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Sample records for severe iron overload

  1. Magnetic resonance imaging of splenic iron overload

    International Nuclear Information System (INIS)

    Arrive, L.; Thurnher, S.; Hricak, H.; Price, D.C.

    1990-01-01

    The value of magnetic resonance (MR) imaging in assessing iron overload in the spleen was retrospectively investigated in 40 consecutive patients. MR appearance, mesaure of signal intensity and T1-and T2-relaxation times were correlated with the histologically determined level of iron in the spleen in each patient. Histologic examination revealed no iron overload in 19 patients, mild iron overload in seven, moderate iron overload in six, and severe iron overload in eight. All 19 patients with no splenic iron overload and 11 of the other 21 patients with splenic iron overload were correctly identified by MR imaging (sensitivity 52%, specificity 100%, accuracy 75%). Splenic iron overload was diagnosed when a decrease of signal intensity of the spleen compared with those of adipose tissue and renal cortex was demonstrated. MR images demonstrated all eight cases of severe, three of the six cases of moderate, and none of the seven cases of mild iron overload. Only spleens with severe iron overload had a significant mean decrease in signal intensity and T1- and T2-relaxation times. Although specific, MR imaging is poorly sensitive to splenic iron overload. (author). 15 refs.; 5 figs.; 3 tabs

  2. ESR spectroscopy of blood serum in thalassemia: discrimination of iron overload severity in deferoxamine-cured patients

    International Nuclear Information System (INIS)

    Preoteasa, E.A.; Schianchi, G.; Giori, D.C.; Pedrazzi, G.

    1997-01-01

    Iron impairments in homozygous β-thalassemia include iron overload syndrome, partially prevented by deferoxamine (DF) and methemalbumin (MHA) in serum. The latter has been studied by electron spin resonance ESR before the clinical use of DF and recently in DF cured subjects. We monitored by X-band ESR at 163 K, the Fe (III) bound in MHA and transferrin (Tf) in serum from transfused, DF-cured patients. Plotting MHA/Tf versus individual DF dose divided the patients into two subgroups, A and B; A with the two variables correlated linearly and B presenting no correlation. The patients in B presented a higher incidence and severity of clinical complications and lower therapy responsiveness as compared to subjects in A. The ratio MHA/Tf evidenced a quadratic dependence on the mass of transfused erythrocytes (TE) in A, and no regularity in B. Similar patterns appeared in plots of ferritin (FT) and hemoglobin (Hb) vs. DF and TE, but all correlation become visible only after A vs. B discrimination by ESR. The results point to a heavier iron overload in B than in A patients, suggesting different Hb degradation pathways in the two subgroups with more toxic 'free' iron produced in B than in A. Therefore, ESR of serum might serve for improving the precision of diagnosis, for prognosis of dissimilar therapeutic efficiency of DF in patients and for monitoring the long-term efficiency of therapy in homozygous β-thalassemia. (authors)

  3. Hepatic iron overload: Quantitative MR imaging

    International Nuclear Information System (INIS)

    Gomori, J.M.; Horev, G.; Tamary, H.; Zandback, J.; Kornreich, L.; Zaizov, R.; Freud, E.; Krief, O.; Ben-Meir, J.; Rotem, H.

    1991-01-01

    Iron deposits demonstrate characteristically shortened T2 relaxation times. Several previously published studies reported poor correlation between the in vivo hepatic 1/T2 measurements made by means of midfield magnetic resonance (MR) units and the hepatic iron content of iron-overloaded patients. In this study, the authors assessed the use of in vivo 1/T2 measurements obtained by means of MR imaging at 0.5 T using short echo times (13.4 and 30 msec) and single-echo-sequences as well as computed tomographic (CT) attenuation as a measure of liver iron concentration in 10 severely iron-overloaded patients with beta-thalassemia major. The iron concentrations in surgical wedge biopsy samples of the liver, which varied between 3 and 9 mg/g of wet weight (normal, less than or equal to 0.5 mg/g), correlated well (r = .93, P less than or equal to .0001) with the preoperative in vivo hepatic 1/T2 measurements. The CT attenuation did not correlate with liver iron concentration. Quantitative MR imaging is a readily available noninvasive method for the assessment of hepatic iron concentration in iron-overloaded patients, reducing the need for needle biopsies of the liver

  4. Severe iron overload and hyporegenerative anemia in a case with rhesus hemolytic disease: therapeutic approach to rare complications

    Directory of Open Access Journals (Sweden)

    Fatih Demircioğlu

    2010-09-01

    Full Text Available A 33 weeks’ gestation, a baby with rhesus hemolytic disease (RHD, who had received intrauterine transfusions twice, developed cholestatic hepatic disease and late hyporegenerative anemia. Her serum ferritin and bilirubin levels increased to 8842 ng/ml and 17.9 mg/dl, respectively. Liver biopsy showed cholestasis and severe iron overload. Treatment with recombinant erythropoietin (rHuEPO decreased the transfusion need, and intravenous deferoxamine resulted in a marked decreased in serum ferritin levels and normalization of liver function. In patients who have undergone intrauterine transfusions due to RHD, hyperferritinemia and late hyporegenerative anemia should be kept in mind. Chelation therapy in cases with symptomatic hyperferritinemia and rHuEPO treatment in cases with severe hyporegenerative anemia should be considered.

  5. Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

    Science.gov (United States)

    Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

    2017-01-23

    Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice.

  6. Iron overload in myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Gattermann, Norbert

    2018-01-01

    Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

  7. Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

    Science.gov (United States)

    Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

    2017-10-15

    Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Iron overload impact on P-ATPases.

    Science.gov (United States)

    Sousa, Leilismara; Pessoa, Marco Tulio C; Costa, Tamara G F; Cortes, Vanessa F; Santos, Herica L; Barbosa, Leandro Augusto

    2018-03-01

    Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na + ,K + -ATPase and the Ca 2+ -ATPase. On the Fe 2+ -ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe 2+ and playing a protection role for the cell. On the Ca 2+ -ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca 2+ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca 2+ concentrations, which could promote an enzyme oxidation, nitration, and fragmentation. However, the iron overload effect on the Na + ,K + -ATPase may change according to the tissue expressions. On the renal cells, as well as on the brain and the heart, iron promotes an enzyme inactivation, whereas its effect on the erythrocytes seems to be the opposite, directly stimulating the ATPase activity, or stimulating it by signaling pathways involving ROS and PKC. Modulations in the ATPase activity may impair the ionic transportation, which is essential for cell viability maintenance, inducing irreversible damage to the cell homeostasis. Here, we will discuss about the iron overload effect on the P-ATPases, such as the Na + ,K + -ATPase, the Ca 2+ -ATPase, and the Fe 2+ -ATPase.

  9. Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

    Science.gov (United States)

    Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

    2015-10-01

    What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane

  10. Iron overload following bone marrow transplantation in children: MR findings

    International Nuclear Information System (INIS)

    Kornreich, L.; Horev, G.; Grunebaum, M.; Yaniv, I.; Stein, J.; Zaizov, R.

    1997-01-01

    Objective. The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. Materials and methods. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. Results. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Conclusion. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis. (orig.)

  11. Iron deficiency and overload in relation to nutrition

    NARCIS (Netherlands)

    Spanjersberg MQI; Jansen EHJM; LEO

    2000-01-01

    Nutritional iron intake in the Netherlands has been reviewed with respect to both iron deficiency and iron overload. In general, iron intake and iron status in the Netherlands are adequate and therefore no change in nutrition policy is required. The following aspects and developments, however, need

  12. Research progress in role of iron overload in non-alcoholic fatty liver disease

    OpenAIRE

    LI Guangming

    2013-01-01

    Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD). The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iro...

  13. Iron overload and chelation therapy in myelodysplastic syndromes.

    Science.gov (United States)

    Temraz, Sally; Santini, Valeria; Musallam, Khaled; Taher, Ali

    2014-07-01

    Iron overload remains a concern in MDS patients especially those requiring recurrent blood transfusions. The consequence of iron overload may be more relevant in patients with low and intermediate-1 risk MDS who may survive long enough to experience such manifestations. It is a matter of debate whether this overload has time to yield organ damage, but it is quite evident that cellular damage and DNA genotoxic effect are induced. Iron overload may play a critical role in exacerbating pre-existing morbidity or even unmask silent ones. Under these circumstances, iron chelation therapy could play an integral role in the management of these patients. This review entails an in depth analysis of iron overload in MDS patients; its pathophysiology, effect on survival, associated risks and diagnostic options. It also discusses management options in relation to chelation therapy used in MDS patients and the impact it has on survival, hematologic response and organ function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Myelodysplastic syndromes and the role of iron overload.

    Science.gov (United States)

    Harvey, R Donald

    2010-04-01

    The epidemiology of myelodysplastic syndromes (MDS) and iron overload, recent clinical findings that highlight the importance of actively managing iron overload, and recommendations for initiating and maintaining iron chelation therapy (ICT) are summarized. MDS are a variety of hematological disorders with differing time courses. Disease morbidities are primarily due to cytopenias and evolution to acute myeloid leukemia. Iron overload is a serious complication in patients with MDS due to the long-term use of red blood cell transfusions in patients with symptomatic anemia. Clinical consequences of iron overload include end-organ damage and dysfunction, an increased frequency of transplant-related complications, and reduced survival rates. To prevent these complications, recommendations for initiating and maintaining ICT should be followed by clinicians caring for patients with MDS and iron overload. As current therapeutic options for patients with MDS do not always reduce the transfusion burden, many patients will still need long-term transfusion therapy. Strategies for the management of iron overload in MDS should be considered early in the disease course and in appropriate patients in order to prevent negative clinical outcomes associated with excessive iron accumulation.

  15. Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

    Directory of Open Access Journals (Sweden)

    Chalmers AW

    2016-02-01

    Full Text Available Anna W Chalmers, Jamile M Shammo Department of Internal Medicine, Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelodysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. Keywords: iron chelation therapy, transfusional iron overload, deferasirox

  16. Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century.

    Science.gov (United States)

    Rostoker, Guy; Vaziri, Nosratola D; Fishbane, Steven

    2016-05-01

    Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

  17. Dietary iron rural blacks overload In southern African

    African Journals Online (AJOL)

    1990-09-15

    Sep 15, 1990 ... suggest that iron overload from any cause may predispose to infection7 and there are .... consumption and acute inflammatory diseases. However, it ..... Addison GM, Beamish MR, Hales C ',Hodgkins M, Jacobs A, Llewellin P.

  18. Iron overload: what is the role of public health?

    Science.gov (United States)

    Hulihan, Mary M; Sayers, Cindy A; Grosse, Scott D; Garrison, Cheryl; Grant, Althea M

    2011-12-01

    Hereditary hemochromatosis type 1, also known as hereditary hemochromatosis classical (HHC), is an iron overload disorder associated, in most cases, with mutations of the hemochromatosis (HFE) gene. Although suggested algorithms for diagnosing iron overload are available, there are still questions about options for genetic and biochemical screening for hemochromatosis and duration of treatment. This article provides a summary of an expert workgroup meeting convened on September 24-25, 2009, entitled "Iron Overload: What is the Role of Public Health?" The purpose of the meeting was to enable subject matter experts to share their most recent clinical and scientific iron overload information and to facilitate the discussion of future endeavors, with special emphasis on the role of public health in this field. The two main topics were the research priorities of the field, including clinical, genetic, and public health issues, and the concerns about the validity of current screening recommendations for the condition. Published by Elsevier Inc.

  19. Quantification of liver fat in the presence of iron overload.

    Science.gov (United States)

    Horng, Debra E; Hernando, Diego; Reeder, Scott B

    2017-02-01

    To evaluate the accuracy of R2* models (1/T 2 * = R2*) for chemical shift-encoded magnetic resonance imaging (CSE-MRI)-based proton density fat-fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard. Two Monte Carlo simulations were implemented to compare the root-mean-squared-error (RMSE) performance of single-R2* and dual-R2* correction in a theoretical liver environment with high iron. Fatty liver was defined as hepatic PDFF >5.6% based on MRS; only subjects with fatty liver were considered for analyses involving fat. From a group of 40 patients with known/suspected iron overload, nine patients were identified at 1.5T, and 13 at 3.0T with fatty liver. MRS linewidth measurements were used to estimate R2* values for water and fat peaks. PDFF was measured from CSE-MRI data using single-R2* and dual-R2* correction with magnitude and complex fitting. Spectroscopy-based R2* analysis demonstrated that the R2* of water and fat remain close in value, both increasing as iron overload increases: linear regression between R2* W and R2* F resulted in slope = 0.95 [0.79-1.12] (95% limits of agreement) at 1.5T and slope = 0.76 [0.49-1.03] at 3.0T. MRI-PDFF using dual-R2* correction had severe artifacts. MRI-PDFF using single-R2* correction had good agreement with MRS-PDFF: Bland-Altman analysis resulted in -0.7% (bias) ± 2.9% (95% limits of agreement) for magnitude-fit and -1.3% ± 4.3% for complex-fit at 1.5T, and -1.5% ± 8.4% for magnitude-fit and -2.2% ± 9.6% for complex-fit at 3.0T. Single-R2* modeling enables accurate PDFF quantification, even in patients with iron overload. 1 J. Magn. Reson. Imaging 2017;45:428-439. © 2016 International Society for Magnetic Resonance in Medicine.

  20. Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

    Science.gov (United States)

    Shammo, Jamile M; Komrokji, Rami S

    2018-06-14

    Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

  1. Assessment of Iron Overload in Homozygous and Heterozygous Beta Thalassemic Children below 5 Years of Age

    Directory of Open Access Journals (Sweden)

    Dhiraj J. Trivedi

    2014-07-01

    Full Text Available Background: Thalassemia is a genetic disease having 3-7% carrier rate in Indians. It is transfusion dependent anemia having high risk of iron overloading. A clinical symptom of iron overload becomes detectable in second decade causing progressive liver, heart and endocrine glands damage. There is a need to assess iron overload in thalassemics below 5 years of age to protect them from complications at later age of life. Aims and objectives: Present study was undertaken to estimate serum iron status and evaluate serum transferrin saturation in both homozygous & heterozygous form of thalassemia as an index of iron overload among children of one to five years of age. Materials and Methods: Clinically diagnosed thirty cases of β thalassemia major & thirty cases of β thalassemia minor having severe anemia, hepatospleenomegaly and between 1 year to 5 years of age were included in study group and same age matched healthy controls were included in the study. RBC indices and HbA, HbA2 and HbF were estimated along with serum iron & serum Total Iron Binding Capacity (TIBC and serum transferrin levels. Results: Significant difference was observed in hemoglobin levels between control and both beta thalassemia groups. Mean Corpuscular Volume (MCV and Mean Corpuscular Hemoglobin (MCH values were reduced. Hemoglobin electrophoresis showed the elevated levels of HbF and HbA2 in both beta thalassemia groups. Among serum iron parameters, serum iron, TIBC and transferrin saturation were elevated whereas serum transferrin levels were low in thalassemia major in children below 5 years of age. Conclusion: Although clinical symptoms of iron overload have been absent in thalassemic children below five years of age, biochemical iron overloading has started at much lower age which is of great concern.

  2. Magnetic and quadrupolar studies of the iron storage overload in livers

    International Nuclear Information System (INIS)

    Rimbert, J.N.; Dumas, F.; Richardot, G.; Kellershohn, C.

    1986-01-01

    Absorption 57 Fe Moessbauer spectra, performed directly on tissues of liver with iron overload due to an excessive intestinal iron absorption or induced by hypertransfusional therapeutics, have pointed out a new high spin ferric storage iron besides the ferritin and hemosiderin. Moessbauer studies, carried out on ferritin and hemosiderin fractions isolated from normal and overloaded livers, show that this compound, only present in the secondary iron overload (transfusional pathway), seems characteristic of the physiological process which induces the iron overload. (Auth.)

  3. Iron overload of organism and current options of chelation treatment in onco haematology

    International Nuclear Information System (INIS)

    Guman, T.; Rothova, E.; Kafkova, A.; Fricova, M.; Dulova, I.; Stecova, N.; Hlebaskova, M.; Surova, M.; Takac, V.

    2011-01-01

    The article summarizes the biological importance of iron in the organism, primary and secondary causes of iron overload, complications in function of liver, heart and endocrine organs due to overload of iron, the pathophysiology of iron overload, transfusion risks associated with the iron overload, assessment of risk groups of patients suitable for chelation treatment fulfilling the indication criteria, treatment modalities of chelation therapy and its significance regarding the prevention and treatment effectiveness. (author)

  4. Transplantation in patients with iron overload: is there a place for magnetic resonance imaging? : Transplantation in iron overload.

    Science.gov (United States)

    Mavrogeni, Sophie; Kolovou, Genovefa; Bigalke, Boris; Rigopoulos, Angelos; Noutsias, Michel; Adamopoulos, Stamatis

    2018-03-01

    In iron overload diseases (thalassemia, sickle cell, and myelodysplastic syndrome), iron is deposited in all internal organs, leading to functional abnormalities. Hematopoietic stem cell transplantation (HSCT) is the only treatment offering a potential cure in these diseases. Our aim was to describe the experience in the field and the role of magnetic resonance imaging in the evaluation of iron overload before and after HSCT. Magnetic resonance imaging (MRI), using T2*, is the most commonly used tool to diagnose myocardial-liver iron overload and guide tailored treatment. Currently, HSCT offers complete cure in thalassemia major, after overcoming the immunologic barrier, and should be considered for all patients who have a suitable donor. The overall thalassemia-free survival of low-risk, HLA-matched sibling stem cell transplantation patients is 85-90%, with a 95% overall survival. The problems of rejection and engraftment are improving with the use of adequate immunosuppression. However, a detailed iron assessment of both heart and liver is necessary for pre- and post-transplant evaluation. In iron overload diseases, heart and liver iron evaluation is indispensable not only for the patients' survival, but also for evaluation before and after HSCT.

  5. Acute iron overload and oxidative stress in brain

    International Nuclear Information System (INIS)

    Piloni, Natacha E.; Fermandez, Virginia; Videla, Luis A.; Puntarulo, Susana

    2013-01-01

    An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A·)/ascorbate (AH − ) ratio, taken as oxidative stress index, was assessed. The A·/AH − ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR·) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR· generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR· generation rate after 6

  6. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

    Science.gov (United States)

    Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

    2014-08-07

    Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology.

  7. Fetal liver iron overload: the role of MR imaging

    International Nuclear Information System (INIS)

    Cassart, Marie; Avni, Freddy Efraim; Guibaud, Laurent; Molho, Marc; D'Haene, Nicky; Paupe, Alain

    2011-01-01

    To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante - (in the case of recurrence) or neonatal treatment, which might improve the prognosis. (orig.)

  8. Fetal liver iron overload: the role of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Cassart, Marie; Avni, Freddy Efraim [Erasme Hospital, Medical imaging, Brussels, Brabant (Belgium); Guibaud, Laurent [Hopital femme mere enfant, Imagerie Pediatrique et Foetale, Lyon-Bron (France); Molho, Marc [C.H.I Poissy/St Germain-en-Laye, Imagerie Medicale, Poissy (France); D' Haene, Nicky [Erasme Hospital, Anatomopathology Department, Brussels (Belgium); Paupe, Alain [C.H.I Poissy/St Germain-en-Laye, Pediatrie, Poissy (France)

    2011-02-15

    To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante - (in the case of recurrence) or neonatal treatment, which might improve the prognosis. (orig.)

  9. Iron overload in patients with myelodysplastic syndromes: An updated overview.

    Science.gov (United States)

    Moukalled, Nour M; El Rassi, Fuad A; Temraz, Sally N; Taher, Ali T

    2018-06-15

    Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  10. Effects of Exogenous Antioxidants on Dietary Iron Overload

    OpenAIRE

    Asare, George A.; Kew, Michael C.; Mossanda, Kensese S.; Paterson, Alan C.; Siziba, Kwanele; Kahler-Venter, Christiana P.

    2008-01-01

    In dietary iron overload, excess hepatic iron promotes liver damage. The aim was to attenuate free radical-induced liver damage using vitamins. Four groups of 60 Wistar rats were studied: group 1 (control) was fed normal diet, group 2 (Fe) 2.5% pentacarbonyl iron (CI) followed by 0.5% Ferrocene, group 3 (Fe + V gp) CI, Ferrocene, plus vitamins A and E (42× and 10× RDA, respectively), group 4 (Fe – V gp) CI, Ferrocene diet, minus vitamins A and E. At 20 months, glutathione peroxidase (GPx), su...

  11. Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

    Science.gov (United States)

    Aziza, Samy Ali Hussein; Azab, Mohammed El-Said; El-Shall, Soheir Kamal

    2014-08-01

    Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT

  12. Iron overload patients with unknown etiology from national survey in Japan.

    Science.gov (United States)

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  13. Research progress in role of iron overload in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    LI Guangming

    2013-12-01

    Full Text Available Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD. The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iron overload and lipid metabolism, and relationship between type of iron deposition and liver damage; the significance of iron overload in the diagnosis and treatment of NAFLD is discussed from iron overload as a new marker of risk stratification and potential therapeutic target in NAFLD. It is currently considered that iron overload, whether the cause or result of NAFLD progression, will promote the progression of NAFLD once it occurs; as a new marker of risk stratification and potential therapeutic target in NAFLD, iron load is worthy of further study.

  14. Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy

    International Nuclear Information System (INIS)

    Kapadia, A J; Tourassi, G D; Sharma, A C; Crowell, A S; Kiser, M R; Howell, C R

    2008-01-01

    Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g -1 or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies

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

    Science.gov (United States)

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

    2017-09-01

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

  16. TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease.

    Science.gov (United States)

    Zhabyeyev, Pavel; Das, Subhash K; Basu, Ratnadeep; Shen, Mengcheng; Patel, Vaibhav B; Kassiri, Zamaneh; Oudit, Gavin Y

    2018-05-01

    Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3 -/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3 -/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3 -/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key

  17. Mild iron overload in patients carrying the HFE S65C gene mutation: a retrospective study in patients with suspected iron overload and healthy controls

    OpenAIRE

    Holmström, P; Marmur, J; Eggertsen, G; Gåfvels, M; Stål, P

    2002-01-01

    Background and aims: The role of the HFE S65C mutation in the development of hepatic iron overload is unknown. The aim of the present study was: (A) to determine the HFE S65C frequency in a Northern European population; and (B) to evaluate whether the presence of the HFE S65C mutation would result in a significant hepatic iron overload.

  18. Iron overload in the liver diagnostic and quantification

    International Nuclear Information System (INIS)

    Alustiza, Jose M.; Castiella, Agustin; Juan, Maria D. de; Emparanza, Jose I.; Artetxe, Jose; Uranga, Maite

    2007-01-01

    Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification

  19. Iron overload in the liver diagnostic and quantification

    Energy Technology Data Exchange (ETDEWEB)

    Alustiza, Jose M. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)]. E-mail: jmalustiza@osatek.es; Castiella, Agustin [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Juan, Maria D. de [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Emparanza, Jose I. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Artetxe, Jose [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Uranga, Maite [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)

    2007-03-15

    Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification.

  20. Liver iron overloading in captive muriquis (Brachyteles spp.).

    Science.gov (United States)

    Santos, Stéfanie V; Strefezzi, Ricardo De F; Pissinatti, Alcides; Catão-Dias, José L

    2011-04-01

    Iron accumulation was investigated qualitatively and quantitatively in the liver of 15 captive Brachyteles spp. Hepatic hemosiderosis index (HHI) was determined as the area percentage of the liver parenchyma occupied by hemosiderin and ferritin deposits, through computerized histomorphometric analysis of Prussian blue-stained histologic sections. All studied animals presented liver hemosiderosis, and HHI ranged from 0.2% to 41.7%. There were no significant differences in HHI between muriqui species or genders, and no correlations were detected among HHI and age, time in captivity or body mass. Iron deposits were accompanied by other hepatic disorders. This is the first study addressing the occurrence and consequences of iron overloading in the liver of muriquis. We propose that hemosiderosis may act as a contribute factor for the development of hepatic injuries. Further studies are advised to clarify the role of diet in the pathogenesis of hemosiderosis in these atelids. © 2010 John Wiley & Sons A/S.

  1. Desferrioxamine treatment of iron overload secondary to RH isoimmunization and intrauterine transfusion in a newborn infant.

    Science.gov (United States)

    Yalaz, Mehmet; Bilgin, Betül Siyah; Köroğlu, Ozge Altun; Ay, Yılmaz; Arıkan, Ciğdem; Sagol, Sermet; Akısü, Mete; Kültürsay, Nilgün

    2011-11-01

    Intrauterine transfusion is the standard of care in the management of severe Rh isoimmunization. Desferrioxamine has been used for the treatment of iron overload secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases. Here, we report a preterm infant born at 34 weeks of gestational age who had formerly received intrauterine transfusions for Rhesus hemolytic disease and presented with severe hyperferritinemia and elevated liver enzymes in the first week of life. Desferrioxamine treatment was started due to a ferritin level of 28,800 ng/ml and continued for 13 weeks. Although the treatment was successful, we observed resistant leukopenia which resolved after the cessation of treatment. In conclusion, iron overload secondary to intrauterine transfusions can be treated successfully with desferrioxamine; however, neonatologists must be aware of the possible side effects of this drug which has been used in only a limited number of newborns.

  2. Females Are Protected From Iron?Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress

    OpenAIRE

    Das, Subhash K.; Patel, Vaibhav B.; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y.

    2017-01-01

    Background Sex?related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron?overload cardiomyopathy is poorly understood. Methods and Results Male and female wild?type and hemojuvelin?null mice were injected and fed with a high?iron diet, respectively, to develop secondary iron overload and geneti...

  3. Melatonin protects bone marrow mesenchymal stem cells against iron overload-induced aberrant differentiation and senescence.

    Science.gov (United States)

    Yang, Fan; Yang, Lei; Li, Yuan; Yan, Gege; Feng, Chao; Liu, Tianyi; Gong, Rui; Yuan, Ye; Wang, Ning; Idiiatullina, Elina; Bikkuzin, Timur; Pavlov, Valentin; Li, Yang; Dong, Chaorun; Wang, Dawei; Cao, Yang; Han, Zhenbo; Zhang, Lai; Huang, Qi; Ding, Fengzhi; Bi, Zhengang; Cai, Benzhi

    2017-10-01

    Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Update on the use of deferasirox in the management of iron overload

    Directory of Open Access Journals (Sweden)

    Ali Taher

    2009-10-01

    Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

  5. Iron overload in very low birth weight infants: Serum Ferritin and adverse outcomes

    LENUS (Irish Health Repository)

    Barrett, M

    2011-11-01

    Adequate iron isessential for growth and haematpoiesis. Oral iron supplementation is the standard of care in VLBW infants. Post mortem evidence has confirmed significant iron overload. Excessive free iron has been associated with free radical formation and brain injury in term infants.

  6. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

    NARCIS (Netherlands)

    de Swart, Louise; Hendriks, Jan C. M.; van der Vorm, Lisa N.; Cabantchik, Z. Ioav; Evans, Patricia J.; Hod, Eldad A.; Brittenham, Gary M.; Furman, Yael; Wojczyk, Boguslaw; Janssen, Mirian C. H.; Porter, John B.; Mattijssen, Vera E. J. M.; Biemond, Bart J.; MacKenzie, Marius A.; Origa, Raffaella; Galanello, Renzo; Hider, Robert C.; Swinkels, Dorine W.

    2016-01-01

    Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron)

  7. Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

    Science.gov (United States)

    Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

    2018-06-11

    Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    Directory of Open Access Journals (Sweden)

    Stephanie Puukila

    Full Text Available Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG, a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  9. A composite mouse model of aplastic anemia complicated with iron overload.

    Science.gov (United States)

    Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Xu, Linlong; Ye, Baodong; Zhou, Yuhong

    2018-02-01

    Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (Poverload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.

  10. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

    2009-01-15

    One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21{+-}4 to 130{+-}7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

  11. Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

    Science.gov (United States)

    Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

    2018-02-14

    Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

  12. Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

    International Nuclear Information System (INIS)

    Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles; Costa, Fernando Ferreira; Silveira, Paulo Augusto Achucarro; Wood, John; Hamerschlak, Nelson

    2013-01-01

    To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions

  13. Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Costa, Fernando Ferreira [Universidade Estadual de Campinas, Campinas, SP (Brazil); Silveira, Paulo Augusto Achucarro [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Wood, John [University of Southern California, California (United States); Hamerschlak, Nelson [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2013-07-01

    To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

  14. Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging.

    Science.gov (United States)

    Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles; Costa, Fernando Ferreira; Silveira, Paulo Augusto Achucarro; Wood, John; Hamerschlak, Nelson

    2013-12-01

    To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

  15. Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Department of Pathology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang 050200, Hebei (China); Zhao, Xin [Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei (China); Chang, Yanzhong [Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei (China); Zhang, Yuanyuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Xi [Department of Pharmacy, The Forth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei (China); Zhang, Xuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Liu, Zhenyi; Guo, Hui [Department of Medicinal Chemistry, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Wang, Na [Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Gao, Yonggang [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Zhang, Jianping, E-mail: zhangjianping14@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Li, E-mail: chuli0614@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei (China)

    2016-06-15

    Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n = 8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. - Highlights: • Calcium channel blockers (CCBs) reduced hepatic iron content. • CCBs decreased hepatic fibrotic areas and collagen expression levels. • CCBs resolve fibrosis by regulating iron transport and

  16. Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice

    International Nuclear Information System (INIS)

    Zhang, Pengjun; Yue, Yuanyuan; Pan, Donghui; Yang, Runlin; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Li, Xiaotian; Yang, Min

    2016-01-01

    Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with 89 Zr, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with 89 Zr directly at pH 5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The 89 Zr-MP was stable in human plasma and PBS for at least 48 h. The half-life of 89 Zr-MP was about 15.70 ± 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that 89 Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy.

  17. Iron overload detection in rats by means of a susceptometer operating at room temperature

    International Nuclear Information System (INIS)

    Marinelli, M; Gianesin, B; Avignolo, C; Parodi, S; Minganti, V

    2008-01-01

    Biosusceptometry is a non-invasive procedure for determination of iron overload in a human body; it is essentially an assessment of the diamagnetic (water) and paramagnetic (iron) properties of tissues. We measured in vivo iron overload in the liver region of 12 rats by a room temperature susceptometer. The rats had been injected with sub-toxic doses of iron dextran. A quantitative relationship has been observed between the measurements and the number of treatments. The assessment of iron overload requires evaluating the magnetic signal corresponding to the same rat ideally without the overload. This background value was extrapolated on the basis of the signal measured in control rats versus body weight (R 2 = 0.73). The mean iron overload values for the treated rats, obtained after each iron injection, were significantly different from the means of the corresponding control rats (p 2 = 0.89). The magnetic moment of iron atoms in liver tissues was measured to be 3.6 Bohr magneton. Evaluation of the background signal is the limit to the measure; the error corresponds to about 30 mg (1 SD) of iron while the instrument sensitivity is more than a factor of 10 better.

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

    Directory of Open Access Journals (Sweden)

    Gao C

    2014-04-01

    Full Text Available Chong Gao, Li Li, Baoan Chen, Huihui Song, Jian Cheng, Xiaoping Zhang, Yunyu SunDepartment of Hematology and Oncology, Key Department of Jiangsu Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaBackground: The purpose of this study was to evaluate the clinical outcomes of transfusion-associated iron overload in patients with chronic refractory anemia.Methods: Clinical manifestations, main organ function, results of computed tomography (CT, endocrine evaluation, and serum ferritin levels were analyzed retrospectively in 13 patients who were transfusion-dependent for more than 1 year (receiving >50 units of red blood cells to determine the degree of iron overload and efficacy of iron-chelating therapy.Results: Serum ferritin levels increased to 1,830–5,740 ng/mL in all patients. Ten patients had abnormal liver function. The CT Hounsfield units in the liver increased significantly in eleven patients, and were proportional to their serum ferritin levels. Skin pigmentation, liver dysfunction, and endocrine dysfunction were observed in nine patients with serum ferritin >3,500 ng/mL, eight of whom have since died. Interestingly, serum ferritin levels did not decrease significantly in nine transfusion-dependent patients who had received 15–60 days of iron-chelating therapy.Conclusion: Transfusion-dependent patients may progress to secondary iron overload with organ impairment, which may be fatal in those who are heavily iron-overloaded. The CT Hounsfield unit is a sensitive indicator of iron overload in the liver. Iron chelation therapy should be initiated when serum ferritin is >1,000 ng/mL and continued until it is <1,000 ng/mL in transfusional iron-overloaded patients.Keywords: anemia, aplastic, iron overload, myelodysplastic syndromes

  19. Hepatic iron overload is associated with hepatocyte apoptosis during Clonorchis sinensis infection.

    Science.gov (United States)

    Han, Su; Tang, Qiaoran; Chen, Rui; Li, Yihong; Shu, Jing; Zhang, Xiaoli

    2017-08-01

    Hepatic iron overload has been implicated in many liver diseases; however, whether it is involved in clonorchiasis remains unknown. The purpose of this study is to investigate whether Clonorchis sinensis (C. sinensis) infection causes hepatic iron overload, analyze the relationship between the iron overload and associated cell apoptosis, so as to determine the role of excess iron plays in C. sinensis-induced liver injury. The Perls' Prussian staining and atomic absorption spectrometry methods were used to investigate the iron overload in hepatic sections of wistar rats and patients infected with C. sinensis. The hepatic apoptosis was detected by transferase uridyl nick end labeling (TUNEL) methods. Spearman analysis was used for determining the correlation of the histological hepatic iron index and the apoptotic index. Blue iron particles were deposited mainly in the hepatocytes, Kupffer cells and endothelial cells, around the liver portal and central vein area of both patients and rats. The total iron score was found to be higher in the infected groups than the respective control from 8 weeks. The hepatic iron concentration was also significantly higher in treatment groups than in control rats from 8 weeks. The hepatocyte apoptosis was found to be significantly higher in the portal area of the liver tissue and around the central vein. However, spearman's rank correlation coefficient revealed that there was a mildly negative correlation between the iron index and hepatocyte apoptosis. This present study confirmed that hepatic iron overload was found during C. sinensis infection. This suggests that iron overload may be associated with hepatocyte apoptosis and involved in liver injury during C. sinensis infection. Further studies are needed to investigate the molecular mechanism involved here.

  20. Iron Overload Is Associated With Oxidative Stress and Nutritional Immunity During Viral Infection in Fish.

    Science.gov (United States)

    Tarifeño-Saldivia, Estefanía; Aguilar, Andrea; Contreras, David; Mercado, Luis; Morales-Lange, Byron; Márquez, Katherine; Henríquez, Adolfo; Riquelme-Vidal, Camila; Boltana, Sebastian

    2018-01-01

    Iron is a trace element, essential to support life due to its inherent ability to exchange electrons with a variety of molecules. The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. During evolution, the shared requirement of micro- and macro-organisms for this important nutrient has shaped the pathogen-host relationship. Infectious pancreatic necrosis virus (IPNv) affects salmonids constituting a sanitary problem for this industry as it has an important impact on post-smolt survival. While immune modulation induced by IPNv infection has been widely characterized on Salmo salar , viral impact on iron host metabolism has not yet been elucidated. In the present work, we evaluate short-term effect of IPNv on several infected tissues from Salmo salar . We observed that IPNv displayed high tropism to headkidney, which directly correlates with a rise in oxidative stress and antiviral responses. Transcriptional profiling on headkidney showed a massive modulation of gene expression, from which biological pathways involved with iron metabolism were remarkable. Our findings suggest that IPNv infection increase oxidative stress on headkidney as a consequence of iron overload induced by a massive upregulation of genes involved in iron metabolism.

  1. MicroRNAs and liver cancer associated with iron overload: Therapeutic targets unravelled

    Science.gov (United States)

    Greene, Catherine M; Varley, Robert B; Lawless, Matthew W

    2013-01-01

    Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes. PMID:23983424

  2. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Mariane de Montalembert

    Full Text Available The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS. In patients with sickle cell anemia (SCA, iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15% patients with thalassemia, none with SCA, and 4 (16% with MDS. The liver iron content (LIC ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29. Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001. Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001. Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  3. Effect of Andrographolide‭ Extract on Blood Glucose and Lipid Profile in Rats with Secondary Iron Overload

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    َArash Mehri Pirayvatlo

    2017-01-01

    Full Text Available Background & objectives: Iron overload is involved in the pathophysiology of many diseases including diabetes. In fact, the excess iron by creating free radicals makes damage to pancreas and leads to insulin resistance and diabetes. Andrographolide extract has hypoglycemic and antioxidant properties. This study has surveyed the effects of andrographolide on blood glucose and lipid profile in rats with secondary iron overload. Methods: In this experimental study, 36 male Wistar rats were randomly divided into 6 groups: the healthy control group, secondary iron overload group, secondary iron overload groups treated with a dose of 3.5 and 7 mg/kg of andrographolide extract, and andrographolide groups treated with a dose of 3.5 and 7 mg/kg of extract. Iron and extract were injected for 6 and 12 days, respectively. Blood samples were taken for measurement of blood glucose and lipid profiles. Data were analyzed using ANOVA test. Results: The pathological results of samples from liver of animals receiving iron showed that the iron was deposited in the liver tissues. Iron injection significantly increased blood glucose levels compared to healthy control group (p<0.05. In the iron overload group, andrographolide extract with a dose of 3.5 mg/kg or 7 mg/kg significantly decreased blood glucose levels (p<0.05. Iron injections did not increase the serum triglyceride and cholesterollevels. Injections of andrographolide extract with a dose of 3.5 mg/kg and 7 mg/kg, significantly decreased the cholesterol levels compared to iron receiving group (p<0.05. Conclusion: Results of this study showed that the andrographolide with different doses may be effective in the treatment of diabetes by reducing serum glucose and cholesterol levels.

  4. Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.

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    Alejandra Rodriguez

    2009-09-01

    Full Text Available Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum. Illumina arrays containing over 47,000 probes were used to study global transcriptional changes. Quantitative RT-PCR (Q-RT-PCR was used to validate the microarray results. In the liver, the expression of 151 genes was altered in Hfe(-/- mice while dietary iron overload changed the expression of 218 genes. There were 173 and 108 differentially expressed genes in the duodenum of Hfe(-/- mice and mice with dietary iron overload, respectively. There was 93.5% concordance between the results obtained by microarray analysis and Q-RT-PCR. Overexpression of genes for acute phase reactants in the liver and a strong induction of digestive enzyme genes in the duodenum were characteristic of the Hfe-deficient genotype. In contrast, dietary iron overload caused a more pronounced change of gene expression responsive to oxidative stress. In conclusion, Hfe deficiency caused a previously unrecognized increase in gene expression of hepatic acute phase proteins and duodenal digestive enzymes.

  5. Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

    2017-07-01

    Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms.

    Science.gov (United States)

    Enculescu, Mihaela; Metzendorf, Christoph; Sparla, Richard; Hahnel, Maximilian; Bode, Johannes; Muckenthaler, Martina U; Legewie, Stefan

    2017-01-01

    Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms. At the systemic level, the iron-regulatory hormone hepcidin is released from the liver in response to these cues, binds to ferroportin and triggers its degradation. The relative importance of individual ferroportin control mechanisms and their interplay at the systemic level is incompletely understood. Here, we built a mathematical model of systemic iron regulation. It incorporates the dynamics of organ iron pools as well as regulation by the hepcidin/ferroportin system. We calibrated and validated the model with time-resolved measurements of iron responses in mice challenged with dietary iron overload and/or inflammation. The model demonstrates that inflammation mainly reduces the amount of iron in the blood stream by reducing intracellular ferroportin transcription, and not by hepcidin-dependent ferroportin protein destabilization. In contrast, ferroportin regulation by hepcidin is the predominant mechanism of iron homeostasis in response to changing iron diets for a big range of dietary iron contents. The model further reveals that additional homeostasis mechanisms must be taken into account at very high dietary iron levels, including the saturation of intestinal uptake of nutritional iron and the uptake of circulating, non-transferrin-bound iron, into liver. Taken together, our model quantitatively describes systemic iron metabolism and generated experimentally testable predictions for additional

  7. The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes.

    Science.gov (United States)

    Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P; Panayiotidis, Panayiotis

    2015-01-01

    Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  8. Diagnosis of hepatic iron overload: a family study illustrating pitfalls in diagnosing hemochromatosis.

    Science.gov (United States)

    Schranz, Melanie; Talasz, Heribert; Graziadei, Ivo; Winder, Thomas; Sergi, Consolato; Bogner, Klaus; Vogel, Wolfgang; Zoller, Heinz

    2009-03-01

    Recent identification of genetic variants in iron storage disease has changed the classification system and diagnostic algorithms for hemochromatosis. Clinical diagnosis of the disease requires phenotypic evidence of iron overload because the commonly disease-associated HFE genotypes have an incomplete penetrance. Furthermore, approximately 20% of patients with a clinical diagnosis of hemochromatosis have no disease-associated genotype, which underlines the importance of clear phenotypic criteria of hemochromatosis. A diagnosis of hemochromatosis cannot be made even in patients with liver cirrhosis simply on the basis of genetic testing that indicates that iron overload is the cause of the disease and not its consequence. Proper diagnosis requires integration of clinical presentation, family history, and the results of biochemical and histopathologic tests. Here we propose a rational diagnostic algorithm for hepatic iron overload syndromes and illustrate potential pitfalls by presenting a family study in a pedigree with rare HFE variants (H63D and E168Q), in cis on the same chromosome. Although the clinical suspicion of hemochromatosis was confirmed by histology, chemical analysis of liver tissue revealed a normal hepatic iron concentration, which is compatible with the genetic finding of 1 normal and 1 doubly mutated allele. In conclusion, clinical suspicion of hemochromatosis and elevated serum iron parameters should prompt HFE genotyping for C282Y and H63D. Should they be uninformative, further genetic tests should be recommended only if iron overload in liver tissue has been confirmed chemically.

  9. Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells

    International Nuclear Information System (INIS)

    Park, Junghyung; Lee, Dong Gil; Kim, Bokyung; Park, Sun-Ji; Kim, Jung-Hak; Lee, Sang-Rae; Chang, Kyu-Tae; Lee, Hyun-Shik; Lee, Dong-Seok

    2015-01-01

    Highlights: • FAC-induced iron overload promotes neuronal apoptosis. • Iron overload causes mitochondrial fragmentation in a Drp1-dependent manner. • Iron-induced Drp1 activation depends on dephosphorylation of Drp1(Ser637). • Calcineurin is a key regulator of Drp1-dependent mitochondrial fission by iron. - Abstract: The accumulation of iron in neurons has been proposed to contribute to the pathology of numerous neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. However, insufficient research has been conducted on the precise mechanism underlying iron toxicity in neurons. In this study, we investigated mitochondrial dynamics in hippocampal HT-22 neurons exposed to ferric ammonium citrate (FAC) as a model of iron overload and neurodegeneration. Incubation with 150 μM FAC for 48 h resulted in decreased cell viability and apoptotic death in HT-22 cells. The FAC-induced iron overload triggered mitochondrial fragmentation, which was accompanied by Drp1(Ser637) dephosphorylation. Iron chelation with deferoxamine prevented the FAC-induced mitochondrial fragmentation and apoptotic cell death by inhibiting Drp1(Ser637) dephosphorylation. In addition, a S637D mutation of Drp1, which resulted in a phosphorylation-mimetic form of Drp1 at Ser637, protected against the FAC-induced mitochondrial fragmentation and neuronal apoptosis. FK506 and cyclosporine A, inhibitors of calcineurin activation, determined that calcineurin was associated with the iron-induced changes in mitochondrial morphology and the phosphorylation levels of Drp1. These results indicate that the FAC-induced dephosphorylation of Drp1-dependent mitochondrial fragmentation was rescued by the inhibition of calcineurin activation. Therefore, these findings suggest that calcineurin-mediated phosphorylation of Drp1(Ser637) acts as a key regulator of neuronal cell loss by modulating mitochondrial dynamics in iron-induced toxicity. These results may contribute to the

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

    Science.gov (United States)

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

    2008-08-01

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

  11. Risk of iron overload is decreased in beating heart coronary artery surgery compared to conventional bypass.

    Science.gov (United States)

    Mumby, S; Koh, T W; Pepper, J R; Gutteridge, J M

    2001-11-29

    Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess 'off-pump' coronary artery surgery on the beating heart for changes in plasma iron chemistry. Seventeen patients undergoing cardiac surgery using the 'Octopus' myocardial wall stabilisation device were monitored at five time points for changes in plasma iron chemistry. This group was further divided into those (n=9) who had one- or two- (n=8) vessel grafts, and compared with eight patients undergoing conventional coronary artery surgery. Patients undergoing beating heart surgery had significantly lower levels of total plasma non-haem iron, and a decreased percentage saturation of their transferrin at all time points compared to conventional bypass patients. Plasma iron overload occurred in only one patient undergoing CCPB. Beating heart surgery appears to decrease red blood cell haemolysis, and tissue damage during the operative procedures and thereby significantly decreases the risk of plasma iron overload associated with conventional bypass.

  12. Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

    Science.gov (United States)

    Ruefer, Axel; Bapst, Christine; Benz, Rudolf; Bremerich, Jens; Cantoni, Nathan; Infanti, Laura; Samii, Kaveh; Schmid, Mathias; Vallée, Jean-Paul

    2017-11-09

    Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists

  13. Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload.

    Science.gov (United States)

    Preziosi, Morgan E; Singh, Sucha; Valore, Erika V; Jung, Grace; Popovic, Branimir; Poddar, Minakshi; Nagarajan, Shanmugam; Ganz, Tomas; Monga, Satdarshan P

    2017-08-01

    Iron overload disorders such as hereditary hemochromatosis and iron loading anemias are a common cause of morbidity from liver diseases and increase risk of hepatic fibrosis and hepatocellular carcinoma (HCC). Treatment options for iron-induced damage are limited, partly because there is lack of animal models of human disease. Therefore, we investigated the effect of iron overload in liver-specific β-catenin knockout mice (KO), which are susceptible to injury, fibrosis and tumorigenesis following chemical carcinogen exposure. Iron overload diet was administered to KO and littermate control (CON) mice for various times. To ameliorate an oxidant-mediated component of tissue injury, N-Acetyl-L-(+)-cysteine (NAC) was added to drinking water of mice on iron overload diet. KO on iron diet (KO +Fe) exhibited remarkable inflammation, followed by steatosis, oxidative stress, fibrosis, regenerating nodules and occurrence of occasional HCC. Increased injury in KO +Fe was associated with activated protein kinase B (AKT), ERK, and NF-κB, along with reappearance of β-catenin and target gene Cyp2e1, which promoted lipid peroxidation and hepatic damage. Addition of NAC to drinking water protected KO +Fe from hepatic steatosis, injury and fibrosis, and prevented activation of AKT, ERK, NF-κB and reappearance of β-catenin. The absence of hepatic β-catenin predisposes mice to hepatic injury and fibrosis following iron overload, which was reminiscent of hemochromatosis and associated with enhanced steatohepatitis and fibrosis. Disease progression was notably alleviated by antioxidant therapy, which supports its chemopreventive role in the management of chronic iron overload disorders. Lack of animal models for iron overload disorders makes it hard to study the disease process for improving therapies. Feeding high iron diet to mice that lack the β-catenin gene in liver cells led to increased inflammation followed by fat accumulation, cell death and wound healing that mimicked

  14. Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform.

    Science.gov (United States)

    Valent, Peter; Stauder, Reinhard; Theurl, Igor; Geissler, Klaus; Sliwa, Thamer; Sperr, Wolfgang R; Bettelheim, Peter; Sill, Heinz; Pfeilstöcker, Michael

    2018-02-01

    Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

  15. Hepatic iron overload following liver transplantation of a C282y homozygous allograft: a case report and literature review.

    LENUS (Irish Health Repository)

    Dwyer, Jeremy P

    2011-11-01

    Hereditary haemochromatosis is a common genetic disease associated with progressive iron overload and parenchymal organ damage including liver, pancreas and heart. We report a case of inadvertent transplantation of a liver from a haemochromatosis donor to a 56-year-old Asian female. Progressive iron overload occurred over a 2 year follow up as assessed by liver biopsy and iron studies in the absence of a secondary cause of iron overload, supporting a primary role of liver rather than small intestine in the regulation of iron homeostasis in hereditary haemochromatosis.

  16. THE EFFECT OF HAEMOCHROMATOSIS MUTATION ON IRON OVERLOAD IN THALASSAEMIA MAJOR PATIENTS

    Directory of Open Access Journals (Sweden)

    Tapas Ranjan Behera

    2016-11-01

    Full Text Available BACKGROUND Haemochromatosis is a genetic form of iron overload due to a defective HFE gene. Secondary iron overload is the main complication in transfusion-dependent thalassaemia major patients. This study aims at evaluating the degree of iron overload in β-thalassaemia major patients with and without HFE mutations (C282Y, H63D and S65C. MATERIALS AND METHODS A descriptive observational study was conducted including fifty diagnosed -thalassaemia major cases. Detailed clinical history and iron profile was estimated. DNA analysis by PCR-RFLP method for HFE gene mutations was performed. RESULTS After DNA analysis of all the thalassaemia major cases, two groups were identified, one with HFE gene mutation and other without HFE gene mutation. Iron profile of both the groups (with and without HFE gene mutation was estimated and compared. Only H63D mutation (out of three HFE gene mutations was detected in 16% cases (8 out of 50 cases, which comprised the group with mutation. Comparison of iron parameters between two groups (with and without HFE gene mutation showed significant difference in percent transferrin saturation (p=0.02, while other iron parameters (serum iron and serum ferritin did not show significant difference. CONCLUSION No significant difference between serum ferritin values (a marker of iron overload of groups with and without mutation (mean ferritin level 4641±2166 ng/mL and 4170±2461 ng/mL, respectively was found (p=0.61, in a patient population in whom transfusion protocol and proper chelation regimen was followed.

  17. Causes of iron overload in blood donors - a clinical study

    DEFF Research Database (Denmark)

    Laursen, A H; Bjerrum, O W; Friis-Hansen, L

    2018-01-01

    BACKGROUND AND OBJECTIVES: Despite the obligate iron loss from blood donation, some donors present with hyperferritinaemia that can result from a wide range of acute and chronic conditions including hereditary haemochromatosis (HH). The objective of our study was to investigate the causes...... of hyperferritinaemia in the blood donor population and explore the value of extensive HH mutational analyses. MATERIALS AND METHODS: Forty-nine consecutive donors (f = 6, m = 43) were included prospectively from the Capital Regional Blood Center. Inclusion criteria were a single ferritin value >1000 μg/l or repeated...... four donors had apparent alternative causes of hyperferritinaemia. CONCLUSION: HH-related mutations were the most frequent cause of hyperferritinaemia in a Danish blood donor population, and it appears that several different HH-genotypes can contribute to hyperferritinaemia. HH screening in blood...

  18. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

    Science.gov (United States)

    Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

    2017-02-01

    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. Copyright© Ferrata Storti Foundation.

  19. Iron Overload Leading to Torsades de Pointes in β-Thalassemia and Long QT Syndrome

    DEFF Research Database (Denmark)

    Refaat, Marwan M; El Hage, Lea; Steffensen, Annette Buur

    2016-01-01

    The authors present a unique case of torsades de pointes in a β-thalassemia patient with early iron overload in the absence of any structural abnormalities as seen in hemochromatosis. Genetic testing showed a novel KCNQ1 gene mutation 1591C>T [Gln531Ter(X)]. Testing of the gene mutation in Xenopus...

  20. Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

    Science.gov (United States)

    Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

    2018-06-05

    Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Iron overload and pregnancy outcome among Sudanese women ...

    African Journals Online (AJOL)

    The mean babies' birth weights were comparable among the IOL and the LSI groups but both were significantly lower than that among the NSI group. Conclusion: Iron supplementation to pregnant women must be rationalized so that women will benefit without developing undesirable effects. Key words: iron, oxidative stress ...

  2. Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

    International Nuclear Information System (INIS)

    Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M.; Shearkhani, Omid

    2017-01-01

    MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

  3. Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

    Energy Technology Data Exchange (ETDEWEB)

    Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M. [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Shearkhani, Omid [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

    2017-06-15

    MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

  4. Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    Full Text Available CONTEXT AND OBJECTIVE: Hemochromatosis is a common inherited disorder of iron metabolism and one of the most important causes of iron overload. The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with clinical and laboratory variables. DESIGN AND SETTING: Prospective study, in Discipline of Hematology and Oncology, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. METHODS: We studied 35 patients with iron overload seen at our outpatient unit between January 2001 and December 2003. Fasting levels of serum iron and ferritin, and total iron-binding capacity, were assayed using standard techniques. Determinations of C282Y, H63D and S65C mutations in the HFE gene and of HLA-A alleles were performed by polymerase chain reaction (PCR. RESULTS: Twenty-six out of 35 patients (74% presented at least one of the HFE gene mutations analyzed. Among these, five (14% were C282Y/C282Y, four (11% C282Y/H63D, one (3% H63D/H63D, six (17% C282Y/WT and ten (29% H63D/WT. No patients had the S65C mutation and nine (25% did not present any of the three HFE mutations. Four out of five patients with C282Y/C282Y genotype (80% and three out of four patients with C282Y/H63D genotype (75% were HLA A*03. CONCLUSION: Analysis of HFE gene mutations constitutes an important procedure in identifying patients with hereditary hemochromatosis, particularly for patients with iron overload.

  5. Iron overload and HFE gene mutations in Polish patients with liver cirrhosis.

    Science.gov (United States)

    Sikorska, Katarzyna; Romanowski, Tomasz; Stalke, Piotr; Iżycka-Świeszewska, Ewa; Bielawski, Krzysztof Piotr

    2011-06-01

    Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins. This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis. Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases. Liver function tests and serum iron markers were assessed in both groups. All patients were screened for HFE mutations (C282Y, H63D, S65C). Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes. The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis. There were no differences in the prevalence of all HFE mutations in both groups. In patients with a diagnosis of hepatocellular carcinoma, no significant associations with iron disorders and HFE gene mutations were found. Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations. Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis. As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease, there is a need for more extensive studies searching for

  6. Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury.

    Science.gov (United States)

    Meng, Fan Xing; Hou, Jing Ming; Sun, Tian Sheng

    2017-02-08

    Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model. Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors. SCI may cause intracranial iron overload through the NOS-iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.

  7. Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

    Science.gov (United States)

    Sikorska, Katarzyna; Stalke, Piotr; Romanowski, Tomasz; Rzepko, Robert; Bielawski, Krzysztof Piotr

    2013-08-01

    Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

  8. The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins.

    Science.gov (United States)

    Szurowska, Edyta; Sikorska, Katarzyna; Izycka-Swieszewska, E; Nowicki, Tomasz; Romanowski, Tomasz; Bielawski, Krzysztof P; Studniarek, Michał

    2010-01-27

    There are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing. MRI shows changes of liver intensity in patients with hepatic iron overload. Changes in MR signal are an indirect consequence of change of relaxation times T2 and T2*, that can be directly measured. The purpose of the study was to evaluate usefulness of MR imaging in the detection of hepatic iron overload in patients with cirrhosis of different origins. MR imaging at 1.5T was prospectively performed in 44 patients with liver cirrhosis who had undergone liver biopsy with histopathological assessment of hepatic iron deposits. In all patients the following sequences were used: SE, Express, GRE in T2 and T1-weighted images. Signal intensity (SI) was measured on images obtained with each T2 weighted sequence by means of regions of interest, placed in the liver and paraspinal muscles. The correlation between iron overload, histopathological score, serum ferritin and SI ratio was analyzed. In 20 patients with iron overload confirmed by the biopsy, the liver parenchyma demonstrated lower signal intensity than that of paraspinal muscles. This effect was visible only in 8 patients with hepatic iron overload in Express T2-weighted images. Higher signal intensity of liver than that of skeletal muscles on GRE - T2 weighted images was noted in 24 patients with cirrhosis and without elevated hepatic iron concentration. We observed a correlation between low and high iron concentration and liver to muscle SI ratio. MR imaging is a useful and fast noninvasive diagnostic tool for the detection of liver iron overload in patients with cirrhosis of different origins.Liver to muscle SI ratio in GRE-T2-weighted sequence facilitates to differentiate patients with low and high degree of hepatic iron overload, which correlates

  9. Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

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    Joana Neves

    2017-06-01

    Full Text Available Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S, increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

  10. HFE MUTATIONS AND IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

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    Luis COSTA-MATOS

    2013-03-01

    Full Text Available Context Alcoholic liver disease (ALD is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment and 52 healthy controls (during elective cholecystectomy. All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations. Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05, but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI: 2.09-142.34, P = 0.008. However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003. Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no

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

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    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

  12. T lymphocytes and iron overload: novel correlations of possible significance to the biology of the immunological system

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    Maria de Sousa

    1992-01-01

    Full Text Available This paper is written in the context of our changing preception of the immunological system as a system with possible biological roles exceding the prevailung view of a system concerned principally with the defense against external pathogens. The view discussed here relates the immunological system inextricably to the metabolism of iron, the circulation of the blood and the resolution of the evolutionary paradox created by oxygen and iron. Indirect evidence for this inextricable relationship between the two systems can be derived from the discrepancy between the theoretical quasi-impossibility of the existence of an iron deficiency state in the adult and the reality of the WHO numbers of people in the world with iron deficiency anemia. With mounting evidence that TNF, IL-1, and T lymphocyte cytokines affect hemopoieisis and iron metabolism it is possible that the reported discrepancy is a reflection of that inextricable interdependence between the two systems in the face of infection. Further direct evidence for a relationship between T cell subset numbers and iron metabolism is presented from the results of a study of T cell populations in patients with hereditary hemochromatosis. The recent finding of a correlation between low CD8+ lymphocite numbers, liver demage associated with HCVpositivity and severity of iron overload in B-thalassemia major patients (umpublished data of RW Grandy; P. Giardina, M. Hilgartner concludes this review.

  13. Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

    Science.gov (United States)

    Maaroufi, Karima; Had-Aissouni, Laurence; Melon, Christophe; Sakly, Mohsen; Abdelmelek, Hafedh; Poucet, Bruno; Save, Etienne

    2014-01-01

    The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia.

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    Bou-Fakhredin, Rayan; Bazarbachi, Abdul-Hamid; Chaya, Bachar; Sleiman, Joseph; Cappellini, Maria Domenica; Taher, Ali T

    2017-12-20

    Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient's needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

  15. Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia

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    Rayan Bou-Fakhredin

    2017-12-01

    Full Text Available Iron overload (IOL due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT, which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient’s needs and on the available facilities. Iron chelation therapy (ICT remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

  16. Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis.

    Science.gov (United States)

    Pirdel, Leila; Pirdel, Manijeh

    2014-06-01

    This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis. © 2014 Society for Reproduction and Fertility.

  17. Virtual iron concentration imaging based on dual-energy CT for noninvasive quantification and grading of liver iron content: An iron overload rabbit model study

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Xian Fu; Yang, Yi; Xie, Xue Qian; Zhang, Huan; Chai, Wei Min; Yan, Fu Hua [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Yan, Jing [Siemens Shanghai Medical Equipment Ltd., Shanghai (China); Wang, Li [Fudan University, Center of Analysis and Measurement, Shanghai (China); Schmidt, Bernhard [Siemens AG, Healthcare Sector, Forchheim (Germany)

    2015-09-15

    To assess the accuracy of liver iron content (LIC) quantification and grading ability associated with clinical LIC stratification using virtual iron concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit model. Fifty-one rabbits were prepared as iron-loaded models by intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC images were derived from an iron-specific algorithm. Postmortem LIC assessments were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation between VIC and LIC was analyzed. VIC were stratified according to the corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g. Diagnostic performance of stratification was evaluated by receiver operating characteristic analysis. VIC linearly correlated with LIC (r = 0.977, P < 0.01). No significant difference was observed between VIC-derived LICs and ICP (P > 0.05). For the four clinical LIC thresholds, the corresponding cutoff values of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity (100 %) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g. Virtual iron concentration imaging on DECT showed potential ability to accurately quantify and stratify hepatic iron accumulation in the iron overload rabbit model. (orig.)

  18. Enhanced iron removal from liver parenchymal cells in experimental iron overload: liposome encapsulation of HBED and phenobarbital administration

    International Nuclear Information System (INIS)

    Rahman, Y.E.; Cerny, E.A.; Lau, E.H.; Carnes, B.A.

    1983-01-01

    The effectiveness of N,N'-bis[2-hydroxybenzyl]-ethylene-diamine-N,N'-diacetic acid (HBED) in removing radioiron introduced into the parenchymal cells of mouse liver as 59 Fe-ferritin has been investigated. The effectiveness of HBED, an iron chelator of low water solubility, has also been compared with that of desferrioxamine (DF), an iron chelator of high water solubility and currently in clinical use for treatment of transfusional iron overload. Using the 59 Fe excretion as the measure of effectiveness of chelation therapy and a standardized single chelator dose of 25 mg/kg, they have found that: (1) a saline suspension of HBED, prepared by sonication and given intraperitoneally to mice, promotes a small but significant increase in excretion of radioiron compared to the untreated controls, whereas DF, in its free form, is ineffective; (2) HBED encapsulated in lipid bilayers of liposomes and given intravenously is superior to nonencapsulated HBED; (3) DF encapsulated in small unilamellar liposomes is ineffective in removing iron given in the form of ferritin; (4) administration of phenobarbital in drinking water, at a concentration of 1 g/liter, induces a 30%-55% increase of iron excretion from untreated control mice and also from mice given HBED either in liposome-encapsulated or nonencapsulated form. HBED is superior to DF for removal of storage iron from liver parenchymal cells and liposomes are useful carriers for iron chelators of low water solubility

  19. Effects of Iron Overload on the Activity of Na,K-ATPase and Lipid Profile of the Human Erythrocyte Membrane.

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    Leilismara Sousa

    Full Text Available Iron is an essential chemical element for human life. However, in some pathological conditions, such as hereditary hemochromatosis type 1 (HH1, iron overload induces the production of reactive oxygen species that may lead to lipid peroxidation and a change in the plasma-membrane lipid profile. In this study, we investigated whether iron overload interferes with the Na,K-ATPase activity of the plasma membrane by studying erythrocytes that were obtained from the whole blood of patients suffering from iron overload. Additionally, we treated erythrocytes of normal subjects with 0.8 mM H2O2 and 1 μM FeCl3 for 24 h. We then analyzed the lipid profile, lipid peroxidation and Na,K-ATPase activity of plasma membranes derived from these cells. Iron overload was more frequent in men (87.5% than in women and was associated with an increase (446% in lipid peroxidation, as indicated by the amount of the thiobarbituric acid reactive substances (TBARS and an increase (327% in the Na,K-ATPase activity in the plasma membrane of erythrocytes. Erythrocytes treated with 1 μM FeCl3 for 24 h showed an increase (132% in the Na,K-ATPase activity but no change in the TBARS levels. Iron treatment also decreased the cholesterol and phospholipid content of the erythrocyte membranes and similar decreases were observed in iron overload patients. In contrast, erythrocytes treated with 0.8 mM H2O2 for 24 h showed no change in the measured parameters. These results indicate that erythrocytes from patients with iron overload exhibit higher Na,K-ATPase activity compared with normal subjects and that this effect is specifically associated with altered iron levels.

  20. Treating thalassemia major-related iron overload: the role of deferiprone

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    Berdoukas V

    2012-10-01

    Full Text Available Vasilios Berdoukas,1 Kallistheni Farmaki,2 Susan Carson,1 John Wood,3 Thomas Coates11Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, CA, USA; 2Thalassemia Unit, General Hospital of Corinth, Corinth, Greece; 3Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA, USAAbstract: Over the last 20 years, management for thalassemia major has improved to the point where we predict that patients' life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients' quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the

  1. A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

    Science.gov (United States)

    Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

    2018-05-01

    Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

  2. Chronic Iron Overload Results in Impaired Bacterial Killing of THP-1 Derived Macrophage through the Inhibition of Lysosomal Acidification

    Science.gov (United States)

    Kao, Jun-Kai; Wang, Shih-Chung; Ho, Li-Wei; Huang, Shi-Wei; Chang, Shu-Hao; Yang, Rei-Cheng; Ke, Yu-Yuan; Wu, Chun-Ying; Wang, Jiu-Yao; Shieh, Jeng-Jer

    2016-01-01

    Iron is essential for living organisms and the disturbance of iron homeostasis is associated with altered immune function. Additionally, bacterial infections can cause major complications in instances of chronic iron overload, such as patients with transfusion-dependent thalassemia. Monocytes and macrophages play important roles in maintaining systemic iron homoeostasis and in defense against invading pathogens. However, the effect of iron overload on the function of monocytes and macrophages is unclear. We elucidated the effects of chronic iron overload on human monocytic cell line (THP-1) and THP-1 derived macrophages (TDM) by continuously exposing them to high levels of iron (100 μM) to create I-THP-1 and I-TDM, respectively. Our results show that iron overload did not affect morphology or granularity of I-THP-1, but increased the granularity of I-TDM. Bactericidal assays for non-pathogenic E. coli DH5α, JM109 and pathogenic P. aeruginosa all revealed decreased efficiency with increasing iron concentration in I-TDM. The impaired P. aeruginosa killing ability of human primary monocyte derived macrophages (hMDM) was also found when cells are cultured in iron contained medium. Further studies on the bactericidal activity of I-TDM revealed lysosomal dysfunction associated with the inhibition of lysosomal acidification resulting in increasing lysosomal pH, the impairment of post-translational processing of cathepsins (especially cathepsin D), and decreased autophagic flux. These findings may explain the impaired innate immunity of thalassemic patients with chronic iron overload, suggesting the manipulation of lysosomal function as a novel therapeutic approach. PMID:27244448

  3. Iron overload by Superparamagnetic Iron Oxide Nanoparticles is a High Risk Factor in Cirrhosis by a Systems Toxicology Assessment

    Science.gov (United States)

    Wei, Yushuang; Zhao, Mengzhu; Yang, Fang; Mao, Yang; Xie, Hang; Zhou, Qibing

    2016-06-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent have been widely used in magnetic resonance imaging for tumor diagnosis and theranostics. However, there has been safety concern of SPIONs with cirrhosis related to excess iron-induced oxidative stress. In this study, the impact of iron overload by SPIONs was assessed on a mouse cirrhosis model. A single dose of SPION injection at 0.5 or 5 mg Fe/kg in the cirrhosis group induced a septic shock response at 24 h with elevated serum levels of liver and kidney function markers and extended impacts over 14 days including high levels of serum cholesterols and persistent low serum iron level. In contrast, full restoration of liver functions was found in the normal group with the same dosages over time. Analysis with PCR array of the toxicity pathways revealed the high dose of SPIONs induced significant expression changes of a distinct subset of genes in the cirrhosis liver. All these results suggested that excess iron of the high dose of SPIONs might be a risk factor for cirrhosis because of the marked impacts of elevated lipid metabolism, disruption of iron homeostasis and possibly, aggravated loss of liver functions.

  4. Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded β-thalassemic mice

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    Supranee Upanan

    2015-12-01

    Conclusions: The GTE + DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent β-thalassemic mice, by chelating toxic iron in plasma and tissues, and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen. There is probably an advantage in giving GTE with DFP when treating patients with iron overload.

  5. Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

    Science.gov (United States)

    Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Mandal, Nripendranath

    2016-07-26

    Crude Spondias pinnata bark extract was previously assessed for its antioxidant, anticancer and iron chelating potentials. The isolated compounds gallic acid (GA) and methyl gallate (MG) were evaluated for their curative potential against iron overload-induced liver fibrosis and hepatocellular damage. In vitro iron chelation property and in vivo ameliorating potential from iron overload induced liver toxicity of GA and MG was assessed by different biochemical assays and histopathological studies. MG and GA demonstrated excellent reducing power activities but iron chelation potential of MG is better than GA. Oral MG treatment in mice displayed excellent efficacy (better than GA) to significantly restore the levels of liver antioxidants, serum markers and cellular reactive oxygen species in a dose-dependent fashion. Apart from these, MG exceptionally prevented lipid peroxidation and protein oxidation whereas GA demonstrated better activity to reduce collagen content, thereby strengthening its position as an efficient drug against hepatic damage/fibrosis, which was further supported by histopathological studies. Alongside, MG efficiently eliminated the cause of liver damage, i.e., excess iron, by chelating free iron and reducing the ferritin-bound iron. The present study confirmed the curative effect of GA and MG against iron overload hepatic damage via their potent antioxidant and iron-chelating potential.

  6. Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload

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    Porter John B

    2010-04-01

    Full Text Available Abstract Aim We aimed to define reference ranges for right ventricular (RV volumes, ejection fraction (EF in thalassemia major patients (TM without myocardial iron overload. Methods and results RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance. All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017, which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%. RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027, with a higher upper limit (132 vs 110 mL/m2 but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2. The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p Conclusion The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients.

  7. Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload.

    Science.gov (United States)

    Enein, Azza Aboul; El Dessouky, Nermine A; Mohamed, Khalda S; Botros, Shahira K A; Abd El Gawad, Mona F; Hamdy, Mona; Dyaa, Nehal

    2016-06-15

    This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status. The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing. Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001). Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients.

  8. Therapeutic Phlebotomy is Safe in Children with Sickle Cell Anaemia and can be Effective Treatment for Transfusional Iron Overload

    OpenAIRE

    Aygun, Banu; Mortier, Nicole A.; Kesler, Karen; Lockhart, Alexandre; Schultz, William H.; Cohen, Alan R.; Alvarez, Ofelia; Rogers, Zora R.; Kwiatkowski, Janet L.; Miller, Scott T.; Sylvestre, Pamela; Iyer, Rathi; Lane, Peter A.; Ware, Russell E.

    2015-01-01

    Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (−8.7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained un...

  9. Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

    Science.gov (United States)

    Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

    2018-01-01

    Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, 30ms, weak relationship. All subjects with T2*20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

  10. MR marrow signs of iron overload in transfusion-dependent patients with sickle cell disease

    International Nuclear Information System (INIS)

    Levin, T.L.; Sheth, S.S.; Hurlet, A.; Comerci, S.C.; Ruzal-Shapiro, C.; Piomelli, S.; Berdon, W.E.

    1995-01-01

    Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of 13 transfusion-dependent and chelated pediatric patients with sickle cell anemia (SSD) was compared with marrow signal in six non-transfusion-dependent patients with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated. Indication for hypertransfusion therapy was primarily prior history of stroke. Transfusion-dependent patients had evidence of iron deposition throughout the imaged marrow and the liver, despite deferoxamine chelation therapy. Non-transfusion-dependent patients did not demonstrate grossly apparent signs of iron overload. Red marrow restoration was present in the spine, pelvis, and long bones and, in some patients, within the epiphyses. Marrow edema secondary to vaso-occlusive crises was evident in the metaphyses and diaphyses of long bones in areas of both red and fatty marrow and was best seen using fat-saturated T2-weighted imaging techniques. (orig.). With 4 figs., 2 tabs

  11. Hepcidin is directly regulated by insulin and plays an important role in iron overload in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Wang, Heyang; Li, Hongxia; Jiang, Xin; Shi, Wencai; Shen, Zhilei; Li, Min

    2014-05-01

    Iron overload is frequently observed in type 2 diabetes mellitus (DM2), but the underlying mechanisms remain unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2. We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption, and liver hepcidin expression in rats treated with streptozotocin (STZ), which was given alone or after insulin resistance induced by a high-fat diet. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells. STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption and serum and hepatic iron content. Insulin obviously upregulated hepcidin expression in HepG2 cells and enhanced signal transducer and activator of transcription 3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when the signal transducer and activator of transcription 3 pathway was blocked and could be partially inhibited by U0126. In conclusion, the current study suggests that hepcidin can be directly regulated by insulin, and the suppressed liver hepcidin synthesis may be an important reason for the iron overload in DM2.

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

    Science.gov (United States)

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

    2003-05-01

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

  13. Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions.

    Science.gov (United States)

    Porter, John B; Cappellini, Maria Domenica; Kattamis, Antonis; Viprakasit, Vip; Musallam, Khaled M; Zhu, Zewen; Taher, Ali T

    2017-01-01

    Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%. © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  14. Comparison of Deferoxamine, Activated Charcoal, and Vitamin C in Changing the Serum Level of Fe in Iron Overloaded Rats

    Directory of Open Access Journals (Sweden)

    Reza Ghafari

    2014-02-01

    Full Text Available Background: Iron is an essential mineral for normal cellular physiology but its overload can lead to cell injury. For many years, deferoxamine injection has been used as an iron chelator for treatment of iron overload. The aim of this study is to compare oral deferoxamine, activated charcoal, and vitamin C, as an absorbent factor of Fe, in changing the serum level of iron in iron overload rats. Methods: In this experimental study, all groups were administered 150 mg iron dextran orally by gavage. After eight hours, rats in the first group received oral deferoxamine while those in the second and third groups received oral activated charcoal 1 mg/kg and oral vitamin C 150 mg, respectively. Then, serum levels of iron ware measured in all rats. Results: The mean serum level of iron in rats that received oral deferoxamine was 258.11±10.49 µg/dl, whereas mean levels of iron in charcoal and vitamin C groups were 380.88±11.21 µg/dl and 401.22±13.28 µg/dl, respectively. None of the measurements were within safety limits of serum iron. Conclusion: It seems that oral deferoxamine per se may not help physicians in the management of cases presented with iron toxicity. Activated charcoal did not reduce serum iron significantly in this study and further investigations may be warranted to assess the potential clinical utility of its mixture with oral deferoxamine as an adjunct in the clinical management of iron ingestions.

  15. Iron overload and HFE gene mutations in Czech patients with chronic liver diseases.

    Science.gov (United States)

    Dostalikova-Cimburova, Marketa; Kratka, Karolina; Stransky, Jaroslav; Putova, Ivana; Cieslarova, Blanka; Horak, Jiri

    2012-01-01

    The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

  16. [Guidelines for diagnosis and treatment of secondary iron overload in patients with congenital anemia].

    Science.gov (United States)

    Cario, H; Grosse, R; Janssen, G; Jarisch, A; Meerpohl, J; Strauss, G

    2010-11-01

    In Germany and Central Europe, congenital disorders leading to secondary hemochromatosis are rare. The majority of these patients are treated in peripheral medical institutions. As a consequence, the experience of each institution in the treatment of secondary hemochromatosis in patients with congenital anemia is limited. Recent developments concerning new chelating agents, their combination for intensified chelation and new possibilities to diagnose and monitor iron overload have important consequences for the management of patients with secondary hemochromatosis and increase its complexity enormously. Therefore, the development of a guideline for rational and efficient diagnostics and treatment was necessary. The new guideline was developed within a formal consensus process and finally approved by a consensus conference with participants from both the pediatric and adult German hematology societies (GPOH and DGHO). Apart from general information and recommendations, the guideline contains 9 consensus statements on diagnostics (iron status, siderotic complications, chelator side-effects), the start of chelation, indications for intensified chelation, iron elimination in specific disorders, and iron elimination after stem cell transplantation. Here, these consensus statements are presented and discussed in detail. For the complete text of the guideline, please visit the AWMF homepage at http://www.leitlinien.net . © Georg Thieme Verlag KG Stuttgart · New York.

  17. Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury.

    Science.gov (United States)

    Lu, Nai-Hao; Chen, Chao; He, Ying-Jie; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

    2013-01-01

    Flavonoids have been widely reported to protect liver injury in iron-overload diseases, where the mechanism of this therapeutic action is dependent on their antioxidant effects, including free radical scavenging and metal-chelating. In this study, in contrast to the significant decrease in iron content, quercetin (Qu) from lower diet (0.3%, w/w) showed pro-oxidant ability on protein carbonyl formation and exhibited unobvious effect on iron-overload rat liver injury. Furthermore, the anti- and pro-oxidant activities of Qu on hemoglobin (Hb)-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate, Hb-induced protein oxidation) were investigated to illustrate the elevated protein oxidation in lower Qu-treated iron-overload rat. It was found that superoxide (O₂·⁻) and hydrogen peroxide (H₂O₂) were generated during the reaction between Qu and Hb. Qu, however, effectively reduced ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. Moreover, Qu could significantly aggravate Hb-H₂O₂-induced protein oxidation at low concentrations and exhibit protective effects at high concentrations. Different from the classic antioxidant mechanisms of Qu, the dual effects on Hb redox reactions in vitro, therefore, may provide new insights into the physiological and pharmacological implications of Qu with iron-overload disease.

  18. Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.

    Science.gov (United States)

    Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Alvarez-Sala-Walther, Luis-Antonio; Cuadrado-Grande, Nuria; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

    2011-03-01

    The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes. © 2011 John Wiley & Sons A/S.

  19. Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

    Science.gov (United States)

    Camacho, A; Simão, M; Ea, H-K; Cohen-Solal, M; Richette, P; Branco, J; Cancela, M L

    2016-03-01

    Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. A free software for the calculation of T2* values for iron overload assessment.

    Science.gov (United States)

    Fernandes, Juliano Lara; Fioravante, Luciana Andrea Barozi; Verissimo, Monica P; Loggetto, Sandra R

    2017-06-01

    Background Iron overload assessment with magnetic resonance imaging (MRI) using T2* has become a key diagnostic method in the management of many diseases. Quantitative analysis of the MRI images with a cost-effective tool has been a limitation to increased use of the method. Purpose To provide a free software solution for this purpose comparing the results with a commercial solution. Material and Methods The free tool was developed as a standalone program to be directly downloaded and ran in a common personal computer platform without the need of a dedicated workstation. Liver and cardiac T2* values were calculated using both tools and the values obtained compared between them in a group of 56 patients with suspected iron overload using Bland-Altman plots and concordance correlation coefficients (CCC). Results In the heart, the mean T2* differences between the two methods was 0.46 ms (95% confidence interval [CI], -0.037 -0.965) and in the liver 0.49 ms (95% CI, 0.257-0.722). The CCC for both the heart and the liver were significantly high (0.98 [95% CI, 0.966-0.988] with a Pearson ρ of 0.9811 and 0.991 [95% CI, 0.986-0.994] with a Pearson ρ of 0.996, respectively. No significant differences were observed when analyzing only patients with abnormal concentrations of iron in both organs compared to the whole cohort. Conclusion The proposed free software tool is accurate for calculation of T2* values of the liver and heart and might be a solution for centers that cannot use paid commercial solutions.

  1. Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons.

    Science.gov (United States)

    Tao, Ling-Xue; Huang, Xiao-Tian; Chen, Yu-Ting; Tang, Xi-Can; Zhang, Hai-Yan

    2016-11-01

    Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine triphosphate (ATP) assays were performed to assess mitochondrial function. The labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified Ellman's method was used to evaluate AChE activity. HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil (Don), at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect.

  2. The impact of iron overload and its treatment on quality of life: results from a literature review

    Directory of Open Access Journals (Sweden)

    Jones Paula

    2006-09-01

    Full Text Available Abstract Background To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT on patients' quality of life (QoL, and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. Methods A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED. Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Results Few studies measuring the impact of ICT with deferoxamine (DFO on patients QoL were located (n = 15. QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. Conclusion A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL.

  3. The impact of iron overload and its treatment on quality of life: results from a literature review.

    Science.gov (United States)

    Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana

    2006-09-28

    To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL.

  4. Severe iron intoxication treated with exchange transfusion

    DEFF Research Database (Denmark)

    Carlsson, M; Cortes, D; Jepsen, S

    2009-01-01

    An 18-month-old previous healthy girl who had ingested 442 mg elemental iron/kg was admitted to a paediatric intensive care unit. The child was treated with gastric lavage, whole bowel irrigation and intravenous deferoxamine. After 2 h of standard therapy serum iron had risen threefold to 1362 µg....../dl (244 µmol/l). The child was treated with exchange transfusion (ET; 52 ml/kg) and serum iron fell to 134 µg/dl (24 µmol/l). The patient made an uncomplicated recovery. ET should be considered in severe iron poisoning when standard therapy is inadequate....

  5. Severe iron intoxication treated with exchange transfusion

    DEFF Research Database (Denmark)

    Carlsson, Marcella; Cortes, Dina; Jepsen, Søren

    2008-01-01

    An 18-month-old previous healthy girl who had ingested 442 mg elemental iron/kg was admitted to a paediatric intensive care unit. The child was treated with gastric lavage, whole bowel irrigation and intravenous deferoxamine. After 2 h of standard therapy serum iron had risen threefold to 1362 mi...... microg/dl (244 micromol/l). The child was treated with exchange transfusion (ET; 52 ml/kg) and serum iron fell to 134 microg/dl (24 micromol/l). The patient made an uncomplicated recovery. ET should be considered in severe iron poisoning when standard therapy is inadequate....

  6. Hemochromatosis C282Y gene mutation as a potential susceptibility factor for iron-overload in Egyptian beta-thalassemia patients

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    G.M. Mokhtar

    2018-04-01

    Full Text Available Background: Hereditary hemochromatosis is the most frequent cause of primary iron overload that is associated with HFE gene’s mutation especially the C282Y mutation. The interaction between hemoglobin chain synthesis’ disorders and the C282Y mutation may worsen the clinical picture of beta-thalassemia major (β-TM. Aim: To establish the prevalence of the C282Y mutations in Egyptian β-TM patients and to address its adverse effects. Methods: Two-hundred and five β-TM patients were recruited and divided into two groups based on their serum ferritin (SF; group I (N = 125 (SF ≤ 2500 ng/dl and group II (N = 80 (SF > 2500 ng/dl. All patients were subjected to clinical and laboratory assessment with special emphasis on iron overload complications. Genotyping was assessed by polymerase chain reaction for detection of C282Y mutation in HFE gene. Results: The C282Y mutation was not detected in the studied β-TM neither in homozygous nor heterozygous state. There were several iron overload complications including cardiac complication (9.1%, liver disease (36.6%, delayed puberty (56.6%, primary (35.71% and secondary amenorrhea (21.42%, short stature (27.3%, diabetes (3.4%, neutropenia (9.7%, arthralgia (10.2%, gastrointestinal (21.1%, depression (2.9% and others (12.05%. Group I showed a statistically significant lower rate of taking iron-rich diet when compared to group II. Group II showed significant longer mean duration of disease, higher total transfusion rate per life, lower mean HbF% level, higher mean HbA% level, and higher rate of elevated liver enzymes than patients with SF ≤ 2500 ng/dl. Conclusion: The C282Y mutation was not detected in the studied cohort of Egyptian β-TM patients neither in homozygous nor heterozygous state in spite of manifestations of iron overload complications. Keywords: Beta-thalassemia major, Hereditary hemochromatosis, The C282Y mutation, Iron overload complications, Egyptian

  7. Quantitative assessment of iron load in myocardial overload rabbit model: preliminary study of MRI T2* map

    International Nuclear Information System (INIS)

    Huang Lu; Han Rui; Li Zhiwei; Yuan Sishu; Xia Liming

    2014-01-01

    Objective: To preliminarily investigate the feasibility of MRI-T 2 * map in evaluating myocardial iron load of myocardial iron overload rabbit models. Methods: Eleven rabbits were included in this study and divided into two groups, myocardial iron overload group (n =10) and the control group (n = 1). Iron dextrin (dose of 50 mg/kg) was injected in muscles of thigh once a week, totally 12 weeks. Serum iron test and MRI examination were performed before iron injection,and 1 week to 12 weeks after iron injection. MRI scan protocol included short axial T 2 * map of the left ventricle and cross-section T 2 * map of the liver. T 2 * and R 2 * of the heart and the liver were measured. One rabbit was killed after MRI examination at pre-iron injection, 1 week to 8 weeks, 11 weeks and 12 weeks after iron injection,respectively. Heart and liver were avulsed to undergo in vitro MRI scan and then paraffin embedded for pathological slices. MRI scan protocol and measurements of the heart and the liver samples were the same to that of in vivo ones. Pearson correlation was used to calculate the relationships between the parameters. Results: Myocardial T 2 * [(32.5 ± 8.3 ms)] and R 2 * values [(38.4 ± 7.9) Hz] had significant correlation with injecting iron content (1033.2 ± 673.4 mg), the Pearson coefficients were -0.799 (P = 0.001) and 0.770 (P = 0.002), respectively. Myocardial T 2 * had no significant correlation with liver T 2 * values (r = 0.556, P = 0.070). T 2 * values of heart and liver in vivo [(32.5 ± 8.3) ms and (8.8 ± 5.4) ms], respectively had strong correlation with those in vitro [(19.4 ± 6.5) ms and (9.8 ± 5.0) ms], respectively (r = 0.757, P = 0.007 and r = 0.861, P = 0.001). T 2 * and R 2 * values of the heart and the liver in vivo and in vitro had no significant correlations with serum iron (P>0.05). On Prussian blue staining slices,blue particles of myocardium, sinus hepaticas and hepatocyte increased with injecting iron content. Conclusions: It is

  8. SUBCHRONIC PULMONARY PATHOLOGY, IRON-OVERLOAD AND TRANSCRIPTIONAL ACTIVITY AFTER LIBBY AMPHIBOLE EXPOSURE IN RAT MODELS OF CARDIOVASCULAR DISEASE

    Science.gov (United States)

    Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be incre...

  9. Glutathione S transferase polymorphisms influence on iron overload in β-thalassemia patients

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    Serena Sclafani

    2013-11-01

    Full Text Available In patients with β-thalassemia iron overload that leads to damage to vital organs is observed. Glutathione S transferase (GST enzymes have an antioxidant role in detoxification processes of toxic substances. This role is determined genetically. In this study, we correlated GSTT1 and GSTM1 genotypes with iron overload measured with direct and indirect non-invasive methods; in particular, we used serum ferritin and signal intensity of the magnetic resonance image (MRI in 42 patients with β-thalassemia, which were regularly subjected to chelation and transfusion therapy. Multiplex polymerase chain reaction was used to determine the genotype. The loss of both alleles leads to a decreased value of liver and heart MRI-signal intensity with a consequent iron accumulation in these organs; the loss of only one allele doesn’t lead to relevant overload. Serum ferritin doesn’t appear to be correlated to iron overload instead. 对于β-地中海贫血患者,由于铁过量而造成重要器官受损的情况也在观察之中。谷胱甘肽S转移酶(GST 酶类在对有毒物质进行解毒的过程中有着抗氧化剂的作用。该作用是由基因决定的。 在这份研究中,我们运用了直接和间接非侵入性的方法对基因型铁过量GSTT1 和GSTM1进行了相关性测量;特别地,我们对42位定期接受螯合和输血治疗的β-地中海贫血患者进行了血清铁蛋白和磁共振强度图像(MRI 的测试。 多重聚合酶链反应的测试也被运用来确定该基因型。 该两种等位基因的缺失,导致了肝功能减损及心脏磁共振强度的下降,并造成了在这些器官中铁含量的积累;其中一种等位基因的缺失并不会导致过度的铁含量。血清蛋白和铁过量之间,看起来并不存在相关性。

  10. Effect of Combined versus Monotherapy with Deferoxamine and Deferiprone in Iron Overloaded Thalassemia Patients: a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Sasan Hejazi

    2016-06-01

    Full Text Available Background: Patients with transfusional iron overload have depended on iron chelation therapy and improving chelation regimens have been of the highest priority. The aim of this study was to compare effect of combined versus monotherapy with Deferoxamine (DFO and Deferiprone (DFP in iron overloaded beta thalassemia (BT major patients Materials and Methods We studied 36 BT major patients (mean age 7.6±4.6; range 3–16 years attending the Ormieh Motahari hospital for regular transfusional support. Patients were randomly allocated to receive one of the following two treatments: DFO in combination with DFP (n=12, DFO alone (n=12 and DFP alone (n=12. Serum ferritin level, liver enzymes, blood urea nitrogen, and creatinine and side effects were monitored over a 12 months period. Results: After one year, serum ferritin decreased more significantly in patients on DFO+DFP therapy compared to patients who only received DFO or DFP alone (P

  11. Heart and liver T2* assessment for iron overload using different software programs

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Juliano L. [University of Campinas, Unicamp, Campinas (Brazil); Radiologia Clinica de Campinas, Campinas (Brazil); Cardiology, Department of Internal Medicine, Campinas, SP (Brazil); Sampaio, Erika Fontana; Coelho, Otavio R. [University of Campinas, Unicamp, Campinas (Brazil); Verissimo, Monica; Pereira, Fabricio B. [Centro Infantil Boldrini, Campinas (Brazil); Silva, Jose Alvaro da; Figueiredo, Gabriel S. de; Kalaf, Jose M. [Radiologia Clinica de Campinas, Campinas (Brazil)

    2011-12-15

    To assess the level of agreement and interchangeability among different software programs for calculation of T2* values for iron overload. T2* images were analysed in 60 patients with thalassaemia major using the truncation method in three software programs. Levels of agreement were assessed using Pearson correlation and Bland-Altman plots. Categorical classification for levels of iron concentration by each software program was also compared. For the heart, all correlation coefficients were significant among the software programs (P < 0.001 for all coefficients). The mean differences and 95% limits of agreement were 0.2 (-4.73 to 5.0); 0.1 (-4.0 to 3.9); and -0.1 (-4.3 to 4.8). For the liver all correlations were also significant with P < 0.001. Bland-Altman plots showed differences of -0.02 (-0.7 to 0.6); 0.01 (-0.4 to 0.4); and -0.02 (-0.6 to 0.6). There were no significant differences in clinical classification among the software programs. All tools used in this study provided very good agreement among heart and liver T2* values. The results indicate that interpretation of T2* data is interchangeable with any of the software programs tested. (orig.)

  12. Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

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    Alexandros Makis

    2013-01-01

    Full Text Available Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10 with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia. The mean duration of treatment was 21.5 months (range 15–31. All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child, mild neutropenia (1 child that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, . This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.

  13. Hyperferritinemia without iron overload in patients with bilateral cataracts: a case series

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    Mumford Andrew

    2011-09-01

    Full Text Available Abstract Introduction Hepatologists and internists often encounter patients with unexplained high serum ferritin concentration. After exclusion of hereditary hemochromatosis and hemosiderosis, rare disorders like hereditary hyperferritinemia cataract syndrome should be considered in the differential diagnosis. This autosomal dominant syndrome, that typically presents with juvenile bilateral cataracts, was first described in 1995 and has an increasing number of recognized molecular defects within a regulatory region of the L-ferritin gene (FTL. Case presentation Two patients (32 and 49-year-old Caucasian men from our ambulatory clinic were suspected as having this syndrome and a genetic analysis was performed. In both patients, sequencing of the FTL 5' region showed previously described mutations within the iron responsive element (FTL c.33 C > A and FTL c.32G > C. Conclusion Hereditary hyperferritinemia cataract syndrome should be considered in all patients with unexplained hyperferritinemia without signs of iron overload, particularly those with juvenile bilateral cataracts. Liver biopsy and phlebotomy should be avoided in this disorder.

  14. Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

    Science.gov (United States)

    Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M

    2016-03-01

    Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. The role of genetic factors in patients with hepatocellular carcinoma and iron overload - a prospective series of 234 patients.

    Science.gov (United States)

    Funakoshi, Natalie; Chaze, Iphigénie; Alary, Anne-Sophie; Tachon, Gaëlle; Cunat, Séverine; Giansily-Blaizot, Muriel; Bismuth, Michael; Larrey, Dominique; Pageaux, Georges-Philippe; Schved, Jean-François; Donnadieu-Rigole, Hélène; Blanc, Pierre; Aguilar-Martinez, Patricia

    2016-05-01

    Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. A total of 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC>70 μmol/g were enrolled in further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe haemochromatosis. Specific haplotypes of SLC40A1 were also studied. Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and the associated at-risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. HFE MUTATIONS AND IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

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    Luís COSTA-MATOS

    2013-03-01

    Full Text Available Context Alcoholic liver disease (ALD is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment and 52 healthy controls (during elective cholecystectomy. All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations. Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P Contexto A doença hepática alcoólica (DHA está geralmente associada à sobrecarga de ferro, que pode contribuir para a sua patogênese, através do aumento do estresse oxidativo e dano celular. As descrições existentes na literatura sobre a associação entre mutações HFE e a gravidade da DHA nem sempre são concordantes. Objetivos Comparar a prevalência de mutações HFE entre um grupo de pacientes com DHA e uma população de controle. Avaliar a relação entre mutações HFE e os depósitos de ferro hepático. Avaliar se a presença dessas mutações está associada com a gravidade da DHA. Métodos Compararam-se 63 pacientes com DHA que efetuaram biopsia hepática com 52 controles saudáveis. A genotipagem HFE (wild type, C282Y, H63D, S65C, E

  17. The critical role of Nramp1 in degrading α-synuclein oligomers in microglia under iron overload condition.

    Science.gov (United States)

    Wu, Kuo-Chen; Liou, Horng-Huei; Kao, Yu-Han; Lee, Chih-Yu; Lin, Chun-Jung

    2017-08-01

    Oligomeric α-synuclein is a key mediator in the pathogenesis of Parkinson's disease (PD) and is mainly cleared by autophagy-lysosomal pathway, whose dysfunction results in the accumulation and cell-to-cell transmission of α-synuclein. In this study, concomitant with the accumulation of iron and oligomeric α-synuclein, higher expression of a lysosomal iron transporter, natural resistance-associated macrophage protein-1 (Nramp1), was observed in microglia in post-mortem striatum of sporadic PD patients. Using Nramp1-deficient macrophage (RAW264.7) and microglial (BV-2) cells as in-vitro models, iron exposure significantly reduced the degradation rate of the administered human α-synuclein oligomers, which can be restored by the expression of the wild-type, but not mutant (D543N), Nramp1. Likewise, under iron overload condition, mice with functional Nramp1 (DBA/2 and C57BL/6 congenic mice carrying functional Nramp1) had a better ability to degrade infused human α-synuclein oligomers than mice with nonfunctional Nramp1 (C57BL/6) in the brain and microglia. The interplay between iron and Nramp1 exhibited parallel effects on the clearance of α-synuclein and the activity of lysosomal cathepsin D in vitro and in vivo. Collectively, these findings suggest that the function of Nramp1 contributes to microglial degradation of oligomeric α-synuclein under iron overload condition and may be implicated in the pathogenesis of PD. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

    Science.gov (United States)

    Henninger, B; Kremser, C; Rauch, S; Eder, R; Zoller, H; Finkenstedt, A; Michaely, H J; Schocke, M

    2012-11-01

    To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms +  n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

  19. Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload.

    Science.gov (United States)

    Meroño, Tomás; Brites, Fernando; Dauteuille, Carolane; Lhomme, Marie; Menafra, Martín; Arteaga, Alejandra; Castro, Marcelo; Saez, María Soledad; Ballerga, Esteban González; Sorroche, Patricia; Rey, Jorge; Lesnik, Philippe; Sordá, Juan Andrés; Chapman, M John; Kontush, Anatol; Daruich, Jorge

    2015-05-01

    Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, PHFE genotypes. C282Y homozygotes (n=7) presented a reduced β-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, PHFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

  20. HFE gene mutation and iron overload in Egyptian pediatric acute lymphoblastic leukemia survivors: a single-center study.

    Science.gov (United States)

    El-Rashedi, Farida H; El-Hawy, Mahmoud A; El-Hefnawy, Sally M; Mohammed, Mona M

    2017-08-01

    Hereditary hemochromatosis gene (HFE) mutations have a role in iron overload in pediatric acute lymphoblastic leukemia (ALL) survivors. We aimed to evaluate the genotype frequency and allelic distribution of the two HFE gene mutations (C282Y and H63D) in a sample of Egyptian pediatric ALL survivors and to detect the impact of these two mutations on their iron profile. This study was performed on 35 ALL survivors during their follow-up visits to the Hematology and Oncology Unit, Pediatric Department, Menoufia University Hospitals. Thirty-five healthy children of matched age and sex were chosen as controls. After completing treatment course, ALL survivors were screened for the prevalence of these two mutations by polymerase chain reaction-restriction fragment length polymorphism. Serum ferritin levels were measured by an enzyme-linked immunosorbent assay technique (ELISA). C282Y mutation cannot be detected in any of the 35 survivors or the 35 controls. The H63D heterozygous state (CG) was detected in 28.6% of the survivors group and in 20% of controls, while the H63D homozygous (GG) state was detected in 17.1% of survivors. No compound heterozygosity (C282Y/H63D) was detected at both groups with high G allele frequency (31.4%) in survivors more than controls (10%). There were significant higher levels of iron parameters in homozygote survivors than heterozygotes and the controls. H63D mutation aggravates the iron overload status in pediatric ALL survivors.

  1. Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer's disease.

    Science.gov (United States)

    Becerril-Ortega, Javier; Bordji, Karim; Fréret, Thomas; Rush, Travis; Buisson, Alain

    2014-10-01

    Iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD); yet, its mechanism is not well understood. Here, we investigated the AD-related mechanism(s) of iron-sulfate exposure in vitro and in vivo, using cultured primary cortical neurons and APP/PS1 AD-model mice, respectively. In both systems, we observed iron-induced disruptions of amyloid precursor protein (APP) processing, neuronal signaling, and cognitive behavior. Iron overload increased production of amyloidogenic KPI-APP and amyloid beta. Further, this APP misprocessing was blocked by MK-801 in vitro, suggesting the effect was N-methyl-D-aspartate receptor (NMDAR) dependent. Calcium imaging confirmed that 24 hours iron exposure led to disrupted synaptic signaling by augmenting GluN2B-containing NMDAR expression-GluN2B messenger RNA and protein levels were increased and promoting excessing extrasynaptic NMDAR signaling. The disrupted GluN2B expression was concurrent with diminished expression of the splicing factors, sc35 and hnRNPA1. In APP/PS1 mice, chronic iron treatment led to hastened progression of cognitive impairment with the novel object recognition discrimination index, revealing a deficit at the age of 4 months, concomitant with augmented GluN2B expression. Together, these data suggest iron-induced APP misprocessing and hastened cognitive decline occur through inordinate extrasynaptic NMDAR activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Association between baseline serum hepcidin levels and infection in kidney transplant recipients: Potential role for iron overload.

    Science.gov (United States)

    Fernández-Ruiz, Mario; Parra, Patricia; Ruiz-Merlo, Tamara; López-Medrano, Francisco; San Juan, Rafael; Polanco, Natalia; González, Esther; Andrés, Amado; Aguado, José María

    2018-02-01

    The liver-synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre-transplant hepcidin-25 levels and infection after kidney transplantation (KT). Serum hepcidin-25 levels were measured at baseline by high-sensitivity ELISA in 91 patients undergoing KT at our institution between December 2011 and March 2013. The impact of this biomarker on the incidence of post-transplant infection (excluding lower urinary tract infection) during the first year was assessed by Cox regression. Mean hepcidin-25 level was 82.3 ± 67.4 ng/mL and strongly correlated with serum ferritin (Spearman's rho = 0.703; P role for iron overload in the individual susceptibility to post-transplant infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    Guenancia, Charles [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Li, Na [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Hachet, Olivier [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Rigal, Eve [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cottin, Yves [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Dutartre, Patrick; Rochette, Luc [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Vergely, Catherine, E-mail: cvergely@u-bourgogne.fr [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France)

    2015-04-15

    Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15 mg/kg) for 3 weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6 mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000 μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+ 22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. - Highlights: • The effects of iron on cardiomyocytes were opposite to those on cancer cell lines. • In our model, iron overload did not potentiate anthracycline cardiotoxicity. • Chronic oxidative stress induced by iron could mitigate doxorubicin cardiotoxicity. • The role of iron in

  4. MRI for the determination of pituitary iron overload in children and young adults with β-thalassaemia major

    International Nuclear Information System (INIS)

    Christoforidis, Athanasios; Haritandi, Afroditi; Perifanis, Vassilios; Tsatra, Ioanna; Athanassiou-Metaxa, Miranda; Dimitriadis, Athanasios S.

    2007-01-01

    Hypogonadism, resulting from iron-induced pituitary dysfunction, is the most frequently reported complication in patients with β-thalassaemia major. The aim of this study was to evaluate pituitary Magnetic Resonance Imaging (MRI) signal intensity reduction, on T2*-weighted images, as a marker of pituitary iron overload. Thirty patients (13 females and 17 males, mean age: 16.6 ± 4.1) with β-thalassaemia major on conventional treatment and 13 healthy volunteers (7 females and 6 males, mean age: 11 ± 4.51 years) were studied with T2*-weighted images of the anterior pituitary using a 1.5 T unit. Four thalassaemic patients (2 females and 2 males) had clinical hypogonadism and required hormonal replacement treatment. Results revealed a statistically significant reduction of pituitary signal intensity in the thalassaemia group compared to controls (p 2 = 0.443, p = 0.001), whereas ferritin levels and pituitary MRI values were moderately correlated (r = -0.56, r 2 = 0.32, p = 0.08) in adult thalassaemic patients. In conclusion, pituitary MRI indices as measured on T2*-weighted images seem to reflect pituitary iron overload and could, therefore, be used for a preclinical detection of patients who are in greater danger of developing hypogonadism

  5. Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract.

    Science.gov (United States)

    Niu, Qiang; He, Ping; Xu, Shangzhi; Ma, Ruling; Ding, Yusong; Mu, Lati; Li, Shugang

    2018-01-01

    Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

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

    Science.gov (United States)

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

    2017-12-01

    The iron overload disorder hereditary haemochromatosis is most commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from any randomised trials, current evidence is insufficient to determine whether individuals with hereditary haemochromatosis and moderately elevated serum ferritin, should undergo iron reduction treatment. This trial aimed to establish whether serum ferritin normalisation in this population improved symptoms and surrogate biomarkers. This study was a multicentre, participant-blinded, randomised controlled trial done at three centres in Australia. We enrolled people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years, with moderately elevated serum ferritin, defined as 300-1000 μg/L, and raised transferrin saturation. Participants were randomly assigned, via a computer-generated random number, to undergo either iron reduction by erythrocytapheresis (treatment group) or sham treatment by plasmapheresis (control group). Randomisation was stratified by baseline serum ferritin (cognitive subcomponent (-3·6, -5·9 to -1·3, p=0·0030), but not in the physical (-1·90 -4·5 to 0·63, p=0·14) and psychosocial (-0·54, -1·2 to 0·11, p=0·10) subcomponents. No serious adverse events occurred in either group. One participant in the control group had a vasovagal event and 17 participants (14 in the treatment group and three in the control group) had transient symptoms assessed as related to hypovolaemia. Mild citrate reactions were more common in the treatment group (32 events [25%] in 129 procedures) compared with the control group (one event [1%] in 93 procedures). To our knowledge, this study is the first to objectively assess the consequences of iron removal in individuals with hereditary haemochromatosis and moderately elevated serum ferritin. Our results suggest that serum ferritin normalisation by iron depletion could be of benefit for all individuals with hereditary haemochromatosis and elevated serum

  7. Sobrecarga e quelação de ferro na anemia falciforme Iron overload and iron chelation in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Rodolfo D. Cançado

    2007-09-01

    Full Text Available Pacientes cronicamente transfundidos desenvolvem sobrecarga de ferro que ocasiona lesão orgânica e morte. Nos últimos trinta anos, pacientes com sobrecarga de ferro transfusional dependem de infusões noturnas de desferroxamina para quelação de ferro. Apesar da dramática melhora da expectativa de vida na era da desferroxamina para pacientes com anemias dependentes de transfusão, 50% dos pacientes com talassemia maior morrem antes dos 30 anos de idade, predominantemente devido à insuficiência cardíaca induzida pelo ferro. A difícil natureza desse tratamento com infusão subcutânea prolongada por meio de aparelho infusor portátil motivou o desenvolvimento de formas alternativas de tratamento que facilitasse a aderência do paciente. Estratégias para reduzir a sobrecarga de ferro e suas conseqüências, através da melhora dos regimes de quelação, foram as prioridades mais importantes nos últimos anos. Nesta revisão, descrevemos os avanços mais importantes da terapia quelante de ferro. Em particular, analisamos os dois quelantes de ferro ativos por via oral: deferiprona e o novo quelante de ferro oral deferasirox.Patients who are chronically dependent on transfusions will develop iron overload that leads to organ damage and eventually to death. For nearly 30 years, patients with transfusional iron overload have been subject to overnight deferoxamine infusions for iron chelation. Despite dramatic gains in terms of life expectancy in the deferoxamine era for patients with transfusion-dependent anemias, 50% of patients with thalassemia major die before the age of 35 years, predominantly due to iron-induced heart failure. The very demanding nature of this treatment with prolonged subcutaneous infusion via portable pump infusions has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. Strategies to reduce iron overload and its consequences by improving chelation

  8. Brain iron overload, insulin resistance, and cognitive performance in obese subjects: a preliminary MRI case-control study.

    Science.gov (United States)

    Blasco, Gerard; Puig, Josep; Daunis-I-Estadella, Josep; Molina, Xavier; Xifra, Gemma; Fernández-Aranda, Fernando; Pedraza, Salvador; Ricart, Wifredo; Portero-Otín, Manuel; Fernández-Real, José Manuel

    2014-11-01

    The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects. We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 ± 7.7 years; BMI 43.7 ± 4.48 kg/m2) and 20 healthy nonobese volunteers (10 women; age 48.8 ± 9.5 years; BMI 24.3 ± 3.54 kg/m2) in whom iron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance. A significant increase in iron load was detected at the caudate nucleus (P cognitive performance. Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.

    Science.gov (United States)

    Hua, Yanni; Wang, Chaomeng; Jiang, Huijuan; Wang, Yihao; Liu, Chunyan; Li, Lijuan; Liu, Hui; Shao, Zonghong; Fu, Rong

    2017-08-01

    The objective of the study was to examine levels of intracellular iron, reactive oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore potential mechanisms by which iron overload (IOL) promotes MDS progression. Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were included. HSPCs and NK cells were isolated by magnetic absorption cell sorting. We used flow cytometry to detect the levels of ROS and intracellular JNK and P38 in NK cells and HSPCs. Total RNA and protein were extracted from NK cells and CD34 + cells to examine the expression of JNK and p38MAPK using RT-PCR and Western blotting. Intracellular iron concentration was detected. Data were analyzed by SPSS 21 statistical software. Intracellular iron concentration and ROS were increased in both NK cells and HSPCs in MDS patients with iron overload (P overload had higher JNK expression and lower p38 expression in NK cells, and higher p38 expression in HSPCs compared with non-iron overload group. IOL may cause alterations in NK cells and HSPCs through the JNK and p38 pathways, and play a role in the transformation to AML from MDS.

  10. Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload.

    Science.gov (United States)

    Koehl, Bérengère; Missud, Florence; Holvoet, Laurent; Ithier, Ghislaine; Sakalian-Black, Oliver; Haouari, Zinedine; Lesprit, Emmanuelle; Baruchel, André; Benkerrou, Malika

    2017-03-14

    Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion. At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

  11. Al-hijamah and oral honey for treating thalassemia, conditions of iron overload, and hyperferremia: toward improving the therapeutic outcomes

    Science.gov (United States)

    El Sayed, Salah Mohamed; Baghdadi, Hussam; Abou-Taleb, Ashraf; Mahmoud, Hany Salah; Maria, Reham A; Ahmed, Nagwa S; Helmy Nabo, Manal Mohamed

    2014-01-01

    Iron overload causes iron deposition and accumulation in the liver, heart, skin, and other tissues resulting in serious tissue damages. Significant blood clearance from iron and ferritin using wet cupping therapy (WCT) has been reported. WCT is an excretory form of treatment that needs more research efforts. WCT is an available, safe, simple, economic, and time-saving outpatient modality of treatment that has no serious side effects. There are no serious limitations or precautions to discontinue WCT. Interestingly, WCT has solid scientific and medical bases (Taibah mechanism) that explain its effectiveness in treating many disease conditions differing in etiology and pathogenesis. WCT utilizes an excretory physiological principle (pressure-dependent excretion) that resembles excretion through renal glomerular filtration and abscess evacuation. WCT exhibits a percutaneous excretory function that clears blood (through fenestrated skin capillaries) and interstitial fluids from pathological substances without adding a metabolic or detoxification burden on the liver and the kidneys. Interestingly, WCT was reported to decrease serum ferritin (circulating iron stores) significantly by about 22.25% in healthy subjects (in one session) and to decrease serum iron significantly to the level of causing iron deficiency (in multiple sessions). WCT was reported to clear blood significantly of triglycerides, low-density lipoprotein (LDL) cholesterol, total cholesterol, uric acid, inflammatory mediators, and immunoglobulin antibodies (rheumatoid factor). Moreover, WCT was reported to enhance the natural immunity, potentiate pharmacological treatments, and to treat many different disease conditions. There are two distinct methods of WCT: traditional WCT and Al-hijamah (WCT of prophetic medicine). Both start and end with skin sterilization. In traditional WCT, there are two steps, skin scarification followed by suction using plastic cups (double S technique); Al-hijamah is a three

  12. Iron overload of human colon adenocarcinoma cells studied by synchrotron-based X-ray techniques

    NARCIS (Netherlands)

    Mihucz, Victor G.; Meirer, Florian; Polgári, Zsófia; Réti, Andrea; Pepponi, Giancarlo; Ingerle, Dieter; Szoboszlai, Norbert; Streli, Christina

    2016-01-01

    Fast- and slow-proliferating human adenocarcinoma colorectal cells, HT-29 and HCA-7, respectively, overloaded with transferrin (Tf), Fe(III) citrate, Fe(III) chloride and Fe(II) sulfate were studied by synchrotron radiation total-reflection X-ray spectrometry (TXRF), TXRF-X-ray absorption near edge

  13. Study of gonadal hormones in Egyptian female children with sickle cell anemia in correlation with iron overload: Single center study.

    Science.gov (United States)

    Hagag, Adel A; El-Farargy, Mohamed S; Elrefaey, Shaymaa; Abo El-enein, Amany M

    2016-03-01

    Sickle cell disease is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production, hemolytic anemia, and intermittent occlusion of small blood vessels, leading to tissue ischemia, chronic organ damage, and organ dysfunction including endocrine organs. The aim of this work was to evaluate some gonadal hormones in female children with sickle cell anemia (SCA) in correlation with iron overload. This study was conducted on 40 female children with SCA with a serum ferritin of > 1000ng/mL, who were attendants at the Hematology Unit, Pediatric Department, Tanta University, Tanta, Egypt in the period from May 2012 to April 2014. Their ages ranged from 11 years to 15years and the mean age value was 12.63±1.36 years (Group I). Forty female children with SCA of matched age with no iron overload served as a control Group (Group II). For all patients in Groups I and II the following were performed/assessed: complete blood count, hemoglobin electrophoresis, serum iron status, serum estrogen, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). There were significantly higher serum ferritin and serum iron levels and significantly lower total iron binding capacity, FSH, LH, and estrogen levels in Group I compared with Group II (mean serum ferritin was 2635.1±918.9 in Group I vs. 292.55±107.2 in Group II with a p value of .001; mean serum iron was 196.3±55.6 in Group I vs. 120±16.57 in Group II with a p value of .001 and mean serum total iron binding capacity was 247.3±28.6 in Group I vs. 327.8.7±21.96 in Group II with a p value of .001; mean FSH level was 1.36±0.22mIU/mL in Group I vs. 2.64±0.81mIU/mL in Group II with a p value of .021; mean LH level was 0.11±0.006mIU/mL in Group I vs. 1.78±1.12mIU/mL in Group II with a p value of .003; mean estrogen level was 21.45±10.23pg/mL in Group I vs. 42.36±15.44pg/mL in Group II with a p value of 0.001) with significant negative correlation between serum gonadal hormones and serum ferritin (r

  14. Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

    DEFF Research Database (Denmark)

    Milman, N.; Byg, K.E.; Ovesen, Lars

    2003-01-01

    Background and objectives: From 1954 to 1986, flour in Denmark was fortified with 30 mg carbonyl iron per kilogram. This mandatory enrichment of cereal products was abolished in 1987. The aim was to evaluate iron status in the Danish female population before and after abolishment of iron...... fortification. Methods: Iron status, serum ferritin and haemoglobin, was assessed in population surveys in 1983-1984 comprising 1221 Caucasian women (1089 non-blood-donors, 130 donors) and in 1993-1994 comprising 1261 women (1155 non-blood-donors, 104 donors) equally distributed in age cohorts of 40, 50, 60......, postmenopausal women had median ferritin of 75 mug/L and in 1994 of 93 mug/L (P iron stores (ferritin iron stores (ferritin less...

  15. Comparison of Deferasirox and deferoxamine treatment in iron-overloaded patients: liver iron concentration determined by quantitative MRI-R_2"*

    International Nuclear Information System (INIS)

    Peng Peng; Long Liling; Huang Zhongkui; Zhang Ling; Feng Xiao; Li Xiaohui; Yang Gaohui

    2013-01-01

    Objective: To explore the value of MRI-R_2"* and to compare clinical effect of two iron chelators (Deferasirox and deferoxamine) in iron-overloaded patients. Methods: By completely randomized balanced design, 24 iron-overloaded patients were randomly divided into 2 groups, which consisted of 12 patients treated with Deferasirox and 12 patients treated with deferoxamine. The planned Deferasirox dose was 40 mg · kg"-"1 · d"-"1, and the deferoxamine dose was no less than 50 mg · kg"-"1 · d"-"1. All patients underwent quantitative MRI at the time points of the primary screening, 6 months and 12 months. Pair Wilcoxon rank sum test was used to compare the differences of liver R_2"* values of the 2 groups at various time points respectively. Wilcoxon rank sum test was used to compare the differences of change rate of liver R_2"* values between the two groups at the time point of 6 months, 12 months, respectively. Results: Deferasirox group's liver R_2"* values of primary screening, 6 months and 12 months were 1081, 889 and 712 Hz, while deferoxamine group's liver R_2"* values were 1042, 838 and 488 Hz. There was no statistically significant difference between liver R_2"* values of two groups at primary screening (Z = -0.029, P > 0.05). The change rate of liver R_2"* of Deferasirox group at 12 month was -32%, while it was -58% for the deferoxamine group, and there was statistically significant difference between the two groups (Z = -3.060, P < 0.01). The change rate of serum ferritin of Deferasirox group at 12 month was -15%, while it was -55% for the deferoxamine group, and there was statistically significant difference between the two groups (Z = -2.945, P < 0.01). Conclusion: By using MRI-R_2"*, it suggest that both Deferasirox and deferoxamine can effectively remove liver iron and deferoxamine is superior to Deferasirox. (authors)

  16. Treating iron overload in patients with non-transfusion-dependent thalassemia

    Science.gov (United States)

    Taher, Ali T; Viprakasit, Vip; Musallam, Khaled M; Cappellini, M Domenica

    2013-01-01

    Despite receiving no or only occasional blood transfusions, patients with non-transfusion-dependent thalassemia (NTDT) have increased intestinal iron absorption and can accumulate iron to levels comparable with transfusion-dependent patients. This iron accumulation occurs more slowly in NTDT patients compared to transfusion-dependent thalassemia patients, and complications do not arise until later in life. It remains crucial for these patients' health to monitor and appropriately treat their iron burden. Based on recent data, including a randomized clinical trial on iron chelation in NTDT, a simple iron chelation treatment algorithm is presented to assist physicians with monitoring iron burden and initiating chelation therapy in this group of patients. Am. J. Hematol. 88:409–415, 2013. © 2013 Wiley Periodicals, Inc. PMID:23475638

  17. Diagnostic value of real-time elastography in the assessment of hepatic fibrosis in patients with liver iron overload

    International Nuclear Information System (INIS)

    Paparo, Francesco; Cevasco, Luca; Zefiro, Daniele; Biscaldi, Ennio; Bacigalupo, Lorenzo; Balocco, Manuela; Pongiglione, Marta; Banderali, Simone; Forni, Gian Luca; Rollandi, Gian Andrea

    2013-01-01

    Objective: The objective of our prospective monocentric work was to determine the diagnostic value of real-time elastography (RTE) in the assessment of liver fibrosis in patients with iron overload, using transient elastography (TE) as reference standard. Methods: Sixty-seven consecutive patients with MRI detectable iron overload (T2* < 6.3 ms) were enrolled. TE and RTE were performed on the same day as MRI. Elastograms were acquired by an experienced operator and analyzed by calculating the elastic ratio between perihepatic soft tissues and liver parenchyma. An elliptical ROI of 1 cm 2 (Z 1 ) was positioned in the liver parenchyma and a smaller elliptical ROI of 2 mm 2 (Z 2 ) was positioned in a homogeneously soft (red) region of the diaphragm, which was considered as internal control to calculate the elastic ratio Z 2 /Z 1 . Results: Seven patients were excluded because of invalid TE or RTE examinations. The remaining 60 patients were 57% males and 43% females (mean age: 42 [21–76] years), including 37 homozygous-β-thalassemics, 13 patients with β-thalassemia intermedia, 6 with primary hemochromatosis, and 4 with myelodysplastic syndrome. Increasing elastic ratios were significantly correlated with increasing TE values (r = 0.645, 95% CI 0.468–0.772, P < 0.0001). The mean elastic ratios for each METAVIR group were as follows: F0/1 = 1.9 ± 0.4; F2 = 2.2 ± 0.4; F3 = 2.9 ± 0.5; F4 = 3.2 ± 0.4. The diagnostic accuracy of RTE for F ≥ 2 evaluated by AUC-ROC analysis was 0.798 (95% CI 0.674–0.890). The diagnostic accuracy of RTE for F ≥ 3 was 0.909 (95% CI 0.806–0.968). At a cut-off ≥ 2.75, RTE showed a sensitivity of 70% (95% CI 45.7–88.1) and a specificity of 97.5% (95% CI 86.8–99.9). Conclusions: In patients with MRI-detectable liver iron-overload RTE allows to discriminate between F0/1–F2 and F3–F4 with a reasonable diagnostic accuracy

  18. Diagnostic value of real-time elastography in the assessment of hepatic fibrosis in patients with liver iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Paparo, Francesco [Department of Radiology, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy); Cevasco, Luca [School of Radiology, University of Genoa, Via Leon Battista Alberti 4, 16132 Genoa (Italy); Zefiro, Daniele [Medical Physics Department, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy); Biscaldi, Ennio; Bacigalupo, Lorenzo [Department of Radiology, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy); Balocco, Manuela [Unit of Microcitemia and Hereditary Anaemias, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy); Pongiglione, Marta; Banderali, Simone [Department of Radiology, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy); Forni, Gian Luca [Unit of Microcitemia and Hereditary Anaemias, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy); Rollandi, Gian Andrea, E-mail: gian.andrea.rollandi@galliera.it [Department of Radiology, E.O. Ospedali Galliera, Mura della Cappuccine 14, 16128 Genoa (Italy)

    2013-12-01

    Objective: The objective of our prospective monocentric work was to determine the diagnostic value of real-time elastography (RTE) in the assessment of liver fibrosis in patients with iron overload, using transient elastography (TE) as reference standard. Methods: Sixty-seven consecutive patients with MRI detectable iron overload (T2* < 6.3 ms) were enrolled. TE and RTE were performed on the same day as MRI. Elastograms were acquired by an experienced operator and analyzed by calculating the elastic ratio between perihepatic soft tissues and liver parenchyma. An elliptical ROI of 1 cm{sup 2} (Z{sub 1}) was positioned in the liver parenchyma and a smaller elliptical ROI of 2 mm{sup 2} (Z{sub 2}) was positioned in a homogeneously soft (red) region of the diaphragm, which was considered as internal control to calculate the elastic ratio Z{sub 2}/Z{sub 1}. Results: Seven patients were excluded because of invalid TE or RTE examinations. The remaining 60 patients were 57% males and 43% females (mean age: 42 [21–76] years), including 37 homozygous-β-thalassemics, 13 patients with β-thalassemia intermedia, 6 with primary hemochromatosis, and 4 with myelodysplastic syndrome. Increasing elastic ratios were significantly correlated with increasing TE values (r = 0.645, 95% CI 0.468–0.772, P < 0.0001). The mean elastic ratios for each METAVIR group were as follows: F0/1 = 1.9 ± 0.4; F2 = 2.2 ± 0.4; F3 = 2.9 ± 0.5; F4 = 3.2 ± 0.4. The diagnostic accuracy of RTE for F ≥ 2 evaluated by AUC-ROC analysis was 0.798 (95% CI 0.674–0.890). The diagnostic accuracy of RTE for F ≥ 3 was 0.909 (95% CI 0.806–0.968). At a cut-off ≥ 2.75, RTE showed a sensitivity of 70% (95% CI 45.7–88.1) and a specificity of 97.5% (95% CI 86.8–99.9). Conclusions: In patients with MRI-detectable liver iron-overload RTE allows to discriminate between F0/1–F2 and F3–F4 with a reasonable diagnostic accuracy.

  19. Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients

    Directory of Open Access Journals (Sweden)

    Yunus Kasım Terzi

    2016-12-01

    Full Text Available Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. Materials and Methods: This is a prospective single-center crosssectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31 was receiving chelation therapy and the second group (group B, n=13 was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. Results: p.H63D mutation was detected in 10 (32.3% patients in group A and in only 1 patient (7.7% in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046. In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05. Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.

  20. Relationship between elevated liver enzyme with iron overload and viralhepatitis in thalassemia major patients in Northern Iran

    International Nuclear Information System (INIS)

    Ameli, M.; Besharati, S.; Nemati, K.; Zamani, F.

    2008-01-01

    Objective was to determine the relationship between elevated liverenzymes with iron overload and viral hepatitis in thalassemia patients. Thisdescriptive cross-sectional study was carried out in the thalassemic ward ofTonekabon Hospital, Mazandaran, Northern Iran from 20 April to 20 Septemberof 2006. Patients were studied with respect to age, liver enzymes,anti-hepatitis C virus (anti-HCV) antibody and hepatitis B surface antigen(HBsAg), transferring saturation (TSAT)and blood transfusion index(multiplication of frequency and units of transfusion). Alanineaminotransferase (ALT) >=40 U/L was considered elevated. Sixty-five patientswere evaluated (median age 19.51+-8.9 years, range 4-54). Eleven patientswere anti-HCV positive (16.9%). The mean serum ferritin was significantlyhigher in patients with ALT>=40 (2553.08 ug/L versus 1783.7750 ug/L)(p=0.012). The mean ALT was significantly higher in patients with TSAT >=60%(41.26 U/L versus 28.82 U/L) (p=0.021). The relationship between ALT>=40 andanti-HCV positively was statistically significant. The mean ALT was 60.91 U/Lin anti-HCV positive patients and 39.29 U/L in the negative group (p=0.001).The mean serum iron and transfusion index were significantly higher inanti-HCV positive versus negative patients (234.0 versus 195.4815; p=0.02),(1693.6 versus 1036.29, p=0.014). Close association between elevated ALT withiron overload, transfusion index, age and anti-HCV positivity in thalassemiapatients of Tonekabon is recommended to re-evaluate transfusion and Desferaldoses and therapies other than blood transfusion. (author)

  1. Al-hijamah and oral honey for treating thalassemia, conditions of iron overload, and hyperferremia: toward improving the therapeutic outcomes

    Directory of Open Access Journals (Sweden)

    El Sayed SM

    2014-10-01

    Full Text Available Salah Mohamed El Sayed,1,2 Hussam Baghdadi,2 Ashraf Abou-Taleb,3 Hany Salah Mahmoud,4 Reham A Maria,2,5 Nagwa S Ahmed,1 Manal Mohamed Helmy Nabo6,71Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt; 2Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia; 3Department of Pediatrics, Sohag Faculty of Medicine, Sohag University, Sohag; 4World Federation of Alternative and Complementary Medicine, Cairo Regional Headquarter, Cairo; 5Department of Medical Biochemistry, Tanta Faulty of Medicine, Tanta University, Tanta; 6Department of Pediatrics, Sohag Teaching Hospital, Sohag, Egypt; 7Division of Pediatric Cardiology, Department of Pediatrics, Maternity and Children Hospital, King Abdullah Medical City, Al-Madinah Al-Munawwarah, Kingdom of Saudi ArabiaAbstract: Iron overload causes iron deposition and accumulation in the liver, heart, skin, and other tissues resulting in serious tissue damages. Significant blood clearance from iron and ferritin using wet cupping therapy (WCT has been reported. WCT is an excretory form of treatment that needs more research efforts. WCT is an available, safe, simple, economic, and time-saving outpatient modality of treatment that has no serious side effects. There are no serious limitations or precautions to discontinue WCT. Interestingly, WCT has solid scientific and medical bases (Taibah mechanism that explain its effectiveness in treating many disease conditions differing in etiology and pathogenesis. WCT utilizes an excretory physiological principle (pressure-dependent excretion that resembles excretion through renal glomerular filtration and abscess evacuation. WCT exhibits a percutaneous excretory function that clears blood (through fenestrated skin capillaries and interstitial fluids from pathological substances without adding a metabolic or detoxification burden on the

  2. Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants.

    Science.gov (United States)

    Aguilar-Martinez, Patricia; Grandchamp, Bernard; Cunat, Séverine; Cadet, Estelle; Blanc, François; Nourrit, Marlène; Lassoued, Kaiss; Schved, Jean-François; Rochette, Jacques

    2011-04-01

    Heterozygotes for the p.Cys282Tyr (C282Y) mutation of the HFE gene do not usually express a hemochromatosis phenotype. Apart from the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele, other rare HFE mutations can be found in trans on chromosome 6. We performed molecular investigation of the genes implicated in hereditary hemochromatosis in six patients who presented with iron overload but were simple heterozygotes for the HFE C282Y mutation at first genetic testing. Functional impairment of new variants was deduced from computational methods including molecular modeling studies. We identified four rare HFE mutant alleles, three of which have not been previously described. One mutation is a 13-nucleotide deletion in exon 6 (c.1022_1034del13, p.His341_Ala345 > LeufsX119), which is predicted to lead to an elongated and unstable protein. The second one is a substitution of the last nucleotide of exon 2 (c.340G > A, p.Glu114Lys) which modifies the relative solvent accessibility in a loop interface. The third mutation, p.Arg67Cys, also lies in exon 2 and introduces a destabilization of the secondary structure within a loop of the α1 domain. We also found the previously reported c.548T > C (p.Leu183Pro) missense mutation in exon 3. No other known iron genes were mutated. We present an algorithm at the clinical and genetic levels for identifying patients deserving further investigation. Conclusions Our results suggest that additional mutations in HFE may have a clinical impact in C282Y carriers. In conjunction with results from previously described cases we conclude that an elevated transferrin saturation level and elevated hepatic iron index should indicate the utility of searching for further HFE mutations in C282Y heterozygotes prior to other iron gene studies.

  3. Reticulocyte Hemoglobin Content Helps Avoid Iron Overload in Hemodialysis Patients: A Retrospective Observational Study.

    Science.gov (United States)

    Capone, Domenico; Cataldi, Mauro; Vinciguerra, Mauro; Mosca, Teresa; Barretta, Salvatore; Ragosta, Annalisa; Sorrentino, Aniello; Vecchione, Alessandra; Barretta, Luca; Tarantino, Giovanni

    2017-01-01

    Anemia in patients suffering from end-stage renal failure is currently treated with Erythropoiesis-Stimulating Agents (ESA). This treatment needs sufficient iron supplementation to avoid an inadequate dosage of ESA. Nowadays modern analytical instruments allow to accurately calculate the content of Hemoglobin (Hb) in reticulocytes (CHr), that can be used as a guide for prescribing patients with the appropriate amount of iron. Patients, undergoing hemodialysis, were retrospectively selected from the database and were divided in two groups: group A received intravenous (IV) iron and subcutaneously ESA, and their dosages were adjusted on the basis of the following parameters: Hb, Mean corpuscular haemoglobin (MCH), CHr with consequent MCH/CHr ratio and reticulocyte count determined by the ADVIA 120 Hematology System of Siemens; group B patients were administered IV iron and ESA monitoring iron storage, Hb and ferritin. The aforementioned parameters and the administered amount of iron and ESA were monitored at baseline, four and eight months from the begining of the study. For ESA supplementation, no difference was observed between the groups at the various observed times. Despite similar Hb levels, the patients of group A needed significant lower doses of IV iron (-57.8%) avoiding risks of organ toxicity and obtaining consequent cost saving of nearly 1 €/patient/month. The use of CHr and its related parameters allows the avoidance of overdosage of IV iron, which can potentially damage organs, and the reduction of health care direct and indirect costs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Hepatic magnetic resonance imaging with T2* mapping of ovariectomized rats: correlation between iron overload and postmenopausal osteoporosis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lingshan; Peng, Xingui; Wang, Yuancheng; Wang, Yaling; Chen, Min; Wang, Qi; Jin, Jiyang [Zhongda Hospital of Southeast University, Department of Radiology, Nanjing (China); Zhu, Zhengqiu [Zhongda Hospital of Southeast University, Department of Endocrinology, Nanjing (China)

    2014-07-15

    To explore the correlation between liver iron overload and bone mineral density (BMD) in an ovariectomy (OVX) rat model, using liver magnetic resonance (MR)-T2* and dual-energy X-ray absorptiometry (DEXA). Sprague-Dawley rats received deferoxamine (DFO) or phosphate-buffered saline 3 months after bilateral OVX. MRI and DEXA were performed pre- and postoperatively. Five rats per group were killed every month for micro-CT, histopathology and biochemical examinations. Statistical analysis was performed with independent-samples t tests, box plots and Pearson's correlation analysis. At 2 months postoperatively, BMD was significantly lower in the OVX group than in the control group (P < 0.01), corresponding to the increased serum ferritin concentration (SFC; P < 0.01) and liver iron concentration (LIC; P < 0.01). Liver T2* values significantly differed between the two groups at 1 month postoperatively (P < 0.001) and improved 1 month after DFO injection (P < 0.05). These values were significantly and positively correlated with BMD in the control (r = 0.527, P < 0.001) and OVX (r = 0.456, P < 0.001) groups. Liver MRI T2* changed markedly earlier than BMD, LIC and SFC, and correlated well with osteoporosis; it may thus be a valuable early indicator of osteoporosis. (orig.)

  5. Diagnosis of iron overload and heart disease by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    J.C. Wood

    2011-12-01

    Full Text Available The use of Magnetic resonance imaging (MRI to estimate tissue iron was initiated nearly three decades ago but has only become a practical reality in the last ten years. MRI is most often used to estimate hepatic and cardiac iron in patients with thalassemia or sickle cell disease and has largely replaced liver biopsy for liver iron quantification. The ability of MRI to image extra hepatic organs has really transformed our understanding of iron mediated toxicity in transfusional siderosis. For decades, iron cardiomyopathy was the leading cause of death in thalassemia major, but it is now relatively rare in centers with regular MRI screening. Early recognition of cardiac iron loading allows more gentle modifications of iron chelation therapy prior to life threatening organ dysfunction. Serial MRI evaluations have demonstrated differential kinetics of uptake and clearance among the difference organs of the body. Although elevated serum ferritin and liver iron concentration increase the risk of cardiac and endocrine toxicities, extra hepatic iron deposition and toxicity occurs in many patients despite having low total body iron stores; there is no safe liver iron level in chronically transfused patients. Instead, the type, dose, and pattern of iron chelation therapy all contribute to whether cardiac iron accumulation will occur. These observations, coupled with the advent of increasing options for iron chelation therapy, are allowing clinicians to more appropriately tailor chelation therapy to individual patient needs, producing greater efficacy with fewer toxicities. With the decline in cardiac mortality, future frontiers in MRI monitoring including better prevention of endocrine toxicities, particularly hypogonadotropic hypogonadism and diabetes. These organs also serve as early warning signals for inadequate control of non-transferrin bound iron, a risk factor for cardiac iron loading. Thus MRI assessment of extra hepatic iron stores is a

  6. Analysis of overload conditions in distance relay under severe system contingencies

    Energy Technology Data Exchange (ETDEWEB)

    Halim Abu Bakar, Ab. [Department of Electrical Engineering, Universiti Malaya (Malaysia); Yatim, Fazilah Mat; Othman, Mohd Ridzal [Transmission Division, Tenaga Nasional Berhad (Malaysia); Yusof, Sallehuddin [Advanced Powor Solutions (Malaysia)

    2010-06-15

    Distance relay protection is widely used worldwide for protection scheme on high voltage transmission lines. This protection tends to be prone to load encroachment condition causing possible undesired tripping condition. Investigations of two system disturbances that occurred in TNB's (Tenaga Nasional Berhad) Grid in the year 2003 and 2005 have clearly revealed the occurrence of load encroachment condition following line overloads after large number of line tripping. Examination of the impedance locus trajectory during the overload events have enabled a distinction be made between power swing and load encroachment phenomena. This paper presents the analysis and findings of the investigation of the load encroachment phenomena of the two events, including other related transmission line contingencies. (author)

  7. Terapia quelante oral com deferiprona em pacientes com sobrecarga de ferro Oral iron chelator therapy with deferiprone in patients with overloaded iron

    Directory of Open Access Journals (Sweden)

    Antonio Fabron Jr

    2003-01-01

    . For these patients, the orally active iron chelator deferiprone is an attractive alternative to control the overloaded iron. It has been estimated that more than six thousands patients have already been treated with deferiprone, with some of them taking the chelator for 10 years or more. The deferiprone-induced iron excretion is directly related to the dose of deferiprone and the patient's iron load. In most of transfusion-dependent patients, a dose of 75 mg/kg/day is sufficient to offset the transfusional iron-load. Recently, it has been demonstrated that desferrioxamine and deferiprone exhibit different chelating capabilities for the removal of iron from the various body iron pools and that the use of both chelators promote an additive or synergistic iron excretion with rapid reduction in the body iron load. It now is possible to consider tailor-made chelation regimens based on individual patient needs.

  8. Study of the effect of HFE gene mutations on iron overload in ...

    African Journals Online (AJOL)

    Background: HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in β-thalassemia patients and carriers remains controversial. Objectives: We aimed to determine the prevalence of HFE gene mutations (C282Y and H63D) in β-thalassemia patients and carriers ...

  9. Two kinds of ferritin protect ixodid ticks from iron overload and consequent oxidative stress.

    Directory of Open Access Journals (Sweden)

    Remil Linggatong Galay

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

  10. Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with β-thalassemia major.

    Science.gov (United States)

    Mirlohi, Maryam Sadat; Yaghooti, Hamid; Shirali, Saeed; Aminasnafi, Ali; Olapour, Samaneh

    2018-04-01

    The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

  11. Iron supplementation decreases severity of allergic inflammation in murine lung.

    Directory of Open Access Journals (Sweden)

    Laura P Hale

    Full Text Available The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans.

  12. Effects of acute dietary iron overload in pigs (Sus scrofa) with induced type 2 diabetes mellitus.

    Science.gov (United States)

    Espinoza, A; Morales, S; Arredondo, M

    2014-06-01

    Epidemiological studies have reported an association between high iron (Fe) levels and elevated risk of developing type 2 diabetes mellitus (T2D). It is believed that the formation of Fe-catalyzed hydroxyl radicals may contribute to the development of diabetes. Our goal was to determine the effect of a diet with a high Fe content on type 2 diabetic pigs. Four groups of piglets were studied: (1) control group, basal diet; (2) Fe group, basal diet with 3,000 ppm ferrous sulfate; (3) diabetic group (streptozotocin-induced type 2 diabetes) with basal diet; (4) diabetic/Fe group, diabetic animals/3,000 ppm ferrous sulfate. For 2 months, biochemical and hematological parameters were evaluated. Tissue samples of liver and duodenum were obtained to determine mRNA relative abundance of DMT1, ferroportin (Fpn), ferritin (Fn), hepcidin (Hpc), and transferrin receptor by qRT-PCR. Fe group presented increased levels of hematological (erythrocytes, hematocrit, and hemoglobin) and iron parameters. Diabetic/Fe group showed similar behavior as Fe group but in lesser extent. The relative abundance of different genes in the four study groups yielded a different expression pattern. DMT1 showed a lower expression in the two iron groups compared with control and diabetic animals, and Hpc showed an increased on its expression in Fe and diabetic/Fe groups. Diabetic/Fe group presents greater expression of Fn and Fpn. These results suggest that there is an interaction between Fe nutrition, inflammation, and oxidative stress in the diabetes development.

  13. Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument.

    Science.gov (United States)

    Rofail, Diana; Abetz, Linda; Viala, Muriel; Gait, Claire; Baladi, Jean-Francois; Payne, Krista

    2009-01-01

    This study assesses satisfaction with iron chelation therapy (ICT) based on a reliable and valid instrument, and explores the relationship between satisfaction and adherence to ICT. Patients in the USA and UK completed a new "Satisfaction with ICT" (SICT) instrument consisting of 28 items, three pertaining to adherence. Simple and multivariate regression analyses assessed the relationship between satisfaction with different aspects of ICT and adherence. First assessments of the SICT instrument indicate its validity and reliability. Recommended thresholds for internal consistency, convergent validity, discriminant validity, and floor and ceiling effects were met. A number of variables were identified in the simple linear regression analyses as significant predictors of "never thinking about stopping ICT," a proxy for adherence. These significant variables were entered into the multivariate model to assess the combined factor effects, explaining 42% of the total variance of "never thinking about stopping ICT." A significant and positive relationship was demonstrated between "never thinking about stopping ICT" and age (P = 0.04), Perceived Effectiveness of ICT (P = 0.003), low Burden of ICT (P = 0.002), and low Side Effects of ICT (P = 0.01). The SICT is a reliable and valid instrument which will be useful in ICT clinical trials. Furthermore, the administration of ICT by slow subcutaneous infusion negatively impacts on satisfaction with ICT which was shown to be a determinant of adherence. This points to the need for new more convenient and less burdensome oral iron chelators to increase adherence, and ultimately to improve patient outcomes.

  14. Radial Ultrashort TE Imaging Removes the Need for Breath-Holding in Hepatic Iron Overload Quantification by R2* MRI.

    Science.gov (United States)

    Tipirneni-Sajja, Aaryani; Krafft, Axel J; McCarville, M Beth; Loeffler, Ralf B; Song, Ruitian; Hankins, Jane S; Hillenbrand, Claudia M

    2017-07-01

    The objective of this study is to evaluate radial free-breathing (FB) multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron content (HIC) in sedated patients and subjects unable to perform breath-hold (BH) maneuvers. FB multiecho GRE imaging and FB multiecho UTE imaging were conducted for 46 test group patients with iron overload who could not complete BH maneuvers (38 patients were sedated, and eight were not sedated) and 16 control patients who could complete BH maneuvers. Control patients also underwent standard BH multiecho GRE imaging. Quantitative R2* maps were calculated, and mean liver R2* values and coefficients of variation (CVs) for different acquisitions and patient groups were compared using statistical analysis. FB multiecho GRE images displayed motion artifacts and significantly lower R2* values, compared with standard BH multiecho GRE images and FB multiecho UTE images in the control cohort and FB multiecho UTE images in the test cohort. In contrast, FB multiecho UTE images produced artifact-free R2* maps, and mean R2* values were not significantly different from those measured by BH multiecho GRE imaging. Motion artifacts on FB multiecho GRE images resulted in an R2* CV that was approximately twofold higher than the R2* CV from BH multiecho GRE imaging and FB multiecho UTE imaging. The R2* CV was relatively constant over the range of R2* values for FB multiecho UTE, but it increased with increases in R2* for FB multiecho GRE imaging, reflecting that motion artifacts had a stronger impact on R2* estimation with increasing iron burden. FB multiecho UTE imaging was less motion sensitive because of radial sampling, produced excellent image quality, and yielded accurate R2* estimates within the same acquisition time used for multiaveraged FB multiecho GRE imaging. Thus, FB multiecho UTE imaging is a viable alternative for accurate HIC assessment

  15. A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload.

    Science.gov (United States)

    Swoboda, Kathryn J; Margraf, Rebecca L; Carey, John C; Zhou, Holly; Newcomb, Tara M; Coonrod, Emily; Durtschi, Jacob; Mallempati, Kalyan; Kumanovics, Attila; Katz, Ben E; Voelkerding, Karl V; Opitz, John M

    2014-01-01

    Three related males presented with a newly recognized x-linked syndrome associated with neurodegeneration, cutaneous abnormalities, and systemic iron overload. Linkage studies demonstrated that they shared a haplotype on Xp21.3-Xp22.2 and exome sequencing was used to identify candidate variants. Of the segregating variants, only a PIGA mutation segregated with disease in the family. The c.328_330delCCT PIGA variant predicts, p.Leu110del (or c.1030_1032delCTT, p.Leu344del depending on the reference sequence). The unaffected great-grandfather shared his X allele with the proband but he did not have the PIGA mutation, indicating that the mutation arose de novo in his daughter. A single family with a germline PIGA mutation has been reported; affected males had a phenotype characterized by multiple congenital anomalies and severe neurologic impairment resulting in infantile lethality. In contrast, affected boys in the family described here were born without anomalies and were neurologically normal prior to onset of seizures after 6 months of age, with two surviving to the second decade. PIGA encodes an enzyme in the GPI anchor biosynthesis pathway. An affected individual in the family studied here was deficient in GPI anchor proteins on granulocytes but not erythrocytes. In conclusion, the PIGA mutation in this family likely causes a reduction in GPI anchor protein cell surface expression in various cell types, resulting in the observed pleiotropic phenotype involving central nervous system, skin, and iron metabolism. © 2013 Wiley Periodicals, Inc.

  16. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis.

    Science.gov (United States)

    Phatak, Pradyumna; Brissot, Pierre; Wurster, Mark; Adams, Paul C; Bonkovsky, Herbert L; Gross, John; Malfertheiner, Peter; McLaren, Gordon D; Niederau, Claus; Piperno, Alberto; Powell, Lawrie W; Russo, Mark W; Stoelzel, Ulrich; Stremmel, Wolfgang; Griffel, Louis; Lynch, Nicola; Zhang, Yiyun; Pietrangelo, Antonello

    2010-11-01

    Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥ 45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase > 3 × baseline and greater than the upper limit of normal range, and eight patients had serum creatinine > 33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to < 250 ng/mL. Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population.

  17. Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

    Science.gov (United States)

    Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

    2013-03-01

    Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

  18. Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study

    International Nuclear Information System (INIS)

    Argyropoulou, Maria I.; Astrakas, Loukas; Metafratzi, Zafiria; Efremidis, Stavros C.; Kiortsis, Dimitrios N.; Chalissos, Nikolaos

    2007-01-01

    Thirty-seven patients with β-thalassemia major, including 14 adolescents (15.2 ± 3.0 years) and 23 adults (26.4 ± 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 ± 15 ms) than in adults (45.3 ± 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 ± 10.3 ms) than in adults (54.4 ± 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62, P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. (orig.)

  19. Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I.; Astrakas, Loukas; Metafratzi, Zafiria; Efremidis, Stavros C. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios N. [University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece); Chalissos, Nikolaos [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece)

    2007-12-15

    Thirty-seven patients with {beta}-thalassemia major, including 14 adolescents (15.2 {+-} 3.0 years) and 23 adults (26.4 {+-} 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 {+-} 15 ms) than in adults (45.3 {+-} 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 {+-} 10.3 ms) than in adults (54.4 {+-} 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62, P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. (orig.)

  20. Can hydroxyurea serve as a free radical scavenger and reduce iron overload in β-thalassemia patients?

    Science.gov (United States)

    Italia, Khushnooma; Chandrakala, S; Ghosh, Kanjaksha; Colah, Roshan

    2016-09-01

    In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in β-thalassemia patients with iron overload. Twenty-one β-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5 g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194 ± 4850 ng/ml to 2129 ± 2380 ng/ml among the responders and from 2955 ± 2909 ng/ml to 2040 ± 2432 ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7 ± 10067.4 mean fluorescence intensity (MFI) to 14888.5 ± 5284.0 MFI among responders and from 17986.3 ± 9079.8 MFI to 15634.8 ± 8976.9 MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2 ± 22.2 MFI to 16.6 ± 6.7 MFI among the responders and from 46.9 ± 33.1 MFI to 39.8 ± 7.4 MFI among the non-responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8 ± 35.5 MFI to 29.0 ± 8.3 MFI among the responders and from 80.9 ± 41.4 MFI to 40.5 ± 15.8 MFI among the non-responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8 ± 201.1 MFI to 715.5 ± 292.4 MFI among the responders and from 359.6 ± 165.6 MFI to 450.3 ± 279.5 MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and

  1. Expression of Hepcidin and Growth Differentiation Factor 15 (GDF-15 Levels in Thalassemia Patients with Iron Overload and Positive Anti Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Nuri Dyah Indrasari

    2016-09-01

    Full Text Available Background: Thalassemia patients who undergo life-long recurrent blood transfusion will experience iron overload in various organs including the liver and possibly suffer from chronic hepatitis C infection which may lead to liver impairment. The liver produces hepcidin, a hormone which plays role in the regulation of iron level in the blood. Various factors may influence hepcidin level in the blood. Chronic hepatitis C causes iron overload and liver impairment. Liver impairment and haemolytic anaemia due to haemoglobinopathy will suppress hepcidin production. Anaemia stimulates growth differentiation factor 15 (GDF-15 to increase erythropoiesis and suppress hepcidin production. Iron overload causes increase in hepcidin level. Presence of factors which decrease or increase hepcidin production will express various levels of hepcidin. This study aimed to identify the expression of hepcidin and GDF-15 levels in thalassemia patients with iron overload and positive anti-HCV. Information on hepcidin and GDF-15 levels are beneficial in the management of iron overload in thalassemia with positive anti-HCV. Method: This study was a descriptive analytic study in thalassemia patients who had received recurrent blood transfusion ≥ 12 times, suffered from iron overload (transferrin saturation > 55% and ferritin > 1,000 ng/mL, which consisted of 31 individuals with positive anti-HCV and 27 individuals with negative anti-HCV. This study was performed in Thalassemia Centre Department of Child Health and Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, in October 2011–January 2012. Serum hepcidin and GDF-15 examinations were performed using enzyme-linked immunosorbent assay (ELISA method. Aspartate aminotransferase (AST and alanine aminotransferase (ALT examinations were performed using colorimetry method. Data on ferritin and transferrin saturation were obtained from medical records in the last 3

  2. Does Fat Suppression via Chemically Selective Saturation (CHESS) Affect R2*-MRI for Transfusional Iron Overload Assessment? A Clinical Evaluation at 1.5 and 3 Tesla

    Science.gov (United States)

    Krafft, Axel J.; Loeffler, Ralf B.; Song, Ruitian; Bian, Xiao; McCarville, M. Beth; Hankins, Jane S.; Hillenbrand, Claudia M.

    2015-01-01

    Purpose Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat-water oscillations in multi-echo gradient echo (mGRE) R2*-MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. Here, we investigate the effect of CHESS on R2* and describe a heuristic correction for the observed CHESS-induced R2* changes. Methods Eighty patients (49/31 female/male, mean age: 18.3±11.7 years) with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at 1.5T and 3T. Mean liver R2* values were evaluated using 3 published fitting approaches. Measured and model-corrected R2* values were compared and statistically analyzed. Results At 1.5T, CHESS led to a systematic R2* reduction (PCHESS-induced R2* bias after correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2* reductions were found at 3T. Conclusion The CHESS-induced R2* bias at 1.5T needs to be considered when applying R2*-LIC biopsy calibrations for clinical LIC assessment which were established without FS at 1.5T. The proposed model corrects the R2* bias and could therefore improve clinical iron overload assessment based on linear R2*-LIC calibrations. PMID:26308155

  3. Improved treatment satisfaction and convenience with deferasirox in iron-overloaded patients with beta-Thalassemia: Results from the ESCALATOR Trial.

    Science.gov (United States)

    Taher, Ali; Al Jefri, Abdullah; Elalfy, Mohsen Saleh; Al Zir, Kusai; Daar, Shahina; Rofail, Diana; Baladi, Jean François; Habr, Dany; Kriemler-Krahn, Ulrike; El-Beshlawy, Amal

    2010-01-01

    Patient-reported outcomes of once-daily oral deferasirox (Exjade) in iron-overloaded patients with beta-thalassemia not achieving successful chelation with prior deferoxamine and/or deferiprone were investigated in a prospective, open-label, 1-year, multicenter study in the Middle East (ESCALATOR). The initial dose of deferasirox was 20 mg/kg/day, with subsequent dose adjustments. At baseline and the end of study (EOS), patients (n = 237) completed a 5-point rating scale for treatment satisfaction and convenience, and recorded time lost to treatment. At EOS, 90.7% of patients were 'satisfied'/'very satisfied' with their iron chelation therapy (ICT) versus 23.2% at baseline. 92.8% (EOS) versus 21.5% (baseline) of patients considered their therapy to be 'convenient'/'very convenient'. Time lost to therapy for daily activities was substantially reduced (3.2 +/- 8.6 [mean +/- SD; EOS] vs. 30.1 +/- 44.2 [baseline] h/month). Patients reported greater satisfaction and convenience, and lower impact on daily activities, with deferasirox than with previous ICT. This may help improve adherence to lifelong ICT in iron-overloaded beta-thalassemia patients. 2010 S. Karger AG, Basel.

  4. Ratiometric measurements of adiponectin by mass spectrometry in bottlenose dolphins (Tursiops truncatus with iron overload reveal an association with insulin resistance and glucagon

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    2013-09-01

    Full Text Available High molecular weight (HMW adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus diagnosed with hemochromatosis (iron overload have higher levels of 2 h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n=4 and without (n=5 iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2 h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean ± S.D. at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91; however, percent unmodified adiponectin was significantly higher in post-prandial cases compared controls (30.0 ± 6.3 versus 17.0 ± 6.6%, respectively; p = 0.016. Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r = 0.999, p < 0.001, but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to HMW adiponectin reported for humans with

  5. Role of Three-Dimensional Speckle Tracking Echocardiography in the Quantification of Myocardial Iron Overload in Patients with Beta-Thalassemia Major.

    Science.gov (United States)

    Li, Shu-Juan; Hwang, Yu-Yan; Ha, Shau-Yin; Chan, Godfrey C F; Mok, Amanda S P; Wong, Sophia J; Cheung, Yiu-Fai

    2016-09-01

    The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* overload. Compared with controls, patients had significantly lower LV global 3D strain (P overload. The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia. © 2016, Wiley Periodicals, Inc.

  6. Work Overload.

    Science.gov (United States)

    Bateman, Thomas S.

    1980-01-01

    To investigate managerial use of work (or role) overload to increase productivity, the author studied 77 nonclerical white-collar employees and found that work overload had negative effects on productivity, supervisors' ratings, employee attitudes, job satisfaction, and health. He recommends ways for managers and employees to reduce work overload.…

  7. Relative iron "overload" in offspring of patients with type 2 diabetes mellitus: a new component in the conundrum of insulin resistance syndrome?

    Science.gov (United States)

    Psyrogiannis, Agathoklis; Kyriazopoulou, Venetsana; Symeonidis, Argiris; Leotsinidis, Michalis; Vagenakis, Apostolos G

    2003-01-01

    There are a few reports suggesting that subtle disturbances of iron metabolism are frequently found in patients with type 2 diabetes (DM2), but it is not known if these disturbances precede or accompany the diabetic state. We investigated the serum iron indices in 41 offspring of DM2 parents (group I) with normal glucose tolerance, and in 49 offspring whose parents had no history of DM2 and were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and blood pressure (group II). Serum iron, ferritin, total iron binding capacity (TIBC), transferrin saturation, serum triglycerides, cholesterol, Apo-B, high density lipoprotein (HDL) and glucose and insulin values during an oral glucose tolerance test were measured. Insulin resistance was assessed using the homeostasis model assessment (HOMA - Insuline resistence index-IRI). In comparison to controls (group II), the offspring of DM2 subjects (group I) had higher fasting serum triglycerides (mean +/- SD 2.25+/-2.08 vs. 1.6+/-0.8 mmol/L, pinsulin in the Area Under the Curve (204.7+/-140.8 v. 153.1 +/- 63.0 microU/ml, pinsulin resistance. Hence, the relative iron "overload" in offspring of type 2 diabetics is present along with insulin resistance and might worsen the hepatic insulin insensitivity already present in these patients.

  8. A time-cost augmented economic evaluation of oral deferasirox versus infusional deferoxamine [corrected] for patients with iron overload in South Korea.

    Science.gov (United States)

    Kim, Jinhyun; Kim, Younhee

    2009-01-01

    This study aims to conduct an economic evaluation of oral deferasirox (DSX) compared with infusional deferoxamine (DFO) in patients with transfusional iron overload. Depending on the methods for measuring time-cost and convenience associated with the mode of administration, either cost-utility analysis or cost-effectiveness analysis was undertaken. The difference in compliance rate between DSX and DFO was applied. Although the drug cost of DSX was US$124,070 higher than that of DFO (US$96,039 vs. US$220,199), all other costs were lower in patients with DSX than in patients with DFO. In the cost-utility analysis, DSX resulted in US$3197 savings with a gain of 2.63 quality-adjusted life-years per patient. The result of the cost-effectiveness analysis also showed that DSX dominated DFO. With a considerable improvement in convenience and injection time rather than efficacy, DSX is considered as a dominant therapy for patients with iron overload.

  9. HFE gene mutations in patients with primary iron overload: is there a significant improvement in molecular diagnosis yield with HFE sequencing?

    Science.gov (United States)

    Santos, Paulo C J L; Pereira, Alexandre C; Cançado, Rodolfo D; Schettert, Isolmar T; Sobreira, Tiago J P; Oliveira, Paulo S L; Hirata, Rosario D C; Hirata, Mario H; Figueiredo, Maria Stella; Chiattone, Carlos S; Krieger, Jose E; Guerra-Shinohara, Elvira M

    2010-12-15

    Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation>50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n=11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and β2-microglobulin (β2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion, screening of HFE through direct sequencing, as compared to p.C282Y/p.H63D genotyping, was not able to increase the molecular diagnosis yield of HH. The novel p.V256I mutation could not be implicated in the molecular basis of the HH phenotype, although its role cannot be completely excluded in HH-phenotype development. Our molecular modeling analysis can help in the analysis of novel, previously undescribed, HFE mutations. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Iron metabolism in mynah birds (Gracula religiosa) resembles human hereditary haemochromatosis

    NARCIS (Netherlands)

    Mete, A; Hendriks, HG; Klaren, PHM; Dorrestein, GM; van Dijk, JE; Marx, JJM

    2003-01-01

    Iron overload is a very frequent finding in several animal species and a genetic predisposition is suggested. In one of the most commonly reported species with susceptibility for iron overload ( mynah bird), it was recently shown that the cause of this pathophysiology is high uptake and retention of

  11. MyD88 Adaptor Protein Is Required for Appropriate Hepcidin Induction in Response to Dietary Iron Overload in Mice

    Directory of Open Access Journals (Sweden)

    Antonio Layoun

    2018-03-01

    Full Text Available Iron homeostasis is tightly regulated to provide virtually all cells in the body, particularly red blood cells, with this essential element while defending against its toxicity. The peptide hormone hepcidin is central to the control of the amount of iron absorbed from the diet and iron recycling from macrophages. Previously, we have shown that hepcidin induction in macrophages following Toll-like receptor (TLR stimulation depends on the presence of myeloid differentiation primary response gene 88 (MyD88. In this study, we analyzed the regulation of iron metabolism in MyD88−/− mice to further investigate MyD88 involvement in iron sensing and hepcidin induction. We show that mice lacking MyD88 accumulate significantly more iron in their livers than wild-type counterparts in response to dietary iron loading as they are unable to appropriately control hepcidin levels. The defect was associated with inappropriately low levels of Smad4 protein and Smad1/5/8 phosphorylation in liver samples found in the MyD88−/− mice compared to wild-type mice. In conclusion, our results reveal a previously unknown link between MyD88 and iron homeostasis, and provide new insights into the regulation of hepcidin through the iron-sensing pathway.

  12. Severe iron-deficiency anemia still an issue in toddlers.

    Science.gov (United States)

    Paoletti, Gabrielle; Bogen, Debra L; Ritchey, A Kim

    2014-12-01

    Chronic, severe iron-deficiency anemia (IDA) in the first years of life increases the risk of irreversibly compromised cognitive, affective, and motor development. While IDA in infants has decreased because of dietary changes (iron-fortified formula and delaying cow's milk), toddlers (13-36 months) are equally vulnerable to the adverse effects of IDA. We aimed to show that despite public health efforts, severe IDA remains a problem in toddlers and is associated with excess milk consumption. Retrospective chart review of children 6 to 36 months admitted to or evaluated by hematology at a children's hospital from January 1, 2005 to December 31, 2010 with a severe microcytic anemia (hemoglobin [Hb] appetite, and pica were the most common symptoms, found in 43%, 29%, and 22% of patients, respectively. Only 41% of parents reported pale skin while 77% of physicians recorded it on physical exam. Daily cow's milk consumption surpassed 24 ounces for 47 of 48 children with reported intake; 11 consumed more than 64 ounces per day. Despite current screening recommendations, severe IDA continues to be a problem in toddlers and strongly correlates with excess cow's milk consumption. This reiterates the importance of screening for IDA into routine toddler care. © The Author(s) 2014.

  13. Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors

    Directory of Open Access Journals (Sweden)

    Nattiya Teawtrakul

    2015-10-01

    Conclusion: The prevalence of bacterial infection in patients with NTDT was found to be moderate. Time after splenectomy >10 years, deferoxamine therapy, and iron overload may be clinical risk factors for severe bacterial infection in patients with NTDT. Bacterial infection should be recognized in splenectomized patients with NTDT, particularly those who have an iron overload.

  14. Assessment and management of iron overload in β-thalassaemia major patients during the 21st century: a real-life experience from the Italian WEBTHAL project.

    Science.gov (United States)

    Piga, Antonio; Longo, Filomena; Musallam, Khaled M; Cappellini, Maria Domenica; Forni, Gian Luca; Quarta, Giovanni; Chiavilli, Francesco; Commendatore, Francesca; Mulas, Sergio; Caruso, Vincenzo; Galanello, Renzo

    2013-06-01

    We conducted a cross-sectional study on 924 β-thalassaemia major patients (mean age 30·1 years) treated at nine Italian centres using the WEBTHAL software, to evaluate real-life application of iron overload assessment and management standards. Serum ferritin 2 years. Patients who never had a cardiac MRI (CMR) T2* measurement were 2 years. Deferoxamine (22·8%) was more commonly used in patients with Hepatitis C Virus or high serum creatinine. Deferiprone (20·6%) was less commonly prescribed in patients with elevated alanine aminotransferase; while a deferoxamine + deferiprone combination (17·9%) was more commonly used in patients with serum ferritin >2500 ng/ml or CMR T2* <20 ms. Deferasirox (38·3%) was more commonly prescribed in patients <18 years, but less commonly used in those with heart disease or high iron intake. These observations largely echoed guidelines at the time, although some practices are expected to change in light of evolving evidence. © 2013 John Wiley & Sons Ltd.

  15. Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

    Directory of Open Access Journals (Sweden)

    Caro J

    2002-11-01

    Full Text Available Abstract Background Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. Methods The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using χ2. Results Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4. The degree of improvement was also larger with desferrioxamine. Conclusions This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis – despite its limitations – should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients.

  16. Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Fader, Kelly A.; Nault, Rance [Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Kirby, Mathew P.; Markous, Gena [Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Matthews, Jason [Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo 0316 (Norway); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States)

    2017-04-15

    Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01–30 μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4 days for 28 days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses. TCDD dose-dependently repressed hepatic expression of hepcidin (Hamp and Hamp2), the master regulator of systemic Fe homeostasis, resulting in a 2.6-fold increase in serum Fe with accumulating Fe spilling into urine. Total hepatic Fe levels were negligibly increased while transferrin saturation remained unchanged. Furthermore, TCDD elicited dose-dependent gene expression changes in heme biosynthesis including the induction of aminolevulinic acid synthase 1 (Alas1) and repression of uroporphyrinogen decarboxylase (Urod), leading to a 50% increase in hepatic hemin and a 13.2-fold increase in total urinary porphyrins. Consistent with this heme accumulation, differential gene expression suggests that heme activated BACH1 and REV-ERBα/β, causing induction of heme oxygenase 1 (Hmox1) and repression of fatty acid biosynthesis, respectively. Collectively, these results suggest that Hamp repression, Fe accumulation, and increased heme levels converge to promote oxidative stress and the progression of TCDD-elicited hepatotoxicity. - Highlights: • TCDD represses hepatic hepcidin expression, leading to systemic iron overloading. • Dysregulation of heme biosynthesis is consistent with heme and porphyrin accumulation. • Heme-activated REV-ERBα/β repress circadian-regulated hepatic lipid metabolism. • Disruption of iron

  17. Role of Cardiovascular Disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation

    Science.gov (United States)

    Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-ove...

  18. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

    DEFF Research Database (Denmark)

    Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della

    2010-01-01

    The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500ng/mL, approximately 50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether...

  19. Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease

    International Nuclear Information System (INIS)

    Ackerman, Z.; Seidenbaum, M.; Loewenthal, E.; Rubinow, A.

    1988-01-01

    The brown pigmentation of the skin associated with venous ulceration is caused by increased local iron deposition. Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for the noninvasive determination of iron levels in the skin of patients with venous ulceration. The mean (+/- SEM) iron concentration in the skin around the venous ulcer was elevated, compared with control values of nonulcerated skin (250 +/- 54 vs 128 +/- 39 micrograms) and compared with normal skin from the forearm (250 +/- 54 vs 14 +/- 2.5 micrograms). These data suggest that dermal iron deposition may not be an incidental by-product of increased venous pressure, but may actively perpetuate tissue damage in venous ulcerations

  20. RF plasma nitriding of severely deformed iron-based alloys

    International Nuclear Information System (INIS)

    Ferkel, H.; Glatzer, M.; Estrin, Y.; Valiev, R.Z.; Blawert, C.; Mordike, B.L.

    2003-01-01

    The effect of severe plastic deformation by cold high pressure torsion (HPT) on radio frequency (RF) plasma nitriding of pure iron, as well as St2K50 and X5CrNi1810 steels was investigated. Nitriding was carried out for 3 h in a nitrogen atmosphere at a pressure of 10 -5 bar and temperatures of 350 and 400 deg. C. Nitrided specimens were analysed by scanning electron microscopy (SEM), X-ray diffraction and micro hardness measurements. It was found that HPT enhances the effect of nitriding leading almost to doubling of the thickness of the nitrided layer for pure iron and the high alloyed steel. The largest increase in hardness was observed when HPT was combined with RF plasma nitriding at 350 deg. C. In the case of pure iron, the X-ray diffraction spectra showed the formation of ε and γ' nitrides in the compound layer, with a preferential formation of γ' at the expense of the α-phase at the higher nitriding temperature. The corresponding surface hardness was up to 950 HV0.01. While the HPT-processed St2K50 exhibits both nitride phases after nitriding at 350 deg. C, only the γ'-phase was observed after nitriding at 400 deg. C. A surface hardness of up to 1050 HV0.01 was measured for this steel. The high alloyed steel X5CrNi1810 exhibited the highest increase in surface hardness when HPT was combined with nitriding at 350 deg. C. The surface hardness of this steel was greater than 1400 HV0.025. The XRD analyses indicate the formation of the expanded austenite (S-phase) in the surface layer as a result of RF plasma nitriding. Furthermore, after HPT X5CrNi1810 was transformed completely into deformation martensite which did not transform back to austenite under thermochemical treatment. However, in the case of nitriding of the HPT-processed high alloyed steel at 400 deg. C, the formation of the S-phase was less pronounced. In view of the observed XRD peak broadening, the formation of nitrides, such as e.g. CrN, cannot be ruled out

  1. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia.

    Science.gov (United States)

    Cappellini, Maria Domenica; Bejaoui, Mohamed; Agaoglu, Leyla; Porter, John; Coates, Thomas; Jeng, Michael; Lai, Maria Eliana; Mangiagli, Antonio; Strauss, Gabriele; Girot, Robert; Watman, Nora; Ferster, Alina; Loggetto, Sandra; Abish, Sharon; Cario, Holger; Zoumbos, Nicolaos; Vichinsky, Elliott; Opitz, Herbert; Ressayre-Djaffer, Catherine; Abetz, Linda; Rofail, Diana; Baladi, Jean-Francois

    2007-05-01

    Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries. This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670). PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication

  2. DFT investigation on the selective complexation of Fe3+ and Al3+ with hydroxypyridinones used for treatment of the aluminium and iron overload diseases.

    Science.gov (United States)

    Kaviani, Sadegh; Izadyar, Mohammad; Housaindokht, Mohammad Reza

    2018-03-01

    The chelating agents for Al 3+ and Fe 3+ metal cations with therapeutic applications have been considered in the recent years. In designing of the hydroxypyridinones (HPOs) as the therapeutic chelating agents for iron and aluminium overload pathologies, quantum mechanical (QM) calculations are necessary for predicting the binding energies and thermodynamic parameters of the metal-HPO complexes. Three derivatives of the HPOs called 3-hydroxy-1,2-dimethylpyridin-4(1H)-one (DFP), 3-hydroxy-4(1H)-pyridinone (HOPO) and 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) were investigated for complexation with Fe 3+ and Al 3+ metal ions. Because of the maximum interaction between Fe 3+ and HPOs, all HPOs form stable complexes with Fe 3+ metal ion. Moreover, it was found that [Fe-P1] 2+ is a more stable complex than [Fe-DFP] 2+ and [Fe-3,4-HOPO] 2+ in the gas phase and water, confirming that P1 is the strongest selective iron chelator. The more stability of [Fe-P1] 2+ was attributed to an intramolecular hydrogen bond formation between the hydrogen atom of NH group and the oxygen atom of CH 2 OH chain. All complexes of the HPOs with Fe 3+ and Al 3+ were formed through the oxygen atoms of the CO and OH groups of the HPO. Natural bond orbital analysis showed that the interaction of the lone pair electrons of the oxygen atom of the chelator and antibonding orbitals of the Al 3+ and Fe 3+ are important in the complex formation. Topological parameters at the bond critical points confirmed the effective interaction between the Al 3+ and Fe 3+ metal ions and HPO as well as the nature of the metal-oxygen bonds. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial

    Directory of Open Access Journals (Sweden)

    John Porter

    2012-01-01

    Full Text Available Treatment of iron overload using deferoxamine (DFO is associated with significant deficits in patients' health-related quality of life (HRQOL and low treatment satisfaction. The current article presents patient-reported HRQOL, satisfaction, adherence, and persistence data from β-thalassemia (n=274 and myelodysplastic syndrome (MDS patients (n=168 patients participating in the Evaluation of Patients' Iron Chelation with Exjade (EPIC study (NCT00171821; a large-scale 1-year, phase IIIb study investigating the efficacy and safety of the once-daily oral iron chelator, deferasirox. HRQOL and satisfaction, adherence, and persistence to iron chelation therapy (ICT data were collected at baseline and end of study using the Medical Outcomes Short-Form 36-item Health Survey (SF-36v2 and the Satisfaction with ICT Questionnaire (SICT. Compared to age-matched norms, β-thalassemia and MDS patients reported lower SF-36 domain scores at baseline. Low levels of treatment satisfaction, adherence, and persistence were also observed. HRQOL improved following treatment with deferasirox, particularly among β-thalassemia patients. Furthermore, patients reported high levels of satisfaction with deferasirox at end of study and greater ICT adherence, and persistence. Findings suggest deferasirox improves HRQOL, treatment satisfaction, adherence, and persistence with ICT in β-thalassemia and MDS patients. Improving such outcomes is an important long-term goal for patients with iron overload.

  4. Carriers of the Complex Allele HFE c.[187C>G;340+4T>C] Have Increased Risk of Iron Overload in São Miguel Island Population (Azores, Portugal).

    Science.gov (United States)

    Branco, Claudia C; Gomes, Cidália T; De Fez, Laura; Bulhões, Sara; Brilhante, Maria José; Pereirinha, Tânia; Cabral, Rita; Rego, Ana Catarina; Fraga, Cristina; Miguel, António G; Brasil, Gracinda; Macedo, Paula; Mota-Vieira, Luisa

    2015-01-01

    Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations- c.845G>A [p.Cys282Tyr], c.187C>G [p.His63Asp], and c.193A>T [p.Ser65Cys]. Results revealed that the family's HH pseudodominant pattern is due to consanguineous marriage of HFE-c.845G>A carriers, and to marriage with a genetically unrelated spouse that is a -c.187G carrier. Regarding unrelated patients, six were homozygous for c.845A, and three were c.845A/c.187G compound heterozygous. We then performed sequencing of HFE exons 2, 4, 5 and their intron-flanking regions. No other mutations were observed, but we identified the -c.340+4C [IVS2+4C] splice variant in 26 (74.3%) patients. Functionally, the c.340+4C may generate alternative splicing by HFE exon 2 skipping and consequently, a protein missing the α1-domain essential for HFE/ transferrin receptor-1 interactions. Finally, we investigated HFE mutations configuration with iron overload by determining haplotypes and genotypic profiles. Results evidenced that carriers of HFE-c.187G allele also carry -c.340+4C, suggesting in-cis configuration. This data is corroborated by the association analysis where carriers of the complex allele HFE-c.[187C>G;340+4T>C] have an increased iron overload risk (RR = 2.08, 95% CI = 1.40-2.94, poverload because they will produce two altered proteins--the p.63Asp [c.187G], and the protein lacking 88 amino acids encoded by exon 2. In summary, we provide evidence that the complex allele HFE-c.[187C>G;340+4T>C] has a role, as genetic predisposition factor, on iron overload in the S

  5. Correlation between T2* cardiovascular magnetic resonance with left ventricular function and mass in adolescent and adult major thalassemia patients with iron overload.

    Science.gov (United States)

    Djer, Mulyadi M; Anggriawan, Shirley L; Gatot, Djajadiman; Amalia, Pustika; Sastroasmoro, Sudigdo; Widjaja, Patricia

    2013-10-01

    to assess for a correlation between T2*CMR with LV function and mass in thalassemic patients with iron overload. a cross-sectional study on thalassemic patients was conducted between July and September 2010 at Cipto Mangunkusumo and Premier Hospitals, Jakarta, Indonesia. Clinical examinations, review of medical charts, electrocardiography, echocardiography, and T2*CMR were performed. Cardiac siderosis was measured by T2*CMR conduction time. Left ventricle diastolic and systolic functions, as well as LV mass index were measured using echocardiography. Correlations between T2*CMR and echocardiography findings, as well as serum ferritin were determined using Pearson's and Spearman's tests. thirty patients aged 13-41 years were enrolled, of whom two-thirds had -thalassemia major and one-third had HbE/-thalassemia. Diastolic dysfunction was identified in 8 patients, whereas systolic function was normal in all patients. Increased LV mass index was found in 3 patients. T2*CMR conduction times ranged from 8.98 to 55.04 ms and a value below 20 ms was demonstrated in 14 patients. There was a statistically significant moderate positive correlation of T2*CMR conduction time with E/A ratio (r = 0.471, P = 0.009), but no correlation was found with LV mass index (r=0.097, P=0.608). A moderate negative correlation was found between T2*CMR and serum ferritin (r = -0.514, P = 0.004), while a moderate negative correlation was found between serum ferritin and E/A ratio (r = -0.425, P = 0.019). T2*CMR myocardial conduction time has a moderate positive correlation with diastolic function, moderate negative correlation with serum ferritin, but not with LV mass index and systolic function.

  6. HFE gene mutation and oxidative damage biomarkers in patients with myelodysplastic syndromes and its relation to transfusional iron overload: an observational cross-sectional study.

    Science.gov (United States)

    De Souza, Geane Felix; Ribeiro, Howard Lopes; De Sousa, Juliana Cordeiro; Heredia, Fabíola Fernandes; De Freitas, Rivelilson Mendes; Martins, Manoel Ricardo Alves; Gonçalves, Romélia Pinheiro; Pinheiro, Ronald Feitosa; Magalhães, Silvia Maria Meira

    2015-04-03

    A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated. An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011. IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry. The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions. We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress

  7. The role of T2*-weighted gradient echo in the diagnosis of tumefactive intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse hepatic iron overload: a case report and review of the literature.

    Science.gov (United States)

    Belay, Abel A; Bellizzi, Andrew M; Stolpen, Alan H

    2018-01-15

    Extramedullary hematopoiesis is the proliferation of hematopoietic cells outside bone marrow secondary to marrow hematopoiesis failure. Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in this case, imaging-based differentiation from primary and metastatic hepatic neoplasms is difficult, often leading to biopsy for definitive diagnosis. We report a case of tumefactive hepatic extramedullary hematopoiesis in the setting of myelodysplastic syndrome with concurrent hepatic iron overload, and the role of T2*-weighted gradient-echo magnetic resonance imaging in differentiating extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been previously described. A 52-year-old white man with myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic lesion on ultrasound during workup for bone marrow transplantation. Magnetic resonance imaging revealed diffuse hepatic iron overload and non-visualization of the lesion on T2* gradient-echo sequence suggesting the presence of iron deposition within the lesion similar to that in background hepatic parenchyma. Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary hematopoiesis. Six months later, while still being evaluated for bone marrow transplant, our patient was found to have poor pulmonary function tests. Follow-up computed tomography angiogram showed a mass within his right main pulmonary artery. Bronchoscopic biopsy of this mass once again revealed extramedullary hematopoiesis. He received radiation therapy to his chest. However, 2 weeks later, he developed mediastinal hematoma and died shortly afterward, secondary to respiratory arrest. Mass-forming extramedullary hematopoiesis is rare; however, our report emphasizes that it needs to be considered in the initial differential

  8. Iron overload in lower international prognostic scoring system risk patients with myelodysplastic syndrome receiving red blood cell transfusions: Relation to infections and possible benefit of iron chelation therapy.

    Science.gov (United States)

    Wong, Colleen A C; Wong, Shannon A Y; Leitch, Heather A

    2018-04-01

    An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). 138 transfused MDS patients were lower IPSS risk. 59 received ICT; median duration was 13 months. There was no significant difference between groups in neutrophil count at first RBC transfusion or first infection. Infections included: bacterial, n = 88; viral; fungal; and mycobacterial; n = 2 each. In ICT and non-ICT patients, respectively, infections were (number [%]): patients, 23 (40.0%) and 22 (27.8%); episodes (median [range]), 2 (1-6) and 2 (1-5); hospitalizations, 16 (27.1%) and 8 (10.1%); and deaths, 0 (0%) and 1 (1.3%), p = NS for all. Median overall survival (OS) from first RBC transfusion was superior in ICT patients, p = 0.01, and remained significant in a multivariate analysis (MVA), p = 0.003. Median time to first infection (TTI) was 27 and 7.8 months, respectively, p < 0.0001, and ICT remained significant for TTI in an MVA, p = 0.02, hazard ratio 0.3. For ICT patients with blast count <5%, TTI was significantly superior (p = 0.004). In this retrospective analysis, for lower IPSS risk MDS patients receiving RBC transfusions, though number and type of infections were similar between groups and despite similar neutrophil counts, time to first infection was significantly longer in ICT patients (p < 0.0001). These results should be confirmed in larger, prospective analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Role of glutaredoxin 3 in iron homeostasis

    Science.gov (United States)

    Iron is an essential mineral nutrient that is tightly regulated through mechanisms involving iron regulatory genes, intracellular storage, and iron recycling. Dysregulation of these mechanisms often results in either excess tissue iron accumulation (overload) or iron deficiency (anemia). Many bioche...

  10. Intravenous iron isomaltoside treatment of women suffering from severe fatigue after postpartum hemorrhage

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars L; Langhoff-Roos, Jens

    2018-01-01

    BACKGROUND AND OBJECTIVES: To explore if intravenous iron isomaltoside (Monofer®) leads to a better relief of fatigue than current treatment practice with oral iron in women suffering from severe fatigue after postpartum hemorrhage. MATERIALS AND METHODS: This is a subanalysis of a single...... isomaltoside. Significant differences in other fatigue and depression scores and hematological parameters were observed and all in favor of iron isomaltoside. There were no differences in side effects between the groups. CONCLUSIONS: In women suffering from severe fatigue after postpartum hemorrhage, a single......-center, open-label, randomized controlled trial conducted in women suffering from postpartum hemorrhage. Participants were randomized 1:1 to 1200 mg iron isomaltoside or current treatment practice with oral iron. We measured fatigue by the Multidimensional Fatigue Inventory (MFI) and Edinburgh Postnatal...

  11. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Gouws, Rufus H.; Tarp, Sven

    2017-01-01

    the often uncritical inclusion of too much data. This paper discusses the general term information overload and its lexicographical counterpart data overload. Different types of data overload are identified and the problems users have when retrieving the necessary information from dictionary articles...

  12. THE DIAGNOSTIC VALUE OF PULSED WAVE TISSUE DOPPLER IMAGING IN ASYMPTOMATIC BETA- THALASSEMIA MAJOR CHILDREN AND YOUNG ADULTS ; RELATION TO CHEMICAL BIOMARKERS OF LEFT VENTRICULAR FUNCTION AND IRON OVERLOAD .

    Directory of Open Access Journals (Sweden)

    Seham Ragab

    2015-08-01

    Full Text Available Background: Cardiac iron toxicity is the leading cause of death among  β-halassaemia major (TM  patients.  Once  heart failure becomes overt , it will be  difficult to reverse . Objectives: To investigate non overt cardiac dysfunctions  in TM patients using  pulsed wave Tissue Doppler  Imaging (TD I and its relation to the iron overload and brain natruritic peptide (BNP. Methods: Thorough  clinical , conventional echo and  pulsed  wave TDI  parameters were compared between  asymtomatic 25 β-TM  patients  and 20 age and gender matched individuals. Serum ferritin and plasma BNP  levels were assayed by  ELISA .  Results: TM patients had significant higher mitral inflow early diastolic (E wave and  non significant other conventional echo  parameters. Pulsed wave TDI revealed systolic and diastolic dysfunctions in the form of significant higher  isovolumetric contraction time (ICT , ejection time ( E T and  isovolumetric relaxation time (IRT with significantly lower  mitral annulus  early diastolic velocity E` (12.07 ±2.06 vs 15.04±2.65 ,P= 0.003  in patients compared to  controls. Plasma BNP was higher in patients compared to the controls.  Plasma BNP and serum ferritin had significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions.  Patients with E/E` ≥ 8 had  significant higher  serum ferritin  and plasma BNP levels compared to those with E/E` ratio < 8 without difference in Hb levels .Conclusion:  Pulsed wave TDI  is an  important diagnostic tool for latent cardiac dysfunction in iron loaded TM patients and is related to iron overload and BNP .

  13. The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload.

    Science.gov (United States)

    Ragab, Seham M; Fathy, Waleed M; El-Aziz, Walaa FAbd; Helal, Rasha T

    2015-01-01

    Cardiac iron toxicity is the leading cause of death among β-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 β-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E' (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E' ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP.

  14. Intravenous iron sucrose therapy for moderate to severe anaemia in pregnancy.

    Science.gov (United States)

    Kriplani, Alka; Mahey, Reeta; Dash, Biswa Bhusan; Kulshreshta, Vidushi; Agarwal, Nutan; Bhatla, Neerja

    2013-01-01

    Iron deficiency anaemia (IDA) is the most common nutritional deficiency in pregnancy. Prophylactic oral iron is recommended during pregnancy to meet the increased requirement. In India, women become pregnant with low baseline haemoglobin level resulting in high incidence of moderate to severe anaemia in pregnancy where oral iron therapy cannot meet the requirement. Pregnant women with moderate anaemia are to be treated with parentral iron therapy. This study was undertaken to evaluate the response and effect of intravenous iron sucrose complex (ISC) given to pregnant women with IDA. A prospective study was conducted (June 2009 to June 2011) in the department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi. One hundred pregnant women with haemoglobin between 5-9 g% with diagnosed iron deficiency attending antenatal clinic were given intravenous iron sucrose complex in a dose of 200 mg twice weekly schedule after calculating the dose requirement. The mean haemoglobin raised from 7.63 ± 0.61 to 11.20 ± 0.73 g% (Panaemia. Intravenous iron sucrose can be used in hospital settings and tertiary urban hospitals where it can replace intramuscular therapy due to injection related side effects. Further, long-term comparative studies are required to recommend its use at peripheral level.

  15. A child with severe iron-deficiency anemia and a complex TMPRSS6 genotype.

    Science.gov (United States)

    Capra, Anna Paola; Ferro, Elisa; Cannavò, Laura; La Rosa, Maria Angela; Zirilli, Giuseppina

    2017-10-01

    We report a case of a 7-year-old girl with severe hypochromic microcytic anemia, who was unresponsive to classical iron supplements. We suspected IRIDA, iron-refractory iron-deficiency anemia, a genetic iron metabolism disorder, caused by TMPRSS6 variations. TMPRSS6 encodes matriptase-2, a negative regulator of hepcidin, and its pathological variants are related to normal to high levels of hepcidin. We analyzed the TMPRSS6 gene and we improved clinical management of the patient, selecting the appropriate supplementation therapy. Intervention & Technique: The parenteral iron therapy was started, but the patient was only partially responsive and the anemia persisted. To confirm the diagnosis, the TMPRSS6 gene sequence was analyzed by DNA sequencing and other relevant biochemical parameters were evaluated. The TMPRSS6 sequence analysis showed a complex genotype with a rare heterozygous missense variant, in addition to other common polymorphisms. The serum hepcidin value was normal. We unexpectedly observed a normalization of patient's hemoglobin (Hb) levels only after liposomal iron treatment. The proband was symptomatic for IRIDA during a critical phase of growth and development, but we did not find a clearly causative genotype. A long-term result, improving stably patient's Hb levels, was obtained only after liposomal iron supplementation. Children may be at greater risk for iron deficiency and the degree of anemia as well as the response to the iron supplements varies markedly patient to patient. Here, we show the importance of comprehensive study of these patients in order to collect useful information about genotype-phenotype association of genes involved in iron metabolism.

  16. Urinary iron excretion induced by intravenous infusion of deferoxamine in ß-thalassemia homozygous patients

    Directory of Open Access Journals (Sweden)

    Boturão-Neto E.

    2002-01-01

    Full Text Available The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent ß-thalassemia and the efficiency of intensive intravenous therapy as an additional tool for the treatment of iron-overloaded patients. Iron overload was evaluated for 26 ß-thalassemia homozygous patients, and 14 of them were submitted to intensive chelation therapy with high doses of intravenous deferoxamine (DF. Patients were classified into six groups of increasing clinical severity and were divided into compliant and non-compliant patients depending on their adherence to chronic chelation treatment. Several methods were used as indicators of iron overload. Total gain of transfusion iron, plasma ferritin, and urinary iron excretion in response to 20 to 60 mg/day subcutaneous DF for 8 to 12 h daily are useful to identify iron overload; however, urinary iron excretion in response to 9 g intravenous DF over 24 h and the increase of urinary iron excretion induced by high doses of the chelator are more reliable to identify different degrees of iron overload because of their correlation with the clinical grades of secondary hemochromatosis and the significant differences observed between the groups of compliant and non-compliant patients. Finally, the use of 3-9 g intravenous DF for 6-12 days led to a urinary iron excretion corresponding to 4.1 to 22.4% of the annual transfusion iron gain. Therefore, continuous intravenous DF at high doses may be an additional treatment for these patients, as a complement to the regular subcutaneous infusion at home, but requires individual planning and close monitoring of adverse reactions.

  17. Severe iron deficiency anemia and marked eosinophilia in adolescent girls with the diagnosis of human fascioliasis.

    Science.gov (United States)

    Tavil, Betül; Ok-Bozkaya, İkbal; Tezer, Hasan; Tunç, Bahattin

    2014-01-01

    Human fascioliasis (HF), caused by the common liver fluke Fasciola hepatica, is an endemic infection in many parts of tropical countries. HF can also be seen in some of the non-tropical countries. This report describes two girls with severe iron deficiency anemia and eosinophilia, who were diagnosed as HF. The infection was successfully eliminated with the administration of triclabendazole. No side effects or recurrence was observed after the treatment. It should be kept in mind that marked eosinophilia with severe iron deficiency anemia should alert pediatricians to the possibility of F. hepatica infection.

  18. Intelligent Overload Control for Composite Web Services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Zivkovic, Miroslav; Meeuwissen, H.B.; Gijsen, B.M.M.

    2009-01-01

    In this paper, we analyze overload control for composite web services in service oriented architectures by an orchestrating broker, and propose two practical access control rules which effectively mitigate the effects of severe overloads at some web services in the composite service. These two rules

  19. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  20. Elliptocytes and tailed poikilocytes correlate with severity of iron-deficiency anemia.

    Science.gov (United States)

    Rodgers, M S; Chang, C C; Kass, L

    1999-05-01

    This study examines the relationships between abnormal RBC morphology, RBC indices measured with an automated hematology analyzer, serum iron studies, and severity of anemia in patients with findings indicative of iron-deficiency anemia. Counts and morphologic classification of 1,000 RBCs from each of 22 patients were performed, and correlations were determined between parameters. The Student t test was used to determine the level of significance for correlations between parameters. Several significant relationships were found. As the percentage of elliptocytes increased, hemoglobin concentration, hematocrit, RBC concentration, and mean corpuscular hemoglobin level decreased (r = .48, .44, .40, and .49, respectively; P < .05). As the percentage of tailed poikilocytes increased, hemoglobin concentration, hematocrit, and RBC concentration decreased (r = .70, .77, and .71, respectively; P < .01) and RBC distribution width increased (r = .73; P < .01). Of significance, serum ferritin levels, long considered the best single indicator of iron deficiency, showed no correlation with the morphologic abnormalities assessed, severity of anemia, or any of the analyzer-generated indices. Our results indicate that microscopic evaluation of RBC morphology remains an important tool for the pathologist to evaluate the severity of anemia in patients with iron deficiency.

  1. Intravenous iron sucrose therapy for moderate to severe anaemia in pregnancy

    Directory of Open Access Journals (Sweden)

    Alka Kriplani

    2013-01-01

    Full Text Available Background & objectives: Iron deficiency anaemia (IDA is the most common nutritional deficiency in pregnancy. Prophylactic oral iron is recommended during pregnancy to meet the increased requirement. In India, women become pregnant with low baseline haemoglobin level resulting in high incidence of moderate to severe anaemia in pregnancy where oral iron therapy cannot meet the requirement. Pregnant women with moderate anaemia are to be treated with parentral iron therapy. This study was undertaken to evaluate the response and effect of intravenous iron sucrose complex (ISC given to pregnant women with IDA. Methods: A prospective study was conducted (June 2009 to June 2011 in the department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi. One hundred pregnant women with haemoglobin between 5-9 g% with diagnosed iron deficiency attending antenatal clinic were given intravenous iron sucrose complex in a dose of 200 mg twice weekly schedule after calculating the dose requirement. Results: The mean haemoglobin raised from 7.63 ± 0.61 to 11.20 ± 0.73 g% (P<0.001 after eight wk of therapy. There was significant rise in serum ferritin levels (from 11.2 ± 4.7 to 69 ± 23.1 μg/l (P<0.001. Reticulocyte count increased significantly after two wk of starting therapy (from 1.5 ± 0.6 to 4.6±0.8%.Other parameters including serum iron levels and red cell indices were also improved significantly. Only one woman was lost to follow up. No major side effects or anaphylactic reactions were noted during study period. Interpretation & conclusions: Parentral iron therapy was effective in increasing haemoglobin, serum ferritin and other haematological parameters in pregnant women with moderate anaemia. Intravenous iron sucrose can be used in hospital settings and tertiary urban hospitals where it can replace intramuscular therapy due to injection related side effects. Further, long-term comparative studies are required to recommend its

  2. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-01-01

    Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

  3. Studies on high iron content in water resources of Moradabad district (UP, India

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    Vipin Kumar

    2017-04-01

    The overload of iron may cause severe health problems such as liver cancer, diabetes, cirrhosis of liver, diseases related to heart and central nervous system, infertility etc. The presence of high concentration of iron leads to adverse changes in colour, odour and taste of water and it also stains clothes and utensils. However, the local health authority's records are not available.

  4. A pharmaco-economic evaluation of deferasirox for treating patients with iron overload caused by transfusion-dependent thalassemia in Taiwan

    Directory of Open Access Journals (Sweden)

    Wan-Ling Ho

    2013-04-01

    Conclusion: Compared with infusional deferoxamine, oral deferasirox improved clinical outcomes and quality of life in terms of iron chelation in transfusion-dependent patients with thalassemia at a reasonable cost from a healthcare perspective.

  5. The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

    Science.gov (United States)

    Sivgin, Serdar; Karamustafaoglu, Mehmet Fatih; Yildizhan, Esra; Zararsiz, Gokmen; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

    2016-08-01

    Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin < 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin ≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P ≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P < .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

    Science.gov (United States)

    da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

    2014-02-01

    We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

  7. Ferrochelatase deficiency of the bone marrow in a syndrome of congenital microcytic anaemia with iron overload of the liver and hyperferraemia

    International Nuclear Information System (INIS)

    Stavem, P.; Hovig, T.; Rootwelt, K.; Emblem, R.; Romslo, I.

    1985-01-01

    By far the most common mechanisms for hypochromic anaemias are either iron deficiency with a limited production of haem or the thalassaemias with a limited production of peptide chains. Some extremely rare congenital hypochromic anaemias have also been reported, in which iron deficiency or thalassaemia is not the cause. One of them is atransferrinaemia. In another rare type of hereditary, congenital hypochromic anaemia, the patients have hyperferraemia with a near fully saturated total iron binding capacity. In spite of heavy haemosiderin deposits in the liver, the bone marrow haemosiderin is reduced. In our studies which where reported in 1983, we found normal transferrin, Hb electrophoresis was normal, and there were no findings indicating thalassaemia minor or lead intoxication. We suggested that the most likely explanation of the condition was a defect in the iron transport mechanism from transferrin into the erythroid cells in the bone marrow, but at that time we had no method for studying this. During the last few years, more reliable methods have become available for assaying ferrochelatase, the enzyme largely responsible for the incorporation of iron into haem. We have therefore repeated our previous studies (with essentially the same results as reported in 1973), and have also assayed ferrochelatase activity of the bone marrow. (author)

  8. Polysynovitis after oligofructose overload in dairy cattle.

    Science.gov (United States)

    Danscher, A M; Enemark, H L; Andersen, P H; Aalbaek, B; Nielsen, O L

    2010-01-01

    Acute bovine laminitis is a systemic disease with local manifestations primarily affecting the claws. However, distension of the tarsocrural joints has been observed after experimental oligofructose overload in dairy heifers as a part of the complex interpreted as acute, clinical laminitis. Therefore, the aim of the present study was to study bovine synovial joints and tendon sheaths after oligofructose overload. Ten dairy heifers received oral oligofructose overload (17 g/kg body weight); four were killed 24h after overload and six after 72 h. Six control heifers received tap water and were killed after 72 or 96 h. Clinical examination included locomotion scoring and palpation of the tarsocrural joints. Ruminal fluid and blood was collected for measurements of pH and hydration status. Total protein concentrations and white blood cell (WBC) counts were determined in synovial fluid collected from tarsocrural joints after death. Synovial joints and tendon sheaths were examined and synovial membranes were studied microscopically. Swabs taken from the synovial cavities were subject to bacteriological culture. Heifers with oligofructose overload developed signs of ruminal and systemic acidosis. Lameness was observed in three of ten heifers 24h after overload and in all remaining heifers after 72 h. Distension of tarsocrural joints was observed from 18 h after overload and peaked at 30 h when all examined joints were moderately or severely distended. The synovial fluid was turbid and protein content and WBC counts were increased at both 24 and 72 h compared with controls. Bacterial culture was negative. Synovial membranes 24 and 72 h after overload had a fibrinous and neutrophil inflammatory reaction that regressed in severity between 24 and 72 h after overload. Heifers subjected to oligofructose overload therefore developed generalized sterile neutrophilic polysynovitis. Focus on this aspect of bovine laminitis may shed new light on the pathogenesis of this complex

  9. Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.

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    Robert Staroń

    Full Text Available Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream.

  10. Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.

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    Konstantinos Gkouvatsos

    Full Text Available Hemojuvelin (Hjv is a bone morphogenetic protein (BMP co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.

  11. Iron metabolism and toxicity

    International Nuclear Information System (INIS)

    Papanikolaou, G.; Pantopoulos, K.

    2005-01-01

    Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

  12. Celiac Disease in Children with Moderate-to-Severe Iron-deficiency Anemia.

    Science.gov (United States)

    Narang, Manish; Natarajan, Ravikumar; Shah, Dheeraj; Puri, Amarender Singh; Manchanda, Vikas; Kotru, Mrinalini

    2018-01-15

    To evaluate the proportion of children with moderate to severe iron-deficiency anemia who have associated celiac disease. This cross-sectional analytical study was conducted among children aged 1 to 12 years of age with moderate-to-severe iron deficiency anemia and control children without anemia. Serum IgA-tissue trans-glutaminase levels were assessed in both cases and controls. All children with positive celiac serology underwent upper gastrointestinal endoscopy and duodenal biopsy; biopsy finding of Marsh grade 3 was considered positive for celiac disease. There were 152 anemic children and 152 controls with mean (SD) hemoglobinof 7.7 (1.8) and 12.2 (0.74) g/dL, respectively. 16 (10.5%) cases and 3 (2%) control patients had positive serology for celiac disease [OR (95% CI) 5.33 (1.52-18.67), P=0.007]. Six (3.9%) children with iron-deficiency anemia and none of the controls had biopsy features diagnostic of celiac disease. In the Northern Indian tertiary-care hospital outpatient setting, Celiac disease was associated with 4% of children presenting with moderate-to-severe anemia.

  13. Iron plasma generation using a Nd:YAG laser pulse of several hundred picoseconds

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Jun, E-mail: jtamura@post.j-parc.jp [J-PARC Center, Japan Atomic Energy Agency, Ibaraki 319-1195 (Japan); Kumaki, Masafumi [Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Kondo, Kotaro [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Tokyo 152-8550 (Japan); Kanesue, Takeshi; Okamura, Masahiro [Collider-Accelerator Department, Brookhaven National Laboratory, Upton, New York 11973 (United States)

    2016-02-15

    We investigated the high intensity plasma generated by using a Nd:YAG laser to apply a laser-produced plasma to the direct plasma injection scheme. The capability of the source to generate high charge state ions strongly depends on the power density of the laser irradiation. Therefore, we focused on using a higher power laser with several hundred picoseconds of pulse width. The iron target was irradiated with the pulsed laser, and the ion current of the laser-produced iron plasma was measured using a Faraday cup and the charge state distribution was investigated using an electrostatic ion analyzer. We found that higher charge state iron ions (up to Fe{sup 21+}) were obtained using a laser pulse of several hundred picoseconds in comparison to those obtained using a laser pulse of several nanoseconds (up to Fe{sup 19+}). We also found that when the laser irradiation area was relatively large, the laser power was absorbed mainly by the contamination on the target surface.

  14. MRI in haemochromatosis: pituitary versus testicular iron deposition in five patients with hypogonadism

    International Nuclear Information System (INIS)

    Miaux, Y.; Daurelle, P.; Zagdanski, A.M.; Passa, P.; Bourrier, P.; Frija, J.

    1995-01-01

    Haemochromatosis is a disease characterised by iron deposition in the liver and other organs. Hypogonadism is a commonly associated condition and may be either primary due to testicular lesions or secondary due to pituitary dysfunction. Hypogonadism secondary to pituitary dysfunction is more frequent and is thought to be related to iron deposition in the anterior pituitary. Increased iron content decreases signal intensity of spin-echo MRI images because T2 values are significantly shortened. Our purpose in this study was to evaluate by MRI iron deposition in the liver, testis and pituitary of 6 patients with haemochromatosis and severe hypogonadotrophic hypogonadism. Six subjects served as controls. There was a significant T2 shortening of the liver and pituitary in patients with haemochromatosis compared with control patients. Therefore MRI detected iron overload in the pituitary and no iron in the testis, supporting the hypothesis of hypogonadotrophic pituitary insufficiency due to cellular damage induced by iron overload in the anterior pituitary gland. (orig.)

  15. Influence of genetic polymorphisms and mutations in the cardiac pathology of iron overload in thalassemia and sickle cell anemia patients: a retrospective study

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    Veronica Agrigento

    2012-11-01

    Full Text Available Cardiac disease in thalassemia is determined by the accumulation of iron in the tissue. Genetic factors could influence the severity and the rapidity of the modifications of the cardiac tissue. Mutations or polymorphisms of genes have already been described as being implicated in cardiac disease. In particular, we studied the polymorphisms C1091T in the Connexin 37 gene (CX 37, 4G -668 5G in the Plasminogen Activator Inhibitor-1 gene (PAI 1 and 5A-1171 6A in the Stromelysin-1 gene (SL in 193 randomly selected patients affected by hemoglobinopathies and 100 normal subjects randomly selected from the general population. A retrospective analysis based on history, clinical data and imaging studies was carried out to assess the presence and type of heart disease. The results of our study do not demonstrate a close association between polymorphism in these candidate genes and cardiac disease, and in particular with myocardial infarction in a cohort of Sicilian patients affected by hemoglobinopathies. 地中海贫血心脏病的关键诱因是组织中的铁沉积。遗传因子可能影响心脏组织修复的严重程度和速度。基因突变或基因多态性与心脏病有关。尤其是,我们研究了193名随机选择的血红蛋白病患者以及从普通人群中随机选择的100名正常受试者的连接蛋白37基因(CX37)的C1091T、纤溶酶原激活物抑制剂-1基因(PAI1)的4G -668 5G 和基质分解素-1基因(SL)的5A-1171 6A等多态性。根据病史、临床资料和影像研究进行回顾性分析,以评估心脏病的存在情况和类型。我们的研究结果并没有表明这些候选基因的多态性和心脏疾病之间存在密切联系,尤其是与一组西西里岛血红蛋白病患者的心肌梗塞存在密切联系。

  16. Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

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    Sarah Straud

    2010-07-01

    Full Text Available Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant of V-ATPase sensitivity in several cancer cell lines. One of the most sensitive cell lines, melanoma derived SK-Mel-5, over-expresses the iron efflux transporter ferroportin and has decreased expression of proteins involved in iron uptake, suggesting that it actively suppresses cytoplasmic iron. SK-Mel-5 cells have increased production of reactive oxygen species and may be seeking to limit additional production of ROS by iron.

  17. Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

    Science.gov (United States)

    Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

    2011-08-01

    To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

  18. Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

    Science.gov (United States)

    Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

    2011-01-01

    To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

  19. Relationship between severity of depression symptoms and iron deficiency anemia in women with major depressive disorder

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    Seyed gholamreza Noorazar

    2015-11-01

    Full Text Available Introduction: Iron deficiency (ID is a common nutritional problem lead to many unintended consequences such as decrease energy, immune system problems, and neurological dysfunction. The most common psychological disorder is depression. A patient with ID anemia (IDA show signs and symptoms of behavioral and mood disorders like depression. Methods: In this study, 100 female patients with diagnosed major depression in years 2010 and 2011 were studied. In all patients standard Hamilton depression rating scale (HDRS was used to evaluate depression severity. Blood samples were taken for complete blood count difference analysis and evaluating anemia and in those with hemoglobin (Hb < 12 mg/dl, ferritin, and total iron binding capacity were checked to evaluate IDA. Results: Patients mean age was 36.34 ± 10.43 years old. Mean HDRS score was 32.20 ± 4.07. 19 had anemia, and among them 8% had IDA. Mean HDRS score in patients with IDA (33.37 ± 1.90 was higher than those without (32.09 ± 4.19, but the difference was not significant (P = 0.39. There was no difference between patients with and without anemia in HDRS score. The negative relation was observed between Hb levels, and HDRS score (Pearson correlation = -0.21, P = 0.03. Conclusion: We observed that the negative correlation between Hb levels and HDRS score. It demonstrates the effect of Hb decrease and anemia occurrence on depression severity; however, it needs more studies.

  20. Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

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    Shun Yao

    2017-08-01

    Full Text Available Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD, 14 patients with major depression disorder (MDD and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression.

  1. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...... of transcription factors, activation of the mitochondrial apoptotic machinery or of other cell death mechanisms. The pro-inflammatory cytokine IL-1β facilitates divalent metal transporter 1 (DMT1)-induced β-cell iron uptake and consequently ROS formation and apoptosis, and we propose that this mechanism provides...

  2. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Bayanzay K

    2016-08-01

    Full Text Available Karim Bayanzay, Lama Alzoebie Department of Hematology, Gulf Medical University, Ajman, United Arab Emirates Abstract: Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. Keywords: hematology, chelators, deferoxamine, deferiserox, deferiprone, liver iron concentration, iron overload, serum ferritin concentration, hepatic iron storage, iron chelation therapy

  3. Genetic/metabolic effect of iron metabolism and rare anemias

    Directory of Open Access Journals (Sweden)

    Clara Camaschella

    2013-03-01

    Full Text Available Advances in iron metabolism have allowed a novel classification of iron disorders and to identify previously unknown diseases. These disorders include genetic iron overload (hemochromatosis and inherited iron-related anemias, in some cases accompanied by iron overload. Rare inherited anemias may affect the hepcidin pathway, iron absorption, transport, utilization and recycling. Among the genetic iron-related anemias the most common form is likely the iron-refractory iron-deficiency anemia (IRIDA, due to mutations of the hepcidin inhibitor TMPRSS6 encoding the serine protease matriptase-2. IRIDA is characterized by hepcidin up-regulation, decrease iron absorption and macrophage recycling and by microcytic- hypochromic anemia, unresponsive to oral iron. High serum hepcidin levels may suggest the diagnosis, which requires demonstrating the causal TMPRSS6 mutations by gene sequencing. Other rare microcytic hypochromic anemias associated with defects of iron transport-uptake are the rare hypotransferrinemia, and DMT1 and STEAP3 mutations. The degree of anemia is variable and accompanied by secondary iron overload even in the absence of blood transfusions. This is due to the iron-deficient or expanded erythropoiesis that inhibits hepcidin transcription, increases iron absorption, through the erythroid regulator, as in untransfused beta-thalassemia. Sideroblastic anemias are due to decreased mitochondrial iron utilization for heme or sulfur cluster synthesis. Their diagnosis requires demonstrating ringed sideroblasts by Perl’s staining of the bone marrow smears. The commonest X-linked form is due to deltaamino- levulinic-synthase-2-acid (ALAS2 mutations. The recessive, more severe form, affects SLC25A38, which encodes a potential mitochondrial importer of glycine, an amino acid essential for ALA synthesis and thus results in heme deficiency. Two disorders affect iron/sulfur cluster biogenesis: deficiency of the ATP-binding cassette B7 (ABCB7 causes X

  4. Iron

    Science.gov (United States)

    ... Share: Search the ODS website Submit Search NIH Office of Dietary Supplements Consumer Datos en español Health ... eating a variety of foods, including the following: Lean meat, seafood, and poultry. Iron-fortified breakfast cereals ...

  5. Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

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    Yu. P. Orlov

    2006-01-01

    Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

  6. Estudo das mutações C282Y, H63D e S65C do gene HFE em doentes brasileiros com sobrecarga de ferro Study of C282Y, H63D and S65C mutations in the HFE gene in Brazilian patients with iron overload

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    Rodolfo D. Cançado

    2007-12-01

    Full Text Available Hemocromatose é uma das doenças genéticas mais freqüentes no ser humano e uma das causas mais importantes de sobrecarga de ferro. Os objetivos deste estudo foram determinar a freqüência das mutações C282Y, H63D e S65C do gene HFE em doentes brasileiros com sobrecarga de ferro, verificar a coexistência de anemia hemolítica hereditária, hepatite C e consumo excessivo de bebida alcoólica nestes doentes e avaliar a influência destas variáveis sobre os depósitos de ferro do organismo. Saturação da transferrina, ferritina sérica e análise das mutações C282Y, H63D e S65C do gene HFE, pelo método da PCR, foram determinadas em cinqüenta doentes com sobrecarga de ferro atendidos no Hemocentro da Santa Casa de São Paulo entre janeiro de 2000 e maio de 2004. A freqüência de mutação do gene HFE nos doentes com sobrecarga de ferro foi de 76,0% (38/50. Saturação da transferrina e ferritina foram significativamente maiores nos doentes homozigotos para a mutação C282Y confirmando a correlação entre genótipo C282Y/C282Y e maior risco de sobrecarga de ferro. A coexistência de hepatite C, consumo excessivo de bebida alcoólica ou anemia hemolítica hereditária estão implicados em aumento dos estoques de ferro e constituem fator de risco adicional em pacientes com mutação do gene HFE para a condição de sobrecarga de ferro.Hemochromatosis is one of the most frequent genetic diseases in humans and one of the most important causes of iron overload. The aims of this study were to determine the frequency of C282Y, H63D and S65C mutations of the HFE gene in Brazilian patients with iron overload, to verify the coexistence of chronic hemolytic anemia, hepatitis C and excessive alcohol consumption and to evaluate the influence of these variables on body iron deposits. Transferrin saturation, serum ferritin and C282Y, H63D and S65C HFE gene mutations (by PCR method were determined in 50 patients with iron overload in the Hemocentro da

  7. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum...... haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. MATERIALS AND METHODS: Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7......) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. RESULTS: We screened 162 women and included 13 (8...

  8. Iron overload and genotype 3 are associated with liver steatosis in chronic hepatitis C Sobrecarga de hierro y genotipo 3 se asocian a la presencia de esteatosis en la hepatitis C

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    L. I. Fernández Salazar

    2004-12-01

    Full Text Available Objective: to determine epidemiological, biochemical, virological, and histological factors associated with liver steatosis in chronic hepatitis C. Subjects: the medical histories of 53 patients biopsied for chronic hepatitis C diagnosis between June 2000 and December 2002 were retrospectively studied. Epidemiological, biochemical, and virological data were collected. Patients with hepatitis B virus or human immunodeficiency virus coinfection were excluded. Liver biopsy specimens were reviewed and scored by one pathologist. Weight and height were measured at liver biopsy time. The statistic association between qualitative and quantitative variables and the presence of liver steatosis was studied. Results: steatosis was identified in 52% of biopsies. There was no statistic association with age, sex, method of transmission, duration of infection, alcohol consumption, other diseases, body mass index, glucose, triglycerides, cholesterol, AST, ALT, GGT, alkaline phosphatase, bilirubin, or viral load. Liver steatosis was associated with serum iron, transferrin saturation, and ferritin. Genotype 3 was also associated with steatosis. Piecemeal necrosis, hepatocellular injury, Kupffer cell hyperplasia, liver iron, and portal fibrosis were also associated with steatosis. A multivariate analysis showed that genotype 3, Kupffer cell hyperplasia, and liver iron were associated with the presence of steatosis. Conclusions: liver steatosis in chronic hepatitis C associates with genotype 3, Kupffer cell hyperplasia, and iron overload. Hepatic steatosis also associates with greater inflammation and fibrosis, and must be considered to contribute to disease progression.Objetivo: determinar los factores epidemiológicos, analíticos, virológicos e histológicos a los que se asocia la esteatosis en la hepatitis C. Pacientes: se revisaron de forma retrospectiva 53 historias clínicas de pacientes biopsiados consecutivamente desde junio de 2000 a dicembre de 2002. Se

  9. Iron content and acid phosphatase activity in hepatic parenchymal lysosomes of patients with hemochromatosis before and after phlebotomy treatment

    International Nuclear Information System (INIS)

    Cleton, M.I.; de Bruijn, W.C.; van Blokland, W.T.; Marx, J.J.; Roelofs, J.M.; Rademakers, L.H.

    1988-01-01

    Lysosomal structures in liver parenchymal cells of 3 patients with iron overload and of 3 subjects without iron-storage disorders were investigated. A combination of enzyme cytochemistry--with cerium as a captive ion to demonstrate lysosomal acid phosphatase activity--and electron probe X-ray microanalysis (EPMA) was used. We were able (1) to define and quantify lysosomal structures as lysosomes, siderosomes, or residual bodies, (2) to quantify the amount of iron and cerium simultaneously in these structures, and (3) to evaluate a possible relation between iron storage and enzyme activity. With histopathologically increased iron storage, the number of siderosomes had increased at the cost of lysosomes, with a corresponding increase in acid phosphatase activity in both organelles. In histopahtologically severe iron overload, however, acid phosphatase activity was low or not detectable and most of the iron was stored in residual bodies. After phlebotomy treatment, the number of siderosomes had decreased in favor of the lysosomes, approaching values obtained in control subjects, and acid phosphatase activity was present in all iron-containing structures. In this way a relationship between iron storage and enzyme activity was established. The iron content of the individual lysosomal structures per unit area had increased with histopathologically increased iron storage and had decreased after phlebotomy treatment. From this observation, it is concluded that the iron status of the patient is not only reflected by the amount of iron-containing hepatocytes but, as well, by the iron content lysosomal unit area

  10. The role of fluid overload in the prediction of outcome in acute kidney injury.

    Science.gov (United States)

    Selewski, David T; Goldstein, Stuart L

    2018-01-01

    Our understanding of the epidemiology and the impact of acute kidney injury (AKI) and fluid overload on outcomes has improved significantly over the past several decades. Fluid overload occurs commonly in critically ill children with and without associated AKI. Researchers in pediatric AKI have been at the forefront of describing the impact of fluid overload on outcomes in a variety of populations. A full understanding of this topic is important as fluid overload represents a potentially modifiable risk factor and a target for intervention. In this state-of-the-art review, we comprehensively describe the definition of fluid overload, the impact of fluid overload on kidney function, the impact of fluid overload on the diagnosis of AKI, the association of fluid overload with outcomes, the targeted therapy of fluid overload, and the impact of the timing of renal replacement therapy on outcomes.

  11. Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

    Directory of Open Access Journals (Sweden)

    Joao Arezes

    Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

  12. Overload road damage model

    CSIR Research Space (South Africa)

    Roux, MP

    2005-03-01

    Full Text Available Not only do overloaded vehicles pose an increased safety risk on the road (reduced stability and braking efficiency etc.), but they also accelerate the rate of deterioration of the road network and increase road maintenance costs, which in turn...

  13. The effect of single overloading on stress corrosion cracking

    International Nuclear Information System (INIS)

    Ito, Yuzuru; Saito, Masahiro

    2008-01-01

    In the normal course of nuclear power plant operation in Japan, proof testing has been performed after periodic plant inspections. In this proof test procedure, the reactor pressure vessel and pipes of the primary coolant loop are subjected to a specified overload with a slightly higher hydraulic pressure than during normal operation. This specified overload is so called a single overload' in material testing. It is well known that the fatigue crack growth rate is decreased after a single overload has been applied to the specimen. However, it is not clear whether the stress corrosion cracking rate is also decreased after a single overload. In this study, the effect of a single overload on the stress corrosion cracking rate under simulated boiling water reactor environment was evaluated by examining a singly overloaded WOL (wedge opening load) specimen. The WOL specimen for the stress corrosion cracking test was machined from sensitized 304 type austenitic stainless steel. Since the crack extension length was 3.2% longer in the case of a more severely overloaded specimen, it was observed than the stress corrosion cracking rate is also decreased after the single overload has been applied to the specimen. (author)

  14. Oligofructose overload induces lameness in cattle.

    Science.gov (United States)

    Danscher, A M; Enemark, J M D; Telezhenko, E; Capion, N; Ekstrøm, C T; Thoefner, M B

    2009-02-01

    The aim was to describe the clinical orthopedic implications of oligofructose overload. A group of 8 nonpregnant dairy heifers were given an oral dose of oligofructose (17 g/kg of body weight). At predefined times during a period spanning 3 d before and 9 d after oligofructose overload, the heifers underwent a clinical examination including locomotion scoring, hoof-testing, and palpation of tarso-crural joints, as well as the collection of blood and ruminal fluid samples. Locomotion sessions were videotaped; subsequently, locomotion was blind-scored. Locomotion scores increased after oligofructose overload and declined toward the end of the study period. The greatest locomotion scores were recorded on d 3 to 5 (60 to 120 h) where 12 of 42 (29%) locomotion scores were 3 and 13 of 42 (32%) were score 2. Positive reactions to hoof-testing were observed from 30 h after oligofructose overload and reached a maximum on d 7 and 9 where 12 of 28 (43%) reactions were marked positive. Distension of the tarso-crural joints was observed from 24 h after oligofructose overload, with maximum distension being observed on d 2, in which 44 of 56 (79%) of observed joints were either moderately or severely distended. The heifers developed classic signs of acute ruminal and systemic acidosis after the oligofructose overload (ruminal pH 4.3 +/- 0.07, standard base excess -10.8 +/- 2.3 at 18 h). With few exceptions, clinical and laboratory variables returned to normal within 9 d of oligofructose overload. But, good body condition and previous feeding with grass apparently predisposed the heifers to more severe systemic affection. Oligofructose overload in dairy heifers induced ruminal and systemic acidosis, diarrhea, dehydration, and, subsequently, lameness, claw pain, and joint effusion, collectively interpreted as signs of acute laminitis. Oligofructose overload at 17 g/kg of body weight represented a relatively mild laminitis model in cattle, as demonstrated by a reasonably quick

  15. PARENTERAL IRON SUCROSE AS AN ALTERNATIVE TO PACKED CELLS/BLOOD TRANSFUSION IN MODERATE-TO-SEVERE ANAEMIA IN PREGNANCY

    Directory of Open Access Journals (Sweden)

    Rama Sarala

    2016-03-01

    Full Text Available AIM This case study focuses on the efficacy of iron sucrose in moderate-to-severe anaemia in pregnancy and to compare the efficacy of iron sucrose with packed cell transfusion and based on the study to establish whether iron sucrose could be an alternative to packed cells transfusion for the management of moderate-to-severe anaemia complicating pregnancy remote from the term gestation. MATERIALS AND METHODS It is a case control study for a period of 2 years. Women were randomly selected where for the study group 50 patients intravenous iron sucrose was given and for control group 50 patients packed cells transfusion was given. RESULTS The study group and the control group had 50 subjects each. On an average 80% were in the age group of 15-24 yrs. in both groups. In both groups, on an average 85% were with moderate anaemia (6-8 g/dL and 15% were with severe anaemia (<6 g/dL. Mean requirement of iron sucrose for moderate anaemia was 1100 mg and for severe anaemia it was 1300 mg. Mean requirement of packed cells for moderate anaemia was 3 units and for severe anaemia 4-5 units. In iron sucrose group, mean haemoglobin% at baseline 7.1±0.8 g/dL, after 1 week 7.9±0.6, after 4 weeks 11±0.5 g/dL and at delivery 11.7±0.6 g/dL. In packed cells group, mean haemoglobin% at baseline 7.0±0.7 g/dL, after 1 week 10.2±0.5 g/dL, after 4 weeks 10.3±0.5 g/dL and at delivery 10.4±0.4 g/dL. The mean haematocrit values in iron sucrose group at baseline 20.9±2.5%, after 1 week 25.3±2.2% and after 4 weeks 33.6±2.0%. The mean haematocrit values in packed cells group at baseline 20.8±2.3%, after 1 week 30.0±1.9% and after 4 weeks 30.2±2.0%. Mean rise of haematocrit from baseline to 1 week in iron sucrose and packed cells group were 4.4±1.3% and 9.1±2.0% respectively. Mean rise of haematocrit from baseline to 4 weeks in iron sucrose and packed cell group were 12.7±2.1% and 9.3±2.3 respectively. The mean ferritin values in iron sucrose group at baseline

  16. A new approach for primary overloads allowance in ratcheting evaluation

    International Nuclear Information System (INIS)

    Cabrillat, M.T.; Gatt, J.M.; Lejeail, Y.

    1995-01-01

    Seismic loading must be taken into account in ratchetting design analysis. In LMFBR structures it mainly produces primary overloads, which are characterised by severe magnitudes but a generally low number of occurrences. Other cases of several primary overloads can also observed in pipes during emptying operations for instance. In the RCC-MR design code rule, the maximum primary stress supported by a structure is considered as permanent. No allowance is made for temporary load. Experimental ratchetting tests conducted on different structures with and without overloads clearly point out that temporary overloads lead to less ratchetting effect. A method using the RCC-MR efficiency diagram framework is proposed. A general theoretical approach allows to extend its field of application of various cases of primary loading: constant or null primary loading or overloads. Experimental results are then used to check the validity of this new approach. (author). 2 refs., 2 figs., 2 tabs

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and severity. Treatments may include iron supplements, procedures, surgery, and dietary ... iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  18. Iron excess in recreational marathon runners

    NARCIS (Netherlands)

    Mettler, S.; Zimmermann, M.B.

    2010-01-01

    Background/Objectives: Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. Methods: We investigated the iron status of 170 male and

  19. IRON CHELATION THERAPY IN THALASSEMIA SYNDROMES

    Directory of Open Access Journals (Sweden)

    Paolo Cianciulli

    2009-06-01

    Full Text Available Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as  thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce  complications, and improve survival and quality of life of transfused patients

  20. Clinical penetrance in hereditary hemochromatosis: estimates of the cumulative incidence of severe liver disease among HFE C282Y homozygotes.

    Science.gov (United States)

    Grosse, Scott D; Gurrin, Lyle C; Bertalli, Nadine A; Allen, Katrina J

    2018-04-01

    Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282Y variant in the HFE gene. Screening of adults for iron overload or associated genotypes is controversial, largely because of a belief that severe phenotypes are uncommon, although cascade testing of first-degree relatives of patients is widely endorsed. We contend that severe liver disease (cirrhosis or hepatocellular cancer) is not at all uncommon among older males with hereditary hemochromatosis. Our review of the published data from a variety of empirical sources indicates that roughly 1 in 10 male HFE C282Y homozygotes is likely to develop severe liver disease during his lifetime unless iron overload is detected early and treated. New evidence from a randomized controlled trial of treatment allows for evidence-based management of presymptomatic patients. Although population screening for HFE C282Y homozygosity faces multiple barriers, a potentially effective strategy for increasing the early detection and prevention of clinical iron overload and severe disease is to include HFE C282Y homozygosity in lists of medically actionable gene variants when reporting the results of genome or exome sequencing.

  1. measurements of iron status and survival in african iron overload

    African Journals Online (AJOL)

    Serum concentrations of lactate dehydrogenase (LDH), AST, alanine aminotransferase (ALT), garnma-glutamyl transpeptidase. (-yGT), bilirubin, glucose and sodi~ were measured using an automated clinical chemistry analyser. Erythrocyte sedimentation rate (ESR) was determined using the Westergren method. C-reactive ...

  2. Investigation of electrochemical synthesis of ferrate, Part I: Electrochemical behavior of iron and its several alloys in concentrated alkaline solutions

    Directory of Open Access Journals (Sweden)

    Čekerevac Milan I.

    2009-01-01

    Full Text Available In recent years, considerable attention has been paid to various applications of Fe(VI due to its unique properties such as oxidizing power, selective reactivity, stability of the salt, and non-toxic decomposition by-products of ferric ion. In environmental remediation processes, Fe(VI has been proposed as green oxidant, coagulant, disinfectant, and antifoulant. Therefore, it is considered as a promising multi-purpose water treatment chemical. Fe(VI has also potential applications in electrochemical energy source, as 'green cathode'. The effectiveness of ferrate as a powerful oxidant in the entire pH range, and its use in environmental applications for the removal of wide range of contaminants has been well documented by several researchers. There is scientific evidence that ferrate can effectively remove arsenic, algae, viruses, pharmaceutical waste, and other toxic heavy metals. Although Fe(VI was first discovered in early eighteen century, detailed studies on physical and chemical properties of Fe(VI had to wait until efficient synthetic and analytical methods of Fe(VI were developed by Schreyer et al. in the 1950s. Actually, there have been developed three ways for the preparation of Fe(VI compounds : the wet oxidation of Fe(II and Fe(III compounds, the dry oxidation of the same, and the electrochemistry method, mainly based on the trans passive oxidation of iron. High purity ferrates Fe(VI can be generated when electrode of the pure iron metal or its alloys are anodized in concentrated alkaline solution. It is known that the efficiency of electrochemical process of Fe(VI production depends on many factors such as current density, composition of anode material, types of electrolyte etc. In this paper, the electrochemical synthesis of ferrate(VI solution by the anodic dissolution of iron and its alloys in concentrated water solution of NaOH and KOH is investigated. The process of transpassive dissolution of iron to ferrate(VI was studied by

  3. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia: a randomized controlled pilot study.

    Science.gov (United States)

    Holm, C; Thomsen, L L; Norgaard, A; Langhoff-Roos, J

    2017-02-01

    There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. We screened 162 women and included 13 (8%). There was no significant difference between groups in fatigue or depression scores. RBC transfusion was associated with a higher Hb on day 1, inhibition of reticulocytosis during the first week and low iron levels. Intravenous iron was associated with increased reticulocytosis during the first week, repleted iron stores and a higher Hb in weeks 3-12. This pilot study shows that intravenous iron could be an attractive alternative to RBC transfusion in severe postpartum anaemia, and that a larger trial is needed and feasible. © 2016 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  5. NCOA4 Deficiency Impairs Systemic Iron Homeostasis

    Directory of Open Access Journals (Sweden)

    Roberto Bellelli

    2016-01-01

    Full Text Available The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2–3 mg/kg, mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg, mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239–614 restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

  6. Serum iron parameters in liver cirrhosis

    Science.gov (United States)

    Siregar, G. A.; Maail, W.

    2018-03-01

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

  7. Fluid overload in the ICU: evaluation and management.

    Science.gov (United States)

    Claure-Del Granado, Rolando; Mehta, Ravindra L

    2016-08-02

    Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients. In critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies. In critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous

  8. Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

    Science.gov (United States)

    Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

    2014-02-01

    Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

  9. Pairing symmetries of several iron-based superconductor families and some similarities with cuprates and heavy-fermions

    Directory of Open Access Journals (Sweden)

    Das Tanmoy

    2012-03-01

    Full Text Available We show that, by using the unit-cell transformation between 1 Fe per unit cell to 2 Fe per unit cell, one can qualitatively understand the pairing symmetry of several families of iron-based superconductors. In iron-pnictides and iron-chalcogenides, the nodeless s±-pairing and the resulting magnetic resonance mode transform nicely between the two unit cells, while retaining all physical properties unchanged. However, when the electron-pocket disappears from the Fermi surface with complete doping in KFe2As2, we find that the unit-cell invariant requirement prohibits the occurrence of s±-pairing symmetry (caused by inter-hole-pocket nesting. However, the intra-pocket nesting is compatible here, which leads to a nodal d-wave pairing. The corresponding Fermi surface topology and the pairing symmetry are similar to Ce-based heavy-fermion superconductors. Furthermore, when the Fermi surface hosts only electron-pockets in KyFe2-xSe2, the inter-electron-pocket nesting induces a nodeless and isotropic d-wave pairing. This situation is analogous to the electron-doped cuprates, where the strong antiferromagnetic order creates similar disconnected electron-pocket Fermi surface, and hence nodeless d-wave pairing appears. The unit-cell transformation in KyFe2-xSe2 exhibits that the d-wave pairing breaks the translational symmetry of the 2 Fe unit cell, and thus cannot be realized unless a vacancy ordering forms to compensate for it. These results are consistent with the coexistence picture of a competing order and nodeless d-wave superconductivity in both cuprates and KyFe1.6Se2.

  10. Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.

    Science.gov (United States)

    Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M

    2016-11-01

    Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Role of work overload toward turnover intention among newly hired public accountants

    OpenAIRE

    Pradana, Andika; Salehudin, Imam

    2013-01-01

    This paper aims to analyze how work overload influences turnover intentions of newly hired public accountants. Job satisfaction, work related stress and work life conflicts are used as mediating variable between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. Six proposed hypotheses was tested using Structural Equation Modeling (SEM). Results showed that work overload has significant effect in increa...

  12. Sensory overload: A concept analysis.

    Science.gov (United States)

    Scheydt, Stefan; Müller Staub, Maria; Frauenfelder, Fritz; Nielsen, Gunnar H; Behrens, Johann; Needham, Ian

    2017-04-01

    In the context of mental disorders sensory overload is a widely described phenomenon used in conjunction with psychiatric interventions such as removal from stimuli. However, the theoretical foundation of sensory overload as addressed in the literature can be described as insufficient and fragmentary. To date, the concept of sensory overload has not yet been sufficiently specified or analyzed. The aim of the study was to analyze the concept of sensory overload in mental health care. A literature search was undertaken using specific electronic databases, specific journals and websites, hand searches, specific library catalogues, and electronic publishing databases. Walker and Avant's method of concept analysis was used to analyze the sources included in the analysis. All aspects of the method of Walker and Avant were covered in this concept analysis. The conceptual understanding has become more focused, the defining attributes, influencing factors and consequences are described and empirical referents identified. The concept analysis is a first step in the development of a middle-range descriptive theory of sensory overload based on social scientific and stress-theoretical approaches. This specification may serve as a fundament for further research, for the development of a nursing diagnosis or for guidelines. © 2017 Australian College of Mental Health Nurses Inc.

  13. Measured neutron beam line shielding effectiveness of several iron/polyethylene configurations

    International Nuclear Information System (INIS)

    Legate, G.L.; Howe, M.L.; Mundis, R.L.

    1988-01-01

    Neutron and gamma-ray leakage measurements were taken at various stages of shield construction of neutron flight path 5 (the Lash-up flight path) at LANSCE, to compare the relative effectiveness of several configurations. Dose equivalent rates were determined for three categories: ''low-energy neutrons'', below 20 MeV; ''high- energy neutrons'', above 20 MeV; and gamma rays, as measured by hand-held survey instruments. The low energy neutrons were measured by activation of an indium foil in a paraffin-filled cadmium canister, sized to be generally insensitive above 20 MeV. High-energy neutrons were measured by (n,2n) production of Carbon 11 in a plastic scintillator with a 20-MeV threshold. Thermal neutrons were not measured at the shield-leakage test points. Room-scattered neutrons were observed by Albatross IV detector readings, which were taken beside the shield as a measure of variation of room background as the shield configuration changed. 1 fig., 1 tab

  14. Intestinal Iron Homeostasis and Colon Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yatrik M. Shah

    2013-06-01

    Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

  15. HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients.

    Science.gov (United States)

    Turkmen, Ercan; Yildirim, Tolga; Yilmaz, Rahmi; Hazirolan, Tuncay; Eldem, Gonca; Yilmaz, Engin; Aybal Kutlugun, Aysun; Altindal, Mahmut; Altun, Bulent

    2017-07-01

    HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation. © 2017 International Society for Hemodialysis.

  16. Iron excess in recreational marathon runners.

    Science.gov (United States)

    Mettler, S; Zimmermann, M B

    2010-05-01

    Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. We investigated the iron status of 170 male and female recreational runners participating in the Zürich marathon. Iron deficiency was defined either as a plasma ferritin (PF) concentration or =4.5 (functional iron deficiency). After excluding subjects with elevated C-reactive protein concentrations, iron overload was defined as PF >200 microg/l. Iron depletion was found in only 2 out of 127 men (1.6% of the male study population) and in 12 out of 43 (28.0%) women. Functional iron deficiency was found in 5 (3.9%) and 11 (25.5%) male and female athletes, respectively. Body iron stores, calculated from the sTfR/PF ratio, were significantly higher (Pmarathon runners. Median PF among males was 104 microg/l, and the upper limit of the PF distribution in males was 628 microg/l. Iron overload was found in 19 out of 127 (15.0%) men but only 2 out of 43 in women (4.7%). Gender (male sex), but not age, was a predictor of higher PF (Pperformance, our findings indicate excess body iron may be common in male recreational runners and suggest supplements should only be used if tests of iron status indicate deficiency.

  17. The Histological Effects of L-arginine on Ventricular Myocardium in Iron Treated Male Rats

    Directory of Open Access Journals (Sweden)

    M Sofiabadi

    2012-05-01

    Full Text Available

    Background and Objectives: Iron overload is detrimental for the body and can create damage to different body tissues, such as myocardium by producing oxidative stress. Therefore, the antioxidant factors can neutralize iron induced damages. According to available reports, L-arginine as a precursor nitric oxide production has antioxidant effects. This study was carried out to evaluate the histological effects of iron overload on ventricular muscle and preventive role of L-arginine in male rats.
    Methods: In this experiment, 40 male rats with weight range of 300-250g were divided at random into five equal groups including:1- Control, 2- Iron (10mg/kg, ip, 3- Iron(10mg/kg, ip+L-arginine (1mg/ml, po, 4- Iron (50mg/kg, ip and 5- Iron (50mg/kg,ip+L-arginine(1mg/ml,po. After treatment (6 weeks, the animals were anesthetized and the samples of left apical ventricular myocardium were taken out and morphological studies were done following fixation with 10% formalin and H&E staining. Microscopic parameters under study were cell swelling, vessel dilatation and hypercongestion, cell necrosis and tissue deformity. The type and severity of damage to the tissue were also noted. Data were analyzed using chi-square statistical procedure, and Pvalue≤0.05 were considered to be significant. 
    Results: The data showed moderate changes in the ventricular myocardium of group 2 that was significant in comparison to the control group (P<0.05. The ventricular myocardium of group 3 showed low changes and wasn't significant in comparison to control group (P=0.84. The ventricular myocardium of the group 4 showed severe changes in comparison to the control group (P<0.01. The low change showed in the ventricular myocardium of group 5 that wasn't significant in comparison to the control group.

    Conclusion: This study showed

  18. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency.

    Directory of Open Access Journals (Sweden)

    Xavier Calvet

    Full Text Available OBJECTIVE: Intravenous iron is widely used to treat iron deficiency in day-care units. Ferric carboxymaltose (FCM allows administration of larger iron doses than iron sucrose (IS in each infusion (1000 mg vs. 200 mg. As FCM reduces the number of infusions required but is more expensive, we performed a cost-minimization analysis to compare the cost impact of the two drugs. MATERIALS AND METHODS: The number of infusions and the iron dose of 111 consecutive patients who received intravenous iron at a gastrointestinal diseases day-care unit from 8/2007 to 7/2008 were retrospectively obtained. Costs of intravenous iron drugs were obtained from the Spanish regulatory agencies. The accounting department of the Hospital determined hospital direct and indirect costs for outpatient iron infusion. Non-hospital direct costs were calculated on the basis of patient interviews. In the pharmacoeconomic model, base case mean costs per patient were calculated for administering 1000 mg of iron per infusion using FCM or 200 mg using IS. Sensitivity analysis and Monte Carlo simulation were performed. RESULTS: Under baseline assumptions, the estimated cost of iron infusion per patient and year was €304 for IS and €274 for FCM, a difference of €30 in favour of FCM. Adding non-hospital direct costs to the model increased the difference to €67 (€354 for IS vs. €287 for FCM. A Monte Carlo simulation taking into account non-hospital direct costs favoured the use of FCM in 97% of simulations. CONCLUSION: In this pharmacoeconomic analysis, FCM infusion reduced the costs of iron infusion at a gastrointestinal day-care unit.

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... making new blood cells. Visit our Aplastic Anemia Health Topic to learn more. ... recommend that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the ... of iron. The recommended daily amounts of iron will depend on your age, sex, and whether you ...

  1. Changes of iron concentrations in skin and plasma of patients with hemochromatosis along therapy

    International Nuclear Information System (INIS)

    Pinheiro, T.; Alves, L.C.; Neres, M.; Pinheiro, T.; Barreiros, A.; Fleming, R.; Silva, J.N.; Filipe, P.; Silva, R.

    2009-01-01

    Skin as a manageable organ can provide direct or indirect information of tissue iron overload resulting from inherited disorders as hemochromatosis. Patients with hemochromatosis were evaluated at three consecutive phases along the therapy programme. Nuclear microprobe techniques were used to assess skin iron and Total Reflection X-ray Fluorescence to determine the plasma iron concentrations. Results showed that iron pools were differently correlated at the three therapy phases. These variations highlighted the value of skin iron content to assess organ iron deposition and therapy efficacy. Skin iron content can be used for a better management of patients with iron overload pathologies. (author)

  2. Potential involvement of iron in the pathogenesis of peritoneal endometriosis.

    Science.gov (United States)

    Defrère, S; Lousse, J C; González-Ramos, R; Colette, S; Donnez, J; Van Langendonckt, A

    2008-07-01

    The aim of this study is to review the current literature associating endometriosis with iron and to discuss the potential causes and consequences of iron overload in the pelvic cavity. Indeed, iron is essential for all living organisms. However, excess iron can result in toxicity and is associated with pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different components of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). Animal models allow us to gather essential information on the origin, metabolism and effect of iron overload in endometriosis, which may originate from erythrocytes carried into the pelvic cavity mainly by retrograde menstruation. Peritoneal macrophages play an important role in the degradation of these erythrocytes and in subsequent peritoneal iron metabolism. Iron overload could affect a wide range of mechanisms involved in endometriosis development, such as oxidative stress or lesion proliferation. In conclusion, excess iron accumulation can result in toxicity and may be one of the factors contributing to the development of endometriosis. Treatment with an iron chelator could thus be beneficial in endometriosis patients to prevent iron overload in the pelvic cavity, thereby diminishing its deleterious effect.

  3. Overload Control in Smart Transformer-Fed Grid

    Directory of Open Access Journals (Sweden)

    Giovanni De Carne

    2017-02-01

    Full Text Available Renewable energy resources and new loads—such as electric vehicles—challenge grid management. Among several scenarios, the smart transformer represents a solution for simultaneously managing low- and medium-voltage grids, providing ancillary services to the distribution grid. However, unlike conventional transformers, the smart transformer has a very limited overload capability, because the junction temperature—which must always be below its maximum limit—is characterized by a short time constant. In this work, an overload control for smart transformer by means of voltage and frequency variations has been proposed and verified by means of simulations and experiments.

  4. A pre-concentration procedure using coprecipitation for determination of lead and iron in several samples using flame atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Saracoglu, S.; Soylak, M.; Peker, D.S. Kacar; Elci, L.; Santos, W.N.L. dos; Lemos, V.A.; Ferreira, S.L.C.

    2006-01-01

    The present paper proposes a pre-concentration procedure for determination of lead and iron in several samples by flame atomic absorption spectrometry. In it, lead(II) and iron(III) ions are coprecipitated using the violuric acid-copper(II) system as collector. Afterwards, the precipitate is dissolved with 1 M HNO 3 solution and the metal ions are determined. The optimization step was performed using factorial design involving the variables: pH, violuric acid mass (VA) and copper concentration (Cu). Using the optimized experimental conditions, the proposed procedure allows the determination these metals with detection limits of 0.18 μg L -1 for iron and 0.16 μg L -1 for lead. The effects of foreign ions on the pre-concentration procedure were also evaluated and the results demonstrated that this method could be applied for determination of iron and lead in several real samples. The proposed method was successfully applied to the analysis of seawater, urine, mineral water, soil and physiological solution samples. The concentrations of lead and iron achieved in these samples agree well with others data reported in the literature

  5. Current understanding of iron homeostasis.

    Science.gov (United States)

    Anderson, Gregory J; Frazer, David M

    2017-12-01

    Iron is an essential trace element, but it is also toxic in excess, and thus mammals have developed elegant mechanisms for keeping both cellular and whole-body iron concentrations within the optimal physiologic range. In the diet, iron is either sequestered within heme or in various nonheme forms. Although the absorption of heme iron is poorly understood, nonheme iron is transported across the apical membrane of the intestinal enterocyte by divalent metal-ion transporter 1 (DMT1) and is exported into the circulation via ferroportin 1 (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around the body to sites of utilization with the erythroid marrow having particularly high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1 on the surface of most body cells, and after endocytosis of the complex, iron enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used for metabolic functions, stored within cytosolic ferritin, or exported from the cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption and iron export from the tissues into the plasma are regulated by the liver-derived peptide hepcidin. When tissue iron demands are high, hepcidin concentrations are low and vice versa. Too little or too much iron can have important clinical consequences. Most iron deficiency reflects an inadequate supply of iron in the diet, whereas iron excess is usually associated with hereditary disorders. These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload. Despite major recent advances, much remains to be learned about iron physiology and pathophysiology. © 2017 American Society for Nutrition.

  6. Real-time PCR Demonstrates Ancylostoma duodenale Is a Key Factor in the Etiology of Severe Anemia and Iron Deficiency in Malawian Pre-school Children

    NARCIS (Netherlands)

    Jonker, Femkje A. M.; Calis, Job C. J.; Phiri, Kamija; Brienen, Eric A. T.; Khoffi, Harriet; Brabin, Bernard J.; Verweij, Jaco J.; van Hensbroek, Michael Boele; van Lieshout, Lisette

    2012-01-01

    Background: Hookworm infections are an important cause of (severe) anemia and iron deficiency in children in the tropics. Type of hookworm species (Ancylostoma duodenale or Necator americanus) and infection load are considered associated with disease burden, although these parameters are rarely

  7. Elbow arthroscopy: valgus extension overload.

    Science.gov (United States)

    Ahmad, Christopher S; Conway, John E

    2011-01-01

    Valgus torque combined with deceleration produces high compression and shear forces acting on the posteromedial olecranon and the posteromedial trochlea. This valgus extension overload process may cause posteromedial trochlea chondromalacia, chondral flap formation, osteochondrosis, subchondral erosion, a subchondral insufficiency fracture, and marginal exostosis formation. Olecranon pathologies include proximal stress reaction, a posteromedial tip stress fracture, a transverse proximal process stress fracture, exostosis formation, exostosis fragmentation, and intra-articular loose bodies. Symptoms include posteromedial elbow pain during the deceleration phase of the throwing motion. The extension impingement test reproduces posterior or posteromedial pain similar to that experienced while throwing. Special radiographic techniques and CT scans can show loose bodies and osteophyte fragmentation. Surgical treatment is indicated when symptoms persist despite nonsurgical management. Based on clinical and basic science research, all patients with valgus extension overload should be comprehensively evaluated for medial ulnar collateral ligament insufficiency. Surgical treatment is limited to the resection of osteophytes only; normal olecranon should not be resected.

  8. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

    Full Text Available Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulates health and lifespan.

  9. Secondary Hemochromatosis due to Chronic Oral Iron Supplementation

    Directory of Open Access Journals (Sweden)

    Ronald Lands

    2017-01-01

    Full Text Available Iron may accumulate in excess due to a mutation in the HFE gene that upregulates absorption or when it is ingested or infused at levels that exceed the body’s ability to clear it. Excess iron deposition in parenchymal tissue causes injury and ultimately organ dysfunction. Diabetes mellitus and hepatic cirrhosis due to pancreas and liver damage are just two examples of diseases that result from iron overload. Despite the rapid growth of information regarding iron metabolism and iron overload states, the most effective treatment is still serial phlebotomies. We present a patient who developed iron overload due to chronic ingestion of oral ferrous sulfate. This case illustrates the importance of querying geriatric patients regarding their use of nonprescription iron products without a medical indication.

  10. Real-time PCR Demonstrates Ancylostoma duodenale Is a Key Factor in the Etiology of Severe Anemia and Iron Deficiency in Malawian Pre-school Children

    Science.gov (United States)

    Jonker, Femkje A. M.; Calis, Job C. J.; Phiri, Kamija; Brienen, Eric A. T.; Khoffi, Harriet; Brabin, Bernard J.; Verweij, Jaco J.; van Hensbroek, Michael Boele; van Lieshout, Lisette

    2012-01-01

    Background Hookworm infections are an important cause of (severe) anemia and iron deficiency in children in the tropics. Type of hookworm species (Ancylostoma duodenale or Necator americanus) and infection load are considered associated with disease burden, although these parameters are rarely assessed due to limitations of currently used diagnostic methods. Using multiplex real-time PCR, we evaluated hookworm species-specific prevalence, infection load and their contribution towards severe anemia and iron deficiency in pre-school children in Malawi. Methodology and Findings A. duodenale and N. americanus DNA loads were determined in 830 fecal samples of pre-school children participating in a case control study investigating severe anemia. Using multiplex real-time PCR, hookworm infections were found in 34.1% of the severely anemic cases and in 27.0% of the non-severely anemic controls (panemia (adjusted odds ratio: 2.49 (95%CI 1.16–5.33) and 9.04 (95%CI 2.52–32.47) respectively). Iron deficiency (assessed through bone marrow examination) was positively associated with intensity of A. duodenale infection (adjusted odds ratio: 3.63 (95%CI 1.18–11.20); 16.98 (95%CI 3.88–74.35) and 44.91 (95%CI 5.23–385.77) for low, moderate and high load respectively). Conclusions/Significance This is the first report assessing the association of hookworm load and species differentiation with severe anemia and bone marrow iron deficiency. By revealing a much higher than expected prevalence of A. duodenale and its significant and load-dependent association with severe anemia and iron deficiency in pre-school children in Malawi, we demonstrated the need for quantitative and species-specific screening of hookworm infections. Multiplex real-time PCR is a powerful diagnostic tool for public health research to combat (severe) anemia and iron deficiency in children living in resource poor settings. PMID:22514750

  11. Studies on Ancylostomiasis: II.Clinical Symptomatology, Effects of Drugs, especially of Iron Compounds, with Relation to the Severity of Artificial Infection

    International Nuclear Information System (INIS)

    Lee, Mun Ho; Kim, Dong Jip; Lee, Jang Kyu; Seo, Byong Sul

    1967-01-01

    This study was aimed; firstly to observe various clinical symptomatology with relation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminics and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology. 1) The most frequently encountered symptoms and signs were general malaise, cough and hoarseness. The tracheal itching and pain, low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2) If the larger number of the larvae was given, the clinical symptomatology was more severe. 3) Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4) In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds. 1) The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from 15-20 days later and a recovery after 2 months. 2) The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3) The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4) The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency

  12. Studies on Ancylostomiasis: II.Clinical Symptomatology, Effects of Drugs, especially of Iron Compounds, with Relation to the Severity of Artificial Infection

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mun Ho; Kim, Dong Jip; Lee, Jang Kyu; Seo, Byong Sul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1967-09-15

    This study was aimed; firstly to observe various clinical symptomatology with relation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminics and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology. 1) The most frequently encountered symptoms and signs were general malaise, cough and hoarseness. The tracheal itching and pain, low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2) If the larger number of the larvae was given, the clinical symptomatology was more severe. 3) Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4) In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds. 1) The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from 15-20 days later and a recovery after 2 months. 2) The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3) The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4) The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency

  13. Transforming growth factor 15 increased in severe aplastic anemia patients.

    Science.gov (United States)

    Shao, Yuanyuan; Wang, Honglei; Liu, Chunyan; Cao, Qiuying; Fu, Rong; Wang, Huaquan; Wang, Ting; Qi, Weiwei; Shao, Zonghong

    2017-10-01

    The patients with severe aplastic anemia (SAA) usually rely on red cell transfusion which lead to secondary iron overload. Transforming growth differentiation factor-15 (GDF-15) plays an important role in erythropoiesis and iron regulation. In this study, we investigated the level of GDF-15 and other indexes of iron metabolism in SAA patients to explore the correlation with GDF-15 and iron overload in SAA. The levels of serum GDF-15, hepcidin (Hepc), and erythropoietin (EPO) were determined by ELISA. The levels of serum iron (SI), ferritin, TIBC, and transferrin saturation (TS) were measured by an auto analyzer. Iron staining of bone marrow cells was used for testing extracellular and intracellular iron. The GDF-15 level in the experimental group was higher than that of the case-control group and normal control group (all p < 0.05). The Hepc level in the experimental group and case-control group were both higher than that of healthy controls (all p < 0.05). The Hepc level was significantly lower in the experimental group patients who had excessive GDF-15 (r = -0.766, p = 0.000). There was a positive correlation between the level of GDF15 and EPO in the experimental group (r = 0.68, p < 0.000). The level of GDF15 in SAA patients was positively correlated with SI levels (r = 0.537, p = 0.008), TS levels (r = 0.466, p = 0.025), and sideroblasts (%) (r = 0.463, p = 0.026). Moreover, there was a positive correlation between GDF-15 level and blood transfusion-dependent time (r = 0.739, p = 0.000). Our data indicated that GDF-15 plays an important role in iron metabolism in SAA. GDF-15 might be a novel target for SAA therapy.

  14. Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

    Science.gov (United States)

    Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-01-01

    Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

  15. Liver iron concentration quantification by MRI: are recommended protocols accurate enough for clinical practice?

    International Nuclear Information System (INIS)

    Castiella, Agustin; Zapata, Eva Mia; Alustiza, Jose M.; Emparanza, Jose I.; Costero, Belen; Diez, Maria I.

    2011-01-01

    To assess the accuracy of quantification of liver iron concentration (LIC) by MRI using the Rennes University (URennes) algorithm. In the overall study period 1999-2006 the LIC in 171 patients was calculated with the URennes model and the results were compared with LIC measured by liver biopsy. The biopsy showed that 107 patients had no overload, 38 moderate overload and 26 high overload. The correlation between MRI and biopsy was r = 0.86. MRI correctly classified 105 patients according to the various levels of LIC. Diagnostic accuracy was 61.4%, with a tendency to overestimate overload: 43% of patients with no overload were diagnosed as having overload, and 44.7% of patients with moderate overload were diagnosed as having high overload. The sensitivity of the URennes method for high overload was 92.3%, and the specificity for the absence of overload was 57.0%. MRI values greater than 170 μmol Fe/g revealed a positive predictive value (PPV) for haemochromatosis of 100% (n = 18); concentrations below 60 μmol Fe/g had a negative predictive value (NPV) of 100% for haemochromatosis (n = 101). The diagnosis in 44 patients with intermediate values remained uncertain. The assessment of LIC with the URennes method was useful in 74.3% of the patients to rule out or to diagnose high iron overload. The method has a tendency to overestimate overload, which limits its diagnostic performance. (orig.)

  16. Liver iron concentration quantification by MRI: are recommended protocols accurate enough for clinical practice?

    Energy Technology Data Exchange (ETDEWEB)

    Castiella, Agustin; Zapata, Eva M. [Mendaro Hospital, Gastroenterology Service, Mendaro (Spain); Alustiza, Jose M. [Osatek Donostia, Radiology Service, Donostia (Spain); Emparanza, Jose I. [Donostia Hospital CASPe, CIBER-ESP, Clinical Epidemiology Unit, Donostia (Spain); Costero, Belen [Principe de Asturias Hospital, Gastroenterology Service, Alcala de Henares (Spain); Diez, Maria I. [Principe de Asturias Hospital, Radiology Service, Alcala de Henares (Spain)

    2011-01-15

    To assess the accuracy of quantification of liver iron concentration (LIC) by MRI using the Rennes University (URennes) algorithm. In the overall study period 1999-2006 the LIC in 171 patients was calculated with the URennes model and the results were compared with LIC measured by liver biopsy. The biopsy showed that 107 patients had no overload, 38 moderate overload and 26 high overload. The correlation between MRI and biopsy was r = 0.86. MRI correctly classified 105 patients according to the various levels of LIC. Diagnostic accuracy was 61.4%, with a tendency to overestimate overload: 43% of patients with no overload were diagnosed as having overload, and 44.7% of patients with moderate overload were diagnosed as having high overload. The sensitivity of the URennes method for high overload was 92.3%, and the specificity for the absence of overload was 57.0%. MRI values greater than 170 {mu}mol Fe/g revealed a positive predictive value (PPV) for haemochromatosis of 100% (n = 18); concentrations below 60 {mu}mol Fe/g had a negative predictive value (NPV) of 100% for haemochromatosis (n = 101). The diagnosis in 44 patients with intermediate values remained uncertain. The assessment of LIC with the URennes method was useful in 74.3% of the patients to rule out or to diagnose high iron overload. The method has a tendency to overestimate overload, which limits its diagnostic performance. (orig.)

  17. Left ventricular function in right ventricular overload

    International Nuclear Information System (INIS)

    Iwanaga, Shiro; Handa, Shunnosuke; Abe, Sumihisa; Onishi, Shohei; Nakamura, Yoshiro; Kunieda, Etsuo; Ogawa, Koichi; Kubo, Atsushi

    1989-01-01

    This study clarified regional and global functions of the distorted left ventricle due to right ventricular overload by gated radionuclide ventriculography (RNV). Cardiac catheterization and RNV were performed in 13 cases of atrial septal defect (ASD), 13 of pure mitral stenosis (MS), 10 of primary pulmonary hypertension (PPH), and 10 of normal subjects (NL). Right ventricular systolic pressure (RVSP) was 32.9±13.9, 45.0±12.2, 88.3±17.1, and 21.2±4.5 mmHg, respectively. The end-systolic LAO view of the left ventricle was halved into septal and free-wall sides. The end-diastolic halves were determined in the same plane. Ejection fractions of the global left ventricle (LVEF), global right ventricle (RVEF), the septal half of the left ventricle (SEPEF), and the free-wall half of the left ventricle (FWEF) were obtained. LVEF was 56.8±9.8% in NL, 52.8±10.5% in ASD, and 49.5±12.9% in PPH. In MS, LVEF (47.0±13.0%) was smaller than those in the other groups. RVEF was 37.0±5.2% in NL, 43.7±15.5% in ASD, and 32.8±11.5% in MS. In PPH, RVEF (25.0±10.6%) was smaller than those in the other groups. SEPEF was smaller in ASD (42.5±13.2%), MS (40.4±13.1%), PPH (40.5±12.5%) than in NL (53.5±8.5%). Systolic function of the septal half of the left ventricle was disturbed by right ventricular overload. RVEF (r=-0.35, p<0.05) and SEPEF (r=-0.51, p<0.01) had negative correlations with RVSP. As RVSP rose, systolic function of the septal half of the left ventricle was more severely disturbed. FWEF was the same among the four groups; NL (57.0±12.6%), ASD (48.6±15.2%), MS (50.5±12.0%), and PPH (51.1±12.3%). There was a good correlation between SEPEF and LVEF in NL (r=0.81), although in PPH this correlation was poor (r=0.64). These data showed that the distorted left ventricular due to right ventricular overload maintains its global function with preserved function of the free-wall side. (J.P.N.)

  18. Iron inhibits respiratory burst of peritoneal phagocytes in vitro

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Jurek, Aleksandra; Kubit, Piotr

    2011-01-01

    Objective. This study examines the effects of iron ions Fe(3+) on the respiratory burst of phagocytes isolated from peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients, as an in vitro model of iron overload in end-stage renal disease (ESRD). Material and Methods....... Respiratory burst of peritoneal phagocytes was measured by chemiluminescence method. Results. At the highest used concentration of iron ions Fe(3+) (100 µM), free radicals production by peritoneal phagocytes was reduced by 90% compared to control. Conclusions. Iron overload may increase the risk of infectious...

  19. Changes in cardiac output and incidence of volume overload in cirrhotics receiving 20% albumin infusion.

    Science.gov (United States)

    Shasthry, Saggere M; Kumar, Manoj; Khumuckham, Jelen S; Sarin, Shiv Kumar

    2017-08-01

    Patients with cirrhosis are prone to develop volume over load, have increased capillary permeability and latent or overt cardiomyopathy. Whether albumin infusion causes volume overload in cirrhotics has not been adequately studied. Ninety nine consecutive cirrhotic patients receiving 1gm per kg albumin infusion were evaluated for development of volume overload. Clinical, echocardiographic and haemodynamic changes were closely monitored during and after albumin infusion. Thirty (30.30%) patients developed volume overload. Patients with higher BMI (P=.003), lower CTP (P=.01) and MELD (P=.034) were more often associated with the development of volume overload. Though baseline diastolic dysfunction was present in 82.8% of the patients, it did not influence the development of volume overload or changes in the cardiac output. The cardiac output increased significantly after albumin infusion (4.9±1.554 L/min to 5.86±1.85 L/min, Palbumin infusion develop volume overload, specially, those with higher BMI and lower severity of liver disease. Cardiac output increases after albumin infusion, and, baseline diastolic dysfunction has little effect on the development of volume overload or changes in cardiac output. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Work Overload and Turnover Intention of Junior Auditors in Greater Jakarta, Indonesia

    OpenAIRE

    Andika Pradana; Imam Salehudin

    2015-01-01

    This paper aims to analyze how work overload influences turnover intentions of newly hired junior auditors in public accounting offices. Job satisfaction, work related stress and work life conflicts are used as mediating variables between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. The sample was selected using purposive sampling. Three mediation hypotheses were tested using Structural Equation M...

  1. Application of the Moessbauer spectroscopy to the investigation of the proton irradiation effects in several iron compounds

    International Nuclear Information System (INIS)

    Kopcewicz, M.; Kotlicki, A.

    1975-01-01

    The results of a study into the influence of proton irradiation on the Moessbauer effect in FeSO 4 x 7H 2 O, K 4 [Fe(CN) 6 ] x 3H 2 O and K 3 [Fe(CN) 6 ] are reported. In the interpretation of the effect observed, the 'spike' model was applied. Chemical decomposition processes due to proton irradiation and formation of the superparamagnetic state of metallic iron were investigated. A Moessbauer observation of interstitial Fe 2+ ions in irradiated FeSO 4 x 7H 2 O was made. (Z.S.)

  2. Moessbauer spectroscopic studies of iron-storage proteins

    Energy Technology Data Exchange (ETDEWEB)

    St. Pierre, T.G.

    1986-01-01

    /sup 57/Fe Moessbauer spectroscopy was used to study iron storage proteins. Various cryostats and a superconducting magnet were used to obtain sample environment temperatures from 1.3 to 200K and applied magnetic fields of up to 10T. The Moessbauer spectra of ferritins isolated from iron-overloaded human spleen, limpet (Patella vulgata), giant limpet (Patella laticostata) and chiton (Clavarizona hirtosa) hemolymph, and bacterial (Pseudomonas aeruginosa) cells are used to gain information on the magnetic ordering- and superparamagnetic transition temperatures of the microcrystalline cores of the proteins. Investigations were made about the cause of the difference in the magnetic anisotropy constants of the cores of iron-overloaded human spleen ferritin and hemosiderin. Livers taken from an iron-overloaded hornbill and artificially iron-loaded rats showed no component with a superparamagnetic transition temperature approaching that of the human spleen hemosiderin.

  3. Work Overload and Turnover Intention of Junior Auditors in Greater Jakarta, Indonesia

    Directory of Open Access Journals (Sweden)

    Andika Pradana

    2015-11-01

    Full Text Available This paper aims to analyze how work overload influences turnover intentions of newly hired junior auditors in public accounting offices. Job satisfaction, work related stress and work life conflicts are used as mediating variables between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. The sample was selected using purposive sampling. Three mediation hypotheses were tested using Structural Equation Modeling (SEM. The results show that work overload has a significant effect on increasing turnover intention through both job satisfaction and work related stress. In comparison, work overload does not influence turnover intention through work life balance. This may be due to the nature of the respondents, in which a majority of the newly hired accountants employed in this study are unmarried.

  4. WORK OVERLOAD AND TURNOVER INTENTION OF JUNIOR AUDITORS IN GREATER JAKARTA, INDONESIA

    Directory of Open Access Journals (Sweden)

    Andika Pradana

    2015-11-01

    Full Text Available This paper aims to analyze how work overload influences turnover intentions of newly hired junior auditors in public accounting offices. Job satisfaction, work related stress and work life conflicts are used as mediating variables between work overload and turnover intention. This study employed 141 auditors from several accounting firms operating in the Greater Jakarta region. The sample was selected using purposive sampling. Three mediation hypotheses were tested using Structural Equation Modeling (SEM. The results show that work overload has a significant effect on increas- ing turnover intention through both job satisfaction and work related stress. In comparison, work overload does not influence turnover intention through work life balance. This may be due to the nature of the respondents, in which a majority of the newly hired accountants employed in this study are unmarried.

  5. Hydroxyurea could be a good clinically relevant iron chelator.

    Science.gov (United States)

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2013-01-01

    Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  6. Hydroxyurea could be a good clinically relevant iron chelator.

    Directory of Open Access Journals (Sweden)

    Khushnooma Italia

    Full Text Available Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  7. Overload protection system for power inverter

    Science.gov (United States)

    Nagano, S. (Inventor)

    1977-01-01

    An overload protection system for a power inverter utilized a first circuit for monitoring current to the load from the power inverter to detect an overload and a control circuit to shut off the power inverter, when an overload condition was detected. At the same time, a monitoring current inverter was turned on to deliver current to the load at a very low power level. A second circuit monitored current to the load, from the monitoring current inverter, to hold the power inverter off through the control circuit, until the overload condition was cleared so that the control circuit may be deactivated in order for the power inverter to be restored after the monitoring current inverter is turned off completely.

  8. The extrahepatic role of TFR2 in iron homeostasis

    Directory of Open Access Journals (Sweden)

    Laura eSilvestri

    2014-05-01

    Full Text Available Transferrin receptor 2 (TFR2, a protein homologous to the cell iron importer transferrin receptor 1 (TFR1, is expressed in the liver and erythroid cells and is reported to bind diferric transferrin, although at lower affinity than TFR1. TFR2 gene is mutated in type 3 hemochromatosis, a disorder characterized by iron overload and inability to upregulate hepcidin in response to iron. Liver TFR2 is considered a sensor of diferric transferrin, possibly in a complex with HFE. In erythroid cells TFR2 is a partner of erythropoietin receptor (EPOR and stabilizes the receptor on the cell surface. However, Tfr2 null mice as well as TFR2 hemochromatosis patients do not show defective erythropoiesis and tolerate repeated phlebotomy. The iron deficient Tfr2-Tmprss6 double knock out mice have higher red cells count and more severe microcytosis than the liver specific Tfr2 and Tmprss6 double knock out mice. TFR2 in the bone marrow might be a sensor of iron deficiency that protects against excessive microcytosis in a way that involves EPOR, although the mechanisms remain to be worked out.

  9. [Iron and invasive fungal infection].

    Science.gov (United States)

    Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

    2013-01-01

    Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... family history and genetics , lifestyle habits, or sex. Age You may be at increased risk for iron ... Signs, Symptoms, and Complications Iron-deficiency anemia can range from mild to severe. People with mild or ...

  11. Overload Control in a SIP Signaling Network

    OpenAIRE

    Masataka Ohta

    2007-01-01

    The Internet telephony employs a new type of Internet communication on which a mutual communication is realized by establishing sessions. Session Initiation Protocol (SIP) is used to establish sessions between end-users. For unreliable transmission (UDP), SIP message should be retransmitted when it is lost. The retransmissions increase a load of the SIP signaling network, and sometimes lead to performance degradation when a network is overloaded. The paper proposes an overload control for a S...

  12. Thermal Characterization of the Overload Carbon Resistors

    Directory of Open Access Journals (Sweden)

    Ivana Kostić

    2013-01-01

    Full Text Available In many applications, the electronic component is not continuously but only intermittently overloaded (e.g., inrush current, short circuit, or discharging interference. With this paper, we provide insight into carbon resistors that have to hold out a rarely occurring transient overload. Using simple electrical circuit, the resistor is overheating with higher current than declared, and dissipation is observed by a thermal camera.

  13. Overloaded CDMA Systems with Displaced Binary Signatures

    Directory of Open Access Journals (Sweden)

    Vanhaverbeke Frederik

    2004-01-01

    Full Text Available We extend three types of overloaded CDMA systems, by displacing in time the binary signature sequences of these systems: (1 random spreading (PN, (2 multiple-OCDMA (MO, and (3 PN/OCDMA (PN/O. For each of these systems, we determine the time shifts that minimize the overall multiuser interference power. The achievable channel load with coded and uncoded data is evaluated for the conventional (without displacement and improved (with displacement systems, as well as for systems based on quasi-Welch-bound-equality (QWBE sequences, by means of several types of turbo detectors. For each system, the best performing turbo detector is selected in order to compare the performance of these systems. It is found that the improved systems substantially outperform their original counterparts. With uncoded data, (improved PN/O yields the highest acceptable channel load. For coded data, MO allows for the highest acceptable channel load over all considered systems, both for the conventional and the improved systems. In the latter case, channel loads of about 280% are achievable with a low degradation as compared to a single user system.

  14. SQUID biosusceptometry in the measurement of hepatic iron

    International Nuclear Information System (INIS)

    Sheth, Sujit

    2003-01-01

    Individuals with primary or secondary abnormalities of iron metabolism, such as hereditary hemochromatosis and transfusional iron loading, may develop potentially lethal systemic iron overload. Over time, this excess iron is progressively deposited in the liver, heart, pancreas, and other organs, resulting in cirrhosis, heart disease, diabetes and other disorders. Unless treated, death usually results from cardiac failure. The amount of iron in the liver is the best indicator of the amount of iron in the whole body. At present, the only sure way to measure the amount of iron in the liver is to remove a sample of the liver by biopsy. Iron stored in the liver can be magnetized to a small degree when placed in a magnetic field. The amount of magnetization is measured by our instrument, called a superconducting quantum interference device (SQUID) susceptometer. In patients with iron overload, our previous studies have shown that magnetic measurements of liver iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy. The safety, ease, rapidity, and comfort of magnetic measurements make frequent, serial studies technically feasible and practically acceptable to patients. (orig.)

  15. Role of electrocardiographic changes in discriminating acute or chronic right ventricular pressure overload.

    Science.gov (United States)

    Can, Mehmet Mustafa; Özveren, Olcay; Biteker, Murat; Şengül, Cihan; Uz, Ömer; Işılak, Zafer; Kırılmaz, Ata

    2013-06-01

    Pulmonary embolism (PE) and severe pulmonary stenosis (PS) are two distinct conditions accompanied by increased pressure load of the right ventricle (RV). Despite major advances in our understanding of the mechanisms of RV adaptation to the increased pressure, substantial gaps in our knowledge remain unsettled. One of much less known aspect of pressure overload of RV is its impact on electrocardiographic (ECG) changes. In this study, we aimed to study whether acute and chronic RV overload are accompanied by different ECG patterns. Thirty-eight patients with PE underwent ECG monitoring were compared with 20 matched patients with PS in this observational retrospective study. ECG abnormalities suggestive of RV overload were recorded and analyzed in both groups. Logistic regression analysis was used to define the predictors of chronic RV overload. Among the ECG changes studied, premature atrial contraction (OR-12.2, 95% CI, 1.3-107, p=0.008), right axis deviation (OR-20.4, 95% CI 4.2-98, poverload. Our data indicate that the ECG changes that attributed to the acute RV pressure loading states may be more prevalent in chronic RV overload as compared with acute RV overload.

  16. The role of iron in patients after bone marrow transplantation.

    NARCIS (Netherlands)

    Witte, T.J.M. de

    2008-01-01

    Haemopoietic stem cell transplantation (HSCT) is an important intervention for malignant and non-malignant blood diseases. However, HSCT is also associated with considerable morbidity and mortality, some of which may be related to iron overload. Levels of serum iron are elevated in patients

  17. Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading

    OpenAIRE

    Makui, Hortence; Soares, Ricardo J.; Jiang, Wenlei; Constante, Marco; Santos, Manuela M.

    2005-01-01

    Hereditary hemochromatosis (HH), an iron overload disease associated with mutations in the HFE gene, is characterized by increased intestinal iron absorption and consequent deposition of excess iron, primarily in the liver. Patients with HH and Hfe-deficient (Hfe−/−) mice manifest inappropriate expression of the iron absorption regulator hepcidin, a peptide hormone produced by the liver in response to iron loading. In this study, we investigated the contribution of Hfe expression in macrophag...

  18. Study on the distribution of radioactive trace elements in vitamin D-overloaded rats using the multitracer technique

    International Nuclear Information System (INIS)

    Hirunuma, Rieko; Enomoto, Shuichi; Ambe, Fumitoshi; Endo, Kazutoyo; Ambe, Shizuko

    1999-01-01

    The uptake and distribution of radioisotopes of beryllium, calcium, scandium, vanadium, chromium, manganese, iron, cobalt, nickel, zinc, gallium, arsenic, strontium and barium in vitamin D (VD)-overloaded rats were investigated and compared with those in control rats, using the multitracer technique. Each element revealed its characteristic distribution among various organs in control and VD-overloaded rats. For some elements, such as cobalt and chromium, the distribution patterns in them were significantly different. These results are discussed in terms of the metabolism of the elements in rats

  19. Physical activity behavior and role overload in mothers.

    Science.gov (United States)

    Lovell, Geoff P; Butler, Frances R

    2015-01-01

    We examined physical activity stages of change, physical activity behavior, and role overload in different stages of motherhood in a predominantly Australian sample. Neither physical activity behavior, stages of physical activity change, nor role overload significantly differed across motherhood groups. Role overload was significantly higher for mothers in the contemplation, planning, and action stages of physical activity than in the maintenance stage of change. Role overload had a weak, although significant, negative correlation with leisure-time physical activity. We conclude that strategies focused upon reducing role overload or perceived role overload have only limited potential to meaningfully increase leisure-time physical activity in mothers.

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s ... making new blood cells. Visit our Aplastic Anemia Health Topic to learn more. ... recommend that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... bleeding or other abnormalities, such as growths or cancer of the lining of the colon. For this test, a ... that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... severity of the condition. Your doctor may recommend healthy eating changes, iron supplements, intravenous iron therapy for mild ... you: Adopt healthy lifestyle changes such as heart-healthy eating patterns. Increase your daily intake of iron-rich ...

  3. The Role of Iron in the Skin & Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Josephine Anne Wright

    2014-07-01

    Full Text Available In this review article we discuss current knowledge about iron in the skin and the cutaneous wound healing process. Iron plays a key role in both oxidative stress and photo-induced skin damage. The main causes of oxidative stress in the skin include reactive oxygen species (ROS generated in the skin by ultraviolet (UVA 320-400 nm portion of the ultraviolet spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anaemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anaemia on wound healing using a variety of experimental methodology to establish anaemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialisation. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localised iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary haemochromatosis. Iron plays a key role in chronic ulceration and conditions such as Rheumatoid Arthritis (RA and Lupus Erythematosus are associated with both anaemia of chronic disease and dysregulation of local cutaneous iron haemostasis. Iron is a potential therapeutic target in the skin by application of topical iron chelators and novel pharmacological agents, and in delayed cutaneous wound healing by treatment of iron deficiency or underlying systemic inflammation.

  4. The Family in Care for the Elderly: Managing the Overload and Coping with Difficulties

    Directory of Open Access Journals (Sweden)

    Lisete dos Santos Mendes Mónico

    2017-08-01

    Full Text Available Introduction: Family is considered the main support of the elderly in a situation of dependency. Caregiving often results in overloading, leading to diverse problems. Aim: To evaluate the self-perception of the family caregiver’s overload and the strategies used to provide informal care to the dependent elderly considering their level of dependence. Method: The sample consisted of 21 children, 16 spouses, and nine other relatives of elderly dependents who responded to the Caregiver’s Overload Scale (Sequeira, 2007, the Portuguese version of Caregivers’ Assessment Management Index (CAMI, Nolan, Keady, & Grant, 1995 and the Barthel Index (Mahoney & Barthel, 1965. Results: The Barthel Index showed 34.8% of the elderly as severely dependent and 37.0% as totally dependent. The care most provided respected to medication, hygiene, food, and monitoring. Above 56.5% of the caregivers had an intense overload, both at the objective (impact of care and interpersonal relationship and subjective (F3-Expectations regarding care and F4-Perceived self-efficacy levels. The main reason for maintaining caregivers was family/personal obligation (95.7%. Caregivers reasonably assessed the effectiveness of their strategies in dealing with their dependent elderly (CAMI; M = 101.0, SD = 15.0. There was a negative relationship between the perception of the caregiver’s overload and the age and health status of the elderly, as well as between the number of strategies used by the caregiver to overcome difficulties and the self-perception of the overload. Conclusion: The multiplicity of daily tasks performed in support of a family member in a situation of severe dependence translates into situations of intense overload, negatively impacting on care, interpersonal relationship, expectations regarding caring, and perception of self-efficacy of care.

  5. Improved R2* liver iron concentration assessment using a novel fuzzy c-mean clustering scheme

    International Nuclear Information System (INIS)

    Saiviroonporn, Pairash; Viprakasit, Vip; Krittayaphong, Rungroj

    2015-01-01

    In thalassemia patients, R2* liver iron concentration (LIC) measurement is a common clinical tool for assessing iron overload and for determining necessary chelator dose and evaluating its efficacy. Despite the importance of accurate LIC measurement, existing methods suffer from LIC variability, especially at the severe iron overload range due to inclusion of vessel parts in LIC calculation. In this study, we build upon previous Fuzzy C-Mean (FCM) clustering work to formulate a scheme with superior performance in segmenting vessel pixels from the parenchyma. Our method (MIX-FCM) combines our novel 2D-FCM with the existing 1D-FCM algorithm. This study further assessed possible optimal clustering parameters (OP scheme) and proposed a semi-automatic (SA) scheme for routine clinical application. Segmentation of liver parenchyma and vessels was performed on T2* images and their LIC maps in 196 studies from 147 thalassemia major patients. We used manual segmentation as the reference. 1D-FCM clustering was performed on the acquired image alone and 2D-FCM used both the acquired image and its LIC data. To execute the MIX-FCM method, the best outcome (OP-MIX-FCM) was selected from the aforementioned methods and was compared to the SA-MIX-FCM scheme. We used the percent value of the normalized interquartile range (nIQR) to its median to evaluate the variability of all methods. 2D-FCM clustering is more effective than 1D-FCM clustering at the severe overload range only, but inferior for other ranges (where 1D-FCM provides suitable results). This complementary performance between the two methods allows MIX-FCM to improve results for all ranges. OP-MIX-FCM clustering error was 2.1 ± 2.3 %, compared with 10.3 ± 9.9 % and 7.0 ± 11.9 % from 1D- and 2D-FCM clustering, respectively. SA-MIX-FCM result was comparable to OP-MIX-FCM result, with both schemes showing ability to decrease overall nIQR by approximately 30 %. Our proposed 2D-FCM algorithm is not as superior to 1D-FCM as

  6. Radionuclide stroke count ratios for assessment of right and left ventricular volume overload in children

    International Nuclear Information System (INIS)

    Parrish, M.D.; Graham, T.P. Jr.; Born, M.L.; Jones, J.P.; Boucek, R.J. Jr.; Artman, M.; Partain, C.L.

    1983-01-01

    The ratio of left ventricular to right ventricular stroke counts measured by radionuclide angiography has been used in adults to estimate the severity of left-sided valvular regurgitation. The validation of this technique in children for assessment of right and left ventricular volume overload is reported herein. Radionuclide stroke count ratios in 60 children aged 0.5 to 19 years (mean 11) were determined. Based on their diagnoses, the patients were divided into 3 groups: (1) normal--40 patients with no shunts or valvular regurgitation, (2) left ventricular volume overload--13 patients with mitral or aortic regurgitation, or both, and (3) right ventricular volume overload--7 patients, 2 with severe tricuspid regurgitation, 3 with atrial septal defects, and 2 with total anomalous pulmonary venous drainage. The radionuclide stroke count ratio clearly differentiated these groups (p less than 0.05): normal patients had a stroke count ratio of 1.04 +/- 0.17 (mean +/- 1 standard deviation), the left ventricular volume overload group had a stroke count ratio of 2.43 +/- 0.86, and the right ventricular volume overload group had a stroke count ratio of 0.44 +/- 0.17. In 22 of our 60 patients, radionuclide stroke count ratios were compared with cineangiographic stroke volume ratios, resulting in a correlation coefficient of 0.88. It is concluded that radionuclide ventriculography is an excellent tool for qualitative and quantitative assessment of valvular regurgitation in children

  7. Peculiarities on voltage - current characteristics of HTS tapes at overloading conditions cooled by liquid nitrogen

    International Nuclear Information System (INIS)

    Vysotsky, V S; Fetisov, S S; Sytnikov, V E

    2008-01-01

    Electro - technical devices are considered as the most prospective use for high temperature superconductors. For such devices the overload currents due to faults in grids are the operational reality. In these cases the fault currents may forcibly go to superconductors being sometimes dozens times more than the critical currents of HTS. Overloads are the working modes for fault current limiters also. To understand the behavior of HTS devices at overloads it is important to study voltage-current characteristics (VCC) of basic HTS tapes in real cooling conditions. The knowledge of VCC permits to model and to simulate properly HTS devices behavior at overloads. We performed the study of VCC of several HTS tapes at currents several times more than their critical ones. Both, 1-G and 2-G tapes were tested. There were found peculiarities or 'spikes' on VCC at rising currents that vanished at decaying currents. It was shown that such peculiarities are determined by the change of cooling conditions from the convective heat exchange to the nucleate boiling. Nucleate boiling activation and development times were determined. Their dependencies on heat release were measured. The data obtained can be used in simulation of heating of real superconducting devices at overload conditions

  8. Control over Permissible Short Emergency Overloads in Power Transformers

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2010-01-01

    Full Text Available The paper proposes a method for determination a permissible duration of short intermittent overloads of power transformers that permits to avoid non-permissible over-heating of winding insulation and fully utilize overloading transformer ability.

  9. MRI evaluation of tissue iron burden in patients with {beta}-thalassaemia major

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I.; Astrakas, Loukas [University of Ioannina, Radiology Department, Medical School, Ioannina (Greece)

    2007-12-15

    {beta}-Thalassaemia major is a hereditary haemolytic anaemia that is treated with multiple blood transfusions. A major complication of this treatment is iron overload, which leads to cell death and organ dysfunction. Chelation therapy, used for iron elimination, requires effective monitoring of the body burden of iron, for which serum ferritin levels and liver iron content measured in liver biopsies are used as markers, but are not reliable. MRI based on iron-induced T2 relaxation enhancement can be used for the evaluation of tissue siderosis. Various MR protocols using signal intensity ratio and mainstream relaxometry methods have been used, sometimes with discrepant results. Relaxometry methods using multiple echoes achieve better sampling of the time domain in which relaxation mechanisms take place and lead to more precise results. In several studies the MRI parameters of liver siderosis have failed to correlate with those of other affected organs, underlining the necessity for MRI iron evaluation in individual organs. Most studies have included children in the evaluated population, but MRI data on very young children are lacking. Wider application of relaxometry methods is indicated, with the establishment of universally accepted MRI protocols, and further studies, including young children, are needed. (orig.)

  10. Prion protein modulates glucose homeostasis by altering intracellular iron.

    Science.gov (United States)

    Ashok, Ajay; Singh, Neena

    2018-04-26

    The prion protein (PrP C ), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP -/- ) were significantly lower than wild type (PrP +/+ ) controls. Silencing of PrP C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP C -dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP +/+ but not PrP -/- mice, indicating PrP C -mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP +/+ relative to PrP -/- mice, suggesting that PrP C -mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer's disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.

  11. Factors for the bioavailability of heme iron preparation in female rats

    OpenAIRE

    村上, 亜由美; 岸本, 三香子; 川口, 真規子; 松浦, 寿喜; 市川, 富夫; Ayumi, Murakami; Mikako, Kishimoto; Makiko, Kawaguchi; Toshiki, Matsuura; Tomio, Ichikawa

    1998-01-01

    Factors for iron absorption in small intestine using heme iron preparation (HIP) and ferric citrate (FC) were investigated. We measured the solubility of iron of experimental diets (FC-normal, FC-overload, HIP-normal, HIP-overload) in water (adjusted pH6.8) and the diffusibility of dietary iron after digestion in vitro. The results did not show significantly differences between FC and HIP. Also, we measured microsomal heme oxygenase (HO) activity in intestinal mucosa of female rats fed experi...

  12. Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

    Science.gov (United States)

    Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

    1987-01-01

    The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

  13. The Aging of Iron Man

    Directory of Open Access Journals (Sweden)

    Azhaar Ashraf

    2018-03-01

    Full Text Available Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases. The aim of the present review is to focus on the age-related alterations in brain iron metabolism from a cellular and molecular biology perspective, alongside genetics, and neuroimaging aspects in man and rodent models, with respect to normal aging and neurodegeneration. In particular, the relationship between iron dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of systemic iron overload on the brain. Based on the evidence discussed here, we suggest a synergistic use of iron-chelators and anti-inflammatories as putative anti-brain aging therapies to counteract pathological aging in neurodegenerative diseases.

  14. The Aging of Iron Man.

    Science.gov (United States)

    Ashraf, Azhaar; Clark, Maryam; So, Po-Wah

    2018-01-01

    Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases. The aim of the present review is to focus on the age-related alterations in brain iron metabolism from a cellular and molecular biology perspective, alongside genetics, and neuroimaging aspects in man and rodent models, with respect to normal aging and neurodegeneration. In particular, the relationship between iron dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of systemic iron overload on the brain. Based on the evidence discussed here, we suggest a synergistic use of iron-chelators and anti-inflammatories as putative anti-brain aging therapies to counteract pathological aging in neurodegenerative diseases.

  15. Plasma protein haptoglobin modulates renal iron loading

    DEFF Research Database (Denmark)

    Fagoonee, Sharmila; Gburek, Jakub; Hirsch, Emilio

    2005-01-01

    Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme...... distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting...... morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload....

  16. Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cycle arrest in MCF-7 cells.

    Science.gov (United States)

    Bajbouj, Khuloud; Shafarin, Jasmin; Abdalla, Maher Y; Ahmad, Iman M; Hamad, Mawieh

    2017-10-01

    It is well established that several forms of cancer associate with significant iron overload. Recent studies have suggested that estrogen (E2) disrupts intracellular iron homeostasis by reducing hepcidin synthesis and maintaining ferroportin integrity. Here, the ability of E2 to alter intracellular iron status and cell growth potential was investigated in MCF-7 cells treated with increasing concentrations of E2. Treated cells were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, oxidative stress, cell survival, growth, and apoptosis. E2 treatment resulted in a significant reduction in hepcidin expression and a significant increase in hypoxia-inducible factor 1 alpha, ferroportin, transferrin receptor, and ferritin expression; a transient decrease in labile iron pool; and a significant increase in total intracellular iron content mainly at 20 nM/48 h E2 dose. Treated cells also showed increased total glutathione and oxidized glutathione levels, increased superoxide dismutase activity, and increased hemoxygenase 1 expression. Treatment with E2 at 20 nM for 48 h resulted in a significant reduction in cell growth (0.35/1 migration rate) and decreased cell survival (iron metabolism and precipitates adverse effects concerning cell viability, membrane integrity, and growth potential.

  17. Occlusal overload investigations by noninvasive technology: fluorescence microscopy and en-face optical coherence tomography

    Science.gov (United States)

    Marcauteanu, Corina; Negrutiu, Meda; Sinescu, Cosmin; Demjan, Enikö; Hughes, Michael; Bradu, Adrian; Dobre, George; Podoleanu, Adrian G.

    2009-07-01

    The aim of this study is the early detection and monitoring of occlusal overload in bruxing patients. En-Face Optical coherence tomography (eF-OCT) and fluorescence microscopy (FM) were used for the imaging of several anterior teeth extracted from patients with light active bruxism. We found a characteristic pattern of enamel cracks, that reached the tooth surface. We concluded that the combination of the en-Face OCT and FM is a promising non-invasive alternative technique for reliable monitoring of occlusal overload.

  18. Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program.

    Science.gov (United States)

    Sruamsiri, Rosarin; Chaiyakunapruk, Nathorn; Pakakasama, Samart; Sirireung, Somtawin; Sripaiboonkij, Nintita; Bunworasate, Udomsak; Hongeng, Suradej

    2013-02-05

    Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.

  19. Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program

    Directory of Open Access Journals (Sweden)

    Sruamsiri Rosarin

    2013-02-01

    Full Text Available Abstract Background Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT for adolescent and young adult with severe thalassemia in Thailand. Methods A Markov model was used to estimate the relevant costs and health outcomes over the patients’ lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs gained, and the incremental cost-effectiveness ratio (ICER in US ($ per QALY gained. One-way and probabilistic sensitivity analyses (PSA were conducted to investigate the effect of parameter uncertainty. Results In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $ 3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita, approximately US $ 4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. Conclusion At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.

  20. SAXS and stability studies of iron-induced oligomers of bacterial frataxin CyaY.

    Directory of Open Access Journals (Sweden)

    Mostafa Fekry

    Full Text Available Frataxin is a highly conserved protein found in both prokaryotes and eukaryotes. It is involved in several central functions in cells, which include iron delivery to biochemical processes, such as heme synthesis, assembly of iron-sulfur clusters (ISC, storage of surplus iron in conditions of iron overload, and repair of ISC in aconitase. Frataxin from different organisms has been shown to undergo iron-dependent oligomerization. At least two different classes of oligomers, with different modes of oligomer packing and stabilization, have been identified. Here, we continue our efforts to explore the factors that control the oligomerization of frataxin from different organisms, and focus on E. coli frataxin CyaY. Using small-angle X-ray scattering (SAXS, we show that higher iron-to-protein ratios lead to larger oligomeric species, and that oligomerization proceeds in a linear fashion as a results of iron oxidation. Native mass spectrometry and online size-exclusion chromatography combined with SAXS show that a dimer is the most common form of CyaY in the presence of iron at atmospheric conditions. Modeling of the dimer using the SAXS data confirms the earlier proposed head-to-tail packing arrangement of monomers. This packing mode brings several conserved acidic residues into close proximity to each other, creating an environment for metal ion binding and possibly even mineralization. Together with negative-stain electron microscopy, the experiments also show that trimers, tetramers, pentamers, and presumably higher-order oligomers may exist in solution. Nano-differential scanning fluorimetry shows that the oligomers have limited stability and may easily dissociate at elevated temperatures. The factors affecting the possible oligomerization mode are discussed.

  1. Fob1 and Fob2 proteins are virulence determinants of Rhizopus oryzae via facilitating iron uptake from ferrioxamine

    Science.gov (United States)

    Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis. Although not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we de...

  2. Effects of iron salts and haemosiderin from a thalassaemia patient on oxygen radical damage as measured in the comet assay

    NARCIS (Netherlands)

    Anderson, D.; Yardley-Jones, A.; Hambly, R.J.; Vives-Bauza, C.; Smykatz-Kloss, V.; Chua-anusorn, W.; Webb, J.

    2000-01-01

    Thalassaemia is a group of genetic diseases where haemoglobin synthesis is impaired. This chronic anaemia leads to increased dietary iron absorption, which develops into iron overload pathology. Treatment through regular transfusions increases oxygen capacity but also provides iron through the red

  3. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    Science.gov (United States)

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Ascorbate status modulates reticuloendothelial iron stores and response to deferasirox iron chelation in ascorbate-deficient rats

    DEFF Research Database (Denmark)

    Brewer, Casey; Otto-Duessel, Maya; Lykkesfeldt, Jens

    2012-01-01

    Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated...... that vitamin C supplementation would improve the availability of transfusional iron to DFX treatment by promoting iron's redox cycling, increasing its soluble ferrous form and promoting its release from reticuloendothelial cells. Osteogenic dystrophy rats (n = 54) were given iron dextran injections for 10...... 12 weeks of sham chelation. Most importantly, ascorbate supplementation at 2250 ppm improved DFX efficiency, allowing DFX to remove 21% more hepatic iron than ascorbate supplementation with 900 ppm or 150 ppm (p vitamin C status modulates the release of iron from...

  5. An Improved Overloading Scheme for Downlink CDMA

    Directory of Open Access Journals (Sweden)

    Marc Moeneclaey

    2005-04-01

    Full Text Available An improved overloading scheme is presented for single-user detection in the downlink of multiple-access systems based on OCDMA/OCDMA (O/O. By displacing in time the orthogonal signatures of the two user sets that make up the overloaded system, the cross-correlation between the users of the two sets is reduced. For random O/O with square-root cosine rolloff chip pulses, the multiuser interference can be decreased by up to 50% (depending on the chip pulse bandwidth as compared to quasiorthogonal sequences (QOS that are presently part of the downlink standard of Cdma2000. This reduction of the multiuser interference gives rise to an increase of the achievable signal-to-interference-plus-noise ratio for a particular channel load.

  6. Electrochemical sensor for predicting transformer overload by phenol measurement

    Energy Technology Data Exchange (ETDEWEB)

    Bosworth, Timothy; Setford, Steven; Saini, Selwayan [Cranfield Centre for Analytical Science, Cranfield University, Silsoe, Beds MK45 4DT (United Kingdom); Heywood, Richard [National Grid Company Plc, Kelvin Avenue, Leatherhead, Surrey KT22 7ST (United Kingdom)

    2003-03-10

    Transformer overload is a significant problem to the power transmission industry, with severe safety and cost implications. Overload may be predicted by measuring phenol levels in the transformer-insulating oil, arising from the thermolytic degradation of phenol-formaldehyde resins. The development of two polyphenol oxidase (PPO) sensors, based on monitoring the enzymatic consumption of oxygen using an oxygen electrode, or reduction of enzymatically generated o-quinone at a screen-printed electrode (SPE), for the measurement of phenol in transformer oil is reported. Ex-service oils were prepared either by extraction into aqueous electrolyte-buffer, or by direct dilution in propan-2-ol, the latter method being more amenable to simple at-line operation. The oxygen electrode, with a sensitivity of 2.87 nA {mu}g{sup -1} ml{sup -1}, RSD of 7.0-19.9% and accuracy of {+-}8.3% versus the industry standard International Electrotechnical Commission (IEC) method, proved superior to the SPE (sensitivity: 3.02 nA {mu}g{sup -1} ml{sup -1}; RSD: 8.9-18.3%; accuracy: {+-}7.9%) and was considerably more accurate at low phenol concentrations. However, the SPE approach is more amenable to field-based usage for reasons of device simplicity. The method has potential as a rapid and simple screening tool for the at-site monitoring of phenol in transformer oils, thereby reducing incidences of transformer failure.

  7. Mapping and characterization of iron compounds in Alzheimer's tissue

    International Nuclear Information System (INIS)

    Collingwood, Joanna; Dobson, Jon

    2006-01-01

    Understanding the management of iron in the brain is of great importance in the study of neurodegeneration, where regional iron overload is frequently evident. A variety of approaches have been employed, from quantifying iron in various anatomical structures, to identifying genetic risk factors related to iron metabolism, and exploring chelation approaches to tackle iron overload in neurodegenerative disease. However, the ease with which iron can change valence state ensures that it is present in vivo in a wide variety of forms, both soluble and insoluble. Here, we review recent developments in approaches to locate and identify iron compounds in neurodegenerative tissue. In addition to complementary techniques that allow us to quantify and identify iron compounds using magnetometry, extraction, and electron microscopy, we are utilizing a powerful combined mapping/characterization approach with synchrotron X-rays. This has enabled the location and characterization of iron accumulations containing magnetite and ferritin in human Alzheimer's disease (AD) brain tissue sections in situ at micron-resolution. It is hoped that such approaches will contribute to our understanding of the role of unusual iron accumulations in disease pathogenesis, and optimise the potential to use brain iron as a clinical biomarker for early detection and diagnosis.

  8. Iron and genome stability: An update

    International Nuclear Information System (INIS)

    Prá, Daniel; Franke, Silvia Isabel Rech; Henriques, João Antonio Pêgas; Fenech, Michael

    2012-01-01

    Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40–45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

  9. Iron and genome stability: An update

    Energy Technology Data Exchange (ETDEWEB)

    Pra, Daniel, E-mail: daniel_pra@yahoo.com [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); PPG em Saude e Comportamento, Universidade Catolica de Pelotas, Pelotas, RS (Brazil); Franke, Silvia Isabel Rech [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); Henriques, Joao Antonio Pegas [Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS (Brazil); Fenech, Michael [CSIRO Food and Nutritional Sciences, Adelaide, SA (Australia)

    2012-05-01

    Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40-45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

  10. Physical and Chemical Characterization of Therapeutic Iron Containing Materials: A Study of Several Superparamagnetic Drug Formulations with the β-FeOOH or Ferrihydrite Structure

    International Nuclear Information System (INIS)

    Funk, Felix; Long, Gary J.; Hautot, Dimitri; Buechi, Ruth; Christl, Iso; Weidler, Peter G.

    2001-01-01

    The effectiveness of therapeutically used iron compounds is related to their physical and chemical properties. Four different iron compounds used in oral, intravenous, and intramuscular therapy have been examined by X-ray powder diffraction, iron-57 Moessbauer spectroscopy, transmission electron microscopy, BET surface area measurement, potentiometric titration and studied through dissolution kinetics determinations using acid, reducing and chelating agents. All compounds are nanosized with particle diameters, as determined by X-ray diffraction, ranging from 1 to 4.1 nm. The superparamagnetic blocking temperatures, as determined by Moessbauer spectroscopy, indicate that the relative diameters of the aggregates range from 2.5 to 4.1 nm. Three of the iron compounds have an akaganeite-like structure, whereas one has a ferrihydrite-like structure. As powders the particles form large and dense aggregates which have a very low surface area on the order of 1 m 2 g -1 . There is evidence, however, that in a colloidal solution the surface area is increased by two to three orders of magnitude, presumably as a result of the break up of the aggregates. Iron release kinetics by acid, chelating and reducing agents reflect the high surface area, the size and crystallinity of the particles, and the presence of the protective carbohydrate layer coating the iron compound. Within a physiologically relevant time period, the iron release produced by acid or large chelating ligands is small. In contrast, iron is rapidly mobilized by small organic chelating agents, such as oxalate, or by chelate-forming reductants, such as thioglycolate

  11. Physical and Chemical Characterization of Therapeutic Iron Containing Materials: A Study of Several Superparamagnetic Drug Formulations with the β-FeOOH or Ferrihydrite Structure

    Science.gov (United States)

    Funk, Felix; Long, Gary J.; Hautot, Dimitri; Büchi, Ruth; Christl, Iso; Weidler, Peter G.

    2001-03-01

    The effectiveness of therapeutically used iron compounds is related to their physical and chemical properties. Four different iron compounds used in oral, intravenous, and intramuscular therapy have been examined by X-ray powder diffraction, iron-57 Mössbauer spectroscopy, transmission electron microscopy, BET surface area measurement, potentiometric titration and studied through dissolution kinetics determinations using acid, reducing and chelating agents. All compounds are nanosized with particle diameters, as determined by X-ray diffraction, ranging from 1 to 4.1 nm. The superparamagnetic blocking temperatures, as determined by Mössbauer spectroscopy, indicate that the relative diameters of the aggregates range from 2.5 to 4.1 nm. Three of the iron compounds have an akaganeite-like structure, whereas one has a ferrihydrite-like structure. As powders the particles form large and dense aggregates which have a very low surface area on the order of 1 m2 g-1. There is evidence, however, that in a colloidal solution the surface area is increased by two to three orders of magnitude, presumably as a result of the break up of the aggregates. Iron release kinetics by acid, chelating and reducing agents reflect the high surface area, the size and crystallinity of the particles, and the presence of the protective carbohydrate layer coating the iron compound. Within a physiologically relevant time period, the iron release produced by acid or large chelating ligands is small. In contrast, iron is rapidly mobilized by small organic chelating agents, such as oxalate, or by chelate-forming reductants, such as thioglycolate.

  12. Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus.

    Science.gov (United States)

    Gonçalves, N; Gomes-Ferreira, C; Moura, C; Roncon-Albuquerque, R; Leite-Moreira, A F; Falcão-Pires, I

    2016-08-15

    Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Iron Loading Selectively Increases Hippocampal Levels of Ubiquitinated Proteins and Impairs Hippocampus-Dependent Memory.

    Science.gov (United States)

    Figueiredo, Luciana Silva; de Freitas, Betânia Souza; Garcia, Vanessa Athaíde; Dargél, Vinícius Ayub; Köbe, Luiza Machado; Kist, Luiza Wilges; Bogo, Maurício Reis; Schröder, Nadja

    2016-11-01

    Alterations of brain iron levels have been observed in a number of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in the adulthood. Protein degradation mediated by the ubiquitin-proteasome system (UPS) plays a central regulatory role in several cellular processes. Impairment of the UPS has been implicated in the pathogenesis of neurodegenerative disorders. Here, we examined the effects of iron exposure in the neonatal period (12th-14th day of postnatal life) on the expression of proteasome β-1, β-2, and β-5 subunits, and ubiquitinated proteins in brains of 15-day-old rats, to evaluate the immediate effect of the treatment, and in adulthood to assess long-lasting effects. Two different memory types, emotionally motivated conditioning and object recognition were assessed in adult animals. We found that iron administered in the neonatal period impairs both emotionally motivated and recognition memory. Polyubiquitinated protein levels were increased in the hippocampus, but not in the cortex, of adult animals treated with iron. Gene expression of subunits β1 and β5 was affected by age, being higher in the early stages of development in the hippocampus, accompanied by an age-related increase in polyubiquitinated protein levels in adults. In the cortex, gene expression of the three proteasome subunits was significantly higher in adulthood than in the neonatal period. These findings suggest that expression of proteasome subunits and activity are age-dependently regulated. Iron exposure in the neonatal period produces long-lasting harmful effects on the UPS functioning, which may be related with iron-induced memory impairment.

  14. Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients

    Directory of Open Access Journals (Sweden)

    Mudge David W

    2009-06-01

    Full Text Available Abstract Background Post-transplant anaemia remains a common problem after kidney transplantation, with an incidence ranging from nearly 80% at day 0 to about 25% at 1 year. It has been associated with poor graft outcome, and recently has also been shown to be associated with increased mortality. Our transplant unit routinely administers oral iron supplements to renal transplant recipients but this is frequently accompanied by side effects, mainly gastrointestinal intolerance. Intravenous iron is frequently administered to dialysis patients and we sought to investigate this mode of administration in transplant recipients after noticing less anaemia in several patients who had received intravenous iron just prior to being called in for transplantation. Methods This study is a single-centre, prospective, open-label, randomised, controlled trial of oral versus intravenous iron supplements in renal transplant recipients and aims to recruit approximately 100 patients over a 12-month period. Patients will be randomised to receive a single dose of 500 mg iron polymaltose (intravenous iron group or 2 ferrous sulphate slow-release tablets daily (oral iron group. The primary outcome is time to normalisation of haemoglobin post-transplant. Prospective power calculations have indicated that a minimum of 48 patients in each group would have to be followed up for 3 months in order to have a 90% probability of detecting a halving of the time to correction of haemoglobin levels to ≥110 g/l in iron-treated patients, assuming an α of 0.05. All eligible adult patients undergoing renal transplantation at the Princess Alexandra Hospital will be offered participation in the trial. Exclusion criteria will include iron overload (transferrin saturation >50% or ferritin >800 μg/l, or previous intolerance of either oral or intravenous iron supplements. Discussion If the trial shows a reduction in the time to correction of anaemia with intravenous iron or less side

  15. MFehi adipose tissue macrophages compensate for tissue iron pertubations in mice.

    Science.gov (United States)

    Hubler, Merla J; Erikson, Keith M; Kennedy, Arion J; Hasty, Alyssa H

    2018-05-16

    Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess FFAs and regulation of extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe hi ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron handling genes. While studies have demonstrated iron homeostasis is important for adipocyte health, little is known about how MFe hi ATMs may respond to and influence AT iron availability. Two methodologies were used to address this question - dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe hi ATMs accumulated excess iron, while the iron content of MFe lo ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe hi ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe hi ATMs incorporated high levels of iron and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe hi ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe lo ATM incorporation into the MFe hi pool. The MFe hi ATM population maintained its low inflammatory profile and iron cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.

  16. The detrimental effects of iron on the joint : a comparison between haemochromatosis and haemophilia

    NARCIS (Netherlands)

    van Vulpen, Lize F D; Roosendaal, Goris; van Asbeck, B Sweder; Mastbergen, Simon C.; Lafeber, Floris P J G; Schutgens, Roger E G

    Joint damage due to (recurrent) joint bleeding in haemophilia causes major morbidity. Although the exact pathogenesis has not been fully elucidated, a central role for iron is hypothesised. Likewise, in hereditary haemochromatosis joint destruction is caused by iron overload. A comparison between

  17. Haemochromatosis gene mutation H63D is a risk factor for iron ...

    African Journals Online (AJOL)

    Introduction: Iron overload is the main cause of morbidity and mortality in patients with β-thalassemia. The Aim: The aim of this study was to evaluate the prevalence of genetic markers (HFE mutations C282Y and H63D) among Egyptian β-thalassemic. Children and its effect on their iron status. Patients and Methods: 59 ...

  18. Morbidity of severe obesity.

    Science.gov (United States)

    Kral, J G

    2001-10-01

    Although obesity is an easy diagnosis to make, its etiologies, pathophysiology, and symptomatology are extraordinarily complex. Progress in surgical technique and anesthesiological management has substantially improved the safety of performing operations on the severely obese in the last 20 years. These improvements have occurred more or less empirically, without a full understanding of etiology or pathophysiology, although this has advanced concomitantly with improvements in practice. This review has attempted to provide a framework to facilitate progress in the neglected areas of patient selection and choice of operation, in an effort to improve long-term outcome. Despite the disparate etiologies of obesity and its diverse comorbidities and complications, there are unifying interdependent pathogenetic mechanisms of great relevance to the practice of antiobesity surgery. The rate of eating, whether driven by HPA dysfunction, ambient stress, or related hereditary susceptibility factors including the increased energy demands of an expanded body fat mass, participates in a cycle that results in disordered satiety (see Fig. 3). This leads to substrate overload, causing extensive metabolic abnormalities such as atherogenesis, insulin resistance, thrombogenesis, and carcinogenesis. This interpretation of the pathophysiology of obesity ironically accords with the original meaning of the word obesity: "to overeat." The ultimate solution to the problem of obesity--preventing it--will not be forthcoming until the food industry is forced to lower production and change its marketing strategies, as the liquor and tobacco industries in the United States were compelled to do. This cannot occur until the large and fast-growing populations of industrialized nations become educated in the personal implications of the energy principle. Regardless of whether school curricula are modified to prioritize health education, the larger problems of cultural and economic change remain for

  19. Body iron is a contributor to oxidative damage of DNA

    DEFF Research Database (Denmark)

    Tuomainen, Tomi-Pekka; Loft, Steffen; Nyyssönen, Kristiina

    2007-01-01

    The transition metal iron is catalytically highly active in vitro, and not surprisingly, body iron has been suggested to promote oxidative stress in vivo. In the current analysis we studied the association of serum ferritin concentration and serum soluble transferrin receptor concentration.......17 (95% CI 0.08-0.26, P = 0.001), and serum soluble transferrin receptor to ferritin concentration ratio (TfR/ferritin) predicted the excretion rate at B = - 0.13 (95% CI - 0.21 to - 0.05, P = 0.002). Our data suggest that body iron contributes to excess oxidative stress already at non-iron overload...

  20. Iron-sulfur cluster biogenesis in mammalian cells: new insights into the molecular mechanisms of cluster delivery

    Science.gov (United States)

    Maio, Nunziata; Rouault, Tracey. A.

    2014-01-01

    Iron-sulfur (Fe-S) clusters are ancient, ubiquitous cofactors composed of iron and inorganic sulfur. The combination of the chemical reactivity of iron and sulfur, together with many variations of cluster composition, oxidation states and protein environments, enables Fe-S clusters to participate in numerous biological processes. Fe-S clusters are essential to redox catalysis in nitrogen fixation, mitochondrial respiration and photosynthesis, to regulatory sensing in key metabolic pathways (i. e. cellular iron homeostasis and oxidative stress response), and to the replication and maintenance of the nuclear genome. Fe-S cluster biogenesis is a multistep process that involves a complex sequence of catalyzed protein- protein interactions and coupled conformational changes between the components of several dedicated multimeric complexes. Intensive studies of the assembly process have clarified key points in the biogenesis of Fe-S proteins. However several critical questions still remain, such as: what is the role of frataxin? Why do some defects of Fe-S cluster biogenesis cause mitochondrial iron overload? How are specific Fe-S recipient proteins recognized in the process of Fe-S transfer? This review focuses on the basic steps of Fe-S cluster biogenesis, drawing attention to recent advances achieved on the identification of molecular features that guide selection of specific subsets of nascent Fe-S recipients by the cochaperone HSC20. Additionally, it outlines the distinctive phenotypes of human diseases due to mutations in the components of the basic pathway. PMID:25245479

  1. The overloaded right heart and ventricular interdependence.

    Science.gov (United States)

    Naeije, Robert; Badagliacca, Roberto

    2017-10-01

    The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights

  2. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or oral iron, by mouth once or several times a day to increase the iron in your body. This is ... and newer recommendations to increase the length of time between donations to protect blood donors. Cardiovascular Health Study identifies predictors ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or oral iron, by mouth once or several times a day to increase the iron in your body. This is the most common treatment ... and newer recommendations to increase the length of time between donations to protect ... in older adults. The NHLBI-sponsored Cardiovascular Health Study ...

  5. Anaemia and Iron Homeostasis in a Cohort of HIV-Infected Patients: A Cross-Sectional Study in Ghana

    Directory of Open Access Journals (Sweden)

    Christian Obirikorang

    2016-01-01

    Full Text Available Aim. We determined the prevalence of anaemia and evaluated markers of iron homeostasis in a cohort of HIV patients. Methods. A comparative cross-sectional study on 319 participants was carried out at the Tamale Teaching Hospital from July 2013 to December 2013, 219 patients on HAART (designated On-HAART and 100 HAART-naive patients. Data gathered include sociodemography, clinical history, and selected laboratory assays. Results. Prevalence of anaemia was 23.8%. On-HAART participants had higher CD4/CD3 lymphocyte counts, Hb, HCT/PCV, MCV, MCH, iron, ferritin, and TSAT (P<0.05. Hb, iron, ferritin, and TSAT decreased from grade 1 to grade 3 anaemia and CD4/CD3 lymphocyte count was lowest in grade 3 anaemia (P<0.05. Iron (P=0.0072 decreased with disease severity whilst transferrin (P=0.0143 and TIBC (P=0.0143 increased with disease severity. Seventy-six (23.8% participants fulfilled the criteria for anaemia, 86 (26.9% for iron deficiency, 41 (12.8% for iron deficiency anaemia, and 17 (5.3% for iron overload. The frequency of anaemia was higher amongst participants not on HAART (OR 2.6 for grade 1 anaemia; OR 3.0 for grade 3 anaemia. Conclusion. In this study population, HIV-associated anaemia is common and is related to HAART status and disease progression. HIV itself is the most important cause of anaemia and treatment of HIV should be a priority compared to iron supplementation.

  6. LRRC10 is required to maintain cardiac function in response to pressure overload.

    Science.gov (United States)

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. Copyright © 2016 the American Physiological Society.

  7. A low noise preamplifier with optoelectronic overload protection for radioactivity measurement

    International Nuclear Information System (INIS)

    Sephton, J.P.; Williams, J.M.; Johansson, L.C.; Philips, H.C.

    2012-01-01

    Pulses from detectors used for radioactivity measurement can vary in size by several orders of magnitude. Large pulses will lead to saturation at the preamplifier output and extension of the pulse length. As a consequence, the dead time of the system increases and pulses may be lost. Electronic design techniques employed to protect against overloading tend to increase the amplifier noise level. However, an optoelectronic method of overload protection has been devised which has only a negligible effect on noise. An infrared light emitting diode interfaced to the output of the preamplifier is linked by fibre optic cable to an ultra-low leakage photodiode at the input. The conduction of the photodiode increases with the amplitude of the preamplifier output signal. Excess current is thereby prevented from entering the preamplifier and causing saturation. The preamplifier has been tested on 4π beta–gamma and gas counting systems and found to give good protection against overloading. - Highlights: ► A preamplifier for radioactivity measurements has been developed. ► Low noise. ► Current sensitive. ► Optoelectronic overload protection.

  8. Functional overload attenuates plantaris atrophy in tumor-bearing rats

    International Nuclear Information System (INIS)

    Otis, Jeffrey S; Lees, Simon J; Williams, Jay H

    2007-01-01

    Late stage cancer malignancies may result in severe skeletal muscle wasting, fatigue and reduced quality of life. Resistance training may attenuate these derangements in cancer patients, but how this hypertrophic response relates to normal muscle adaptations in healthy subjects is unknown. Here, we determined the effect of resistance training on muscle mass and myosin heavy chain (MHC) isoform composition in plantaris muscles from tumor-bearing (TB) rats. Age- and gender-matched Buffalo rats were used for all studies (n = 6/group). Suspensions of Morris Hepatoma MH7777 cells or normal saline were injected subcutaneously into the dorsum. Six weeks after cell implantation, muscles from TB rats were harvested, weighed and processed for ATP-independent proteasome activity assays. Once tumor-induced atrophy had been established, subgroups of TB rats underwent unilateral, functional overload (FO). Healthy, sham-operated rats served as controls. After six weeks, the extent of plantaris hypertrophy was calculated and MHC isoform compositions were determined by gel electrophoresis. Six weeks of tumor growth reduced body mass and the relative masses of gastrocnemius, plantaris, tibialis anterior, extensor digitorum longus, and diaphragm muscles (p ≤ 0.05). Percent reductions in body mass had a strong, negative correlation to final tumor size (r = -0.78). ATP-independent proteasome activity was increased in plantaris muscles from TB rats (p ≤ 0.05). In healthy rats, functional overload (FO) increased plantaris mass ~44% compared to the contralateral control muscle, and increased the relative percentage of MHC type I and decreased the relative percentage of MHC type IIb compared to the sham-operated controls (p ≤ 0.05). Importantly, plantaris mass was increased ~24% in TB-FO rats and adaptations to MHC isoform composition were consistent with normal, resistance-trained muscles. Despite significant skeletal muscle derangements due to cancer, muscle retains the capacity to

  9. Anemia and iron homeostasis in a cohort of HIV-infected patients in Indonesia

    Directory of Open Access Journals (Sweden)

    Jusuf Hadi

    2011-08-01

    Full Text Available Abstract Background Anemia is a common clinical finding in HIV-infected patients and iron deficiency or redistribution may contribute to the development of low hemoglobin levels. Iron overload is associated with a poor prognosis in HIV and Hepatitis C virus infections. Iron redistribution may be caused by inflammation but possibly also by hepatitis C co-infection. We examined the prevalence of anemia and its relation to mortality in a cohort of HIV patients in a setting where injecting drug use (IDU is a main mode of HIV transmission, and measured serum ferritin and sTfR, in relation to anemia, inflammation, stage of HIV disease, ART and HCV infection. Methods Patient characteristics, ART history and iron parameters were recorded from adult HIV patients presenting between September 2007 and August 2009 in the referral hospital for West Java, Indonesia. Kaplan-Meier estimates and Cox's regression were used to assess factors affecting survival. Logistic regression was used to identity parameters associated with high ferritin concentrations. Results Anemia was found in 49.6% of 611 ART-naïve patients, with mild (Hb 10.5 - 12.99 g/dL for men; and 10.5 - 11.99 g/dL for women anemia in 62.0%, and moderate to severe anemia (Hb Conclusion HIV-associated anemia is common among HIV-infected patients in Indonesia and strongly related to mortality. High ferritin with low sTfR levels suggest that iron redistribution and low erythropoietic activity, rather than iron deficiency, contribute to anemia. Serum ferritin and sTfR should be used cautiously to assess iron status in patients with advanced HIV infection.

  10. The ''red'' decline of Norway spruce or ''røde rødgraner'' - is it ammonium overload or top-dying?

    DEFF Research Database (Denmark)

    Engvild, K.C.

    2005-01-01

    by nitrogen overload was investigated. A sensitive biochemical indicator of nitrogen status of conifer trees is the content of free amino acids of the urea cycle,arginine and ornithine. In pot experiments with four times overload of N as ammonium nitrate the free arginine content increased more than 100 times....... There was no indication of nitrogen overload. The “red” Norway spruce maysuffer from “top-dying” a common disorder of Norway spruce in Great Britain, believed to be caused by several mild winters in a row. In that case the symptoms should diminish after the very cold winter 1995-96....

  11. Using Pattern Recognition Techniques for Server Overload Detection

    NARCIS (Netherlands)

    Bezemer, C.P.; Cheplygina, V.; Zaidman, A.

    2011-01-01

    One of the key factors in customer satisfaction is application performance. To be able to guarantee good performance, it is necessary to take appropriate measures before a server overload occurs. While in small systems it is usually possible to predict server overload using a subjective human

  12. Effect of overloads on fatigue crack propagation rate

    International Nuclear Information System (INIS)

    Kogaev, V.P.; Bojtsov, B.V.; Petukhov, Yu.V

    1986-01-01

    An overload coefficient Q, the number of overload cycles Nsub(0), the value of the stress intensity coefficient swing of basic loading conditions ΔK are experimentally studied for their effect on the delay of the fatigue crack propagation Nsub(D) in 30KhGSNA steel. Results of the study are presented. It is shown that as a result of single overloads the value attains 60 - 10 thous. cycles. The delay Nsub(D) grows with the overload coefficient Q=Ksub(max)sup(0)/Ksub(max) and the number of the overload cycles Nsub(0). The regularity indicated is described by the equations valid within the limits of variation in Q and Nsub(0) values studied in the paper

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness ... If your doctor diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the condition. Your ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... symptoms. More severe iron-deficiency anemia may cause fatigue or tiredness, shortness of breath, or chest pain. ... in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the most common symptom. ...

  15. Iron status in 358 apparently healthy 80-year-old Danish men and women: relation to food composition and dietary and supplemental iron intake

    DEFF Research Database (Denmark)

    Milman, Nils; Pedersen, Agnes Nadelmann; Ovesen, Lars

    2004-01-01

    of age from a 1914 cohort study. Blood samples included serum ferritin and hemoglobin (Hb). A dietary survey was performed in 232 subjects (120 men, 112 women) using a dietary history method. Median serum ferritin was 100 mug/l in men and 78 mug/l in women (p300 mug/l (i.e., iron overload) were found......In Denmark, the intake of dietary iron has decreased since 1987, when the mandatory iron fortification of flour (30 mg carbonyl iron/kg) was stopped. Since there have been no studies of iron status in elderly Danes after the abolishment of iron fortification, there is a need to assess actual iron...... status in the elderly population. The objective was to evaluate iron status and the relationship with food composition and dietary and supplemental iron intake in an elderly population in Copenhagen County. Participants in this health examination survey were 358 subjects (171 men, 187 women) 80 years...

  16. Dietary iron intake, iron status, and gestational diabetes.

    Science.gov (United States)

    Zhang, Cuilin; Rawal, Shristi

    2017-12-01

    Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM. © 2017 American Society for Nutrition.

  17. Evaluation of thermal overload in boiler operators.

    Science.gov (United States)

    Braga, Camila Soares; Rodrigues, Valéria Antônia Justino; Campos, Julio César Costa; de Souza, Amaury Paulo; Minette, Luciano José; de Moraes, Angêlo Casali; Sensato, Guilherme Luciano

    2012-01-01

    The Brazilians educational institutions need a large energy demand for the operation of laundries, restaurants and accommodation of students. Much of that energy comes from steam generated in boilers with wood fuel. The laboral activity in boiler may present problems for the operator's health due to exposure to excessive heat, and its operation has a high degree of risk. This paper describes an analysis made the conditions of thermal environment in the operation of a B category boiler, located at a Higher Education Institution, located in the Zona da Mata Mineira The equipments used to collect data were Meter WBGT of the Heat Index; Meter of Wet Bulb Index and Globe Thermometer (WBGT); Politeste Instruments, an anemometer and an Infrared Thermometer. By the application of questionnaires, the second phase consisted of collecting data on environmental factors (temperature natural environment, globe temperature, relative humidity and air velocity). The study concluded that during the period evaluated, the activity had thermal overload.

  18. Protein quality control in protection against systolic overload cardiomyopathy: the long term role of small heat shock proteins.

    Science.gov (United States)

    Kumarapeli, Asangi R K; Horak, Kathleen; Wang, Xuejun

    2010-07-21

    Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short-term protection against various insults and injuries. Previously, we reported that the small HSP alphaB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressingtransgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overex-pression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload.

  19. Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves

    Directory of Open Access Journals (Sweden)

    Robert Kupczyński

    2017-07-01

    Full Text Available The objective of this study was to determine the effects of feeding protein-iron complex (PIC on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf’s life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast. Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose 10 g/day calf of protein-iron complex, HFe (height iron dose 20 g/day calf, and control group. Dietary supplements containing the lower dose of concentrate had a significant positive effect on iron metabolism, while the higher dose of concentrate resulted in increase of total iron binding capacity (TIBC, saturation of transferrin and decrease of and unsaturated iron binding capacity (UIBC, which suggest iron overload. Additionally, treatment with the lower dose of iron remarkably increased the antioxidant parameters, mainly total antioxidant (TAS and glutathione peroxidase activity (GPx. Higher doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin, glucose, TNFα and IGF-1 concentration did not change significantly in either group after supplementation. In practice, the use of protein-iron complex concentrate requires taking into account the iron content in milk replacers and other feedstuffs.

  20. Use of radionuclides in the study of iron metabolism in iron deficient states

    International Nuclear Information System (INIS)

    Anatkov, A.; Karakostov, K.; Iliev, Z.; Dimitrov, L.

    1977-01-01

    A study of erythropoiesis in iron deficient anemias by simultaneous labelling with the radionuclides iron 59 and chromium 51 revealed accelerated iron circuit, higher percentage of daily hemolysis, severely reduced or even absent labile reserves, decreased volume of packed red cells with no decrease of blood volume. Adequate iron 59 utilization was observed after administration of large doses of iron (500 mg) in the treatment of iron deficient anemias. (author)

  1. Serum Iron Protects from Renal Postischemic Injury.

    Science.gov (United States)

    Vaugier, Céline; Amano, Mariane T; Chemouny, Jonathan M; Dussiot, Michael; Berrou, Claire; Matignon, Marie; Ben Mkaddem, Sanae; Wang, Pamella H M; Fricot, Aurélie; Maciel, Thiago T; Grapton, Damien; Mathieu, Jacques R R; Beaumont, Carole; Peraldi, Marie-Noëlle; Peyssonnaux, Carole; Mesnard, Laurent; Daugas, Eric; Vrtovsnik, François; Monteiro, Renato C; Hermine, Olivier; Ginzburg, Yelena Z; Benhamou, Marc; Camara, Niels O S; Flamant, Martin; Moura, Ivan C

    2017-12-01

    Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients ( n =169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF- κ B and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants. Copyright © 2017 by the American Society of Nephrology.

  2. LABILE IRON IN CELLS AND BODY FLUIDS . Physiology, Pathology and Pharmacology

    Directory of Open Access Journals (Sweden)

    Zvi Ioav Cabantchik

    2014-03-01

    Full Text Available In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI composition varies with metal concentration and substances with chelating groups but also with pH and the redox potential. Although physiologically in the lower µM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (that renders iron essentially non-labile, in systemic iron overload (IO, the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma transferrin approaches iron saturation, labile plasma iron (LPI emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of iron overload, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in iv iron formulations per se as well as in plasma (LPI following parenteral iron

  3. Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

    Science.gov (United States)

    Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

    2012-01-01

    Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

  4. Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations.

    Directory of Open Access Journals (Sweden)

    Christine E McLaren

    Full Text Available The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs using DNA from white men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS Study with serum ferritin (SF ≤ 12 µg/L (cases and controls (SF >100 µg/L in men, SF >50 µg/L in women. We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7 × 10(-6 and replicated in African Americans (p = 0.0012.Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p<4.4 × 10(-5; six SNPs replicated in other ethnicities (p<0.01. SNP rs10904850 in the CUBN gene on 10p13 was associated with serum iron in African Americans (P = 1.0 × 10(-5. These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.

  5. Competition of dipositive metal ions for Fe (III) binding sites in chelation therapy of Iron Load

    International Nuclear Information System (INIS)

    Rehmani, Fouzia S.

    2005-01-01

    Iron overload is a condition in which excessive iron deposited in the liver, kidney and spleen of human beings in the patients of beta thalassemia and sickle cell anemia. Instead of its importance iron could be toxic when in excess, it damages the tissues. For the treatment of iron overload, a drug desferrioxamine mesylate has been used. It is linear trihydroxamic acid, a natural siderophore produced by streptomyces which removes the extra iron from body. Salicylhydroxamate type siderphore. In present research salicylhydroxamate was used for the complexation with dipositive metal ions which are available in biological environments such as Mn (II), Co (II), Ni (II) and Cu (II). The aim of our work was to study the competition reactions between Fe (III) and other dipositive ions; to calculate the thermodynamic data of chelation of these metal ions complexes with hydroxamate by computer program and comparison with hydroxamate complexes. (author)

  6. VOLUME OVERLOAD IS ASSOCIATED WITH MALNUTRITION IN PERITONEAL DIALYSIS

    Directory of Open Access Journals (Sweden)

    Jin Joo Cha

    2012-06-01

    Volume overload is associated with malnutrition and seems to be an independent predictor of mortality in PD population. Further study should evaluate the effects of intervention of volume control in PD patients.

  7. Fatigue crack growth due to overloads in plain concrete using ...

    Indian Academy of Sciences (India)

    cation of overload on concrete structures, acceleration in the crack growth process .... study by the same authors, Ray & Chandra Kishen (2010), they have employed the population growth ...... Institute of Technology, University of Trondheim.

  8. [Role of melatonin in calcium overload-induced heart injury].

    Science.gov (United States)

    Kong, Lingheng; Wei, Ming; Sun, Na; Zhu, Juanxia; Su, Xingli

    2017-06-28

    To investigate the role of melatonin in calcium overload-induced heart injury.
 Methods: Thirty-two rats were divided into 4 groups: a control group (Control), a melatonin control group (Mel), a calcium overload group (CaP), and a calcium overload plus melatonin group (Mel+CaP). Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium. Lactate dehydrogenase (LDH) activity in the coronary flow was determined. The expressions of caspase-3 and cytochrome c were determined by Western blot. The pathological morphological changes in myocardial fiber were analyzed by HE staining.
 Results: Compared with the control group, calcium overload significantly induced an enlarged infarct size (Poverload-induced heart injury.

  9. Network overload due to massive attacks

    Science.gov (United States)

    Kornbluth, Yosef; Barach, Gilad; Tuchman, Yaakov; Kadish, Benjamin; Cwilich, Gabriel; Buldyrev, Sergey V.

    2018-05-01

    We study the cascading failure of networks due to overload, using the betweenness centrality of a node as the measure of its load following the Motter and Lai model. We study the fraction of survived nodes at the end of the cascade pf as a function of the strength of the initial attack, measured by the fraction of nodes p that survive the initial attack for different values of tolerance α in random regular and Erdös-Renyi graphs. We find the existence of a first-order phase-transition line pt(α ) on a p -α plane, such that if p pt , pf is large and the giant component of the network is still present. Exactly at pt, the function pf(p ) undergoes a first-order discontinuity. We find that the line pt(α ) ends at a critical point (pc,αc) , in which the cascading failures are replaced by a second-order percolation transition. We find analytically the average betweenness of nodes with different degrees before and after the initial attack, we investigate their roles in the cascading failures, and we find a lower bound for pt(α ) . We also study the difference between localized and random attacks.

  10. Application of Chaos Theory in Trucks' Overloading Enforcement

    Directory of Open Access Journals (Sweden)

    Abbas Mahmoudabadi

    2013-01-01

    Full Text Available Trucks' overloading is considered as one of the most substantial concerns in road transport due to a possible road surface damage, as well as, are less reliable performance of trucks' braking system. Sufficient human resource and adequate time scheduling are to be planned for surveying trucks' overloading; hence, it seems required to prepare an all-around model to be able to predict the number of overloaded vehicles. In the present research work, the concept of chaos theory has been utilized to predict the ratio of trucks which might be guessed overloaded. The largest Lyapunov exponent is utilized to determine the presence of chaos using experimental data and concluded that the ratio of overloaded trucks reflects chaotic behavior. The prediction based on chaos theory is compared with the results of simple smoothing and moving average methods according to the well-known criterion of mean square errors. The results have also revealed that the chaotic prediction model would act more capably comparing the analogous methods including simple smoothing and moving average to predict the ratio of passing trucks to be possibly overloaded.

  11. Characterization of ancient Indian iron and entrapped slag ...

    Indian Academy of Sciences (India)

    year old Indian iron using microprobe techniques (EDS, XRD and PIXE). Several different local locations in the iron matrix and in the entrapped slag inclusions were analyzed. The P content of the metallic iron matrix was very heterogeneous.

  12. The influence of iron status and genetic polymorphisms in the HFE gene on the risk for postoperative complications after bariatric surgery: a prospective cohort study in 1,064 patients

    Directory of Open Access Journals (Sweden)

    Freedman-Weiss Mollie

    2011-01-01

    Full Text Available Abstract Background Gastric bypass surgery is a highly effective therapy for long-term weight loss in severely obese patients, but carries significant perioperative risks including infection, wound dehiscence, and leaks from staple breakdown. Iron status can affect immune function and wound healing, thus may influence peri-operative complications. Common mutations in the HFE gene, the gene responsible for the iron overload disorder hereditary hemochromatosis, may impact iron status. Methods We analyzed 1064 extremely obese Caucasian individuals who underwent open and laparoscopic Roux-n-Y gastric bypass surgery at the Geisinger Clinic. Serum iron, ferritin, transferrin, and iron binding capacity were measured pre-operatively. All patients had intra-operative liver biopsies and were genotyped for the C282Y and H63D mutations in the HFE gene. Associations between surgical complications and serum iron measures, HFE gene status, and liver iron histology were determined. Results We found that increased serum iron and transferrin saturation were present in patients with any post-operative complication, and that increased serum ferritin was also increased in patients with major complications. Increased serum transferrin saturation was also associated with wound complications in open RYGB, and transferrin saturation and ferritin with prolonged lengths of stay. The presence of 2 or more HFE mutations was associated with overall complications as well as wound complications in open RYGB. No differences were found in complication rates between those with stainable liver iron and those without. Conclusion Serum iron status and HFE genotype may be associated with complications following RYGB surgery in the extremely obese.

  13. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: A cluster-randomised trial

    International Nuclear Information System (INIS)

    Soofi, Sajid

    2014-01-01

    Full text: Background: Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children. We assessed the effects of provision of two micronutrient powder formulations, with or without zinc, to children in Pakistan. Methods: We did a cluster randomised trial in urban and rural sites in Sindh, Pakistan. A baseline survey identified 256 clusters, which were randomly assigned (within urban and rural strata, by computer-generated random numbers) to one of three groups: non-supplemented control (group A), micronutrient powder without zinc (group B), or micronutrient powder with 10 mg zinc (group C). Children in the clusters aged 6 months were eligible for inclusion in the study. Powders were to be given daily between 6 and 18 months of age; follow-up was to age 2 years. Micronutrient powder sachets for groups B and C were identical except for colour; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion. Parents knew whether their child was receiving supplementation, but did not know whether the powder contained zinc. Primary outcomes were growth, episodes of diarrhoea, acute lower respiratory tract infection, fever, and incidence of admission to hospital. This trial is registered with ClinicalTrials.gov, number NCT00705445. Results: The trial was done between Nov 1, 2008, and Dec 31, 2011. 947 children were enrolled in group A clusters, 910 in group B clusters, and 889 in group C clusters. Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group (odds ratio [OR] for micronutrient powder without zinc = 0•20, 95% CI 0•11–0•36; OR for micronutrient powder with zinc = 0•25, 95% CI 0•14–0•44). Compared with the control group, children in the group receiving micronutrient powder without zinc gained an extra 0•31 cm

  14. Decreased erythrocyte CCS content is a biomarker of copper overload in rats.

    Science.gov (United States)

    Bertinato, Jesse; Sherrard, Lindsey; Plouffe, Louise J

    2010-07-02

    Copper (Cu) is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS content in erythrocytes is particularly sensitive to decreased Cu status. Given the lack of a non-invasive, sensitive and specific biomarker for the assessment of Cu excess, we investigated whether CCS expression in erythrocytes reflects Cu overload. Rats were fed diets containing normal or high levels of Cu for 13 weeks. Diets contained 6.3 +/- 0.6 (Cu-N), 985 +/- 14 (Cu-1000) or 1944 +/- 19 (Cu-2000) mg Cu/kg diet. Rats showed a variable response to the high Cu diets. Some rats showed severe Cu toxicity, while other rats showed no visible signs of toxicity and grew normally. Also, some rats had high levels of Cu in liver, whereas others had liver Cu concentrations within the normal range. Erythrocyte CCS protein expression was 30% lower in Cu-2000 rats compared to Cu-N rats (P CCS (47% reduction, P CCS content is associated with Cu overload in rats and should be evaluated further as a potential biomarker for assessing Cu excess in humans.

  15. Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload

    Directory of Open Access Journals (Sweden)

    Sujith Dassanayaka

    2018-07-01

    Full Text Available Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2. An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

  16. Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Mitchell C. Coleman

    2017-11-01

    Full Text Available Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios.

  17. Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse.

    Science.gov (United States)

    Cupesi, Mihaela; Yoshioka, Jun; Gannon, Joseph; Kudinova, Anastacia; Stewart, Colin L; Lammerding, Jan

    2010-06-01

    Inherited mutations cause approximately 30% of all dilated cardiomyopathy cases, with autosomal dominant mutations in the LMNA gene accounting for more than one third of these. The LMNA gene encodes the nuclear envelope proteins lamins A and C, which provide structural support to the nucleus and also play critical roles in transcriptional regulation. Functional deletion of a single allele is sufficient to trigger dilated cardiomyopathy in humans and mice. However, whereas Lmna(-/-) mice develop severe muscular dystrophy and dilated cardiomyopathy and die by 8 weeks of age, heterozygous Lmna(+/-) mice have a much milder phenotype, with changes in ventricular function and morphology only becoming apparent at 1 year of age. Here, we studied 8- to 20-week-old Lmna(+/-) mice and wild-type littermates in a pressure overload model to examine whether increased mechanical load can accelerate or exacerbate myocardial dysfunction in the heterozygotes. While overall survival was similar between genotypes, Lmna(+/-) animals had a significantly attenuated hypertrophic response to pressure overload as evidenced by reduced ventricular mass and myocyte size. Analysis of pressure overload-induced transcriptional changes suggested that the reduced hypertrophy in the Lmna(+/-) mice was accompanied by impaired activation of the mechanosensitive gene Egr-1. In conclusion, our findings provide further support for a critical role of lamins A and C in regulating the cellular response to mechanical stress in cardiomyocytes and demonstrate that haploinsufficiency of lamins A and C alone is sufficient to alter hypertrophic responses and cardiac function in the face of pressure overload in the heart. (c) 2009 Elsevier Ltd. All rights reserved.

  18. Therapeutic iron : Evaluation of methods to assess intravenous iron safety profiles and the development of a novel formulation for oral iron delivery

    NARCIS (Netherlands)

    Span, K.|info:eu-repo/dai/nl/357800842

    2018-01-01

    Iron treatment is necessary to replenish iron deficit due to several clinical conditions such as chronic diseases. However, as an excess of iron can result in redox imbalance resulting in oxidative stress and thus severe damage to tissue and organs, it is of utmost importance to develop iron

  19. Combination effect of sponge iron and calcium nitrate on severely eutrophic urban landscape water: an integrated study from laboratory to fields.

    Science.gov (United States)

    Wang, Guan-Bai; Wang, Yi; Zhang, Ying

    2018-03-01

    In this study, the in situ restoration of urban landscape water through the combined application of sponge iron (SI) and calcium nitrate (CN) was conducted in the Xi'an Moat of China. The combination effect of SI and CN on the phosphorus (P) control was explored through laboratory and field experiments. Results showed that the optimum mass ratio of SI and CN was 4:1, and the optimum dosage of combined SI and CN was 1.4 g/L for controlling eutrophication in the water body at Xi'an Moat. The field experiment demonstrated that SI and CN efficiently controlled P concentration in overlying and interstitial water and obtained a maximum efficiency of 88.6 and 65.2% in soluble reactive P locking, respectively. The total P, organic P, and Ca-bound P contents in sediment simultaneously increased by 7.7, 15.2, and 2.4%, respectively, after 56 days. Therefore, the combined application of SI and CN achieved the goal of transferring the P from overlying and interstitial water to the sediment. Considering the environmental effect and economic investment, the combined application of SI and CN at a mass ratio of 4:1 and dosage of 1.4 g/L is an excellent choice for the in situ rehabilitation of eutrophic water with a high internal P load.

  20. Intestinal absorbtion from therapeutic iron doses

    International Nuclear Information System (INIS)

    Werner, E.

    1977-01-01

    On a total of 105 persons with normal iron stores, iron depletion, and iron deficiency the intestinal absorption from therapeutic iron doses (100 mg Fe and 50 mg Fe as ferrous glycocoll sulphate) of a special galenic form was measured. The measurements were performed by means of a whole-body counter and preparations labelled with radio iron ( 59 Fe). Mean values of absorption rates from 100 mg Fe in healthy males were 5.0% and in healthy females 5.6% whereas in latent iron deficiency and in iron deficiency anemia mean values of 10% and 13% were obtained, respectively. The maximum absorption rate of 20 to 25% is reached already in the late stage of latent iron deficiency. Advancing severeness of iron deficiency is not followed by an increase of iron absorption. Investigations an 21 persons showed no significant difference between absorption rates of the galenic preparations used when administered orally before or after breakfast, respectively. (orig.) [de

  1. Aldosterone and mortality in hemodialysis patients: role of volume overload.

    Science.gov (United States)

    Hung, Szu-Chun; Lin, Yao-Ping; Huang, Hsin-Lei; Pu, Hsiao-Fung; Tarng, Der-Cherng

    2013-01-01

    Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality. We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (280 pg/mL). Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15) in the absence of volume overload. The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

  2. The interaction of iron and the genome: For better and for worse.

    Science.gov (United States)

    Troadec, Marie-Bérengère; Loréal, Olivier; Brissot, Pierre

    2017-10-01

    Iron, as an essential nutrient, and the DNA, as the carrier of genetic information which is physically compacted into chromosomes, are both needed for normal life and well-being. Therefore, it is not surprising that close interactions exist between iron and the genome. On the one hand, iron, especially when present in excess, may alter genome stability through oxidative stress, and may favor cell cycle abnormalities and the development of malignant diseases. The genome also receives a feedback signal from the systemic iron status, leading to promotion of expression of genes that regulate iron metabolism. Conversely, on the other hand, DNA mutations may cause genetic iron-related diseases such as hemochromatosis, archetype of iron-overload diseases, or refractory iron deficiency anemia (IRIDA). Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effect of chronic ethanol administration on iron metabolism in the rat

    International Nuclear Information System (INIS)

    Sanchez, J.; Casas, M.; Rama, R.

    1988-01-01

    This study shows that the ingestion of ethanol provokes alterations in iron metabolism which may lead to iron overload. Impaired release of reticuloendothelial iron was shown by a decrease of the maximum red blood cell utilization when radioactive iron was supplied as colloidal iron. An impairment in the erythropoietic activity of ethanoltreated animals was also observed, as can be seen from the reduced plasma iron turnover and red blood cell utilization within 24 h of iron administration. A rise in marrow transit time was also observed. In ethanol-treated rats there was an increase in the amount of iron retained both in the liver and the spleen. This was observed in both sexes and also in the offspring from ethanol-treated mothers. (author)

  4. Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Elena Gammella

    2015-01-01

    Full Text Available The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies.

  5. Blood Transfusion, Serum Ferritin, and Iron in Hemodialysis Patients in Africa

    Science.gov (United States)

    Kouegnigan Rerambiah, Leonard; Essola Rerambiah, Laurence; Mbourou Etomba, Armel; Mouguiama, Rose Marlène; Issanga, Phanie Brunelle; Biyoghe, Axel Sydney; Batchilili, Batchelili; Akone Assembe, Sylvestre; Djoba Siawaya, Joel Fleury

    2015-01-01

    Background and Objectives. There is no data analyzing the outcome of blood transfusions and oral iron therapy in patients with kidneys failure in sub-Saharan Africa. The present study aimed to fill that gap and assess the value of ferritin in the diagnosis of iron overload and deficiency. Design. From January to February 2012, we prospectively studied 85 hemodialysis patients (78% of males and 22% of females aged 20 to 79 years) attending the Gabonese National Hemodialysis Centre. Results. Correlation studies showed (a) a strong positive linear relationship between the number of blood transfusions and high serum ferritin in hemodialysis patient (Spearman r : 0.74; P value: 0.0001); (b) a weak association between the number of blood transfusions and serum iron concentrations (Spearman r : 0.32; P value: 0.04); (c) a weak association between serum ferritin and serum iron (Spearman r : 0.32; P value: 0.003). Also, the strength of agreement beyond chance between the levels of ferritin and iron in the serum was poor (κ = 0.14). The prevalence of iron overload was 10.6%, whereas the prevalence of iron deficiency was 2.3%, comparing (1) patients with a maximum of one transfusion not on iron therapy; (2) patients with a maximum of one transfusion on iron therapy; (3) polytransfused patients not on iron therapy; and (4) polytransfused patients on oral iron therapy. The “Kruskal-Wallis test” showed that ferritin levels varied significantly between the groups (P value: 0.0001). Conclusion. Serum ferritin is not reliable as a marker of iron overload. For patients undergoing regular transfusion we recommend routine serum ferritin measurement and yearly measurement of LIC. PMID:25685597

  6. Mechanism Research of Arch Dam Abutment Forces during Overload

    Directory of Open Access Journals (Sweden)

    Yu Xia

    2015-01-01

    Full Text Available This paper presents research on the abutment forces of a double-curvature arch dam during overload based on numerical calculation results obtained through finite element method by Ansys. Results show that, with an increase in elevation, the abutment forces and bending moment of the arch dam increase first and then decrease from the bottom to the top of the dam. Abutment forces and bending moment reach their maximum at the middle or middle-down portion of the dam. The distributions of abutment forces and moment do not change during overload. The magnitude of each arch layer’s forces and moment increases linearly during overload. This result indicates that each arch layer transmits bearing loads to the rocks of the left and right banks steadily. This research explains the operating mechanism of an arch dam under normal and overload conditions. It provides a simple method to calculate the distribution of forces Fx and Fy and a new method to calculate the overload factor of an arch dam through the estimation of arch layers based on the redistribution characteristic of arch abutment forces.

  7. Cast irons

    CERN Document Server

    1996-01-01

    Cast iron offers the design engineer a low-cost, high-strength material that can be easily melted and poured into a wide variety of useful, and sometimes complex, shapes. This latest handbook from ASM covers the entire spectrum of one of the most widely used and versatile of all engineered materials. The reader will find the basic, but vital, information on metallurgy, solidification characteristics, and properties. Extensive reviews are presented on the low-alloy gray, ductile, compacted graphite, and malleable irons. New and expanded material has been added covering high-alloy white irons used for abrasion resistance and high-alloy graphitic irons for heat and corrosion resistance. Also discussed are melting furnaces and foundry practices such as melting, inoculation, alloying, pouring, gating and rising, and molding. Heat treating practices including stress relieving, annealing, normalizing, hardening and tempering, autempering (of ductile irons), and surface-hardening treatments are covered, too. ASM Spec...

  8. Quantification of liver iron concentration with magnetic resonance imaging by combining T1-, T2-weighted spin echo sequences and a gradient echo sequence

    NARCIS (Netherlands)

    Kreeftenberg, HG; Mooyaart, EL; Sluiter, WJ; Kreeftenberg, HG; Huizenga, Reint

    Background: The aim of the study was to quantify hepatic iron by MRI for practical use. Methods: In twenty-three patients with various degrees of iron overload, measurements were carried out with a 1.5 Tesla MR unit. A combination of pulse sequences (T1, T2 and gradient echo) enabled us to quantify

  9. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead...... involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake, and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells...

  10. Role of the NMDA receptor and iron on free radical production and brain damage following transient middle cerebral artery occlusion.

    Science.gov (United States)

    Im, Doo Soon; Jeon, Jeong Wook; Lee, Jin Soo; Won, Seok Joon; Cho, Sung Ig; Lee, Yong Beom; Gwag, Byoung Joo

    2012-05-21

    Excess activation of ionotropic glutamate receptors and iron is believed to contribute to free radical production and neuronal death following hypoxic ischemia. We examined the possibility that both NMDA receptor activation and iron overload determine spatial and temporal patterns of free radical production after transient middle cerebral artery occlusion (tMCAO) in male Sprague-Dawley rats. Mitochondrial free radical (MFR) levels were maximally increased in neurons in the core at 1 h and 24 h after tMCAO. Early MFR production was blocked by administration of MK-801, an NMDA receptor antagonist, but not deferoxamine, an iron chelator. Neither MK-801 nor deferoxamine attenuated late MFR production in the core. Increased MFRs were observed in penumbral neurons within 6 h and gradually increased over 24 h after tMCAO. Slowly-evolving MFRs in the core and penumbra were accompanied by iron overload. Deferoxamine blocked iron overload but reduced MFR production only in the penumbra. Combined MK-801/deferoxamine reduced late MFR production in both core and penumbra in an additive manner. Combination therapy significantly ameliorated infarction compared with monotherapy. These findings suggest that the NMDA receptor activation and iron overload mediate late MFR production and infarction after tMCAO. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Universal iron fortification of foods: the view of a hematologist

    Directory of Open Access Journals (Sweden)

    José Murilo Martins

    2012-01-01

    Full Text Available With the objective of reducing the high incidence of iron deficiency anemia, the Brazilian National Health Surveillance Agency (ANVISA adopted Resolution 344 in December 2002, which made the addition of iron and folic acid to all industrialized wheat and maize flours in Brazil compulsory. After a series of doubts about this universal measure of food fortification, a review of case reports on long-term medicinal iron intake published in the medical literature was undertaken to investigate the clinical behavior of this hematological conduct. Long-term medicinal iron ingestion is an extremely rare and serious situation. The data suggest that there are cases of hemochromatosis in women whose illnesses were accelerated with this therapy. It is very difficult to determine the amount of iron ingested by Brazilian citizens in the current system of fortification, but there is evidence that there has been an appreciable increase. Although iron fortification of food has been recognized by some authors as a good strategy to combat iron deficiency, some nation shave abandoned this measure. The patient with hemochromatosis is the most affected by compulsory iron fortification and as this disease is now considered a public health problem, we believe that Resolution 344 of ANVISA should be reviewed in order to find a solution beneficial to all segments of the Brazilian population; one should not try to correct one condition (iron deficiency by exacerbating another (acceleration of iron overload cases.

  12. The Battle for Iron between Humans and Microbes.

    Science.gov (United States)

    Carver, Peggy L

    2018-01-01

    Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment. To describe complex 'tug of war' for iron that has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. A review of current literature was performed, to assess current approaches and controversies in iron therapy and chelation in humans. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection. The administration of iron chelating agents and siderophore- conjugate drugs to infected hosts seems a biologically plausible approach as adjunctive therapy in the treatment of infections caused by pathogens dependent on host iron supply (e.g. tuberculosis, malaria, and many bacterial and fungal pathogens); however, thus far, studies in humans have proved unsuccessful. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ...

  14. Symmetrical and overloaded effect of diffusion in information filtering

    Science.gov (United States)

    Zhu, Xuzhen; Tian, Hui; Chen, Guilin; Cai, Shimin

    2017-10-01

    In physical dynamics, mass diffusion theory has been applied to design effective information filtering models on bipartite network. In previous works, researchers unilaterally believe objects' similarities are determined by single directional mass diffusion from the collected object to the uncollected, meanwhile, inadvertently ignore adverse influence of diffusion overload. It in some extent veils the essence of diffusion in physical dynamics and hurts the recommendation accuracy and diversity. After delicate investigation, we argue that symmetrical diffusion effectively discloses essence of mass diffusion, and high diffusion overload should be published. Accordingly, in this paper, we propose an symmetrical and overload penalized diffusion based model (SOPD), which shows excellent performances in extensive experiments on benchmark datasets Movielens and Netflix.

  15. Testing of camera performance standards at steady and local overloading

    International Nuclear Information System (INIS)

    Keszthelyine Landori, S.; Adorjanne Farkas, M.; Csirik, J.

    1983-01-01

    Camera performance standards are usually given for low count rates and uniform irradiation. A conventional analog gamma camera system (Gamma MB 9100 manufactured under the know-how of Picker DC 4/12 in Hungary) was studied on the basis of the Picker test procedure and the NEMA standard system. Uniformity, linearity, spatial and energy resolution were measured at high count rates and uniform irradiation (steady overloading). Linearity was studied at local overloading. Linearity, spatial and energy resolution were measured by a 1024-channel analyzer-computer system of KFKI, Hungary. The data were evaluated on the basis of NEMA standards, while uniformity was measured by the Gamma data processing system and evaluated by special SEGAMS programs. Performance variations were studied between 7500 cps and 75.000 cps pulse rates. Spatial and energy resolution were influenced strongly, uniformity slightly by pulse rates, while linearity did not change at all. Linearity was not influenced even by local overloading. (author)

  16. Overloaded and stressed: A case study of women working in the health care sector.

    Science.gov (United States)

    Stevenson, Maggie; Duxbury, Linda

    2018-04-23

    Although role overload has been shown to be prevalent and consequential, there has been little attempt to develop the associated theory. The fact that the consequences of role overload can be positive or negative implies that the relationship between role overload and perceived stress depends partly on the environment within which role overload is experienced (i.e., the perceived situation) and how the situation is evaluated (i.e., appraised). Guided by cognitive appraisal theory, this study applies qualitative methodology to identify the situation properties that contribute to variable stress reactions to role overload. In this in-depth examination, overloaded female hospital workers were asked to describe what makes role overload situations potentially stressful, to gain an insight into how role overload is appraised. A taxonomy listing 12 role overload situation properties was developed from the findings, providing the first known classification of the situation properties of role overload that can create the potential for stress. The results also reveal clues as to why some people suffer more stress during role overload than others, increase our understanding of the relationship between role overload and perceived stress, and provide a useful tool for examining the environment of role overload. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  17. New Insights on Iron Study in Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Noha M. El Husseiny

    2014-12-01

    Full Text Available OBJECTIVE: Hepcidin plays a pivotal role in iron homeostasis. It is predominantly produced by hepatocytes and inhibits iron release from macrophages and iron uptake by intestinal epithelial cells. Competitive ELISA is the current method of choice for the quantification of serum hepcidin because of its lower detection limit, low costs, and high throughput. This study aims to discuss the role of hepcidin in the pathogenesis of iron overload in recently diagnosed myelodysplasia (MDS cases. METHODS: The study included 21 recently diagnosed MDS patients and 13 healthy controls. Ferritin, hepcidin, and soluble transferrin receptor (sTFR were measured in all subjects. RESULTS: There were 7 cases of hypocellular MDS, 8 cases of refractory cytopenia with multilineage dysplasia, and 6 cases of refractory anemia with excess blasts. No difference was observed among the 3 MDS subtypes in terms of hepcidin, sTFR, and ferritin levels (p>0.05. Mean hepcidin levels in the MDS and control groups were 55.8±21.5 ng/mL and 19.9±2.6 ng/ mL, respectively. Mean sTFR was 45.7±8.8 nmol/L in MDS patients and 31.1±5.6 nmol/L in the controls. Mean ferritin levels were significantly higher in MDS patients than in controls (539.14±83.5 ng/mL vs. 104.6±42.9 ng/mL, p0.05. CONCLUSION: Hepcidin may not be the main cause of iron overload in MDS. Further studies are required to test failure of production or peripheral unresponsiveness to hepcidin in MDS cases.

  18. Monitoring body iron burden using X-ray fluorescence (XRF)

    International Nuclear Information System (INIS)

    Farquharson, M.J.; Bagshaw, A.P.

    2001-01-01

    X-ray fluorescence, using Cu K alpha and K beta radiation, has been used to measure the Fe content of skin of two groups of rats, one Fe overloaded and one control group. These skin Fe levels were compared to the liver and heart Fe levels measured using colorimetry. Correlation coefficients of 0.86 and 0.88 respectively were found indicating that skin Fe levels may be a potential marker for body iron burden.

  19. Thermal overload protection for electric motors on safety-related motor-operated valves: Generic Issue II.E.6.1

    International Nuclear Information System (INIS)

    Rothberg, O.

    1988-06-01

    NRC regulatory positions, as stated in Regulatory Guide 1.106, Revision 1, have been identified by the Office for Analysis and Evaluation of Operational Data (AEOD) as potential contributors to valve motor burnout. AEOD is particularly concerned about the allowed policy of bypassing thermal overload devices during normal or accident conditions. Regulatory Guide 1.106 favors compromising the function of thermal overload devices in favor of completing the safety-related action of valves. The purpose of this study was to determine if the guidance contained in Regulatory Guide 1.106 is appropriate and, if not, to recommend the necessary changes. This report describes thermal overload devices commonly used to protect safety-related valve operator motors. The regulatory guidelines stated in Regulatory Guide 1.106 along with the limitations of thermal overload protection are discussed. Supplements and alternatives to thermal overload protection are also described. Findings and conclusions of several AEOD reports are discussed. Information obtained from the standard review plan, standard technical specifications, technical specifications from representative plants, and several papers are cited

  20. Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

    Science.gov (United States)

    Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

    2015-09-01

    The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and

  1. Facile and sustainable synthesis of shaped iron oxide nanoparticles: effect of iron precursor salts on the shapes of iron oxides.

    Science.gov (United States)

    Sayed, Farheen N; Polshettiwar, Vivek

    2015-05-05

    A facile and sustainable protocol for synthesis of six different shaped iron oxides is developed. Notably, all the six shapes of iron oxides can be synthesised using exactly same synthetic protocol, by simply changing the precursor iron salts. Several of the synthesised shapes are not reported before. This novel protocol is relatively easy to implement and could contribute to overcome the challenge of obtaining various shaped iron oxides in economical and sustainable manner.

  2. Can We Ever Escape from Data Overload? A Cognitive Systems Diagnosis

    National Research Council Canada - National Science Library

    Woods, David

    1998-01-01

    Data overload is a generic and tremendously difficult problem. In this report, we diagnose why this is the case and how intelligence analysis presents a particularly difficult version of data overload...

  3. Iron as a possible aggravating factor for osteopathy in itai-itai disease, a disease associated with chronic cadmium intoxication

    International Nuclear Information System (INIS)

    Noda, M.; Yasuda, M.; Kitagawa, M.

    1991-01-01

    Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. We examined 23 autopsy cases of itai-itai disease and 18 cases of sudden death as controls. Urine and blood samples from 10 patients were collected before they died and revealed the presence of severe anemia and renal tubular injuries. Undecalcified sections of iliac bone were stained with Aluminon reagent, and ammonium salt of aurintricarboxylic acid, and Prussian blue reagent in all cases of itai-itai disease. These two reagents reacted at the same mineralization fronts. X-ray microanalysis revealed the presence of iron at mineralization fronts in itai-itai disease. Five patients showed evidence of hemosiderosis in the liver, spleen, and pancreas, probably as a result of post transfusion iron overload. Renal calculi and calcified aortic walls were also stained with Prussian blue reagent in several patients. Neither ferritin nor transferrin were visualized at mineralization fronts in itai-itai disease by immunohistochemical staining. These results suggest that iron is bound to calcium or to calcium phosphate by a physicochemical reaction. A marked osteomalacia was observed in 10 cases of itai-itai disease by histomorphometry. Regression analyses of data from cases of itai-itai disease suggested that an Aluminon-positive metal inhibited mineralization and that renal tubules were injured. Since bone Cd levels were increased in itai-itai disease, it is likely that renal tubules were injured by exposure to Cd. Therefore, stainable bone iron is another possible aggravating factor for osteopathy in itai-itai disease, and a synergistic effect between iron and Cd on mineralization is proposed

  4. Iron as a possible aggravating factor for osteopathy in itai-itai disease, a disease associated with chronic cadmium intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Noda, M.; Yasuda, M.; Kitagawa, M. (Toyama Medical and Pharmaceutical Univ. (Japan))

    1991-03-01

    Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. We examined 23 autopsy cases of itai-itai disease and 18 cases of sudden death as controls. Urine and blood samples from 10 patients were collected before they died and revealed the presence of severe anemia and renal tubular injuries. Undecalcified sections of iliac bone were stained with Aluminon reagent, and ammonium salt of aurintricarboxylic acid, and Prussian blue reagent in all cases of itai-itai disease. These two reagents reacted at the same mineralization fronts. X-ray microanalysis revealed the presence of iron at mineralization fronts in itai-itai disease. Five patients showed evidence of hemosiderosis in the liver, spleen, and pancreas, probably as a result of post transfusion iron overload. Renal calculi and calcified aortic walls were also stained with Prussian blue reagent in several patients. Neither ferritin nor transferrin were visualized at mineralization fronts in itai-itai disease by immunohistochemical staining. These results suggest that iron is bound to calcium or to calcium phosphate by a physicochemical reaction. A marked osteomalacia was observed in 10 cases of itai-itai disease by histomorphometry. Regression analyses of data from cases of itai-itai disease suggested that an Aluminon-positive metal inhibited mineralization and that renal tubules were injured. Since bone Cd levels were increased in itai-itai disease, it is likely that renal tubules were injured by exposure to Cd. Therefore, stainable bone iron is another possible aggravating factor for osteopathy in itai-itai disease, and a synergistic effect between iron and Cd on mineralization is proposed.

  5. IRON DOME

    African Journals Online (AJOL)

    6 Israeli Navy 'First Arm of the Sea: The Successful Interception of the Iron Dome Rocket .... sky to destroy them whilst in flight to minimise civilian casualties. ..... Including The Moon and Celestial Bodies.53 Demeyere further emphasises the.

  6. Iron overdose

    Science.gov (United States)

    ... tracing) X-ray to detect and track iron tablets through the stomach and intestines Treatment may include: ... BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016: ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of the body. When your heart has to work harder, this can lead to several conditions: irregular heartbeats called arrhythmias , a heart murmur , an ... chronic conditions, iron-deficiency anemia can make their condition worse or result in treatments not working as well. Look for Diagnosis will discuss any ...

  8. Determination of Permissible Short-Time Emergency Overloading of Turbo-Generators and Synchronous Compensators

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2011-01-01

    Full Text Available The paper shows that failure to take into account variable ratio of short-time emergency overloading of turbo-generators (synchronous compensators that can lead to underestimation of overloading capacity or impermissible insulation over-heating.A method has been developed for determination of permissible duration of short-time emergency over-loading that takes into account changes of over-loading ratio in case of a failure.

  9. A Room Temperature Ultrasensitive Magnetoelectric Susceptometer for Quantitative Tissue Iron Detection

    Science.gov (United States)

    Xi, Hao; Qian, Xiaoshi; Lu, Meng-Chien; Mei, Lei; Rupprecht, Sebastian; Yang, Qing X.; Zhang, Q. M.

    2016-07-01

    Iron is a trace mineral that plays a vital role in the human body. However, absorbing and accumulating excessive iron in body organs (iron overload) can damage or even destroy an organ. Even after many decades of research, progress on the development of noninvasive and low-cost tissue iron detection methods is very limited. Here we report a recent advance in a room-temperature ultrasensitive biomagnetic susceptometer for quantitative tissue iron detection. The biomagnetic susceptometer exploits recent advances in the magnetoelectric (ME) composite sensors that exhibit an ultrahigh AC magnetic sensitivity under the presence of a strong DC magnetic field. The first order gradiometer based on piezoelectric and magnetostrictive laminate (ME composite) structure shows an equivalent magnetic noise of 0.99 nT/rt Hz at 1 Hz in the presence of a DC magnetic field of 0.1 Tesla and a great common mode noise rejection ability. A prototype magnetoelectric liver susceptometry has been demonstrated with liver phantoms. The results indicate its output signals to be linearly responsive to iron concentrations from normal iron dose (0.05 mg Fe/g liver phantom) to 5 mg Fe/g liver phantom iron overload (100X overdose). The results here open up many innovative possibilities for compact-size, portable, cost-affordable, and room-temperature operated medical systems for quantitative determinations of tissue iron.

  10. Theoretical and experimental investigations on the behaviour of iodine during severe accidents: organic iodide, iodine/silver reaction, iodine/iron reaction. Pt. 4: organic iodide. Final report

    International Nuclear Information System (INIS)

    Hellmann, S.; Greger, G.U.; Funke, F.; Bleier, A.; Zeeh, W.

    1995-11-01

    Analysis of the consequences of severe accidents in nuclear power plants requires knowledge of the behaviour of radionuclides relevant from the radiological viewpoint. The role played by radioiodine is particularly important. In the current modelling of iodine behaviour the heterogeneous formation of organic iodide is not adequately taken into consideration owing to a lack of data or insufficient accuracy of data. This project is intended to eliminate some gaps in critical areas. This final report, part 4, describes the tests carried out in the two relevant areas - heterogeneous formation of organic coatings in the gas phase (containment atmosphere) - heterogeneous formation of organic iodide at organic coatings in aqueous phase (containment sump). Moreover, modelling suggestions how to include the resulting knowledge in the iodine accident behaviour code IMPAIR are given. (orig.) [de

  11. Obesity as an Emerging Risk Factor for Iron Deficiency

    Directory of Open Access Journals (Sweden)

    Elmar Aigner

    2014-09-01

    Full Text Available Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS or nonalcoholic fatty liver disease (NAFLD. This constellation has been named the “dysmetabolic iron overload syndrome (DIOS”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

  12. Information Overload and Viral Marketing: Countermeasures and Strategies

    Science.gov (United States)

    Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

    Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

  13. The association between role overload and women's mental health.

    Science.gov (United States)

    Glynn, Keva; Maclean, Heather; Forte, Tonia; Cohen, Marsha

    2009-02-01

    To determine the importance of role overload (the extent to which a person feels overwhelmed by her total responsibilities) relative to other known social determinants of women's mental health. A Canadian national, random sample, cross-sectional telephone survey in 2003 assessed the association among role overload, types and quality of roles (parent, employee, spouse), sociodemographics, and mental health (using the SF-12) using linear regression. Analysis included 716 women aged 25-54 who indicated that their youngest child living in the household was aged < or =17 years. Perceptions of greater role overload were associated with poorer mental health (p < 0.0001). Women working <35 hours per week (p = 0.04) or 35-40 hours per week (p 5 0.002) reported better mental health than nonemployed women, as did women with the highest annual household income ($70,000+)(p = 0.001). Also associated with better mental health were higher marital status quality scores for both married and single women (p < 0.001), higher job quality scores among employed women (p = 0.02), greater homemaking quality scores among unemployed women (p = 0.03), and women reporting high parental quality (p = 0.04) Role overload showed a stronger relationship to mental health than other sociodemographic variables, including income. Our findings indicate the importance of measuring women's experience of their multiple roles rather than focusing on single roles. More research is warranted on the totality of women's experiences of their many social role obligations.

  14. Glycolytic overload and the genesis of breast cancer.

    Science.gov (United States)

    Robson, J R

    1984-03-01

    It is suggested that the development of breast cancer is due to overloading of the glycolytic pathways. An excess of substrates or an excessive delivery rate of substrates to the Krebs Cycle is believed to result in the formation of acetyl CoA. Feedback mechanisms controlling the conversion of acetyl CoA to cholesterol may be overcome; the resulting high concentration of cholesterol induces the formation of pregnenolone which may then be converted into androgens, estrogens and progesterone. These steroids are in addition to those produced by gonads and adrenal glands. Glycolytic overload is also associated with an increase in fat stores which have been shown to be the site of interconversion of sex hormones. Excess sex hormones or abnormal sex hormones are believed to be the cause of breast cancer. The hypothesis presented links glycolytic overload with clinical biochemical phenomena and explains some of the anomalies observed in breast cancer experience in different ethnic groups. Changes in dietary habits during the history of man resulting in " gorging " and the consumption of highly refined sugars are possible causes of glycolytic overload. So, also, is impaired thermogenesis due to Brown Fat deficits in certain ethnic groups.

  15. Random fluid limit of an overloaded polling model

    NARCIS (Netherlands)

    M. Frolkova (Masha); S.G. Foss (Sergey); A.P. Zwart (Bert)

    2014-01-01

    htmlabstractIn the present paper, we study the evolution of an overloaded cyclic polling model that starts empty. Exploiting a connection with multitype branching processes, we derive fluid asymptotics for the joint queue length process. Under passage to the fluid dynamics, the server switches

  16. Random fluid limit of an overloaded polling model

    NARCIS (Netherlands)

    M. Frolkova (Masha); S.G. Foss (Sergey); A.P. Zwart (Bert)

    2013-01-01

    htmlabstractIn the present paper, we study the evolution of an~overloaded cyclic polling model that starts empty. Exploiting a~connection with multitype branching processes, we derive fluid asymptotics for the joint queue length process. Under passage to the fluid dynamics, the server switches

  17. Information Overload in Multi-Stage Selection Procedures

    NARCIS (Netherlands)

    S.S. Ficco (Stefano); V.A. Karamychev (Vladimir)

    2004-01-01

    textabstractThe paper studies information processing imperfections in a fully rational decision-making network. It is shown that imperfect information transmission and imperfect information acquisition in a multi-stage selection game yield information overload. The paper analyses the mechanisms

  18. Modeling of Unidirectional-Overloaded Transition in Catalytic Tubular Microjets

    NARCIS (Netherlands)

    Klingner, Anke; Khalil, Islam S. M.; Magdanz, Veronika; Fomin, Vladimir M.; Schmidt, Oliver G.; Misra, Sarthak

    2017-01-01

    A numerical time-resolved model is presented for predicting the transition between unidirectional and overloaded motion of catalytic tubular microjets (Ti/Fe/Pt rolled-up microtubes) in an aqueous solution of hydrogen peroxide. Unidirectional movement is achieved by periodic ejection of gas bubbles

  19. Tools to Reduce Overload in the School Social Worker Role

    Science.gov (United States)

    Leyba, Erin Gleason

    2009-01-01

    This article addresses how school social workers can decrease overload in their roles. A two-step process of envisioning an ideal role is outlined: (1) indentifying priorities and activities that are effective or in need of expansion and (2) weeding out activities that could be done differently or no longer serve their purpose. The author…

  20. Shift Work, Role Overload, and the Transition to Parenthood

    Science.gov (United States)

    Perry-Jenkins, Maureen; Goldberg, Abbie E.; Pierce, Courtney P.; Sayer, Aline G.

    2007-01-01

    This article examines how the work hours, work schedules, and role overload of working-class couples are related to depressive symptoms and relationship conflict across the transition to parenthood. Data are from 132 dual-earner couples interviewed 5 times across the transition. Multilevel modeling analyses revealed that working evening or night…

  1. A Confirmatory Factor Analysis of Reilly's Role Overload Scale

    Science.gov (United States)

    Thiagarajan, Palaniappan; Chakrabarty, Subhra; Taylor, Ronald D.

    2006-01-01

    In 1982, Reilly developed a 13-item scale to measure role overload. This scale has been widely used, but most studies did not assess the unidimensionality of the scale. Given the significance of unidimensionality in scale development, the current study reports a confirmatory factor analysis of the 13-item scale in two samples. Based on the…

  2. Sport coaching officials and their stressors: Work overload, role ...

    African Journals Online (AJOL)

    Sport officials' concerns over job stressors have become common due to the adverse effect on health. The study sought to examine the associations of work overload, role ambiguity and role conflict, as well as their predictive influence on job satisfaction of sport coaches in Gauteng, South Africa. Data were collected from a ...

  3. Overload prevention in model supports for wind tunnel model testing

    Directory of Open Access Journals (Sweden)

    Anton IVANOVICI

    2015-09-01

    Full Text Available Preventing overloads in wind tunnel model supports is crucial to the integrity of the tested system. Results can only be interpreted as valid if the model support, conventionally called a sting remains sufficiently rigid during testing. Modeling and preliminary calculation can only give an estimate of the sting’s behavior under known forces and moments but sometimes unpredictable, aerodynamically caused model behavior can cause large transient overloads that cannot be taken into account at the sting design phase. To ensure model integrity and data validity an analog fast protection circuit was designed and tested. A post-factum analysis was carried out to optimize the overload detection and a short discussion on aeroelastic phenomena is included to show why such a detector has to be very fast. The last refinement of the concept consists in a fast detector coupled with a slightly slower one to differentiate between transient overloads that decay in time and those that are the result of aeroelastic unwanted phenomena. The decision to stop or continue the test is therefore conservatively taken preserving data and model integrity while allowing normal startup loads and transients to manifest.

  4. Stress 2.0: Social Media Overload among Swiss Teenagers

    NARCIS (Netherlands)

    Lutz, Christoph; Ranzini, Giulia; Meckel, Miriam

    2014-01-01

    Technostress and information overload are serious challenges of the information age. An alarming number of people exhibit dangerously intensive media consumption, while Internet and mobile phone addictions are a widespread phenomenon. At the same time, new media overexposure among young people is

  5. 30 CFR 75.518-2 - Incandescent lamps, overload and short circuit protection.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Incandescent lamps, overload and short circuit...-General § 75.518-2 Incandescent lamps, overload and short circuit protection. Incandescent lamps installed... or direct current feeder circuits, need not be provided with separate short circuit or overload...

  6. Fisiologia e metabolismo do ferro Iron physiology and metabolism

    Directory of Open Access Journals (Sweden)

    Helena Z. W. Grotto

    2010-06-01

    iron absorption, recycling, mobilization, utilization and storage. Disturbances in the synchronism among those processes may lead either to iron deficiency or to iron overload, both of which have important clinical consequences. This mini-review attempts to describe aspects related to iron metabolism and the participation of several proteins and mediators involved in these mechanisms. Moreover, intracellular and systemic regulation mechanisms responsible for providing the most suitable iron concentration for iron homeostasis maintenance will be presented.

  7. Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

    Science.gov (United States)

    Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

    2017-01-01

    Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2). The BPAN patients showed a concomitant increase of intracellular ferrous iron after starvation. An altered pattern of iron transporters with iron overload is highlighted in BPAN human fibroblasts, supporting for a role of DMT1 in NBIA. We here present a novel element, about iron accumulation, to the existing knowledge in field of NBIA. Attention is focused to a starvation-dependent iron overload, possibly accounting for iron accumulation in the basal ganglia. Further investigation could clarify iron regulation in BPAN.

  8. Body iron is a contributor to oxidative damage of DNA

    DEFF Research Database (Denmark)

    Tuomainen, T.P.; Loft, Steffen Huitfeldt; Nyyssonen, K.

    2007-01-01

    The transition metal iron is catalytically highly active in vitro, and not surprisingly, body iron has been suggested to promote oxidative stress in vivo. In the current analysis we studied the association of serum ferritin concentration and serum soluble transferrin receptor concentration...... with daily urinary 8-hydroxydeoxyguanosine excretion, a marker of oxidative stress, in 48 mildly dyslipidemic men in East Finland. In multivariate linear regression analyses allowing for age, smoking, body mass index and physical exercise, serum ferritin concentration predicted the excretion rate at B = 0.......17 (95% CI 0.08-0.26, P = 0.001), and serum soluble transferrin receptor to ferritin concentration ratio (TfR/ferritin) predicted the excretion rate at B = - 0.13 (95% CI - 0.21 to - 0.05, P = 0.002). Our data suggest that body iron contributes to excess oxidative stress already at non-iron overload...

  9. Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

    Science.gov (United States)

    Singh, Ajay; Haldar, Swati; Horback, Katharine; Tom, Cynthia; Zhou, Lan; Meyerson, Howard; Singh, Neena

    2017-01-01

    Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP−/−). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP−/− mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP−/− mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP−/− mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP−/− BM-macrophages incorporate significantly less NTB-59Fe in the absence or presence of excess extracellular iron, indicating reduced uptake and/or storage of available iron in the absence of PrPC. When expressed in neuroblastoma cells, PrPC exhibits NAD(P)H-dependent cell-surface and intracellular FR activity that requires the copper-binding octa-peptide-repeat region and linkage to the plasma membrane for optimal function. Incorporation of NTB-59Fe by neuroblastoma cells correlates with FR activity of PrPC, implicating PrPC in cellular iron uptake and metabolism. These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. PMID:23478311

  10. Amphiphile-induced heart muscle-cell (myocyte) injury: effects of intracellular fatty acid overload.

    Science.gov (United States)

    Janero, D R; Burghardt, C; Feldman, D

    1988-10-01

    Lipid amphiphile toxicity may be an important contributor to myocardial injury, especially during ischemia/reperfusion. In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)-induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5-(tetradecyloxy)-2-furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high-energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile-induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA "wash-out." Although the development and severity of amphiphile-induced myocyte injury could be correlated with both the intracellular TOFA/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid beta oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile-induced bioenergetic abnormalities appeared to constitute a state of "metabolic anoxia" underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.

  11. Effect of overload on the fatigue crack propagation in metastable beta Ti-V alloys

    International Nuclear Information System (INIS)

    Chakrabortty, S.B.; Starke, E.A. Jr.; Lee, E.W.

    1984-01-01

    The effects of overload on the fatigue crack propagation behavior of two Ti-V alloys having different deformation mechanisms were studied. The results are explained in terms of residual stress effects associated with the overload and the removal of these stresses during post-overload cycling. An additional effect occurs during multiple cycle overload when the deformation structure representative of the strain amplitude is believed to form in the overload reverse plastic zone. This structure must be rearranged during cycling at Delta Kb before the baseline FCGR is reached and the process is responsible for part of the delay period. 46 references

  12. Effects of overload on the threshold stress intensity factor for SCC

    International Nuclear Information System (INIS)

    Takahashi, Koji; Ando, Kotoji; Miyazaki, Yuji; Hashikura, Yasuaki

    2009-01-01

    The effects of overload on the threshold stress intensity factor for stress corrosion crack (K ISCC ) of stainless steel were studied. Tensile overload was applied to a wedge opening loaded (WOL) specimen of SUS316. Then, SCC tests were carried out to determine the resultant K ISCC . As a result, the apparent value of K ISCC increases as increasing a stress intensity factor by tensile overload (K OV ). The effects of tensile overload on K ISCC and the threshold stress intensity factor range for fatigue (ΔK th ) were compared. It was found that the effects of tensile overload on K ISCC were larger than that on ΔK th . (author)

  13. Isolation and characterization of iron chelators from turmeric (Curcuma longa): selective metal binding by curcuminoids.

    Science.gov (United States)

    Messner, Donald J; Surrago, Christine; Fiordalisi, Celia; Chung, Wing Yin; Kowdley, Kris V

    2017-10-01

    Iron overload disorders may be treated by chelation therapy. This study describes a novel method for isolating iron chelators from complex mixtures including plant extracts. We demonstrate the one-step isolation of curcuminoids from turmeric, the medicinal food spice derived from Curcuma longa. The method uses iron-nitrilotriacetic acid (NTA)-agarose, to which curcumin binds rapidly, specifically, and reversibly. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin each bound iron-NTA-agarose with comparable affinities and a stoichiometry near 1. Analyses of binding efficiencies and purity demonstrated that curcuminoids comprise the primary iron binding compounds recovered from a crude turmeric extract. Competition of curcuminoid binding to the iron resin was used to characterize the metal binding site on curcumin and to detect iron binding by added chelators. Curcumin-Iron-NTA-agarose binding was inhibited by other metals with relative potency: (>90% inhibition) Cu 2+  ~ Al 3+  > Zn 2+  ≥ Ca 2+  ~ Mg 2+  ~ Mn 2+ (80% by addition of iron to the media; uptake was completely restored by desferoxamine. Ranking of metals by relative potencies for blocking curcumin uptake agreed with their relative potencies in blocking curcumin binding to iron-NTA-agarose. We conclude that curcumin can selectively bind toxic metals including iron in a physiological setting, and propose inhibition of curcumin binding to iron-NTA-agarose for iron chelator screening.

  14. Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver.

    Science.gov (United States)

    Pardo-Andreu, Gilberto L; Barrios, Mariela Forrellat; Curti, Carlos; Hernández, Ivones; Merino, Nelson; Lemus, Yeny; Martínez, Ioanna; Riaño, Annia; Delgado, René

    2008-01-01

    In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases.

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich foods, especially during certain stages of life when more iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, salmon, iron- ... of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other dark ...

  17. Iron in diet

    Science.gov (United States)

    ... Reasonable amounts of iron are also found in lamb, pork, and shellfish. Iron from vegetables, fruits, grains, ... strawberries, tomatoes, and potatoes) also increase iron absorption. Cooking foods in a cast-iron skillet can also ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for your body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, ... iron deficiency. Endurance athletes lose iron through their gastrointestinal tracts. They also lose iron through the breakdown of ...