investigated using the cyclic voltammetry technique. It was found that although both species exhibit important redox properties in the presence of an external applied potential, CdSO4 played a leading role not only in the nucleation process but also in the growth behavior and morphology of ferritin crystals.

  3. 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.

  4. Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development

    PubMed Central

    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. PMID:26192321

  5. Permanganate-Based Synthesis of Manganese Oxide Nanoparticles in Ferritin.

    PubMed

    Olsen, Cameron; Smith, Trevor; Embley, Jacob; Maxfield, Jake; Hansen, Kameron; Peterson, J; Henrichsen, Andrew; Erickson, Stephen; Buck, David; Colton, John S; Watt, Richard

    2017-03-23

    This paper investigates the comproportionation reaction of MnII with MnO4- as a route for manganese oxide nanoparticle synthesis in the protein ferritin. We report that MnO4- 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 eV 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.

  6. Cellular regulation and molecular interactions of the ferritins.

    PubMed

    Hintze, K J; Theil, E C

    2006-03-01

    Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA (mRNA) structures, signaling pathways and protein catalysts. Ferritin, a protein nanocage around an iron/oxy mineral, centralizes the control. Complementary DNA (antioxidant responsive element/Maf recognition element) and mRNA (iron responsive element) responses regulate ferritin synthesis rates. Multiple iron-protein interactions control iron and oxygen substrate movement through the protein cage, from dynamic gated pores to catalytic sites related to di-iron oxygenase cofactor sites. Maxi-ferritins concentrate iron for the bio-synthesis of iron/heme proteins, trapping oxygen; bacterial mini-ferritins, DNA protection during starvation proteins, reverse the substrate roles, destroying oxidants, trapping iron and protecting DNA. Ferritin is nature's unique and conserved approach to controlled, safe use of iron and oxygen, with protein synthesis in animals adjusted by dual, genetic DNA and mRNA sequences that selectively respond to iron or oxidant signals and link ferritin to proteins of iron, oxygen and antioxidant metabolism.

  7. 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.

  8. The Kidney Donor Profile Index (KDPI) of Marginal Donors Allocated by Standardized Pre-Transplant Donor Biopsy Assessment: Distribution and Association with Graft Outcomes

    PubMed Central

    Gandolfini, I.; Buzio, C.; Zanelli, P.; Palmisano, A.; Cremaschi, E.; Vaglio, A.; Piotti, G.; Melfa, L.; La Manna, G.; Feliciangeli, G.; Cappuccilli, M.; Scolari, M.P.; Capelli, I.; Panicali, L.; Baraldi, O.; Stefoni, S.; Buscaroli, A.; Ridolfi, L.; D'Errico, A.; Cappelli, G.; Bonucchi, D.; Rubbiani, E.; Albertazzi, A.; Mehrotra, A.; Cravedi, P.; Maggiore, U.

    2015-01-01

    Pre-transplant donor biopsy (PTDB)-based marginal-donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the US. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 [median KDPI:87; interquartile range(IQR):78-94] and 62 with a score =4 [median KDPI:87; IQR:76-93]; 102 dual transplants [median KDPI: 93; IQR:86-96]) and 248 single standard transplant controls [median KDPI:36; IQR:18-51]. PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year eGFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9, and -18.8ml/min, for dual transplants, single kidneys with PTDB score <4, and =4, respectively; P<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80 to 1.79; P=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded. PMID:25155294

  9. Pre-transplant donor CD4(-) invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease.

    PubMed

    Rubio, M-T; Bouillié, M; Bouazza, N; Coman, T; Trebeden-Nègre, H; Gomez, A; Suarez, F; Sibon, D; Brignier, A; Paubelle, E; Nguyen-Khoc, S; Cavazzana, M; Lantz, O; Mohty, M; Urien, S; Hermine, O

    2017-04-01

    Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34(+), NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4(-) iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4(-) iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4(-) iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4(-) iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.

  10. Pre-transplant panel reactive antibody in lung transplant recipients is associated with significantly worse post-transplant survival in a multicenter study.

    PubMed

    Hadjiliadis, Denis; Chaparro, Cecilia; Reinsmoen, Nancy L; Gutierrez, Carlos; Singer, Lianne G; Steele, Mark P; Waddell, Thomas K; Davis, Robert D; Hutcheon, Michael A; Palmer, Scott M; Keshavjee, Shaf

    2005-07-01

    The presence of antibodies to human leukocyte antigens (HLA) prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. The effect of these antibodies is less clear in lung transplant recipients, although previous studies have suggested an increased incidence of allograft dysfunction. A retrospective study of all first lung transplant recipients from the University of Toronto (November 1983-July 2001, n = 380) and Duke University (April 1992-June 2000, n = 276) was performed. Demographic data, survival information, and level of last pre-transplant panel reactive antibody (PRA) were collected. PRA level was measured by the complement-dependent cell cytotoxicity assay at both centers. Survival analysis was performed using the Kaplan-Meier method, and groups were compared with the Wilcoxon rank sum test. Of 656 lung transplant recipients, 101 (15.4%) had a PRA greater than 0, 37 (5.6%) had a PRA greater than 10%, and 20 (3.0%) had a PRA greater than 25%. Patients with a PRA greater than 25% had decreased median survival than did the rest of the patients (1.5 vs 5.2 years) and at 1 month (70% vs 90%), 1 year (65% vs 76%), and 5 years (31% vs 50%), respectively (p = 0.006, Wilcoxon's rank sum test) test). Significant elevation of PRA prior to lung transplantation is associated with worse survival, especially in the early post-transplant period. This may be due to a direct effect of anti-HLA antibodies on the allograft. The effectiveness of treatments such as plasmapheresis and intravenous immunoglobulin prior to transplantation needs to be evaluated.

  11. Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation.

    PubMed

    See, Sarah B; Clerkin, Kevin J; Kennel, Peter J; Zhang, Feifan; Weber, Matthew P; Rogers, Kortney J; Chatterjee, Debanjana; Vasilescu, Elena R; Vlad, George; Naka, Yoshifumi; Restaino, Susan W; Farr, Maryjane A; Topkara, Veli K; Colombo, Paolo C; Mancini, Donna M; Schulze, P Christian; Levin, Bruce; Zorn, Emmanuel

    2017-08-01

    Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome. IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant recipients, including 128 patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients). Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked immunosorbent assay. No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared with no-VAD patients. This increase was likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels before implantation. Elevated pre-transplant IgG Nabs level was associated with development of primary graft dysfunction (PGD). Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with development of PGD suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Lipoprotein(a), ferritin, and albumin in acute phase reaction predicts severity and mortality of acute ischemic stroke in North Indian Patients.

    PubMed

    Chakraborty, Baidarbhi; Vishnoi, Gaurav; Goswami, Binita; Gowda, Srinivas H; Chowdhury, Debashish; Agarwal, Sarita

    2013-10-01

    Inflammation plays a crucial role in the pathogenesis and prognosis of stroke. We studied the behavior of lipoprotein(a) [Lp(a)], ferritin, and albumin as acute phase reactants and their roles in the severity and mortality of stroke. We recruited 100 consecutive patients with acute ischemic stroke and 120 controls. Blood samples were drawn on days 1 and 7 and at both 3 and 6 months. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment classification. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Prognosis at 6 months was assessed using the modified Rankin Scale, and mortality was assessed using the Kaplan-Meier analysis. Serum levels of interleukin-6 (IL-6), Lp(a), ferritin, and albumin were measured using enzyme-linked immunosorbent assay, immunoturbidimetry, and chemiluminescence commercial kits, respectively. Levels of IL-6, Lp(a), and ferritin were consistently higher among cases than controls (P < .0001). Serum Lp(a) levels peaked at day 7 after stroke and tapered thereafter. Albumin levels were lower than controls on admission day and increased subsequently. In our study, Lp(a) acted as an acute phase reactant while albumin acted as a negative acute phase reactant. There was no association between Trial of Org 10172 in Acute Stroke Treatment subtype and elevated serum levels of Lp(a), albumin, and ferritin. Lp(a) and ferritin were high in patients with severe stroke. Albumin was negatively correlated with stroke severity. Serum levels of Lp(a) ≥ 77 mg/dL, albumin ≤ 3.5 g/dL, and ferritin ≥ 370 ng/dL is associated with a significantly increased risk of having a poorer outcome in stroke. Serum levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL were also associated with increased mortality. High levels of Lp(a) and ferritin and low levels of albumin are associated with increased severity and poorer long term prognosis of stroke. Patients with admission levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL had

  13. Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease.

    PubMed

    Valenti, Luca; Dongiovanni, Paola; Fargion, Silvia

    2012-08-07

    Nonalcoholic fatty liver disease (NAFLD), defined by excessive liver fat deposition related to the metabolic syndrome, is a leading cause of progressive liver disease, for which accurate non-invasive staging systems and effective treatments are still lacking. Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome, and higher hepatic iron and fat content. Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD, and iron depletion reduced insulin resistance and liver enzymes. Recently, Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD, and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis. These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD, and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.

  14. Soybean Ferritin Forms an Iron-Containing Oligomer in Tofu Even after Heat Treatment.

    PubMed

    Masuda, Taro

    2015-10-14

    Ferritin, a multimeric iron storage protein distributed in almost all living kingdoms, has been highlighted recently as a nutritional iron source in plant-derived foodstuffs, because ferritin iron is suggested to have high bioavailability. In soybean seeds, ferritin contributes largely to the net iron contents. Here, the oligomeric states and iron contents of soybean ferritin during food processing (especially tofu gel formation) were analyzed. Ferritin was purified from tofu gel as an iron-containing oligomer (approximately 1000 Fe atoms per oligomer), which was composed of two types of subunits similar to the native soybean seed ferritin. Circular dichroism spectra also showed no differences in α-helical structure between native soybean ferritin and tofu ferritin. The present data demonstrate that ferritin was stable during the heat treatment (boiling procedure) in food processing, although partial denaturation was observed at temperatures higher than 80 °C.

  15. Iron at the center of ferritin, metal/oxygen homeostasis and novel dietary strategies.

    PubMed

    Liu, X; Hintze, K; Lonnerdal, B; Theil, E C

    2006-01-01

    Bioiron - central to respiration, photosynthesis and DNA synthesis and complicated by radical chemistry with oxygen - depends on ferritin, the super family of protein nanocages (maxi-ferritins in humans, animals, plant, and bacteria, and mini-ferritins, also called DPS proteins, in bacteria) for iron and oxygen control. Regulation of ferritin synthesis, best studied in animals, uses DNA transcription and mRNA translation check points. Ferritin is a member of both the "oxidant stress response" gene family that includes thioredoxin reductase and quinine reductase, and a member of the iron responsive gene family that includes ferroportin and mt-aconitase ferritin DNA regulation responds preferentially to oxidant response inducers and ferritin mRNA to iron inducers: heme confers regulator synergy. Ferritin proteins manage iron and oxygen, with ferroxidase sites and iron + oxygen substrates to form mineral of both Fe and O atoms; maxi-ferritins contribute more to cellular iron metabolism and mini-ferritins to stress responses. Iron recovery from ferritin is controlled by gated protein pores, possibly contributing to iron absorption from ferritin, a significant dietary iron source. Ferritin gene regulation is a model for integrating DNA/mRNA controls, while ferritin protein function is central to molecular nutrition cellular metabolism at the crossroads of iron and oxygen in biology.

  16. Ferritin-iron is released during boiling and in vitro gastric digestion.

    PubMed

    Hoppler, Matthias; Schönbächler, Andrea; Meile, Leo; Hurrell, Richard F; Walczyk, Thomas

    2008-05-01

    Biofortification of staple foods with iron in the form of ferritin-iron is a promising approach to fighting iron-deficiency anemia in developing countries. However, contradictory results regarding iron bioavailability to humans from ferritin are not yet fully clarified. Furthermore, the question has been raised whether ferritin can potentially survive gastric passage intact and be absorbed via a ferritin-specific uptake mechanism. We studied changes of ferritin-iron and protein during cooking and in vitro gastric digestion. Water soluble, native ferritin-iron, measured in different legumes, represented 18% (soybeans) up to maximally 42% (peas) of total seed iron. Ferritin-iron was no longer detectable after boiling the legumes for 50 min in excess water. When the same cooking treatment was applied to recombinant bean ferritin propagated in Escherichia coli, some ferritin-iron remained measurable. During in vitro gastric digestion of recombinant bean ferritin and red kidney bean extract, ferritin-iron was fully released from the protein and dissolved at pH 2. Stability tests at varying pH at 37 degrees C showed that the release of ferritin-iron starts at pH 5 and is complete at pH 2. We concluded that ferritin-iron is efficiently released from the ferritin molecule during cooking and at gastric pH and that it should be absorbed as efficiently as all other nonheme iron in food.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Ferritin as a label for high-gradient magnetic separation.

    PubMed Central

    Owen, C S; Lindsay, J G

    1983-01-01

    In three model systems, particles the size of cells or smaller have been surface labeled with ferritin to make them slightly paramagnetic, by virtue of the iron in the ferritin. In each case it was possible to show that labeled particles could be magnetically removed from a flowing suspension by the high-gradient magnetic separation (HGMS) technique. The first system of particles consisted of small (1 micron) carboxylate-modified latex spheres to which ferritin was covalently bound to create stable paramagnetic particles analogous to a ferritin-labeled subcellular membrane preparation. In the second system polyacrylamide beads that more closely approximated whole cells in size (5-50 microns) were labeled with immunoferritin. The third system was a biomembrane preparation: erythrocyte ghosts labeled with a ferritin-lectin conjugate. A field of 7 T (tesla) (70 kG) was used in each case, along with buffer flow rates through the HGMS column in the range 0.1-1.0 ml/min. PMID:6860772

  3. Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin.

    PubMed

    Volatron, Jeanne; Kolosnjaj-Tabi, Jelena; Javed, Yasir; Vuong, Quoc Lam; Gossuin, Yves; Neveu, Sophie; Luciani, Nathalie; Hémadi, Miryana; Carn, Florent; Alloyeau, Damien; Gazeau, Florence

    2017-01-09

    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.

  4. Propensity Score-Based Survival Benefit of Simultaneous Liver-Kidney Transplant over Liver Transplant Alone for Recipients with Pre-Transplant Renal Dysfunction

    PubMed Central

    Sharma, Pratima; Shu, Xu; Schaubel, Douglas E.; Sung, Randall S.; Magee, John C.

    2015-01-01

    Survival benefit of simultaneous liver-kidney transplant (SLKT) over liver transplant alone (LTA) is unclear from the current literature. Additionally, the role of donor kidney quality, measured by kidney donor risk index (KDRI), in survival benefit of SLKT is not studied. We compared survival benefit after SLKT and LTA among recipients with similar pre-transplant renal dysfunction using novel methodology, specifically with respect to survival probability and area under the survival curve by dialysis status and KDRI. Methods Data were obtained from the Scientific Registry of Transplant Recipients. The study cohort included patients with pre-LT renal dysfunction who were waitlisted and received either a SLKT (n=1,326) or a LTA (n=4,283) between 3/1/02–12/31/09. Inverse Probability of Treatment Weighted (IPTW) – SLKT and LTA survival curves, along with the 5-year area under the survival curve were computed by dialysis status at transplant. The difference in the area under the curve represents the average additional survival time gained via SLKT over LTA. Results For patients not on dialysis, SLKT resulted in a significant 3.7 month gain in 5-year mean post-transplant survival time. The decrease in mortality rate differs significantly by KDRI, and an estimated 76% of SLKT recipients received a kidney with KDRI sufficiently low for mortality. The mortality decrease for SLKT was concentrated in the first year post-transplant. The difference between SLK and LTA 5-year mean post-transplant survival time was 1.4 months and non-significant for patients not on dialysis. Conclusion The propensity score-adjusted survival among SLKT and LTA recipients was similar for those who were dialysis at LT. Although statistically significant, the survival advantage of SLKT over LTA was of marginal clinical significance among patients not on dialysis; and occurred only if the donor kidney was of sufficient quality. These results should be considered in the ongoing debate regarding the

  5. Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans.

    PubMed

    Wang, Haizhen; Jiang, Xue; Wu, Jieyu; Zhang, Linqiang; Huang, Jingfei; Zhang, Yuru; Zou, Xiaoju; Liang, Bin

    2016-05-01

    The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.

  6. Stimulation of the ferroxidase activity of ceruloplasmin during iron loading into ferritin.

    PubMed

    Reilly, C A; Aust, S D

    1997-11-15

    Ceruloplasmin purified from horse serum was rapidly reduced upon addition of increasing equivalents of ferrous iron, generating an electronically and conformationally distinct form. This form of ceruloplasmin was characterized by significant (80%) loss of EPR detectable type I and type II copper(II), complete loss of visible absorbance at 610 nm, as well as decreased hydrophobic surface area. The reduced form of ceruloplasmin slowly reduced molecular oxygen to complete its catalytic cycle. The presence of varied concentrations of apoferritin, but not apotransferrin, significantly enhanced the rate of ceruloplasmin oxidation. The magnitude of this stimulatory effect increased as the molar ratio of ceruloplasmin to apoferritin approached 1.0, shown previously to be the optimum ratio for loading iron into ferritin. The rate of ferrous iron oxidation by ceruloplasmin was significantly stimulated by the presence of apoferritin; however, apotransferrin had no effect. The length of time required for ceruloplasmin to oxidize all the iron and return to the native form of the enzyme was also affected by the concentration of iron. In addition, the rate of iron loading into ferritin was dependent upon ferrous iron concentration. These results provide evidence for the formation of a specific complex between the reduced form of ceruloplasmin and apoferritin and that reduction of ceruloplasmin by ferrous iron may be the signal for complex formation.

  7. Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans

    PubMed Central

    Wang, Haizhen; Jiang, Xue; Wu, Jieyu; Zhang, Linqiang; Huang, Jingfei; Zhang, Yuru; Zou, Xiaoju; Liang, Bin

    2016-01-01

    The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases. PMID:27017620

  8. High ferritin levels have major effects on the morphology of erythrocytes in Alzheimer's disease

    PubMed Central

    Bester, Janette; Buys, Antoinette V.; Lipinski, Boguslaw; Kell, Douglas B.; Pretorius, Etheresia

    2013-01-01

    Introduction: 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. Methods: 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. Results: 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). Conclusion: 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. PMID:24367334

  9. Ferritin: Design and Formation of an Iron-Storage Molecule

    NASA Astrophysics Data System (ADS)

    Ford, G. C.; Harrison, P. M.; Rice, D. W.; Smith, J. M. A.; Treffry, A.; White, J. L.; Yariv, J.

    1984-02-01

    Although essential for most forms of life, too much iron is harmful. To cope with these antagonistic phenomena an iron-storage molecule, ferritin, has evolved. The structure of horse spleen apoferritin, which has recently been refined, consists of 24 symmetrically related subunits forming a near-spherical hollow shell. In ferritin the central cavity is occupied by an iron core of 'ferrihydrite', a geologically ephemeral mineral found in hot or cold springs and in mine workings, or produced in the laboratory by heating solutions of ferric salts. Ferritin itself forms most readily from apoferritin, in the presence of dioxygen, from FeII, not FeIII. Access to its interior is through small intersubunit channels, and the protein influences both the rate of FeII-oxidation and the form of oxide produced.

  10. 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...

  11. 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...

  12. Serum transferrin receptor: a quantitative measure of tissue iron deficiency.

    PubMed

    Skikne, B S; Flowers, C H; Cook, J D

    1990-05-01

    This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.

  13. Crosslinking of hemin to a specific site on the 90-kDa ferritin repressor protein

    SciTech Connect

    Lin, Jihjing; Thach, R.E. ); Patino, M.M.; Gaffield, L.; Walden. W.E. ); Smith, A. )

    1991-07-15

    Incubation of a 90-kDa ferritin repressor protein (FRP) with small amounts of radiolabeled hemin resulted in the formation of a strong interaction between the two that was stable to SDS/PAGE. Of seven other proteins tested individually, only apohemopexin and bovine serum albumin showed similar crosslinking ability, albeit to a much lower extent. ({sup 14}C)Hemin specifically crosslinked to FRP in the presence of a 50-fold excess of total wheat germ proteins. Inclusion of catalase did not prevent the reaction of hemin with FRP, suggesting that H{sub 2}O{sub 2} is not involved. The subsequent addition of a stoichiometric amount of apohemopexin did not reverse the reaction. Exhaustive digestion of the complex with Staphylococcus aureus V8 protease produced a major labeled peptide of 17 kDa. These results show the existence of a highly specific, uniquely reactive hemin binding site on FRP.

  14. The ratio of sTfR/ferritin is associated with the expression level of TfR in rat bone marrow cells after endurance exercise.

    PubMed

    Tian, Ye; Zhao, Jiexiu; Zhao, Binxiu; Gao, Qi; Xu, Jincheng; Liu, Dongsen

    2012-06-01

    Currently, it is unclear which index of haematological parameters could be used to most easily monitor iron deficiency during endurance training. To address this question, 16 male Wistar rats were randomly assigned to two groups: a sedentary group (n = 8) and an exercised group (n = 8). Initially, animals in the exercise group started running on a treadmill at a rate of 30 m/min, on a 0% grade, for 1 min/session. Running time was gradually increased by 2 min/day. The training plan was one session per day during the initial 2 weeks and two sessions per day during the third to ninth week. At the end of the 9-week experiment, we analysed the blood of the experimental animals for haemoglobin levels, erythrocyte numbers, haematocrit, serum iron levels, total iron binding capacity, transferrin saturation, serum ferritin levels and soluble transferrin receptor (sTfR) levels, and we calculated the ratio of sTfR/ferritin. Erythrocyte numbers, haemoglobin levels and haematocrit values were decreased after 9 weeks of exercise, but sTfR and sTfR/ferritin values were increased (P < 0.01 or P < 0.05). The training regime significantly increased TfR mRNA levels in the bone marrow cells of the exercised rats compared with the sedentary group (1.8 ± 0.5 vs. 1.1 ± 0.2, P < 0.01). These results revealed a significant correlation between TfR levels in the bone marrow cells and the ratio of sTfR/ferritin (r = 0.517; P < 0.01) and sTfR levels (r = 0.206; P < 0.05) in sedentary and exercised rats. In conclusion, we show that sTfR indices and the ratio of sTfR/ferritin could be useful indicators for monitoring iron deficiency during endurance training.

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

    PubMed

    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.

  16. 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.

  17. Toluene diisocyanate (TDI) regulates haem oxygenase-1/ferritin expression: implications for toluene diisocyanate-induced asthma.

    PubMed

    Kim, S-H; Choi, G-S; Ye, Y-M; Jou, I; Park, H-S; Park, S M

    2010-06-01

    Diisocyanate is a leading cause of occupational asthma (OA). Diisocyanate-induced OA is an inflammatory disease of the airways that is associated with airway remodelling. Although the pathogenic mechanisms are unclear, oxidative stress may be related to the pathogenesis of diisocyanate-induced OA. In our previous report, we observed that the expression of ferritin light chain (FTL) was decreased in both of bronchoalveolar lavage fluid and serum of patients with diphenyl-methane diisocyanate (MDI)-induced OA compared to those of asymptomatic exposed controls and unexposed healthy controls. In this study of toluene diisocyanate (TDI)-OA, we found identical findings with increased transferrin and decreased ferritin levels in the serum of patients with TDI-OA. To elucidate whether diisocyanate suppresses FTL synthesis directly, we tested the effect of TDI on the FTL synthesis in A549 cells, a human airway epithelial cell line. We found that haem oxygenase-1 as well as FTL was suppressed by treatment with TDI in dose- and time-dependent manners. We also found that the synthesis of other anti-oxidant proteins such as thioredoxin-1, glutathione peroxidase, peroxiredoxin 1 and catalase were suppressed by TDI. Furthermore, TDI suppressed nuclear translocation of Nrf2 through suppressing the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular-regulated kinase 1/2 (ERK1/2); p38; and c-Jun N-terminal kinase (JNK). Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, 15-deoxy-Delta(12,14)-PGJ2 and rosiglitazone rescued the effect of TDI on HO-1/FTL expression. Collectively, our findings suggest that TDI suppressed HO-1/FTL expression through the MAPK-Nrf2 signalling pathway, which may be involved in the pathogenesis of TDI-induced OA. Therefore, elucidating these observations further should help to develop the therapeutic strategies of diisocyanate-induced OA.

  18. 21 CFR 866.5340 - Ferritin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  19. 21 CFR 866.5340 - Ferritin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  20. 21 CFR 866.5340 - Ferritin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  1. 21 CFR 866.5340 - Ferritin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ferritin immunological test system. 866.5340 Section 866.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  2. [The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life: a randomized, controlled trial].

    PubMed

    Ceriani Cernadas, José M; Carroli, Guillermo; Pellegrini, Liliana; Ferreira, Marina; Ricci, Carolina; Casas, Ofelia; Lardizabal, Jaime; Morasso, María Del Carmen

    2010-06-01

    Delayed umbilical cord clamping could increase iron stores and prevent iron deficiency in infants. To test this hypothesis we measured serum ferritin and hemoglobin levels at six months of age in term infants who had participated in a randomized controlled trial, assessing the effect of cord clamping timing on neonatal hematocrit values and clinical outcome. Main outcome measure. Serum ferritin level at six months of age. Out of the 276 mothers and their infants that participated in the initial study, 255 (92.4%) were followed up to six months and included in this study. Of these, 86 had their cords clamped within the first 15 seconds (early clamping), 83 at one minute, and 83 at three minutes. The pediatricians in charge of the evaluations during the follow-up period and personnel in charge of the biochemical tests were blinded to the assignment group. In all but 3 infants the ferritin levels and hemoglobin levels were measured at six months of age. Mothers and infants in the three groups had similar baseline characteristics. Serum ferritin levels were significantly higher in the infants of the three minutes group than in the infants of the early group: 33.2 microg/L vs. 20.9 microg/L (geometric mean ratio: 1.6; 95% CI: 1.2 to 2.11) but no difference was observed in one minute group (25.5 microg/L) vs. early group. There were no significant differences in mean hemoglobin values, 10.6 g/dl (SD 1,1); 10.8 g/dl (SD 0.9) and 10.7 g/dl (SD 1.0) between groups early, one minute, and three minutes, respectively. Although there were no significant differences between groups, the prevalence of iron deficiency anemia (hemoglobin < 10.5 g/dl and ferritin < 9 microg/L) was 3 times more frequent in early clampling group (7.2%) than in three minutes group (2.4%) (RR: 0.30; IC 95%: 0.10-1.60). Delayed umbilical cord clamping at three minutes significantly increases serum ferritin levels in infants at 6 months of age. No significant differences were found between groups in mean

  3. Serum hepcidin level correlates with hyperlipidemia status in patients following allograft renal transplantation.

    PubMed

    Xue, D; He, X; Zhou, C

    2014-01-01

    Hepcidin is synthesized and secreted by liver cells and has been reported as one of the hormone molecules that regulates iron homeostasis. To determine whether serum level of hepcidin can be used as a biomarker for the evaluation of chronic inflammatory status, iron level and renal function in patients following allograft renal transplantation, serum levels of hepcidin, interleukin (IL)-6, ferritin, serum iron, and renal functions were measured. Sixty patients were included in the current study and were further separated into groups with or without hyperlipidemia. We found that allogeneic kidney transplant recipients with hyperlipidemia have significantly increased serum levels of hepcidin, IL-6, and ferritin. The increased serum hepcidin is positively correlated with serum IL-6 and ferritin as analyzed by single-factor correlation analysis. Multivariant correlation analysis in all specimens further demonstrated that serum hepcidin negatively correlated with glomerular filtration rate, and positively correlated with serum total cholesterol, triglycerides, serum ferritin, and IL-6. Our study demonstrated that serum level of hepcidin after allogeneic kidney transplantation not only reflects the status of chronic inflammation but can also indicate changes in renal function. Thus, hepcidin has the potential to be used as a promising marker for the detection and monitoring of the status of chronic inflammation, hyperlipidemia, and renal function in patients following allograft renal transplantation.

  4. Haemopexin affects iron distribution and ferritin expression in mouse brain

    PubMed Central

    Morello, Noemi; Tonoli, Elisabetta; Logrand, Federica; Fiorito, Veronica; Fagoonee, Sharmila; Turco, Emilia; Silengo, Lorenzo; Vercelli, Alessandro; Altruda, Fiorella; Tolosano, Emanuela

    2009-01-01

    Haemopexin (Hx) is an acute phase plasma glycoprotein, mainly produced by the liver and released into plasma where it binds heme with high affinity and delivers it to the liver. This system provides protection against free heme-mediated oxidative stress, limits access by pathogens to heme and contributes to iron homeostasis by recycling heme iron. Hx protein has been found in the sciatic nerve, skeletal muscle, retina, brain and cerebrospinal fluid (CSF). Recently, a comparative proteomic analysis has shown an increase of Hx in CSF from patients with Alzheimer’s disease, thus suggesting its involvement in heme detoxification in brain. Here, we report that Hx is synthesised in brain by the ventricular ependymal cells. To verify whether Hx is involved in heme scavenging in brain, and consequently, in the control of iron level, iron deposits and ferritin expression were analysed in cerebral regions known for iron accumulation. We show a twofold increase in the number of iron-loaded oligodendrocytes in the basal ganglia and thalamus of Hx-null mice compared to wild-type controls. Interestingly, there was no increase in H- and L-ferritin expression in these regions. This condition is common to several human neurological disorders such as Alzheimer’s disease and Parkinson’s disease in which iron loading is not associated with an adequate increase in ferritin expression. However, a strong reduction in the number of ferritin-positive cells was observed in the cerebral cortex of Hx-null animals. Consistent with increased iron deposits and inadequate ferritin expression, malondialdehyde level and Cu–Zn superoxide dismutase-1 expression were higher in the brain of Hx-null mice than in that of wild-type controls. These data demonstrate that Hx plays an important role in controlling iron distribution within brain, thus suggesting its involvement in iron-related neurodegenerative diseases. PMID:19120692

  5. Crystal structure of plant ferritin reveals a novel metal binding site that functions as a transit site for metal transfer in ferritin.

    PubMed

    Masuda, Taro; Goto, Fumiyuki; Yoshihara, Toshihiro; Mikami, Bunzo

    2010-02-05

    Ferritins are important iron storage and detoxification proteins that are widely distributed in living kingdoms. Because plant ferritin possesses both a ferroxidase site and a ferrihydrite nucleation site, it is a suitable model for studying the mechanism of iron storage in ferritin. This article presents for the first time the crystal structure of a plant ferritin from soybean at 1.8-A resolution. The soybean ferritin 4 (SFER4) had a high structural similarity to vertebrate ferritin, except for the N-terminal extension region, the C-terminal short helix E, and the end of the BC-loop. Similar to the crystal structures of other ferritins, metal binding sites were observed in the iron entry channel, ferroxidase center, and nucleation site of SFER4. In addition to these conventional sites, a novel metal binding site was discovered intermediate between the iron entry channel and the ferroxidase site. This site was coordinated by the acidic side chain of Glu(173) and carbonyl oxygen of Thr(168), which correspond, respectively, to Glu(140) and Thr(135) of human H chain ferritin according to their sequences. A comparison of the ferroxidase activities of the native and the E173A mutant of SFER4 clearly showed a delay in the iron oxidation rate of the mutant. This indicated that the glutamate residue functions as a transit site of iron from the 3-fold entry channel to the ferroxidase site, which may be universal among ferritins.

  6. 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.

  7. Evidence for a protein-protein complex during iron loading into ferritin by ceruloplasmin.

    PubMed

    Reilly, C A; Sorlie, M; Aust, S D

    1998-06-01

    The formation of a protein-protein complex for the loading of iron into ferritin by ceruloplasmin was investigated. Ferritin stimulated the ferroxidase activity of ceruloplasmin unless the ferritin was fully loaded, in which case it inhibited the ferroxidase activity of ceruloplasmin. The apparent association constant for the interaction of ferritin and ceruloplasmin was 24 nM. Isothermal titration calorimetry indicated that the interaction of ceruloplasmin and ferritin was endothermic, driven by positive changes in entropy. The association constants for complex formation between ferritin and ceruloplasmin were 4.5 +/- 0.7 x 10(5) and 9.5 +/- 0.3 x 10(4) M-1 for the reduced and oxidized forms of ceruloplasmin, respectively. The oxidized form of ceruloplasmin was retained on an affinity column with ferritin immobilized as the ligand and remained bound to the column with mobile phases of increased hydrophobicity, but was eluted with increased ionic strength. The ability of ceruloplasmin to remain bound to the affinity resin was affected by the species from which ceruloplasmin was isolated. Gradient ultracentrifugation also provided evidence that the two proteins were associated, since ferritin promoted migration of ceruloplasmin through the gradient. Including ferrous iron in the gradient resulted in reduction of ceruloplasmin and increased the mobility of ceruloplasmin with ferritin. These data provide evidence that ferritin and ceruloplasmin form a protein-protein complex during iron loading into ferritin, which may limit redox cycling of iron in vivo.

  8. APPEARANCE AND DISTRIBUTION OF FERRITIN IN MOUSE PERITONEAL MACROPHAGES IN VITRO AFTER UPTAKE OF HETEROLOGOUS ERYTHROCYTES

    PubMed Central

    Fedorko, Martha E.; Cross, Nicholas L.; Hirsch, James G.

    1973-01-01

    Mouse peritoneal macrophages have been studied in vitro after ingestion of treated rat, rabbit, or sheep erythrocytes. Under light microscopy, phagocytic vacuoles persist up to 24 h. Macrophages lose benzidine reactivity about 5 h after red cell ingestion, and they become prussian blue positive at 2 days. Ultrastructural studies show little or no ferritin in control macrophages not fed erythrocytes. In contrast, after red cell ingestion, ferritin is widely distributed in the cytoplasmic matrix and in some cytoplasmic granules by 48 h. The Golgi complex, pinocytic vacuoles, endoplasmic reticulum, nuclei, and mitochondria do not contain ferritin. Between 2 and 4 days, ferritin in cytoplasmic granules increases, concomitant with decrease in the ferritin in the cytoplasmic matrix. Evidence is presented suggesting that ferritin in the cytoplasmic matrix is translocated into cytoplasmic granules by autophagy. Polyacrylamide gel studies on macrophages after uptake of red blood cells labeled with radioiron confirm that macrophages produce radiolabeled ferritin by 4 days. PMID:4348785

  9. Mechanisms by which ascorbic acid increases ferritin levels in cultured lens epithelial cells.

    PubMed

    Goralska, M; Harned, J; Grimes, A M; Fleisher, L N; McGahan, M C

    1997-03-01

    A previous study demonstrated that ascorbic acid increased the concentration of the iron storage protein, ferritin. In cultured lens epithelial cells. The current study was designed to determine the mechanism by which ascorbic acid exerts this effect. Ascorbic acid increased both ferritin mRNA levels (by about 30%) and translation of ferritin (de novo synthesis was increased up to 15-fold) within 6 hr. Cycloheximide completely abolished the ability of ascorbic acid to increase ferritin levels, whereas actinomycin D only decreased it by about 30%. Therefore, the ascorbic-acid induced increase in ferritin concentration is due mainly to an increase in ferritin synthesis at the translational levels. This is a novel role for ascorbic acid. Addition of iron with ascorbic acid further increased de novo synthesis of ferritin, but this additive effect was only noted at a later time point (20 hr). Factors which decrease ferritin mRNA translation, such as the reducing agent dithiothreitol or the iron chelator desferrioxamine, reduced the ascorbic acid effect on de novo ferritin synthesis. The effects of ascorbic acid on ferritin mRNA levels may be mediated by its oxidation product, H2O2, since, like ascorbic acid, H2O2 increased ferritin mRNA levels by 30%. However, in contrast to the ascorbic acid-induced increase in translation of ferritin, H2O2 substantially decreased de novo ferritin synthesis. This effect of H2O2 could have physiological significance in eyes where concentrations of H2O2 in the aqueous humor are elevated. High levels of H2O2 could decrease the concentration of ferritin within the lens. Since ferritin sequesters iron and has been shown to decrease oxidative damage by limiting the availability of iron to catalyse free radical reactions, H2O2-induced reduction in ferritin concentration in the lens could have deleterious effects. The ability of ascorbic acid to increase ferritin concentration in lens epithelial cells could provide an additional protective

  10. 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

  11. Electrical conductivity of cationized ferritin decorated gold nanoshells

    NASA Astrophysics Data System (ADS)

    Cortez, Rebecca; Slocik, Joseph M.; Van Nostrand, Joseph E.; Halas, Naomi J.; Naik, Rajesh R.

    2012-06-01

    We report on a novel method of controlling the resistance of nanodimensional, gold-coated SiO2 nanoparticles by utilizing biomolecules chemisorbed to the nanoshell surface. Local electronic transport properties of gold-coated nanoshells were measured using scanning conductance microscopy. These results were compared to transport properties of identical gold nanoshells biofunctionalized with cationized ferritin protein both with and without an iron oxide core (apoferritin). Measured resistances were on the order of mega-ohms. White light irradiation effects on transport properties were also explored. The results suggest that the light energy influences the nanoshells' conductivity. A mechanism for assembly of gold nanoshells with cationized ferritin or cationized apoferritin is proposed to explain the resistivity dependence on irradiation.

  12. Folic acid conjugated ferritins as photosensitizer carriers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhen, Zipeng; Tang, Wei; Zhang, Weizhong; Xie, Jin

    2015-06-01

    We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis.We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis. Electronic supplementary information (ESI) available: Details of experiments and ex vivo imaging results. See DOI: 10.1039/c5nr01833a

  13. Creation of energetic biothermite inks using ferritin liquid protein

    NASA Astrophysics Data System (ADS)

    Slocik, Joseph M.; McKenzie, Ruel; Dennis, Patrick B.; Naik, Rajesh R.

    2017-04-01

    Energetic liquids function mainly as fuels due to low energy densities and slow combustion kinetics. Consequently, these properties can be significantly increased through the addition of metal nanomaterials such as aluminium. Unfortunately, nanoparticle additives are restricted to low mass fractions in liquids because of increased viscosities and severe particle agglomeration. Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to overcoming low mass fractions of nanoparticles, producing stable nanoparticle dispersions and simultaneously offering a source of oxidizing agents for combustion of reactive nanomaterials. Here, we use iron oxide-loaded ferritin proteins to create a stable and highly energetic liquid composed of aluminium nanoparticles and ferritin proteins for printing and forming 3D shapes and structures. In total, this bioenergetic liquid exhibits increased energy output and performance, enhanced dispersion and oxidation stability, lower activation temperatures, and greater processability and functionality.

  14. Creation of energetic biothermite inks using ferritin liquid protein

    PubMed Central

    Slocik, Joseph M.; McKenzie, Ruel; Dennis, Patrick B.; Naik, Rajesh R.

    2017-01-01

    Energetic liquids function mainly as fuels due to low energy densities and slow combustion kinetics. Consequently, these properties can be significantly increased through the addition of metal nanomaterials such as aluminium. Unfortunately, nanoparticle additives are restricted to low mass fractions in liquids because of increased viscosities and severe particle agglomeration. Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to overcoming low mass fractions of nanoparticles, producing stable nanoparticle dispersions and simultaneously offering a source of oxidizing agents for combustion of reactive nanomaterials. Here, we use iron oxide-loaded ferritin proteins to create a stable and highly energetic liquid composed of aluminium nanoparticles and ferritin proteins for printing and forming 3D shapes and structures. In total, this bioenergetic liquid exhibits increased energy output and performance, enhanced dispersion and oxidation stability, lower activation temperatures, and greater processability and functionality. PMID:28447665

  15. Creation of energetic biothermite inks using ferritin liquid protein.

    PubMed

    Slocik, Joseph M; McKenzie, Ruel; Dennis, Patrick B; Naik, Rajesh R

    2017-04-27

    Energetic liquids function mainly as fuels due to low energy densities and slow combustion kinetics. Consequently, these properties can be significantly increased through the addition of metal nanomaterials such as aluminium. Unfortunately, nanoparticle additives are restricted to low mass fractions in liquids because of increased viscosities and severe particle agglomeration. Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to overcoming low mass fractions of nanoparticles, producing stable nanoparticle dispersions and simultaneously offering a source of oxidizing agents for combustion of reactive nanomaterials. Here, we use iron oxide-loaded ferritin proteins to create a stable and highly energetic liquid composed of aluminium nanoparticles and ferritin proteins for printing and forming 3D shapes and structures. In total, this bioenergetic liquid exhibits increased energy output and performance, enhanced dispersion and oxidation stability, lower activation temperatures, and greater processability and functionality.

  16. Comparison of plasma ferritin concentration versus the ratio of plasma transferrin receptor to ferritin in estimating body iron stores: results of 4 intervention trials

    USDA-ARS?s Scientific Manuscript database

    Background: To develop global programs for the control of iron deficiency, simple, low-cost, accurate indicators of iron status are needed. Objectives: To compare estimates of body iron stores, as calculated from either plasma ferritin concentration alone (BI-ferritin) or the ratio of plasma transf...

  17. Influence of blood donation time intervals on ferritin and hemoglobin concentration.

    PubMed

    Manascero-Gómez, Aura R; Bravo-Espinosa, Melisa; Solano-Muriel, Katherine; Poutou-Piñales, Raúl A

    2015-10-01

    Identify possible significant hemoglobin level variations between blood donations, and observe the effect of periodic donations on iron store. Seventy-seven subjects were monitored in the course of 1 year to evaluate if repetitive blood donations had an effect on hemoglobin and ferritin concentrations. Furthermore, we determined if hemoglobin concentration variation, detected by the cyanmethemoglobin method, could be used as an early marker for decreased ferritin concentration, quantified by ELISA. No association between hemoglobin and ferritin variations was observed, as evidenced from our results. Ferritin variations were greater than 50% between donations; in contrast, hemoglobin remained unchanged within intra-individual biological fluctuations. We observed decreased ferritin values during the first blood donation in 15% of the men and 14% of the women evaluated. During the second blood donation 22% of men and 23% of women had decreased ferritin levels. During the third blood donation 43% of men and 50% of women had decreased ferritin values. Only men donated blood four times during the course of the year with all men having decreased ferritin levels. Decrease in ferritin was conditioned both by the number of blood donations as well as the periodicity between them. Spans greater than 6 months between blood donations reduced the risk of iron store reduction. We determined hemoglobin is not a sensitive marker for monitoring repetitive blood donor follow-up, since hemoglobin did not vary significantly between donations despite having very low or nil ferritin concentration values. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Translational control of ferritin synthesis: a study of repression using natural and synthetic mRNAs

    SciTech Connect

    Dickey, L.F.; Wang, Y.H.; Wortman, I.; Shull, G.E.; Theil, E.C.

    1987-05-01

    Ferritin synthesis is a dramatic example of mRNA repression: excess iron causes recruitment of ferritin mRNA, increasing synthesis less than or equal to 40 x. Using the iron-storing tadpole red cell as a simple and accessible model, isolated poly(A+) RNA directed the synthesis of ferritin and globin in cell-free extracts from wheat germ (WG); in contrast, ferritin mRNA was specifically repressed (72%) in extracts from rabbit reticulocytes (RR) as it is in vivo. Translatable and hybridizable ferritin mRNA did not enter polysomes of RR in contrast to globin mRNA and to both ferritin and globin mRNA in WG. Single-sequence mRNA, uncapped, was prepared in vitro for both a ferritin M chain and a globin beta chain; both were translated with similar efficiency in RR (164 +/- 66) x 10/sup -3/ and (205 +/- 144) x 10/sup -3/ cpm (/sup 3/H)leucine/h/..mu..g RNA for ferritin and globin, respectively). Ferritin with the expected immunoreactivity and mobility in SDS gel electrophoresis was obtained. The results suggest that ferritin mRNA repression may require a cap or factors present in poly(A+) RNA and that repression can be released in WG but not in RR.

  19. 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.

  20. A novel ferritin subunit involved in shell formation from the pearl oyster (Pinctada fucata).

    PubMed

    Zhang, Yong; Meng, Qingxiong; Jiang, Tiemin; Wang, Hongzhong; Xie, Liping; Zhang, Rongqing

    2003-05-01

    Iron is one of the most important minor elements in the shell of bivalves. This study was designed to investigate the involvement of ferritin, the principal protein for iron storage, in shell formation. A novel ferritin cDNA from the pearl oyster (Pinctada fucata) was isolated and characterized. The ferritin cDNA encodes a 206 amino acid polypeptide, which shares high similarity with snail soma ferritin and the H-chains of mammalian ferritins. Oyster ferritin mRNA shows the highest level of expression in the mantle, the organ for shell formation. In situ hybridization analysis revealed that oyster ferritin mRNA is expressed at the highest level at the mantle fold, a region essential for metal accumulation and contributes to metal incorporation into the shell. Taken together, these results suggest that ferritin is involved in shell formation by iron storage. The identification and characterization of oyster ferritin also helps to further understand the structural and functional properties of molluscan ferritins.

  1. Electrical Conductivity of Ferritin Proteins by Conductive AFM

    NASA Technical Reports Server (NTRS)

    Xu, Degao; Watt, Gerald D.; Harb, John N.; Davis, Robert C.

    2005-01-01

    Electrical conductivity measurements were performed on single apoferritin and holoferritin molecules by conductive atomic force microscopy. Conductivity of self-assembled monolayer films of ferritin molecules on gold surfaces was also measured. Holoferritin was 5-25 times more conductive than apoferritin, indicating that for holoferritin most electron-transfer goes through the ferrihydrite core. With 1 V applied, the average electrical currents through single holoferritin and apoferritin molecules were 2.6 PA and 0.19 PA, respectively.

  2. Electrical Conductivity of Ferritin Proteins by Conductive AFM

    NASA Technical Reports Server (NTRS)

    Xu, Degao; Watt, Gerald D.; Harb, John N.; Davis, Robert C.

    2005-01-01

    Electrical conductivity measurements were performed on single apoferritin and holoferritin molecules by conductive atomic force microscopy. Conductivity of self-assembled monolayer films of ferritin molecules on gold surfaces was also measured. Holoferritin was 5-25 times more conductive than apoferritin, indicating that for holoferritin most electron-transfer goes through the ferrihydrite core. With 1 V applied, the average electrical currents through single holoferritin and apoferritin molecules were 2.6 PA and 0.19 PA, respectively.

  3. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    PubMed

    Lyberopoulou, Aggeliki; Chachami, Georgia; Gatselis, Nikolaos K; Kyratzopoulou, Eleni; Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K; Mamalaki, Avgi; Dalekos, George N; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  4. The Ferritin Superfamily: Supramolecular Templates for Materials Synthesis

    PubMed Central

    Uchida, Masaki; Kang, Sebyung; Reichhardt, Courtney; Harlen, Kevin; Douglas, Trevor

    2013-01-01

    Members of the ferritin superfamily are multi-subunit cage-like proteins with a hollow interior cavity. These proteins possess three distinct surfaces, i.e. interior and exterior surfaces of the cages and interface between subunits. The interior cavity provides a unique reaction environment in which the interior reaction is separated from the external environment. In biology the cavity is utilized for sequestration of irons and biomineralization as a mechanism to render Fe inert and sequester it from the external environment. Material scientists have been inspired by this system and exploited a range of ferritin superfamily proteins as supramolecular templates to encapsulate nanoparticles and/or as well-defined building blocks for fabrication of higher order assembly. Besides the interior cavity, the exterior surface of the protein cages can be modified without altering the interior characteristics. This allows us to deliver the protein cages to a targeted tissue in vivo or to achieve controlled assembly on a solid substrate to fabricate higher order structures. Furthermore, the interface between subunits is utilized for manipulating chimeric self-assembly of the protein cages and in the generation of symmetry-broken Janus particles. Utilizing these ideas, the ferritin superfamily has been exploited for development of a broad range of materials with applications from biomedicine to electronics. PMID:20026386

  5. Effect of systemic inflammation on level of ferritin seminal in chronic renal male patient undergoing hemodialysis

    PubMed Central

    2014-01-01

    Background Most hemodialysis patients present with chronic systemic inflammation characterized by the elevation of serum C-reactive protein (CRP) levels and/or the production of proinflammatory interleukins by the immune system in response to the hemodialysis process. Plasma ferritin(PF) is one of the parameters used to correct anemia. An PF level of >500 ng/mL is not recommended for correction of anemia because of the uncertainty of whether these levels are elevated because of anemia or a mere reaction to inflammation. we aimed to study the effects of inflammation on seminal ferritin (SF) levels and hypothesized that SF is not affected because of the testicular immune privilege. Methods A prospective prevalence study was conducted at the Department of Hemodialysis of the University Hospital of Brasília (HuB) between June 2010 and July 2011. The sample included 60 chronic renal patients undergoing hemodialysis and 20 control subjects from the health promotion general outpatient clinic. All participants were males aged 18–60 years. Inflammation was assessed through serum CRP levels, and the testicular condition was determined by measuring sex hormone levels. In the patient group, inflammation was considered to be present when CRP was >5 mg/L (n = 27) and absent when CRP was ≤5 mg/L (n = 33). Control group (n = 20) CRP was ≤1 mg/L. Blood and semen were collected via arm venoclysis and after voluntary masturbation, respectively. CRP was measured by turbidimetry; PF, SF, and sex hormone levels by immunochemoluminescence. Statistical significance was set at p < 0.05. Results There was no significant difference in mean SF levels among patients with inflammation (295.34 ± 145.39 ng/mL), those without inflammation (324.42 ± 145.51 mg/mL), and controls (335.70 ± 075.90 ng/mL; p = 0.49). There was no correlation between mean SF and PF levels in the patients with and without inflammation). All participants were eugonadal with mean

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

    PubMed

    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.

  7. 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

  8. Proanthocyanidins inhibit iron absorption from soybean (Glycine max) seed ferritin in rats with iron deficiency anemia.

    PubMed

    Yun, Shaojun; Zhang, Tuo; Li, Meiliang; Chen, Bin; Zhao, Guanghua

    2011-09-01

    The objective of this study was to evaluate the effect of proanthocyanidins (PAs) on iron uptake from soybean seed ferritin (SSF) crude by rats with iron deficiency anemia (IDA) for the first time. Six groups of Sprague-Dawley (SD) rats (n = 10) were used, which contain (1) SSF crude group; (2) SSF crude + PAs group; (3) PAs group; (4) FeSO(4) group; (5) iron deficiency control group; and (6) control group. The bioavailability of iron was examined by measuring hemoglobin (Hb) concentration value, red blood cell (RBC) numbers, and serum iron stores. After 8 weeks, Hb concentration was almost recovered to the normal level upon feeding SSF crude or FeSO(4) to rats. In contrast, Hb concentration was recovered to less extent when SSF crude plus PAs was used instead of SSF crude alone (P < 0.05). A similar profile was observed with these three sample groups when serum iron and RBC were used as parameters. All rats in PAs group died at the 8th week. Taken together, all these results demonstrated that PAs inhibited iron uptake of rats from SSF, and are toxic for rats with IDA.

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

    SciTech Connect

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

    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 indicated very rapid plasma ferritin turnover.

  10. Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload

    PubMed Central

    Miyazaki, E; Kato, J; Kobune, M; Okumura, K; Sasaki, K; Shintani, N; Arosio, P; Niitsu, Y

    2002-01-01

    Background and aims: Iron is stored in hepatocytes in the form of ferritin and haemosiderin. There is a marked increase in iron rich haemosiderin in iron overloaded livers, and ferric iron in amounts exceeding the ferritin and haemosiderin binding capacity may promote free radical generation, causing cellular damage. The aim of this study was to characterise hepatic haemosiderin using four antibodies specific for either native or denatured H/L-ferritin subunits. Methods: Ferritin and haemosiderin were prepared from the livers of three patients with post-transfusional iron overload. The assembled ferritin molecules were analysed by non-denaturing polyacrylamide gel electrophoresis (PAGE)-immunoblotting. Ferritin subunits in the haemosiderin fraction were assessed by denaturing sodium dodecyl sulphate (SDS)-PAGE-immunoblotting. Distribution of native and denatured ferritin subunits in hepatocytes was examined by immunogold electron microscopy. Results: Non-denaturing PAGE-immunoblot analyses showed that the assembled liver ferritins were recognised by the antibodies for native ferritins and not by those for the denatured subunits. Both SDS-PAGE-immunoblot and immunogold electron microscopic analyses disclosed that haemosiderin of iron overloaded liver reacted predominantly to the monoclonal antibody for the denatured H-ferritin subunit, to a lesser degree to that for denatured L-ferritin, and very weakly, if any, with antibodies for native H-ferritin or L-ferritin. Conclusions: These results suggest that in iron overloaded liver, haemosiderin consists predominantly of denatured H-ferritin subunits. PMID:11839724

  11. Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis

    DTIC Science & Technology

    2013-12-01

    Treatment for Amyotrophic Lateral Sclerosis PRINCIPAL INVESTIGATOR: James R. Connor, Ph.D. CONTRACTING ORGANIZATION: Pennsylvania...Apo-Ferritin as a Therapeutic Treatment for Amyotrophic Lateral Sclerosis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0733 5c...2.0 mg/ml of ferritin was the lowest dose reported to be effective. The data in Figure 3 indicate that treatment with CSF or 4.0 mg/ml H-ferritin

  12. A facile synthesis of fluorescent silver nanoclusters with human ferritin as a synthetic and interfacing ligand.

    PubMed

    Lee, In Hwan; Ahn, Byungjun; Lee, Jeong Min; Lee, Chang Soo; Jung, Yongwon

    2015-05-21

    Water-soluble fluorescent silver nanoclusters (NCs) formed on biomolecule ligands have been extensively studied due to their great potential as new biocompatible fluorescent materials for biosensors. As synthetic ligands, proteins in particular can provide unique structures and functions to the assembled fluorescent silver clusters. A key challenge, however, is to develop appropriate protein ligands and synthetic approaches for cluster formation, especially using native aqueous solutions, to fully preserve the valuable properties of the protein templates. Here we report a human ferritin-templated synthesis of fluorescent silver NCs under neutral aqueous buffer conditions. The unique metal binding property of ferritin and an optimized silver ion reduction allowed us to produce highly stable fluorescent silver NCs that are steadily assembled in the cage-like ferritin proteins. The fluorescent clusters were also successfully assembled on genetically engineered ferritin with antibody-binding protein G. The resulting protein G-ferritin-silver NC complex fully retained the ferritin structure as well as the antibody binding ability. The present silver nanoclusters on ferritin (Ft-Ag NCs) also showed highly specific Cu(2+)-induced fluorescence quenching. By exploiting the large but stable nature of ferritin, we fabricated a highly robust and porous hydrogel sensor system for rapid Cu(2+) detection, where the Ft-Ag NCs were stably encapsulated in surface-bound hydrogels with large pore sizes. Our Ft-Ag NCs that are formed under native aqueous conditions will have great potential as a new fluorescent material with the high structural and functional diversities of ferritin.

  13. Phosphate and arsenate removal efficiency by thermostable ferritin enzyme from Pyrococcus furiosus using radioisotopes.

    PubMed

    Sevcenco, Ana-Maria; Paravidino, Monica; Vrouwenvelder, Johannes S; Wolterbeek, Hubert Th; van Loosdrecht, Mark C M; Hagen, Wilfred R

    2015-06-01

    Oxo-anion binding properties of the thermostable enzyme ferritin from Pyrococcus furiosus were characterized with radiography. Radioisotopes (32)P and (76)As present as oxoanions were used to measure the extent and the rate of their absorption by the ferritin. Thermostable ferritin proved to be an excellent system for rapid phosphate and arsenate removal from aqueous solutions down to residual concentrations at the picomolar level. These very low concentrations make thermostable ferritin a potential tool to considerably mitigate industrial biofouling by phosphate limitation or to remove arsenate from drinking water.

  14. Human-brain ferritin studied by muon spin rotation: a pilot study.

    PubMed

    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

    2017-09-05

    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.

  15. Mutated recombinant human heavy-chain ferritins and myelosuppression in vitro and in vivo: a link between ferritin ferroxidase activity and biological function.

    PubMed Central

    Broxmeyer, H E; Cooper, S; Levi, S; Arosio, P

    1991-01-01

    Human heavy-chain (H-) ferritin muteins obtained by oligonucleotide site-directed mutagenesis, together with wild-type recombinant human H- and light-chain (L-) ferritins, were evaluated for in vitro effects on the suppression of human bone marrow myeloid progenitor cells and for in vivo effects on marrow and splenic myelopoiesis in C3H/HeJ mice. The 10 H-ferritin muteins exhibited alterations of various regions of the molecule, including ones exposed on the outer surface, on the inner cavity, and on the hydrophilic and hydrophobic channels and of the four-alpha-helix bundle forming the subunit structure. They were stable and were electrophoretically analogous to wild-type H-ferritin. The muteins showed in vitro and in vivo myelosuppressive activity analogous to wild type, except for mutein 222, which was totally inactive and which lacked ferroxidase activity. Recombinant human L-ferritin, devoid of ferroxidase activity, was also inactive as a suppressor. The results demonstrate that H-ferritin myelosuppressive and ferroxidase activities are linked. One possibility is that ferroxidase activity may interfere with the cellular uptake of transferrin iron that is needed for cell proliferation, an interpretation consistent with the presently described ability of hemin to overcome H-ferritin suppressive effects. PMID:1992468

  16. 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

  17. Serum sickness

    MedlinePlus

    Drug allergy - serum sickness; Allergic reaction - serum sickness; Allergy - serum sickness ... penicillin, cefaclor, and sulfa) can cause a similar reaction. Injected proteins such as antithymocyte globulin (used to ...

  18. Magnetic properties of ferritin and akaganeite nanoparticles in aqueous suspension

    NASA Astrophysics Data System (ADS)

    Koralewski, Marceli; Pochylski, Mikołaj; Gierszewski, Jacek

    2013-09-01

    We have studied the magnetically induced optical birefringence Δ n of horse spleen ferritin (HSF) and aqueous suspensions of several different-sized iron oxyhydroxide nanoparticles coated with different polysaccharides mimicking ferritin. The structure and dimensions of the akaganeite mineral core were characterized by XRD and TEM, respectively. The stability of the suspensions in the measurement temperature range from 278 to 358 K was confirmed by UV-Vis absorption spectroscopy. The values of optical polarizability anisotropy Δ α, magnetic susceptibility anisotropy Δ χ, and permanent magnetic dipole moment μ m of the akaganeite nanoparticles have been estimated on the basis of the temperature dependence of the Cotton-Mouton (C-M) constant. The magnetic birefringence of Fe-sucrose has been described tentatively by different types of Langevin function allowing another estimation of Δ χ and μ m. The obtained permanent magnetic dipole moment μ m of the studied akaganeite nanoparticles proves small and comparable to that of HSF. The value of μ m is found to increase with decreasing nanoparticle diameter. Observed in a range spanning more than five orders of magnitude, the linear relation between the C-M constant and the iron concentration provides a basis for possible analytical application of the C-M effect in biomedicine. The established relation between the C-M constant and the nanoparticle diameter confirms that the dominant contribution to the measured magnetic birefringence comes from the magnetic susceptibility anisotropy Δ χ. A comparison of the C-M constants of the studied akaganeite nanoparticles with the data obtained for HSF provides evidence that the ferritin core behaves as a non-Euclidian solid.

  19. Electrical conductivity of ferritin proteins by conductive AFM.

    PubMed

    Xu, Degao; Watt, Gerald D; Harb, John N; Davis, Robert C

    2005-04-01

    Electrical conductivity measurements were performed on single apoferritin and holoferritin molecules by conductive atomic force microscopy. Conductivity of self-assembled monolayer films of ferritin molecules on gold surfaces was also measured. Holoferritin was 5-15 times more conductive than apoferritin, indicating that for holoferritin most electron-transfer goes through the ferrihydrite core. With 1 V applied, the average electrical currents through single holoferritin and apoferritin molecules were 2.6 pA and 0.19 pA, respectively.

  20. 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

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

    PubMed

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

    2016-05-15

    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. 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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Loading of iron into recombinant rat liver ferritin heteropolymers by ceruloplasmin.

    PubMed

    Juan, S H; Guo, J H; Aust, S D

    1997-05-15

    We have reported previously that the heavy chain of ferritin is required for iron incorporation by ceruloplasmin (J.-H. Guo, M. Abedi, and S. D. Aust (1996) Arch. Biochem. Biophys. 335(1)). The purpose of this study was to determine how many heavy chains were required for ceruloplasmin to interact with ferritin such that iron loading occurred. The cDNA sequences encoding the heavy and light chains of rat liver ferritin were cloned into the baculovirus transfer vector pA-cUW51 under the control of polyhedrin and p10 promoters, respectively, which was then incorporated by homologous recombination into the infections Autographa californica nuclear polyhedrosis virus genome. Both ferritin chains were expressed and assembled into two heteropolymers following the infection of insect cells by recombinant virus, which were separated by DEAE-Sepharose chromatography. The percentage of heavy (H) and light (L) chains making up the two heteropolymers, determined by gel scanning following the resolution of chains on SDS-PAGE, were equivalent to 1 H and 23 L chains and 2 H and 22 L chains. The maximal extent of iron loading was observed using 1 mol of rat ceruloplasmin per mole of H chain in the two heteropolymers. The extent of iron incorporation decreased with additional ceruloplasmin. Iron incorporation into rat liver ferritin, found to contain 10 H chains, increased as the molar ratio of ceruloplasmin to ferritin increased to 4:1 and remained the same up to 8:1. Iron loading into horse spleen ferritin, found to have one H chain, appeared similar to that for recombinant ferritin, having only one H chain. Therefore, we propose that the optimal molar ratio of ceruloplasmin to ferritin depends upon the numbers of H chain making up the ferritin molecule for the maximal incorporation of iron into ferritin. These results also suggest that the iron loading channel is contained within a single H chain subunit.

  3. Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.

    PubMed

    Madenci, Gulizar; Bilen, Sule; Arli, Berna; Saka, Mustafa; Ak, Fikri

    2012-07-01

    We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.

  4. Effect of supplementation with ferrous sulfate or iron bis-glycinate chelate on ferritin concentration in Mexican schoolchildren: a randomized controlled trial.

    PubMed

    Duque, Ximena; Martinez, Homero; Vilchis-Gil, Jenny; Mendoza, Eugenia; Flores-Hernández, Sergio; Morán, Segundo; Navarro, Fabiola; Roque-Evangelista, Victoria; Serrano, Anayeli; Mera, Robertino M

    2014-07-15

    Iron deficiency is one of the most common nutritional deficiencies worldwide. It is more prevalent when iron requirements are increased during pregnancy and during growth spurts of infancy and adolescence. The last stage in the process of iron depletion is characterized by a decrease in hemoglobin concentration, resulting in iron deficiency anemia. Iron deficiency, even before it is clinically identified as anemia, compromises the immune response, physical capacity for work, and intellectual functions such as attention level. Therefore, interventions addressing iron deficiency should be based on prevention rather than on treatment of anemia. The aim of this study was to compare short- and medium-term effects on ferritin concentration of daily supplementation with ferrous sulfate or iron bis-glycinate chelate in schoolchildren with iron deficiency but without anemia. Two hundred schoolchildren from public boarding schools in Mexico City who had low iron stores as assessed by serum ferritin concentration but without anemia were randomly assigned to a daily supplement of 30 mg/day of elemental iron as ferrous sulfate or iron bis-glycinate chelate for 12 weeks. Iron status was evaluated at baseline, one week post-supplementation (short term), and 6 months (medium term) after supplementation. Ferritin concentration increased significantly between baseline and post-supplementation as well as between baseline and 6 months after supplementation. One week post-supplementation no difference was found in ferritin concentration between iron compounds, but 6 months after supplementation ferritin concentration was higher in the group that received bis-glycinate chelate iron. However, there is no difference in the odds for low iron storage between 6 months after supplementation versus the odds after supplementation; nor were these odds different by type of supplement. Hemoglobin concentration did not change significantly in either group after supplementation. Supplementing

  5. Effect of supplementation with ferrous sulfate or iron bis-glycinate chelate on ferritin concentration in Mexican schoolchildren: a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Iron deficiency is one of the most common nutritional deficiencies worldwide. It is more prevalent when iron requirements are increased during pregnancy and during growth spurts of infancy and adolescence. The last stage in the process of iron depletion is characterized by a decrease in hemoglobin concentration, resulting in iron deficiency anemia. Iron deficiency, even before it is clinically identified as anemia, compromises the immune response, physical capacity for work, and intellectual functions such as attention level. Therefore, interventions addressing iron deficiency should be based on prevention rather than on treatment of anemia. The aim of this study was to compare short- and medium-term effects on ferritin concentration of daily supplementation with ferrous sulfate or iron bis-glycinate chelate in schoolchildren with iron deficiency but without anemia. Methods Two hundred schoolchildren from public boarding schools in Mexico City who had low iron stores as assessed by serum ferritin concentration but without anemia were randomly assigned to a daily supplement of 30 mg/day of elemental iron as ferrous sulfate or iron bis-glycinate chelate for 12 weeks. Iron status was evaluated at baseline, one week post-supplementation (short term), and 6 months (medium term) after supplementation. Results Ferritin concentration increased significantly between baseline and post-supplementation as well as between baseline and 6 months after supplementation. One week post-supplementation no difference was found in ferritin concentration between iron compounds, but 6 months after supplementation ferritin concentration was higher in the group that received bis-glycinate chelate iron. However, there is no difference in the odds for low iron storage between 6 months after supplementation versus the odds after supplementation; nor were these odds different by type of supplement. Hemoglobin concentration did not change significantly in either group after

  6. Expression and purification of intact and functional soybean (Glycine max) seed ferritin complex in Escherichia coli.

    PubMed

    Dong, Xiangbai; Tang, Bo; Li, Jie; Xu, Qian; Fang, Shentong; Hua, Zichun

    2008-02-01

    Soybean seed ferritin is essential for human iron supplementation and iron deficiency anemia prevention because it contains abundant bioavailable iron and is frequently consumed in the human diet. However, it is poorly understood in regards its several properties, such as iron mineralization, subunit assembly, and protein folding. To address these issues, we decided to prepare the soybean seed ferritin complex via a recombinant DNA approach. In this paper, we report a rapid and simple Escherichia coli expression system to produce the soybean seed ferritin complex. In this system, two subunits of soybean seed ferritin, H-2 and H-1, were encoded in a single plasmid, and optimal expression was achieved by additionally coexpressing a team of molecular chaperones, trigger factor and GroEL-GroES. The His-tagged ferritin complex was purified by Ni2+ affinity chromatography, and an intact ferritin complex was obtained following His-tagged enterokinase (His-EK) digestion. The purified ferritin complex synthesized in E. coli demonstrated some reported features of its native counterpart from soybean seed, including an apparent molecular weight, multimeric assembly, and iron uptake activity. We believe that the strategy described in this paper may be of general utility in producing other recombinant plant ferritins built up from two types of subunits.

  7. Comparative Study of Human Liver Ferritin and Chicken Liver by Mössbauer Spectroscopy. Preliminary Results

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-12-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Mössbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Mössbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  8. Differential expression of ferritin genes in response to abiotic stresses and hormones in pear (Pyrus pyrifolia).

    PubMed

    Xi, Li; Xu, Kuanyong; Qiao, Yushan; Qu, Shenchun; Zhang, Zhen; Dai, Wenhao

    2011-10-01

    In this study, the expression patterns of four ferritin genes (PpFer1, PpFer2, PpFer3, and PpFer4) in pear were investigated using quantitative real-time PCR. Analysis of tissue-specific expression revealed higher expression level of these genes in leaves than in other tested tissues. These ferritin genes were differentially expressed in response to various abiotic stresses and hormones treatments. The expression of ferritin wasn't affected by Fe(III)-citrate treatment. Abscisic acid significantly enhanced the expression of all four ferritin genes, especially PpFer2, followed by N-benzylyminopurine, gibberellic acid, and indole-3-acetic acid. The expression peaks of PpFer1 and PpFer3 in leaves appeared at 6, 6, and 12 h, respectively, after pear plant was exposed to oxidative stress (5 mM H(2)O(2)), salt stress (200 mM NaCl), and heat stress (40°C). A significant increase in PpFer4 expression was detected at 6 h after salt stress or heat stress. The expression of ferritin genes was not altered by cold stress. These results suggested that ferritin genes might be functionally important in acclimation of pear to salt and oxidative stresses. Hormone treatments had no significant effect on expression of ferritin genes compared to abiotic stresses. This showed accumulation of ferritin genes could be operated by different transduction pathways under abiotic stresses and hormones treatments.

  9. 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. ...

  10. 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

  11. Induction of ferritin synthesis by water deficit and iron excess in common bean (Phaseolus vulgaris L.).

    PubMed

    DeLaat, Daiane Mariele; Colombo, Carlos Augusto; Chiorato, Alisson Fernando; Carbonell, Sergio Augusto Morais

    2014-03-01

    Ferritins are molecules for iron storage present in most living beings. In plants, ferritin is an essential iron homeostasis regulator and therefore plays a fundamental role in control of iron induced by oxidative stress or by excess of iron ions. Ferritin gene expression is modulated by various environmental factors, including the intensity of drought, cold, light and pathogenic attack. Common bean, one of the most important species in the Brazilian diet, is also affected by insufficiency or lack of water. Thus, the present study was conducted for the purpose of determining the levels of expression of ferritins transcripts in leaf tissues of three common bean cultivars (BAT 477, Carioca Comum and IAC-Diplomata) under osmotic shock caused by polyethylene glycol 6000 and by iron excess. The expression of three ferritins genes (PvFer1, PvFer2 and PvFer3), determined by quantitative PCR, indicated a difference in the expression kinetics among the cultivars. All the ferritin genes were actively transcribed under iron excess and water deficit conditions. The cultivars most responsive to treatments were BAT 477 and IAC-Diplomata. All the cultivars responded to treatments. Nevertheless, the ferritin genes were differentially regulated according to the cultivars. Analysis of variance indicated differences among cultivars in expression of the genes PvFer1 and PvFer3. Both genes were most responsive to treatments. This result suggests that ferritin genes may be functionally important in acclimatization of common bean under iron excess or water deficit conditions.

  12. Ferritin protect shrimp Litopenaeus vannamei from WSSV infection by inhibiting virus replication.

    PubMed

    Ye, Ting; Wu, Xiaoting; Wu, Wenlin; Dai, Congjie; Yuan, Jianjun

    2015-01-01

    Iron is considered as an essential element for all living organisms. Therefore, limiting iron availability may be key part of the host's innate immune response to various pathogens. Ferritin is a major iron storage protein in living cells and plays an important role in iron homeostasis. One way the host can transiently reduce iron bioavailability is by ferritin over expression. In invertebrates, ferritin was found to be up-regulated after pathogens challenge and is considered to be an important element in the innate immune system. This study was designed to investigate the involvement of ferritin in shrimp Litopenaeus vannamei defense against WSSV. We discovered that the viral load of shrimp injected with recombinant ferritin protein was lower than that of control group. The suppression of ferritin by dsRNA increased susceptibility to WSSV with 3-fold high viral copies. The present study documented that ferritin protected shrimp L. vannamei from WSSV by inhibiting virus replication. We presume that ferritin reduce iron availability, leading to inhibit the activity of ribonucleotide reductase and delay the replication of virus genome. This study provided new insights into the understanding of molecular responses and defense mechanisms in shrimp against WSSV.

  13. 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. ...

  14. On the mineral core of ferritin-like proteins: structural and magnetic characterization.

    PubMed

    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

    2016-01-14

    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.

  15. Salsolinol, a catechol neurotoxin, induces modification of ferritin: Protection by histidine dipeptide.

    PubMed

    Kang, Jung Hoon

    2010-05-01

    1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), an endogenous neurotoxin present in the mammalian brain, is known to perform a role in the pathogenesis of Parkinson's disease. In this study, we evaluated oxidative modifications of ferritin occurring after incubation with salsolinol. When ferritin was incubated with salsolinol, protein aggregation increased in a time-dependent manner. Free radical scavengers inhibited this salsolinol-mediated ferritin modification. The exposure of ferritin to salsolinol also results in the generation of protein carbonyl compounds and the formation of dityrosine. The results of this study show that free radicals may perform a pivotal role in salsolinol-mediated ferritin modification. Histidine dipeptides, such as carnosine, have been proposed to function as antioxidant agents in vivo. In this study, we also attempted to determine whether the histidine dipeptides, carnosine and N-acetyl-carnosine, could prevent salsolinol-mediated oxidative modification of ferritin. Our results showed that both carnosine and N-acetyl-carnosine significantly reduced ferritin aggregation. Both compounds effectively inhibited the formation of both carbonyl compounds and dityrosine. These results suggest that carnosine derivatives can, indeed, protect against salsolinol-mediated ferritin modification, as the consequence of free radical-scavenging activity.

  16. 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.

  17. Crystal structure of iron-oxide nanoparticles synthesized from ferritin

    NASA Astrophysics Data System (ADS)

    Krispin, Michael; Ullrich, Aladin; Horn, Siegfried

    2012-02-01

    We have investigated the crystal structure of nanosized iron-oxide by X-ray diffraction (XRD), extended X-ray absorption fine structure measurements at the iron K-edge as well as by transmission electron microscopy (TEM). Iron-oxide nanoparticles were produced by thermal treatment of horse spleen ferritin molecules. The structure of these particles was compared to α-Fe2O3 and γ-Fe2O3 nanopowder references. The thermal treatment of a submonolayer film of ferritin molecules results in pure γ-Fe2O3 nanoparticles, while for films above a certain thickness α-Fe2O3 and γ-Fe2O3 coexist, exhibiting two different crystallite sizes. TEM shows a characteristic particle diameter of 7 nm for γ-Fe2O3 resulting from thermal treatment of monolayers, consistent with the crystallite size of the γ-phase as obtained from XRD measurements on multi-layered samples. XRD shows the α-Fe2O3 phase to be characterized by a crystallite size of 34 nm.

  18. Serum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria.

    PubMed

    Verhoef, H; West, C E; Ndeto, P; Burema, J; Beguin, Y; Kok, F J

    2001-12-01

    Serum transferrin receptor concentrations indicate both erythropoietic activity and the deficit of functional iron in the erythron. In contrast with serum ferritin concentrations, serum transferrin receptor concentrations are not or are only marginally influenced by the inflammatory response to infection. We assessed iron status and examined the relation between serum transferrin receptor concentrations and malaria in children aged 2-36 mo who were asymptomatic for malaria. This was a community-based cluster survey (n = 318). Prevalences of malaria, anemia (hemoglobin concentration <110 g/L), iron deficiency (serum ferritin concentration <12 microg/L), and iron deficiency anemia were 18%, 69%, 53%, and 46%, respectively. Malaria was associated with lower mean hemoglobin concentrations (92.7 compared with 104.1 g/L; P = 0.0001) and higher geometric mean serum concentrations of transferrin receptor (11.4 compared with 7.8 mg/L; P = 0.005), ferritin (21.6 compared with 11.9 microg/L; P = 0.05), and C-reactive protein (12.5 compared with 6.8 mg/L; P = 0.004). There was no evidence for an association between serum concentrations of C-reactive protein and transferrin receptor. Children with malaria had higher serum transferrin receptor concentrations than expected for the degree of anemia, even after adjustment for inflammation indicated by serum C-reactive protein concentration quartiles (P = 0.02). Our findings are consistent with the notion that malaria-induced hemolysis is accompanied by increased erythropoiesis. Serum transferrin receptor concentration is not useful for detecting iron deficiency in individuals with malaria. Individuals with high concentrations of serum C-reactive protein or similar acute phase reactants should be excluded from analysis if serum ferritin concentrations <12 microg/L are to be used to measure iron deficiency in malaria-endemic areas.

  19. Absorption of iron from ferritin is independent of heme iron and ferrous salts in women and rat intestinal segments.

    PubMed

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

    2012-03-01

    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 (59)Fe) 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.

  20. 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.

  1. 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

  2. Ferritin-Polymer Conjugates: Grafting Chemistry and Integration into Nanoscale Assemblies

    SciTech Connect

    Y Hu; D Samanta; S Parelkar; S Hong; Q Wang; T Russell; T Emrick

    2011-12-31

    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(ethylene oxide) copolymers, and selective integration into the PEO domains of microphase-separated copolymer structures.

  3. Magnetically induced behaviour of ferritin corpuscles in avian ears: can cuticulosomes function as magnetosomes?

    PubMed

    Jandacka, Petr; Burda, Hynek; Pistora, Jaromir

    2015-01-06

    Magnetoreception is an enigmatic, poorly understood sensory ability, described mainly on the basis of behavioural studies in animals of diverse taxa. Recently, corpuscles containing superparamagnetic iron-storage protein ferritin were found in the inner ear hair cells of birds, a predominantly single ferritin corpuscle per cell. It was suggested that these corpuscles might represent magnetosomes and function as magnetosensors. Here we determine ferritin low-field paramagnetic susceptibility to estimate its magnetically induced intracellular behaviour. Physical simulations show that ferritin corpuscles cannot be deformed or rotate in weak geomagnetic fields, and thus cannot provide magnetoreception via deformation of the cuticular plate. Furthermore, we reached an alternative hypothesis that ferritin corpuscle in avian ears may function as an intracellular electromagnetic oscillator. Such an oscillator would generate additional cellular electric potential related to normal cell conditions. Though the phenomenon seems to be weak, this effect deserves further analyses.

  4. 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.

  5. 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

  6. Molecular characterization and gene expression of the channel catfish Ferritin H subunit after bacterial infection and iron treatment

    USDA-ARS?s Scientific Manuscript database

    Ferritins are the major iron storage protein in the cytoplasm of cells, responsible for regulating levels of intracellular iron. Ferritin genes are widely distributed in both prokaryotes and eukaryotes. In mammals, ferritin molecules are composed of heavy- (H) and light- (L) chain subunits; amphibia...

  7. Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation.

    PubMed

    Vaughn, Jennifer E; Storer, Barry E; Armand, Philippe; Raimondi, Roberto; Gibson, Christopher; Rambaldi, Alessandro; Ciceri, Fabio; Oneto, Rosi; Bruno, Benedetto; Martin, Paul J; Sandmaier, Brenda M; Storb, Rainer; Sorror, Mohamed L

    2015-08-01

    Pretransplant values of serum ferritin, albumin, and peripheral blood counts were previously suggested to provide prognostic information about hematopoietic cell transplantation (HCT) outcomes. Whether these "biomarkers" have prognostic value independent of each other and the HCT-comorbidity index (HCT-CI) is unknown. We analyzed data from 3917 allogeneic HCT recipients at multiple sites in the United States and Italy using multivariate models including each biomarker and the HCT-CI. Data from all sites were then randomly divided into a training set (n = 2352) to develop weights for the relevant biomarkers to be added to the HCT-CI scores and a validation set (n = 1407) to validate an augmented HCT-CI compared with the original index. Multivariate analysis with data from one site showed that ferritin, albumin, and platelets-not neutrophils or hemoglobin-were independently associated with increased nonrelapse mortality (NRM) and decreased overall survival. Findings were validated in data from the other sites. Subsequently, in a training set from all sites, ferritin >2500 mg/dL (hazard ratio [HR], 1.69); albumin 3 to 3.5 g/dL (HR, 1.61) and <3.0 g/dL (HR, 2.27); and platelets 50 to <100,000 (HR, 1.28), 20 to <50,000 (HR, 1.29), and <20,000 (HR, 1.55) were statistically significantly associated with NRM. Weights were assigned to these laboratory values following the same equation used to design the original index. In the validation set, the addition of the biomarkers to the original index to develop an augmented HCT-CI resulted in a statistically significant increase in a higher c-statistic estimate for prediction of NRM (P = .0007). Ferritin, albumin, and platelet counts are important prognostic markers that further refine the discriminative power of the HCT-CI for transplant outcomes.

  8. Toxicity, biodistribution, and ex vivo MRI detection of intravenously injected cationized ferritin.

    PubMed

    Beeman, Scott C; Georges, Joseph F; Bennett, Kevin M

    2013-03-01

    The goal of the work was to establish the toxicity and biodistribution of the superparamagnetic protein cationized ferritin (CF) after intravenous injection. Intravenously injected CF has been used to target the extracellular matrix with high specificity in the kidney glomerulus, allowing measurements of individual glomeruli using T2*-weighted MRI. For the routine use of CF as an extracellular matrix-specific tracer, it is important to determine whether CF is toxic. In this work, we investigated the renal and hepatic toxicity, leukocyte count, and clearance of intravenously injected CF. Furthermore, we studied CF labeling in several organs using MRI and immunohistochemistry. Serum measurements of biomarkers suggest that intravenous injection of CF is neither nephrotoxic nor hepatotoxic and does not increase leukocyte counts in healthy rats at a dose of 5.75 mg/100 g. In addition to known glomerular labeling, confocal and MRI suggest that intravenously injected CF labels the extracellular matrix of the hepatic sinusoid, extracellular glycocalyx of alveolar endothelial cells, and macrophages in the spleen. Liver T2* values suggest that CF is cleared by 7 days after injection. These results suggest that CF may serve as a useful contrast agent for detection of a number of structures and functions with minimal toxicity.

  9. The Faraday effect of natural and artificial ferritins.

    PubMed

    Koralewski, M; Kłos, J W; Baranowski, M; Mitróová, Z; Kopčanský, P; Melníková, L; Okuda, M; Schwarzacher, W

    2012-09-07

    Measurements of the Faraday rotation at room temperature over the light wavelength range of 300-680 nm for horse spleen ferritin (HSF), magnetoferritin with different loading factors (LFs) and nanoscale magnetite and Fe(2)O(3) suspensions are reported. The Faraday rotation and the magnetization of the materials studied present similar magnetic field dependences and are characteristic of a superparamagnetic system. The dependence of the Faraday rotation on the magnetic field is described, excluding HSF and Fe(2)O(3), by a Langevin function with a log-normal distribution of the particle size allowing the core diameters of the substances studied to be calculated. It was found that the specific Verdet constant depends linearly on the LF. Differences in the Faraday rotation spectra and their magnetic field dependences allow discrimination between magnetoferritin with maghemite and magnetite cores which can be very useful in biomedicine.