WorldWideScience

Sample records for iron overload detection

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

    Energy Technology Data Exchange (ETDEWEB)

    Marinelli, M; Gianesin, B [Department of Physics, University of Genoa, Via Dodecaneso 33, 16146 Genoa (Italy); Avignolo, C; Parodi, S [Department of Oncology, Biology and Genetics, Largo R Benzi 10, 16132 (Italy); Minganti, V [Department of Chemistry and Pharmaceutical and Alimentary Technology, Via Brigata Salerno 13, 16147 Genoa (Italy)

    2008-12-07

    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{sup 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 < 0.01). The in vivo measurements have been complemented by chemical analysis on excised livers and other organs (R{sup 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.

  2. 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

  3. Dysmetabolic iron overload syndrome (DIOS).

    Science.gov (United States)

    Deugnier, Yves; Bardou-Jacquet, Édouard; Lainé, Fabrice

    2017-12-01

    Dysmetabolic iron overload syndrome (DIOS) corresponds to mild increase in both liver and body iron stores associated with various components of metabolic syndrome in the absence of any identifiable cause of iron excess. It is characterized by hyperferritinemia with normal or moderately increased transferrin saturation, one or several metabolic abnormalities (increased body mass index with android distribution of fat, elevated blood pressure, dyslipidaemia, abnormal glucose metabolism, steatohepatitis), and mild hepatic iron excess at magnetic resonance imaging or liver biopsy. Alteration of iron metabolism in DIOS likely results from a multifactorial and dynamic process triggered by an excessively rich diet, facilitated by environmental and genetic cofactors and implying a cross-talk between the liver and visceral adipose tissue. Phlebotomy therapy cannot be currently considered as a valuable option in DIOS patients. Sustained modification of diet and life-style habits remains the first therapeutic intervention in these patients together with drug control of increased blood pressure, abnormal blood glucose and dyslipidaemia when necessary. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism.

    Science.gov (United States)

    Mousa, Amany A; Ghonem, Mohamed; Elhadidy, El Hadidy M; Azmy, Emad; Elbackry, Magda; Elbaiomy, Azza A; Elzehery, Rasha R; Shaker, Gehan A; Saleh, Omyma

    2016-05-01

    to assess the growth and pubertal development among a group of patients with β-Thalassemia Major (β-TM) and to evaluate the role of the pituitary gland and liver MRI signal intensity (SI) reduction in assessing and predicting the clinical severity of growth and pubertal dysfunctions. Thirty-eight patients with β-TM were examined and divided into two groups: Group I patients were of normal height and puberty and Group II patients had short statures and hypogonadism. Laboratory investigations included serum ferritin, LH, FSH, prolactin, TSH, and basal and dynamic growth hormones. Pituitary and liver MRIs were performed to assess the pituitary to fat (P/F) and liver to muscle (L/M) signal intensities (SI), respectively. Fifteen healthy and sex- and age-matched subjects were included as controls. Both patient groups had significantly elevated serum ferritin and significantly decreased prolactin and IGF1 compared to control subjects. Group II showed a significant reduction in LH, FSH, and IGF1 and a significant increase in ferritin in comparison with Group I and the control group, and it had a highly significant reduction in both P/F and L/M SI in comparison with Group I (p<0.001 and 0.008, respectively). The reduced P/F ratio was significantly correlated with FSH and LH, and a cutoff for a P/F ratio ≥0.94 was obtained to differentiate between Group I and II. MRI in conjunction with the P/F signal intensity ratio is a useful and noninvasive tool for the early diagnosis of pituitary iron overload.

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

    African Journals Online (AJOL)

    Introduction. Dietary iron overload is common in southern. Africa and there is a misconception that the condition is benign. 'Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of iron status to diagnose this form of iron overload has not been clarified. Methods. The study ...

  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. EXERCISE STRESS ECHOCARDIOGRAPHY WITH TISSUE DOPPLER IMAGING (TDI DETECTS EARLY SYSTOLIC DYSFUNCTION IN BETA-THALASSEMIA MAJOR PATIENTS WITHOUT CARDIAC IRON OVERLOAD

    Directory of Open Access Journals (Sweden)

    Umberto Barbero

    2012-01-01

    Full Text Available

    Iron Overload Cardiomyopathy (IOC is still the main cause of death in thalassemia major (TM patients. Unfortunately, Conventional Echocardiography fails to predict early cardiac dysfunction. As Tissue Doppler Imaging (TDI may demonstrate regional myocardial dysfunction, we wondered if exercise may reveal abnormalities at TDI which are not evident at rest. To try to evaluate left and right myocardial performances at rest and after maximal exercise by both conventional and TDI parameters, 46 beta-TM adult patients and 39 control subjects were enrolled. All patients had a liver iron quantification by Superconducting Quantum Interference Device (SQUID and also a cardiac iron assessment by MRI (T2*: 38 TM patients had no evidence of cardiac iron overload. Whereas TM patients did not shown diastolic dysfunction and all of them presented a good global response to exercise, TDI detected a reduced increase of the S’ waves of left ventricle basal segment during exercise. This finding seems to have some weak but interesting relations with iron overload markers. In conclusion, in our study, exercise stress TDI-echocardiography was able to demonstrate subtle systolic abnormalities that were missed by Conventional Echocardiography. Further studies are required to determine the meaning and the clinical impact of these results.

  8. EXERCISE STRESS ECHOCARDIOGRAPHY WITH TISSUE DOPPLER IMAGING (TDI DETECTS EARLY SYSTOLIC DYSFUNCTION IN BETA-THALASSEMIA MAJOR PATIENTS WITHOUT CARDIAC IRON OVERLOAD

    Directory of Open Access Journals (Sweden)

    Umberto Barbero

    2012-06-01

    Full Text Available Iron Overload Cardiomyopathy (IOC is still the main cause of death in thalassemia major (TM patients. Unfortunately, Conventional Echocardiography fails to predict early cardiac dysfunction. As Tissue Doppler Imaging (TDI may demonstrate regional myocardial dysfunction, we wondered if exercise may reveal abnormalities at TDI which are not evident at rest. To try to evaluate left and right myocardial performances at rest and after maximal exercise by both conventional and TDI parameters, 46 beta-TM adult patients and 39 control subjects were enrolled. All patients had a liver iron quantification by Superconducting Quantum Interference Device (SQUID and also a cardiac iron assessment by MRI (T2*: 38 TM patients had no evidence of cardiac iron overload. Whereas TM patients did not shown diastolic dysfunction and all of them presented a good global response to exercise, TDI detected a reduced increase of the S’ waves of left ventricle basal segment during exercise. This finding seems to have some weak but interesting relations with iron overload markers. In conclusion, in our study, exercise stress TDI-echocardiography was able to demonstrate subtle systolic abnormalities that were missed by Conventional Echocardiography. Further studies are required to determine the meaning and the clinical impact of these results.

  9. Prooxidant Mechanisms in Iron Overload Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ching-Feng Cheng

    2013-01-01

    Full Text Available Iron overload cardiomyopathy (IOC, defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading.

  10. 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

  11. Screening for Iron Overload: Lessons from the HEmochromatosis and IRon Overload Screening (HEIRS Study

    Directory of Open Access Journals (Sweden)

    Paul C Adams

    2009-01-01

    Full Text Available BACKGROUND: The HEmochromatosis and IRon Overload Screening (HEIRS Study provided data on a racially, ethnically and geographically diverse cohort of participants in North America screened from primary care populations.

  12. Biological tissue magnetism in the frame of iron overload diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lazaro, Francisco J. [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain) and Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Zaragoza 50009 (Spain)]. E-mail: osoro@unizar.es; Gutierrez, Lucia [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain); Abadia, Ana R. [Departamento de Farmacologia y Fisiologia, Universidad de Zaragoza, Zaragoza 50013 (Spain); Romero, Maria S. [Departamento de Medicina y Psiquiatria, Universidad de Zaragoza, Zaragoza 50009 (Spain); Lopez, A. [CNAM-Salesianos Zaragoza, Zaragoza 50009 (Spain)

    2007-09-15

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest.

  13. Biological tissue magnetism in the frame of iron overload diseases

    Science.gov (United States)

    Lázaro, Francisco J.; Gutiérrez, Lucía; Abadía, Ana R.; Romero, María S.; López, A.

    2007-09-01

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest.

  14. 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

  15. 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.

  16. Hepatoprotective Potential of Caesalpinia crista against Iron-Overload-Induced Liver Toxicity in Mice

    Directory of Open Access Journals (Sweden)

    Rhitajit Sarkar

    2012-01-01

    Full Text Available The present study was carried out to evaluate the ameliorating effect of Caesalpinia crista Linn. (CCME extract on iron-overload-induced liver injury. Iron overload was induced by intraperitoneal administration of iron dextran into mice. CCME attenuated the percentage increase in liver iron and serum ferritin levels when compared to control group. CCME also showed a dose-dependent inhibition of lipid peroxidation, protein oxidation, and liver fibrosis. The serum enzyme markers were found to be less, whereas enhanced levels of liver antioxidant enzymes were detected in CCME-treated group. In presence of CCME, the reductive release of ferritin iron was increased significantly. Furthermore, CCME exhibited DPPH radical scavenging and protection against Fe2+-mediated oxidative DNA damage. The current study confirmed the hepatoprotective effect of CCME against the model hepatotoxicant iron overload and the activity is likely related to its potent antioxidant and iron-chelating property.

  17. Dietary iron overload in southern African rural blacks | Friedman ...

    African Journals Online (AJOL)

    A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), 1'-glutamyltransferase (GGn and serological screening ...

  18. Determination of ferritin and hemosiderin iron in patients with normal iron stores and iron overload by serum ferritin kinetics.

    Science.gov (United States)

    Saito, Hiroshi; Tomita, Akihiro; Ohashi, Haruhiko; Maeda, Hideaki; Hayashi, Hisao; Naoe, Tomoki

    2012-02-01

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

  19. Diagnosis and quantification of the iron overload through Magnetic resonance.

    Science.gov (United States)

    Alústiza Echeverría, J M; Barrera Portillo, M C; Guisasola Iñiguiz, A; Ugarte Muño, A

    There are different magnetic resonance techniques and models to quantify liver iron concentration. T2 relaxometry methods evaluate the iron concentration in the myocardium, and they are able to discriminate all the levels of iron overload in the liver. Signal intensity ratio methods saturate with high levels of liver overload and can not assess iron concentration in the myocardium but they are more accessible and are very standardized. This article reviews, in different clinical scenarios, when Magnetic Resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the aplication of the technique and to be it included in the clinical guidelines. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. 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.

  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. Recent acquisitions in the management of iron overload.

    Science.gov (United States)

    Franchini, Massimo

    2005-10-01

    Chronically transfused patients develop iron overload, which leads to organ damage and ultimately to death. The introduction of the iron-chelating agent desferrioxamine mesylate dramatically improved the life expectancy of these patients. However, the very demanding nature of this treatment (subcutaneous, continuous infusion via a battery-operated portable pump) has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. In this review, we describe the most important advances in iron-chelation therapy.

  3. 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

  4. Deferasirox, an oral chelator in the treatment of iron overload

    Directory of Open Access Journals (Sweden)

    I. Portioli

    2013-05-01

    Full Text Available BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years old with beta-thalassemia and transfusional emosiderosis randomized to once-daily oral 5, 10, 20, 30 mg/kg/day in comparison of subcutaneous deferoxamine 20-60 mg/mg/kg/day x 5/week. CONCLUSIONS Deferasirox 20-30 mg/kg/day produced reductions in liver iron concentration (LIC similar to those with deferoxamine. Adverse effect of deferasirox (increases of serum creatinine and aminotransferases, including the gastrointestinal ones, are similar but more frequent than those occurring with deferoxamine. Information is lacking on the effects of deferasirox on cardiac iron and cardiac dysfunction which is the most serious complication of transfusional iron overload.

  5. Proteomic Profiling of Iron Overload-Induced Human Hepatic Cells Reveals Activation of TLR2-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2016-03-01

    Full Text Available Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. Methods and Results: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-κB pathway. Conclusions: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-κB signaling pathway in HH4 cells.

  6. Dietary iron rural blacks overload In southern African

    African Journals Online (AJOL)

    1990-09-15

    Sep 15, 1990 ... This finding was ascribed to the fact that traditional brews are not only associated with alcohol- induced hepatic damage but are also a very rich source of ... liver/,J glucose intolerance;4 scurvy and osteoporosis;5 and possibly oesophageal carcinoma.6. There is also evidence to suggest that iron overload ...

  7. 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.)

  8. Iron Loading and Overloading due to Ineffective Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Toshihiko Tanno

    2010-01-01

    Full Text Available Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.

  9. Myocardial deformation in iron overload cardiomyopathy: speckle tracking imaging in a beta-thalassemia major population.

    Science.gov (United States)

    Di Odoardo, Luca Antonio Felice; Giuditta, Marianna; Cassinerio, Elena; Roghi, Alberto; Pedrotti, Patrizia; Vicenzi, Marco; Sciumbata, Veronica Maria; Cappellini, Maria Domenica; Pierini, Alberto

    2017-09-01

    Traditional echocardiography is unable to detect neither the early stages of iron overload cardiomyopathy nor myocardial iron deposition. The aim of the study is to determine myocardial systolic strain indices in thalassemia major (TM), and assess their relationship with T2*, a cardiac magnetic resonance index of the severity of cardiac iron overload. 55 TM cases with recent cardiac magnetic resonance (CMR-T2*) underwent speckle tracking analysis to assess regional myocardial strains and rotation. The results were compared with a normal control group (n = 20), and were subsequently analyzed on the basis of the CMR-T2* values. Two TM groups were studied: TM with significant cardiac iron overload ("low" T2*, ≤20 ms; n = 21), and TM with normal T2* values ("normal" T2*, >20 ms; n = 34). TM patients show significant, uniform decrease in circumferential and radial strain (P < 0.05), and a remarkable reduction in end-systolic rotation, both global, and for all segments (P < 0.001). No significant differences were found between the low- and the normal T2* group either in regional strains and rotation or in standard echocardiographic and CMR parameters. Spearman's correlation coefficient shows no significant correlation between myocardial strains, rotation and cardiac T2* values. In conclusion, our results are in accordance with recent evidence that myocardial iron overload is not the only mechanism underlying iron cardiomyopathy in TM. Strain imaging can predict subclinical myocardial dysfunction irrespective of CMR-T2* values, although it cannot replace CMR-T2* in assessing cardiac iron overload. Finally, it might be useful to appropriately time cardioactive treatment.

  10. Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron.

    Science.gov (United States)

    Wu, Ed X; Kim, Daniel; Tosti, Christina L; Tang, Haiying; Jensen, Jens H; Cheung, Jerry S; Feng, Li; Au, Wing-Yan; Ha, Shau-Yin; Sheth, Sujit S; Brown, Truman R; Brittenham, Gary M

    2010-08-01

    With transfusional iron overload, almost all the excess iron is sequestered intracellularly as rapidly mobilizable, dispersed, soluble ferritin iron, and as aggregated, insoluble hemosiderin iron for long-term storage. Established magnetic resonance imaging (MRI) indicators of tissue iron (R(2), R(2)*) are principally influenced by hemosiderin iron and change slowly, even with intensive iron chelation. Intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool that can change rapidly with iron chelation. We have developed a new MRI method to separately measure ferritin and hemosiderin iron, based on the non-monoexponential signal decay induced by aggregated iron in multiple-spin-echo sequences. We have initially validated the method in agarose phantoms and in human liver explants and shown the feasibility of its application in patients with thalassemia major. Measurement of tissue ferritin iron is a promising new means to rapidly evaluate the effectiveness of iron-chelating regimens.

  11. Renal iron overload in rats with diabetic nephropathy.

    Science.gov (United States)

    Dominguez, Jesus H; Liu, Yunlong; Kelly, Katherine J

    2015-12-01

    Diabetic nephropathy (DN) remains incurable and is the main cause of end-stage renal disease. We approached the pathophysiology of DN with systems biology, and a comprehensive profile of renal transcripts was obtained with RNA-Seq in ZS (F1 hybrids of Zucker and spontaneously hypertensive heart failure) rats, a model of diabetic nephropathy. We included sham-operated lean control rats (LS), sham-operated diabetic (DS), and diabetic rats with induced renal ischemia (DI). Diabetic nephropathy in DI was accelerated by the single episode of renal ischemia. This progressive renal decline was associated with renal iron accumulation, although serum and urinary iron levels were far lower in DI than in LS. Furthermore, obese/diabetic ZS rats have severe dyslipidemia, a condition that has been linked to hepatic iron overload. Hence, we tested and found that the fatty acids oleic acid and palmitate stimulated iron accumulation in renal tubular cells in vitro. Renal mRNAs encoding several key proteins that promote iron accumulation were increased in DI. Moreover, renal mRNAs encoding the antioxidant proteins superoxide dismutase, catalase, and most of the glutathione synthetic system were suppressed, which would magnify the prooxidant effects of renal iron loads. Substantial renal iron loads occur in obese/diabetic rats. We propose that in diabetes, specific renal gene activation is partly responsible for iron accumulation. This state might be further aggravated by lipid-stimulated iron uptake. We suggest that progressive renal iron overload may further advance renal injury in obese/diabetic ZS rats. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. Ciprofloxacin: a novel therapeutic agent for iron overload?

    Directory of Open Access Journals (Sweden)

    Mitra Elmi

    2009-09-01

    Full Text Available Objective: Major thalassemia is one of the hematological diseases requiring multiple blood transfusions, which results in iron overload in the liver, heart and other organs. Current iron chelation therapy consists of intravenous (IV deferoxamine and oral deferasirox and deferiprone. Although these chelators are effective, many side effects are reported. In the present study, the iron-chelating effect of ciprofloxacin with good oral absorption was investigated. Material and Methods: Thirty male albino Wistar rats were used for the study. Ciprofloxacin (7 or 14 mg/kg per day was administered simultaneously with iron (0.03 g/kg per day or after one-month administration of iron. Ciprofloxacin effect on iron absorption in the liver and heart was studied carefully using atomic absorption. Results: A significant decrease in the liver and heart iron following the ciprofloxacin (14 mg/kg per day administration was observed, when compared with the control group. This ciprofloxacin-induced tissue iron depletion was more pronounced when it was administered simultaneously with iron, when it was administered for a longer duration (2 months rather than 1 month and when it was given in higher doses (14 mg/kg per day. Conclusion: Administration of ciprofloxacin may help to decrease the burden of parenteral administration, thereby improving compliance and also the life expectancy of thalassemic patients.

  13. Deferasirox for managing iron overload in people with myelodysplastic syndrome.

    Science.gov (United States)

    Meerpohl, Joerg J; Schell, Lisa K; Rücker, Gerta; Fleeman, Nigel; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk

    2014-10-28

    The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit. To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS). We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de). Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule. We did not identify any trials eligible for inclusion in this review. No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment. We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and

  14. Spondias pinnata stem bark extract lessens iron overloaded liver toxicity due to hemosiderosis in Swiss albino mice.

    Science.gov (United States)

    Hazra, Bibhabasu; Sarkar, Rhitajit; Mandal, Nripendranath

    2013-01-01

    The present study was designed to evaluate the ameliorating effect of 70% methanol extract of Spondias pinnata (SPME) on iron overload induced liver injury. Iron overload was induced by intraperitoneal administration of iron-dextran into mice and resulting liver damage was manifested by significant rise in serum enzyme markers (ALT, AST, ALP and bilirubin) and reduction in liver antioxidants (SOD, CAT, GST and GSH). Hepatic iron, serum ferritin, lipid peroxidation, protein carbonyl and hydroxyproline contents were measured in response to the oral administration of SPME of different doses (50, 100 and 200 mg/kg body weight). In order to determine the efficiency as iron chelating drug, the release of iron from ferritin by SPME was further studied. Enhanced levels of antioxidant enzymes were detected in SPME treated mice. SPME produced a dose dependent inhibition of lipid peroxidation, protein oxidation, liver fibrosis; and levels of serum enzyme markers and ferritin were also reduced dose dependently. The liver iron content was also found to be less in SPME treated group compared to control group. The reductive release of ferritin iron was augmented significantly after dose dependent addition of SPME. The ameliorating effect of SPME on damaged liver was furthermore supported by the histopathological studies that showed improved histological appearances. In conclusion, the present results demonstrate the hepatoprotective efficiency of SPME in iron intoxicated mice, and hence possibly useful as iron chelating drug for iron overload diseases.

  15. 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 

  16. Iron overload syndrome in the black rhinoceros (Diceros bicornis): microscopical lesions and comparison with other rhinoceros species.

    Science.gov (United States)

    Olias, P; Mundhenk, L; Bothe, M; Ochs, A; Gruber, A D; Klopfleisch, R

    2012-11-01

    The African black rhinoceros (Diceros bicornis) has adapted to a low iron diet during evolution and is thus prone to iron overload in captivity, which is associated with a number of serious disorders. A S88T polymorphism in the HFE gene has been suggested as a potential genetic basis of increased iron uptake in the black rhinoceros, while the Indian rhinoceros is thought to be unaffected by iron overload in captivity. In the present study, the histopathology and distribution of iron accumulations in five black rhinoceroses with iron overload syndrome were characterized and compared with three Indian rhinoceroses (Rhinoceros unicornis) and one African white rhinoceros (Ceratotherium simum). At necropsy examination, iron storage in black rhinoceroses was not associated with gross lesions. Microscopically, the most consistent and highest degree of iron load was found in the spleen, liver, small intestine and lung. There was minimal fibrosis and single cell necrosis in the liver. Endocrine organs, lymph nodes, heart and kidney were less often and less markedly affected. Unexpectedly, Indian rhinoceroses also showed iron load in the spleen and smaller amounts in organs similar to the black rhinoceros except for in the heart, while the white rhinoceros had only minor detectable iron storage in intestine, liver and lung. Sequence analysis confirmed the HFE S88T polymorphism in black but not in Indian rhinoceroses. The results indicate that Indian rhinoceroses may also be affected by iron storage in captivity, although in a milder form than the black rhinoceros, and therefore challenge the relevance of the S88T polymorphism in the HFE gene of black rhinoceroses as the underlying cause for iron overload. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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.

  19. Deferasirox for managing iron overload in people with thalassaemia.

    Science.gov (United States)

    Bollig, Claudia; Schell, Lisa K; Rücker, Gerta; Allert, Roman; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk; Meerpohl, Joerg J

    2017-08-15

    Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload. We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 August 2016.We also searched MEDLINE, Embase, the Cochrane Library, Biosis Previews, Web of Science Core Collection and three trial registries: ClinicalTrials.gov; the WHO International Clinical Trials Registry Platform; and the Internet Portal of the German Clinical Trials Register: 06 and 07 August 2015. Randomised controlled studies comparing deferasirox with no therapy or placebo or with another iron-chelating treatment. Two authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. Sixteen studies involving 1807 randomised participants (range 23 to 586 participants) were included. Twelve two-arm studies compared deferasirox to placebo (two studies) or deferoxamine (seven studies) or deferiprone (one study) or the combination of deferasirox and deferoxamine to deferoxamine alone (one study). One study compared the combination of deferasirox and deferiprone to deferiprone in combination with deferoxamine. Three three-arm studies compared deferasirox to deferoxamine and deferiprone (two studies) or the combination of deferasirox and deferiprone to deferiprone and deferasirox monotherapy respectively (one study). One four-arm study compared two different doses of deferasirox to matching placebo groups.The two studies (a pharmacokinetic and a dose-escalation study

  20. 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.)

  1. 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)

  2. 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.

  3. 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.

  4. 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

  5. Danshen (Salvia miltiorrhiza injection suppresses kidney injury induced by iron overload in mice.

    Directory of Open Access Journals (Sweden)

    Shengjiang Guan

    Full Text Available OBJECTIVES: Excessive iron can accumulate in the kidney and induce tissue damage. Danshen (Salvia miltiorrhiza injection is a traditional Chinese medicinal preparation used for preventing and treating chronic renal failure. The aim of the present study was to evaluate the effects of treatment with Danshen injection on iron overload-induced kidney damage. METHODS: Mice were mock-treated with saline (control group or given a single dose of iron dextran without treatment (iron overload group, 50 mg/kg/day for 2 weeks or with daily treatments of low-dose Danshen (3 g/kg/day, high-dose Danshen (6 g/kg/day or deferoxamine (100 mg/kg/day. RESULTS: Treatment of iron-overloaded mice with Danshen injection led to significant improvements of body weight and decreased iron levels in the kidney. Danshen injection treatment also reduced concentrations of blood urea nitrogen, creatinine and malondialdehyde and enhanced glutathione peroxidase and superoxide dismutase activities. Histopathological examinations showed that Danshen injection ameliorated pathological changes and reduced iron deposition in kidneys of iron overloaded mice. Furthermore, the treatment was demonstrated to suppress apoptosis in nephrocytes. CONCLUSIONS: These results indicated that Danshen injection exerted significant renal protective effects in iron-overloaded mice, which were closely associated with the decrease of iron deposition and suppression of lipid peroxidation and apoptosis in the kidney.

  6. The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders.

    Science.gov (United States)

    Ganz, Tomas; Nemeth, Elizabeta

    2011-01-01

    The review summarizes the current understanding of the role of hepcidin and ferroportin in normal iron homeostasis and its disorders. The various approaches to therapeutic targeting of hepcidin and ferroportin in iron-overload disorders (mainly hereditary hemochromatosis and β-thalassemia) and iron-restrictive anemias (anemias associated with infections, inflammatory disorders, and certain malignancies, anemia of chronic kidney diseases, and iron-refractory iron-deficiency anemia) are also discussed.

  7. Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

    OpenAIRE

    Shen, J.C.; Zhang, Y.C.; Zhao, M.F.

    2017-01-01

    Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload mark...

  8. Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

    Science.gov (United States)

    Shen, J.C.; Zhang, Y.C.; Zhao, M.F.

    2017-01-01

    Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC. PMID:29069221

  9. Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

    Directory of Open Access Journals (Sweden)

    J.C. Shen

    2017-10-01

    Full Text Available Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX and N-acetyl-L-cysteine (NAC on injured bone marrow hematopoietic stem/progenitor cells (HSPC induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC, and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.

  10. Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M

    2010-01-01

    We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH).......We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH)....

  11. 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

  12. 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.

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

    Science.gov (United States)

    Saito, Hiroshi; Hayashi, Hisao

    2015-01-01

    ABSTRACT Ferritin iron, hemosiderin iron, total iron stores and transformation rate were determined by serum ferritin kinetics. The transformation rate between ferritin and hemosiderin is motivated by the potential difference between them. The transformer determines transformation rate according to the potential difference in iron mobilization and deposition. The correlations between transformation rate and iron stores were studied in 11 patients with chronic hepatitis C (CHC), 1 patent with treated iron deficiency anemia (TIDA), 9 patients with hereditary hemochromatosis (HH) and 4 patients with transfusion-dependent anemia (TD). The power regression curve of approximation showed an inverse correlation between transformation rate and ferritin iron, hemosiderin iron in part and total iron stores in HH. Such an inverse correlation between transformation rate and iron stores implies that the larger the amount of iron stores, the smaller the transformation of iron stores. On the other hand, a minimal inverse correlation between transformation rate and ferritin iron and no correlation between transformation rate and hemosiderin iron or total iron stores in CHC indicate the derangement of storage iron metabolism in the cells with CHC. Radio-iron fixation on the iron storing tissue in iron overload was larger than that in normal subjects by ferrokinetics. This is consistent with the inverse correlation between transformation rate and total iron stores in HH. The characteristics of iron turnover between ferritin and hemosiderin were disclosed from the correlation between transformation rate and ferritin iron, hemosiderin iron or total iron stores. PMID:26663936

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

    Science.gov (United States)

    Saito, Hiroshi; Hayashi, Hisao

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    َ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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. An alternating current superconductor susceptometric system to evaluate liver iron overload

    Science.gov (United States)

    Carneiro, A. A. O.; Fernandes, J. P.; Zago, M. A.; Covas, D. T.; Ángulo, I. L.; Baffa, O.

    2003-06-01

    An ac susceptometric system to quantify liver iron overload composed of a second order axial gradiometer coil coupled to a rf superconducting quantum interference device detector and a large field coil array is presented. A homogeneous ac magnetizing field with low frequency (7.7 Hz) and low intensity (114 μT) is used. Preliminary measurements over a group of 34 normal individuals and 20 patients with iron overload show the ability of the instrument to perform the measurement and to distinguish normal and pathological individuals. The diamagnetic signature of the surrounding tissues is minimized using a special water bag on the torso. In summary it was shown that with a relatively simple instrumentation it was possible to build a superconducting susceptometer dedicated to quantify in vivo iron concentrations, which is clinically important information in the assessment and management of patients with liver iron overload, mainly those who regularly receive blood transfusion.

  19. Iron overload and apoptosis of HL-1 cardiomyocytes: effects of calcium channel blockade.

    Directory of Open Access Journals (Sweden)

    Mei-pian Chen

    Full Text Available Iron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC and T-type calcium channels (TTCC have been proposed to be the main portals of non-transferrinic iron into heart cells, but controversies remain. Here, we investigated the roles of LTCC and TTCC as mediators of cardiac iron overload and cellular damage by using specific Calcium channel blockers as potential suppressors of labile Fe(II and Fe(III ingress in cultured cardiomyocytes and ensuing apoptosis.Fe(II and Fe(III uptake was assessed by exposing HL-1 cardiomyocytes to iron sources and quantitative real-time fluorescence imaging of cytosolic labile iron with the fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively measured by flow cytometry analysis with Annexin V. The role of calcium channels as routes of iron uptake was assessed by cell pretreatment with specific blockers of LTCC and TTCC.Iron entered HL-1 cardiomyocytes in a time- and dose-dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase-3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the uptake of ferric but not of ferrous iron. However, neither channel blocker conferred cardiomyocytes with protection from iron-induced apoptosis.Our study implicates LTCC as major mediators of Fe(III uptake into cardiomyocytes exposed to ferric salts but not necessarily as contributors to ensuing apoptosis. Thus, to the extent that apoptosis can be considered a biological indicator of damage, the etiopathology of cardiosiderotic damage that accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or TTCC, but rather to other routes of iron ingress present in

  20. 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

  1. 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

  2. Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats.

    Directory of Open Access Journals (Sweden)

    Suwakon Wongjaikam

    Full Text Available Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO, deferiprone (DFP and deferasirox (DFX or an antioxidant (N-acetyl cysteine (NAC with a combined DFP and NAC treatments on left ventricular (LV function with iron overload has not been investigated.Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day, DFP (75 mg/kg/day, DFX (20 mg/kg/day, NAC (100 mg/kg/day or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI, malondialdehyde (MDA, cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function.The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats.

  3. 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.

  4. 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...... laevis oocytes showed loss of function of the IKs current. The authors hypothesize that iron overload combined with the KCNQ1 gene mutation leads to prolongation of QTc and torsades de pointes....

  5. 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.

  6. 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...... in Danish women from 12 to 9 mg/d. Despite the absence of food iron fortification, from 1984 to 1994, body iron stores were unchanged in premenopausal women, whereas iron stores and the prevalence of iron overload in postmenopausal women had increased significantly. The reason appears to be the changes...... 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...

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

    Science.gov (United States)

    Chalmers, Anna W; Shammo, Jamile M

    2016-01-01

    Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelo-dysplastic 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.

  8. Clinical Pharmacist-Provided Services In Iron-Overloaded Beta-Thalassaemia Major Children: A New Insight Into Patient Care.

    Science.gov (United States)

    Bahnasawy, Salma M; El Wakeel, Lamia M; Beblawy, Nagham El; El-Hamamsy, Manal

    2017-04-01

    Iron-overloaded β-thalassaemia major (BTM) children have high risk of delayed sexual/physical maturation, liver/heart diseases and reduced life expectancy. The lifelong need to use iron chelators, their unpleasant administration, side effects and lack of awareness regarding iron overload risks all hamper BTM patient compliance to iron chelators. This study evaluated the impact of clinical pharmacist-provided services on the outcome of iron-overloaded BTM children. Forty-eight BTM children were randomly assigned to either control group, who received standard medical care, or intervention group, who received standard medical care plus clinical pharmacist-provided services. Services included detection of drug-related problems (DRPs) and their management, patient education regarding disease nature and iron chelators, as well as providing patient-tailored medication charts. After six months of study implementation, there was a highly significant difference between the control and intervention groups in serum ferritin (SF) (mean: 3871 versus 2362, μg/l, p = 0.0042), patient healthcare satisfaction (median: 24.47 versus 90.29, p < 0.0001) and quality of life (QoL) (median: 49.84 versus 63.51, p = 0.0049). The intervention group showed a decline from baseline to the end of study in DRPs (64-4), the number of non-compliant patients (24-3) and mean SF levels (3949-2362 μg/l, p < 0.0001). Clinical pharmacist-provided services can positively impact the outcome of BTM children. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  9. 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.

  10. Fine-mapping and genetic analysis of the loci affecting hepatic iron overload in mice.

    Directory of Open Access Journals (Sweden)

    Xin Guo

    Full Text Available The liver, as the major organ for iron storage and production of hepcidin, plays pivotal roles in maintaining mammalian iron homeostasis. A previous study showed that Quantitative Trait Loci (QTLs on chromosome 7 (Chr7 and 16 (Chr16 may control hepatic non-heme iron overload in an F2 intercross derived from C57BL/6J (B6 and SWR/J (SWR mice. In this study, we aimed to validate the existence of these loci and identify the genes responsible for the phenotypic variations by generating congenic mice carrying SWR chromosome segments expanding these QTLs (D7Mit68-D7Mit71 and D16Mit125-D16Mit185, respectively. We excluded involvement of Chr7 based on the lack of iron accumulation in congenic mice. In contrast, liver iron accumulation was observed in Chr16 congenic mice. Through use of a series of subcongenic murine lines the interval on Chr16 was further fine-mapped to a 0.8 Mb segment spanning 11 genes. We found that the mRNA expression pattern in the liver remained unchanged for all 11 genes tested. Most importantly, we detected 4 missense mutations in 3 candidate genes including Sidt1 (P172R, Spice1(R708S, Boc (Q1051R and Boc (S450-insertion in B6 allele in the liver of SWR homozygous congenic mice. To further delineate potential modifier gene(s, we reconstituted seven candidate genes, Sidt1, Boc, Zdhhc23, Gramd1c, Atp6v1a, Naa50 and Gtpbp8, in mouse liver through hydrodynamic transfection. However, we were unable to detect significant changes in liver iron levels upon reconstitution of these candidate genes. Taken together, our work provides strong genetic evidence of the existence of iron modifiers on Chr16. Moreover, we were able to delineate the phenotypically responsible region to a 0.8 Mb region containing 11 coding genes, 3 of which harbor missense mutations, using a series of congenic mice.

  11. The Protective Effect Of Turmeric On Iron Overload In Albino Rats ...

    African Journals Online (AJOL)

    A total of 40 male albino rats were divided into four groups (10 rats each) to study the antioxidant activity and protective effect of Turmeric on iron overload. The first group fed basal diet only and served as a control. Rats of the second group were injected intrapritoneally (I/P) with iron dextran at a dose of 200 mg/kg body ...

  12. 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 ...

  13. 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.)

  14. 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.)

  15. Oral iron chelation and the treatment of iron overload in a pediatric hematology center.

    Science.gov (United States)

    Raphael, Jean L; Bernhardt, M Brooke; Mahoney, Donald H; Mueller, Brigitta U

    2009-05-01

    Recent advances have led to the development of oral iron chelators, which have changed clinical practice. The objective of this study was to descriptively assess the use of one such agent, deferasirox, as standard of care treatment in a large pediatric hematology center. We retrospectively studied all patients at the Texas Children's Hematology Center who were previously or currently treated with deferasirox. We gathered data on demographics, clinical diagnoses, length of time on chronic transfusions, previous use of deferoxamine, adherence to therapy, and reasons for discontinuation. We also assessed changes in serum ferritin, liver function tests, and creatinine for those on deferasirox for a minimum of 12 months. Fifty-nine patients were studied. Eighty-one percent of patients treated with deferasirox had a diagnosis of sickle cell disease. The mean baseline ferritin level for our study population was 2,117 ng/ml (range 754-7,211). Fifty-three percent of patients had been previously treated with deferoxamine. Adherence to oral therapy was documented in 76% of patients. For those on deferasirox for a minimum of 12 months, serum ferritin decreased in 30% of patients (44% of compliant patients, 11% of poorly compliant patients). Changes in creatinine and liver function tests were mild and did not result in long-term discontinuation of deferasirox in any cases. Outside of controlled clinical trials, deferasirox can be utilized safely as an oral iron chelator in children although adherence to therapy and the complex interaction of factors that contribute to iron overload still present challenges for clinicians. (c) 2009 Wiley-Liss, Inc.

  16. Hepatic iron overload in thalassemic patients: proposal and validation of an MRI method of assessment

    International Nuclear Information System (INIS)

    Bonetti, M.G.; Sacco, M.; Masi, C.

    1996-01-01

    Background. A simple, accurate reproducible and noninvasive method of body iorn overload assessment whoul be of great clinical use. Objective. The purpose of the study was the implementation of a 0.5-T MRI method for liver iron overload measurement. Materials and methods. Thirty paptients with thalassemia major took part in the study. Liver and paraspinal muscle signal intensity (SI) measurements were performed on T1-weighted images and normalized on a standard phantom, and a subjective hemochromatosis grading scale was made on both T1-and T2-weighted images. Serum ferritin levels and tissue iron from liver biopsy specimes were determined for comparison. Results. A close correlation was found between biotopic liver iron and both the liver-to-phantom SI ratio (r=-0.88) and the subjective grading scale (rho=0.89). Serum ferritin correlated poorly with liver iron deposition, whether assesssed by biopsy (r=0.62) of MRI (r=-0.69). Conclusions. Both the subjective and the quantitative MRI methods proposed here are clinicaly valuable, with the former being adequate for a gross, the latter for an accurate estimation of tissue iron overload

  17. Hepatic iron overload in thalassemic patients: proposal and validation of an MRI method of assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bonetti, M.G. [Servicio di Radiologia e Diagnostica per Immagini, Ancona (Italy)]|[IRCCS, San Giovanni Rotondo (Italy). Dipt. di Diagnostica per Immagini; Castriota-Scanderberg, A. [IRCCS, San Giovanni Rotondo (Italy). Dipt. di Diagnostica per Immagini; Criconia, G.M. [IRCCS, San Giovanni Rotondo (Italy). Reparto di Cardiologia; Mazza, P. [Servizio di Ematologia, Ospedale SS. Annunziata., Taranto (Italy); Sacco, M. [IRCCS, San Giovanni Rotondo (Italy). Reparto di Pediatria; Amurri, B. [Servizio di Ematologia, Ospedale SS. Annunziata., Taranto (Italy); Masi, C. [Servizio di Ematologia, Ospedale SS. Annunziata., Taranto (Italy)

    1996-09-01

    Background. A simple, accurate reproducible and noninvasive method of body iorn overload assessment whoul be of great clinical use. Objective. The purpose of the study was the implementation of a 0.5-T MRI method for liver iron overload measurement. Materials and methods. Thirty paptients with thalassemia major took part in the study. Liver and paraspinal muscle signal intensity (SI) measurements were performed on T1-weighted images and normalized on a standard phantom, and a subjective hemochromatosis grading scale was made on both T1- and T2-weighted images. Serum ferritin levels and tissue iron from liver biopsy specimes were determined for comparison. Results. A close correlation was found between biotopic liver iron and both the liver-to-phantom SI ratio (r=-0.88) and the subjective grading scale (rho=0.89). Serum ferritin correlated poorly with liver iron deposition, whether assesssed by biopsy (r=0.62) of MRI (r=-0.69). Conclusions. Both the subjective and the quantitative MRI methods proposed here are clinicaly valuable, with the former being adequate for a gross, the latter for an accurate estimation of tissue iron overload.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen, a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO in mice. Kunming male mice (8 weeks old were randomized to six groups of 10 animals each: control (CONT, CIO, low-dose SM (L-SM, high-dose SM (H-SM, verapamil (VRP and deferoxamine (DFO groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp quantitative assay. Superoxide dismutase (SOD activity, malondialdehyde (MDA content and protein expression levels of type I collagen (COL I, type I collagen (COL III, transforming growth factor-β1 (TGF-β1 and matrix metalloproteinase-9 (MMP-9 were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative

  20. 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.

  1. 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

    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......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...... 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...

  2. 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.

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

    Science.gov (United States)

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

    2016-04-01

    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 structure (TXRF-XANES), and micro-X-ray fluorescence imaging to obtain information on the intracellular storage of overloaded iron (Fe). The determined TfR1 mRNA expression for the investigated cells correlated with their proliferation rate. In all cases, the Fe XANES of cells overloaded with inorganic Fe was found to be similar to that of deliquescent Fe(III) sulfate characterized by a distorted octahedral geometry. A fitting model using a linear combination of the XANES of Tf and deliquescent Fe(III) sulfate allowed to explain the near edge structure recorded for HT-29 cells indicating that cellular overload with inorganic Fe results in a non-ferritin-like fast Fe storage. Hierarchical cluster analysis of XANES spectra recorded for Fe overloaded HT-29 and HCA-7 cells was able to distinguish between Fe treatments performed with different Fe species with a 95% hit rate, indicating clear differences in the Fe storage system. Micro-X-ray fluorescence imaging of Fe overloaded HT-29 cells revealed that Fe is primarily located in the cytosol of the cells. By characterizing the cellular Fe uptake, Fe/S content ratios were calculated based on the X-ray fluorescence signals of the analytes. These Fe/S ratios were dramatically lower for HCA-7 treated with organic Fe(III) treatments suggesting dissimilarities from the Tf-like Fe uptake.

  4. TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

    Science.gov (United States)

    Kalanaky, Somayeh; Hafizi, Maryam; Safari, Sepideh; Mousavizadeh, Kazem; Kabiri, Mahboubeh; Farsinejad, Alireza; Fakharzadeh, Saideh; Nazaran, Mohammad Hassan

    2016-03-01

    Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

  5. 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.)

  6. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    Science.gov (United States)

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

  11. Welder's pulmonary hemosiderosis associated with systemic iron overload following exacerbation of acute adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Imoto, Naoto; Shiraki, Akira; Furukawa, Katsuya; Tange, Naoyuki; Murase, Atsushi; Hayakawa, Masaya; Iwata, Yosuke; Kosugi, Hiroshi

    2017-10-12

    Herein, we describe a 61-year-old man diagnosed with pulmonary hemosiderosis following chemotherapy for acute adult T-cell leukemia/lymphoma (ATLL). Liver and heart biopsy confirmed hemosiderosis. ATLL progressed, and the patient died from multiorgan damage. Welder's lung may have been involved in hemosiderosis and systemic iron overload. Abnormal iron metabolism or immune reactions may have influenced the clinical course, but these were not validated. Detailed analyses of family medical and lifestyle histories, and genetic examination should be performed in cases of systemic iron overload.

  12. Porphyria cutanea tarda associated with HFE C282Y homozygosity, iron overload, and use of a contraceptive vaginal ring

    Directory of Open Access Journals (Sweden)

    James C. Barton

    2016-02-01

    Full Text Available Porphyria cutanea tarda (PCT is characterized by decreased uroporphyrinogen decarboxylase activity in hepatocytes, uroporphyrin I and heptacarboxyl porphyrin III accumulation, photosensitivity dermatitis, and increased storage iron. In women, estrogen therapy, including oral contraceptives, postmenopausal hormone replacement, and tamoxifen for breast cancer treatment, is a risk factor for PCT. We report the case of a woman who presented with PCT, HFE C282Y homozygosity, and hepatic iron overload and was using a contraceptive vaginal ring containing ethinyl estradiol, an estrogen. We discuss this case in the context of characteristics of other persons with PCT, including common HFE mutations, iron overload, and estrogen exposure.

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

    Directory of Open Access Journals (Sweden)

    Yasuo Miura

    2010-01-01

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

  14. Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2016-09-01

    Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Methods: BMSCs were exposed to ferric ammonium citrate (FAC with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, β-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. Results: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 μg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. Conclusion: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Deferasirox: a review of its use for chronic iron overload in patients with non-transfusion-dependent thalassaemia.

    Science.gov (United States)

    Shirley, Matt; Plosker, Greg L

    2014-06-01

    Deferasirox (Exjade(®)) is a once-daily orally administered iron chelator which has been approved for use in the treatment of transfusional-dependent chronic iron overload since 2005. Based primarily on the findings of the THALASSA (Assessment of Exjade(®) in Non-Transfusion-Dependent THALASSemiA) trial, the approval for deferasirox has recently been expanded to include the management of chronic iron overload in patients with non-transfusion-dependent thalassaemia (NTDT) syndromes. Despite the lack of regular blood transfusions, NTDT patients can still develop clinically relevant iron overload, primarily due to increased gastrointestinal absorption secondary to ineffective erythropoiesis, and may require chelation therapy. The THALASSA trial, the first placebo-controlled clinical trial of an iron chelator in NTDT patients, demonstrated that deferasirox was effective in reducing liver iron and serum ferritin levels in this population. Deferasirox has an acceptable tolerability profile, with the most common adverse events reported in the THALASSA trial being related to mild to moderate gastrointestinal disorders. Although further long-term studies will be required to clearly demonstrate the clinical benefit of chelation therapy in NTDT patients, deferasirox presents a useful tool in the management of iron overload in this population.

  19. MRI for the determination of pituitary iron overload in children and young adults with {beta}-thalassaemia major

    Energy Technology Data Exchange (ETDEWEB)

    Christoforidis, Athanasios [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece)]. E-mail: christoforidis@doctors.org.uk; Haritandi, Afroditi [Radiology Department, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki (Greece); Perifanis, Vassilios [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece); Tsatra, Ioanna [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece); Athanassiou-Metaxa, Miranda [Thalassaemia Unit, ' Hippokration' Hospital, 49 Konstantinoupoleos str., 54642 Thessaloniki (Greece); Dimitriadis, Athanasios S. [Radiology Department, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki (Greece)

    2007-04-15

    Hypogonadism, resulting from iron-induced pituitary dysfunction, is the most frequently reported complication in patients with {beta}-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 {beta}-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 < 0.001). Moreover, hypogonadal patients had significantly decreased MRI values compared to thalassaemic patients without hypogonadism (p = 0.017). Relatively decreased adeno-hypophyseal MRI signal intensity was recorded in pubertal thalassaemic patients. A significant negative correlation was observed between pituitary MRI values and age (r = -0.67, r {sup 2} = 0.443, p = 0.001), whereas ferritin levels and pituitary MRI values were moderately correlated (r = -0.56, r {sup 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.

  20. 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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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

  3. Management of transfusional iron overload – differential properties and efficacy of iron chelating agents

    Directory of Open Access Journals (Sweden)

    Kwiatkowski JL

    2011-09-01

    Full Text Available Janet L Kwiatkowski The Children's Hospital of Philadelphia, Division of Hematology and University of Pennsylvania School of Medicine, Philadelphia, PA, USA Abstract: Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols. These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading. Keywords: transfusion, iron, chelation, magnetic resonance imaging

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

    Science.gov (United States)

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

    2016-09-01

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

  5. Assessment of the role of α-lipoic acid against the oxidative stress of induced iron overload

    Directory of Open Access Journals (Sweden)

    Yasser F. Ali

    2015-01-01

    Full Text Available This work was aimed to study the protective role of α-lipoic acid against the oxidative damage of induced iron overload. Iron (Fe overload is a complication of the treatment, by chronic transfusion, of a number of genetic diseases associated with inadequate red cell production (anemias and of other genetic diseases that lead to excessive iron absorption from the diet. Male rats were injected ip with 5 mg/kg body weight ferrous sulfate for 50 days. The animals were injected ip with α-lipoic acid 20 mg per kg body weight for 21 days. Serum iron, Total Iron Binding Capacity (TIBC, Malonyldialdehyde (MDA, Electron paramagnetic resonance (EPR spectroscopy, UV-visible absorption spectrum of hemoglobin and osmotic fragility were studied. Results showed significant increase in serum iron, total iron binding capacity, and malonyldialdehyde levels in iron-loaded rats. Treatment with lipoic acid (LA resulted in decreasing serum iron and TIBC levels by 47%and 29% respectively. At the same time the lipoic acid decreased the level of the MDA in liver, brain and plasma by 54%, 42% and 74% respectively. Also LA diminished the effect of iron-induced free radicals on erythrocyte membrane integrity; it decreased the elevated average osmotic fragility and decreased the elevated rate of hemolysis. Results from UV-visible spectrophotometric measurement of hemoglobin revealed that no oxidative changes of hemoglobin occurred in iron-loaded rats. EPR spectra showed increased in non-heme ferric ions Fe+3 and free radicals in iron-loaded rats. Whereas the injection of the lipoic acid leads to decreased in such toxic result. In conclusion, these observations suggested that lipoic acid might be a beneficial antioxidant that can be effective for limiting damage from oxidative stress of iron overload.

  6. 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.

  7. 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.

  8. 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.

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

    OpenAIRE

    Chalmers, Anna W; Shammo, Jamile M

    2016-01-01

    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 correcti...

  10. Evaluation of iron overload in healthy adult residents of Mexico City.

    Science.gov (United States)

    Baptista-González, Héctor; Rosenfeld-Mann, Fanny; Trueba-Gómez, Rocío; Méndez-Sánchez, Nahum; Uribe, Misael

    2005-01-01

    We described the effects of age, gender and body mass index (BMI) on the prevalence of iron overload (IO) in blood donors from Mexico City. A cross-sectional study of clinically healthy adults was performed. We evaluated serum ferritin (SF) concentration to allow us to establish groups with normal iron stores (SF >30 microg/L) and with IO (SF >200 microg/L and >300 microg/L for women and men), in the following ages groups: 18-29 years, 30-49 years, and 50-64 years, divided by gender. The study included 1757 subjects. Prevalence of IO was 12% in men and 4.8% in women, and prevalence increased in parallel with increasing age (15.6, 25.0 and 29.9% and 3.5, 5.2 and 9.6%, for men and women, respectively). Regression analysis showed that in men there was a significant association of SF and IO with age, BMI and recent blood donation (p BMI and recent blood donation. IO is highly prevalent in blood donors residing in Mexico City, more so in men than in women. Age, gender and BMI had a positive association with iron stores. This report is the initial contribution towards the study of IO in the Mexican population.

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

    Directory of Open Access Journals (Sweden)

    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。

  12. Effect of deferasirox on iron overload in patients with transfusion-dependent haemoglobinopathies.

    Science.gov (United States)

    Fragomeno, Concetta; Roccabruna, Emilio; D'Ascola, Domenico Giuseppe

    2015-12-01

    Patients with haematopoietic disorders requiring long-term blood transfusions are at risk of iron overload. This study aimed to investigate the efficacy and safety of long-term deferasirox monotherapy in patients with transfusion-dependent anaemia in the routine clinical practice setting. This was a retrospective analysis of patients who commenced deferasirox therapy at the Hospital Bianchi Melacrino Morelli in Reggio Calabria, Italy. Data collected included cardiac and hepatic iron load (assessed by magnetic resonance imaging); left ventricular ejection fraction (LVEF). Patients were divided into two groups for analysis: group A (baseline information collected prior to deferasirox initiation) and group B (baseline information collected after deferasirox initiation). Forty-six patients were included (group A: n=25; group B: n=21). The overall population was 63% male, with a mean age of 33 years. The majority of patients (65%) had thalassaemia major. In the overall population, cardiac iron levels between the baseline and first follow-up visits improved in both groups A and B (29.2 vs. 32.5 ms; p=0.04 and 28.4 vs. 31.4 ms; p=0.038). Liver iron levels improved significantly from baseline to visit 1 in group A (7.2 vs. 12.1 ms; pDeferasirox was well tolerated and was not associated with significant adverse events. Long-term treatment with deferasirox is effective and safe in patients with transfusion-dependent haemoglobinopathies monitored in the clinical practice setting. Copyright © 2015. Published by Elsevier Inc.

  13. 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

  14. Absence of cardiac siderosis despite hepatic iron overload in Italian patients with thalassemia intermedia: an MRI T2* study.

    Science.gov (United States)

    Roghi, Alberto; Cappellini, Maria Domenica; Wood, John C; Musallam, Khaled M; Patrizia, Pedrotti; Fasulo, Maria Rosaria; Cesaretti, Claudia; Taher, Ali T

    2010-06-01

    Cardiac involvement in patients with thalassemia intermedia (TI) is characterized by a high-output state and pulmonary hypertension, with systolic left ventricle function usually being preserved. Myocardial iron overload in patients with TI has not been extensively studied. We conducted a cross-sectional study of 49 Italian patients with TI. Patient charts were reviewed and data collected for transfusion and iron chelation history, status of the spleen, and comorbid illnesses or infections. Blood samples were obtained for assessment of hemoglobin, serum ferritin, and liver enzyme levels. Doppler echocardiography was done for all patients. Cardiac and hepatic iron levels were measured by magnetic resonance imaging T2*. The mean age was 40.5 +/- 8.3 years, with a male to female ratio of 29:20. A total of 34 (69.4%) patients were splenectomized, and four patients had evidence of hepatitis C infection. Around 45% of patients were transfusion naïve while the rest received infrequent (47%) or regular (8%) transfusions. A total of 31 (63.3%) patients were maintained on iron chelation therapy. None of the patients had evidence of heart failure. Mean serum ferritin and liver iron concentration were 1,060.2 ng/ml and 8.2 mg Fe per gram dry weight, respectively. None of the patients had evidence of cardiac iron overload (mean cardiac T2* = 38.7 +/- 11.0 ms). There were no statistically significant correlation between cardiac T2* values and liver iron concentration, serum ferritin, or any patient, disease, or treatment-related parameters. Patients with TI show absence of cardiac iron overload even if hepatic iron accumulation is significant.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading

    Directory of Open Access Journals (Sweden)

    Yang Qiao

    2016-09-01

    Full Text Available Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU. We determined the protective role of SF against liver injury by examining liver-to-body ratio (%, transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection. In addition, antioxidative enzymes activities, ROS formation, mitochondrial swelling, and mitochondrial membrane potential (MMP were all evaluated to clarify the mechanism of protective effect of SF associated with oxidative stress. After 15 weeks of SF treatment, we found a significant reduction in liver-to-body weight radio and elevation in both transaminase and hepatocyte apoptosis associated with iron-injected to levels comparable to those achieved with TAU. Both SF and TAU significantly attenuated the impaired liver function associated with iron-overloaded in mice, whereas neither showed any significant effect on the iron uptake. Furthermore, treatment with either SF or TAU in iron-overloaded mice attenuated oxidative stress, associated with elevated oxidant enzymes activities, decreased ROS production, prevented mitochondrial swelling and dissipation of MMP and then inhibited hepatic apoptosis. Taken together, the current study shows that, SF alleviated oxidative stress and liver damage associated with iron-overload conditions compared to the standard ROS scavenger (TAU, and potentially could encourage higher consumption and utilization as healthy and sustainable ingredients by the food and drink.

  19. Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias.

    Science.gov (United States)

    Kohgo, Yutaka; Urabe, Akio; Kilinç, Yurdanur; Agaoglu, Leyla; Warzocha, Krzysztof; Miyamura, Koichi; Lim, Lay Cheng; Glaser, Sabine; Wang, Candace; Wiktor-Jedrzejczak, Wieslaw

    2015-01-01

    Iron overload in transfusion-dependent patients with rare anemias can be managed with chelation therapy. This study evaluated deferasirox efficacy and safety in patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemias. A 1-year, open-label, multicenter, single-arm, phase II trial was performed with deferasirox (10–40 mg/kg/day, based on transfusion frequency and therapeutic goals), including an optional 1-year extension. The primary end point was a change in liver iron concentration (LIC) after 1 year. Secondary end points included changes in efficacy and safety parameters (including ophthalmologic assessments) overall as well as in a Japanese subpopulation. Overall, 102 patients (42 with MDS, 29 with AA and 31 with other rare anemias) were enrolled; 57 continued into the extension. Mean absolute change in LIC was –10.9 mg Fe/g dry weight (d.w.) after 1 year (baseline: 24.5 mg Fe/g d.w.) and –13.5 mg Fe/g d.w. after 2 years. The most common drug-related adverse event was increased serum creatinine (23.5%), predominantly in MDS patients. Four patients had suspected drug-related ophthalmologic abnormalities. Outcomes in Japanese patients were generally consistent with the overall population. Results confirm deferasirox efficacy in patients with rare anemias, including a Japanese subpopulation. The safety profile was consistent with previous studies and ophthalmologic parameters generally agreed with baseline values (EUDRACT 2006-003337-32).

  20. [Predictive factors of response to erytrhocytapheresis in patients with biochemical iron overload with or without hereditary hemochromatosis type 1].

    Science.gov (United States)

    Parra Salinas, Ingrid; Montes Limon, Anel; Recasens Flores, Valle; Fernandez-Mosteirin, Nuria; Garcia-Erce, Jose Antonio

    2014-03-04

    Progressive increase of iron stores leads to the development of varied diseases, some of them irreversible. Until now, phlebotomy has been the cornerstone in the treatment of iron overload. Nevertheless, each erytrhocytapheresis procedure removes more than twice the volume of red cells and iron than phlebotomy, allowing to achieve iron depletion in shorter time. Our aim was to describe clinical features and analytical tests parameters of patients with iron overload, to analyze global and subsets results, to suggest predictive factors of response and to evaluate security of the procedure. Descriptive, longitudinal and prospective study of 663 procedures corresponding to 35 patients (December 2002 to October 2011). Response was defined as a serum ferritine value lower than 50 ng/mL during two months. Statistical analysis was done with SPSS(®) v 17.0 and the minimum level of statistical significance was defined as p-value < 0,05. Seventy-seven percent of patients reached response with 11 (interquartile range 1-42) erytrhocytapheresis procedures and at 11 (1-108) months. Eighty-seven point five percent of patients who did not achieve response had their ferritine values reduced in more than 50%. The decrease of all iron metabolism parameters was statistically significant. Statistically significant predictive factors of response to erytrhocytapheresis were: patients younger than 60 years-old, hereditary hemochromatosis cases, and patients who had received treatment with phlebotomies prior to erytrhocytapheresis. Erytrhocytapheresis is a secure and effective procedure for iron depletion in patients with iron overload, especially in high risk hereditary hemochromatosis cases that do not respond to phlebotomies. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Combination iron chelation therapy with deferiprone and deferasirox in iron-overloaded patients with transfusiondependent β-thalassemia major

    Directory of Open Access Journals (Sweden)

    Hossein Karami

    2017-01-01

    Full Text Available There are few papers on the combination therapy of deferiprone (DFP and deferasirox (DFX in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM. A total of 6 patients with β-TM (5 males and 1 female with a mean age of 23.8±5.8 years (ranging from 17 to 31 used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6. Their cardiac magnetic resonance imaging (MRI T2* values were 16.69±15.35 vs 17.38±5.74 millisecond (ms before and after treatment, respectively (p < 0.9. Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01; Further, their liver T2* values and liver iron concentration (LIC were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in β-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading.

  2. Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin.

    Science.gov (United States)

    Yang, Fan; Li, Yuan; Yan, Gege; Liu, Tianyi; Feng, Chao; Gong, Rui; Yuan, Ye; Ding, Fengzhi; Zhang, Lai; Idiiatullina, Elina; Pavlov, Valentin; Han, Zhenbo; Ma, Wenya; Huang, Qi; Yu, Ying; Bao, Zhengyi; Wang, Xiuxiu; Hua, Bingjie; Du, Zhimin; Cai, Benzhi; Yang, Lei

    2017-05-09

    Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls' Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways.

  3. Deferasirox for managing transfusional iron overload in people with sickle cell disease.

    Science.gov (United States)

    Meerpohl, Joerg J; Schell, Lisa K; Rücker, Gerta; Motschall, Edith; Fleeman, Nigel; Niemeyer, Charlotte M; Bassler, Dirk

    2014-05-27

    Sickle cell disease (SCD) is a group of genetic haemoglobin disorders, that occurs in about 2.2 per 1000 births worldwide. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood cell transfusions or are on long-term transfusion programmes for e.g. secondary stroke prevention. Iron chelation therapy can prevent long-term complications.Deferoxamine and deferiprone have been found to be efficacious. However, questions exist about the effectiveness and safety of the newer oral chelator deferasirox. To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload. We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register: date of most recent search:13 March 2014.We searched MEDLINE, Embase, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE, EBMR and The Cochrane Library, respectively; date of most recent searches: 02 August 2013.We searched four trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/; www.drks.de; date of most recent searches: 03 June 2013. Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment schedule. Two authors independently assessed risk of bias and extracted data. We contacted the corresponding study authors for additional information. Two studies (with 203 and 212 people) comparing the efficacy and safety of deferasirox and deferoxamine after 12 months and 24 weeks, respectively, were included. The overall quality, according to GRADE, for the main outcomes was moderate to low. Only limited data were available on mortality and end-organ damage, although one study did assess mortality, relative risk 1.26 (95% confidence interval 0.05 to 30.41), the 24-week follow up was too short to allow us to draw firm conclusions. One study reported a relative risk of 1.26 for the incidence of type 2 diabetes mellitus (95% confidence

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

    Directory of Open Access Journals (Sweden)

    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

  5. Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia

    Science.gov (United States)

    Daar, Shahina; Pathare, Anil; Nick, Hanspeter; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Habr, Dany; Taher, Ali

    2009-01-01

    This subgroup analysis evaluated the effect of once-daily oral deferasirox on labile plasma iron (LPI) levels in patients from the prospective, 1-yr, multicentre ESCALATOR study. Mean baseline liver iron concentration and median serum ferritin levels were 28.6 ± 10.3 mg Fe/g dry weight and 6334 ng/mL respectively, indicating high iron burden despite prior chelation therapy. Baseline LPI levels (0.98 ± 0.82 μmol/L) decreased significantly to 0.12 ± 0.16 μmol/L, 2 h after first deferasirox dose (P=0.0006). Reductions from pre- to post-deferasirox administration were also observed at all other time points. Compared to baseline, there was a significant reduction in preadministration LPI that reached the normal range at week 4 and throughout the remainder of the study (P≤0.02). Pharmacokinetic analysis demonstrated an inverse relationship between preadministration LPI levels and trough deferasirox plasma concentrations. Once-daily dosing with deferasirox ≥20 mg/kg/d provided sustained reduction in LPI levels in these heavily iron-overloaded patients, suggesting 24-h protection from LPI. Deferasirox may therefore reduce unregulated tissue iron loading and prevent further end-organ damage. PMID:19191863

  6. Comparison of deferasirox and deferoxamine effects on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia

    Directory of Open Access Journals (Sweden)

    Hayder M Al-Kuraishy

    2017-01-01

    Conclusion: This study indicated that deferasirox is more effective than deferoxamine regarding the iron overload but not in the immunological profile in patients with blood transfusion-dependent β-thalassemia.

  7. Effects of iron overload on the bone marrow microenvironment in mice.

    Directory of Open Access Journals (Sweden)

    Yuchen Zhang

    Full Text Available Using a mouse model, Iron Overload (IO induced bone marrow microenvironment injury was investigated, focusing on the involvement of reactive oxygen species (ROS.Mice were intraperitoneally injected with iron dextran (12.5, 25, or 50 mg every three days for two, four, and six week durations. Deferasirox(DFX125 mg/ml and N-acetyl-L-cysteine (NAC 40 mM were co-administered. Then, bone marrow derived mesenchymal stem cells (BM-MSCs were isolated and assessed for proliferation and differentiation ability, as well as related gene changes. Immunohistochemical analysis assessed the expression of haematopoietic chemokines. Supporting functions of BM-MSCs were studied by co-culture system.In IO condition (25 mg/ml for 4 weeks, BM-MSCs exhibited proliferation deficiencies and unbalanced osteogenic/adipogenic differentiation. The IO BM-MSCs showed a longer double time (2.07±0.14 days than control (1.03±0.07 days (P<0.05. The immunohistochemical analysis demonstrated that chemokine stromal cell-derived factor-1, stem cell factor -1, and vascular endothelial growth factor-1 expression were decreased. The co-cultured system demonstrated that bone marrow mononuclear cells (BMMNCs co-cultured with IO BM-MSCs had decreased colony forming unit (CFU count (p<0.01, which indicates IO could lead to decreased hematopoietic supporting functions of BM-MSCs. This effect was associated with elevated phosphatidylinositol 3 kinase (PI3K and reduced of Forkhead box protein O3 (FOXO3 mRNA expression, which could induce the generation of ROS. Results also demonstrated that NAC or DFX treatment could partially attenuate cell injury and inhibit signaling pathway striggered by IO.These results demonstrated that IO can impair the bone marrow microenvironment, including the quantity and quality of BM-MSCs.

  8. IRON CHELATION THERAPY WITH DEFERASIROX IN THE MANAGEMENT OF IRON OVERLOAD IN PRIMARY MYELOFIBROSIS

    Directory of Open Access Journals (Sweden)

    Elena Maria Elli

    2014-05-01

    Full Text Available Deferasirox (DSX is the principal option currently available for iron-chelation-therapy (ICT, principally in the management of myelodysplastic syndromes (MDS, while in primary myelofibrosis (PMF the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day, with 3 transient interruption of treatment for drug-related adverse events (AEs and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%, 2 of them (20% obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin were greater in hematologic responder (HR compared with non-responder (NR  patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP. Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP.  However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

  9. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study

    Science.gov (United States)

    Taher, Ali; El-Beshlawy, Amal; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Habr, Dany; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Al Jefri, Abdullah

    2009-01-01

    Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20–30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1–7 mg Fe/g dw for patients with baseline LIC of 2 to deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden. PMID:19187278

  10. 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)

  11. A 5-year follow-up in deferasirox treatment: improvement of cardiac and hepatic iron overload and amelioration in cardiac function in thalassemia major patients.

    Science.gov (United States)

    Cassinerio, E; Roghi, A; Orofino, N; Pedrotti, P; Zanaboni, L; Poggiali, E; Giuditta, M; Consonni, D; Cappellini, M D

    2015-06-01

    Deferasirox (DFX) is an oral iron chelator with established efficacy and safety. We evaluated by T2* cardiovascular magnetic resonance (CMR) the efficacy of DFX in preventing and removing cardiac and liver iron load and cardiac volume changes, along 5 years in adult thalassemia major (TM) patients. Twenty-three TM patients (9 males/14 women, mean age 36 ± 4 years) were included in this study. Repeated CMR was performed to assess myocardial and liver iron load (baseline t0, after 2.5 years t1, after 5 years t2). Myocardial T2* values changed progressively and increased significantly between t0 and t2 (t0: 27.15 ± 9.58 vs t2: 36.64 ± 6.68, p = 0.0001). At baseline evaluation, a cardiac T2* value <20 ms was detected in six patients (26 %): they showed an improvement of cardiac T2* values between t0 and t1, with normal T2* levels reached in all patients at t2. In the overall population, a significant reduction of both end-diastolic and end-systolic left ventricular volumes (EDV, ESV) were detected between t0 and t2 (EDV, t0: 132 ± 31 ml vs t2: 124 ± 22 ml, p = 0.033; ESV, t0: 48 ± 14 ml vs t2: 41 ± 10 ml, p = 0.0007). A significant reduction in liver iron concentration (LIC) was detected at t1 (5.36 ± 3.58 mg/g dw at baseline vs 3.35 ± 2.68 mg/g dw at t1, p = 0.004). In patients with cardiac iron overload at baseline (n.6), mean cardiac T2* values doubled at t2, and mean LIC value is reduced of 29 %. After 5 years of treatment, DFX continually and significantly reduced myocardial and liver iron overload, and it prevented further iron deposition.

  12. 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.

  13. Load characterization, overload prediction, and anomaly detection for voice over IP traffic

    NARCIS (Netherlands)

    Mandjes, Michel; Saniee, Iraj; Stolyar, Alexander; Heidelberger, P.

    2001-01-01

    We consider the problem of traffic anomaly detection in IP networks. Traffic anomalies arise when there is overload due to failures in a network. We present general formulae for the variance of the cumulative traffic over a fixed time interval and show how the derived analytical expression

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

    Science.gov (United States)

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

    2016-01-01

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

  15. 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.

  16. Retrospective epidemiological study of Latin American patients with transfusional hemosiderosis: the first Latin American epidemiological study in iron overload--the RELATH study.

    Science.gov (United States)

    Lobo, Clarisse; Angulo, Ivan L; Aparicio, Lidia R; Drelichman, Guillermo I; Zanichelli, Maria A; Cancado, Rodolfo

    2011-09-01

    The retrospective epidemiological study of Latin Americans with transfusional hemosiderosis is the first regional patient registry to gather data regarding the burden of transfusional hemosiderosis and patterns of care in these patients. Retrospective and cross-sectional data were collected on patients ≥2 years with selected chronic anemias and minimum 20 transfusions. In the 960 patients analyzed, sickle-cell disease (48·3%) and thalassemias (24·0%) were the most frequent underlying diagnoses. The registry enrolled 355 pediatric patients (187 with sickle-cell disease/94 with thalassemia). Serum ferritin was the most frequent method used to detect iron overload. Complications from transfusional hemosiderosis were reported in ~80% of patients; hepatic (65·3%), endocrine (27·5%), and cardiac (18·2%) being the most frequent. These data indicate that hemoglobinopathies and complications due to transfusional hemosiderosis are a significant clinical problem in the Latin American population with iron overload. Chelation therapy is used insufficiently and has a high rate of discontinuation.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. Iron Chelation

    Science.gov (United States)

    Skip to main content Menu Donate Treatments Therapies Iron Chelation Iron chelation therapy is the main treatment ... have iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you ...

  20. Impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome.

    Science.gov (United States)

    Escudero-Vilaplana, V; Garcia-Gonzalez, X; Osorio-Prendes, S; Romero-Jimenez, R M; Sanjurjo-Saez, M

    2016-02-01

    Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. Thirty-five patients were included in the study. Median SF at baseline was 1636 μg/L, and it decreased to 1399 μg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF (r = -0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient's death (25%). Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care. © 2016 John Wiley & Sons Ltd.

  1. The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload.

    Science.gov (United States)

    Sivgin, Serdar; Baldane, Suleyman; Akyol, Gulsah; Keklik, Muzaffer; Kaynar, Leylagül; Kurnaz, Fatih; Pala, Cigdem; Zararsiz, Gokmen; Cetin, Mustafa; Eser, Bulent; Unal, Ali

    2013-10-01

    Iron overload (IO) has been shown to be an important cause of mortality and morbidity in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to evaluate the possible effect of oral iron-chelation treatment (deferasirox) on survival in alloHSCT recipients in the posttransplant period. A total of 80 alloHSCT recipients with IO were analyzed, retrospectively. Pretransplant and posttransplant data were obtained from the patients' files. Patients were divided into two groups. Group 1; patients who did not receive any chelator treatment due to side effects or compliance problems. These patients were treated by phlebotomy. Group 2 consisted of patients who received deferasirox treatment. The median treatment duration with deferasirox was 122 days (min-max:91-225). The iron chelating treatment significantly reduced serum ferritin levels administered at a dosage of 20-30 mg/kg/day (pdeferasirox (Exjade) treatment may improve survival in patients with iron overload who underwent alloHSCT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Empirical assessment of VoIP overload detection tests

    NARCIS (Netherlands)

    Żuraniewski, P.; Mandjes, M.; Mellia, M.

    2010-01-01

    The control of communication networks critically relies on procedures capable of detecting unanticipated load changes. In this paper we explore such techniques, in a setting in which each connection consumes roughly the same amount of bandwidth (with VoIP as a leading example). We focus on

  3. Studying Irony Detection Beyond Ironic Criticism: Let's Include Ironic Praise

    Directory of Open Access Journals (Sweden)

    Richard Bruntsch

    2017-04-01

    Full Text Available Studies of irony detection have commonly used ironic criticisms (i.e., mock positive evaluation of negative circumstances as stimulus materials. Another basic type of verbal irony, ironic praise (i.e., mock negative evaluation of positive circumstances is largely absent from studies on individuals' aptitude to detect verbal irony. However, it can be argued that ironic praise needs to be considered in order to investigate the detection of irony in the variety of its facets. To explore whether the detection ironic praise has a benefit beyond ironic criticism, three studies were conducted. In Study 1, an instrument (Test of Verbal Irony Detection Aptitude; TOVIDA was constructed and its factorial structure was tested using N = 311 subjects. The TOVIDA contains 26 scenario-based items and contains two scales for the detection of ironic criticism vs. ironic praise. To validate the measurement method, the two scales of the TOVIDA were experimentally evaluated with N = 154 subjects in Study 2. In Study 3, N = 183 subjects were tested to explore personality and ability correlates of the two TOVIDA scales. Results indicate that the co-variance between the ironic TOVIDA items was organized by two inter-correlated but distinct factors: one representing ironic praise detection aptitude and one representing ironic criticism detection aptitude. Experimental validation showed that the TOVIDA items truly contain irony and that item scores reflect irony detection. Trait bad mood and benevolent humor (as a facet of the sense of humor were found as joint correlates for both ironic criticism and ironic praise detection scores. In contrast, intelligence, trait cheerfulness, and corrective humor were found as unique correlates of ironic praise detection scores, even when statistically controlling for the aptitude to detect ironic criticism. Our results indicate that the aptitude to detect ironic praise can be seen as distinct from the aptitude to detect ironic

  4. Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

    Science.gov (United States)

    Cançado, Rodolfo; Melo, Murilo R; de Moraes Bastos, Roberto; Santos, Paulo C J L; Guerra-Shinohara, Elivira M; Chiattone, Carlos; Ballas, Samir K

    2015-12-01

    This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    OpenAIRE

    Saito, Hiroshi; Hayashi, Hisao

    2015-01-01

    ABSTRACT Ferritin iron, hemosiderin iron, total iron stores and transformation rate were determined by serum ferritin kinetics. The transformation rate between ferritin and hemosiderin is motivated by the potential difference between them. The transformer determines transformation rate according to the potential difference in iron mobilization and deposition. The correlations between transformation rate and iron stores were studied in 11 patients with chronic hepatitis C (CHC), 1 patent with ...

  6. 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

  7. Rapid excretion of gallium-67 isotope in an iron-overloaded patient receiving high-dose intravenous deferoxamine

    Energy Technology Data Exchange (ETDEWEB)

    Baker, D.L.; Manno, C.S.

    1988-12-01

    A 23 year-old black male with homozygous sickle cell disease (Hb SS disease) and transfusional iron overload was admitted for evaluation of response to intravenous deferoxamine (DFO) therapy. Soon after admission, the patient suffered an intraventricular hemorrhage and during his subsequent hospitalization developed a persistent fever of undetermined origin (f.u.o.). Included in the diagnostic evaluation of fever was a gallium 67 scan (Ga-67), which was initially nondiagnostic because of Ga-67 citrate's preferential chelation by DFO. After DFO was discontinued, a repeat scan demonstrated a lesion above the left kidney. To our knowledge the unusual interaction in vivo of DFO with Ga-67 citrate has not been reported in the clinical literature. With the anticipated increased use of chelation therapy for patients with transfusional iron overload, this interaction may be encountered more frequently. DFO should be discontinued before the use of Ga-67 scanning in this clinical situation, or an alternative isotopic scan, such as indium-labelled white cells, should be considered.

  8. 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

  9. 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

  10. Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload

    Science.gov (United States)

    2017-11-07

    Iron Overload; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult

  11. 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

  12. 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.

  13. 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

  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. A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Cermak, Jaroslav; Jonasova, Anna; Vondrakova, Jana; Cervinek, Libor; Belohlavkova, Petra; Neuwirtova, Radana

    2013-12-01

    One hundred thirteen patients with myelodysplastic syndromes (MDS) with deferasirox in a daily dose of 10-40 mg/kg (65 patients). Median duration of treatment was 10,9 months for deferiprone and 13,7 months for deferasirox. A substantial reduction of iron stores evaluated as a decrease in serum ferritin of more than 50% of pretreatment level was achieved in 18 patients in deferasirox group (27.7%) but not in any patient treated with deferiprone, The incidence of adverse effects (mostly gastrointestinal symptoms) was similar after administration of both the drugs. The symptoms of deferasirox toxicity were mild and mostly transient and no drug related myelosuppresive effect was observed in contrast to deferiprone where agranulocytosis occurred in 4% of patients and the treatment had to be discontinued due to side effects in 20% of patients. The results confirmed the usefulness of deferasirox as an effective and safe iron chelator in MDS patients and indication of deferiprone as an alternative treatment only in patients with mild or moderate iron overload clearly not indicated for deferasirox. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, B.; Kremser, C.; Rauch, S.; Eder, R.; Schocke, M. [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Zoller, H.; Finkenstedt, A. [Innsbruck Medical University, Department of Internal Medicine, Innsbruck (Austria); Michaely, H.J. [Medical Faculty Mannheim - Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim (Germany)

    2012-11-15

    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 x 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. (orig.)

  17. 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.

  18. Deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation: multicenter phase I study (KSGCT1302).

    Science.gov (United States)

    Tachibana, Takayoshi; Kanda, Junya; Machida, Shinichiro; Saito, Takeshi; Tanaka, Masatsugu; Najima, Yuho; Koyama, Satoshi; Miyazaki, Takuya; Yamamoto, Eri; Takeuchi, Masahiro; Morita, Satoshi; Kanda, Yoshinobu; Kanamori, Heiwa; Okamoto, Shinichiro

    2018-01-05

    The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22-68). Median time from HCT to deferasirox administration was 9 months (range 6-84). Deferasirox was started at a dose of 5 mg/kg, and the dose was increased to 7.5 and 10 mg/kg every 4 weeks unless there were no grade ≥ 2 of adverse events. Achievement rates of planned medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in 10 mg/kg (9 of 15), respectively. The reasons for discontinuation of the drug were grade 2 of adverse events (n = 4), late relapse (n = 1), and self-cessation (n = 1). None of the patients developed grade ≥ 3 of adverse events or exacerbation of GVHD. Among 11 evaluable cases, mean value of ferritin decreased from 1560 ng/ml pre-treatment to 1285 ng/ml post-treatment. These data suggested that 10 mg/kg of deferasirox may be maximum tolerated dose when given after HCT. Our dose escalating method of deferasirox is useful to identify the optimal dosage of the drug in each patient. UMIN000011251.

  19. 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)

  20. 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

  1. Gradient-echo magnetic resonance imaging study of pancreatic iron overload in young Egyptian beta-thalassemia major patients and effect of splenectomy

    Directory of Open Access Journals (Sweden)

    Matter Randa M

    2010-04-01

    Full Text Available Abstract Background Thalassemic patients suffer from diabetes mellitus secondary to hemosiderosis. Aims The study aimed to evaluate pancreatic iron overload by T2*-weighted Gradient-echo magnetic resonance imaging (MRI in young beta-thalassemia major patients and to correlate it with glucose disturbances, hepatic hemosiderosis, serum ferritin and splenectomy. Methods Forty thalassemic patients (20 non diabetic, 10 diabetic, and 10 with impaired glucose tolerance were recruited from Pediatric Hematology Clinic, in addition to 20 healthy controls. All patients underwent clinical assessment and laboratory investigations included complete blood count, liver function tests, serum ferritin and oral glucose tolerance test (OGTT. A T2*-weighted gradient-echo sequence MRI was performed with 1.5 T scanner and signal intensity ratio (SIR of the liver and the pancreas to noise were calculated. Results Significant reduction in signal intensity ratio (SIR of the liver and the pancreas was shown in thalassemic patients compared to controls (P Conclusions pancreatic siderosis can be detected by T2* gradient-echo MRI since childhood in thalassemic patients, and is more evident in patients with abnormal glucose tolerance. After splenectomy, iron deposition may be accelerated in the pancreas. Follow up of thalassemic patients using pancreatic MRI together with intensive chelation therapy may help to prevent the development of overt diabetes.

  2. 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.

  3. 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.)

  4. The preventive effect of Mangifera foetida L. leaf extract administered simultaneously to excess iron on markers of iron overload in Spraque-Dawley rats

    Directory of Open Access Journals (Sweden)

    Purnama Fajri

    2018-02-01

    Full Text Available Background: Recently, there is no agent available for the prevention of iron overload (IO in thalassemia patients. Previous studies showed that Mangifera foetida L. leaf extracts reduced the levels of iron in IO in vitro and in vivo models. The present study aimed to determine the efficacy of Mangifera foetida L. leaf extract in the prevention of IO induced in rats.Methods: Thirty male Sprague-Dawley rats were divided into 5 groups: control (untreated, IO, 3 treatment groups with leaf extract equivalent to 50, 100, and 200 mg of mangiferin per kg BW. Fe-dextran (15 mg was administered intraperitoneally twice a week for 4 weeks to all groups except control (IO, DSM50, DSM100, and DSM200. Urine and blood samples were taken before and after treatments. After 4 weeks of treatment, rats were terminated, and samples of spleen, liver, and heart were taken. Ferritin and mangiferin levels and SOD activities were determined in plasma. Iron levels were measured in plasma, urine, and spleen.Results: Experimental IO increased plasma Fe content 4.23 times and plasma ferritin levels 6.9 times vs normal. Mangifera foetida L. leaf extract DSM50 resulted in the highest blood levels of 212 ng mangiferin per mL and moderately, although not significant, prevented increased plasma ferritin levels and IO in organs and protected against oxidative stress.Conclusion: Aqueous Mangifera foetida L. leaf extract may be useful to prevent IO and oxidative stress in thalassemia patients.

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

    African Journals Online (AJOL)

    Carriers homozygotes for H63D mutation showed significantly higher serum ferritin levels compared to those without mutation (p< 0.001). Conclusion: Homozygosity for H63D mutation tends to be associated with higher ferritin levels in beta-thalassemia patients and carriers suggesting its modulating effect on iron load in ...

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

    African Journals Online (AJOL)

    Manal Michel Wilson

    2015-03-04

    Mar 4, 2015 ... Abstract Background: HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in b-thalassemia patients and carriers remains contro- versial. Objectives: We aimed to determine the prevalence of HFE gene mutations (C282Y and H63D) in.

  8. Utility of labile plasma iron and transferrin saturation in addition to serum ferritin as iron overload markers in different underlying anemias before and after deferasirox treatment.

    Science.gov (United States)

    Porter, John B; El-Alfy, Mohsen; Viprakasit, Vip; Giraudier, Stephane; Chan, Lee Lee; Lai, Yongrong; El-Ali, Ali; Han, Jackie; Cappellini, Maria D

    2016-01-01

    Plasma markers in addition to serum ferritin (SF) may be useful for the assessment of iron overload; however, predictive utility may differ depending on underlying, transfusion-dependent, anemias. Data were collected before and after 1 year of deferasirox treatment (end of study; EOS) from the large, 1-year EPIC (Evaluation of Patients' Iron Chelation with Exjade(®) ) study. Trends were evaluated between liver iron concentration (LIC), transferrin saturation (TfSat), predose labile plasma iron (LPI) and their relationship to SF categories in 1530 patients: thalassemia major (TM; n = 1114), myelodysplastic syndromes (MDS, n = 336), and sickle-cell disease (SCD, n = 80). Baseline and EOS SF values showed a clear and similar relationship to LIC for all disease groups. TfSat also showed a relationship to SF, most clearly in patients with SCD, where TfSat was lowest in the lowest relative SF category. Unlike SF or LIC, TfSat did not decrease at EOS in any disease group. Baseline LPI was raised in TM and MDS, but not in patients with SCD, decreasing at EOS in both patient groups. After 1 year of chelation therapy, there was a significant trend for greater LPI reduction in patients with TM achieving LIC <7 mg Fe/g dw (P = 0.0137). Despite limitations, SF showed the clearest relationship, of the plasma markers evaluated, to LIC before and after 1 year of deferasirox in patients with TM, MDS, and SCD. In patients with TM, changes in LPI with chelation show a significant relationship to EOS LIC and may provide an additional indicator of chelation response (clinicaltrials.gov identifier: NCT00171821). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Effect of the Hemochromatosis Mutations on Iron Overload among the Indian β Thalassemia Carriers.

    Science.gov (United States)

    Nadkarni, Anita H; Singh, Aradhana A; Colaco, Stacy; Hariharan, Priya; Colah, Roshan B; Ghosh, Kanjaksha

    2017-05-01

    Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron absorption.HFE gene mutations C282Y and H63D are responsible for the majority of hereditary hemochromatosis cases. We tried to look at the effect of HFE mutations on the iron status. A total of 100 β thalassemia traits (BTT) with 100 normal individuals were screened for the C282Y and H63D mutations using PCR-RFLP. The serum ferritin levels were determined using ELISA kit. We did not find the C282Y mutation in our study group. The allelic frequencies for H63D mutation did not differ significantly between β-thalassemia traits (8.5%) and normal controls (9%). ΒΤΤ with H63D genotype of H/D (143.16 ± 80.3 ng/ml) and D/D (504 ng/ml) showed higher ferritin levels as against H/H genotype (88.64 ± 92.43 ng/ml). The statistically significant difference was observed in the mean serum ferritin levels among the individuals showing H/H and D/D genotypes (P < 0.002) and H/D and D/D genotype (P < 0.01) in both the groups. This suggests that iron load in BTT tends to aggravated with the co-inheritance of the H63D mutation. The mutant H63D gene showed the presence of haplotype 6 which is reported in the European population suggesting a common origin. © 2016 Wiley Periodicals, Inc.

  10. Comparison of deferasirox and deferoxamine effects on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia.

    Science.gov (United States)

    Al-Kuraishy, Hayder M; Al-Gareeb, Ali I

    2017-01-01

    Beta-thalassemias are a cluster of inherited (autosomal recessive) hematological disorders prevalent in the Mediterranean area due to defects in synthesis of β chains of hemoglobin. The aim of present study was to compare the effects of deferasirox and deferoxamine on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia major and intermedia. This study involved 64 patients with known cases of β-thalassemia major or intermedia that has been treated with blood transfusion and iron chelators. Serum ferritin, serum iron, serum total iron binding, unsaturated iron-binding capacity (UIBC), and immunological parameters were assessed in deferoxamine and deferasirox-treated patients. In deferoxamine-treated patients, serum ferritin levels were high (8160.33 ± 233.75 ng/dL) compared to deferasirox-treated patients (3000.62 ± 188.23 ng/dL; P deferasirox-treated patients compared to deferoxamine-treated patients. Immunological changes between two treated groups showed insignificant differences in levels of complements (C3 and C4) and immunoglobulin levels (IgM, IgG, and IgA) P > 0.05. This study indicated that deferasirox is more effective than deferoxamine regarding the iron overload but not in the immunological profile in patients with blood transfusion-dependent β-thalassemia.

  11. Prevalence and distribution of iron overload in patients with transfusion-dependent anemias differs across geographic regions: results from the CORDELIA study.

    Science.gov (United States)

    Aydinok, Yesim; Porter, John B; Piga, Antonio; Elalfy, Mohsen; El-Beshlawy, Amal; Kilinç, Yurdanur; Viprakasit, Vip; Yesilipek, Akif; Habr, Dany; Quebe-Fehling, Erhard; Pennell, Dudley J

    2015-09-01

    The randomized comparison of deferasirox to deferoxamine for myocardial iron removal in patients with transfusion-dependent anemias (CORDELIA) gave the opportunity to assess relative prevalence and body distribution of iron overload in screened patients. Patients aged ≥ 10 yr with transfusion-dependent anemias from 11 countries were screened. Data were summarized descriptively, overall and across regions. Among 925 patients (99.1% with β-thalassemia major; 98.5% receiving prior chelation; mean age 19.2 yr), 36.7% had myocardial iron overload (myocardial T2* ≤ 20 ms), 12.1% had low left ventricular ejection fraction. Liver iron concentration (LIC) (mean 25.8 mg Fe/g dw) and serum ferritin (median 3702 ng/mL) were high. Fewer patients in the Middle East (ME; 28.5%) had myocardial T2* ≤ 20 ms vs. patients in the West (45.9%) and Far East (FE, 40.9%). Patients in the West had highest myocardial iron burden, but lowest LIC (26.9% with LIC < 7 mg Fe/g dw) and serum ferritin. Among patients with normal myocardial iron, a higher proportion of patients from the ME and FE had LIC ≥ 15 than < 7 mg Fe/g dw (ME, 56.7% vs. 17.2%; FE, 78.6% vs. 7.8%, respectively), a trend which was less evident in the West (44.6% vs. 33.9%, respectively). Transfusion and chelation practices differed between regions. Evidence of substantial myocardial and liver iron burden across regions revealed a need for optimization of effective, convenient iron chelation regimens. Significant regional variation exists in myocardial and liver iron loading that are not well explained; improved understanding of factors contributing to differences in body iron distribution may be of clinical benefit. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  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. An Automated Segmentation of R2* Iron-Overloaded Liver Images Using a Fuzzy C-Mean Clustering Scheme.

    Science.gov (United States)

    Saiviroonporn, Pairash; Korpraphong, Pornpim; Viprakasit, Vip; Krittayaphong, Rungroj

    2018-02-13

    The objectives of this study were to develop and test an automated segmentation of R2* iron-overloaded liver images using fuzzy c-mean (FCM) clustering and to evaluate the observer variations. Liver R2* images and liver iron concentration (LIC) maps of 660 thalassemia examinations were randomly separated into training (70%) and testing (30%) cohorts for development and evaluation purposes, respectively. Two-dimensional FCM used R2* images, and the LIC map was implemented to segment vessels from the parenchyma. Two automated FCM variables were investigated using new echo time and membership threshold selection criteria based on the FCM centroid distance and LIC levels, respectively. The new method was developed on a training cohort and compared with manual segmentation for segmentation accuracy and to a previous semiautomated method, and a semiautomated scheme was suggested to improve unsuccessful results. The automated variables found from the training cohort were assessed for their effectiveness in the testing cohort, both quantitatively and qualitatively (the latter by 2 abdominal radiologists using a grading method, with evaluations of observer variations). A segmentation error of less than 30% was considered to be a successful result in both cohorts, whereas, in the testing cohort, a good grade obtained from satisfactory automated results was considered a success. The centroid distance method has a segmentation accuracy comparable with the previous-best, semiautomated method. About 94% and 90% of the examinations in the training and testing cohorts were automatically segmented out successfully, respectively. The failed examinations were successfully segmented out with thresholding adjustment (3% and 8%) or by using alternative results from the previous 1-dimensional FCM method (3% and 2%) in the training and testing cohorts, respectively. There were no failed segmentation examinations in either cohort. The intraobserver and interobserver variabilities were

  14. Role of ferritin in the rice tolerance to iron overload Papel da ferritina na tolerância de arroz ao excesso de ferro

    Directory of Open Access Journals (Sweden)

    Vivian Chagas da Silveira

    2009-08-01

    Full Text Available Plants ordinarily face iron (Fe deficiency, since this mineral is poorly available in soils under aerobic conditions. Nonetheless, wetland and irrigated rice plants can be exposed to excess, highly toxic Fe. Ferritin is a ubiquitous Fe-storage protein, important for iron homeostasis. Increased ferritin accumulation resulting from higher Fe availability was shown in some plant species. However, the role of ferritin in tolerance mechanisms to Fe overload in rice is yet to be established. In this study, recombinant rice ferritin was expressed in Escherichia coli, producing an anti-rice ferritin polyclonal antibody which was used to evaluate ferritin accumulation in two rice (Oryza sativa L. cultivars, either susceptible (BR-IRGA 409 or tolerant (EPAGRI 108 to Fe toxicity. Increased ferritin mRNA and protein levels resulting from excess Fe treatment were detected in both cultivars, with higher ferritin protein accumulation in EPAGRI 108 plants, which also reached lower shoot Fe concentrations when submitted to iron overload. The tolerance mechanism to excess Fe in EPAGRI 108 seems to include both restricted Fe translocation and increased ferritin accumulation. This is the first work that shows higher accumulation of the ferritin protein in an iron-excess tolerant Oryza sativa cultivar, providing evidence of a possible role of this protein in iron tolerance mechanisms.Deficiência de ferro (Fe ocorre freqüentemente em plantas, uma vez que este mineral é pouco disponível em condições aeróbicas. Plantas de arroz cultivadas sob alagamento, no entanto, estão sujeitas ao excesso de Fe, que pode ser extremamente tóxico. Alguns cultivares de arroz são resistentes a altas concentrações de ferro, mas os mecanismos fisiológicos responsáveis por essa resistência são pouco conhecidos. A ferritina é uma proteína de ampla distribuição e capaz de armazenar ferro, sendo considerada importante para a homeostase deste metal. Acúmulo de ferritina em

  15. CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced Hepatic Inflammation

    Directory of Open Access Journals (Sweden)

    Yuxiao Tang

    2017-11-01

    Full Text Available Background/Aims: Iron overload (IO is accompanied by hepatic inflammation. The chemokine (C-C motif ligand 2 (CCL2 mediates inflammation, and its overexpression is associated with IO. However, whether IO results in CCL2 overexpression in the liver and the underlying mechanisms are unclear. Methods: We subjected mice to IO by administering intraperitoneal injections of dextran-iron or by feeding mice a 3% dextran-iron diet to observe the effects of IO on miR-122/CCL2 expression through real-time qPCR and Western blot analysis. We also used indicators, including the expression of the inflammatory cytokine, the inflammation score based on H&E staining and the serum content of ALT and AST to evaluate the effects of IO on hepatic inflammation. Meanwhile, we observed the effects of vitamin E on IO-induced hepatic inflammation. In cells, we used 100 µΜ FeSO4 or 30 µΜ Holo-Tf to produce IO and observed the roles of miR-122 in regulating CCL2 expression by using miR-122 mimics or inhibitors to overexpress or inhibit miR-122. Then, we used a dual-luciferase reporter assay to prove that miR-122 regulates CCL2 expression through direct binding to its complementary sequence in the CCL2 mRNA 3’UTR. Results: IO induces the downregulation of miR-122 and the upregulation of CCL2, as well as inflammatory responses both in vitro and in vivo. Although IO-induced oxidative stress is eliminated by the antioxidant vitamin E, IO-induced hepatic inflammation still exists, which probably can be explained by the fact that vitamin E has no effects on the miR-122/CCL2 pathway. In in vitro experiments, the overexpression and inhibition of miR-122 significantly reduced and increased CCL2 expression, respectively. The dual-luciferase reporter assay indicates that miR-122 binds CCL2 mRNA 3’UTR. Conclusion: We propose the roles of miR-122/CCL2 in IO-induced hepatic inflammation. Our studies should provide a new clue for developing clinical strategies for patients with IO.

  16. Lifetime cost-utility analyses of deferasirox in beta-thalassaemia patients with chronic iron overload: a UK perspective.

    Science.gov (United States)

    Karnon, Jonathan; Tolley, Keith; Vieira, Joao; Chandiwana, David

    2012-12-01

    Regular blood transfusions for beta-thalassaemia patients lead to the accumulation of iron deposits in the body. In order to remove such deposits, iron chelation therapy is required. Subcutaneously administered deferoxamine has been the gold standard chelation therapy for over 40 years. Deferasirox is a newer chelation therapy that is taken orally once daily. The objective of this study was to estimate the long-term costs and quality-adjusted life-years (QALYs) associated with deferoxamine and deferasirox in a cohort of transfusion-dependent beta-thalassaemia patients from a UK health service perspective. A 50-year annual cycle state transition model comprised three core health states: alive without cardiac complications, alive with cardiac complications, and dead, as well as representing other chronic complications of iron overload: diabetes, hypogonadism, hypoparathyroidism and hypothyroidism. The model was calibrated to identify sets of convergent input parameter values that predicted observed overall survival by mean lifetime compliance with chelation therapy. A pivotal non-inferiority trial informed the main estimates of the effectiveness of deferasirox, which were applied to the calibrated model. Using cost values for the year 2011, costs and utilities were summed over patients' lifetimes to estimate lifetime costs and QALY gains. Mean lifetime treatment costs for patients receiving deferoxamine were £70,000 higher than deferasirox. Drug acquisition costs were £100,000 higher for deferasirox, but administration costs associated with deferoxamine were £170,000 higher. Higher compliance associated with oral deferasirox administration led to fewer complications. Combined with the quality-of-life effects of an oral mode of administration, an average gain of 4.85 QALYs for deferasirox was estimated. In the base case, deferasirox dominates deferoxamine, i.e., costs less and patients gain more QALYs. The key parameter is the proportion of deferoxamine patients

  17. Pharmacoeconomic considerations in treating iron overload in patients with β-thalassaemia, sickle cell disease and myelodysplastic syndromes in the US: a literature review.

    Science.gov (United States)

    Zhang, Bin; Donga, Prina Z; Corral, Mitra; Sasane, Medha; Miller, Jeffrey D; Pashos, Chris L

    2011-06-01

    Patients with β-thalassaemia, sickle cell disease (SCD) and myelodysplastic syndromes (MDS) require chronic blood transfusions, which can lead to iron overload and substantial morbidity and mortality. To reduce the excess iron and its deleterious effects, available iron chelation therapy (ICT) in the US includes oral deferasirox or infusional deferoxamine (DFO). The aim of this study was to review and synthesize the available pharmacoeconomic evidence on ICT in patients with β-thalassaemia, SCD and MDS in the US. We systematically identified and reviewed pharmacoeconomic studies of ICT in patients with β-thalassaemia, SCD and MDS that either were published in MEDLINE-indexed, English-language journals from 1999 to 2009, or appeared in medical society websites and scientific meeting abstracts. We assessed available cost-of-illness, cost-of-treatment, cost-consequence, cost-effectiveness, utility and patient-satisfaction studies. The majority of the 20 identified studies assessed cost of treatment, mainly focusing on acquisition and administration costs of ICTs. Gaps in the published literature include current data on direct medical costs for patients with MDS, direct medical costs associated with complications of iron overload, direct non-medical costs, indirect costs and patient utilities. Different underlying model assumptions, methodologies and comparators were found in the cost-effectiveness studies, which yielded a broad range of incremental cost-effectiveness ratios for different ICTs. Comprehensive cost-of-illness studies are needed to address data gaps in the published literature regarding the economic burden of iron overload. Comparative-effectiveness studies that evaluate clinical, economic and patient-reported outcomes would help the medical community to better understand the value of different ICTs.

  18. Myocardial and liver iron overload, assessed using T2* magnetic resonance imaging with an excel spreadsheet for post processing in Tunisian thalassemia major patients.

    Science.gov (United States)

    Ouederni, Monia; Ben Khaled, Monia; Mellouli, Fethi; Ben Fraj, Elhem; Dhouib, Nawel; Yakoub, Ismehen Ben; Abbes, Selem; Mnif, Nejla; Bejaoui, Mohamed

    2017-01-01

    Thalassemia is a common genetic disorder in Tunisia. Early iron concentration assessment is a crucial and challenging issue. Most of annual deaths due to iron overload occurred in underdeveloped regions of the world. Limited access to liver and heart MRI monitoring might partially explain these poor prognostic results. Standard software programs are not available in Tunisia. This study is the first to evaluate iron overload in heart and liver using the MRI T2* with excel spreadsheet for post processing. Association of this MRI tool results to serum ferritin level, and echocardiography was also investigated. One hundred Tunisian-transfused thalassemia patients older than 10 years (16.1 ± 5.2) were enrolled in the study. The mean myocardial iron concentration (MIC) was 1.26 ± 1.65 mg/g dw (0.06-8.32). Cardiac T2* (CT2*) was under 20 ms in 30 % of patients and under 10 ms in 21 % of patients. Left ventricular ejection function was significantly lower in patients with CT2* 3 mg/g dw) was found in 95 % of patients. LIC was over 15 mg/g dw in 25 % of patients. MIC was more correlated than CT2* to LIC and serum ferritin. Among patients with SF excel spreadsheet for routine follow-up of iron overload might improve the prognosis of thalassemia major patients in developing countries, such as Tunisia, where standard MRI tools are not available or expensive.

  19. 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.)

  20. 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.)

  1. Deferasirox effectively reduces iron overload in non-transfusion-dependent thalassemia (NTDT) patients: 1-year extension results from the THALASSA study.

    Science.gov (United States)

    Taher, Ali T; Porter, John B; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Galanello, Renzo; Karakas, Zeynep; Lawniczek, Tomasz; Habr, Dany; Ros, Jacqueline; Zhu, Zewen; Cappellini, M Domenica

    2013-11-01

    Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload that requires chelation to levels below the threshold associated with complications. This can take several years in patients with high iron burden, highlighting the value of long-term chelation data. Here, we report the 1-year extension of the THALASSA trial assessing deferasirox in NTDT; patients continued with deferasirox or crossed from placebo to deferasirox. Of 133 patients entering extension, 130 completed. Liver iron concentration (LIC) continued to decrease with deferasirox over 2 years; mean change was -7.14 mg Fe/g dry weight (dw) (mean dose 9.8 ± 3.6 mg/kg/day). In patients originally randomized to placebo, whose LIC had increased by the end of the core study, LIC decreased in the extension with deferasirox with a mean change of -6.66 mg Fe/g dw (baseline to month 24; mean dose in extension 13.7 ± 4.6 mg/kg/day). Of 166 patients enrolled, 64 (38.6 %) and 24 (14.5 %) patients achieved LIC Deferasirox progressively decreases iron overload over 2 years in NTDT patients with both low and high LIC. Safety profile of deferasirox over 2 years was consistent with that in the core study.

  2. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Taher, Ali T; Porter, John; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Galanello, Renzo; Karakas, Zeynep; Lawniczek, Tomasz; Ros, Jacqueline; Zhang, Yiyun; Habr, Dany; Cappellini, Maria Domenica

    2012-08-02

    Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, -2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and -4.18 ± 0.69 mg Fe/g dw, P deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM -235 and -337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.

  3. 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

  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. 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.

  6. Long-term results using hydroxyurea/phlebotomy for reducing secondary stroke risk in children with sickle cell anemia and iron overload.

    Science.gov (United States)

    Greenway, Anthea; Ware, Russell E; Thornburg, Courtney D

    2011-04-01

    Children with sickle cell anemia (SCA) and a primary overt stroke are at high risk of recurrent (secondary) stroke. Chronic transfusion therapy dramatically reduces but does not eliminate this high risk, and inevitably results in transfusion-related hemosiderosis. We previously reported the use of hydroxyurea/phlebotomy as an alternative to transfusions to reduce the risk of secondary stroke and improve management of iron overload in 35 children with SCA. To report long-term results, we retrospectively reviewed clinical and laboratory data through October 2008. With a median of 5.6 years and total of 219 patient-years of follow-up, 10 of 35 patients (29%) had recurrent stroke after switching to hydroxyurea; seven were previously reported and three new strokes occurred during extended follow-up. The overall secondary stroke event rate was 4.6 per 100 patient-years. Children on hydroxyurea received serial phlebotomy and had lower mean serum ferritin values than children on transfusions (591 ng/mL vs. 3410 ng/mL, P = 0.02). In this cohort, long-term hydroxyurea treatment reduced but did not eliminate the risk of stroke recurrence and, uniquely, allowed phlebotomy to reduce iron overload. Long-term assessments of this therapy should evaluate risk factors for secondary stroke and assessments of hemosiderosis, neurocognitive outcome, and health-related quality of life. Copyright © 2011 Wiley-Liss, Inc.

  7. Iranian experience of deferasirox (Exjade(®)) in transfusion-dependent patients with iron overload: what is the most effective dose based on serum ferritin levels?

    Science.gov (United States)

    Karimi, Mehran; Azarkeivan, Azita; Zareifar, Soheila; Cohan, Nader; Bordbar, Mohammad Reza; Haghpanah, Sezaneh

    2012-11-01

    The aim of this study was to evaluate the efficacy and safety of deferasirox in patients from Iran. This was a retrospective, observational study in regularly transfused, iron-overloaded patients who received deferasirox 20-38 mg/kg/day for up to 12 months. Changes in serum ferritin were assessed as follows: from baseline to 3 months with deferasirox doses of 20-24 mg/kg/day; from 3 to 6 months with doses of 25-29 mg/kg/day; and from 6 to 12 months with doses of 30-38 mg/kg/day. The safety of deferasirox was evaluated monthly. Patients' satisfaction with treatment was assessed after 9 months. One hundred and nineteen patients were included. Overall mean serum ferritin levels were significantly decreased from baseline after 12 months of deferasirox therapy (2510 ± 1210 to 1665 ± 1240 ng/ml; P deferasirox in heavily iron-overloaded patients from Iran and confirms that deferasirox is effective and well tolerated; however, dose increases to ≥30 mg/kg/day should be considered if efficacy is insufficient.

  8. A prospective phase II randomized study of deferasirox to prevent iatrogenic iron overload in patients undertaking induction/consolidation chemotherapy for acute myeloid leukaemia.

    Science.gov (United States)

    Kennedy, Glen A; Morris, Kirk L; Subramonpillai, Elango; Curley, Cameron; Butler, Jason; Durrant, Simon

    2013-06-01

    This prospective randomized phase II study aimed to determine the safety and efficacy of deferasirox in preventing iatrogenic iron overload in patients receiving induction/consolidation chemotherapy for acute myeloid leukaemia (AML) ize. Serum ferritin, transferrin saturation and CRP were measured pre-, mid- and post- each chemotherapy cycle. Patients were randomized to receive either therapy with deferasirox vs. no deferasirox therapy once serum ferritin increased to >500 μg/l. The trial was stopped prematurely due to excess gastrointestinal (GI) and infectious toxicity demonstrable in the deferasirox arm, after 10 patients had been randomized to deferasirox and 6 patients to the control arm. Overall, deferasirox was poorly tolerated, with median maximum tolerated dose only 13·8 mg/kg/d and no patient able to tolerate doses >20 mg/kg/d. Median duration of deferasirox therapy was only 72 d (range 19-130 d), with 9/10 patients requiring unplanned dose interruptions and 4/10 patients unable to continue the drug predominantly due to GI effects. Although all 3 treatment-related deaths occurred in the deferasirox arm (P = 0·25), median overall survival was similar between treatment arms. Use of deferasirox to prevent iatrogenic iron overload in AML patients undertaking induction/consolidation is poorly tolerated and appears to be associated with excess GI and infectious toxicity. © 2013 John Wiley & Sons Ltd.

  9. [Efficacy and safety of deferasirox in aplastic anemia patients with iron overload: a single arm, multi-center,prospective study in China].

    Science.gov (United States)

    Shi, Jun; Chang, Hong; Zhang, Li; Shao, Yinqi; Nie, Neng; Zhang, Jing; Huang, Jinbo; Zhang, Li; Tang, Xudong; Quan, Richeng; Zheng, Chunmei; Xiao, Haiyan; Hu, Dengming; Hu, Lingyan; Liu, Feng; Zhou, Yongming; Zheng, Yizhou; Zhang, Fengkui

    2016-01-01

    To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload. A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload. All patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period. AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment

  10. Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine.

    Science.gov (United States)

    Pennell, Dudley J; Porter, John B; Piga, Antonio; Lai, Yong-Rong; El-Beshlawy, Amal; Elalfy, Mohsen; Yesilipek, Akif; Kilinç, Yurdanur; Habr, Dany; Musallam, Khaled M; Shen, Junwu; Aydinok, Yesim

    2015-02-01

    Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean ] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long-term safety profile of deferasirox or DFO was consistent with previous reports; serious drug-related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron-overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron (Clinicaltrials.gov identifier: NCT00600938). © 2014 Wiley Periodicals, Inc.

  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. Elevated metals compromise repair of oxidative DNA damage via the base excision repair pathway: implications of pathologic iron overload in the brain on integrity of neuronal DNA.

    Science.gov (United States)

    Li, Hui; Swiercz, Rafal; Englander, Ella W

    2009-09-01

    Tissue-specific iron content is tightly regulated to simultaneously satisfy specialized metabolic needs and avoid cytotoxicity. In the brain, disruption of iron homeostasis may occur in acute as well as progressive injuries associated with neuronal dysfunction and death. We hypothesized that adverse effects of disrupted metal homeostasis on brain function may involve impairment of DNA repair processes. Because in the brain, the base excision repair (BER) pathway is central for handling oxidatively damaged DNA, we investigated effects of elevated iron and zinc on key BER enzymes. In vitro DNA repair assays revealed inhibitory effects of metals on BER activities, including the incision of abasic sites, 5'-flap cleavage, gap filling DNA synthesis and ligation. Using the comet assay, we showed that while metals at concentrations which inhibit BER activities in in vitro assays, did not induce direct genomic damage in cultured primary neurons, they significantly delayed repair of genomic DNA damage induced by sublethal exposure to H(2)O(2). Thus, in the brain even a mild transient metal overload, may adversely affect the DNA repair capacity and thereby compromise genomic integrity and initiate long-term deleterious sequelae including neuronal dysfunction and death.

  13. Elevated metals compromise repair of oxidative DNA damage via the base excision repair pathway: implications of pathologic iron-overload in the brain on integrity of neuronal DNA

    Science.gov (United States)

    Li, Hui; Swiercz, Rafal; Englander, Ella W.

    2009-01-01

    Tissue-specific iron content is tightly regulated to simultaneously satisfy specialized metabolic needs and avoid cytotoxicity. In the brain, disruption of iron homeostasis may occur in acute as well as progressive injuries associated with neuronal dysfunction and death. We hypothesized that adverse effects of disrupted metal homeostasis on brain function may involve impairment of DNA repair processes. Since in the brain, the base excision repair (BER) pathway is central for handling oxidatively damaged DNA, we investigated effects of elevated iron and zinc on key BER enzymes. In vitro DNA repair assays revealed inhibitory effects of metals on BER activities, including the incision of abasic sites, 5’-flap cleavage, gap filling DNA synthesis and ligation. Using the comet assay, we showed that while metals at concentrations, which inhibit BER activities in in vitro assays, do not induce direct genomic damage in cultured primary neurons, they significantly delay repair of genomic DNA damage induced by sub-lethal exposure to H2O2. Thus, in the brain even a mild transient metal overload, may adversely affect the DNA repair capacity and thereby compromise genomic integrity and initiate long-term deleterious sequelae including neuronal dysfunction and death. PMID:19619136

  14. 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

    patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS...

  15. Surface electrocardiogram detects signs of right ventricular pressure overload among acute-decompensated heart failure with preserved ejection fraction patients.

    Science.gov (United States)

    Martínez Santos, Paula; Vilacosta, Isidre; Batlle López, Elena; Sánchez Sauce, Beatriz; España Barrio, Elena; Jiménez Valtierra, Julia; de la Rosa Riestra, Adriana; Campuzano Ruiz, Raquel

    2016-01-01

    Pulmonary hypertension (PH) is a common finding among patients with heart failure and preserved ejection fraction (HFpEF) and contributes to develop right ventricular systolic dysfunction (RVSD). We evaluated the diagnostic accuracy of Flowers and Horan electrocardiographic criteria to detect significant right ventricular pressure overload. 123 patients were prospectively included. We used the Flowers and Horan (FH) ECG criteria to define RV enlargement (score >10). Echocardiographic measurements were performed blinded to the electrocardiographic results. Severe PH was found in 51.5%. Seventeen patients (16.5%) had a FH score >10 points. This was associated to RVSD (RR 2.66; 1.51-4.67 CI 95%, p=0.002), with 90.5% specificity and 34.4% sensitivity and to severe PH (RR 1.70; 1.16-2.50 CI 95%, p=0.028) with 91.9% specificity and 27.5% sensitivity. The ECG is a useful tool to classify HFpEF patients with echocardiographic signs of right ventricular pressure overload, in the absence of RBBB. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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.

  18. THERAPEUTIC VALUE OF COMBINED THERAPY WITH DEFERASIROX AND SILYMARIN ON IRON OVERLOAD IN CHILDREN WITH BETA THALASSEMIA

    Directory of Open Access Journals (Sweden)

    adel abd elhaleim hagag

    2013-11-01

    Patients and Methods: This study was conducted on 40 children with beta thalassemia major under follow-up at Hematology Unit, Pediatric Department, Tanta University Hospital having serum ferritin level more than 1000 ng/ml and was divided in two groups. Group IA: Received oral Deferasirox (Exjade and silymarin for 6 months. Group IB: Received oral Deferasirox (Exjade and placebo for 6 months and 20 healthy children serving as a control group in the period between April 2011 and August 2012 and was performed after approval from research ethical committee center in Tanta University Hospital and obtaining an informed written parental consent from all participants in this research. Results: Serum ferritin levels were markedly decreased in group IA cases compared with group IB (P= 0.001. Conclusion: From this study we concluded that, silymarin in combination with Exjade can be safely used in treatment of iron-loaded thalassemic patients as it showed good iron chelation with no sign of toxicity. Recommendations: Extensive multicenter studies in large number of patients with longer duration of follow up and more advanced methods of assessment of iron status is recommended to clarify the exact role of silymarin in reduction of iron over load in children with beta thalassemia.

  19. 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...

  20. Efficacy of Deferasirox for the treatment of iron overload in Chinese thalassaemia major patients: results from a prospective, open-label, multicentre clinical trial.

    Science.gov (United States)

    Lai, Y-R; Liu, R-R; Li, C-F; Huang, S-L; Li, Q; Habr, D; Martin, N; Shen, Z-X

    2013-12-01

    To assess the efficacy and safety of deferasirox in Chinese thalassaemia major (TM) patients EPIC (Evaluation of Patients' Iron Chelation with Exjade(®)) was a large multi-national study and, notably, the first clinical trial of an iron chelator registered with the Chinese State Food and Drug Administration. Efficacy and safety of deferasirox were compared in Chinese (n = 117) and non-Chinese (n = 998) TM patients. Deferasirox was initiated at 20 mg kg(-1)  day(-1), with titration increments of 5-10 mg kg(-1) day(-1), based on serum ferritin trends and safety parameters. At baseline, Chinese patients were younger than non-Chinese (mean age 6·8 versus 19·5 years), with higher median serum ferritin (4519 vs 3058 ng mL(-1)). Over 1 year, mean actual deferasirox dose was similar for Chinese and non-Chinese patients (24·6 and 24·0 mg kg(-1)  day(-1), respectively); median serum ferritin did not change significantly from baseline in Chinese patients (+340 ng mL(-1), P = 0·102) and significantly decreased in non-Chinese patients (-220 ng mL(-1); P deferasirox dose 33·6 mg kg(-1)  day(-1)), median serum ferritin decreased (-756 ng mL(-1); P = 0·0397), with a numerically higher reduction in patients aged ≥6 to  deferasirox in Chinese patients was similar to the overall population with respect to clinically-relevant findings. Age and deferasirox exposure influenced study findings, supporting the need for longer-term treatment and dose escalation to ≥30 mg kg(-1)  day(-1) to achieve neutral or negative iron balance in heavily iron overloaded and younger Chinese patients. © 2013 The Authors. Transfusion Medicine © 2013 British Blood Transfusion Society.

  1. 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.

  2. 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.

  3. Reticulocyte hemoglobin content (MCHr) in the detection of iron deficiency.

    Science.gov (United States)

    Urrechaga Igartua, Eloísa; Hoffmann, Johannes J M L; Izquierdo-Álvarez, Silvia; Escanero, Jesús F

    2017-09-01

    Blood hemoglobin (Hb) concentration within the reference interval does not exclude iron deficiency (ID): individuals with normal stores lose iron during a long period before their Hb falls below of the level that is defined as anemia. The process entails a decrease of storage iron, shown by serum ferritin below reference range, followed by iron depletion, eventually leading to iron restricted erythropoiesis; consequence of an imbalance between erythropoietic iron requirements and too low supply is a reduction of Hb synthesis in reticulocytes. We study the potential utility of mean reticulocyte hemoglobin content (MCHr), reported by CELL-DYN Sapphire (Abbott Diagnostics) analyzer, in the detection of ID in non-anemic adults. 207 patients with Hb within the reference range were enrolled. ID was defined as Hb>120g/L (women), >130g/L (men) and serum ferritin iron deficient adults. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

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

    2011-01-01

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

  5. 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.

  6. Serum transferrin receptors in detection of iron deficiency in pregnancy.

    Science.gov (United States)

    Rusia, U; Flowers, C; Madan, N; Agarwal, N; Sood, S K; Sikka, M

    1999-08-01

    A prospective hospital-based study was conducted to evaluate the efficacy of serum transferrin receptors in the detection of iron deficiency in pregnant women. The iron status of 100 pregnant women with single uncomplicated term pregnancies in the first stage of labor was established using standard laboratory measures. These included complete hemogram, red cell indices, serum iron, percent transferrin saturation, and serum ferritin. In addition, serum transferrin receptor (STFR) was estimated. The results of 81 women with complete laboratory profiles were analyzed. Thirty-five (43.2%) women were anemic (hemoglobin <11 g/dl). Hemoglobin (Hb) showed a significant correlation with MCH, MCHC, serum iron, and percent transferrin saturation, suggesting that the anemia was likely to be due to iron deficiency. The mean STFR level was 18.05+/-9.9 mg/l in the anemic women and was significantly raised (p<0.001) compared with that of the nonanemic women. STFR correlated significantly with Hb (p<0.001), MCH (p<0.05), MCHC (p<0.01), serum iron (p<0.01), and percent transferrin saturation (p<0.01) and also showed a highly significant correlation with the degree of anemia. Serum ferritin in these women did not correlate with Hb, and only 54.4% of the women had levels <12 ng/ml, which does not reflect the true prevalence of iron deficiency. Serum transferrin receptor estimation is thus a useful measure for detecting iron deficiency in pregnancy.

  7. Determination of iron-overload in thalassemia by hepatic MRI and ferritin Determinação da sobrecarga de ferro na talassemia pela IRM hepática e ferritina

    Directory of Open Access Journals (Sweden)

    Ivan L. Angulo

    2008-12-01

    Full Text Available Accumulation of iron in thalassemia causes organ damage and reduces patient survival due to heart lesions in the second decade of life. Iron deposits are monitored by direct (biopsy and indirect methods (ferritin with sequential data being better than isolated measurements. This paper compares two indirect measurements of iron overload; a single hepatic iron concentration (HIC by magnetic resonance and mean ferritin levels over four years. A retrospective study of 25 patients from the Centro Regional de Hemoterapia in Ribeirão Preto, Brazil was carried out. High HIC (above 7 mg per gram of dry weight was found in 20 patients and high mean serum ferritin (above 2500 μg/L in 10 patients. Stratification into three levels (low, moderate and high of iron overload gave similar results in both tests. Many other factors influence de degree of iron overload in thalassemia. No correlation was found using a non-parametric statistical test between HIC and mean serum ferritin. Both methods provide better planning of chelation therapy.O acúmulo de ferro na talassemia causa lesões orgânicas e reduz a sobrevida do paciente por lesão cardíaca na segunda década da vida, e tem sido avaliado por medidas diretas (biópsia e indiretas (ferritina. As medidas isoladas carecem de valor, sendo preferidas as sequenciais. Este trabalho pretende comparar medidas indiretas de sobrecarga de ferro, uma medida da concentração de ferro hepático por ressonância magnética, e a ferritina sérica média dos últimos quatro anos. Trata-se de estudo retrospectivo de 25 pacientes do Centro Regional de Hemoterapia, em Ribeirão Preto, Brasil. Encontrou-se em vinte pacientes ferro hepático acima de 7 mg/g peso seco e ferritina média elevada acima de 2.500 ug/l em dez. Estratificação em três níveis de sobrecarga (leve, moderada e grave produziu resultados semelhantes em ambos os testes. Vários outros fatores influenciam o grau de sobrecarga de ferro na talassemia. N

  8. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Gouws, Rufus H.; Tarp, Sven

    2017-01-01

    Too often online dictionaries still display too many features determined by the restrictions that applied to printed dictionaries. Data overload in dictionary articles can be regarded as one such relic from the past. However, the idea that online dictionaries have unlimited space has furthered...... 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...

  9. 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 .

  10. 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...

  11. One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation.

    Science.gov (United States)

    Inati, Adlette; Kahale, Mario; Sbeiti, Nada; Cappellini, Maria Domenica; Taher, Ali T; Koussa, Suzanne; Nasr, Therese A; Musallam, Khaled M; Abbas, Hussein A; Porter, John B

    2017-01-01

    Iron overload is well documented in patients with β-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with β-thalassemia major following HSCT. Patients (aged 12.4 years) received deferasirox (n = 12, 10 mg/kg/day starting dose) or phlebotomy (n = 14, 6 ml/kg/2 weeks) for 1 year. In two and five patients, deferasirox dose was increased to 15 and 20 mg/kg/day, respectively. Magnetic resonance imaging (MRI)-assessed liver iron concentration (LIC) decreased with deferasirox (mean 12.5 ± 10.1 to 8.5 ± 9.3 mg Fe/g dry weight [dw]; P = 0.0005 vs. baseline) and phlebotomy (10.2 ± 6.8 to 8.3 ± 9.2 mg Fe/g dw; P = 0.05). LIC reductions were greater with deferasirox than with phlebotomy for patients with baseline serum ferritin 1,000 ng/ml or higher (-8.1 ± 1.5 vs. -3.5 ± 5.7 mg Fe/g dw; P = 0.048). Serum ferritin and non-transferrin-bound iron also decreased significantly. In two patients with severe cardiac siderosis, a clinically relevant improvement in myocardial T2* was seen, following phlebotomy and deferasirox therapy (n = 1 each). Adverse effects with deferasirox were skin rash, gastrointestinal upset, and increased liver function tests (all n = 1), while those for phlebotomy were difficulty with venous access (n = 4) and distress during procedure (n = 1). Parents of 13/14 children receiving phlebotomy wished to switch to deferasirox, with 1/14 being satisfied with phlebotomy. Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with β- thalassemia major post-HSCT, with a manageable safety profile. © 2016 Wiley Periodicals, Inc.

  12. [Iron dysregulation and anemias].

    Science.gov (United States)

    Ikuta, Katsuya

    2015-10-01

    Most iron in the body is utilized as a component of hemoglobin that delivers oxygen to the entire body. Under normal conditions, the iron balance is tightly regulated. However, iron dysregulation does occasionally occur; total iron content reductions cause iron deficiency anemia and overexpression of the iron regulatory peptide hepcidin disturbs iron utilization resulting in anemia of chronic disease. Conversely, the presence of anemia may ultimately lead to iron overload; for example, thalassemia, a common hereditary anemia worldwide, often requires transfusion, but long-term transfusions cause iron accumulation that leads to organ damage and other poor outcomes. On the other hand, there is a possibility that iron overload itself can cause anemia; iron chelation therapy for the post-transfusion iron overload observed in myelodysplastic syndrome or aplastic anemia improves dependency on transfusions in some cases. These observations reflect the extremely close relationship between anemias and iron metabolism.

  13. 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.

  14. 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.

  15. Biogenic iron mineralization at Iron Mountain, CA with implications for detection with the Mars Curiosity rover

    Science.gov (United States)

    Williams, Amy J.; Sumner, Dawn Y.; Alpers, Charles N.; Campbell, Kate M.; Nordstrom, D. Kirk

    2014-01-01

    (Introduction) Microbe-mineral interactions and biosignature preservation in oxidized sulfidic ore bodies (gossans) are prime candidates for astrobiological study. Such oxidized iron systems have been proposed as analogs for some Martian environments. Recent studies identified microbial fossils preserved as mineral-coated filaments. This study documents microbially-mediated mineral biosignatures in hydrous ferric oxide (HFO) and ferric oxyhydroxysulfates (FOHS) in three environments at Iron Mountain, CA. We investigated microbial community preservation via HFO and FOHS precipitation and the formation of filamentous mineral biosignatures. These environments included 1) actively precipitating (1000's yrs), naturally weathered HFO from in situ gossan, and 3) remobilized iron deposits, which contained lithified clastics and zones of HFO precipitate. We used published biogenicity criteria as guidelines to characterize the biogenicity of mineral filaments. These criteria included A) an actively precipitating environment where microbes are known to be coated in minerals, B) presence of extant microbial communities with carbon signatures, C) structures observable as a part of the host rock, and D) biological morphology, including cellular lumina, multiple member population, numerous taxa, variable and 3-D preservation, biological size ranges, uniform diameter, and evidence of flexibility. This study explores the relevance and detection of these biosignatures to possible Martian biosignatures. Similar filamentous biosignatures are resolvable by the Mars Hand Lens Imager (MAHLI) onboard the Mars Science Laboratory (MSL) rover, Curiosity, and may be identifiable as biogenic if present on Mars.

  16. 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)

  17. 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.

  18. Deferasirox treatment of iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange

    Science.gov (United States)

    Gattermann, Norbert; Jarisch, Andrea; Schlag, Rudolf; Blumenstengel, Klaus; Goebeler, Mariele; Groschek, Matthias; Losem, Christoph; Procaccianti, Maria; Junkes, Alexia; Leismann, Oliver; Germing, Ulrich

    2012-01-01

    EXtend and eXjange were prospective, 1-yr, non-interventional, observational, multicentre studies that investigated deferasirox, a once-daily oral iron chelator, in iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes (MDS), respectively, treated in the daily-routine setting of office-based physicians. No inclusion or exclusion criteria or additional monitoring procedures were applied. Deferasirox was administered as recommended in the European Summary of Product Characteristics. Haematological parameters and adverse events (AEs) were collected at two-monthly intervals. Data from 123 chelation-naïve patients with MDS (mean age 70.4 yrs) with median baseline serum ferritin level of 2679 (range 184–16 500) ng/mL, and 44 prechelated patients with MDS (mean age 69.6 yrs) with median baseline serum ferritin level of 2442 (range 521–8565) ng/mL, were assessed. The mean prescribed daily dose of deferasirox at the first visit was 15.7 and 18.7 mg/kg/d, respectively. Treatment with deferasirox produced a significant reduction in median serum ferritin levels in chelation-naïve patients with MDS from 2679 to 2000 ng/mL (P = 0.0002) and a pronounced decrease in prechelated patients with MDS from 2442 to 2077 ng/mL (P = 0.06). The most common drug-related AEs were gastrointestinal, increased serum creatinine levels and rash. These studies demonstrate that deferasirox used in physicians’ medical practices is effective in managing iron burden in transfusion-dependent patients with MDS. PMID:22023452

  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. Biocompatible capped iron oxide nanoparticles for Vibrio cholerae detection

    Science.gov (United States)

    Sharma, Anshu; Baral, Dinesh; Rawat, Kamla; Solanki, Pratima R.; Bohidar, H. B.

    2015-05-01

    We report the studies relating to fabrication of an efficient immunosensor for Vibrio cholerae detection. Magnetite (iron oxide (Fe3O4)) nanoparticles (NPs) have been synthesized by the co-precipitation method and capped by citric acid (CA). These NPs were electrophoretically deposited onto indium-tin-oxide (ITO)-coated glass substrate and used for immobilization of monoclonal antibodies against Vibrio cholerae (Ab) and bovine serum albumin (BSA) for Vibrio cholerae detection using an electrochemical technique. The structural and morphological studies of Fe3O4 and CA-Fe3O4/ITO were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) techniques. The average crystalline size of Fe3O4, CA-Fe3O4 nanoparticles obtained were about 29 ± 1 nm and 37 ± 1 nm, respectively. The hydrodynamic radius of the nanoparticles was found to be 77.35 nm (Fe3O4) and 189.51 nm (CA-Fe3O4) by DLS measurement. The results of electrochemical response studies of the fabricated BSA/Ab/CA-Fe2O3/ITO immunosensor exhibits a good detection range of 12.5-500 ng mL-1 with a low detection limit of 0.32 ng mL-1, sensitivity 0.03 Ω/ng ml-1 cm-2, and reproducibility more than 11 times.

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

    Energy Technology Data Exchange (ETDEWEB)

    Miaux, Y. [Dept. of Radiology, Hopital Saint-Louis, 75 Paris (France); Daurelle, P. [Dept. of Endocrinology, Hopital Saint-Louis, 75 Paris (France); Zagdanski, A.M. [Dept. of Radiology, Hopital Saint-Louis, 75 Paris (France); Passa, P. [Dept. of Endocrinology, Hopital Saint-Louis, 75 Paris (France); Bourrier, P. [Dept. of Radiology, Hopital Saint-Louis, 75 Paris (France); Frija, J. [Dept. of Radiology, Hopital Saint-Louis, 75 Paris (France)

    1995-08-01

    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.)

  2. 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

  3. 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.

  4. Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload

    Science.gov (United States)

    Taher, Ali; Cappellini, Maria D; Vichinsky, Elliott; Galanello, Renzo; Piga, Antonio; Lawniczek, Tomasz; Clark, Joan; Habr, Dany; Porter, John B

    2009-01-01

    The highest approved dose of deferasirox is currently 30 mg/kg per d in many countries; however, some patients require escalation above 30 mg/kg per d to achieve their therapeutic goals. This retrospective analysis investigated the efficacy (based on change in serum ferritin levels) and safety of deferasirox >30 mg/kg per d in adult and paediatric patients with transfusion-dependent anaemias, including β-thalassaemia, sickle cell disease and the myelodysplastic syndromes. In total, 264 patients pooled from four clinical trials received doses of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks. In the overall population there was a statistically significant median decrease in serum ferritin of 440 μg/l (Pdeferasirox doses of >30 mg/kg per d was consistent with previously published data. There was no worsening of renal or liver function following dose escalation. Deferasirox >30 mg/kg per d effectively reduced iron burden to levels lower than those achieved prior to dose escalation in patients with transfusion-dependent anaemias. This has important implications for patients who are heavily transfused and may require higher doses to reduce body iron burden. PMID:19764988

  5. Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload

    Science.gov (United States)

    Pennell, Dudley J.; Porter, John B.; Cappellini, Maria Domenica; Chan, Lee Lee; El-Beshlawy, Amal; Aydinok, Yesim; Ibrahim, Hishamshah; Li, Chi-Kong; Viprakasit, Vip; Elalfy, Mohsen Saleh; Kattamis, Antonis; Smith, Gillian; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Taher, Ali

    2011-01-01

    Background The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with β-thalassemia major in the cardiac sub-study of the EPIC trial. Design and Methods Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years. Results Baseline myocardial T2* was severe (>5 to deferasirox dose was 33.1±3.7 mg/kg/d in the one-year core study increasing to 36.1±7.7 mg/kg/d during the second year of treatment. Geometric mean myocardial T2* increased from a baseline of 11.2 to 14.8 ms at two years (Pdeferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with β-thalassemia major and mild, moderate and severe cardiac siderosis. (Clinicaltrials.gov identifier: NCT 00171821) PMID:21071497

  6. Evaluation of iron status in lemurs by analysis of serum iron and ferritin concentrations, total iron-binding capacity, and transferrin saturation.

    Science.gov (United States)

    Williams, Cathy V; Junge, Randall E; Stalis, Ilse H

    2008-02-15

    To assess serum iron and ferritin concentrations, total iron-binding capacity, and transferrin saturation as indicators of iron metabolic status in 3 genera of lemurs and determine whether these variables are useful for screening for iron overload. Cross-sectional study. 11 ring-tailed lemurs (Lemur catta), 11 black lemurs (Eulemur macaco macaco), and 11 red-ruffed lemurs (Varecia rubra). Blood samples were collected weekly for 3 weeks and assayed for serum iron and ferritin concentrations and total iron-binding capacity. Liver biopsy specimens were evaluated histologically and assayed for total iron, nonheme iron, and trace mineral concentrations. Deposition of iron was scored on Prussian blue-stained slides. Hepatic iron content ranged from 497 to 12,800 Pg/g dry weight (median, 2,165 Pg/g). Differences were seen in mean hepatic iron content across genera, with ruffed lemurs having the highest concentrations and ring-tailed lemurs having the lowest. Iron accumulation in the liver was mild, and cellular pathologic changes associated with iron storage disease were not detected in any lemur. Ferritin concentration was the only variable that correlated significantly with hepatic iron content in all 3 genera of lemurs; however, both transferrin saturation and serum iron concentration were correlated with hepatic iron concentration in ring-tailed and ruffed lemurs. Serum ferritin concentration was the only variable that was consistently correlated with hepatic iron content in all 3 genera. Mean hepatic iron content varied across genera, suggesting that the propensity for lemurs to develop iron overload in captivity may vary across taxa.

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

    OpenAIRE

    Clara Camaschella

    2013-01-01

    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 (I...

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

    Science.gov (United States)

    Ho, Wan-Ling; Chung, Kuo-Piao; Yang, Szu-Sheng; Lu, Meng-Yao; Jou, Shiann-Tarng; Chang, Hsiu-Hao; Yang, Yung-Li; Lin, Dong-Tsamn; Lin, Kai-Hsin

    2013-04-01

    The newly available iron chelator deferasirox (Exjade, Novartis) is expected to provide better long-term clinical outcomes and improved quality of life for patients with thalassemia than its predecessor, deferoxamine (Desferal, Novartis), because of its oral tablet form. We used the Markov model to estimate total additional lifetime costs and quality-adjusted life years (QALYs) gained with deferasirox versus deferoxamine in patients with transfusion-dependent thalassemia. Patients were assumed to be 2 years of age at initiation of chelation therapy. Clinical outcomes in terms of morbidity and mortality from associated complications and life expectancy for the study population were estimated using the databases of the Bureau of National Health Insurance and the Health and Vital Statistics of Taiwan. Treatment costs were based on analyses of health insurance claims for patients with transfusion-dependent thalassemia. Utilities in terms of quality of life were also included in the model. The incremental cost-utility ratio of deferasirox versus deferoxamine was defined by the ratio of the difference in expected lifetime costs to the difference in QALYs. One-way sensitivity analyses were performed to examine the robustness of the results to key assumptions. Patients treated with deferasirox are expected to experience a lower incidence of associated complications and obtain 2.3 QALYs (discounted) at an additional lifetime cost of US$36,291 per patient (US$15,596 per QALY). Sensitivity analyses showed that the unit drug cost of deferasirox had the greatest impact on the incremental cost-utility ratio. In addition, the incremental cost-utility ratio will increase by delaying the starting age (2 years of age in our study) of chelation therapy. 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

  9. Biocompatible capped iron oxide nanoparticles for Vibrio cholerae detection

    International Nuclear Information System (INIS)

    Sharma, Anshu; Rawat, Kamla; Solanki, Pratima R; Bohidar, H B; Baral, Dinesh

    2015-01-01

    We report the studies relating to fabrication of an efficient immunosensor for Vibrio cholerae detection. Magnetite (iron oxide (Fe 3 O 4 )) nanoparticles (NPs) have been synthesized by the co-precipitation method and capped by citric acid (CA). These NPs were electrophoretically deposited onto indium-tin-oxide (ITO)-coated glass substrate and used for immobilization of monoclonal antibodies against Vibrio cholerae (Ab) and bovine serum albumin (BSA) for Vibrio cholerae detection using an electrochemical technique. The structural and morphological studies of Fe 3 O 4 and CA-Fe 3 O 4 /ITO were characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) techniques. The average crystalline size of Fe 3 O 4 , CA-Fe 3 O 4 nanoparticles obtained were about 29 ± 1 nm and 37 ± 1 nm, respectively. The hydrodynamic radius of the nanoparticles was found to be 77.35 nm (Fe 3 O 4 ) and 189.51 nm (CA-Fe 3 O 4 ) by DLS measurement. The results of electrochemical response studies of the fabricated BSA/Ab/CA-Fe 2 O 3 /ITO immunosensor exhibits a good detection range of 12.5–500 ng mL −1 with a low detection limit of 0.32 ng mL −1 , sensitivity 0.03 Ω/ng ml −1 cm −2 , and reproducibility more than 11 times. (paper)

  10. 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

  11. Iron

    DEFF Research Database (Denmark)

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

    2014-01-01

    The interest in the role of ferrous iron in diabetes pathophysiology has been revived by recent evidence of iron as an important determinant of pancreatic islet inflammation and as a biomarker of diabetes risk and mortality. The iron metabolism in the β-cell is complex. Excess free iron is toxic......, but at the same time, iron is required for normal β-cell function and thereby glucose homeostasis. In the pathogenesis of diabetes, iron generates reactive oxygen species (ROS) by participating in the Fenton chemistry, which can induce oxidative damage and apoptosis. The aim of this review is to present...... 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...

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

    Directory of Open Access Journals (Sweden)

    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。

  13. 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...

  14. 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.

  15. 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

    Directory of Open Access Journals (Sweden)

    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

  16. 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

    Directory of Open Access Journals (Sweden)

    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

  17. Combination therapies in iron chelation

    Directory of Open Access Journals (Sweden)

    Raffaella Origa

    2014-12-01

    Full Text Available The availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with b thalassemia major. However, monotherapy is not effective in all patients for a variety of reasons. We analyzed the most relevant reports recently published on alternating or combined chelation therapies in thalassemia major with special attention to safety aspects and to their effects in terms of reduction of iron overload in different organs, improvement of complications, and survival. When adverse effects, such as gastrointestinal upset with deferasirox or infusional site reactions with deferoxamine are not tolerable and organ iron is in an acceptable range, alternating use of two chelators (drugs taken sequentially on different days, but not taken on the same day together may be a winning choice. The association deferiprone and deferoxamine should be the first choice in case of heart failure and when dangerously high levels of cardiac iron exist. Further research regarding the safety and efficacy of the most appealing combination treatment, deferiprone and deferasirox, is needed before recommendations for routine clinical practice can be made.

  18. Quantitative Positron Emission Tomography Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure Overload Left Ventricular Hypertrophy in vivo

    Science.gov (United States)

    Zhong, Min; Alonso, Clayton E.; Taegtmeyer, Heinrich; Kundu, Bijoy K.

    2013-01-01

    We proposed that metabolic remodeling in the form of increased myocardial glucose analogue 2-[18F] fluoro-2deoxy-D-glucose (FDG) uptake precedes and triggers the onset of severe contractile dysfunction in pressure overload left ventricular hypertrophy (LVH) in vivo. To test this hypothesis we used a mouse model of transverse aortic constriction (TAC) together with Positron Emission Tomography (PET) and assessed serial changes in cardiac metabolism and function over 7 days. Methods PET scans of 16 C57BL/6 male mice were performed using a microPET scanner under sevofluorane anesthesia. A 10-minute transmission scan was followed by a 60-minute dynamic FDG-PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. Transverse aortic constriction (TAC) and sham surgeries were performed after baseline imaging. Osmotic mini-pumps containing either propranolol (5 mg/kg/day) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spill-over and partial volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial FDG influx constant, Ki. The rate of myocardial glucose use, rMGU, was also computed. Estimations of the ejection fractions (EF) were based on the high resolution gated PET images Results Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose usage the day after surgery indicating early adaptive response. On day 7 the EF had decreased by 24% indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC Mice treated with propranolol attenuated rate of FDG uptake, diminished mismatch between Ki and rMGU (9%) and rescued cardiac function. Conclusions Metabolic maladaptation precedes

  19. Maximal standard dose of parenteral iron for hemodialysis patients: an MRI-based decision tree learning analysis.

    Directory of Open Access Journals (Sweden)

    Guy Rostoker

    Full Text Available Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients.We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin, in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2* contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID analysis.The CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%. The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4 with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex and the hepcidin level also influenced liver iron content on MRI.The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products.

  20. 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

  1. Laboratory Elements for Accurate Detection of Iron Deficiency In ...

    African Journals Online (AJOL)

    et al. in India [3] who found a 96% sensitivity for the. RDW >15% and a 69% sensitivity for the MCH 15% [4]. These two parameters that are present on a simple CBC, would allow for the early discovery of iron deficiency. Therefore. KNIGHT et ...

  2. Irradiation effects detected by Moessbauer spectroscopy in iron complexes

    International Nuclear Information System (INIS)

    Ladriere, J.

    1998-01-01

    The nature and the extent of the 60 Co gamma radiolysis of several iron coordination compounds have been analysed by Moessbauer absorption spectroscopy. The comparison of the radiolytic yields with the after effects observed by Moessbauer emission spectroscopy in similar 57 Co-doped compounds, supports the self-radiolysis model

  3. 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 ...

  4. Overload blunts baroreflex only in overreached athletes.

    Science.gov (United States)

    Bourdillon, Nicolas; Yazdani, Sasan; Nilchian, Masih; Mariano, Alessio; Vesin, Jean-Marc; Millet, Grégoire P

    2018-01-31

    Heart rate variability (HRV) is commonly used to diagnose overreaching and monitor athletes' responses to training. Baroreflex sensitivity (BRS) is modified by changes in training load and might be another means to detect overreaching. The goal of this study was to assess BRS and HRV changes in two groups of athletes responding either negatively (FOR) or positively (AF) to similar training overload. Fifteen athletes performed 2-week baseline (BSL) training followed by 3-week overload (+45%; OVL) and 2-week recovery (-20%; RCV). HRV, training load and subjective fatigue were measured daily via questionnaires. BRS, salivary cortisol and testosterone, and submaximal exercise and maximal 3-km run performances were measured at the end of each period. Based on their performance change during OVL, 8 athletes were diagnosed as FOR and 7 as AF. Subjective fatigue was increased in FOR athletes during OVL. BRS increased in AF but not in FOR athletes during RCV. At the end of RCV, cortisol and testosterone were higher than BSL in both groups. Three weeks of similar training overload can induce either performance enhancement or overreaching. The changes in submaximal exercise and maximal performances and in subjective fatigue were the fastest-responding parameters that distinguished the two groups of athletes during OVL. Training overload blunted the increase in BRS in FOR only. Most of the differences in BRS were observed during the recovery period. BRS appears to be a more sensitive parameter than HRV for early monitoring of responses to training. Copyright © 2018. Published by Elsevier Ltd.

  5. The detection of HBV DNA with gold-coated iron oxide nanoparticle gene probes

    International Nuclear Information System (INIS)

    Xi Dong; Luo Xiaoping; Lu Qianghua; Yao Kailun; Liu Zuli; Ning Qin

    2008-01-01

    Gold-coated iron oxide nanoparticle Hepatitis B virus (HBV) DNA probes were prepared, and their application for HBV DNA measurement was studied. Gold-coated iron oxide nanoparticles were prepared by the citrate reduction of tetra-chloroauric acid in the presence of iron oxide nanoparticles which were added as seeds. With a fluorescence-based method, the maximal surface coverage of hexaethiol 30-mer oligonucleotides and the maximal percentage of hybridization strands on gold-coated iron oxide nanoparticles were (120 ± 8) oligonucleotides per nanoparticle, and (14 ± 2%), respectively, which were comparable with those of (132 ± 10) and (22 ± 3%) in Au nanoparticle groups. Large network aggregates were formed when gold-coated iron oxide nanoparticle HBV DNA gene probe was applied to detect HBV DNA molecules as evidenced by transmission electron microscopy and the high specificity was verified by blot hybridization. Our results further suggested that detecting DNA with iron oxide nanoparticles and magnetic separator was feasible and might be an alternative effective method

  6. Site-selective detection of vibrational modes of an iron atom in a trinuclear complex

    Energy Technology Data Exchange (ETDEWEB)

    Faus, Isabelle, E-mail: faus@rhrk.uni-kl.de; Rackwitz, Sergej; Wolny, Juliusz A. [University of Kaiserslautern, Department of Physics (Germany); Banerjee, Atanu; Kelm, Harald; Krüger, Hans-Jörg [University of Kaiserslautern, Department of Chemistry (Germany); Schlage, Kai; Wille, Hans-Christian [DESY, PETRA III, P01 (Germany); Schünemann, Volker [University of Kaiserslautern, Department of Physics (Germany)

    2016-12-15

    Nuclear inelastic scattering (NIS) experiments on the trinuclear complex [{sup 57}Fe{L-N_4(CH_2Fc)_2} (CH{sub 3}CN){sub 2}](ClO{sub 4}){sub 2} have been performed. The octahedral iron ion in the complex was labelled with {sup 57}Fe and thereby exclusively the vibrational modes of this iron ion have been detected with NIS. The analysis of nuclear forward scattering (NFS) data yields a ferrous low-spin state for the {sup 57}Fe labelled iron ion. The simulation of the partial density of states (pDOS) for the octahedral low-spin iron(II) ion of the complex by density functional theory (DFT) calculations is in excellent agreement with the experimental pDOS of the complex determined from the NIS data obtained at 80 K. Thereby it was possible to assign almost each of the experimentally observed NIS bands to the corresponding molecular vibrational modes.

  7. 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.

  8. Electrocatalytic detection of dopamine at single-walled carbon nanotubes–iron (III) oxide nanoparticles platform

    CSIR Research Space (South Africa)

    Adekunle, AS

    2010-06-01

    Full Text Available Electrochemical sensors using edge-plane pyrolytic graphite electrode (EPPGEs) modified with singlewall carbon nanotubes–iron (III) oxide (SWCNT/Fe2O3) nanoparticles for the sensitive detection of dopamine (DA) are described for the first time...

  9. 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.

  10. Theory, simulation and experimental results of the acoustic detection of magnetization changes in superparamagnetic iron oxide

    Directory of Open Access Journals (Sweden)

    Borgert Jörn

    2011-06-01

    Full Text Available Abstract Background Magnetic Particle Imaging is a novel method for medical imaging. It can be used to measure the local concentration of a tracer material based on iron oxide nanoparticles. While the resulting images show the distribution of the tracer material in phantoms or anatomic structures of subjects under examination, no information about the tissue is being acquired. To expand Magnetic Particle Imaging into the detection of soft tissue properties, a new method is proposed, which detects acoustic emissions caused by magnetization changes in superparamagnetic iron oxide. Methods Starting from an introduction to the theory of acoustically detected Magnetic Particle Imaging, a comparison to magnetically detected Magnetic Particle Imaging is presented. Furthermore, an experimental setup for the detection of acoustic emissions is described, which consists of the necessary field generating components, i.e. coils and permanent magnets, as well as a calibrated microphone to perform the detection. Results The estimated detection limit of acoustic Magnetic Particle Imaging is comparable to the detection limit of magnetic resonance imaging for iron oxide nanoparticles, whereas both are inferior to the theoretical detection limit for magnetically detected Magnetic Particle Imaging. Sufficient data was acquired to perform a comparison to the simulated data. The experimental results are in agreement with the simulations. The remaining differences can be well explained. Conclusions It was possible to demonstrate the detection of acoustic emissions of magnetic tracer materials in Magnetic Particle Imaging. The processing of acoustic emission in addition to the tracer distribution acquired by magnetic detection might allow for the extraction of mechanical tissue parameters. Such parameters, like for example the velocity of sound and the attenuation caused by the tissue, might also be used to support and improve ultrasound imaging. However, the method

  11. Tris(2-methyl-8-quinolinolato)iron(III) as a novel spectrophotometric probe for silanol detection.

    Science.gov (United States)

    Uehara, Nobuo; Kawata, Sumiko; Shimizu, Tokuo

    2006-03-01

    Tris(2-methyl-8-quinolinolato)iron(III) was proposed as a sensitive spectrophotometric silanol-detecting probe based on the coordination ability of silanol groups on the surface of octadecylsylanized silica gel (ODS silica gel) for reversed-phase high-performance liquid chromatography. A peak of the iron(III) complex on a chromatogram abruptly collapsed as the silanol content in an ODS column increased, indicating that the iron(III) complex could sense trace amounts of silanol groups. The change of the peak parameters, such as the peak height and the peak area was highly related to the output of some nitrogen-containing compounds used as silanol-detecting probes as a function of the silanol content in an ODS column. The response of the peak height of the iron(III) complex to the silanol content was much more sensitive than the response of the nitrogen-containing probes, and was comparable to that of tris(2-methyl-8-quinolinolato)gallium(III), which had been proposed as a fluorometric silanol-detecting probe based on the coordination ability of the silanol groups.

  12. New insights into transfusion-related iron toxicity: Implications for the oncologist

    NARCIS (Netherlands)

    Porter, J.B.; Witte, T.J. de; Cappellini, M.D.; Gattermann, N.

    2016-01-01

    Iron overload is a potentially life-threatening consequence of multiple red-blood-cell transfusions. Here, we review factors affecting excess iron distribution and its damage to specific tissues, as well as mechanisms of oncogenesis by iron. Although consequences of transfusional iron overload are

  13. Randomised controlled trials of iron chelators for the treatment of cardiac siderosis in thalassaemia major

    Directory of Open Access Journals (Sweden)

    Arun John Baksi

    2014-09-01

    Full Text Available In conditions requiring repeated blood transfusion or where iron metabolism is abnormal, heart failure may result from accumulation of iron in the heart (cardiac siderosis. Death due to heart failure from cardiac iron overload has accounted for considerable early mortality in β-thalassemia major. The ability to detect iron loading in the heart by cardiovascular magnetic resonance using T2* sequences has created an opportunity to intervene in the natural history of such conditions. However, effective and well tolerated therapy is required to remove iron from the heart. There are currently 3 approved commercially available iron chelators: deferoxamine, deferiprone and deferasirox. We review the high quality randomised controlled trials in this area for iron chelation therapy in the management of cardiac siderosis.

  14. Phytochemical profile of a microalgae Euglena tuba and its hepatoprotective effect against iron-induced liver damage in Swiss albino mice.

    Science.gov (United States)

    Panja, S; Chaudhuri, D; Ghate, N B; Mandal, N

    2014-12-01

    This study was aimed to evaluate different phytochemical constituents and the ameliorating effect of 70% methanol extract of Euglena tuba (ETME) on iron overload-induced liver injury, along with its in vitro iron-chelating and DNA protection effects. Phytochemicals of ETME were identified by GC-MS analysis. Iron chelation and protection of Fenton reaction-induced DNA damage was conducted in vitro. Post oral administration of ETME to iron-overloaded mice, the levels of serum parameters, antioxidant enzymes, liver iron, lipid peroxidation, protein carbonyl and hydroxyproline contents were measured. ETME showed inhibition of lipid peroxidation, protein oxidation and liver fibrosis. The serum markers and liver iron were lessened, whereas enhanced levels of liver antioxidant enzymes were detected in ETME-treated group. Furthermore, the histopathological observations also substantiated the protective effects of the extract. Several bioactive compounds identified by GC-MS may be the basis of hepatoprotective as well as antioxidant and iron-chelating effect of ETME. Currently available iron-chelating agents show several side effects and limitations which may be overcome by ETME, which suggest its benefit against pathology of iron overload-linked diseases. Hence, ETME can be used as a promising hepatoprotective agent. © 2014 The Society for Applied Microbiology.

  15. Detection of supernova neutrinos with neutrino-iron scattering

    International Nuclear Information System (INIS)

    Samana, A. R.; Bertulani, C. A.

    2008-01-01

    The ν e - 56 Fe cross section is evaluated in the projected quasiparticle random phase approximation (PQRPA). This model solves the puzzle observed in RPA for nuclei with mass around 12 C, because it is the only RPA model that treats the Pauli Principle correctly. The cross sections as a function of the incident neutrino energy are compared with recent theoretical calculations of similar models. The average cross section weighted with the flux spectrum yields a good agreement with the experimental data. The expected number of events in the detection of supernova neutrinos is calculated for the LVD detector, leading to an upper limit for the electron neutrino energy of particular importance in this experiment

  16. 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

  17. Plasma protein haptoglobin modulates renal iron loading

    DEFF Research Database (Denmark)

    Fagoonee, Sharmila; Gburek, Jakub; Hirsch, Emilio

    2005-01-01

    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....

  18. Raman hyperspectral imaging of iron transport across membranes in cells

    Science.gov (United States)

    Das, Anupam; Costa, Xavier Felipe; Khmaladze, Alexander; Barroso, Margarida; Sharikova, Anna

    2016-09-01

    Raman scattering microscopy is a powerful imaging technique used to identify chemical composition, structural and conformational state of molecules of complex samples in biology, biophysics, medicine and materials science. In this work, we have shown that Raman techniques allow the measurement of the iron content in protein mixtures and cells. Since the mechanisms of iron acquisition, storage, and excretion by cells are not completely understood, improved knowledge of iron metabolism can offer insight into many diseases in which iron plays a role in the pathogenic process, such as diabetes, neurodegenerative diseases, cancer, and metabolic syndrome. Understanding of the processes involved in cellular iron metabolism will improve our knowledge of cell functioning. It will also have a big impact on treatment of diseases caused by iron deficiency (anemias) and iron overload (hereditary hemochromatosis). Previously, Raman studies have shown substantial differences in spectra of transferrin with and without bound iron, thus proving that it is an appropriate technique to determine the levels of bound iron in the protein mixture. We have extended these studies to obtain hyperspectral images of transferrin in cells. By employing a Raman scanning microscope together with spectral detection by a highly sensitive back-illuminated cooled CCD camera, we were able to rapidly acquire and process images of fixed cells with chemical selectivity. We discuss and compare various methods of hyperspectral Raman image analysis and demonstrate the use of these methods to characterize cellular iron content without the need for dye labeling.

  19. 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.

  20. Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip.

    Science.gov (United States)

    Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M

    2016-02-17

    Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure.

  1. Methodology description for detection of cellular uptake of PVA coated superparamagnetic iron oxide nanoparticles (SPION) in synovial cells of sheep

    Energy Technology Data Exchange (ETDEWEB)

    Schoepf, Bernhard [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Neuberger, Tobias [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Schulze, Katja [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Petri, Alke [Powder Technology Laboratory, Institute of Materials, Swiss Federal Institute of Technology Lausanne, EPFL, MX-D Ecublens, 1015 Lausanne (Switzerland); Chastellain, Matthieu [Powder Technology Laboratory, Institute of Materials, Swiss Federal Institute of Technology Lausanne, EPFL, MX-D Ecublens, 1015 Lausanne (Switzerland); Hofmann, Margarete [MatSearch, Ch. Jean Pavillard 14, 1009 Pully (Switzerland); Hofmann, Heinrich [Powder Technology Laboratory, Institute of Materials, Swiss Federal Institute of Technology Lausanne, EPFL, MX-D Ecublens, 1015 Lausanne (Switzerland); Rechenberg, Brigitte von [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland)]. E-mail: bvonrechenberg@vetclinics.unizh.ch

    2005-05-15

    The detection of superparamagnetic iron oxide nanoparticles (SPION) in synoviocytes is reported. Synoviocytes were incubated for 2, 12, 24 and 48 h with 1.5 mg/ml of PVA coated SPION under the influence of magnets (12 h). Particles were well tolerated by the synoviocytes, were easily detected using the Turnbulls and Prussian blue reactions between 12 and 24 h.

  2. Nuclear resonance fluorescence: new technique for in vivo iron determination in man

    International Nuclear Information System (INIS)

    Vartsky, D.; Ellis, K.J.; Cohn, S.H.

    1979-01-01

    A technique for the measurement of body iron stores utilizing nuclear resonant scattering of gamma-rays has been developed. 847keV photons emitted from a gaseous 56 MnCl 2 source are resonantly scattered from 56 Fe present in the liver and are detected by two large volume Ge(Li) detectors. Due to the very narrow resonance of the absorption cross section the technique is very specific to the element under investigation. The spatial uniformity of activation, the sensitivity of the detection system and the limits of detection have been investigated. Measurements were made of liver of a man-like phantom. The sensitivity and the limit of detection obtained for the NRS technique developed in this study are adequate for detection of iron in livers of normal individuals and are certainly sufficient for livers of persons with iron overload

  3. Efficacy and safety of Iranian made Deferasirox (Osveral®in Iranian major thalassemic patients with transfusional iron overload: A one year prospective multicentric open-label non-comparative study

    Directory of Open Access Journals (Sweden)

    P Eshghi

    2011-07-01

    Full Text Available       Purpose of the study:to determine the efficacy, adverse effects and safety of a new Iranian generic product of deferasirox (Osveral® in Iranian transfusion dependent major thalassemic (TD-MT patients. Methods:In 9 main thalassemia treatment centers, all of TD-MT patients (aged ≥2 yrs with serum ferritin (SF levels≥1000 ng/ml, or >100 ml/kg of RBC transfusion ,who could not tolerate parental iron chelating were recruited regardless of their previous iron chelation therapy. Periodical clinical and laboratory evaluations were conducted for adverse effects (AEs. Primary efficacy end point was Mean of Relative Change of Serum Ferritin (MRC-SF from the baseline level during one year. Analysis of variance (ANOVA, t test, chi-square or Fisher exact test were used for statistic analysis appropriately (P values <0.05 were considered as statistical significant. Results:In 407 cases the male/female ratio was 0.98. Mean age was 11.5±7.4 (2-58 years. The mean of initiating dose of Osveral® and mean usage dose during the study was 23.5±4.9 mg/kg and 24.9 ± 4.9 mg/kg respectively. MRC-SF was -11.44% ±38.92 and it showed significant decline in SF (P value<0.001 one hundred and forty eight patients out of 407 patients experienced at least one. AE, the most common of them were transient increase in serum creatinin (97;24.1% and > 5 time increase in transaminases (24;5.89%.The causes of discontinuation of treatment were non-satisfactory treatment ( 24; 5.8%, poor or non-compliance of patients (21;5.1%, and adverse effects (13; 3.1% . Conclusion:A detailed comparison with similar studies on deferasirox (Exjade® shows a promising efficacy and safety for its Iranian generic product (Osveral ®.

  4. 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.

  5. Guardian: a router mechanism for extreme overload prevention

    Science.gov (United States)

    Jiang, Hao; Dovrolis, Constantinos

    2002-07-01

    Disasters such as the 9/11 attacks, as well as major and unpredictable events, can cause extreme network overload. By "extreme overload" we mean, first, that the offered load at a link is significantly higher than the link's capacity, and second, that the average throughput per session is too low. Under such conditions, the network can suffer from a form of "livelock" in which even though links are fully utilized, most users cannot complete their transfers. The underlying reasons are that the network carries many retransmitted packets, and that it services flows that are finally aborted by users or applications. To prevent extreme network overload, we propose a router mechanism called Guardian. Guardian is a form of admission control module that is automatically activated when it detects the onset of extreme overload at a network link. Guardian's objective is to allow at least some sessions to complete, rejecting new TCP or UDP sessions that would probably not manage to acquire a minimum acceptable throughput. Guardian does not require signalling, and it can be implemented using standard techniques for session counting and caching. This paper describes on-going work. As such, we focus on the motivation for the proposed mechanism, and on Guardian's main design.

  6. An iron detection system determines bacterial swarming initiation and biofilm formation

    NARCIS (Netherlands)

    Lin, Chuan-Sheng; Tsai, Yu-Huan; Chang, Chih-Jung; Tseng, Shun-Fu; Wu, Tsung-Ru; Lu, Chia-Chen; Wu, Ting-Shu; Lu, Jang-Jih; Horng, Jim-Tong; Martel, Jan; Ojcius, David M.; Lai, Hsin-Chih; Young, John D.; Andrews, S. C.; Robinson, A. K.; Rodriguez-Quinones, F.; Touati, D.; Yeom, J.; Imlay, J. A.; Park, W.; Marx, J. J.; Braun, V.; Hantke, K.; Cornelis, P.; Wei, Q.; Vinckx, T.; Troxell, B.; Hassan, H. M.; Verstraeten, N.; Lewis, K.; Hall-Stoodley, L.; Costerton, J. W.; Stoodley, P.; Kearns, D. B.; Losick, R.; Butler, M. T.; Wang, Q.; Harshey, R. M.; Lai, S.; Tremblay, J.; Deziel, E.; Overhage, J.; Bains, M.; Brazas, M. D.; Hancock, R. E.; Partridge, J. D.; Kim, W.; Surette, M. G.; Givskov, M.; Rather, P. N.; Houdt, R. Van; Michiels, C. W.; Mukherjee, S.; Inoue, T.; Frye, J. G.; McClelland, M.; McCarter, L.; Silverman, M.; Matilla, M. A.; Wu, Y.; Outten, F. W.; Singh, P. K.; Parsek, M. R.; Greenberg, E. P.; Welsh, M. J.; Banin, E.; Vasil, M. L.; Wosten, M. M.; Kox, L. F.; Chamnongpol, S.; Soncini, F. C.; Groisman, E. A.; Laub, M. T.; Goulian, M.; Krell, T.; Lai, H. C.; Lin, C. S.; Soo, P. C.; Tsai, Y. H.; Wei, J. R.; Wyckoff, E. E.; Mey, A. R.; Leimbach, A.; Fisher, C. F.; Payne, S. M.; Livak, K. J.; Schmittgen, T. D.; Clarke, M. B.; Hughes, D. T.; Zhu, C.; Boedeker, E. C.; Sperandio, V.; Stintzi, A.; Clarke-Pearson, M. F.; Brady, S. F.; Drake, E. J.; Gulick, A. M.; Qaisar, U.; Rowland, M. A.; Deeds, E. J.; Garcia, C. A.; Alcaraz, E. S.; Franco, M. A.; Rossi, B. N. Passerini de; Mehi, O.; Skaar, E. P.; Visaggio, D.; Nishino, K.; Dietz, P.; Gerlach, G.; Beier, D.; Bustin, S. A.; Schwyn, B.; Neilands, J. B.

    2016-01-01

    Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising

  7. Ultra-small particles of iron oxide as peroxidase for immunohistochemical detection

    International Nuclear Information System (INIS)

    Wu Yihang; Song Mengjie; Zhang Xiaoqing; Zhang Yu; Wang Chunyu; Gu Ning; Xin Zhuang; Li Suyi

    2011-01-01

    Dimercaptosuccinic acid (DMSA) modified ultra-small particles of iron oxide (USPIO) were synthesized through a two-step process. The first step: oleic acid (OA) capped Fe 3 O 4 (OA-USPIO) were synthesized by a novel oxidation coprecipitation method in H 2 O/DMSO mixing system, where DMSO acts as an oxidant simultaneously. The second step: OA was replaced by DMSA to obtain water-soluble nanoparticles. The as-synthesized nanoparticles were characterized by TEM, FTIR, TGA, VSM, DLS, EDS and UV-vis. Hydrodynamic sizes and Peroxidase-like catalytic activity of the nanoparticles were investigated. The hydrodynamic sizes of the nanoparticles (around 24.4 nm) were well suited to developing stable nanoprobes for bio-detection. The kinetic studies were performed to quantitatively evaluate the catalytic ability of the peroxidase-like nanoparticles. The calculated kinetic parameters indicated that the DMSA-USPIO possesses high catalytic activity. Based on the high activity, immunohistochemical experiments were established: using low-cost nanoparticles as the enzyme instead of expensive HRP, Nimotuzumab was conjugated onto the surface of the nanoparticles to construct a kind of ultra-small nanoprobe which was employed to detect epidermal growth factor receptor (EGFR) over-expressed on the membrane of esophageal cancer cell. The proper sizes of the probes and the result of membranous immunohistochemical staining suggest that the probes can be served as a useful diagnostic reagent for bio-detection.

  8. 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

  9. Intelligent overload control for composite web services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Živković, M.; 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

  10. 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)

  11. 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.

  12. A Combination of Fecal Immunochemical Test Results and Iron Deficiency Anemia for Detection of Advanced Colorectal Neoplasia in Asymptomatic Men

    OpenAIRE

    Kim, Nam Hee; Lee, Mi Yeon; Park, Jung Ho; Park, Dong Il; Sohn, Chong Il; Choi, Kyuyong; Jung, Yoon Suk

    2017-01-01

    Purpose A substantial proportion of patients with colorectal cancer (CRC) present with iron deficiency anemia (IDA), and fecal immunochemical test (FIT) has proven to be an effective method for detecting the majority of CRC cases. A combination strategy of FIT results and IDA may be useful for risk stratification for detecting advanced colorectal neoplasia (ACRN). We compared the prevalence of ACRN among four groups stratified by FIT results and the presence of IDA. Materials and Methods A cr...

  13. Detection of copper, lead, cadmium and iron in wine using electronic tongue sensor system.

    Science.gov (United States)

    Simões da Costa, A M; Delgadillo, I; Rudnitskaya, A

    2014-11-01

    An array of 10 potentiometric chemical sensors has been applied to the detection of total Fe, Cu, Pb and Cd content in digested wine. As digestion of organic matter of wine is necessary prior to the trace metal detection using potentiometric sensors, sample preparation procedures have been optimized. Different variants of wet and microwave digestion and dry ashing, 14 conditions in total, have been tested. Decomposition of organic matter was assessed using Fourier transform mid-infrared spectroscopy and total phenolic content. Dry ashing was found to be the most effective method of wine digestion. Measurements with sensors in individual solutions of Fe(III), Cu(II), Pb(II) and Cd(II) prepared on different backgrounds have shown that their detection limits were below typical concentration levels of these metals in wines and, in the case of Cu, Pb and Cd below maximum allowed concentrations. Detection of Fe in digested wine samples was possible using discrete iron-sensitive sensors with chalcogenide glass membranes with RMSEP of 0.05 mmol L(-1) in the concentration range from 0.0786 to 0.472 mmol L(-1). Low concentration levels of Cu, Pb and Cd in wine and cross-sensitivity of respective sensors resulted in the non-linearity of their responses, requiring back-propagation neural network for the calibration. Calibration models have been calculated using measurements in the model mixed solutions containing all three metals and a set of digested wine sample. RMSEP values for Cu, Pb and Cd were 3.9, 39 and 1.2 μmol L(-1) in model solutions and 2, 150 and 1 μmol L(-1) in digested wine samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Clinical management of gastrointestinal disturbances in patients with myelodysplastic syndromes receiving iron chelation treatment with deferasirox

    NARCIS (Netherlands)

    Nolte, F.; Angelucci, E.; Beris, P.; Macwhannell, A.; Selleslag, D.; Schumann, C.; Xicoy, B.; Almeida, A.; Guerci-Bresler, A.; Sliwa, T.; Muus, P.; Porter, J.; Hofmann, W.K.

    2011-01-01

    Myelodysplastic syndromes are characterized by ineffective hematopoiesis resulting in peripheral cytopenias. The majority of patients is dependent on regular transfusions of packed red blood cells leading to a secondary iron overload which might result in organ damage. Therefore, sufficient iron

  15. 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

  16. 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.

  17. 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

  18. Deferasirox protects against iron-induced hepatic injury in Mongolian gerbil.

    Science.gov (United States)

    Al-Rousan, Rabaa M; Rice, Kevin M; Katta, Anjaiah; Laurino, Joseph; Walker, Ernest M; Wu, Miaozong; Triest, William E; Blough, Eric R

    2011-06-01

    Iron overload is associated with an increased risk of liver complications including fibrosis, cirrhosis, and hepatocellular carcinoma. Deferasirox is a new oral chelator with high iron-binding potency and selectivity. Here we investigate the ability of deferasirox to remove excessive hepatic iron and prevent iron-induced hepatic injury. Adult male Mongolian gerbils were divided into 3 groups (n=5/group)-control, iron overload (100 mg iron-dextran/kg body weight/5 days; intraperitoneal for 10 weeks), and iron overload followed by deferasirox treatment (100 mg deferasirox/kg body weight/d; pulse oral for 1 or 3 months). Compared with the nontreated iron overload group, deferasirox reduced hepatic iron concentration by 44% after 3 months of treatment (Pdeferasirox treatment, and no evidence of lipid accumulation was observed. Immunoblotting demonstrated that iron overload caused approximately 2-fold increase in hepatic ferritin expression (Pdeferasirox treatment (PDeferasirox treatment also was associated with reduced hepatic protein oxidation, superoxide abundance, and cell death. The percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in the deferasirox-treated livers was 41% lower than that of iron overloaded group (Pdeferasirox treatment. These findings suggest that deferasirox may confer protection against iron-induced hepatic toxicity. Published by Mosby, Inc.

  19. Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

    Directory of Open Access Journals (Sweden)

    Dinusha N. Udukala

    2016-03-01

    Full Text Available Proteases, including matrix metalloproteinases (MMPs, tissue serine proteases, and cathepsins (CTS exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenylporphyrin (TCPP that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5 that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA, MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

  20. Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection

    Directory of Open Access Journals (Sweden)

    Murali K. Matta

    2018-02-01

    Full Text Available A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI, transferrin bound iron (TBI, drug bound iron (DI and total iron (TI in the same rat serum sample after intravenous (IV administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®. Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2 of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg.

  1. Overload protection device for pulsed electric systems

    International Nuclear Information System (INIS)

    Glushchenko, V.G.; Kurskov, I.A.; Semina, R.S.

    1976-01-01

    Results of pulsed electric system protection development from effective pulse current overload depending on pulse duration are described. An integrating circuit, charge resistance of which is connected in parallel with a stabilitron, is used in a protection diagram. Given were time responses of overload protection of an output lens of slow root particle extraction channel from synchrophasotron; the responses have been obtained by the experimental and calculation methods

  2. 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.

  3. 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.)

  4. Dietary iron rural blacks overload In southern African

    African Journals Online (AJOL)

    1990-09-15

    Sep 15, 1990 ... ferritin, C-reactive protein (CRP), 1'-glutamyltransferase (GGn and serological screening for hepatitis B ... with the condition include: portal fibrosis and cirrhosis of the liver/,J glucose intolerance;4 scurvy and ... or a Coulter Model-S electronic counter with standard cali- bration. The ESR was determined by ...

  5. Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients.

    Science.gov (United States)

    Mudge, David W; Tan, Ken-Soon; Miles, Rhianna; Johnson, David W; Campbell, Scott B; Hawley, Carmel M; Isbel, Nicole M; Van Eps, Carolyn L; Nicol, David L

    2009-06-06

    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. 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 > or =110 g/l in iron-treated patients, assuming an alpha 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 microg/l), or previous intolerance of either oral or intravenous iron supplements. If the trial shows a reduction in the time to correction of anaemia with intravenous iron or less side effects than oral iron, then intravenous iron may

  6. The detection of iron protoporphyrin (heme b) in phytoplankton and marine particulate material by electrospray ionisation mass spectrometry – comparison with diode array detection

    Energy Technology Data Exchange (ETDEWEB)

    Gledhill, Martha, E-mail: m.gledhill@geomar.de

    2014-09-02

    Highlights: • Mass spectrometry was applied to the analysis of heme b in biological material. • Optimal conditions involved selective reactant monitoring of the heme b product ion. • The isotopic signature for this iron tetrapyrrole further improved selectivity. • Mass spectrometry and spectrophotometry were compared for heme b analysis. • Combining techniques made a powerful tool for analysis of heme in marine microbes. - Abstract: A mass spectrometric (MS) method for the identification of iron protoporphyrin (IX) (FePTP, heme b) in marine particulate material and phytoplankton is described. Electrospray ionisation of FePTP produced the molecular Fe(III)PTP{sup +} ion (m/z = 616) or the pseudomolecular [Fe(II)PTP + H]{sup +} ion (m/z = 617), depending on the oxidation state of the central iron ion. Collision induced dissociation (CID) in the ion trap mass spectrometer resulted in a single detected product ion (m/z = 557) indicative of loss of ethanoic acid from a carboxylic acid side chain. Widening the isolation width to 616 ± 3 resulted in production of a mass spectrum demonstrating the distinctive isotopic ratio of the iron containing fragment, further increasing the specificity of the analysis. Selective reactant monitoring (SRM) of the fragment ion (m/z = 557) was applied to the detection of FePTP after chromatography of ammoniacal OGP extracts of marine samples. The detection limit for FePTP analysed by SRM after chromatography was 1.2 ± 0.5 fmol. For phytoplankton samples, reasonably good agreement was achieved between results obtained with SRM and those obtained by monitoring absorbance at λ = 400 nm using a diode array detector (DAD). Use of SRM for analysis of particulate material obtained from the high latitude North Atlantic allowed for the analysis of FePTP in the presence of a co-eluting compound that interfered with detection by DAD. Simultaneous collection of mass spectra from m/z = 300 to 1500 resulted in identification of the

  7. Hydroxyl radical-modified fibrinogen as a marker of thrombosis: the role of iron.

    Science.gov (United States)

    Lipinski, B; Pretorius, E

    2012-07-01

    Excessive free iron in blood and in organ tissues (so called iron overload) has been observed in degenerative diseases such as atherosclerosis, cancer, neurological, and certain autoimmune diseases, in which fibrin-like deposits are also found. Although most of the body iron is bound to hemoglobin and myoglobin in a divalent ferrous form, a certain amount of iron exists in blood as a trivalent (ferric) ion. This particular chemical state of iron has been shown to be toxic to the human body when not controlled by endogenous and/or dietary chelating agents. Experiments described in this paper show for the first time that ferric ions (Fe(3+)) can generate hydroxyl radicals without participation of any redox agent, thus making it a special case of the Fenton reaction. Ferric chloride was also demonstrated to induce aggregation of purified fibrinogen at the same molar concentrations that were used for the generation of hydroxyl radicals. Iron-aggregated fibrinogen, by contrast to native molecule, could not be dissociated into polypeptide subunit chains as shown in a polyacrylamide gel electrophoresis. The mechanism of this phenomenon is very likely based on hydroxyl radical-induced modification of fibrinogen tertiary structure with the formation of insoluble aggregates resistant to enzymatic and chemical degradations. Soluble modified fibrinogen species can be determined in blood of thrombotic patients by the reaction with protamine sulfate and/or by scanning electron microscopy. In view of these findings, it is postulated that iron-induced alterations in fibrinogen structure is involved in pathogenesis of certain degenerative diseases associated with iron overload and persistent thrombosis. It is concluded that the detection of hydroxyl radical-modified fibrinogen may be utilized as a marker of a thrombotic condition in human subjects.

  8. Fatigue crack growth behavior and overload effect of AISI 304 stainless steel in different atmospheres

    Science.gov (United States)

    Kelestemur, Mehmet Halidun

    1998-12-01

    acceleration right after the overload application was observed. However, the acceleration was not detected on the interior of the material along the crack tip. Only the surface in which the plane stress was effective showed crack propagation in acceleration zone. This result were explained by strain hardening and plastic deformation of grains at the overload zone. Discontinuous crack closure occurred following the overload. In other words, at the overload position, fracture surfaces on which stretching occurred came into contact at high stress intensity factor values and far away from the overload position. As a result of discontinuous crack closure, crack opening or closing data were very high although the fatigue crack growth rate reached its original value.

  9. 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

  10. 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...

  11. Iron oxide nanostructured electrodes for detection of copper(II) ions.

    Science.gov (United States)

    Santos, J G M; Souza, J R; Letti, C J; Soler, M A G; Morais, P C; Pereira-da-Silva, M A; Paterno, L G

    2014-09-01

    Iron oxide nanostructured (ION) electrodes were assembled layer-by-layer onto ITO-coated glass substrates and their structure, morphology, and electrochemical properties were investigated, the latter aiming at the development of a chemical sensor for Cu2+. The electrodes were built by immersing the substrate alternately into an aqueous colloidal suspension of positively charged magnetite nanoparticles (np-Fe3O4, 8 nm) and an aqueous solution of anionic sodium sulfonated polystyrene (PSS). The adsorbed amount of both materials was monitored ex-situ by UV-vis spectroscopy and it was found to increase linearly with the number of deposition cycles. The resulting films feature a densely-packed structure of magnetite nanoparticles, as suggested by AFM and Raman spectroscopy, respectively. Cyclic voltammograms of electrodes immersed in acetate buffer (pH 4.6) displayed three electrochemical events that were tentatively ascribed to the reduction of Fe(III) oxy-hydroxide to magnetite, reduction of maghemite to magnetite, and finally oxidation of magnetite to maghemite. The effect of np-Fe3O4/PSS bilayers on the ION electrode performance was to increase the anodic and cathodic currents produced during electrochemical oxidation-reduction of the Fe(CN)(3-/4-) redox couple. With more bilayers, the ION electrode provided higher anodic/cathodic currents. Moreover, the redox couple exhibited a quasi-reversible behavior at the ION electrode as already observed with other working electrode systems. Fitting of voltammetry data provided the apparent electron transfer constants, which were found to be higher in ION electrodes for both redox couples (Fe(CN)(3-/4-) and Cu(2+/0)). By means of differential pulsed anodic stripping voltammetry, the ION electrodes were found to respond linearly to the presence of Cu2+ in aqueous samples in the range between 1.0 and 8.0 x 10(-6) mol x L(-1) and displayed a limit of detection of 0.3 x 10(-8) mol x L(-1). The sensitivity was - 0.6μA/μmol x L

  12. Astrophysical detection of heavy-particle-induced spectral shifts in muonic iron

    International Nuclear Information System (INIS)

    Guffin, J.; Nixon, G.; Fischbach, E.; Javorsek, D. II; Colafrancesco, S.

    2002-01-01

    By significantly increasing the nuclear mass, a strongly interacting massive particle (SIMP) bound to an iron nucleus would cause a characteristic change in the spectrum of muonic iron. At temperatures high enough that such atoms are completely stripped of electrons, the effect is directly observable as a 0.2% shift in the energies of high angular momentum states. This phenomenon provides a new test for the existence of SIMPs, which have been proposed as dark matter candidates, and as candidates for the lightest supersymmetric particle

  13. Adrenal and renal corticomedullary junction iron deposition in red cell aplasia

    Energy Technology Data Exchange (ETDEWEB)

    Rakow-Penner, Rebecca; Vasanawala, Shreyas [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States); Glader, Bert [Stanford University School of Medicine, Department of Pediatric Hematology and Oncology, Stanford, CA (United States); Yu, Huanzhou [Global MR Applied Science Lab, GE Healthcare, Menlo Park, CA (United States)

    2010-12-15

    Iron deposition can occur in the kidneys as a result of hemolysis or extensive iron overload from transfusions. With T2* MRI, renal iron deposition can be visualized. In this report, renal corticomedullary junction iron deposition is noted using T2* MRI in a boy with red cell aplasia. The renal corticomedullary junction iron deposition is an indication of the severity of his iron overload. This is an unusual finding and brings clinical attention to the boy's renal function for further evaluation. (orig.)

  14. The transplant iron score as a predictor of stem cell transplant survival

    Directory of Open Access Journals (Sweden)

    Keung Yi K

    2009-10-01

    Full Text Available Abstract Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1 greater than 25 red cell units transfused prior to transplantation; (2 serum ferritin > 1000 ng/ml; and (3 a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3 was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01 primarily attributable to an increase in early treatment-related deaths (p = 0.02 and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (≥ 2 was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections.

  15. Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

    Directory of Open Access Journals (Sweden)

    Monica Pinheiro de Almeida Verissimo

    2013-01-01

    Full Text Available In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA, presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams and the role of T2* magnetic resonance imaging (MRI to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

  16. 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.

  17. Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major.

    Science.gov (United States)

    Meloni, Antonella; Restaino, Gennaro; Borsellino, Zelia; Caruso, Vincenzo; Spasiano, Anna; Zuccarelli, Angelo; Valeri, Gianluca; Toia, Patrizia; Salvatori, Cristina; Positano, Vincenzo; Midiri, Massimo; Pepe, Alessia

    2014-12-20

    The multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. We considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. We identified 4 groups of patients: 138 with homogeneous MIO (all segments with T2* heart iron (global heart T2* heart iron, and 339 with no MIO (all segments with T2* ≥ 20 ms). Compared to patients with no MIO, patients with homogeneous MIO were more likely to have cardiac complications (odds ratio-OR = 2.67), heart failure (OR = 2.54), LV dysfunction (OR = 5.59), and RV dysfunction (OR = 2.26); patients with heterogeneous MIO and significant global heart iron were more likely to have heart failure (OR = 2.38) and LV dysfunction (OR = 2.39). Cardiac complications, heart failure and dysfunction were correlated with MIO distribution with an increasing risk from the TM patients with no MIO to those with homogeneous MIO. Using a segmental approach, early iron deposit or homogeneous MIO patterns can be characterized to better tailor chelation therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Magnetic relaxation switch and colorimetric detection of thrombin using aptamer-functionalized gold-coated iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Liang Guohai; Cai Shaoyu; Zhang Peng [Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433 (China); Peng Youyuan [Department of Chemistry, Quanzhou Normal University, Quanzhou 362000 (China); Chen Hui; Zhang Song [Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433 (China); Kong Jilie, E-mail: jlkong@fudan.edu.cn [Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433 (China)

    2011-03-18

    We describe a sensitive biosensing system combining magnetic relaxation switch diagnosis and colorimetric detection of human {alpha}-thrombin, based on the aptamer-protein interaction induced aggregation of Fe{sub 3}O{sub 4}-Au nanoparticles. To demonstrate the concept, gold-coated iron oxide nanoparticle was synthesized by iterative reduction of HAuCl{sub 4} onto the dextran-coated Fe{sub 3}O{sub 4} nanoparticles. The resulting core-shell structure had a flowerlike shape with pretty narrow size distribution (referred to as 'nanorose'). The two aptamers corresponding to human {alpha}-thrombin were conjugated separately to two distinct nanorose populations. Once a solution containing human {alpha}-thrombin was introduced, the nanoroses switched from a well dispersed state to an aggregated one, leading to a change in the spin-spin relaxation time (T{sub 2}) as well as the UV-Vis absorption spectra of the solution. Thus the qualitative and quantitative detection method for human {alpha}-thrombin was established. The dual-mode detection is clearly advantageous in obtaining a more reliable result; the detection range is widened as well. By using the dual-mode detection method, a detectable T{sub 2} change is observed with 1.0 nM human {alpha}-thrombin, and the detection range is from 1.6 nM to 30.4 nM.

  19. [The Iron-man: a case-report].

    Science.gov (United States)

    Einarsdóttir, Margrét Jóna; Reykdal, Sigrún Edda; Vidarsson, Brynjar

    2011-01-01

    The most common cause of microcytic anemia is iron deficiency. We report a 29 year old man with history of dyspnea, fatigue and severe microcytic anemia despite iron therapy for 3 years. Blood transfusions elevated the hemoglobin levels temporarily, but iv iron did not. Bone marrow showed sideroblastic anemia. The anemia resolved with pyridoxine treatment but severe iron overload necessitated multiple phlebotomies. Today the patient is asymptomatic on pyridoxine with a normal hemoglobin level.

  20. Rapid monitoring of iron-chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate

    Science.gov (United States)

    Kim, Daniel; Jensen, Jens H.; Wu, Ed X.; Feng, Li; Au, Wing-Yan; Cheung, Jerry S.; Ha, Shau-Yin; Sheth, Sujit S.; Brittenham, Gary M.

    2011-01-01

    In iron overload, almost all the excess iron is stored intracellularly as rapidly mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in cytosolic iron may produce oxidative damage that ultimately results in cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool, measurements of ferritin iron potentially provide a clinically useful indicator of changes in cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron used clinically, the effective transverse relaxation rate (R2*), is principally influenced by hemosiderin iron and changes only slowly over several months, even with intensive iron-chelating therapy. Another conventional CMR index of cardiac iron, the transverse relaxation rate (R2), is sensitive to both hemosiderin iron and ferritin iron. We have developed a new MRI measure, the ‘reduced transverse relaxation rate’ (RR2), and have proposed in previous studies that this measure is primarily sensitive to ferritin iron and largely independent of hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We hypothesized that RR2 could detect changes produced by 1 week of iron-chelating therapy in patients with transfusion-dependent thalassemia. We imaged 10 patients with thalassemia major at 1.5 T in mid-ventricular short-axis planes of the heart, initially after suspending iron-chelating therapy for 1 week and subsequently after resuming oral deferasirox. After resuming iron-chelating therapy, significant decreases were observed in the mean myocardial RR2 (7.8%, p 0.90). Although the difference between changes in RR2 and R2 was not significant (p > 0.3), RR2 was consistently more sensitive than R2 (and R2*) to the resumption of iron-chelating therapy, as judged by the effect sizes of relaxation rate differences detected. Although further studies are needed, myocardial RR2 may be a promising

  1. 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.

  2. Detection and mapping of the iron ore occurrence in the sea floor sediments in the coastal zone of the Sepetiba Bay. Rio de Janeiro. Brasil

    International Nuclear Information System (INIS)

    Vieira, P.

    2010-01-01

    This work is about the detection and mapping of the iron occurrence in the sea floor sediments in the coastal zone of the Sepetiba Bay. Rio de Janeiro. Brasil. The results of geochemical analysis revealed that the area around the mangrove forest located near the Itacuruca channel, the perpendicular direction to the Muriqui Yacht Club channel and the immediate vicinity of the the Guaiba Island Terminal were respectively the areas of highest iron ore concentration

  3. 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.

  4. 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.

  5. Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions

    Directory of Open Access Journals (Sweden)

    Saliba AN

    2015-06-01

    Full Text Available Antoine N Saliba, Afif R Harb, Ali T Taher Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut, Beirut, Lebanon Abstract: Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. Keywords: thalassemia, transfusion-dependent thalassemia, iron overload, iron chelation therapy, transfusion

  6. Effect of surface coating on the biocompatibility and in vivo MRI detection of iron oxide nanoparticles after intrapulmonary administration.

    Science.gov (United States)

    Al Faraj, Achraf; Shaik, Abjal Pasha; Shaik, Asma Sultana

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted special attention as novel nanoprobes capable of improving both the therapy and diagnosis of lung diseases. For safe prospective clinical applications, their biocompatibility has to be assessed after intrapulmonary administration. This study was therefore conducted to understand the biological impact of SPIONs and their further surface-functionalization with polyethylene glycol (PEG) having either negative (i.e. carboxyl) or positive (i.e. amine) terminal in a 1-month longitudinal study following acute and sub-acute exposures. Noninvasive free-breathing MR imaging protocols were first optimized to validate SPIONs detection in the lung and investigate possible subsequent systemic translocation to abdominal organs. Pulmonary Magnetic Resonance Imaging (MRI) allowed successful in vivo detection of SPIONs in the lung using ultra-short echo time sequence. Following high-dose lung administration, MR imaging performed on abdominal organs detected transient accumulation of SPIONs in the liver. Iron quantification using Inductive coupled plasma - Mass mass spectroscopy (ICP-MS) confirmed MRI readouts. Oxidative stress induction and genotoxicity were then conducted to evaluate the biocompatibility of SPIONs with their different formulations in a mouse model. A significant increase in lipid peroxidation was observed in both acute and sub-acute sets and found to regress in a time-dependent manner. PEG functionalized SPIONs revealed a lower effect with no difference between both terminal modifications. Genotoxicity assessments revealed an increase in DNA damage and gene expression of CCL-17 and IL-10 biomarkers following SPIONs administration, which was significantly higher than surface-modified nanoparticles and decreased in a time-dependent manner. However, SPIONs with carboxyl terminal showed a slightly prominent effect compared to amine modification.

  7. Detection of Dientamoeba fragilis in patients with HIV/AIDS by using a simplified iron hematoxylin technique

    Directory of Open Access Journals (Sweden)

    Juliana Alves Garcia

    2012-04-01

    Full Text Available INTRODUCTION: Studies strongly indicate Dientamoeba fragilis as one of the causes of diarrhea in human immunodeficiency virus (HIV patients. METHODS: The objective of the present study was to evaluate the prevalence of D. fragilis associated with the causes of diarrhea in 82 HIV/ AIDS patients hospitalized at the Instituto de Infectologia Emílio Ribas from September 2006 to November 2008. RESULTS: In total, 105 samples were collected from 82 patients. Unprotected sex was the most frequent cause of HIV infection (46.3%, followed by the use of injectable or non-injectable drugs (14.6%. Patients presented with viral loads of 49-750,000 copies/ mL (average: 73,849 ± 124,850 copies/mL and CD4 counts ranging of 2-1,306 cells/mm³ (average: 159 ± 250 cells/mm³. On an average, the odds of obtaining a positive result by using the other techniques (Hoffman, Pons and Janer or Lutz; Ritchie were 2.7 times higher than the chance of obtaining a positive result by using the simplified iron hematoxylin method. Significant differences were found between the methods (p = 0.003. CONCLUSIONS: The other techniques can detect a significantly greater amount of parasites than the simplified iron hematoxylin method, especially with respect to Isospora belli, Cryptosporidium sp., Schistosoma mansoni, and Strongyloides stercoralis, which were not detected using hematoxylin. Endolimax nana and D. fragilis were detected more frequently on using hematoxylin, and the only parasite not found by the other methods was D. fragilis.

  8. 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

  9. SQUID biosusceptometry in the measurement of hepatic iron

    Energy Technology Data Exchange (ETDEWEB)

    Sheth, Sujit [Department of Pediatrics, Columbia University College of Physicians and Surgeons, Harkness Pavilion, Room HP570, 180 Fort Washington Avenue, NY 10032, New York (United States)

    2003-06-01

    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.)

  10. CQ Switch Analysis under Traffic Overload

    Directory of Open Access Journals (Sweden)

    I. Maljević

    2011-06-01

    Full Text Available An analysis of 2x2 crossbar packet switch with buffers at crosspoints and round robin scheduling algorithm is presented in this paper. The analysis is performed for a non-admissible traffic pattern, where output ports are overloaded. The case of full offered load is observed and output ports are loaded with packets that have different arrival probabilities. In addition to the parameters that are commonly observed in such an analysis (throughput and average packet delay, memory requirements for the implementation of the buffer, as well as fair representation when servicing the buffer - the so-called fairness are also analyzed. The results show that even for a switch with a small number of ports very large buffers should be implemented, if we want to achieve satisfactory performance under traffic overload.

  11. Detection of iron-depositing Pedomicrobium species in native biofilms from the Odertal National Park by a new, specific FISH probe.

    Science.gov (United States)

    Braun, Burga; Richert, Inga; Szewzyk, Ulrich

    2009-10-01

    Iron-depositing bacteria play an important role in technical water systems (water wells, distribution systems) due to their intense deposition of iron oxides and resulting clogging effects. Pedomicrobium is known as iron- and manganese-oxidizing and accumulating bacterium. The ability to detect and quantify members of this species in biofilm communities is therefore desirable. In this study the fluorescence in situ hybridization (FISH) method was used to detect Pedomicrobium in iron and manganese incrusted biofilms. Based on comparative sequence analysis, we designed and evaluated a specific oligonucleotide probe (Pedo 1250) complementary to the hypervariable region 8 of the 16S rRNA gene for Pedomicrobium. Probe specificities were tested against 3 different strains of Pedomicrobium and Sphingobium yanoikuyae as non-target organism. Using optimized conditions the probe hybridized with all tested strains of Pedomicrobium with an efficiency of 80%. The non-target organism showed no hybridization signals. The new FISH probe was applied successfully for the in situ detection of Pedomicrobium in different native, iron-depositing biofilms. The hybridization results of native bioflims using probe Pedo_1250 agreed with the results of the morphological structure of Pedomicrobium bioflims based on scanning electron microscopy.

  12. Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

    NARCIS (Netherlands)

    Benyamin, Beben; Esko, Tonu; Ried, Janina S.; Radhakrishnan, Aparna; Vermeulen, Sita H.; Traglia, Michela; Goegele, Martin; Anderson, Denise; Broer, Linda; Podmore, Clara; Luan, Jian'an; Kutalik, Zoltan; Sanna, Serena; van der Meer, Peter; Tanaka, Toshiko; Wang, Fudi; Westra, Harm-Jan; Franke, Lude; Mihailov, Evelin; Milani, Lili; Haeldin, Jonas; Winkelmann, Juliane; Meitinger, Thomas; Thiery, Joachim; Peters, Annette; Waldenberger, Melanie; Rendon, Augusto; Jolley, Jennifer; Sambrook, Jennifer; Kiemeney, Lambertus A.; Sweep, Fred C.; Sala, Cinzia F.; Schwienbacher, Christine; Pichler, Irene; Hui, Jennie; Demirkan, Ayse; Isaacs, Aaron; Amin, Najaf; Steri, Maristella; Waeber, Gerard; Verweij, Niek; Powell, Joseph E.; Nyholt, Dale R.; Heath, Andrew C.; Madden, Pamela A. F.; Visscher, Peter M.; Wright, Margaret J.; Montgomery, Grant W.; Martin, Nicholas G.; Hernandez, Dena; Bandinelli, Stefania; van der Harst, Pim; Uda, Manuela; Vollenweider, Peter; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; van Duijn, Cornelia; Beilby, John; Pramstaller, Peter P.; Hicks, Andrew A.; Ouwehand, Willem H.; Oexle, Konrad; Gieger, Christian; Metspalu, Andres; Camaschella, Clara; Toniolo, Daniela; Swinkels, Dorine W.; Whitfield, John B.

    2014-01-01

    Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find

  13. Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

    NARCIS (Netherlands)

    B. Benyamin (Beben); T. Esko (Tõnu); J.S. Ried (Janina); A. Radhakrishnan (Aparna); S.H.H.M. Vermeulen (Sita); M. Traglia (Michela); M. Gögele (Martin); D. Anderson (Denise); L. Broer (Linda); C. Podmore (Clara); J. Luan; Z. Kutalik (Zoltán); S. Sanna (Serena); P. van der Meer (Peter); T. Tanaka (Toshiko); F. Wang (Fudi); H.J. Westra (Harm-Jan); L. Franke (Lude); E. Mihailov (Evelin); L. Milani (Lili); J. Häldin (Jonas); B. Winkelmann; T. Meitinger (Thomas); J. Thiery (Joachim); A. Peters (Annette); M. Waldenberger (Melanie); A. Rendon (Augusto); G.J. Jolley (Jason); J.G. Sambrook (Jennifer); L.A.L.M. Kiemeney (Bart); F.C. Sweep (Fred); C. Sala (Cinzia); C. Schwienbacher (Christine); I. Pichler (Irene); J. Hui (Jennie); A. Demirkan (Ayşe); A. Isaacs (Aaron); N. Amin (Najaf); M. Steri (Maristella); G. Waeber (Gérard); N. Verweij (Niek); J.E. Powell (Joseph); A.S. Dimas (Antigone); A.C. Heath (Andrew); P.A. Madden (Pamela); P.M. Visscher (Peter); M.J. Wright (Margaret); G.W. Montgomery (Grant); N.G. Martin (Nicholas); D.G. Hernandez (Dena); S. Bandinelli (Stefania); P. van der Harst (Pim); M. Uda (Manuela); P. Vollenweider (Peter); R.A. Scott (Robert); C. Langenberg (Claudia); N.J. Wareham (Nick); C.M. van Duijn (Cornelia); J. Beilby (John); P.P. Pramstaller (Peter Paul); A.A. Hicks (Andrew); W.H. Ouwehand (Willem); K. Oexle (Konrad); C. Gieger (Christian); A. Metspalu (Andres); C. Camaschella (Clara); D. Toniolo (Daniela); D.W. Swinkels (Dorine); J. Whitfield (John)

    2014-01-01

    textabstractVariation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972

  14. Advances in iron chelation therapy: transitioning to a new oral formulation

    OpenAIRE

    Shah, Nirmish R.

    2017-01-01

    Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consid...

  15. Magnetic Iron Oxide Nanoparticles and a Polydiacetylene Coating to Create a Biocompatible and Stable Molecule for Use in Cancer Diagnostics and Early Detection in Molecular Medicine

    Science.gov (United States)

    Bhatnagar, Shweta

    Earlier cancer detection and diagnosis is essential to prevent cancer mortality in nanomedicine and nanotechnology. Fluorescence and magnetic signals provide a way for earlier detection through imaging systems. Magnetic iron oxide nanoparticles have a superparamagnetism feature that allows them to act as contrast agents that can be detected through a magnetic resonance imaging system. These iron oxide cores have a polymer coating around them to provide stability, prevent aggregation, and allow for biocompatibility within the body. In addition, these functional coatings can have ligands and peptides for detection and therapy purposes. One functional coating is a polydiacetylene coating due to its chromatic and optical properties. When polymerized, it has the ability to change color in the visible spectrum to blue (not a fluorescent signal) and when heated, it changes to a red color (fluorescent signal). This way a strong and stable layer is formed around the iron oxide cores. These coatings are placed on the iron cores using a modified dual solvent exchange method, in which DMSO is slowly replaced by water without the use of organic solvents previous used. In addition, these nanoparticles can then be PEGylated, which provides a more stable and water soluble compound in aqueous solutions. Measurements can be taken through dynamic light scattering for size distributions and zeta potential and the Nanodrop for absorbance. Ideal sizes are about 30 nm for MNPs. Moreover, for future directions, there can be more molecules attached to the coated layers to use for molecular detection and analysis.

  16. Dispersive liquid-liquid microextraction coupled with digital image colorimetric analysis for detection of total iron in water and food samples.

    Science.gov (United States)

    Peng, Bo; Chen, Guorong; Li, Kai; Zhou, Min; Zhang, Ji; Zhao, Shengguo

    2017-09-01

    A simple and low cost assay for total iron in various samples based on dispersive liquid-liquid microextraction (DLLME) coupled with digital scanning image analysis was proposed. Orthogonal experiment design was utilized to optimize the amount of extraction solvent and disperser solvent, O-phenanthroline concentration and buffer pH. Under the optimum conditions, the calibration curve was linear over the range of 0.047-1.0μgmL -1 (R 2 >0.99) of iron. The limit of detection (LOD) for iron was 14.1μgL -1 and limit of quantification (LOQ) was 46.5μgL -1 . The relative standard deviations for seven replicate determinations of 0.5μgmL -1 of iron was 3.75%. The method was successfully applied for analysis of total iron in water and food samples without using any spectral instrument and it could have a potential industrial impact in developing fast and portable devices to analyze the iron content in water and certain foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Scavenger Receptor-AI-Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions

    NARCIS (Netherlands)

    Segers, Filip M. E.; den Adel, Brigit; Bot, Ilze; van der Graaf, Linda M.; van der Veer, Eric P.; Gonzalez, Walter; Raynal, Isabelle; de Winther, Menno; Wodzig, Will K.; Poelmann, Robert E.; van Berkel, Theo J. C.; van der Weerd, Louise; Biessen, Erik A. L.

    2013-01-01

    In search of molecular imaging modalities for specific detection of inflammatory atherosclerotic plaques, we explored the potential of targeting scavenger receptor-AI (SR-AI), which is highly expressed by lesional macrophages and linked to effective internalization machinery. Ultrasmall

  18. Red cell indices and discriminant functions in the detection of beta-thalassaemia trait in a population with high prevalence of iron deficiency anaemia.

    Science.gov (United States)

    Madan, N; Sikka, M; Sharma, S; Rusia, U; Kela, K

    1999-01-01

    Red cell indices and discriminant functions were studied in 463 heterozygous beta-thalassaemics (337 without iron deficiency, 126 with iron deficiency) and 195 patients of iron deficiency anaemia (IDA) to ascertain their utility in the detection of betathalassaemia trait (BTT). Majority of traits in both groups had an elevated RBC count (> or = 5.0 x 10(12)/L). The counts were significantly higher than of patients with IDA, only 4.6% of whom had this degree of erythrocytosis. Mean Hb concentration was significantly higher in traits as compared to iron deficient subjects (p < 0.0001). Mean MCV and MCH were significantly (p < 0.0001) lower in traits more so in those with ID as compared to patients of IDA. MCV < 80 fl and MCH < 27 pg were found to be sensitive markers in the detection of traits even in the presence of ID. Of the four discriminant functions studied MCSQ was found to be most sensitive in detection of BTT and it identified 97.9% traits. DF of England and Fraser was most specific for BTT being < 8.4 in only 6.2% patients with IDA. Detection of erythrocytosis especially in the presence of mild anaemia and calculation of discriminant functions derived from red cell indices were found to play an important role in screening for BTT even in the presence of ID and helped identify those patients who required further laboratory evaluation.

  19. Optimal labeling dose, labeling time, and magnetic resonance imaging detection limits of ultrasmall superparamagnetic iron-oxide nanoparticle labeled mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Hansen, Louise; Friis, Tina

    2013-01-01

    Background. Regenerative therapy is an emerging treatment modality. To determine migration and retention of implanted cells, it is crucial to develop noninvasive tracking methods. The aim was to determine ex vivo magnetic resonance imaging (MRI) detection limits of ultrasmall superparamagnetic iron...

  20. [Iron deficiency towards the year 2000].

    Science.gov (United States)

    Layrisse, M

    1999-09-01

    This is a non-comprehensive overview of the latest 50 years about the evolution of iron metabolism and the methodology we currently have for the diagnosis of iron deficiency and its effects on human health. In the 40's iron absorption was determined by chemistry. The amount of iron absorbed was calculated as the difference between dietary iron and excreted iron. The other methods used to measure dietary iron was hemoglobin repletion. In the 70's the measurement of plasmatic ferritin was an important contribution to iron metabolism to assess iron deficiency and iron overload. In the same decade the extrinsic and intrinsic labelled methodology was an important advancement. The 70's and 80's were years where scientists aimed at finding iron absorption inhibitors, namely coffee, calcium, tea, zinc and fiber. The 80's and 90's were characterized for the emerging knowledge an iron absorption from a food, a meal and a complete diet and for the favorable effect of food iron fortification in developing countries. Also for the effect of iron excess in overall health and myocardial infarction in developed countries were studied.

  1. INCREASING AND DECREASING PHASES OF FERRITIN AND HEMOSIDERIN IRON DETERMINED BY SERUM FERRITIN KINETICS

    OpenAIRE

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

    2013-01-01

    ABSTRACT We attempted to clarify the mechanism of the storage iron metabolism. A new program of serum ferritin kinetics was applied for studying the increasing and decreasing phases of ferritin and hemosiderin iron in iron addition and removal in patients with a normal level of iron stores or iron overload. The change of ferritin iron in response to iron addition and removal was rapid in the initial stage, but it was slow later. In contrast, the change of hemosiderin iron was slow in the init...

  2. 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.

  3. 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

  4. Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli

    Directory of Open Access Journals (Sweden)

    İlker Dinçer

    2013-03-01

    Full Text Available We report the preparation and characterization of spherical core-shell structured Fe3O4–Au magnetic nanoparticles, modified with two component self-assembled monolayers (SAMs consisting of 3–mercaptophenylboronic acid (3–MBA and 1–decanethiol (1–DT. The rapid and room temperature synthesis of magnetic nanoparticles was achieved using the hydroxylamine reduction of HAuCl4 on the surface of ethylenediaminetetraacetic acid (EDTA-immobilized iron (magnetite Fe3O4 nanoparticles in the presence of an aqueous solution of hexadecyltrimetylammonium bromide (CTAB as a dispersant. The reduction of gold on the surface of Fe3O4 nanoparticles exhibits a uniform, highly stable, and narrow particle size distribution of Fe3O4–Au nanoparticles with an average diameter of 9 ± 2 nm. The saturation magnetization value for the resulting nanoparticles was found to be 15 emu/g at 298 K. Subsequent surface modification with SAMs against glucoside moieties on the surface of bacteria provided effective magnetic separation. Comparison of the bacteria capturing efficiency, by means of different molecular recognition agents 3–MBA, 1–DT and the mixed monolayer of 3–MBA and 1–DT was presented. The best capturing efficiency of E. coli was achieved with the mixed monolayer of 3–MBA and 1–DT-modified nanoparticles. Molecular specificity and selectivity were also demonstrated by comparing the surface-enhanced Raman scattering (SERS spectrum of E. coli-nanoparticle conjugates with bacterial growth media.

  5. Preparation and evaluation of MRI detectable poly (acrylic acid) microspheres loaded with superparamagnetic iron oxide nanoparticles for transcatheter arterial embolization.

    Science.gov (United States)

    Wang, Huan; Qin, Xiao-Ya; Li, Zi-Yuan; Guo, Li-Ying; Zheng, Zhuo-Zhao; Liu, Li-Si; Fan, Tian-Yuan

    2016-09-25

    To monitor the spatial distribution of embolic particles inside the target tissues during and after embolization, blank poly (acrylic acid) microspheres (PMs) were initially prepared by inverse suspension polymerization method and then loaded with superparamagnetic iron oxide (SPIO) nanoparticles by in situ precipitation method to obtain magnetic resonance imaging (MRI) detectable SPIO-loaded poly (acrylic acid) microspheres (SPMs). The loading of SPIO nanoparticles in SPMs was confirmed by vibrating sample magnetometer, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and infrared spectrum, respectively. The results showed that SPMs exhibited excellent superparamagnetism and the SPIO embedded in SPMs were proved to be inverse spinel magnetite. The content of SPIO loaded in wet SPMs of subgroups of 100-300, 300-500, 500-700 and 700-900μm was measured to be 11.84±0.07, 10.20±0.05, 9.98±0.00 and 8.79±0.01mg/ml, corresponding to the weight percentage in freeze-dried SPMs to be 18.07±0.28%, 18.54±0.13%, 18.66±0.01% and 18.50±0.07%, respectively. The SPMs were spherical in shape, had smooth surface, and were within the size range of clinical demands for embolization. The compression tests indicated that SPMs were more rigid than PMs and commercially used Embospheres (P<0.01). The MRI detectability of SPMs was evaluated with the SPMs embedded in gel phantom in vitro and injected subcutaneously into the back of mice in vivo. Both the results demonstrated that the SPMs could provide distinct negative contrast enhancement and be sensitively detected by T2-weighted MR imaging. All the results show that SPMs are potential MRI detectable embolic microspheres for the future embolotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Automated electrochemical detection of iron ions in erythrocytes from melim minipigs suffering from melanoma

    Czech Academy of Sciences Publication Activity Database

    Kremplová, M.; Krejcová, l.; Hynek, D.; Barath, P.; Majzlík, P.; Horák, Vratislav; Adam, V.; Sochor, J.; Cernei, N.; Hubálek, J.; Vrba, R.; Kižek, R.

    2012-01-01

    Roč. 7, č. 7 (2012), s. 5893-5909 ISSN 1452-3981 Institutional research plan: CEZ:AV0Z50450515 Keywords : Automation * Biological sample * Electrochemical detection Subject RIV: CG - Electrochemistry Impact factor: 3.729, year: 2011

  7. Non-destructive Leak Detection in Galvanized Iron Pipe Using Nonlinear Acoustic Modulation Method

    OpenAIRE

    Priyandoko, Gigih

    2018-01-01

    Non-destructive testing is a wide group of analysis techniques used in science and industry to evaluate the properties of a structure without causing damage to it. The main objective of this project is to carry out experiment to detect leakage in pipeline using nonlinear acoustic modulation method. The nonlinear acoustic modulation approach with low frequency excitation and high frequency acoustic wave is used to reveal modulations in the presence of leak. The pipe used in this experiment was...

  8. Increasing and decreasing phases of ferritin and hemosiderin iron determined by serum ferritin kinetics.

    Science.gov (United States)

    Saito, Hiroshi; Hayashi, Hisao; Tomita, Akihiro; Ohashi, Haruhiko; Maeda, Hideaki; Naoe, Tomoki

    2013-08-01

    We attempted to clarify the mechanism of the storage iron metabolism. A new program of serum ferritin kinetics was applied for studying the increasing and decreasing phases of ferritin and hemosiderin iron in iron addition and removal in patients with a normal level of iron stores or iron overload. The change of ferritin iron in response to iron addition and removal was rapid in the initial stage, but it was slow later. In contrast, the change of hemosiderin iron was slow in the initial stage, but it became rapid later. These changes of ferritin and hemosiderin iron suggest that the turnover of ferritin iron is preferential to that of hemosiderin iron, and that the initially existed ferritin iron is gradually replaced by the ferritin iron recovered by taking iron from hemosiderin in iron mobilization. The crossing of the increasing curves of ferritin and hemosiderin iron in iron addition indicates a switching of the principal storage iron from ferritin to hemosiderin. The crossing point shifted toward a higher storage iron level in the increase of iron deposition. Iron storing capacity can be increased not only by the transformation of ferritin into hemosiderin, but also by the expansion of cell space as seen by hepatomegaly in hereditary hemochromatosis. The amounts of hemosiderin iron exceeded ferritin iron in all 10 patients with chronic hepatitis C even though they had normal storage iron levels. This suggests it is difficult to store iron in the form of ferritin in chronic hepatitis C.

  9. Detect, map, and preserve Bronze & Iron Age monuments along the pre-historic Silk Road

    Science.gov (United States)

    Balz, Timo; Caspari, Gino; Fu, Bihong

    2017-02-01

    Central Asia is rich in cultural heritage generated by thousands of years of human occupation. Aiming for a better understanding of Central Asia’s archaeology and how this unique heritage can be protected, the region should be studied as a whole with regard to its cultural ties with China and combined efforts should be undertaken in shielding the archaeological monuments from destruction. So far, international research campaigns have focused predominantly on single-sites or small-scale surveys, mainly due to the bureaucratic and security related issues involved in cross-border research. This is why we created the Dzungaria Landscape Project. Since 2013, we have worked on collecting remote sensing data of Xinjiang including IKONOS, WorldView-2, and TerraSAR-X data. We have developed a method for the automatic detection of larger grave mound structures in optical and SAR data. Gravemounds are typically spatially clustered and the detection of larger mound structures is a sufficient hint towards areas of high archaeological interest in a region. A meticulous remote sensing survey is the best planning tool for subsequent ground surveys and excavation. In summer 2015, we undertook a survey in the Chinese Altai in order to establish ground-truth in the Hailiutan valley. We categorized over 1000 monuments in just three weeks thanks to the previous detection and classification work using remote sensing data. Creating accurate maps of the cemeteries in northern Xinjiang is a crucial step to preserving the cultural heritage of the region since graves in remote areas are especially prone to looting. We will continue our efforts with the ultimate aim to map and monitor all large gravemounds in Dzungaria and potentially neighbouring eastern Kazakhstan.

  10. Resonance Raman detection of iron-ligand vibrations in cyano(pyridine)(octaethylporphinato)iron(III): Effects of pyridine basicity on the Fe-CN bond strength

    International Nuclear Information System (INIS)

    Uno, Tadayuki; Hatano, Keiichiro; Nishimura, Yoshifumi; Arata, Yoji

    1988-01-01

    The influence of axial ligand basicity on the bonding of iron(III) in cyano adducts of octaethylporphyrin has been studied by resonance Raman spectroscopy. In a six-coordinate ferric low-spin complex, cyano(pyridine)(octaethylporphinato)iron(III), Fe(OEP)(CN)(py), Raman lines at 449 and 191 cm -1 were assigned to the ν(Fe-CN) and ν(Fe-py) stretching modes, respectively. When pyridine was displaced with its derivatives, py-X, where X = 4-cyano, 3-acetyl, 3-methyl, 4-methyl, 3,4-dimethyl, and 4-dimethylamino, the ν(Fe-CN) stretching frequency was found to decrease in the complex with a high pyridine basicity. It was concluded that the stronger the trans pyridine basicity, the weaker the iron-carbon (cyanide) bond. A clear frequency shift was observed in the ν 4 model, though most of the porphyrin vibrations were insensitive to the ligand substitution. The frequency of the ν 4 mode, which is the C a -N(pyrrole) breathing vibration of the porphyrin skeleton, was found to increase with an increase in pyridine basicity. This is contrary to what was found in ferrous low-spin hemes as CO complexes. The ν 4 shift in the CN complexes was explained in terms of forward π donation; donation of electrons from the porphyrin π orbital to the d π vacancy of the low-spin iron(III) weakened the C a -N(pyrrole) bonds and hence decreased the ν 4 frequency. 32 references, 8 figures

  11. 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.

  12. 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...

  13. 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

  14. Biliary excretion of iron and ferritin in idiopathic hemochromatosis

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  15. A New Approach for Border Detection of the Dumluca (Turkey) Iron Ore Area: Wavelet Cellular Neural Networks

    Science.gov (United States)

    Albora, A. Muhittin; Bal, Abdullah; Ucan, Osman N.

    2007-01-01

    Anomaly analysis is used for various geophysics applications such as determination of geophysical structure's location and border detections. Besides the classical geophysical techniques, artificial intelligence based image processing algorithms have been found attractive for geophysical anomaly analysis. Recently, cellular neural networks (CNN) have been applied to geophysical data and satisfactory results are reported. CNN provides fast and parallel computational capability for geophysical image processing applications due to its filtering structure. The behavior of CNN is defined by two template matrices that are adjusted by a properly supervised learning algorithm. After training stage for geophysical data, Bouguer anomaly maps can be processed and analyzed sequentially. In this paper, CNN learning and processing capability have been improved, combining Wavelet functions and backpropagation learning algorithms. The new architecture is denoted as Wavelet-Cellular Neural networks (Wave-CNN) and it is employed to analyze Bouguer anomaly maps which are important to extract useful information in geophysics. At first, Wave-CNN performance is tested on synthetic geophysical data, which are created by a computer environment. Then, Bouguer anomaly maps of the Dumluca iron ore field have been analyzed and results are reported in comparison to real drilling results.

  16. Role ambiguity, role conflict and work overload and their influence ...

    African Journals Online (AJOL)

    Bivarate correlations and regression analysis were used to test the nature of the relationships between the measures of job stressors (role ambiguity, role conflict, work overload) and job satisfaction. Significant negative relationships were found between the measures of role ambiguity, role conflict, work overload and job ...

  17. A sensitive electrochemical sensor using an iron oxide/graphene composite for the simultaneous detection of heavy metal ions.

    Science.gov (United States)

    Lee, Sohee; Oh, Jiseop; Kim, Dongwon; Piao, Yuanzhe

    2016-11-01

    We report an analytical assessment of an iron oxide (Fe2O3)/graphene (G) nanocomposite electrode used in combination with in situ plated bismuth (Bi) working as an electrochemical sensor for the determination of trace Zn(2+), Cd(2+), and Pb(2+). The as-synthesized nanocomposites were characterized by transmission electron microscopy, scanning electron microscopy, thermo-gravimetric analyzer, and X-ray diffraction. The electrochemical properties of the Fe2O3/G/Bi composite modified electrode were investigated. Differential pulse anodic stripping voltammetry was applied for the detection of metal ions. Due to the synergetic effect between graphene and the Fe2O3 nanoparticles, the modified electrode showed improved electrochemical catalytic activity high sensitivity toward trace heavy metal ions. Several parameters such as the preconcentration potential, bismuth concentration, preconcentration time, and pH were carefully optimized to determine the target metal ions. Under optimized conditions, the linear range of the electrode was 1-100μgL(-1) for Zn(2+), Cd(2+), and Pb(2+), and the detection limits were 0.11μgL(-1), 0.08μgL(-1), and 0.07μgL(-1), respectively (S/N =3). Repeatability (% RSD) was found to be 1.68% for Zn(2+), 0.92% for Cd(2+), and 1.69% for Pb(2+) for single sensor with 10 measurements and 0.89% for Zn(2+), 1.15% for Cd(2+), and 0.91% for Pb(2+) for 5 different electrodes. The Fe2O3/G/Bi composite electrode was successfully applied to the analysis of trace metal ions in real samples. The solventless thermal decomposition method applied to the simple and easy synthesis of nanocomposite electrode materials can be extended to the synthesis of nanocomposites and promising electrode materials for the determination of heavy metal ions. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Simultaneous Electrochemical Detection of Dopamine and Ascorbic Acid Using an Iron Oxide/Reduced Graphene Oxide Modified Glassy Carbon Electrode

    Directory of Open Access Journals (Sweden)

    Teo Peik-See

    2014-08-01

    Full Text Available The fabrication of an electrochemical sensor based on an iron oxide/graphene modified glassy carbon electrode (Fe3O4/rGO/GCE and its simultaneous detection of dopamine (DA and ascorbic acid (AA is described here. The Fe3O4/rGO nanocomposite was synthesized via a simple, one step in-situ wet chemical method and characterized by different techniques. The presence of Fe3O4 nanoparticles on the surface of rGO sheets was confirmed by FESEM and TEM images. The electrochemical behavior of Fe3O4/rGO/GCE towards electrocatalytic oxidation of DA was investigated by cyclic voltammetry (CV and differential pulse voltammetry (DPV analysis. The electrochemical studies revealed that the Fe3O4/rGO/GCE dramatically increased the current response against the DA, due to the synergistic effect emerged between Fe3O4 and rGO. This implies that Fe3O4/rGO/GCE could exhibit excellent electrocatalytic activity and remarkable electron transfer kinetics towards the oxidation of DA. Moreover, the modified sensor electrode portrayed sensitivity and selectivity for simultaneous determination of AA and DA. The observed DPVs response linearly depends on AA and DA concentration in the range of 1–9 mM and 0.5–100 µM, with correlation coefficients of 0.995 and 0.996, respectively. The detection limit of (S/N = 3 was found to be 0.42 and 0.12 µM for AA and DA, respectively.

  19. Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity.

    Science.gov (United States)

    Coates, Alexandra M; Incognito, Anthony V; Seed, Jeremy D; Doherty, Connor J; Millar, Philip J; Burr, Jamie F

    2018-05-01

    Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P 0.05). Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance.

  20. 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

    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......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...... weeks. Cardiac and liver iron levels were measured after iron loading (n = 18), 12 weeks of sham chelation (n = 18), and 12 weeks of DFX chelation (n = 18) at 75 mg/kg/day. Ascorbate supplementation of 150 ppm, 900 ppm, and 2250 ppm was used in the chow to mimic a broad range of ascorbate status; plasma...

  1. Fluid Overload and Cumulative Thoracostomy Output Are Associated With Surgical Site Infection After Pediatric Cardiothoracic Surgery.

    Science.gov (United States)

    Sochet, Anthony A; Nyhan, Aoibhinn; Spaeder, Michael C; Cartron, Alexander M; Song, Xiaoyan; Klugman, Darren; Brown, Anna T

    2017-08-01

    To determine the impact of cumulative, postoperative thoracostomy output, amount of bolus IV fluids and peak fluid overload on the incidence and odds of developing a deep surgical site infection following pediatric cardiothoracic surgery. A single-center, nested, retrospective, matched case-control study. A 26-bed cardiac ICU in a 303-bed tertiary care pediatric hospital. Cases with deep surgical site infection following cardiothoracic surgery were identified retrospectively from January 2010 through December 2013 and individually matched to controls at a ratio of 1:2 by age, gender, Risk Adjustment for Congenital Heart Surgery score, Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category, primary cardiac diagnosis, and procedure. None. Twelve cases with deep surgical site infection were identified and matched to 24 controls without detectable differences in perioperative clinical characteristics. Deep surgical site infection cases had larger thoracostomy output and bolus IV fluid volumes at 6, 24, and 48 hours postoperatively compared with controls. For every 1 mL/kg of thoracostomy output, the odds of developing a deep surgical site infection increase by 13%. By receiver operative characteristic curve analysis, a cutoff of 49 mL/kg of thoracostomy output at 48 hours best discriminates the development of deep surgical site infection (sensitivity 83%, specificity 83%). Peak fluid overload was greater in cases than matched controls (12.5% vs 6%; p operative characteristic curve analysis, a threshold value of 10% peak fluid overload was observed to identify deep surgical site infection (sensitivity 67%, specificity 79%). Conditional logistic regression of peak fluid overload greater than 10% on the development of deep surgical site infection yielded an odds ratio of 9.4 (95% CI, 2-46.2). Increased postoperative peak fluid overload and cumulative thoracostomy output were associated with deep surgical site infection after pediatric

  2. Planetary Overload, Limits to Growth and Health.

    Science.gov (United States)

    Butler, Colin D

    2016-12-01

    Since the use of atomic weapons in 1945 visionaries have warned that without major changes the survival of global civilization is in question. These concerns deepened in following decades, during the Cold War, with The Limits to Growth, the best-selling environmental book of the 1970s. Yet, since then, most concern has faded, fuelled by technological developments and a shift in dominant global ideology. Public health, with a few exceptions (one of which is the book Planetary Overload), has been slow to recognize this debate, even as evidence emerges that civilization may indeed be at risk, driven by an increasingly ominous complex of events. This article outlines the key relevant literature and concepts, attempting to bring emerging and future health consequences to the attention of health workers, including the idea of a "social vaccine," conveying sufficient anxiety to provoke action for environmental protection, but insufficient to induce paralysis.

  3. Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival.

    Directory of Open Access Journals (Sweden)

    Imke H E Schmidt

    2018-01-01

    Full Text Available The control over iron homeostasis is critical in host-pathogen-interaction. Iron plays not only multiple roles for bacterial growth and pathogenicity, but also for modulation of innate immune responses. Hepcidin is a key regulator of host iron metabolism triggering degradation of the iron exporter ferroportin. Although iron overload in humans is known to increase susceptibility to Burkholderia pseudomallei, it is unclear how the pathogen competes with the host for the metal during infection. This study aimed to investigate whether B. pseudomallei, the causative agent of melioidosis, modulates iron balance and how regulation of host cell iron content affects intracellular bacterial proliferation.Upon infection of primary macrophages with B. pseudomallei, expression of ferroportin was downregulated resulting in higher iron availability within macrophages. Exogenous modification of iron export function by hepcidin or iron supplementation by ferric ammonium citrate led to increased intracellular iron pool stimulating B. pseudomallei growth, whereas the iron chelator deferoxamine reduced bacterial survival. Iron-loaded macrophages exhibited a lower expression of NADPH oxidase, iNOS, lipocalin 2, cytokines and activation of caspase-1. Infection of mice with the pathogen caused a diminished hepatic ferroportin expression, higher iron retention in the liver and lower iron levels in the serum (hypoferremia. In vivo administration of ferric ammonium citrate tended to promote the bacterial growth and inflammatory response, whereas limitation of iron availability significantly ameliorated bacterial clearance, attenuated serum cytokine levels and improved survival of infected mice.Our data indicate that modulation of the cellular iron balance is likely to be a strategy of B. pseudomallei to improve iron acquisition and to restrict antibacterial immune effector mechanisms and thereby to promote its intracellular growth. Moreover, we provide evidence that

  4. Fluid overload in hemodialysis patients: a cross-sectional study to determine its association with cardiac biomarkers and nutritional status.

    Science.gov (United States)

    Antlanger, Marlies; Hecking, Manfred; Haidinger, Michael; Werzowa, Johannes; Kovarik, Johannes J; Paul, Gernot; Eigner, Manfred; Bonderman, Diana; Hörl, Walter H; Säemann, Marcus D

    2013-12-02

    Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status. We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna (Austria) and determined associations with volume measurements using the body composition monitor (Fresenius/Germany). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters. We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters. Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease.

  5. 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

  6. A computational model of liver iron metabolism.

    Directory of Open Access Journals (Sweden)

    Simon Mitchell

    Full Text Available Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system.

  7. 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.

  8. 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.

  9. 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

  10. A novel method of adrenaline concentration detection using fiber optical biosensor based on the catalysis of iron(II) phthalocyanine

    Science.gov (United States)

    Zhou, Xuan; Huang, Jun; Li, Mingtian; Wang, Bin

    2008-12-01

    As an effective alternative to the nature enzyme, metallophthalocyanine (MPc), having the advantages of easy accessibility, good stability and low cost, are used as catalyzer for the adrenaline (AD) oxidation. In this paper, the oxidation of AD by dioxygen using iron(II) phthalocyanine (FePc) as the catalyst was studied by electronic absorption spectra. The experimental results indicate that the oxidation product of AD catalyzed by FePc is adrenochrome with characteristic peaks at 298 nm and 267 nm. The catalytic activities of FePc are evaluated by the ratios of the absorbance at 298 nm of adrenochrome. The optimal concentration, pH and temperature for the oxidation of AD are 5.0×10-5 M, 8.0 and 55 oC, respectively. By using lock-in technology, the fiber optic adrenaline biosensor based on FePc catalysis and fluorescence quenching was fabricated and studied. A linear relationship between φ, the phase delay of the sensor head, and AD concentration was observed in the range of 2.0×10-6 to 9.0×10-6 M and 2.0×10-5 to 9.0×10-5 M. The standard deviation (SD) values are 4.7×10-8 (n = 5) and 5.9×10-7 (n = 5) M, respectively, while the detection limit is 4.0×10-7 M. The biosensor has the response time of about 15 min and the preferred reproducibility and stability.

  11. TDCPP protects cardiomyocytes from hypoxia-reoxygenation injury induced apoptosis through mitigating calcium overload and promotion GSK-3β phosphorylation.

    Science.gov (United States)

    He, Xiju; Li, Shoutian; Fang, Xiaoxia; Liao, Yanhong

    2018-02-01

    TDCPP, Tris (1, 3-dichloro-2-propyl) phosphate belongs to a group of chemicals known as triester organophosphate flame retardants, It can alter calcium homeostasis at much lower concentrations in normal conditions, but the mechanism is unclear till now. Calcium overload is a leading cause of apoptosis in myocardial ischemia/reperfusion (I/R) injury, thus how to mitigate Ca 2+ -overload is deserved to be investigated. We therefore hypothesized that TDCPP could attenuate cardiomyocytes apoptosis in I/R injury. H/R (hypoxia/reoxygenation) experiments in vitro were used to simulate in vivo I/R injury. The present study aimed to explore the potential effect of TDCPP in cardiomyocytes after H/R injury, Ca 2+ imaging technique was used to explore SOCE(store-operated calcium entry) and Ca 2+ -overload levels, western blot technique was used to explore the potential target, the cell morphology, cell viability and mitochondrial membrane potential were also detected. The results have shown that: TDCPP could decrease SOCE, restore H9c2 cell viability, mitigate Ca 2+ -overload in H/R injury and reduce the mitochondrial membrane potential. Furthermore, TDCPP decreased STIM1 expression and promoted GSK3β phosphorylation. Collectively, for the first time, this study suggest the antiapoptosis roles of TDCPP in H/R injury are via mitigation Ca 2+ -overload and promoting GSK-3β phosphorylation. Copyright © 2017. Published by Elsevier Inc.

  12. Reducing power and iron chelating property of Terminalia chebula (Retz. alleviates iron induced liver toxicity in mice

    Directory of Open Access Journals (Sweden)

    Sarkar Rhitajit

    2012-08-01

    Full Text Available Abstract Background The 70% methanol extract of Terminalia chebula Retz. fruit (TCME was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice. Methods The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound. Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied. Results In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p. caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT, aspartate aminotransferase (ASAT, alkaline phosphatase (ALP and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract

  13. The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

    Science.gov (United States)

    Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

    2017-04-04

    The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

  14. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Precise coulometric determination of iron in iron ores with electrogenerated manganese(III) fluoride.

    Science.gov (United States)

    Yoshimori, T; Tanaka, T

    1975-01-01

    Iron in Mohr's salt, electrolytic iron and iron ores has been determined by precision coulometric titration with electrolytically generated manganese (III) fluoride, with biamperometric end-point detection. The titration curve indicated the irreversibility of the electrode reaction of manganese(III) fluoride. Total iron in several standard samples of iron ores was determined with standard deviations of about 0.012%.

  17. 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.

  18. 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.......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...

  19. Nuclear resonance scattering measurement of human iron stores

    Energy Technology Data Exchange (ETDEWEB)

    Wielopolski, L.; Ancona, R.C.; Mossey, R.T.; Vaswani, A.N.; Cohn, S.H.

    1985-07-01

    Hepatic iron stores were measured noninvasively in 31 patients (thalassemia, hemodialysis, hemosiderosis, refractory anemia) with suspected iron overload, employing a nuclear resonance scattering (NRS) technique. The thalassemia patients were undergoing desferrioxamine chelation therapy during the NRS measurements. The hemodialysis patients were measured before chelation therapy. Iron levels measured by NRS were in general agreement with those determined in liver biopsies by atomic absorption spectroscopy. In addition, NRS measurements from the thorax of some of these patients suggest that this method may also prove useful for clinical assessment of cardiac iron.

  20. Use of Mishell-Dutton culture for the detection of the immunosuppressive effect of iron-containing compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ban, M.; Hettich, D.; Cavelier, C. [Institut National de Recherche et de Securite, Vandoeuvre (France)

    1995-11-15

    Mishell-Dutton culture, known as an in vitro model for the evaluation of the humoral immune response of mice spleen cells to sheep red blood cells (SRBC), was used to study the immunosuppressive effect of iron-containing compounds. This response was indicated by the number of anitbody forming cell (AFC) per million nucleated cells. Ferrous sulfate and ferric citrate (0.1 mM), when continuously present in Mishell-Dutton culture, significantly decreased the SRBC AFC response by approximately 63% and 86% of the control values, respectively. Ferric citrate, preincubated (24h) with spleen cells and followed by lavage, significantly decreased the SRBC AFC response by approximately 54% for the control values. Primary and iron-treated coal, in concentration ranging from 40{mu}g ml{sup -1} to 120{mu}g.m{sup -1}, significantly decreased the SRBC AFC response when continuously present in Mishell-Dutton culture. Iron-treated coal, suppressed this response in dose-dependent amounts, to a greater extent than did the primary coal: 73% versus 54% at 120{mu}g.ml{sup -1}. It was concluded that Mishell-Dutton culture is suitable for studying the immunotoxicity of iron and these results may contribute to explain a decrease of host resistance against parasitic and bacterial infection in workers exposed to iron. 28 refs., 3 tabs.

  1. Differential Responses of Soleus and Plantaris Muscle Fibers to Overloading

    Science.gov (United States)

    Kawano, Fuminori; Shibaguchi, Tsubasa; Ohira, Takashi; Nakai, Naoya; Ohira, Yoshinobu

    2013-02-01

    Responses of slow and fast fibers in soleus and plantaris muscles of adult rats to overloading by the tendon transection of synergists were studied. Overloading-related hypertrophy was noted in the slow fibers of plantaris and soleus, although the magnitude was greater in plantaris. Five genes with minor expression in slow soleus muscle were identified by microarray analysis. Base-line expressions of these genes in slow fibers of plantaris were also low. Further, repressive effects of overloading on these genes were seen in some fast fibers of plantaris, not in whole plantaris and soleus. The data suggested that the repression of particular genes might be related to the pronounced morphological response of fibers expressing type II, including I+II, myosin heavy chain (MyHC), although these genes with lower base-line expression in slow fibers did not respond to overloading.

  2. Overload truck wheel load distribution on bridge decks.

    Science.gov (United States)

    2009-04-01

    There is a need to accurately analyze the load effects on bridge decks from permitted overload trucks on : Michigans roads. The AASHTO Standard Specifications for Highway Bridges, 17th edition, provides a : distribution width of live loads when re...

  3. 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.

  4. OVERLOAD CAPABILITY OF POWER CABLES IN ACTUAL POWER CONSUMPTION SYSTEMS

    Directory of Open Access Journals (Sweden)

    L.A. Szhebenyuk

    2013-09-01

    Full Text Available Results of overload capability calculations for 6-kV power cables are analyzed. The work is aimed at creating a computation system for the current rating of high-voltage cross-linked polyethylene power cables.

  5. Suppressive effects of subchronic aluminum overload on the splenic immune function may be related to oxidative stress in mice.

    Science.gov (United States)

    Luo, Xue; Jia, Shujie; Ma, Qinlong; Zhong, Min; Gao, Peng; Yu, Zhengping; Zhang, Yanwen

    2014-03-01

    Aluminum (Al) is widely used in daily life and was recently recognized as a possible source of human intoxication because of its ability to accumulate in organs. The objective of the present study was to investigate the effects of subchronic Al overload on splenic immune function in mice. Furthermore, we have preliminarily explored its mechanism. The Al overload model was established via intragastric administration of Al once a day for 60 days. The body weight, spleen weight, and splenic coefficient were determined. The concentration of Al in the spleen was detected by inductively coupled plasma-mass spectrometry. The cytokine mRNA expression of spleen tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Biochemical methods were used to detect superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) contents in spleen tissue. Body weight, spleen weight, and cytokine mRNA expression of spleen tissues were significantly reduced by Al overload. SOD and GSH-Px activities were also decreased, while the MDA content was increased in subchronic Al overload mice. The results indicate that subchronic exposure to aluminum trichloride (AlCl3) would result in Al accumulation, which suppressed spleen immune function through a mechanism related to oxidative stress.

  6. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

    Science.gov (United States)

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption. PMID:26893541

  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. Non-invasive diagnosis and follow-up of right ventricular overload

    NARCIS (Netherlands)

    Henkens, Ivo Reinier

    2008-01-01

    Right ventricular overload covers a spectrum ranging from volume overload to pressure overload, and often is a combination of these, compromising cardiac function. Part I focuses on right ventricular volume overload in adults with Fallot’s tetralogy corrected in early childhood. We determined

  9. 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.

  10. Detecting Organic Compounds Released from Iron Oxidizing Bacteria using Sample Analysis at Mars (SAM) Like Instrument Protocols

    Science.gov (United States)

    Glavin, D. P.; Popa, R.; Martin, M. G.; Freissinet, C.; Fisk, M. R.; Dworkin, J. P.; Mahaffy, P. R.

    2012-01-01

    Mars is a planet of great interest for Astrobiology since its past environmental conditions are thought to have been favourable for the emergence life. At present, the Red Planet is extremely cold and dry and the surface is exposed to intense UV and ionizing radiation, conditions generally considered to be incompatible with life as we know it on Earth. It was proposed that the shallow subsurface of Mars, where temperatures can be above freezing and liquid water can exist on rock surfaces, could harbor chemolithoautotrophic bacteria such as the iron oxidizing microorganism Pseudomonas sp. HerB. The Mars Science Laboratory (MSL) mission will provide the next opportunity to carry out in situ measurements for organic compounds of possible biological origin on Mars. One instrument onboard MSL, called the Sample Analysis at Mars (SAM) instrument suite, will carry out a broad and sensitive search for organic compounds in surface samples using either high temperature pyrolysis or chemical extraction followed by gas chromatography mass spectrometry. We present gas chromatograph mass spectrometer (GC/MS) data on crushed olivine rock powders that have been inoculated with Pseudomonas sp. HerB at different concentrations ranging from approx 10(exp 2) to 10(exp 7) cells per gram. The inoculated olivine samples were heated under helium carrier gas flow at 500 C and the pyrolysis products concentrated using a SAM-like hydrocarbon trap set at -20 C followed by trap heating and analysis by GC/Ms. In addition, the samples were also extracted using a low temperature "one-pot" chemical extraction technique using N-methyl, N-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA) as the silylating agent prior to GC/MS analysis. We identified several aldehydes, thiols, and alkene nitriles after pyrolysis GC/MS analysis of the bacteria that were not found in the olivine control samples that had not been inoculated with bacteria. The distribution of pyrolysis products extracted from the

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is caused by strong muscle contractions and the impact of feet repeatedly striking the ground, such as ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ... to your doctor if you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, ...

  13. L–Carnitine ameliorates the iron mediated DNA degradation in ...

    African Journals Online (AJOL)

    Background: Iron overload is a common complication in β-thalassemia that induces intracellular oxidative stress producing lesions in the DNA including double strand breaks. Objectives: The aim of this study was to evaluate DNA damage in peripheral leukocytes of β -thalassemic children and to investigate its association ...

  14. Iron chelating activity, phenol and flavonoid content of some ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... Thalassemia major is characterized by anemia, iron overload, further potentiation of reactive oxygen species (ROS) and damage to major organs, especially the cardiovascular system. Antioxidant and other supportive therapies protect red blood cells (RBC) against antioxidant damage. Chelation therapy.

  15. Salicylate Detection by Complexation with Iron(III) and Optical Absorbance Spectroscopy: An Undergraduate Quantitative Analysis Experiment

    Science.gov (United States)

    Mitchell-Koch, Jeremy T.; Reid, Kendra R.; Meyerhoff, Mark E.

    2008-01-01

    An experiment for the undergraduate quantitative analysis laboratory involving applications of visible spectrophotometry is described. Salicylate, a component found in several medications, as well as the active by-product of aspirin decomposition, is quantified. The addition of excess iron(III) to a solution of salicylate generates a deeply…

  16. 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

  17. Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron.

    Science.gov (United States)

    Jensen, Jens H; Tang, Haiying; Tosti, Christina L; Swaminathan, Srirama V; Nunez, Alvaro; Hultman, Kristi; Szulc, Kamila U; Wu, Ed X; Kim, Daniel; Sheth, Sujit; Brown, Truman R; Brittenham, Gary M

    2010-05-01

    A new MRI method is proposed for separately quantifying the two principal forms of tissue storage (nonheme) iron: ferritin iron, a dispersed, soluble fraction that can be rapidly mobilized, and hemosiderin iron, an aggregated, insoluble fraction that serves as a long-term reserve. The method utilizes multiple spin echo sequences, exploiting the fact that aggregated iron can induce nonmonoexponential signal decay for multiple spin echo sequences. The method is validated in vitro for agarose phantoms, simulating dispersed iron with manganese chloride, and aggregated iron with iron oxide microspheres. To demonstrate feasibility for human studies, preliminary in vivo data from two healthy controls and six patients with transfusional iron overload are presented. For both phantoms and human subjects, conventional R(2) and R(2)* relaxation rates are also measured in order to contrast the proposed method with established MRI iron quantification techniques. Quantification of dispersed (ferritin-like) iron may provide a new means of monitoring the risk of iron-induced toxicity in patients with iron overload and, together with quantification of aggregated (hemosiderin-like) iron, improve the accuracy of estimates for total storage iron. (c) 2010 Wiley-Liss, Inc.

  18. Construction of iron-polymer-graphene nanocomposites with low nonspecific adsorption and strong quenching ability for competitive immunofluorescent detection of biomarkers in GM crops.

    Science.gov (United States)

    Yin, Kaifei; Liu, Anran; Shangguan, Li; Mi, Li; Liu, Xu; Liu, Yuanjian; Zhao, Yuewu; Li, Ying; Wei, Wei; Zhang, Yuanjian; Liu, Songqin

    2017-04-15

    We developed a new immunofluorescent biosensor by utilizing a novel nanobody (Nb) and iron-polymer-graphene nanocomposites for sensitive detection of 5-enolpyruvylshikimate-3-phosphate synthase from Agrobacdterium tumefaciens strain CP4 (CP4-EPSPS), which considered as biomarkers of genetically modified (GM) crops. Specifically, we prepared iron doped polyacrylic hydrazide modified reduced graphene nanocomposites (Fe@RGO/PAH) by in-situ polymerization approach and subsequent a one-pot reaction with hydrazine. The resulting Fe@RGO/PAH nanocomposites displayed low nonspecific adsorption to analytes (11% quenching caused by nonspecific adsorption) due to electrostatic, energetic and steric effect of the nanocomposites. After Nb immobilizing, the as-prepared Fe@RGO/PAH/Nbs showed good selectivity and high quenching ability (92% quenching) in the presence of antigen (Ag) and polyethylene glycol (PEG) modified CdTe QDs (Ag/QDs@PEG), which is a nearly 4 fold than that of the unmodified GO in same condition. The high quenching ability of Fe@RGO/PAH/Nbs can be used for detection of CP4-EPSPS based on competitive immunoassay with a linearly proportional concentration range of 5-100ng/mL and a detection limit of 0.34ng/mL. The good stability, reproducibility and specificity of the resulting immunofluorescent biosensor are demonstrated and might open a new window for investigation of fluorescent sensing with numerous multifunctional graphene based materials. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary excretion of plasma non-transferrin-bound iron in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zanninelli, G.; Loreal, O. [Pontchaillou Univ. Hospital, INSERM U-49, Liver Research Unit, Rennes (France); Choudury, R. [King`s College, Dept. of Pharmacey, London (United Kingdom)] [and others

    1997-10-01

    Background/Aims: It is well documented that levels of plasma non-transferrin-bound iron (NTBI), a particularly toxic form of iron, are increased in iron overload disorders. In light of the pathogenetic importance of NTBI in chronic iron overload, we have studied the ability of new orally active iron chelators to promote the biliary excretion of iron originating as plasma {sup 55}Fe-NTBI. Methods: Biliary iron kinetics of plasma {sup 55}Fe-labeled NTBI and cumulative recoveries of {sup 55}Fe in bile were determined in normal and carbonyl iron-loaded rats receiving a single intragastric dose of iron chelator. These chelators were the novel hydroxypyridin-4-one compounds CP102, CP41, and their respective prodrugs CP117 and CP165. Results: The cumulative recovery of {sup 5} {sup 5}Fe in bile of normal rats was increased by 5.2-, 7.9-, 11.5-, and 9.2-fold with CP102, CP117, CP41 and CP165, respectively. In iron overloaded rats, these compounds increased the cumulative recovery by 28.6-, 48.6-, 72.6-, and 32-fold, respectively. All the chelators had a choleretic effect, were metabolized by the liver as demonstrated by HPLC study of bile, and were not cytotoxic since normal plasma transaminase levels were maintained at the end of the experiments. Conclusions: These chelators have potential interest for the treatment of iron overload conditions and may offer advantages over simple N-alkyl-hydroxypyridinones such as deferiprone (CP20, L1). (au) 29 refs.

  20. Iron hypothesis of cardiovascular disease: still controversial.

    Science.gov (United States)

    Aursulesei, Viviana; Cozma, A; Krasniqi, A

    2014-01-01

    Iron hypothesis has been a controversial subject for over 30 years as many studies support its role as a risk factor for cardiovascular disease, while other studies found no evidence to support it. The conflicting results are accounted for by the non-homogeneity of trial design in terms of population inclusion criteria and different endpoints, non-uniform use of parameters for assessing iron role, and incomplete understanding of the mechanisms of action. The nature of iron is dual, being of crucial importance for the human body, but also toxic as "free iron" induces oxidative stress. Under physiological conditions, there are efficient and complex mechanisms against iron-induced oxidative stress, which could be reproduced for creating new, intelligent antioxidants. Iron depletion improves the cardiovascular prognosis only if serum concentration is at the lowest limit of normal ranges. However, low iron levels and the type of dietary iron intake correlate with atherosclerotic cardiovascular disease, influence the ischemic endpoints in the elderly, and exert negative impact on heart failure prognosis. So far, the causal relation and involved mechanisms are not fully elucidated. Iron overload is a difficult and frequent condition, involving the cardiovascular system by specific pathogenic pathways, therefore determining a particular form of restrictive cardiomyopathy and vaso-occlusive arterial damage.

  1. Effect of Iron Fortified Wheat Flour on the Biology and Physiology of Red Flour Beetle, (Herbst)

    OpenAIRE

    Sohail Ahmed; Waqas Wakil; H.M. Salman Saleem; Mohammad Shahid; M. Usman Ghazanfar

    2010-01-01

    Iron overload in the fortified flour can influence the life stages and physiology of the insects. The present study was carried out to evaluate the effect of commercially available premix iron fortified flour as well as effect of different concentrations of post-mix iron fortified flour (30–5 ppm) on biology of red flour beetle, Tribolium castaneum (Hebrst.). Larval and pupal duration, total developmental time, fecundity and larval weights in two consecutive generations of beetle were compare...

  2. Early detection of injuries in leaves of Clusia hilariana Schltdl. (Clusiaceae caused by particulate deposition of iron

    Directory of Open Access Journals (Sweden)

    Diego Ismael Rocha

    2014-06-01

    Full Text Available This study aims to evaluate the prognostic value of microscopic parameters of asymptomatic leaves of Clusia hilariana Schltdl. subjected to particulate deposition of iron (2.14 mg cm-2 day-1 for 45 consecutive days. Samples of young and expanded leaves without symptoms were collected and subjected to light and scanning electron microscopy techniques. The height of the epidermal cells on both surfaces of the leaf and the thickness of the hypodermis, the chlorophyll parenchyma, and the leaf blade were measured. Micromorphological injury occurred in the abaxial surface of young leaves and on both surfaces of expanded leaves. Erosion of the epicuticular wax and cuticle rupture were frequent on the adaxial surface, while on the abaxial surface of both leaves there was a loss of sinuosity on the anticlinal wall of the epidermal cells, stomatal deformity and obstruction. Micromorphometric alterations were seen in all leaf tissues except in the height of epidermic cells, probably due to the thick cuticle and prominent cuticular flanges. The highest difference in thickness of the leaf blade was seen in young leaves of plants subjected to SPMFe, indicating greater sensibility to particulate iron in comparison to the expanded leaves. The micromorphological and micromorphometric alterations in the leaf blade of Clusia hilariana Schltdl. showed the prognostic potential of these tools on the evaluation of impacts caused by the deposition of particulate matter, especially in the 'Restinga' natural vegetation, where the exposure is increasing due to the presence of iron ore industry in their surroundings.

  3. Deferasirox-TAT(47-57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine.

    Science.gov (United States)

    Goswami, Dibakar; Vitorino, Hector A; Alta, Roxana Y P; Silvestre, Daniel M; Nomura, Cassiana S; Machini, M Teresa; Espósito, Breno P

    2015-10-01

    Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47-57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood-brain barrier. The water-soluble conjugate was able to remove labile iron from buffered solution as well as from iron overloaded sera, and the permeability of DFX-TAT(47-57) conjugate into RBE4 cells was not affected compared to parent deferasirox. The iron bound conjugate was also able to translocate through the cell membrane.

  4. Electrocatalytic Detection of Amitrole on the Multi-Walled Carbon Nanotube – Iron (II tetra-aminophthalocyanine Platform

    Directory of Open Access Journals (Sweden)

    Tebello Nyokong

    2008-08-01

    Full Text Available It is shown that iron(II tetra-aminophthalocyanine complex electropolymerized onto a multi-walled carbon nanotube-modified basal plane pyrolytic graphite electrode greatly enhanced the electrocatalytic detetion of amitrole (a toxic herbicide, resulting in a very low detection limit (0.5 nM and excellent sensitivity of 8.80±0.44 μA/nM, compared to any known work reported so far. The electrocatalytic detection of amitrole at this electrode occurred at less positive potential (~0.3 V vs Ag|ACl and also revealed a typical coupled chemical reaction. The mechanism for this response is proposed. The electrode gave satisfactory selectivity to amitrole in the presence of other potential interfering pesticides in aqueous solutions.

  5. 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.

  6. The Influence of Domestic Overload on the Association between Job Strain and Ambulatory Blood Pressure among Female Nursing Workers

    Directory of Open Access Journals (Sweden)

    Luciana Fernandes Portela

    2013-11-01

    Full Text Available Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers.

  7. The influence of domestic overload on the association between job strain and ambulatory blood pressure among female nursing workers.

    Science.gov (United States)

    Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

    2013-11-27

    Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers.

  8. [Effect of lead exposure on brain iron in aged rats based on the MRI].

    Science.gov (United States)

    Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun; Du, Guihua; Feng, Chang; Yan, Ji; Liu, Zhenghua; Xiao, Xinlan; Fan, Guangqin

    2013-01-01

    To explore the effect of long-term lead exposure on brain iron in aged rats. SPF female and male Sprague-Dawley rats were respectively randomly divided into three groups: control, low lead-exposed, high lead-exposed. Lead-exposed female rats drank 0.8g/L or 1.5g/L lead acetate solutions through pregnancy until weaning and then the pups received 0.3g/L or 0.9g/L lead acetate solution depending on their group. Control group rats drank deionized water throughout the experiment. At the postnatal 18 months, one pup for per group was given an ultra structural detection of hippocampus, and the other male pups were measured the lead and iron concentration of blood and brain by GE MR 3.0T MR scanner and ICP-AES. In comparing with control group, the lead concentrations of blood and brain in lead-exposed groups were significantly higher, and the iron contents of brain and cortex, hippocampus, thalamus were significantly higher in 0.9g/L lead-exposed group. Also, it was highly positively correlated between blood lead and iron of blood, cortex, hippocampus, thalamus, respectively. With the dose of lead-exposed increased, cytoplasm, nucleus, mitochondrial structure and synaptic structure had suffered vary degrees of damage from ultra structural detection of hippocampus, it could be observed early neuronal apoptosis. Lead induced neurodegenerative diseases might be related to iron overload which caused by lead exposure.

  9. 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.

  10. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

    Directory of Open Access Journals (Sweden)

    Kontoghiorghe CN

    2016-01-01

    Full Text Available Christina N Kontoghiorghe, George J Kontoghiorghes Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus Abstract: The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM. Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO, oral deferiprone (L1, and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve

  11. Iron induced RNA-oxidation in the general population and in mouse tissue

    DEFF Research Database (Denmark)

    Cejvanovic, Vanja; Kjær, Laura Kofoed; Bergholdt, Helle Kirstine Mørup

    2018-01-01

    Iron promotes formation of hydroxyl radicals by the Fenton reaction, subsequently leading to potential oxidatively generated damage of nucleic acids. Oxidatively generated damage to RNA, measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine, is increased in patients with genetic iron overload......, which have led us to test the hypothesis that high iron status, assessed by iron biomarkers and genetic disposition, increases urinary excretion of 8-oxoGuo. In a general Danish population study we used a Mendelian randomization design with HFE genotypes as a proxy for iron status and supplemented...

  12. 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.

  13. Current status of iron metabolism: Clinical and therapeutic implications.

    Science.gov (United States)

    Conde Diez, Susana; de Las Cuevas Allende, Ricardo; Conde García, Eulogio

    2017-03-03

    Hepcidin is the main regulator of iron metabolism and a pathogenic factor in iron disorders. Hepcidin deficiency causes iron overload, whereas hepcidin excess causes or contributes to the development of iron-restricted anaemia in chronic inflammatory diseases. We know the mechanisms involved in the synthesis of hepcidin and, under physiological conditions, there is a balance between activating signals and inhibitory signals that regulate its synthesis. The former include those related to plasmatic iron level and also those related to chronic inflammatory diseases. The most important inhibitory signals are related to active erythropoiesis and to matriptase-2. Knowing how hepcidin is synthesised has helped design new pharmacological treatments whose main target is the hepcidin. In the near future, there will be effective treatments aimed at correcting the defect of many of these iron metabolism disorders. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Native iron

    DEFF Research Database (Denmark)

    Brooks, Charles Kent

    2015-01-01

    , a situation unique in the Solar System. In such a world, iron metal is unstable and, as we all know, oxidizes to the ferric iron compounds we call 'rust'. If we require iron metal it must be produced at high temperatures by reacting iron ore, usually a mixture of ferrous (Fe2+) and ferric (Fe3+) oxides (Fe2O3......, hematite, or FeO.Fe2O3, magnetite), with carbon in the form of coke. This is carried out in a blast furnace. Although the Earth's core consists of metallic iron, which may also be present in parts of the mantle, this is inaccessible to us, so we must make our own. In West Greenland, however, some almost...... unique examples of iron metal, otherwise called 'native iron' or 'telluric iron', occur naturally....

  15. 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)

  16. Iron biomineralization by anaerobic neutrophilic iron-oxidizing bacteria

    DEFF Research Database (Denmark)

    Miot, Jennyfer; Benzerara, Karim; Morin, Guillaume

    2009-01-01

    precipitation in the periplasm (in a few tens of minutes), followed by the formation of surface-bound globules. Moreover, we frequently observed an asymmetric mineral thickening at the cell poles. In parallel, the evolution of iron oxidation was quantified by STXM: iron both contained in the bacteria......Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate......-dependent iron-oxidizing bacterium Acidovorax sp. strain BoFeN1 in the presence of dissolved Fe(II) using electron microscopy and Scanning Transmission X-ray Microscopy (STXM). All detected minerals consisted mainly of amorphous iron phosphates, but based on their morphology and localization, three types...

  17. The Investigation of Perchlorate/Iron Phase Mixtures as A Possible Source of Oxygen Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater, Mars

    Science.gov (United States)

    Sutter, B.; Heil, E.; Morris, R. V.; Archer, P. D.; Ming, D. W.; Niles, P. B.; Eigenbrode, J. L.; Franz, H.; Freissinet C.; Glavin, D. P.; hide

    2015-01-01

    The Sample Analysis at Mars (SAM) instrument onboard the Curiosity rover detected O2 and HCl gas releases from the Rocknest (RN) eolian bedform and the John Klein (JK) and Cumberland (CB) drill hole materials in Gale Crater. Chlorinated hydrocarbons have also been detected by the SAM quadrupole mass spectrometer (QMS) and gas chromatography/mass spectrometer (GCMS). These detections along with the detection of perchlorate (ClO4-) by the Mars Phoenix Lander's Wet Chemistry Laboratory (WCL) suggesting perchlorate is a possible candidate for evolved O2 and chlorine species. Laboratory thermal analysis of individual per-chlorates has yet to provide an unequivocal temperature match to the SAM O2 and HCl release data. These detections along with the detection of perchlorate (ClO4-) by the Mars Phoenix Lander's Wet Chemistry Laboratory suggested perchlorate is a possible candidate for evolved O2 and chlorine species. Laboratory thermal analysis of pure perchlorates has yet to provide an unequivocal temperature match to the SAM O2 and HCl release data. Analog laboratory analysis of iron mineralogy detected in Gale materials that was physically mixed with Ca- and Mg-perchlorate has been shown to catalyze lower O2 release temperatures and approach some SAM O2 release data. Instead of physical mixtures used in previous work, the work presented here utilized perchlorate solutions added to Fe phases. This technique allowed for perchlorate to come in closer contact with the Fe-phase and may more closely mimic Mars conditions where humidity can increase enough to cause deliquescence of the highly hygroscopic perchlorate phases. The objective of this work is to: 1) Utilize a laboratory SAM analog instrument to evaluate the O2 release temperatures from Mg- and Ca-perchlorates solutions applied to Fephases detetected in Gale Crate; and 2) Determine if perchlorate solutions can provide improved matches with the SAM O2 temperature release profiles.

  18. 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.

  19. Biochemical and biophysical methods for studying mitochondrial iron metabolism.

    Science.gov (United States)

    Holmes-Hampton, Gregory P; Tong, Wing-Hang; Rouault, Tracey A

    2014-01-01

    Iron is a heavily utilized element in organisms and numerous mechanisms accordingly regulate the trafficking, metabolism, and storage of iron. Despite the high regulation of iron homeostasis, several diseases and mutations can lead to the misregulation and often accumulation of iron in the cytosol or mitochondria of tissues. To understand the genesis of iron overload, it is necessary to employ various techniques to quantify iron in organisms and mitochondria. This chapter discusses techniques for determining the total iron content of tissue samples, ranging from colorimetric determination of iron concentrations, atomic absorption spectroscopy, inductively coupled plasma-optical emission spectroscopy, and inductively coupled plasma-mass spectrometry. In addition, we discuss in situ techniques for analyzing iron including electron microscopic nonheme iron histochemistry, electron energy loss spectroscopy, synchrotron X-ray fluorescence imaging, and confocal Raman microscopy. Finally, we discuss biophysical methods for studying iron in isolated mitochondria, including ultraviolet-visible, electron paramagnetic resonance, X-ray absorbance, and Mössbauer spectroscopies. This chapter should aid researchers to select and interpret mitochondrial iron quantifications.

  20. Comparing the detection of iron-based pottery pigment on a carbon-coated sherd by SEM-EDS and by Micro-XRF-SEM.

    Science.gov (United States)

    Pendleton, Michael W; Washburn, Dorothy K; Ellis, E Ann; Pendleton, Bonnie B

    2014-03-01

    The same sherd was analyzed using a scanning electron microscope with energy dispersive spectroscopy (SEM-EDS) and a micro X-ray fluorescence tube attached to a scanning electron microscope (Micro-XRF-SEM) to compare the effectiveness of elemental detection of iron-based pigment. To enhance SEM-EDS mapping, the sherd was carbon coated. The carbon coating was not required to produce Micro-XRF-SEM maps but was applied to maintain an unbiased comparison between the systems. The Micro-XRF-SEM analysis was capable of lower limits of detection than that of the SEM-EDS system, and therefore the Micro-XRF-SEM system could produce elemental maps of elements not easily detected by SEM-EDS mapping systems. Because SEM-EDS and Micro-XRF-SEM have been used for imaging and chemical analysis of biological samples, this comparison of the detection systems should be useful to biologists, especially those involved in bone or tooth (hard tissue) analysis.

  1. Synchrotron radiation X-ray phase micro-computed tomography as a new method to detect iron oxide nanoparticles in the brain.

    Science.gov (United States)

    Marinescu, M; Langer, M; Durand, A; Olivier, C; Chabrol, A; Rositi, H; Chauveau, F; Cho, T H; Nighoghossian, N; Berthezène, Y; Peyrin, F; Wiart, M

    2013-10-01

    The purpose of this study was to introduce synchrotron radiation X-ray phase computed tomography (SR-PCT) as a new method of visualizing ultrasmall superparamagnetic particles of iron oxide (USPIO) distribution into the brains of mice with neuroinflammation. The sensitivity of the technique was assessed by performing back-to-back SR-PCT and magnetic resonance imaging (MRI) in mice stereotaxically injected with a range of USPIO concentrations. Eight mice with cerebral ischemia were then intravenously injected with USPIOs and imaged back-to-back with MRI and SR-PCT. SR-PCT proved sensitive enough to detect iron in nanomolar quantities. In stroke-induced animals, SR-PCT showed hyperintense areas in the regions of MR signal loss and immunostaining for macrophages. SR-PCT, moreover, identified brain anatomy as clearly as histology, without the need for sectioning or staining, with an examination time of 44 min per brain at an isotropic spatial resolution of 8 μm. SR-PCT has potential for cellular imaging in intact brain, with unequaled neuroanatomy.

  2. Simultaneous Determination of Iron, Copper and Cobalt in Food Samples by CCD-diode Array Detection-Flow Injection Analysis with Partial Least Squares Calibration Model

    Energy Technology Data Exchange (ETDEWEB)

    Mi Jiaping; Li Yuanqian; Zhou Xiaoli; Zheng Bo; Zhou Ying [West China School of Public Health, Sichuan University, Chengdu, 610041 (China)

    2006-01-01

    A flow injection-CCD diode array detection spectrophotometry with partial least squares (PLS) program for simultaneous determination of iron, copper and cobalt in food samples has been established. The method was based on the chromogenic reaction of the three metal ions and 2- (5-Bromo-2-pyridylazo)-5-diethylaminophenol, 5-Br-PADAP in acetic acid - sodium acetate buffer solution (pH5) with Triton X-100 and ascorbic acid. The overlapped spectra of the colored complexes were collected by charge-coupled device (CCD) - diode array detector and the multi-wavelength absorbance data was processed using partial least squares (PLS) algorithm. Optimum reaction conditions and parameters of flow injection analysis were investigated. The samples of tea, sesame, laver, millet, cornmeal, mung bean and soybean powder were determined by the proposed method. The average recoveries of spiked samples were 91.80%{approx}100.9% for Iron, 92.50%{approx}108.0% for Copper, 93.00%{approx}110.5% for Cobalt, respectively with relative standard deviation (R.S.D) of 1.1%{approx}12.1%. The sampling rate is 45 samples h{sup -1}. The determination results of the food samples were in good agreement between the proposed method and ICP-AES.

  3. Sport coaching officials and their stressors: Work overload, role ...

    African Journals Online (AJOL)

    Sport coaching officials and their stressors: Work overload, role ambiguity, role conflict and the influence on job satisfaction of sport coaching officials in ... African Journal for Physical Activity and Health Sciences ... Sport officials' concerns over job stressors have become common due to the adverse effect on health.

  4. 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.

  5. Biochemical assessment of lead overload and the protective effect of ...

    African Journals Online (AJOL)

    Therefore the biochemical assessment of the effect of lead overload and the possible protective effect of zinc were carried out in guinea pigs. Graded doses of lead (0ppm, 300ppm, 600ppm and 1200ppm) were administered alone or in combination with 800ppm zinc to guinea pigs for a period of 20 weeks. Blood samples ...

  6. 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

  7. 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.

  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. Diagnostic accuracy of dual-echo (in- and opposed-phase) T1-weighted gradient recalled echo for detection and grading of hepatic iron using quantitative and visual assessment

    Energy Technology Data Exchange (ETDEWEB)

    Schieda, Nicola; Ramanathan, Subramaniyan; Ryan, John; Khanna, Maneesh; Virmani, Vivek; Avruch, Leonard [The University of Ottawa, The Ottawa Hospital, Ottawa, Ontario (Canada)

    2014-07-15

    Detection and quantification of hepatic iron with dual-echo gradient recalled echo (GRE) has been proposed as a rapid alternative to other magnetic resonance imaging (MRI) techniques. Co-existing steatosis and T1 weighting are limitations. This study assesses the accuracy of routine dual-echo GRE. Between 2010 and 2013, 109 consecutive patients underwent multi-echo (ME) MRI and dual-echo GRE for quantification of hepatic iron. Liver iron concentration (LIC) was calculated from ME-MRI. Relative signal intensity (RSI) and fat signal fraction (FSF) were calculated from dual-echo GRE. Four radiologists subjectively evaluated dual-echo GRE (±subtraction). Diagnostic accuracy was compared between techniques and correlated with biopsy using Fisher's exact test, Spearman correlation and regression. The sensitivity of visual detection of iron ranged from 48 to 55 %. Subtraction did not increase sensitivity (p < 0.001). Inter-observer variability was substantial (κ = 0.72). The specificity of visual detection of iron approached 100 % with false-positive diagnoses observed using subtraction. LIC showed a higher correlation with histopathological iron grade (r = 0.94, p < 0.001) compared with RSI (r = 0.65, p = 0.02). Univariate regression showed an association between RSI and LIC (B = 0.98, p < 0.001, CI 0.73-1.23); however, the association was not significant with multi-variate regression including FSF (p = 0.28). Dual-echo GRE has low sensitivity for hepatic iron. Subtraction imaging can result in false-positive diagnoses. (orig.)

  10. Modification of glassy carbon electrode with multi-walled carbon nanotubes and iron(III)-porphyrin film: Application to chlorate, bromate and iodate detection

    International Nuclear Information System (INIS)

    Salimi, Abdollah; MamKhezri, Hussein; Hallaj, Rahman; Zandi, Shiva

    2007-01-01

    In this study, multi-wall carbon nanotubes (MWCTs) is evaluated as a transducer, stabilizer and immobilization matrix for the construction of amperometric sensor based on iron-porphyrin. 5,10,15,20-Tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)P) adsorbed on MWCNTs immobilized on the surface of glassy carbon electrode. Cyclic voltammograms of the Fe(III)P-incorporated-MWCNTs indicate a pair of well-defined and nearly reversible redox couple with surface confined characteristics at wide pH range (2-12). The surface coverage (Γ) and charge transfer rate constant (k s ) of Fe(III)P immobilized on MWCNTs were 7.68 x 10 -9 mol cm -2 and 1.8 s -1 , respectively, indicating high loading ability of MWCNTs for Fe(III)P and great facilitation of the electron transfer between Fe(III)P and carbon nanotubes immobilized on the electrode surface. Modified electrodes exhibit excellent electrocatalytic activity toward reduction of ClO 3 - , IO 3 - and BrO 3 - in acidic solutions. The catalytic rate constants for catalytic reduction of bromate, chlorate and iodate were 6.8 x 10 3 , 7.4 x 10 3 and 4.8 x 10 2 M -1 s -1 , respectively. The hydrodynamic amperometry of rotating-modified electrode at constant potential versus reference electrode was used for detection of bromate, chlorate and iodate. The detection limit, linear calibration range and sensitivity for chlorate, bromate and iodate detections were 0.5 μM, 2 μM to 1 mM, 8.4 nA/μM, 0.6 μM, 2 μM to 0.15 mM, 11 nA/μM, and 2.5 μM, 10 μM to 4 mM and 1.5 nA/μM, respectively. Excellent electrochemical reversibility of the redox couple, good reproducibility, high stability, low detection limit, long life time, fast amperometric response time, wide linear concentration range, technical simplicity and possibility of rapid preparation are great advantages of this sensor. The obtained results show promising practical application of the Fe(III)P-MWCNTs-modified electrode as an amperometric sensor for chlorate, iodate and

  11. Iron Indices in Bottlenose Dolphins (Tursiops truncatus)

    Science.gov (United States)

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

    2012-01-01

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

  12. 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

  13. Fabrication of a solution-gated transistor based on valinomycin modified iron oxide nanoparticles decorated zinc oxide nanorods for potassium detection.

    Science.gov (United States)

    Ahn, Min-Sang; Ahmad, Rafiq; Bhat, Kiesar Sideeq; Yoo, Jin-Young; Mahmoudi, Tahmineh; Hahn, Yoon-Bong

    2018-05-15

    There are considerable interests to detect and monitor the abnormal level of minerals in water for avoiding/preventing any toxic effects after consumption. Herein, we report the fabrication of solution-gated field-effect-transistor (FET) based potassium sensor using iron oxide nanoparticles (Fe 2 O 3 NPs) modified directly grown zinc oxide nanorods (ZnO NRs). The Fe 2 O 3 NPs modification of ZnO NRs provided stability to nanorods surface and improved surface area for valinomycin immobilization. As-fabricated potassium sensor (valinomycin-Fe 2 O 3 NPs-ZnO NRs/SiO 2 /Si) provided enhanced current response with increasing potassium concentration. During sensing measurements, FET sensor showed high sensitivity (4.65 μA/μM/cm 2 ) in the linear range of 0.1 μM to 125 μM, low limit of detection (∼0.04 μM), good stability, excellent reproducibility, and favorable selectivity. Thus, good sensing performance of the FET based potassium sensor presents it as simple, low-cost, and convenient device for selective detection of potassium in solution. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Christian E. Zaugg

    2004-04-01

    Full Text Available Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

  15. Influence of welding fume on systemic iron status.

    Science.gov (United States)

    Casjens, Swaantje; Henry, Jana; Rihs, Hans-Peter; Lehnert, Martin; Raulf-Heimsoth, Monika; Welge, Peter; Lotz, Anne; Gelder, Rainer Van; Hahn, Jens-Uwe; Stiegler, Hugo; Eisele, Lewin; Weiss, Tobias; Hartwig, Andrea; Brüning, Thomas; Pesch, Beate

    2014-11-01

    Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum ferritin (SF) is a recognized biomarker for iron stores, with high concentrations linked to inflammation and potentially also cancer. However, little is known about iron overload in welders. Within this study, we assessed the iron status and quantitative associations between airborne iron, body iron stores, and iron homeostasis in 192 welders not wearing dust masks. Welders were equipped with personal samplers in order to determine the levels of respirable iron in the breathing zone during a working shift. SF, prohepcidin and other markers of iron status were determined in blood samples collected after shift. The impact of iron exposure and other factors on SF and prohepcidin were estimated using multiple regression models. Our results indicate that respirable iron is a significant predictor of SF and prohepcidin. Concentrations of SF varied according to the welding technique and respiratory protection used, with a median of 103 μg l(-1) in tungsten inert gas welders, 125 μg l(-1) in those wearing air-purifying respirators, and 161 μg l(-1) in other welders. Compared to welders with low iron stores (SF < 25 μg l(-1)), those with excess body iron (SF ≥ 400 μg l(-1)) worked under a higher median concentration of airborne iron (60 μg m(-3) versus 148 μg m(-3)). Even though air concentrations of respirable iron and manganese were highly correlated, and low iron stores have been reported to increase manganese uptake in the gastrointestinal tract, no correlation was seen between SF and manganese in blood. In conclusion, monitoring SF may be a reasonable method for health surveillance of welders. Respiratory protection with air-purifying respirators can decrease iron exposure and avoid chronically higher SF in welders working with

  16. Assessment of cadmium and iron adsorption in sediment, employing a flow injection analysis system with on line filtration and detection by flame atomic absorption spectrometry and thermospray flame furnace atomic absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Fagner Moreira de; Marchioni, Camila; Barros, Juan A. V de A. [Universidade Federal de Alfenas (UNIFAL-MG), Instituto de Química, Rua GabrielMonteiro da Silva, 714, CEP 37130-000, Alfenas-MG (Brazil); Lago, Ayla Campos do [Universidade Federal de São Carlos (UFSCar-SP), Departamento de Química, 10Rodovia Washington Luís, Km 235-SP 310, CEP 16565-905, São Carlos-SP (Brazil); Wisniewski, Célio [Universidade Federal de Alfenas (UNIFAL-MG), Instituto de Química, Rua GabrielMonteiro da Silva, 714, CEP 37130-000, Alfenas-MG (Brazil); Luccas, Pedro Orival, E-mail: pedro.luccas@unifal-mg.edu.br [Universidade Federal de Alfenas (UNIFAL-MG), Instituto de Química, Rua GabrielMonteiro da Silva, 714, CEP 37130-000, Alfenas-MG (Brazil)

    2014-01-27

    Graphical abstract: -- Highlights: •A FIA system with on-line filtration for isotherms adsorption studies was proposed. •Isotherms for iron and cadmium elements in bottom lake sediment were done. •Inferences about adsorption/desorption mechanisms were feasible. •The proposed method turns the isotherm studies fast and reliable. -- Abstract: This work presents an evaluation of iron and cadmium adsorption in sediment of the Furnas Hydroelectric Plant Reservatory located in Alfenas, Minas Gerais (Brazil). The metal determination was done employing a flow injection analysis (FIA) with an on-line filtering system. As detection techniques, flame atomic absorption spectrometry (FAAS) for iron and thermospray flame furnace atomic absorption spectrometry (TS-FF-AAS) for cadmium determinations were used. The developed methodology presented good limits of detection, being 190 μg L{sup −1} for iron and 1.36 μg L{sup −1} for cadmium, and high sampling frequency for both metals 144 and 60 readings h{sup −1} for iron and cadmium, respectively. Both metals obey the Langmuir model, with maximum adsorptive capacity of 0⋅169 mg g{sup −1} for iron and 7⋅991 mg g{sup −1} for cadmium. For iron, a pseudo-first-order kinetic model was obtained with a theoretical Q{sub e} = 9⋅8355 mg g{sup −1} (experimental Q{sub e} = 9⋅5432 mg g{sup −1}), while for cadmium, a pseudo-second-order kinetic model was obtained, with a theoretical Q{sub e} = 0.3123 mg g{sup −1} (experimental Q{sub e} = 0⋅3052 mg g{sup −1})

  17. 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.

  18. 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)

  19. 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

  20. Culinary plants and their potential impact on metabolic overload.

    Science.gov (United States)

    Kim, Ji Yeon; Kwon, Oran

    2011-07-01

    Contemporary human behavior has led a large proportion of the population to metabolic overload and obesity. Postprandial hyperlipidemia and hyperglycemia evoke redox imbalance in the short term and lead to complex chronic disease in the long term with repeated occurrence. Complex diseases are best prevented with complex components of plants; thus, current nutrition research has begun to focus on the development of plant-based functional foods and dietary supplements for health and well-being. Furthermore, given the wide range of species, parts, and secondary metabolites, culinary plants can contribute significant variety and complexity to the human diet. Although understanding the health benefits of culinary plants has been one of the great challenges in nutritional science due to their inherent complexity, it is an advantageous pursuit. This review will address the challenges and opportunities relating to studies of the health benefits of culinary plants, with an emphasis on obesity attributed to metabolic overload. © 2011 New York Academy of Sciences.

  1. CHIP protects against cardiac pressure overload through regulation of AMPK

    Science.gov (United States)

    Schisler, Jonathan C.; Rubel, Carrie E.; Zhang, Chunlian; Lockyer, Pamela; Cyr, Douglas M.; Patterson, Cam

    2013-01-01

    Protein quality control and metabolic homeostasis are integral to maintaining cardiac function during stress; however, little is known about if or how these systems interact. Here we demonstrate that C terminus of HSC70-interacting protein (CHIP), a regulator of protein quality control, influences the metabolic response to pressure overload by direct regulation of the catalytic α subunit of AMPK. Induction of cardiac pressure overload in Chip–/– mice resulted in robust hypertrophy and decreased cardiac function and energy generation stemming from a failure to activate AMPK. Mechanistically, CHIP promoted LKB1-mediated phosphorylation of AMPK, increased the specific activity of AMPK, and was necessary and sufficient for stress-dependent activation of AMPK. CHIP-dependent effects on AMPK activity were accompanied by conformational changes specific to the α subunit, both in vitro and in vivo, identifying AMPK as the first physiological substrate for CHIP chaperone activity and establishing a link between cardiac proteolytic and metabolic pathways. PMID:23863712

  2. Debris Hazards Due to Overloaded Conventional Construction Facades

    Science.gov (United States)

    2015-12-01

    cubic meter (m 3 ) Mass/ Density pound (lb) 4.535 924 × 10 –1 kilogram (kg) unified atomic mass unit (amu) 1.660 539 × 10 –27 kilogram (kg...hazards to buildings. This work will present results for experiments involving conventional façade materials (glass, concrete , and mason- ry) that have...been overloaded to generate debris data at the structural and material levels. The material level samples have been loaded at high pressures using a

  3. Selective extraction by dissolvable (nitriloacetic acid-nickel)-layered double hydroxide coupled with reaction with potassium thiocyanate for sensitive detection of iron(III).

    Science.gov (United States)

    Tang, Sheng; Chang, Yuepeng; Shen, Wei; Lee, Hian Kee

    2016-07-01

    A highly selective method has been proposed for the determination of iron cation (Fe(3+)). (Nitriloacetic acid-nickel)-layered double hydroxide ((NTA-Ni)-LDH) was successfully synthesized and used as dissolvable sorbent in dispersive solid-phase extraction to pre-concentrate and separate Fe(3+) from aqueous phase. Since Fe(3+) has a larger formation constant with NTA compared to Ni(2+), subsequently ion exchange occurred when (NTA-Ni)-LDH was added to the sample solution. The resultant (NTA-Fe)-LDH sol was isolated and transferred in an acidic medium containing potassium thiocyanate (KSCN). Since (NTA-Fe)-LDH could be dissolved in acidic conditions, Fe(3+)was released and reacted with SCN(-) to form an Fe-SCN complex. The resulting product was measured by ultraviolet-visible spectrometry for quantitative detection of Fe(3+). Extraction factors, including sample pH, reaction pH, extraction temperature, extraction time, reaction time and concentration of KSCN were optimized. This method achieved a low limit of detection of 15.2nM and a good linear range from 0.05 to 50μM (r(2)=0.9937). A nearly 18-fold enhancement of signal intensity was achieved after selective extraction. The optimized conditions were validated by applying the method to determine Fe(3+) in seawater samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. National Metal Casting Research Institute final report. Development of an automated ultrasonic inspection cell for detecting subsurface discontinuities in cast gray iron. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    Burningham, J.S. [University of Northern Iowa, Cedar Falls, IA (United States). Dept. of Industrial Technology

    1995-08-01

    This inspection cell consisted of an ultrasonic flaw detector, transducer, robot, immersion tank, computer, and software. Normal beam pulse-echo ultrasonic nondestructive testing, using the developed automated cell, was performed on 17 bosses on each rough casting. Ultrasonic transducer selection, initial inspection criteria, and ultrasonic flow detector (UFD) setup parameters were developed for the gray iron castings used in this study. The software were developed for control of the robot and UFD in real time. The software performed two main tasks: emulating the manual operation of the UFD, and evaluating the ultrasonic signatures for detecting subsurface discontinuities. A random lot of 105 castings were tested; the 100 castings that passed were returned to the manufacturer for machining into finished parts and then inspection. The other 5 castings had one boss each with ultrasonic signatures consistent with subsurface discontinuities. The cell was successful in quantifying the ultrasonic echo signatures for the existence of signature characteristics consistent with Go/NoGo criteria developed from simulated defects. Manual inspection showed that no defects in the areas inspected by the automated cell avoided detection in the 100 castings machined into finished parts. Of the 5 bosses found to have subsurface discontinuities, two were verified by manual inspection. The cell correctly classified 1782 of the 1785 bosses (99.832%) inspected.

  5. 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.

  6. Oxidation-Induced Degradable Nanogels for Iron Chelation

    Science.gov (United States)

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

    2016-02-01

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

  7. The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss.

    Science.gov (United States)

    Xu, Zi; Sun, Weijia; Li, Yuheng; Ling, Shukuan; Zhao, Chenyang; Zhong, Guohui; Zhao, Dingsheng; Song, Jinping; Song, Hailin; Li, Jinqiao; You, Linhao; Nie, Guangjun; Chang, Yanzhong; Li, Yingxian

    2017-01-01

    Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1+IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Formal Constraints on Memory Management for Composite Overloaded Operations

    Directory of Open Access Journals (Sweden)

    Damian W.I. Rouson

    2006-01-01

    Full Text Available The memory management rules for abstract data type calculus presented by Rouson, Morris & Xu [15] are recast as formal statements in the Object Constraint Language (OCL and applied to the design of a thermal energy equation solver. One set of constraints eliminates memory leaks observed in composite overloaded expressions with three current Fortran 95/2003 compilers. A second set of constraints ensures economical memory recycling. The constraints are preconditions, postconditions and invariants on overloaded operators and the objects they receive and return. It is demonstrated that systematic run-time assertion checking inspired by the formal constraints facilitated the pinpointing of an exceptionally hard-to-reproduce compiler bug. It is further demonstrated that the interplay between OCL's modeling capabilities and Fortran's programming capabilities led to a conceptual breakthrough that greatly improved the readability of our code by facilitating operator overloading. The advantages and disadvantages of our memory management rules are discussed in light of other published solutions [11,19]. Finally, it is demonstrated that the run-time assertion checking has a negligible impact on performance.

  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. Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    International Nuclear Information System (INIS)

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao; Hu, Jin; Zhang, Qiang; Liu, Bo; Wang, Min; Xu, Hui-bo; Sun, Xiao-bo

    2014-01-01

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na + channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca 2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca 2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca 2+ overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca 2+ handling proteins demonstrated that aconitine promoted Ca 2+ overload through the expression regulation of Ca 2+ handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca 2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca 2+ overload causes arrhythmia in rats

  11. Iron refractory iron deficiency anemia

    Science.gov (United States)

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  12. Iron deficiency in cancer patients

    Directory of Open Access Journals (Sweden)

    Flávio Augusto Naoum

    Full Text Available ABSTRACT Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.

  13. 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.

  14. 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.

  15. Magnetic Marking and Intraoperative Detection of Primary Draining Lymph Nodes in High-Risk Prostate Cancer Using Superparamagnetic Iron Oxide Nanoparticles: Additional Diagnostic Value

    Directory of Open Access Journals (Sweden)

    Alexander Winter

    2017-12-01

    Full Text Available Sentinel lymph node dissection (sLND using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs as a tracer was successfully applied in prostate cancer (PCa. Radioisotope-guided sLND combined with extended pelvic LND (ePLND achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/mL and/or Gleason score ≥ 8 and/or cT2c from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%. sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template. These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes/lymph node metastases outside the established node template in high-risk PCa.

  16. Host iron withholding demands siderophore utilization for Candida glabrata to survive macrophage killing.

    Directory of Open Access Journals (Sweden)

    Tracy Nevitt

    2011-03-01

    Full Text Available The fungal pathogen Candida glabrata has risen from an innocuous commensal to a major human pathogen that causes life-threatening infections with an associated mortality rate of up to 50%. The dramatic rise in the number of immunocompromised individuals from HIV infection, tuberculosis, and as a result of immunosuppressive regimens in cancer treatment and transplant interventions have created a new and hitherto unchartered niche for the proliferation of C. glabrata. Iron acquisition is a known microbial virulence determinant and human diseases of iron overload have been found to correlate with increased bacterial burden. Given that more than 2 billion people worldwide suffer from iron deficiency and that iron overload is one of the most common single-gene inherited diseases, it is important to understand whether host iron status may influence C. glabrata infectious disease progression. Here we identify Sit1 as the sole siderophore-iron transporter in C. glabrata and demonstrate that siderophore-mediated iron acquisition is critical for enhancing C. glabrata survival to the microbicidal activities of macrophages. Within the Sit1 transporter, we identify a conserved extracellular SIderophore Transporter Domain (SITD that is critical for siderophore-mediated ability of C. glabrata to resist macrophage killing. Using macrophage models of human iron overload disease, we demonstrate that C. glabrata senses altered iron levels within the phagosomal compartment. Moreover, Sit1 functions as a determinant for C. glabrata to survive macrophage killing in a manner that is dependent on macrophage iron status. These studies suggest that host iron status is a modifier of infectious disease that modulates the dependence on distinct mechanisms of microbial Fe acquisition.

  17. 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...

  18. Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils

    Directory of Open Access Journals (Sweden)

    Skaat H

    2013-10-01

    Full Text Available Hadas Skaat,1 Enav Corem-Slakmon,1 Igor Grinberg,1 David Last,2 David Goez,2 Yael Mardor,2,3 Shlomo Margel1 1Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Ramat-Gan, Israel; 2Advanced Technology Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; 3Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Abstract: Amyloid-β (Aβ peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer's disease (AD and is related to the pathogenesis of AD. Passive anti-Aβ immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific anti-Aβ monoclonal antibodies (aAβmAbs to delay Aβ aggregation in the brain. However, the main disadvantage of this approach is the required readministration of the aAβmAbs at frequent intervals. There are only a few reports describing in vitro study for the immobilization of aAβmAbs to nanoparticles as potential targeting agents of Aβ aggregates. In this article, we report the immobilization of the aAβmAb clone BAM10 to near-infrared fluorescent maghemite nanoparticles for the inhibition of Aβ40 fibrillation kinetics and the specific detection of Aβ40 fibrils. The BAM10-conjugated iron oxide nanoparticles were well-characterized, including their immunogold labeling and cytotoxic effect on PC-12 (pheochromocytoma cell line. Indeed, these antibody-conjugated nanoparticles significantly inhibit the Aβ40 fibrillation kinetics compared with the same concentration, or even five times higher, of the free BAM10. This inhibitory effect was confirmed by different assays such as the photo-induced crosslinking of unmodified proteins combined with sodium dodecyl sulfate–polyacrylamide gel electrophoresis. A cell viability assay also confirmed that these antibody-conjugated nanoparticles significantly reduced the Aβ40-induced cytotoxicity to PC-12 cells. Furthermore, the selective

  19. Effect of iron on pancreatic beta cell function and insulin resistance

    African Journals Online (AJOL)

    Dr Olaleye

    the incidence of diabetes mellitus was investigated on the pancreatic beta cell function and insulin resistance in normal ... hyperglycaemia, insulin resistance, hyperinsulinaemia, inflammation and pancreatic beta cell dysfunction thus predisposing the ..... and antioxidant status in alpha-thalassemia major: iron overload and ...

  20. Demonstration of iron in exfoliated buccal cells of β-thalassemia major patients

    Directory of Open Access Journals (Sweden)

    Atul A Bhat

    2013-01-01

    Conclusion: Oral exfoliative cytology can be a useful tool in demonstration of iron overload in thalassemic patients, however, further research in this field in the direction of quantification of these procedures is required, which can establish this non-invasive procedure as an ideal screening tool.

  1. Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

    Science.gov (United States)

    2017-12-22

    Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Langerhans Cell Histiocytosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Mast Cell Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelofibrosis; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Waldenstrom Macroglobulinemia

  2. Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats

    Czech Academy of Sciences Publication Activity Database

    Frýdlová, J.; Přikryl, P.; Truksa, Jaroslav; Falke, L. L.; Du, X.; Gurieva, I.; Vokurka, M.; Krijt, J.

    2016-01-01

    Roč. 11, č. 2 (2016), č. článku e0148540. E-ISSN 1932-6203 R&D Projects: GA ČR GA13-28830S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : HEPCIDIN EXPRESSION * SERINE-PROTEASE * GENE-EXPRESSION Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  3. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

    Science.gov (United States)

    Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2016-01-01

    Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

  4. Role of iron metabolism genetic determinants in response to chelation therapy in a cohort of β-thalassemia and sickle cell syndromes Italian patients

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2014-09-01

    Full Text Available In patients with β-thalassemia and sickle cell syndromes there is an important secondary iron overload due to regular blood transfusions and increased duodenal iron absorption. As in genetic hemochromatosis, also the secondary iron storage leads to tissue injury that involves all the major organs: liver, heart, kidney, endocrine glands. At present, in patients with β-thalassemia and sickle cell syndrome, iron chelation therapy is widely used for the treatment of secondary hemochromatosis, to limit the toxic effects of iron overload. In order to maintain the correct homeostasis, several genes are involved in the metabolic pathways of iron, including HFE, FPN (ferroportin and TF (transferrin. In this study we analyzed the genes HFE, FPN and TF, to assess their possible effects on response to therapy with deferasirox and deferiprone, either as monotherapy or in combination therapy in a cohort of patients with β-thalassemia and sickle cell syndromes.

  5. Detection and Monitoring of Surface Motions in Active Open Pit Iron Mine in the Amazon Region, Using Persistent Scatterer Interferometry with TerraSAR-X Satellite Data

    Directory of Open Access Journals (Sweden)

    Marcos E. Hartwig

    2013-09-01

    Full Text Available Persistent Scatterer interferometry (PSI represents a powerful tool for the detection and monitoring of tiny surface deformations in vast areas, allowing a better understanding of its triggering mechanisms, planning of mitigation measures, as well as to find better solutions for social and environmental issues. However, there is no record hitherto of its use in active open pit mine in tropical rainforest environment. In this paper we evaluate the use of the PSI technique for the detection and monitoring of mine slope deformations in the N4W iron mine and its surroundings, Pará State, Northern Brazil. The PSI processing was performed with 18 ascending SAR scenes of the TerraSAR-X satellite acquired in the dry season of 2012. The results showed a significant number of widely distributed persistent scatterers. It was observed that most of the study area was stable during the time span. Nevertheless, high deformation rates (312 mm/year were mapped over the mine waste piles, but do not offer any hazard, since they are expected displacements of meters in magnitude for these manmade land structures. Additionally, it was mapped tiny deformation rates in both the east and west flanks of pits 1 and 2. The main underlying reasons can be assigned to the accommodation phenomena of very poor rock masses, to the local geometric variations of the slope cuts, to the geological contact between ironstones and the country rocks, to the exploitation activities, as well as to the major geological structures. This study showed the applicability of the PSI technique using TerraSAR-X scenes in active open pit mines in tropical moist environment. However, the PSI technique is not capable in providing real-time warnings, and faces limitations due to SAR viewing geometry. In this sense, we strongly recommend the use of radar scenes acquired in both ascending and descending orbits, which would also provide a more complete understanding of the deformation patterns.

  6. Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

    Science.gov (United States)

    Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Wei, Yuling; Ji, Chaonan; Yang, Junqing

    2016-01-01

    Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE2-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels, while there was a dose-dependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE2 through a negative feedback mechanism, increasing the EP3 expression level, decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients. PMID:27033056

  7. 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.

  8. Protection of insulated cables and lines in case of overload

    Energy Technology Data Exchange (ETDEWEB)

    Goltz, M.

    1983-01-01

    After DIN 57100 Part 430/VDE 0100 part 430 for the protection of lines and cables was published in June 1981, the discussion flared up again whether this DIN/VDE-regulation is sufficient. Some papers have already been published on the right selection and arrangement of overload protection under normal operational conditions. The aim of this contribution is to explain abnormal operational conditions which are dealt with in DIN 57100 part 430/VDE 0100 part 430 in comments and the annex, and to supply some help for planning and projecting.

  9. The body of women and the overload of sexuality

    Directory of Open Access Journals (Sweden)

    Rosa Cobo Bedia

    2015-12-01

    Full Text Available This work is approaching to a historically recent social phenomenon: the hipersexualization of women. It looks into its origins and finds that the idea of the sexual freedom that is developed in the 60s, on one side, and the exaltation of the free market, which was developed from the 80s, on the other, come together in the goal of overloading women sexuality. The context in which this process takes place is a free and unlimited market which has understood that women`s bodies are a commodity from which are extracted necessaries appreciations for the social reproduction of contemporary patriarchy and neoliberal capitalism.

  10. 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

    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......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...

  11. Survey and clinical application of serum iron, total iron binding capacity, transferrin saturation, and serum ferritin in captive black and white ruffed lemurs (Varecia variegata variegata).

    Science.gov (United States)

    Crawford, Graham C; Andrews, Gordon A; Chavey, Patricia S; Dunker, Freeland H; Garner, Michael M; Sargent, Eva L

    2005-12-01

    Serum samples from 63 clinically normal captive black and white ruffed lemurs (Varecia variegata variegata) were analyzed to survey serum iron, total iron binding capacity, transferrin saturation, and serum ferritin levels. Data analysis showed no differences in these analytes attributable to sex, but significantly higher levels of serum iron, transferrin saturation, and serum ferritin in older animals. The survey data were examined in light of two black and white ruffed lemurs that were treated for iron overload with serial phlebotomies. Prior to therapy, both phlebotomized lemurs had excess hepatic iron deposition, but had serum iron, transferrin saturation, and serum ferritin below the upper limits observed in the survey animals, suggesting that some clinically normal animals included in the survey may have accumulated excess systemic iron. Serial phlebotomy therapy reduced serum iron, transferrin saturation, and serum ferritin in both animals. Three years after the conclusion of therapy in the one remaining case, serum iron and transferrin saturation have risen substantially, whereas serum ferritin has risen slightly. Serum iron, transferrin saturation, and serum ferritin may be useful predictors of systemic iron stores in this species, though the correlation between these parameters and systemic iron stores needs to be determined.

  12. Bezafibrate Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis

    Directory of Open Access Journals (Sweden)

    Si-Chi Xu

    2017-01-01

    Full Text Available Background. Peroxisome proliferator-activated receptor-α (PPAR-α is closely associated with the development of cardiac hypertrophy. Previous studies have indicated that bezafibrate (BZA, a PPAR-α agonist, could attenuate insulin resistance and obesity. This study was designed to determine whether BZA could protect against pressure overload-induced cardiac hypertrophy. Methods. Mice were orally given BZA (100 mg/kg for 7 weeks beginning 1 week after aortic banding (AB surgery. Cardiac hypertrophy was assessed based on echocardiographic, histological, and molecular aspects. Moreover, neonatal rat ventricular cardiomyocytes (NRVMs were used to investigate the effects of BZA on the cardiomyocyte hypertrophic response in vitro. Results. Our study demonstrated that BZA could alleviate cardiac hypertrophy and fibrosis in mice subjected to AB surgery. BZA treatment also reduced the phosphorylation of protein kinase B (AKT/glycogen synthase kinase-3β (GSK3β and mitogen-activated protein kinases (MAPKs. BZA suppressed phenylephrine- (PE- induced hypertrophy of cardiomyocyte in vitro. The protective effects of BZA were abolished by the treatment of the PPAR-α antagonist in vitro. Conclusions. BZA could attenuate pressure overload-induced cardiac hypertrophy and fibrosis.

  13. 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.

  14. Immune overload: Parental attitudes toward combination and single antigen vaccines.

    Science.gov (United States)

    Hulsey, Ella; Bland, Tami

    2015-05-21

    Parental concerns have led to a recent decline in immunization coverage, resulting in outbreaks of diseases that were once under control in the US. As the CDC vaccination schedule continues to increase in complexity, the number of required injections per office visit increases as well. Some parents perceive that there is trauma associated with the administration of multiple injections, and research shows that having multiple vaccines due in a single visit is associated with delays and lower immunization rates. Combination vaccines make vaccination more efficient by incorporating the antigens of several different diseases into a single injection, but many parents worry that they may overload the child's developing immune system and leave him or her susceptible to secondary infections. This literature review synthesizes current evidence regarding the parental fear of vaccine-induced immune system overload and the fear of vaccine-associated trauma, in an attempt to understand the scope and nature of these fears. Despite the wealth of knowledge about each of these fears individually, it is still unknown which is of greater concern and how this affects parental decision-making. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Criterion validation of a stress measure: the Stress Overload Scale.

    Science.gov (United States)

    Amirkhan, James H; Urizar, Guido G; Clark, Sarah

    2015-09-01

    Validating stress scales poses problems beyond those of other psychological measures. Here, 3 studies were conducted to address those problems and assess the criterion validity of scores from a new theory-derived measure, the Stress Overload Scale (SOS; Amirkhan, 2012). In Study 1, the SOS was tested for its ability to predict postsemester illness in a sample of college students (n = 127). Even with precautions to minimize criterion contamination, scores were found to predict health problems in the month following a final exam on all of 5 different criteria. In Study 2, a community sample (n = 231) was used to test the SOS' ability to differentiate people in stressful circumstances from those in more relaxed contexts. SOS scores demonstrated excellent sensitivity (96%) and specificity (100%) in this general population application. In Study 3, the SOS was tested for its ability to differentiate salivary cortisol responses to a laboratory stressor in a group of pregnant women (n = 40). High scores were found to be associated with a blunted cortisol response, which is indicative of HPA-axis overload and typical of persons suffering chronic stress and stress-related pathology. Across all 3 studies, despite variations in the stressor, criterion, population, and methods, SOS scores emerged as valid indicators of stress. However, each study also introduced new problems that beg additional corrective steps in future stress-scale validity tests. These strategies, and the SOS' utility as a research and diagnostic tool in varied applications and populations, are discussed. (c) 2015 APA, all rights reserved.

  16. Stress overload: a new approach to the assessment of stress.

    Science.gov (United States)

    Amirkhan, James H

    2012-03-01

    The link between stress and health has not received strong empirical support, possibly due to problems in the stress measures used. Here, the first wholly empirical development of a new "Stress Overload Scale" is described. A pool of 150 items was formed to reflect "overload", a common denominator in stress theories. Then, the results of five sequenced studies, conducted in heterogeneous community samples, were used to pare the item pool. Exploratory (n = 431) and confirmatory (n = 433) analyses revealed two factors (Event Load and Personal Vulnerability) corresponding to theoretical constructs; only the best factor markers were submitted to further construct validity (n = 310) and reliability tests (n = 342). The 24 strongest items were selected for the SOS, which demonstrated criterion validity in predicting who (n = 285) would become sick following a common stressor. The SOS is (1) psychometrically strong, especially in its validity relative to popular measures; (2) appropriate to community research, due to its brevity and fit to a broad demographic spectrum; (3) unique in its ability to cross-section individuals into risk categories. It should prove useful to community psychologists in determining etiology, diagnosing risk for pathology, and evaluating the efficacy of interventions.

  17. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle.

    Science.gov (United States)

    Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

    2016-01-01

    Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

  18. Myosin isoenzyme distribution in overloaded human atrial tissue.

    Science.gov (United States)

    Buttrick, P M; Malhotra, A; Brodman, R; McDermott, L; Lam, L

    1986-09-01

    Using nondenaturing polyacrylamide gel electrophoresis, we have identified two distinct myosin isoenzymes in human atrial tissue that correspond to the V1 and V3 isomyosins found in rat ventricular tissue. Normal left and right atrial appendages have approximately 50% V3. When the left atrium was exposed to hemodynamic overload secondary to mitral stenosis, the percent V3 increased to 77 +/- 10% (n = 10); exposure to hemodynamic overload secondary to mitral regurgitation caused an increase to 70 +/- 14% (n = 6). Changes in the isoenzyme pattern were seen in the right atria of patients with mitral stenosis and markedly elevated pulmonary arterial pressures compared with control subjects and patients with mitral stenosis without severe pulmonary hypertension. Several clinical variables were examined to determine which factors might influence isoenzyme expression. Age, sex, the presence of atrial fibrillation, and pulmonary capillary wedge pressure did not predict the isoenzyme pattern. However, patients with mitral valvular disease and only slightly enlarged left atria tended to have a higher percent V3 than those with massively enlarged atria. These data confirm that human atrial tissue, like rat ventricular tissue, can alter its isomyosin composition in response to a hemodynamic load. The data further suggest that the isoenzyme shift is an early adaptation to the imposed load.

  19. Intestinal bacterial overgrowth includes potential pathogens in the carbohydrate overload models of equine acute laminitis.

    Science.gov (United States)

    Onishi, Janet C; Park, Joong-Wook; Prado, Julio; Eades, Susan C; Mirza, Mustajab H; Fugaro, Michael N; Häggblom, Max M; Reinemeyer, Craig R

    2012-10-12

    Carbohydrate overload models of equine acute laminitis are used to study the development of lameness. It is hypothesized that a diet-induced shift in cecal bacterial communities contributes to the development of the pro-inflammatory state that progresses to laminar failure. It is proposed that vasoactive amines, protease activators and endotoxin, all bacterial derived bioactive metabolites, play a role in disease development. Questions regarding the oral bioavailability of many of the bacterial derived bioactive metabolites remain. This study evaluates the possibility that a carbohydrate-induced overgrowth of potentially pathogenic cecal bacteria occurs and that bacterial translocation contributes toward the development of the pro-inflammatory state. Two groups of mixed-breed horses were used, those with laminitis induced by cornstarch (n=6) or oligofructan (n=6) and non-laminitic controls (n=8). Cecal fluid and tissue homogenates of extra-intestinal sites including the laminae were used to enumerate Gram-negative and -positive bacteria. Hors