WorldWideScience

Sample records for cardiac iron overload

  1. Secoisolariciresinol Diglucoside Abrogates Oxidative Stress-Induced Damage in Cardiac Iron Overload Condition

    OpenAIRE

    Stephanie Puukila; Sean Bryan; Anna Laakso; Jessica Abdel-Malak; Carli Gurney; Adrian Agostino; Adriane Belló-Klein; Kailash Prasad; Neelam Khaper

    2015-01-01

    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 ...

  2. Iron Overload

    Science.gov (United States)

    ... drug called an iron chelator to remove excess iron from your body because of transfusion-dependent anemias. Be sure to talk with your doctor about the potential benefits and risks of using these drugs. Previous Article ...

  3. Iron overload and immunity

    Institute of Scientific and Technical Information of China (English)

    Gra(c)a Porto; Maria De Sousa

    2007-01-01

    Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage.Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.

  4. 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.

  5. 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.

  6. Hepcidin in iron overload disorders

    OpenAIRE

    Papanikolaou, George; Tzilianos, Michalis; Christakis, John I.; Bogdanos, Dionisios; Tsimirika, Konstantina; MacFarlane, Julie; Goldberg, Y. Paul; Sakellaropoulos, Nikos; Ganz, Tomas; Nemeth, Elizabeta

    2005-01-01

    Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in ...

  7. Pathology of hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Yves Deugnier; Bruno Turlin

    2007-01-01

    Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available.Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis,nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome,noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

  8. Current and future treatment strategies for iron overload cardiomyopathy.

    Science.gov (United States)

    Wongjaikam, Suwakon; Kumfu, Sirinart; Chattipakorn, Siriporn C; Fucharoen, Suthat; Chattipakorn, Nipon

    2015-10-15

    Iron overload cardiomyopathy is the major cause of death in transfusion-dependent thalassemia (TDT) patients. Growing evidence demonstrates that combined iron chelators, or the combination of an iron chelator with antioxidant(s) are effective in diminishing myocardial iron deposition and attenuating cardiac dysfunction. This review comprehensively summarizes basic and clinical reports on the therapeutic efficacy of combined iron chelators, or the combination of an iron chelator with antioxidant(s) on the heart. Promising benefits of these treatments in preventing cardiac dysfunction due to iron overload could provide extensive insight into future therapeutic strategies for better treatment and prevention of cardiomyopathy in TDT patients. PMID:26291660

  9. Cardiac iron across different transfusion-dependent diseases

    OpenAIRE

    Wood, John C.

    2008-01-01

    Iron overload occurs in patients who require regular blood transfusions to correct genetic and acquired anaemias, such as β-thalassaemia major, sickle cell disease, and myelodysplastic syndromes. Although iron overload causes damage in many organs, accumulation of cardiac iron is a leading cause of death in transfused patients with β-thalassaemia major. The symptoms of cardiac iron overload will occur long after the first cardiac iron accumulation, at a point when treatment is more complex th...

  10. Hyperferritinaemia in the absence of iron overload

    OpenAIRE

    Arnold, J.; Mumford, A.; Lindsay, J.; Hegde, U; Hagan, M.; Hawkins, J.

    1997-01-01

    Background—Serum ferritin is normally a marker of iron overload. Ferritin genes are sited at chromosomes 19 and 11. Regulation of ferritin synthesis involves an interaction between an iron regulatory protein (IRP) and part of the ferritin mRNA designated the iron regulatory element (IRE). A disorder of ferritin synthesis resulting in hyperferritinaemia in the absence of iron overload has been described recently. 
Patients and methods—Hyperferriti- naemia in the absence of iron ove...

  11. Iron overload in sickle cell disease.

    Science.gov (United States)

    Raghupathy, Radha; Manwani, Deepa; Little, Jane A

    2010-01-01

    In sickle cell disease transfusions improve blood flow by reducing the proportion of red cells capable of forming sickle hemoglobin polymer. This limits hemolysis and the endothelial damage that result from high proportions of sickle polymer-containing red cells. Additionally, transfusions are used to increase blood oxygen carrying capacity in sickle cell patients with severe chronic anemia or with severe anemic episodes. Transfusion is well-defined as prophylaxis (stroke) and as therapy (acute chest syndrome and stroke) for major complications of sickle cell disease and has been instituted, based on less conclusive data, for a range of additional complications, such as priapism, vaso-occlusive crises, leg ulcers, pulmonary hypertension, and during complicated pregnancies. The major and unavoidable complication of transfusions in sickle cell disease is iron overload. This paper provides an overview of normal iron metabolism, iron overload in transfused patients with sickle cell disease, patterns of end organ damage, diagnosis, treatment, and prevention of iron overload. PMID:20490352

  12. Hepatic iron overload: Quantitative MR imaging

    International Nuclear Information System (INIS)

    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

  13. 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 

  14. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  15. Iron Overload Assessment in Adult Thalassaemic Patients Using MRI T2

    Directory of Open Access Journals (Sweden)

    Azita Azarkeivan

    2009-01-01

    Full Text Available "nd anemia in our country. Blood transfusion is the continual treatment of this disease. But transfusion causes a serious side effect which is iron overload in vital organs such as the heart, liver and the endocrine system. Accumulated iron in these organs may cause high risk secondary problems which threaten the patients' life. Early assessment of the iron overload in vital organs and applying for early treatment can be beneficial for increasing life quality in these patients. Assessment of cardiac and hepatic iron overload using MRI T2 technique and comparing it with serum ferritin level was the goal of this study. "nMaterials and Methods: The referred thalassaemic patients to Zafar adult thalassaemia clinic were the population of this study. Serum ferritin test was carried out for all these patients. Cardiac and hepatic iron overload assessment of these patients was performed in Noor medical imaging center using MRI T2 technique. The iron overload results of all patients were classified as normal, mild, moderate and severe. We compared them with the patients’ clinical parameters, especially the serum ferritin level. Results were analyzed by SPSS software. "nResults: 700 adult patients with the mean age of 25.76 (SD±10.4 were studied in this research project. There were 360 males (51.4% and 340 (48.6% females enrolled in this study. Among them, there were 502 (71.7% major thalassaemia, 158 (22.6% intermediate thalassaemia, 7 alpha thalassaemia, 9 sickle cell anemia and 10 hemochromatosis patients. The mean of serum ferritin level was 2327.6 mg/dl (SD±2095.8. Classified results of cardiac iron overload assessment were normal in 366 (66.5% patients, mild in 44 (8% patients, moderate in 64 (11.6% patients, and severe in 76 (13.8%patients. The classified results of hepatic iron overload assessment were: normal in 122 (22.2% patients, mild in 137 (25% patients, moderate in 235 (42.8% patients and severe in 55 (10% patients. Iron overload

  16. CHELATION THERAPY FOR IRON OVERLOAD: NURSING PRACTICE IMPLICATIONS

    OpenAIRE

    Eckes, Ellen J.

    2011-01-01

    Many diseases of the blood are treated with blood transfusion therapy. Chronic transfusions can cause iron overload, and, if untreated, can cause end-organ damage. Chelation therapy provides a way of treating iron overload and minimizing its adverse effects. Nurses need to understand that iron overload is a consequence of chronic blood transfusion, and they need to know what effects it has on end-organs and what treatment options are available.

  17. Iron overload in non-transfusion-dependent thalassemia: association with genotype and clinical risk factors.

    Science.gov (United States)

    Tantiworawit, Adisak; Charoenkwan, Pimlak; Hantrakool, Sasinee; Choeyprasert, Worawut; Sivasomboon, Chate; Sanguansermsri, Torpong

    2016-06-01

    In the present study, we sought to determine the prevalence of iron overload in patients with non-transfusion-dependent thalassemia (NTDT) and its association with genotype and other clinical risk factors, and to evaluate the correlation between serum ferritin (SF) and liver iron concentration (LIC). Myocardial and liver iron concentration was measured by MRI using a T2* gradient multi-echo sequence in NTDT patients, aged 10-50 years. Of 91 patients, 54 (59 %) had hepatic iron overload. None had cardiac iron overload. The clinical risk factors for hepatic iron overload were age >20 years (adjusted OR 30.2, 95 % CI 4.5-203, p 10 units (adjusted OR 53.6, 95 % CI 3.2-884, p = 0.005). Beta-thalassemia genotype was associated with higher risk of iron overload by univariate analysis, but the association was not significant when adjusted for other clinical factors. The correlation coefficient between SF and LIC was 0.60 (p < 0.001). In conclusion, the prevalence of hepatic iron overload is high in NTDT. Older age, lower hemoglobin level, and higher cumulative RBC transfusion are significant risk factors. SF and LIC show a significant positive correlation. PMID:27052211

  18. Progress in evaluation and treatment of hepatic iron overload

    Directory of Open Access Journals (Sweden)

    DING Rui

    2014-09-01

    Full Text Available Iron overload is a metabolic disorder characterized by excessive iron deposition in the liver, pancreas, heart, endocrine organs, etc., resulting in structural damage and dysfunction. The liver is the primary organ for iron storage, and excessive iron deposition induces liver inflammation and fibrosis, which may progress to cirrhosis and even liver cancer, with a poor prognosis. Accurate evaluation and effective treatment can reduce liver injury caused by iron overload and improve patients′ survival.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Sripetchwandee, Jirapas; Srichairatanakool, Somdet; Fucharoen, Suthat; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2016-01-01

    Background 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. Methods and Findings 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. Conclusions 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. PMID:27428732

  1. 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

  2. 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

  3. Iron overload in MDS-pathophysiology, diagnosis, and complications.

    Science.gov (United States)

    Gattermann, Norbert; Rachmilewitz, Eliezer A

    2011-01-01

    Many patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Here, we discuss our current understanding of the effects of transfusion dependency and iron overload in MDS, indicate our knowledge gaps, and suggest that particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron, which may be as important as the total iron burden. PMID:20938663

  4. Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

    OpenAIRE

    Adams, Brian D.; Lazova, Rossitza; Andrews, Nancy C.; Milstone, Leonard M

    2005-01-01

    In human hemochromatosis, tissue toxicity is a function of tissue iron levels. Despite reports of skin toxicity in hemochromatosis, little is known about iron levels in skin of individuals with systemic iron overload. We measured skin iron and studied skin histology in three mouse models of systemic iron overload: mice with a deletion of the hemochromatosis (Hfe) gene, mice fed a high iron diet, and mice given parenteral injections of iron. In Hfe−/− mice, iron content in the epidermis and de...

  5. 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。

  6. 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. PMID:26929633

  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. PMID:26929633

  8. Effects of iron overload on the immune system.

    Science.gov (United States)

    Walker, E M; Walker, S M

    2000-10-01

    Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in

  9. Correlation of cardiac T2* value with cardiac iron overload in myelodysplastic syndrome patients%骨髓增生异常综合征患者MRI检查心脏T2*值与心脏铁过载关系的初步探讨

    Institute of Scientific and Technical Information of China (English)

    肖超; 顾树程; 张曦; 赵佑山; 常春康

    2013-01-01

    Objective To determine the cardiac T2* value of magnetic resonance imaging and the related index of cardiac iron overload-left ventricular ejection fraction in myelodysplastic syndrome patients and analyze the relationship between cardiac T2* value and cardiac function. Methods Cardiac T2* and liver T2* value were measured by MRI examination in 20 MDS patients, MIC (myocardial iron concentration) and LIC (liver iron concentration) were calculated from cardiac T2* and liver T2*, respectively. And LVEF (left ventricular ejection fraction) was measured by echocardiographic examination. Results Correlation of cardiac T2* value with LVEF was statistically significant (r=0.565, P=0.009). However, cardiac T2* value had no correlation with WHO classification, IPSS score, gender, blood transfusion, disease time, LIC and SF (serum ferritin). Conclusions Cardiac T2* value has considerable predictability for cardiac function and is superior to serum ferritin and liver iron.%目的:检测骨髓增生异常综合征(MDS)患者MRI检查中心脏T2*值和心脏铁过载的相关指标——左心室射血分数(LVEF),并探讨心脏T2*值与心脏功能的关系.方法:20例MDS患者行MRI检查,得到心脏、肝脏I2*数值,并换算成心铁、肝铁浓度(LIC),同时进行心脏超声检测,得到LVEF.结果:MDS患者的心脏T2*值与LVEF间存在相关性(r=-0.565,P=0.009),而心脏T2*值与国际预后积分系统(IPSS)评分、患者病程时间、LIC、SF间则均无相关性(P>0.05).不同WHO分型、IPSS分层、性别、是否输血、近一年输血量患者间的心脏T2*值无统计学差异.结论:心脏T2*值对MDS患者心脏功能有一定预测性,比同期的LIC及血清铁蛋白可能更有价值.

  10. Genetics Home Reference: African iron overload

    Science.gov (United States)

    ... shedding of excess iron through blood loss in menstruation and childbirth. The prevalence of increased iron stores ... is absorbed through the walls of the small intestine. Ferroportin then transports iron from the small intestine ...

  11. Iron overload in MDS?pathophysiology, diagnosis, and complications

    OpenAIRE

    Gattermann, Norbert; Rachmilewitz, Eliezer A

    2010-01-01

    Abstract Many patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Here, we discuss our current understanding of the effects of transfusion dependenc...

  12. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  13. Aceruloplasminaemia: a rare but important cause of iron overload.

    Science.gov (United States)

    Doyle, Adam; Rusli, Ferry; Bhathal, Prithi

    2015-01-01

    We present a case of a 20-year-old man referred to our service with iron overload and mildly deranged liver biochemistry. Although liver histopathology was consistent with haemochromatosis, iron studies were not consistent with this diagnosis. Serum ceruloplasmin levels were undetectable, leading to a diagnosis of aceruloplasminaemia. Unlike other iron overload disorders, neurological complications are a unique feature of this illness, and often irreversible, once established. The patient was treated with iron chelation prior to the onset of neurological injury, and experienced progressive normalisation of his ferritin and liver biochemistry. This is one of the youngest diagnosed cases in the published literature and, crucially, was a rare case of diagnosis and treatment prior to the onset of neurological sequelae. This is presented alongside a review of previously published cases of aceruloplasminaemia, including responses to iron chelation therapy. PMID:25976187

  14. Study on abnormal iron metabolism and iron overload in patients with aplastic anemia

    Institute of Scientific and Technical Information of China (English)

    金朋

    2013-01-01

    Objective To investigate the abnormalities of iron metabolism,the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA) .Methods A cross-sectional study was conducted on 520 newly diagnosed AA patients.Results Iron overload was observed in 66 (13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections (19/86,22%) than those without infections (47/434,11%,P<0.01) ,but also in patients with hepatitis associated AA

  15. 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.)

  16. Neurotoxic effects of iron overload under high glucose concentration

    Institute of Scientific and Technical Information of China (English)

    Shi Zhao; Lin Zhang; Zihui Xu; Weiqun Chen

    2013-01-01

    Iron overload can lead to cytotoxicity, and it is a risk factor for diabetic peripheral neuropathy. However, the underlying mechanism remains unclear. We conjectured that iron overload-induced neurotoxicity might be associated with oxidative stress and the NF-E2-related factor 2 (Nrf2)/ARE signaling pathway. As an in vitro cellular model of diabetic peripheral neuropathy, PC12 cells ex-posed to high glucose concentration were used in this study. PC12 cells were cultured with ferric ammonium citrate at different concentrations to create iron overload. PC12 cells cultured in ferric ammonium citrate under high glucose concentration had significantly low cellviability, a high rate of apoptosis, and elevated reactive oxygen species and malondialdehyde levels. These changes were dependent on ferric ammonium citrate concentration. Nrf2 mRNA and protein expression in the fer-ric ammonium citrate groups were inhibited markedly in a dose-dependent manner. Al changes could be inhibited by addition of deferoxamine. These results indicate that iron overload aggravates oxidative stress injury in neural cells under high glucose concentration and that the Nrf2/ARE sig-naling pathway might play an important role in this process.

  17. Korean Guideline for Iron Chelation Therapy in Transfusion-Induced Iron Overload

    OpenAIRE

    Jang, Jun Ho; Lee, Je-Hwan; Yoon, Sung-Soo; Jo, Deog-Yeon; Kim, Hyeoung-Joon; Chung, Jooseop; Lee, Jong Wook

    2013-01-01

    Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducin...

  18. Mysterious link between iron overload and CDKN2A/2B

    OpenAIRE

    Toyokuni, Shinya

    2010-01-01

    Persistent oxidative stress has been associated with carcinogenesis. Iron overload is considered one such condition that causes oxidative stress. Epidemiological studies support a close link between iron overload and carcinogenesis. Reportedly, regular semiannual phlebotomies reduced cancer risk in an otherwise normal population. More specifically, genetic hemochromatosis, chronic viral hepatitis, ovarian endometriosis and asbestosis induce iron overload, which can lead to hepatocellular carc...

  19. Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload.

    Science.gov (United States)

    Gattermann, Norbert

    2007-12-01

    Experts believe that iron overload is an important problem which could be avoided with suitable treatment. Guidelines on treating myelodysplastic syndromes (MDS) include sections on using iron chelation therapy to prevent or ameliorate transfusional iron overload. The proportion of MDS patients who may benefit from iron chelation therapy is 35-55%, depending on the length of survival necessary for iron to accumulate to a detrimental level. Candidates for iron chelation are mainly patients with dyserythropoietic and cytopenic subtypes of disease, which fall into the International Prognostic Scoring System (IPSS) Low-risk or Intermediate-1-risk categories, with median survival of 3-6 years. PMID:18037413

  20. 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.

  1. Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload.

    Science.gov (United States)

    Gattermann, Norbert

    2008-07-01

    Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional iron overload with iron chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines show that the approaches to managing iron overload in patients with MDS are region specific, differing in their recommendations for when iron chelation therapy should be initiated and strategies for the ongoing management of iron overload. The guidelines all agree that red blood cell transfusions are clinically beneficial to treat the symptomatic anemia in MDS, and that patients with low-risk MDS receiving transfusions are the most likely to benefit from iron chelation therapy. PMID:18581200

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

    International Nuclear Information System (INIS)

    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

  3. Quantification of severe liver iron overload using MRI offset echoes

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) has become the clinical standard to estimate liver iron overload. The most commonly used method is to measure the transversal relaxation time, T2*, from a multi gradient recalled echo sequence (MGRE). While this technique is reliable in low to moderate liver iron concentrations (LIC), it will be inaccurate when it is severe. We report a case with severe liver hemochromatosis and show the benefit of using an easily implemented MRI offset echo sequence to more accurately estimate LIC. After adjusting treatment, both Ferritin and LIC decreased. Using standard MGRE this reduction could not have been detected

  4. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model

    OpenAIRE

    Zhang, Zeyu; Liu, Dan; Yi, Bo; LIAO, ZHANGPING; Tang, Lei; Yin, Dong; He, Ming

    2014-01-01

    We previously demonstrated that iron overload induces liver damage by causing the formation of reactive oxygen species (ROS). Taurine is a potent free radical scavenger that attenuates the damage caused by excessive oxygen free radicals. Therefore, the aim of the present study was to investigate whether taurine could reduce the hepatotoxicity of iron overload with regard to ROS production. Mice were intraperitoneally injected with iron 5 days/week for 13 weeks to achieve iron overload. It was...

  5. High fat diet subverts hepatocellular iron uptake determining dysmetabolic iron overload

    OpenAIRE

    Paola Dongiovanni; Claudia Lanti; Stefano Gatti; Raffaela Rametta; Stefania Recalcati; Marco Maggioni; Anna Ludovica Fracanzani; Patrizia Riso; Gaetano Cairo; Silvia Fargion; Luca Valenti

    2015-01-01

    Increased serum ferritin associated with mild hepatic iron accumulation, despite preserved upregulation of the iron hormone hepcidin, is frequently observed in patients with dysmetabolic overload syndrome (DIOS). Genetic factors and Western diet represent predisposing conditions, but the mechanisms favoring iron accumulation in DIOS are still unclear. Aims of this study were to assess the effect a high-fat diet (HFD) on hepatic iron metabolism in an experimental model in rats, to further char...

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

    OpenAIRE

    Saito, Hiroshi; Tomita, Akihiro; Ohashi, Haruhiko; MAEDA, HIDEAKI; Hayashi, Hisao; Naoe, Tomoki

    2012-01-01

    ABSTRACT We attempted to clarify the storage iron metabolism from the change in the serum ferritin level. We assumed that the nonlinear decrease in serum ferritin was caused by serum ferritin increase in iron mobilization. Under this assumption, we determined both ferritin and hemosiderin iron levels by computer-assisted simulation of the row of decreasing assay-dots of serum ferritin in 11 patients with normal iron stores free of both iron deficiency and iron overload; chronic hepatitis C (C...

  7. Iron and immunity: immunological consequences of iron deficiency and overload

    OpenAIRE

    Cherayil, Bobby J.

    2010-01-01

    The influence of iron on immune function has been long appreciated. However, the molecular basis for this interaction is less well understood. Recently, there have been several important advances that have shed light on the mechanisms that regulate mammalian iron metabolism. The new insights provide a conceptual framework for understanding and manipulating the cross-talk between iron homeostasis and the immune system. This article will review what is currently known about how disturbances of ...

  8. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

    Institute of Scientific and Technical Information of China (English)

    Yong-nan FU; Han XIAO; Xiao-wei MA; Sheng-yang JIANG; Ming XU; You-yi ZHANG

    2011-01-01

    Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.Methods: Wild type and AMPKα2 knockout (AMPKα2-/-) littermates were subjected to left ventricular pressure overload caused by evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKx2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2-/-mice.Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

  9. Diagnosis and management of transfusion iron overload: The role of imaging

    OpenAIRE

    Wood, John C.

    2007-01-01

    The characterization of iron stores is important to prevent and treat iron overload. Serum markers such as ferritin, serum iron, iron binding capacity, transferrin saturation, and nontransferrin-bound iron can be used to follow trends in iron status; however, variability in these markers limits predictive power for any given individual. Liver iron represents the best single marker of total iron balance. Measures of liver iron include biopsy, superconducting quantum interference device, comput...

  10. The Role of Iron and Iron Overload in Chronic Liver Disease

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  11. The Role of Iron and Iron Overload in Chronic Liver Disease.

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  12. Acute iron overload and oxidative stress in brain

    International Nuclear Information System (INIS)

    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 h

  13. Acute iron overload and oxidative stress in brain.

    Science.gov (United States)

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

    2013-12-01

    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, 6h 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 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h 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 6h after Fe administration. CAT activity was significantly increased after 8h 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 6h of Fe overload

  14. Revaluation of clinical and histological criteria for diagnosis of dysrnetabolic iron overload syndrome

    Institute of Scientific and Technical Information of China (English)

    Alessia Riva; Giorgio Bovo; Alberto Piperno; Paola Trombini; Raffaella Mariani; Alessandra Salvioni; Sabina Coletti; Silvia Bonfadini; Valentina Paolini; Matteo Pozzi; Rita Facchetti

    2008-01-01

    AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical,biochemical and histopathological findings.METHODS: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes.The metabolic syndrome (MS) was defined according to ATPⅢ criteria.Iron overload was assessed by liver biopsy.Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in ≥ 5% of hepatocytes.RESULTS: According to transferrin saturation levels,we observed significant differences in the amount of hepatic iron overload and iron distribution,as well as the number of metabolic abnormalities.Using Receiving Operating Curve analysis,we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload (P < 0.0001).Patients with ≥ 2 metabolic alterations and steatosis had lower amount of hepatic iron,lower transferrin saturation and higher sinusoidal iron than patients with < 2 MS components and absence of steatosis.CONCLUSION: In our patients,the presence of ≥2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation,suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation.These patients may have the typical dysmetabolic iron overload syndrome.By contrast,patients with transferrin saturation ≥ 60% had more severe iron overload,few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.

  15. The relationship between non transferrin bound iron and iron overload in thalassaemia and sickle syndromes.

    OpenAIRE

    Shah, F. T.

    2007-01-01

    Iron overload is a major cause of morbidity and subsequent mortality in patients with thalassaemia major, its effects in thalassaemia intermedia and sickle cell anaemia are however less well known. The presence of non transferrin bound iron is well described in adult thalassaemia patients but it is unclear as to when NTBI appears and what relationship it has to ineffective erythropoiesis and end organ damage. Data is presented on children with thalassaemia from a five-year prospective study s...

  16. Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload

    OpenAIRE

    Gattermann, Norbert

    2008-01-01

    Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional iron overload with iron chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines ...

  17. Mycobacterium avium Complex Infection in a Patient with Sickle Cell Disease and Severe Iron Overload

    Directory of Open Access Journals (Sweden)

    Kamal Shemisa

    2014-01-01

    Full Text Available A 34-year-old female with sickle cell anemia (hemoglobin SS disease and severe iron overload presented to our institution with the subacute presentation of recurrent pain crisis, fever of unknown origin, pancytopenia, and weight loss. A CT scan demonstrated both lung and liver nodules concerning for granulomatous disease. Subsequent biopsies of the liver and bone marrow confirmed the presence of noncaseating granulomas and blood cultures isolated Mycobacterium avium complex MAC. Disseminated MAC is considered an opportunistic infection typically diagnosed in the immunocompromised and rarely in immunocompetent patients. An appreciable number of mycobacterial infection cases have been reported in sickle cell disease patients without immune dysfunction. It has been reported that iron overload is known to increase the risk for mycobacterial infection in vitro and in vivo studies. While iron overload is primarily known to cause end organ dysfunction, the clinical relationship with sickle cell disease and disseminated MAC infection has not been reported. Clinical iron overload is a common condition diagnosed in the sub-Saharan African population. High dietary iron, genetic defects in iron trafficking, as well as hemoglobinopathy are believed to be the etiologies for iron overload in this region. Patients with iron overload in this region were 17-fold more likely to die from Mycobacterium tuberculosis. Both experimental and clinical evidence suggest a possible link to iron overload and mycobacterial infections; however larger observational studies are necessary to determine true causality.

  18. 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

  19. Consensus statement on iron overload in myelodysplastic syndromes.

    Science.gov (United States)

    Bennett, John M

    2008-11-01

    In May 2005 at the 8th International Symposium on Myelodysplastic Syndromes (MDS), a consensus meeting was held on iron overload in MDS (Seymour, Hematol Oncol Clin 2005; Suppl 1:18-25). The recommendations of the 2005 consensus meeting were discussed in the context of currently available evidence at the 9th International Symposium on Myelodysplastic Syndromes in Florence Italy, May 2007. The recommendations of the consensus working group are presented here. The recommendations are a continued refinement of the outcome of the 2005 consensus meeting and the ground-breaking work of others in this area (Seymour, Hematol Oncol Clin 2005; Suppl 1:18-25; Gattermann, Int J Hematol 2008;88:24-29; Alessandrino et al., Haematologica 2002;87:1286-1306; NCCN practice guidelines: Myelodysplastic Syndromes, version 2.2008). PMID:18767130

  20. Effect of iron overload and iron deficiency on liver hemojuvelin protein.

    Directory of Open Access Journals (Sweden)

    Jan Krijt

    Full Text Available INTRODUCTION: Hemojuvelin (Hjv is a key component of the signaling cascade that regulates liver hepcidin (Hamp expression. The purpose of this study was to determine Hjv protein levels in mice and rats subjected to iron overload and iron deficiency. METHODS: C57BL/6 mice were injected with iron (200 mg/kg; iron deficiency was induced by feeding of an iron-deficient diet, or by repeated phlebotomies. Erythropoietin (EPO-treated mice were administered recombinant EPO at 50 U/mouse. Wistar rats were injected with iron (1200 mg/kg, or fed an iron-deficient diet. Hjv protein was determined by immunoblotting, liver samples from Hjv-/- mice were used as negative controls. Mouse plasma Hjv content was determined by a commercial ELISA kit. RESULTS: Liver crude membrane fraction from both mice and rats displayed a major Hjv-specific band at 35 kDa, and a weaker band of 20 kDa. In mice, the intensity of these bands was not changed following iron injection, repeated bleeding, low iron diet or EPO administration. No change in liver crude membrane Hjv protein was observed in iron-treated or iron-deficient rats. ELISA assay for mouse plasma Hjv did not show significant difference between Hjv+/+ and Hjv-/- mice. Liver Hamp mRNA, Bmp6 mRNA and Id1 mRNA displayed the expected response to iron overload and iron deficiency. EPO treatment decreased Id1 mRNA, suggesting possible participation of the bone morphogenetic protein pathway in EPO-mediated downregulation of Hamp mRNA. DISCUSSION: Since no differences between Hjv protein levels were found following various experimental manipulations of body iron status, the results indicate that, in vivo, substantial changes in Hamp mRNA can occur without noticeable changes of membrane hemojuvelin content. Therefore, modulation of hemojuvelin protein content apparently does not represent the limiting step in the control of Hamp gene expression.

  1. 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.

  2. 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.

  3. 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.)

  4. IRON OVERLOAD AND GROWTH OF THALASSEMIC PATIENTS IN MARWAR REGION

    Directory of Open Access Journals (Sweden)

    Bhavana Singhal , Neha Shama* and Ranjana Mathur

    2012-07-01

    Full Text Available Growth disturbances are a major clinical feature of thalassemic patients. Regular blood transfusions and iron-chelation therapy greatly contribute to the quality and longevity of thalassemic patients. The main objective of present study was to compare the current growth of Thalassemia major patients, taking into accounts the iron overload, transfusion and iron chelation therapy, therefore we planned this study. The present study was conducted on 63 Thalassemic patients were enrolled in this study from June 2008 to October 2008. These subjects were categorised into two groups: 36 children (10 years. Enrolled subjects were examined for various anthropometric parameters as height, weight and body mass index. Venous blood samples were obtained for estimating serum ferritin. Family history (carrier status of father, mother or siblings, age of diagnosis, age of first blood transfusion, frequency of blood transfusion and details of chelation therapy were recorded during the study Serum Ferritin level was very significantly elevated in the adolescents when compared to children because the number of transfusion increases as age advance. Percentile curves (NCHS growth curves showed pronounced growth retardation in height and weight after 10 years of age in both sexes. A very significant difference (t=3.43, p<0.01was observed between the serum Ferritin value of total no. of thalassemic children (1496.59 ±74.05 ng/ML and the thalassemic adolescents (2397.97 ± 1199.57 ng/ML. Determination of serum ferritin and routine growth monitoring at regular intervals is necessary to detect any disturbance in growth and to establish an appropriate protocol for investigation and treatment.

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

    Science.gov (United States)

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

    2016-05-01

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

  6. Whey protein inhibits iron overload-induced oxidative stress in rats.

    Science.gov (United States)

    Kim, Jungmi; Paik, Hyun-Dong; Yoon, Yoh-Chang; Park, Eunju

    2013-01-01

    In this study, we evaluated the effects of whey protein on oxidative stress in rats that were subjected to oxidative stress induced by iron overload. Thirty male rats were assigned to 3 groups: the control group (regular [50 mg/kg diet] dose of iron+20% casein), iron overload group (high [2,000 mg/kg] dose of iron+20% casein, IO), and whey protein group (high dose of iron+10% casein+10% whey protein, IO+whey). After 6 wk, the IO group showed a reduction in the plasma total radical trapping antioxidant parameter and the activity of erythrocyte superoxide dismutase and an increase in lipid peroxidation (determined from the proportion of conjugated dienes). However, whey protein ameliorated the oxidative changes induced by iron overload. The concentration of erythrocyte glutathione was significantly higher in the IO+whey group than in the IO group. In addition, whey protein supplementation fully inhibited iron overload-induced DNA damage in leukocytes and colonocytes. A highly significant positive correlation was observed between plasma iron levels and DNA damage in leukocytes and colonocytes. These results show the antioxidative and antigenotoxic effects of whey protein in an in vivo model of iron overload-induced oxidative stress. PMID:23883690

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

    OpenAIRE

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

    1996-01-01

    Nineteen children and adolescents receiving repeated transfusions and subcutaneous desferrioxamine treatment were investigated in an attempt to quantitate iron overload non-invasively. Before patients were started on desferrioxamine individual relationships were correlated for 12 to 36 months between transfused iron, absorbed iron estimated gastrointestinally, and increasing serum ferritin concentrations. Patients with inflammation, increased liver enzymes, or haemolysis were excluded from an...

  8. Global Transcriptional Response to Hfe Deficiency and Dietary Iron Overload in Mouse Liver and Duodenum

    OpenAIRE

    Alejandra Rodriguez; Tiina Luukkaala; Fleming, Robert E.; Britton, Robert S.; Bacon, Bruce R.; Seppo Parkkila

    2009-01-01

    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...

  9. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload.

    Science.gov (United States)

    Aydinok, Yesim; Kattamis, Antonis; Cappellini, M Domenica; El-Beshlawy, Amal; Origa, Raffaella; Elalfy, Mohsen; Kilinç, Yurdanur; Perrotta, Silverio; Karakas, Zeynep; Viprakasit, Vip; Habr, Dany; Constantinovici, Niculae; Shen, Junwu; Porter, John B

    2015-06-18

    Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2* 5-10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2* ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2* ≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2*. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (-52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2* <5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2* in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227. PMID:25934475

  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. Bone Marrow SSEA1+ Cells Support the Myocardium in Cardiac Pressure Overload

    OpenAIRE

    Finan, Amanda; Sopko, Nikolai; Dong, Feng; Turturice, Ben; Kiedrowski, Matthew; Penn, Marc S.

    2013-01-01

    Rationale Stage specific embryonic antigen 1+ (SSEA1+) cells have been described as the most primitive mesenchymal progenitor cell in the bone marrow. Cardiac injury mobilizes SSEA1+ cells into the peripheral blood but their in vivo function has not been characterized. Objective We generated animals with chimeric bone marrow to determine the fate and function of bone marrow SSEA1+ cells in response to acute cardiac pressure overload. Methods and Results Lethally irradiated mice were transplan...

  13. Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

    OpenAIRE

    Zhao, Mingming; Fajardo, Giovanni; Urashima, Takashi; Spin, Joshua M; Poorfarahani, Sara; Rajagopalan, Viswanathan; Huynh, Diem; Connolly, Andrew; Quertermous, Thomas; Bernstein, Daniel

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

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

    Science.gov (United States)

    Zhang, Ying; Zhao, Xin; Chang, Yanzhong; Zhang, Yuanyuan; Chu, Xi; Zhang, Xuan; Liu, Zhenyi; Guo, Hui; Wang, Na; Gao, Yonggang; Zhang, Jianping; Chu, Li

    2016-06-15

    Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n=8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. PMID:27095094

  15. 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.

  16. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

    Directory of Open Access Journals (Sweden)

    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  17. 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

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

    International Nuclear Information System (INIS)

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

    Directory of Open Access Journals (Sweden)

    Alejandra Rodriguez

    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.

  20. 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. PMID:26663936

  1. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation.

    Directory of Open Access Journals (Sweden)

    Heidi Ehrentraut

    Full Text Available Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15 mg/g bodyweight or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced

  2. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation

    Science.gov (United States)

    Boehm, Olaf; El Aissati, Sakina; Foltz, Fabian; Goelz, Lina; Goertz, David; Kebir, Sied; Weisheit, Christina; Wolf, Michael; Meyer, Rainer; Baumgarten, Georg

    2015-01-01

    Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR)-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15mg/g bodyweight) or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization) signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced hyperinflammatory

  3. The relationship between cardiac and liver iron evaluated by MR imaging in haematological malignancies and chronic liver disease

    International Nuclear Information System (INIS)

    Although iron overload is clinically significant, only limited data have been published on iron overload in haematological diseases. We investigated cardiac and liver iron accumulation by magnetic resonance imaging (MRI) in a cohort of 87 subjects who did not receive chelation, including 59 haematological patients. M-HIC (MRI-based hepatic iron concentration, normal values <36 μmol/g) is a non-invasive, liver biopsy-calibrated method to analyse iron concentration. This method, calibrated to R2 (transverse relaxation rate), was used as a reference standard (M-HIC(R2)). Transfusions and ferritin were evaluated. Mean M-HIC(R2) and cardiac R* of all patients were 142 μmol/g (95% CI, 114–170) and 36.4 1/s (95% CI, 34.2–38.5), respectively. M-HIC(R2) was higher in haematological patients than in patients with chronic liver disease or normal controls (P<0.001). Clearly elevated cardiac R2* was found in two myelodysplastic syndrome (MDS) patients with severe liver iron overload. A poor correlation was found between liver and cardiac iron (n=82, r=0.322, P=0.003), in contrast to a stronger correlation in MDS (n=7, r=0.905, P=0.005). In addition to transfusions, MDS seemed to be an independent factor in iron accumulation. In conclusion, the risk for cardiac iron overload in haematological diseases other than MDS is very low, despite the frequently found liver iron overload

  4. Acute iron overload leads to hypothalamic-pituitary-gonadal axis abnormalities in female rats.

    Science.gov (United States)

    Rossi, Emilly M; Marques, Vinicius B; Nunes, Dieli de O; Carneiro, Maria T W D; Podratz, Priscila L; Merlo, Eduardo; dos Santos, Leonardo; Graceli, Jones B

    2016-01-01

    Iron plays a critical role in a mammal's physiological processes. However, iron tissue deposits have been shown to act as endocrine disrupters. Studies that evaluate the effect of acute iron overload on hypothalamic-pituitary-gonadal (HPG) axis health are particularly sparse. This study demonstrates that acute iron overload leads to HPG axis abnormalities, including iron accumulation and impairment in reproductive tract morphology. Female rats were treated with iron-dextran (Fe rats) to assess their HPG morphophysiology. The increasing serum iron levels due to iron-dextran treatment were positively correlated with higher iron accumulation in the HPG axis and uterus of Fe rats than in control rats. An increase in the production of superoxide anions was observed in the pituitary, uterus and ovary of Fe rats. Morphophysiological reproductive tract abnormalities, such as abnormal ovarian follicular development and the reduction of serum estrogen levels, were observed in Fe rats. In addition, a significant negative correlation was obtained between ovary superoxide anion and serum estrogen levels. Together, these data provide in vivo evidence that acute iron overload is toxic for the HPG axis, a finding that may be associated with the subsequent development of the risk of reproductive dysfunction. PMID:26536400

  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. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  7. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  8. Heterozygous Mutations in BMP6 Pro-peptide Lead to Inappropriate Hepcidin Synthesis and Moderate Iron Overload in Humans

    OpenAIRE

    Daher, Raed; Kannengiesser, Caroline; Houamel, Dounia; Lefebvre, Thibaud; Bardou-Jacquet, Edouard; Ducrot, Nicolas; Kerguenec, Caroline,; Jouanolle, Anne-Marie; Robreau, Anne-Marie; Oudin, Claire; Le Gac, Gerald; Moulouel, Boualem; Loustaud-Ratti, Véronique; Bedossa, Pierre; Valla, Dominique

    2015-01-01

    Background & Aims Hereditary hemochromatosis is a heterogeneous group of genetic disorders characterized by parenchymal iron overload. It is caused by defective expression of liver hepcidin, the main regulator of iron homeostasis. Iron stimulates the gene encoding (HAMP) hepcidin via the BMP6 signaling to SMAD. Although several genetic factors have been found to cause late-onset hemochromatosis, many patients have unexplained signs of iron overload. We investigated BMP6 function in these indi...

  9. When is iron overload deleterious, and when and how should iron chelation therapy be administered in myelodysplastic syndromes?

    Science.gov (United States)

    Steensma, David P; Gattermann, Norbert

    2013-12-01

    Iron overload in MDS starts even before patients become red-blood cell transfusion dependent, because disease-associated ineffective erythropoiesis suppresses hepcidin production in the liver and thus causes unrestrained iron absorption in the duodenum. However, the main cause of iron overload is regular transfusion therapy, which in MDS is associated with a risk of unclear magnitude for iron-related complications. Iron deposition in tissues can now be detected with non-invasive techniques such as T2* MRI. Iron toxicity in MDS may not only depend on the degree of tissue iron accumulation but also on the extent of chronic exposure to non-transferrin-bound iron (NTBI), including labile plasma iron (LPI) and intracellular labile iron pools, which increase the level of oxidative stress. Iron chelation therapy (ICT) can rapidly lower NTBI and LPI and more slowly mobilizes tissue iron stores. Further studies, including the ongoing TELESTO controlled trial, will more clearly define the role of ICT in MDS, including any effect on specific morbidities or mortality in the MDS setting. PMID:24507819

  10. Evidence for angiotensin II type 2 receptor–mediated cardiac myocyte enlargement during in vivo pressure overload

    OpenAIRE

    Senbonmatsu, Takaaki; Ichihara, Sahoko; Price, Edward; Gaffney, F.Andrew; Inagami, Tadashi

    2000-01-01

    The pathophysiological roles of the angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT2 we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT2 is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT2 deletion were independent of activation of embryonic genes for cardiac hypertrophy. ...

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

    Science.gov (United States)

    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) as part of an international inter-laboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and β-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated β-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low within-sample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating non-transferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assays. PMID:26385212

  12. Metabolic response to subacute and subchronic iron overload in a rat model.

    Science.gov (United States)

    Adham, Khadiga G; Farhood, Manal H; Daghestani, Maha H; Aleisa, Nadia A; Alkhalifa, Ahlam A; El Amin, Maha H; Virk, Promy; Al-Obeid, Mai A; Al-Humaidhi, Eman M H

    2015-12-01

    One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg⁻¹) and subchronic (0.1 mg kg⁻¹) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L⁻¹ and 13.2 μmol g⁻¹ wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities "TIBC, UIBC" as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system. PMID:26616369

  13. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

    Institute of Scientific and Technical Information of China (English)

    Xian-hui Dong; Cong Liu; Jiang-tao Bai; Wei-na Kong; Xiao-ping He; Peng Yan; Tie-mei Shao; Wen-guo Yu; Xi-qing Chai; Yan-hua Wu

    2015-01-01

    Abnormally increased levels of iron in the brain trigger cascade ampliifcation in Alzheimer’s dis-ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer’s disease patients. An APPswe/PS1ΔE9 double transgenic mouse model of Alzheimer’s disease was used. The intragas-tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer’s disease. These com-pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer’s disease.

  14. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

    Directory of Open Access Journals (Sweden)

    Xian-hui Dong

    2015-01-01

    Full Text Available Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer′s disease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer′s disease patients. An APP swe/PS1ΔE9 double transgenic mouse model of Alzheimer′s disease was used. The intragastric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer′s disease. These compounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer′s disease.

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

    OpenAIRE

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

    1983-01-01

    The erythrocyte ferritin content was measured in patients with either idiopathic haemochromatosis or alcoholic liver disease and iron overload to define its value as a marker for an excess of tissue iron. The mean erythrocyte ferritin content in patients with untreated idiopathic haemochromatosis was increased 60-fold and fell with phlebotomy. After phlebotomy many patients had an increased red cell ferritin content despite normal serum ferritin concentrations. That this reflected persistent ...

  16. A Longitudinal Study of Growth and Relation With Anemia and Iron Overload in Pediatric Patients With Transfusion-dependent Thalassemia.

    Science.gov (United States)

    Nokeaingtong, Kwannapas; Charoenkwan, Pimlak; Silvilairat, Suchaya; Saekho, Suwit; Pongprot, Yupada; Dejkhamron, Prapai

    2016-08-01

    Short stature is one of the most common endocrinopathies in transfusion-dependent thalassemia (TDT). This study aimed to determine the longitudinal pattern of growth in pediatric patients with TDT and study the relationship between growth and hemoglobin level, serum ferritin level/iron overload parameters, and other clinical factors. The interval height-for-age Z-scores (HAZ) of 50 patients with TDT, of a mean age of 13.3±2.8 years, were analyzed using linear mixed model analysis. Nineteen patients (38%) had short stature with HAZ≤-2.0. The prevalence of short stature increased with age. The estimated mean HAZ decreased by 0.19 SD per year from the age of 5 years until approximately 14 years (95% confidence interval [CI], -0.22 to -0.16, Pferritin level ≥1800 ng/mL (estimate, -0.44; 95% CI, -0.59 to -0.29; P<0.001), and cardiac T2* ≤20 ms (estimate, -1.05; 95% CI, -1.34 to -0.77; P<0.001) were significantly associated with short stature. In conclusion, short stature in patients with TDT is common and relates significantly with increasing age, male sex, hemoglobin level, and iron overload status. PMID:27438019

  17. 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.

  18. Binding of serum ferritin to concanavalin A in patients with iron overload and with chronic liver disease.

    OpenAIRE

    Chapman, R W; Gorman, A; Laulicht, M; Hussain, M.A.; Sherlock, S; Hoffbrand, A V

    1982-01-01

    Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in ...

  19. Iron overload in human hepatoma cells - proteomic analysis

    Czech Academy of Sciences Publication Activity Database

    Petrák, J.; Myslivcová, D.; Man, Petr; Babušiak, M.; Vyoral, D.

    Lednice, 2005, s. 38-38. [Czech Proteomic Conference /2./. Lednice (CZ), 17.10.2005-20.10.2005] Institutional research plan: CEZ:AV0Z50200510 Keywords : iron * proteomic analysis Subject RIV: EE - Microbiology, Virology

  20. 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.

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

    International Nuclear Information System (INIS)

    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

  2. Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Maritza Cavalcante Barbosa

    2013-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. METHODS: A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15 and Non-iron overload (n = 15. Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0 and statistical significance was established for p-values < 0.05 in all analyses. RESULTS: Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL, alanine aminotransferase (ALT, lactate dehydrogenase (LDH, urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL and low-density lipoprotein (LDL. Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05. The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. CONCLUSION: The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.

  3. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYP ERTROPHY

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王一理; 刘勇; 李恒力; 田红燕

    2002-01-01

    Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expressi on on the model of rat cardiac volume-overload hyper trophy was examined by immunohistochemical study. Results The immunohistochemica l study indicated the expression of c-myc protein was increased obviously at 4 -6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-o verload, then decreased gradually along with development of volume-overload hyp ertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic respon se of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on, c-myc gene and the product of it do not act anymore;While it may be that c-my c gene and the product of it increased following with myocardial hypertrophy, an d have not direct relation to the occurrence and development of myocardial hyper trophy.

  4. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYPERTROPHY

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To investigate the change of c-myc protein,which was chosen as the response indicator to volume-overloab.Methods:The time and spatial course of c-myc protein expression on the model of rat cardiac volume-overload hypertrophy was examined by immunohistochemical study.Results:The immunohistochemical study indicated the expression of c-myc protein was increased obviously at 4-6 hours(62.73%)than that of control(45.41%,P<0.01) after the volume-overload,then decreased gradually along with development of volume-overload hypertrophy and was decreased extremely at 5 months(r=-0.514,p<0.01),Conclusion:There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in hypertrophic myocardium.C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy.Once switching on,c-myc gene and the product of it do not act anymore;While it may be that c-myc gene and the product of it increased following with myocardial hypertrophy,and have not direct relation to the occurrence and development of myocardial hypertrophy.

  5. Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.

    Science.gov (United States)

    Schaefer, Benedikt; Haschka, David; Finkenstedt, Armin; Petersen, Britt-Sabina; Theurl, Igor; Henninger, Benjamin; Janecke, Andreas R; Wang, Chia-Yu; Lin, Herbert Y; Veits, Lothar; Vogel, Wolfgang; Weiss, Günter; Franke, Andre; Zoller, Heinz

    2015-11-01

    Liver disease due to alpha-1-antitrypsin deficiency (A1ATD) is associated with hepatic iron overload in a subgroup of patients. The underlying cause for this association is unknown. The aim of the present study was to define the genetics of this correlation and the effect of alpha-1-antitrypsin (A1AT) on the expression of the iron hormone hepcidin. Full exome and candidate gene sequencing were carried out in a family with A1ATD and hepatic iron overload. Regulation of hepcidin expression by A1AT was studied in primary murine hepatocytes. Cells co-transfected with hemojuvelin (HJV) and matriptase-2 (MT-2) were used as a model to investigate the molecular mechanism of this regulation. Observed familial clustering of hepatic iron overload with A1ATD suggests a genetic cause, but genotypes known to be associated with hemochromatosis were absent. Individuals homozygous for the A1AT Z-allele with environmental or genetic risk factors such as steatosis or heterozygosity for the HAMP non-sense mutation p.Arg59* presented with severe hepatic siderosis. In hepatocytes, A1AT induced hepcidin mRNA expression in a dose-dependent manner. Experiments in overexpressing cells show that A1AT reduces cleavage of the hepcidin inducing bone morphogenetic protein co-receptor HJV via inhibition of the membrane-bound serine protease MT-2. The acute-phase protein A1AT is an inducer of hepcidin expression. Through this mechanism, A1ATD could be a trigger of hepatic iron overload in genetically predisposed individuals or patients with environmental risk factors for hepatic siderosis. PMID:26310624

  6. Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Christina Westphal

    Full Text Available The aim of this study was to investigate the effects of 17β-estradiol (E2, the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM raloxifene on remodeling processes during the development of myocardial hypertrophy (MH in a mouse model of pressure overload. Myocardial hypertrophy in ovariectomized female C57Bl/6J mice was induced by transverse aortic constriction (TAC. Two weeks after TAC, placebo treated mice developed left ventricular hypertrophy and mild systolic dysfunction. Estrogen treatment, but not 16α-LE2 or raloxifene reduced TAC induced MH compared to placebo. E2, 16α-LE2 and raloxifene supported maintenance of cardiac function in comparison with placebo. Nine weeks after induction of pressure overload, MH was present in all TAC groups, most pronounced in the raloxifene treated group. Ejection fraction (EF was decreased in all animals. However, 16α-LE2 treated animals showed a smaller reduction of EF than animals treated with placebo. E2 and 16α-LE2, but not raloxifene diminished the development of fibrosis and reduced the TGFβ and CTGF gene expression. Treatment with E2 or 16α-LE2 but not with raloxifene reduced survival rate after TAC significantly in comparison with placebo treatment. In conclusion, E2 and 16α-LE2 slowed down the progression of MH and reduced systolic dysfunction after nine weeks of pressure overload. Raloxifene did not reduce MH but improved cardiac function two weeks after TAC. However, raloxifene was not able to maintain EF in the long term period.

  7. Steroidal and Nonsteroidal Mineralocorticoid Receptor Antagonists Cause Differential Cardiac Gene Expression in Pressure Overload-induced Cardiac Hypertrophy.

    Science.gov (United States)

    Grune, Jana; Benz, Verena; Brix, Sarah; Salatzki, Janek; Blumrich, Annelie; Höft, Beata; Klopfleisch, Robert; Foryst-Ludwig, Anna; Kolkhof, Peter; Kintscher, Ulrich

    2016-05-01

    Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. Therapy with steroidal MR antagonists such as spironolactone or eplerenone (EPL) is often limited because of side effects. Recently, a new highly selective and potent, nonsteroidal MR antagonist, finerenone (FIN), has been developed. To investigate the effects of FIN on pressure-induced cardiac hypertrophy, the transverse aortic constriction (TAC) model was used in C57BL/6 mice treated with FIN (10 mg·kg·d), EPL (200 mg·kg·d) or vehicle (VEH). First, we analyzed cardiac gene expression 4 weeks after TAC using a pathway-focused quantitative polymerase chain reaction array. FIN caused a distinct cardiac gene expression profile compared to VEH and EPL, including differential expression of BNP (brain natriuretic peptide) and Tnnt2 (troponin T type 2). FIN treatment led to a significant reduction of TAC-induced left ventricular (LV) wall thickening assessed by echocardiography. In accordance, FIN-treated mice showed a significant lower increase of calculated left ventricular mass compared with VEH- and EPL-treated mice (FIN: 28.4 ± 3.7 mg; EPL: 38.4 ± 4.3 mg; VEH: 39.3 ± 3.1 mg; P < 0.05). These data show beneficial effects of nonsteroidal MR antagonism by FIN on left ventricular mass development in pressure overload associated with a distinct cardiac gene expression profile. PMID:26859196

  8. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

    OpenAIRE

    Remacha, Angel F.; Arrizabalaga, Beatriz; Cañizo, Consuelo; Sanz, Guillermo; Villegas, Ana

    2009-01-01

    Abstract The main objective of the study was to analyze the incidence of iron overload (IO) and its management in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) before the license of deferasirox. This observational, cross-sectional, and multicenter study was conducted from January to May 2007 in 81 Spanish hospitals. Eligible patients had a low or intermediate-1 risk score and had to have received at least ten units of packed red blood cell (PRBC). Of t...

  9. Heart Rate Variability as an Alternative Indicator for Identifying Cardiac Iron Status in Non-Transfusion Dependent Thalassemia Patients.

    Directory of Open Access Journals (Sweden)

    Karn Wijarnpreecha

    Full Text Available Iron-overload cardiomyopathy is a major cause of death in thalassemia patients due to the lack of an early detection strategy. Although cardiac magnetic resonance (CMR T2* is used for early detection of cardiac iron accumulation, its availability is limited. Heart rate variability (HRV has been used to evaluate cardiac autonomic function and found to be depressed in thalassemia. However, its direct correlation with cardiac iron accumulation has never been investigated. We investigated whether HRV can be used as an alternative indicator for early identification of cardiac iron deposition in thalassemia patients.Ninety-nine non-transfusion dependent thalassemia patients (23.00 (17.00, 32.75 years, 35 male were enrolled. The correlation between HRV recorded using 24-hour Holter monitoring and non-transferrin bound iron (NTBI, hemoglobin (Hb, serum ferritin, LV ejection fraction (LVEF, and CMR-T2* were determined.The median NTBI value was 3.15 (1.11, 6.59 μM. Both time and frequency domains of HRV showed a significant correlation with the NTBI level, supporting HRV as a marker of iron overload. Moreover, the LF/HF ratio showed a significant correlation with CMR-T2* with the receiver operating characteristic (ROC curve of 0.684±0.063, suggesting that it could represent the cardiac iron deposit in thalassemia patients. HRV was also significantly correlated with serum ferritin and Hb.This novel finding regarding the correlation between HRV and CMR-T2* indicates that HRV could be a potential marker in identifying early cardiac iron deposition prior to the development of LV dysfunction, and may be used as an alternative to CMR-T2* for screening cardiac iron status in thalassemia patients.

  10. Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

    DEFF Research Database (Denmark)

    Christoffersen, Tue E.H.; Aplin, Mark; Strom, Claes C.;

    2006-01-01

    Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system...... also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system in...

  11. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

    OpenAIRE

    Nicolas, Gaël; Bennoun, Myriam; Devaux, Isabelle; Beaumont, Carole; Grandchamp, Bernard; Kahn, Axel; Vaulont, Sophie

    2001-01-01

    We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animal...

  12. 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. PMID:26830968

  13. Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Keith Dadson

    Full Text Available Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM remodeling in response to pressure overload (PO. Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO and wild-type (WT mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson's trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects.

  14. Nonalcoholic steatohepatitis in Asian Indians is neither associated with iron overload nor with HFE gene mutations

    Institute of Scientific and Technical Information of China (English)

    Ajay Duseja; Reena Das; Mohit Nanda; Ashim Das; Gurjeewan Garewal; Yogesh Chawla

    2005-01-01

    AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH.METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Peris' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined.RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients.On histology, 71% of the patients had negative iron staining,21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P = 0.55) and fibrosis stage (P = 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation.CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.

  15. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis.

    Science.gov (United States)

    Nicolas, Gaël; Viatte, Lydie; Lou, Dan-Qing; Bennoun, Myriam; Beaumont, Carole; Kahn, Axel; Andrews, Nancy C; Vaulont, Sophie

    2003-05-01

    Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes. Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200). Mice lacking Hfe or producing a C282Y mutant Hfe protein develop hyperferremia and have high hepatic iron levels. In both humans and mice, hereditary hemochromatosis is associated with a paucity of iron in reticuloendothelial cells. It has been suggested that HFE modulates uptake of transferrin-bound iron by undifferentiated intestinal crypt cells, thereby programming the absorptive capacity of enterocytes derived from these cells; however, this model is unproven and controversial. Hepcidin, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE. Although expression of mouse Hamp is normally greater during iron overload, Hfe-/- mice have inappropriately low expression of Hamp. We crossed Hfe-/- mice with transgenic mice overexpressing Hamp and found that Hamp inhibited the iron accumulation normally observed in the Hfe-/- mice. This argues against the crypt programming model and suggests that failure of Hamp induction contributes to the pathogenesis of hemochromatosis, providing a rationale for the use of HAMP in the treatment of this disease. PMID:12704388

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

    Science.gov (United States)

    Barton, James C; Edwards, Corwin Q

    2016-01-01

    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. PMID:26908385

  17. 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.

  18. 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.)

  19. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload

    OpenAIRE

    Porto, G.; CARDOSO, C.S.; Gordeuk, V; Cruz, E.; Fraga, J.; Areias, J; Oliveira, J. C.; Bravo, F. (Federico); GANGAIDZO, I.T.; MACPHAIL, A.P.; GOMO, Z.A.; MOYO, V.M.; Melo, G.; Silva, C.; JUSTICA, B.

    2001-01-01

    Eur J Haematol. 2001 Aug;67(2):110-8. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload. Porto G, Cardoso CS, Gordeuk V, Cruz E, Fraga J, Areias J, Oliveira JC, Bravo F, Gangaidzo IT, MacPhail AP, Gomo ZA, Moyo VM, Melo G, Silva C, Justiça B, de Sousa M. Haematology, Santo António General Hospital, Porto, Portugal. Abstract To identify a new marker of expression of diseas...

  20. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    Science.gov (United States)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  1. Dasatinib Attenuates Pressure Overload Induced Cardiac Fibrosis in a Murine Transverse Aortic Constriction Model.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available Reactive cardiac fibrosis resulting from chronic pressure overload (PO compromises ventricular function and contributes to congestive heart failure. We explored whether nonreceptor tyrosine kinases (NTKs play a key role in fibrosis by activating cardiac fibroblasts (CFb, and could potentially serve as a target to reduce PO-induced cardiac fibrosis. Our studies were carried out in PO mouse myocardium induced by transverse aortic constriction (TAC. Administration of a tyrosine kinase inhibitor, dasatinib, via an intraperitoneally implanted mini-osmotic pump at 0.44 mg/kg/day reduced PO-induced accumulation of extracellular matrix (ECM proteins and improved left ventricular geometry and function. Furthermore, dasatinib treatment inhibited NTK activation (primarily Pyk2 and Fak and reduced the level of FSP1 positive cells in the PO myocardium. In vitro studies using cultured mouse CFb showed that dasatinib treatment at 50 nM reduced: (i extracellular accumulation of both collagen and fibronectin, (ii both basal and PDGF-stimulated activation of Pyk2, (iii nuclear accumulation of Ki67, SKP2 and histone-H2B and (iv PDGF-stimulated CFb proliferation and migration. However, dasatinib did not affect cardiomyocyte morphologies in either the ventricular tissue after in vivo administration or in isolated cells after in vitro treatment. Mass spectrometric quantification of dasatinib in cultured cells indicated that the uptake of dasatinib by CFb was greater that that taken up by cardiomyocytes. Dasatinib treatment primarily suppressed PDGF but not insulin-stimulated signaling (Erk versus Akt activation in both CFb and cardiomyocytes. These data indicate that dasatinib treatment at lower doses than that used in chemotherapy has the capacity to reduce hypertrophy-associated fibrosis and improve ventricular function.

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

    Science.gov (United States)

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

    2016-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent have been widely used in magnetic resonance imaging for tumor diagnosis and theranostics. However, there has been safety concern of SPIONs with cirrhosis related to excess iron-induced oxidative stress. In this study, the impact of iron overload by SPIONs was assessed on a mouse cirrhosis model. A single dose of SPION injection at 0.5 or 5 mg Fe/kg in the cirrhosis group induced a septic shock response at 24 h with elevated serum levels of liver and kidney function markers and extended impacts over 14 days including high levels of serum cholesterols and persistent low serum iron level. In contrast, full restoration of liver functions was found in the normal group with the same dosages over time. Analysis with PCR array of the toxicity pathways revealed the high dose of SPIONs induced significant expression changes of a distinct subset of genes in the cirrhosis liver. All these results suggested that excess iron of the high dose of SPIONs might be a risk factor for cirrhosis because of the marked impacts of elevated lipid metabolism, disruption of iron homeostasis and possibly, aggravated loss of liver functions. PMID:27357559

  3. Canine cardiac myosin with special referrence to pressure overload cardiac hypertrophy. I. Subunit composition.

    Science.gov (United States)

    Siemankowski, R F; Dreizen, P

    1978-12-10

    In studies of myosin from left and right ventricles of normal hearts and hypertrophic hearts at 5 weeks and 13 weeks after aortic banding, polyacrylamide gel electrophoresis shows intermediate molecular weight components which derive from heavy chains fragmented in the presence of dodecyl sulfate. The proportion of degraded heavy chains is greater in myosin from hypertrophic hearts than normal hearts, with comparable degradation in left and right ventricle myosin. The observed fragmentation of myosin results from proteolysis due to contaminant proteases or a thermally activated, heat-stable nonenzymatic process, or both. The susceptibility of heavy chains to crude myofibrillar proteases differs in normal and hypertrophic cardiac myosin; however, the kinetics of tryptic digestion are identical for both myosins. With precautions to minimize proteolytic artifacts on dodecyl sulfate-polyacrylamide gel electrophoresis, preparations of myosin from left and right ventricles of normal and hypertrophic hearts exhibit comparable subunit composition, with approximately molar ratios of heavy chains, light chain L1, and light chain L2. Comparable stoichiometry for the light chain fraction is determined by high speed sedimentation equilibrium at pH 11 and direct fractionation of the different cardiac myosins. We do not confirm reports (e.g. Wikman-Coffelt, J., Fenner, C., Smith, A., and Mason, D. T. (1975) J. Biol. Chem. 250, 1257-1262) of different proportions of light chains in left and right ventricle myosin of normal and hypertrophic canine hearts. The light chains display microheterogeneity, with L1 generating two isoelectric variants and L2 generating two major and two minor variants, but identical mobilities and isoelectric values are obtained in the different myosin preparations. PMID:152317

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Hurlet, A. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Comerci, S.C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Piomelli, S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States)

    1995-11-01

    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.

  6. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy.

    Science.gov (United States)

    Dadson, Keith; Turdi, Subat; Hashemi, Sarah; Zhao, Jianzhong; Polidovitch, Nazar; Beca, Sanja; Backx, Peter H; McDermott, John C; Sweeney, Gary

    2015-09-01

    Cardiomyocyte (CM) hypertrophy and increased heart mass in response to pressure overload are associated with hyper-activation of the myocyte enhancer factor-2 (MEF2) family of transcriptional regulators, and concomitant initiation of the fetal gene program. Adiponectin, an adipokine that is reduced in individuals with obesity and diabetes, has been characterized both as a negative regulator or permissive factor in cardiac hypertrophy. We therefore sought to analyze temporal regulation of MEF2 activity in response to pressure overload (PO) and changes in adiponectin status. To address this we crossed a well characterized transgenic MEF2 "sensor" mouse (MEF2-lacZ) with adiponectin null mice (Ad-KO) to create compound MEF2 lacZ/Ad-KO mice. Initially, we established that transverse aortic banding induced PO in wild-type (WT) mice increased heart mass and CM hypertrophy from 1 to 4weeks following surgery, indicated by increased CM diameter and heart weight/tibia length ratio. This was associated with cardiac dysfunction determined by echocardiography. Hypertrophic changes and dysfunction were observed in Ad-KO mice 4weeks following surgery. MEF2 lacZ activity and endogenous ANF mRNA levels, used as indicators of hypertrophic gene activation, were both robustly increased in WT mice after MTAB but attenuated in the Ad-KO background. Furthermore, activation of the pro-hypertrophic molecule p38 was increased following MTAB surgery in WT mice, but not in Ad-KO animals, and treatment of primary isolated CM with recombinant adiponectin induced p38 phosphorylation in a time dependent manner. Adiponectin also increased MEF2 activation in primary cardiomyocytes, an effect attenuated by p38 MAPK inhibition. In conclusion, our data indicate that robust hypertrophic MEF2 activation in the heart in vivo requires a background of adiponectin signaling and that adiponectin signaling in primary isolated CM directly enhances MEF2 activity through activation of p38 MAPK. We conclude that

  7. Are extrinsic black stains of teeth iron-saturated bovine lactoferrin and a sign of iron deficient anemia or iron overload?

    Science.gov (United States)

    Mesonjesi, Ilir

    2012-08-01

    Extrinsic black stains on teeth are shown to have a relation with a low incidence of caries and are made of a ferric compound. Whole composition and why those stains are formed are not fully understood. Studies have shown low incidence of caries in individuals eating cheese. Lactoferrin is the major iron-binding protein, constituent of milk, stays almost intact during cheese making and has antibacterial activity against dental cavity-inducing Streptococcus mutans. Lactoferrin has a high affinity for iron and whenever it is present it will bind iron and release it only in values of pHblack stains on teeth eat >50 g of cheese per day and a good number of them, in addition to cheese, drink one cup of milk per day. Cheese stays much longer in contact with tooth surface than does' milk and bovine lactoferrin has four glycan chains that may contribute to a better adherence. Extrinsic black stains are made of a ferric compound, and people that eat good amounts of cheese (where lactoferrin plays a central role) show to have black stains. Iron must be in sufficient amounts in saliva so that lactoferrin can bind it and as a result making the black stains appear. In iron deficient anemia and in iron overload the concentration of iron present in saliva is much higher than in individuals with no anemia. In conclusion, extrinsic black stains of teeth may be iron-saturated bovine lactoferrin and a sign of iron deficient anemia or iron overload if no iron supplements are taken or individuals have no frequent gingival bleeding. PMID:22632844

  8. Carnitine Palmitoyltransferase-1b (CPT1b) Deficiency Aggravates Pressure-Overload-Induced Cardiac Hypertrophy due to Lipotoxicity

    Science.gov (United States)

    He, Lan; Kim, Teayoun; Long, Qinqiang; Liu, Jian; Wang, Peiyong; Zhou, Yiqun; Ding, Yishu; Prasain, Jeevan; Wood, Philip A.; Yang, Qinglin

    2012-01-01

    Background Carnitine palmitoyltransferase 1(CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT-1 activity by specific CPT-1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby posting concerns on the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 in order to evaluate it as a safe and effective therapeutic approach. Methods and Results Heterozygous CPT1b knockout mice (CPT1b+/−) were subjected to transverse aorta constriction (TAC)-induced pressure-overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by two weeks of transverse aorta constriction (TAC), CPT1b+/− mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b+/− mice exhibited exacerbated cardiac hypertrophy and remodeling compared with that in wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b+/− than in controlled mice. Moreover, the CPT1b+/− heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocytes apoptosis. Conclusions We conclude that CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be applied in the clinical use of CPT-1 inhibitors. PMID:22932257

  9. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Zhen-lun GU; Mei-lin XIE; Wen-xuan ZHOU; Ci-yi GUO

    2007-01-01

    Aim: To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Methods: Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. Results: In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Inthe Western blot analysis, EGCG significantly inhibited pressure overload-inducedp53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. Conclusion: EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload in-duced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

  10. Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy cntribute to adverse LV remodeling

    OpenAIRE

    Vandenwijngaert, Sara; Pokreisz, Peter; Hermans, Hadewich; Gillijns, Hilde; Pellens, Marijke; Bax, Noortje A M; Coppiello, Giulia; Oosterlinck, Wouter; Balogh, Agnes; Papp, Zoltan; Bouten, Carlijn V. C.; Bartunek, Jozef; D'Hooge, Jan; Luttun, Aernout; Verbeken, Erik

    2013-01-01

    Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings: In patients with severe aortic stenosi...

  11. The MRI marker gene MagA attenuates the oxidative damage induced by iron overload in transgenic mice.

    Science.gov (United States)

    Guan, Xiaoying; Jiang, Xinhua; Yang, Chuan; Tian, Xiumei; Li, Li

    2016-06-01

    We aimed to create transgenic (Tg) mice engineered for magnetic resonance imaging (MRI). To ascertain if MagA expression contributes to oxidative stress and iron metabolism, we report the generation of Tg mice in which ubiquitous expression of MagA can be detected by MRI in vivo. Expression of MagA in diverse tissues of Tg mice was assessed, and iron accumulation and deposition of nanoparticles in tissues were analyzed. Levels of antioxidant enzymes, lipid peroxidation and cytokine production were determined, and iron metabolism-related proteins were also detected. MagA Tg showed no apparent pathologic symptoms and no histologic changes compared with wild-type (WT) mice. Overexpression of MagA resulted in specific alterations of the transverse relaxation rate (R2) of water. Transgene-dependent changes in R2 were detectable by MRI in iron-overloaded mice. We also evaluated antioxidant abilities between WT and Tg groups or two iron-overloaded groups. Together with the data of cytokines and iron metabolism-related proteins, we inferred that MagA could regulate nanoparticle production and thus attenuate the oxidative damage induced by iron overload. The novel MagA Tg mouse, which expresses an MRI reporter in many tissues, would be a valuable model of MagA molecular imaging in which to study diseases related to iron metabolism. PMID:26488480

  12. Association of cardiac injury with iron-increased oxidative and nitrative modifications of the SERCA2a isoform of sarcoplasmic reticulum Ca(2+)-ATPase in diabetic rats.

    Science.gov (United States)

    Li, Xueli; Li, Wenliang; Gao, Zhonghong; Li, Hailing

    2016-08-01

    The role of iron in the etiology of diabetes complications is not well established. Thus, this study was performed to test whether the iron-induced increase of oxidative/nitrative damage is involved in SERCA2a-related diabetic heart complication. Four randomly divided groups of rats were used: normal control group; iron overload group; diabetes group, and diabetic plus iron overload group. Iron supplementation stimulated cardiomyocyte hypertrophy and led to an increase in cardiac protein carbonyls, nitrotyrosine (3-NT) formation, and iNOS protein expression, thus resulting in abnormal myocardium calcium homeostasis of diabetic rats. The levels of SECA2a oxidation/nitration were significantly increased in the iron overload diabetic rats, along with a decrease in SECA2a expression and activity. In order to elucidate the possible role of iron in SERCA2a dysfunction, the effects of iron (Fe(3+) or hemin) on peroxynitrite (ONOO(-)) induced SERCA2a oxidation and nitration were further investigated in vitro. It was found that tyrosine nitration played more important role in SERCA2a inactivation than thiol oxidation. These results present a potential mechanism in which iron exacerbates the diabetes-induced oxidative/nitrative modification of SERCA2a, which may cause functional deficits in the myocyte associated with diabetic cardiac dysfunction. Our findings may help to further understand the role of iron in the pathogenesis of diabetic complications. PMID:27222135

  13. Non cardiopatic and cardiopatic beta thalassaemic patients: quantitative and qualitative cardiac iron deposition evaluation with MRI

    International Nuclear Information System (INIS)

    Purpose: Cardiomyopathy is one of the major complications of β thalassaemia major as a result of transfusion iron overload. The aim of our study is to evaluate with MR if there is any difference of iron deposition signal intensity (SI) or distribution between non-cardiopatic and cardiopatic thalassaemic patients in order to establish if there is a relationship between cardiopathy and iron deposition. Materials and methods: We studied 20 patients affected by β thalassaemia major, of whom 10 cardiopatic and 10 non-cardiopatic, and 10 healthy volunteers as control group. Serum ferritin and left ventricular ejection fraction were calculated in thalassaemic patients. All patients were examinated using a 1.5 MR unit with ECG-gated GE cine-MR T2*-weighted, SE T1-weighted and GE T2*-weighted sequences. In all cases, using an adequate ROI, the myocardial and skeletal muscle signal intensity (SI), the myocardial/skeletal muscle signal intensity radio (SIR) and the SI average of the myocardium and skeletal muscle were calculated for every study group. The qualitative evaluation of iron deposition distribution was independently performed by three radiologists who analysed the extension, the site and the morphology of iron deposition on the MR images and reported their observations on the basis of a four-level rating scale: 0 (absent), 1 (limited), 2 (partial), 3 (widespread deposition). The results of quantitative and qualitative evaluation were analysed with statistical tests. Results: Cardiac iron deposition was found in 8/10 non-cardiopatic thalassaemic patients and in all cardiopatic thalassaemic patients. We noticed a significant SI difference (p>0.05) between the healthy volunteer control group and the thalassaemic patients with iron deposition, but no significant SI difference in iron deposition between non-cardiopatic thalassaemic patients in the areas evaluated. The qualitative evaluation revealed a different distribution of iron deposition between the two

  14. 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.

  15. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

    Science.gov (United States)

    Nicolas, G; Bennoun, M; Devaux, I; Beaumont, C; Grandchamp, B; Kahn, A; Vaulont, S

    2001-07-17

    We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animals than in controls. To identify genes that may account for the abnormalities of iron homeostasis in Usf2(-/-) mice, we used suppressive subtractive hybridization between livers from Usf2(-/-) and wild-type mice. We isolated a cDNA encoding a peptide, hepcidin (also referred to as LEAP-1, for liver-expressed antimicrobial peptide), that was very recently purified from human blood ultrafiltrate and from urine as a disulfide-bonded peptide exhibiting antimicrobial activity. Accumulation of iron in the liver has been recently reported to up-regulate hepcidin expression, whereas our data clearly show that a complete defect in hepcidin expression is responsible for progressive tissue iron overload. The striking similarity of the alterations in iron metabolism between HFE knockout mice, a murine model of hereditary hemochromatosis, and the Usf2(-/-) hepcidin-deficient mice suggests that hepcidin may function in the same regulatory pathway as HFE. We propose that hepcidin acts as a signaling molecule that is required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages. PMID:11447267

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

    Science.gov (United States)

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

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

    OpenAIRE

    Chalmers AW; Shammo JM

    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...

  18. Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels

    OpenAIRE

    Rossi, Francesca; Perrotta, Silverio; Bellini, Giulia; Luongo, Livio; Tortora, Chiara; Siniscalco, Dario; Francese, Matteo; Torella, Marco; Nobili, Bruno; Di Marzo, Vincenzo; Maione, Sabatino

    2014-01-01

    The pathogenesis of bone resorption in β-thalassemia major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, it may be instructive to examine a potential role for this system in the development of osteoporosis in patients with β-thalassemia major and its relationship with iron overload and iron chelation therapy. This study demonstra...

  19. Influence of lead on repetitive behavior and dopamine metabolism in a mouse model of iron overload.

    Science.gov (United States)

    Chang, JuOae; Kueon, Chojin; Kim, Jonghan

    2014-12-01

    Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity. PMID:25584146

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

    International Nuclear Information System (INIS)

    Objective: To preliminarily investigate the feasibility of MRI-T2* map in evaluating myocardial iron load of myocardial iron overload rabbit models. Methods: Eleven rabbits were included in this study and divided into two groups, myocardial iron overload group (n =10) and the control group (n = 1). Iron dextrin (dose of 50 mg/kg) was injected in muscles of thigh once a week, totally 12 weeks. Serum iron test and MRI examination were performed before iron injection,and 1 week to 12 weeks after iron injection. MRI scan protocol included short axial T2* map of the left ventricle and cross-section T2* map of the liver. T2* and R2* of the heart and the liver were measured. One rabbit was killed after MRI examination at pre-iron injection, 1 week to 8 weeks, 11 weeks and 12 weeks after iron injection,respectively. Heart and liver were avulsed to undergo in vitro MRI scan and then paraffin embedded for pathological slices. MRI scan protocol and measurements of the heart and the liver samples were the same to that of in vivo ones. Pearson correlation was used to calculate the relationships between the parameters. Results: Myocardial T2* [(32.5 ± 8.3 ms)] and R2* values [(38.4 ± 7.9) Hz] had significant correlation with injecting iron content (1033.2 ± 673.4 mg), the Pearson coefficients were -0.799 (P = 0.001) and 0.770 (P = 0.002), respectively. Myocardial T2* had no significant correlation with liver T2* values (r = 0.556, P = 0.070). T2* values of heart and liver in vivo [(32.5 ± 8.3) ms and (8.8 ± 5.4) ms], respectively had strong correlation with those in vitro [(19.4 ± 6.5) ms and (9.8 ± 5.0) ms], respectively (r = 0.757, P = 0.007 and r = 0.861, P = 0.001). T2* and R2* values of the heart and the liver in vivo and in vitro had no significant correlations with serum iron (P>0.05). On Prussian blue staining slices,blue particles of myocardium, sinus hepaticas and hepatocyte increased with injecting iron content. Conclusions: It is feasible for MRI-T2* map to

  1. Intravenous iron supplementation in the anaemia of renal and cardiac failure--a double-edged sword?

    Science.gov (United States)

    Slotki, Itzchak

    2005-07-01

    The anaemia of chronic kidney disease (CKD) is efficiently corrected with a combination of recombinant erythropoietin (rhEPO) and intravenous iron supplementation. Recently, patients with severe cardiac failure and anaemia have also been shown to benefit from this treatment. However, iron excess may lead to the production of free radicals and has been incriminated in the pathogenesis of atherosclerosis and increased risk of infection, the two major causes of death in end-stage renal disease. The exact risk of excess iron supplementation has not been defined and, in the absence of sensitive and specific indicators of iron overload, the risk remains difficult to quantify. There is increasing epidemiological evidence incriminating iron overload as a risk factor in CKD, but direct evidence is still hard to obtain. The precise role of iron is complicated further by the complex inter-relationships between iron metabolism and the inflammatory process characteristic of CKD. The recent discovery of the antimicrobial peptide, hepcidin, may shed light on these inter-relationships. New methods for quantifying non-transferrin-bound (or labile plasma) iron may help in the future to identify patients at risk for toxicity from excess iron supplementation. PMID:16024827

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

    Directory of Open Access Journals (Sweden)

    Jana Frýdlová

    Full Text Available Matriptase-2 (TMPRSS6 is an important negative regulator of hepcidin expression; however, the effects of iron overload or accelerated erythropoiesis on liver TMPRSS6 protein content in vivo are largely unknown. We determined TMPRSS6 protein content in plasma membrane-enriched fractions of liver homogenates by immunoblotting, using a commercial antibody raised against the catalytic domain of TMPRSS6. Plasma membrane-enriched fractions were obtained by centrifugation at 3000 g and washing. TMPRSS6 was detected in the 3000 g fraction as a 120 kDa full-length protein in both mice and rats. Feeding of iron-deficient diet as well as erythropoietin treatment increased TMPRSS6 protein content in rats and mice by a posttranscriptional mechanism; the increase in TMPRSS6 protein by erythropoietin was also observed in Bmp6-mutant mice. Administration of high doses of iron to mice (200, 350 and 700 mg/kg decreased TMPRSS6 protein content. Hemojuvelin was detected in the plasma membrane-enriched fractions of control animals as a full length protein of approximately 52 kDa; in iron deficient animals, the full length protein was partially cleaved at the N-terminus, resulting in an additional weak band of approximately 47 kDa. In livers from hemojuvelin-mutant mice, TMPRSS6 protein content was strongly decreased, suggesting that intact hemojuvelin is necessary for stable TMPRSS6 expression in the membrane. Overall, the results demonstrate posttranscriptional regulation of liver TMPRSS6 protein by iron status and erythropoietin administration, and provide support for the interaction of TMPRSS6 and hemojuvelin proteins in vivo.

  3. 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.

  4. 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

  5. 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.)

  6. 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.

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

    International Nuclear Information System (INIS)

    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.)

  8. Comparison of myocardial T1 and T2 values in 3 T with T2* in 1.5 T in patients with iron overload and controls.

    Science.gov (United States)

    Camargo, Gabriel C; Rothstein, Tamara; Junqueira, Flavia P; Fernandes, Elsa; Greiser, Andreas; Strecker, Ralph; Pessoa, Viviani; Lima, Ronaldo S L; Gottlieb, Ilan

    2016-05-01

    Myocardial iron quantification remains limited to 1.5 T systems with T2* measurement. The present study aimed at comparing myocardial T2* values at 1.5 T to T1 and T2 mapping at 3.0 T in patients with iron overload and healthy controls. A total of 17 normal volunteers and seven patients with a history of myocardial iron overload were prospectively enrolled. Mid-interventricular septum T2*, native T1 and T2 times were quantified on the same day, using a multi-echo gradient-echo sequence at 1.5 T and T1 and T2 mapping sequences at 3.0 T, respectively. Subjects with myocardial iron overload (T2* analysis. Native myocardial T1 and T2 times at 3 T correlate closely with T2* times at 1.5 T and may be useful for myocardial iron overload quantification. PMID:26872908

  9. Optimized Method for the Assessment of Liver Iron Overload by MRI in Thalassemia Patientd (R2 or R2*

    Directory of Open Access Journals (Sweden)

    E. Fatemizadeh

    2010-05-01

    Full Text Available Background/Objective: Iron overload represents a critical health problem in patients with primary and secondary hemosiderosis. The most important of these conditions is beta thalassemia major. Although heart failure remains the main cause of mortality in thalassemia major patients, liver is the foremost affected organ as exceeded parenchymal iron accumulation. Among the available noninvasive techniques for iron store determination, MRI has been shown to provide reliable estimation of tissue iron load. Different MRI protocols such as spin echo (T2 and gradient echo (T2* were used for calculation of iron load. The reciprocals of T2 and T2*, known as R2 and R2*, are directly proportional to iron load. The purpose of this study was to validate an optimized method for the measurement of iron overload in the liver."nPatients and Methods: Using MRI settings for liver iron estimation, we compared the relationship of R2 and R2* values to one another in 30 patients with iron overload. MRI was validated to phantom with different range of iron concentration. Liver R2* was measured from a single midhepatic slice using multi echo gradient echo sequence. For R2 measurement, axial images were acquired with a multislice single spin-echo (SSE pulse sequence. The signal intensity versus TE of gradient echo and spin-echo images were fit to single monoexponential equation, then R2 and R2* were calculated."nResults: Linear agreement between R2* and hepatic iron concentration was found. The variability (CoV was larger in the R2* measurements. R2-iron relationship appeared close to linear and the curvature trend is pronounced only for low HIC. R2 and R*2 had significant correlation with each other (r =0.94 in the liver."nConclusion: R2 and R2* methods have theoretical advantages and disadvantages compared with one another. Different chemical forms of iron deposition could have differential effects between R2 and R2*. Both MRI measurements using gradient and spin

  10. 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

  11. Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Craig Bolte

    Full Text Available Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2 plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

  12. correlation study between MR quantitative cardiac iron accumulated and serum ferritin, liver iron concentration in patients with β-thalassemia major

    International Nuclear Information System (INIS)

    Objective: Using MRI-T2* method to quantify the cardiac iron overload in patients with β-thalassemia major and to evaluate the correlation between cardiac T2* values and serum ferritin (SF), liver iron concentration (LIC). Methods: Fifty-eight over 10 years old transfusion-dependent patients with β-thalassemia major were underwent MRI heart measurement to obtain T2* values. Spearman rank correlation was used to analyze the relationship between cardiac T2*, SF, and LIC. Patients were divided into two groups based on standard setting (SF>2500 μg/L or LIC>15 mg/g of dry tissue). Differences of cardiac T2* values between two groups were evaluated by Wilcoxon rank sum test with cardiac T2*<20 ms as diagnosis standard. The sensibilities and specificities of prediction for cardiac iron deposition with the index of SF>2500 μg/L or LIC>15 mg/g dry tissue were calculated, and receiver operating characteristic (ROC) curve analysis was performed. Results: The range (median) of cardiac T2* values, SF and LIC in 58 patients were 4.7-51.1 ms (14.0 ms), 1345-23640 μg/L (5741 μg/L), 9.0->43.0 mg/g dry tissue (41.4 mg/g), respectively. There was no linear correlation between cardiac T2* values and SF (r=-0.240, P=0.070). Cardiac T2* values and LIC was weakly correlated (r=-0.420, P=0.002). The range (median) of cardiac T2* values was 6.1-47.6 ms (23.7 ms) in 7 patients of SF ≤ 2500 μg/L group. The range (median) of cardiac T2* values was 4.7-51.1 ms(13.5 ms) in 51 patients of SF>2500 μg/L group. There was no statistically significant difference between two groups (Z=-0.489, P=0.625). The range (median) of cardiac T2* values was 24.4-51.1 ms (44.8 ms) in 5 patients of the LIC ≤15 mg/g dry tissue group. The range (median) of cardiac T2* values was 4.7-45.5 ms (13.2 ms) in 53 patients of HIC>15 mg/g dry tissue group. There was significant difference between T2* values of the two groups(Z=-2.895, P=0.004). To predict cardiac iron deposition, the sensibilities and

  13. 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.

  14. Astragalus polysaccharide upregulates hepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Ren, Feng; Qian, Xin-Hua; Qian, Xin-Lai

    2016-03-25

    Thalassemia is a genetic disease characterized by iron overload which is a major detrimental factor contributing to mortality and organ damage. The hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. Lowering iron load in thalassemia patients by means of increasing hepcidin might be a therapeutic strategy. In this study, we first found that astragalus polysaccharide (APS) significantly increased hepcidin expression in HepG2 and L-02 cell lines originating from hepatocytes and mice liver, respectively. Following treatment with APS, the iron concentrations in serum, liver, spleen, and heart were significantly reduced in comparison to saline treated control mice. In further experiments, upregulation of interleukin-6 (IL-6) and enhanced p38 MAPK phosphorylation were detected in APS treated cells and mice, and as documented in previous studies, IL-6 and P38 MAPK phosphorylation are involved in the regulation of hepcidin expression. We also found that the effects of APS on upregulating hepcidin and IL-6 expressions could be antagonized by pretreatment with SB203580, an inhibitor of p38 MAPK signaling. These findings suggest that activation of p38 MAPK and release of IL-6 might mediate induction of hepcidin by APS. It is concluded that APS might have therapeutic implications in patients with iron overload, especially for thalassemia patients. PMID:26915800

  15. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    Science.gov (United States)

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  16. Effect of Systemic Iron Overload and a Chelation Therapy in a Mouse Model of the Neurodegenerative Disease Hereditary Ferritinopathy.

    Science.gov (United States)

    Garringer, Holly J; Irimia, Jose M; Li, Wei; Goodwin, Charles B; Richine, Briana; Acton, Anthony; Chan, Rebecca J; Peacock, Munro; Muhoberac, Barry B; Ghetti, Bernardino; Vidal, Ruben

    2016-01-01

    Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuroferritinopathy or hereditary ferritinopathy (HF). HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic iron-containing ferritin inclusion bodies (IBs) in glia and neurons throughout the central nervous system (CNS) and in tissues of multiple organ systems. Herein, using primary mouse embryonic fibroblasts from a mouse model of HF, we show significant intracellular accumulation of ferritin and an increase in susceptibility to oxidative damage when cells are exposed to iron. Treatment of the cells with the iron chelator deferiprone (DFP) led to a significant improvement in cell viability and a decrease in iron content. In vivo, iron overload and DFP treatment of the mouse model had remarkable effects on systemic iron homeostasis and ferritin deposition, without significantly affecting CNS pathology. Our study highlights the role of iron in modulating ferritin aggregation in vivo in the disease HF. It also puts emphasis on the potential usefulness of a therapy based on chelators that can target the CNS to remove and redistribute iron and to resolubilize or prevent ferritin aggregation while maintaining normal systemic iron stores. PMID:27574973

  17. Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

    Directory of Open Access Journals (Sweden)

    Tim Peters

    Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1 is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC in mice.Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p<0.001 but to a similar extend also in Malat-1 knockout (KO mice (sham: 6.21±1.12, TAC 8.91±1.74 g/mm; p<0.01 with no significant difference between genotypes. As expected, TAC significantly reduced left ventricular fractional shortening in WT (sham: 38.81±6.53%, TAC: 23.14±11.99%; p<0.01 but to a comparable degree also in KO mice (sham: 37.01±4.19%, TAC: 25.98±9.75%; p<0.05. Histological hallmarks of myocardial remodeling, such as cardiomyocyte hypertrophy, increased interstitial fibrosis, reduced capillary density, and immune cell infiltration, did not differ significantly between WT and KO mice after TAC. In line, the absence of Malat-1 did not significantly affect angiotensin II-induced cardiac hypertrophy, dysfunction, and overall remodeling. Above that, pressure overload by TAC significantly induced mRNA levels of the hypertrophy marker genes Nppa, Nppb and Acta1, to a similar extend in both genotypes. Alternative splicing of Ndrg2 after TAC was apparent in WT (isoform ratio

  18. Microarray analysis of rat pancreas reveals altered expression of Alox15 and regenerating islet-derived genes in response to iron deficiency and overload.

    Directory of Open Access Journals (Sweden)

    Richard Coffey

    Full Text Available It is well known that iron overload can result in pancreatic iron deposition, beta-cell destruction, and diabetes in humans. Recent studies in animals have extended the link between iron status and pancreatic function by showing that iron depletion confers protection against beta-cell dysfunction and diabetes. The aim of the present study was to identify genes in the pancreas that are differentially expressed in response to iron deficiency or overload. Weanling male Sprague-Dawley rats (n = 6/group were fed iron-deficient, iron-adequate, or iron-overloaded diets for 3 weeks to alter their iron status. Total RNA was isolated from the pancreases and pooled within each group for microarray analyses in which gene expression levels were compared to those in iron-adequate controls. In iron-deficient pancreas, a total of 66 genes were found to be differentially regulated (10 up, 56 down, whereas in iron-overloaded pancreas, 164 genes were affected (82 up, 82 down. The most up-regulated transcript in iron-deficient pancreas was arachidonate 15-lipoxygenase (Alox15, which has been implicated in the development of diabetes. In iron-overloaded pancreas, the most upregulated transcripts were Reg1a, Reg3a, and Reg3b belonging to the regenerating islet-derived gene (Reg family. Reg expression has been observed in response to pancreatic stress and is thought to facilitate pancreatic regeneration. Subsequent qRT-PCR validation indicated that Alox15 mRNA levels were 4 times higher in iron-deficient than in iron-adequate pancreas and that Reg1a, Reg3a, and Reg3b mRNA levels were 17-36 times higher in iron-overloaded pancreas. The elevated Alox15 mRNA levels in iron-deficient pancreas were associated with 8-fold higher levels of Alox15 protein as indicated by Western blotting. Overall, these data raise the possibility that Reg expression may serve as a biomarker for iron-related pancreatic stress, and that iron deficiency may adversely affect the risk of

  19. Pressure overload stimulated cardiac hypertrophy leads to a rapid decrease in the mRNA for creatine kinase

    International Nuclear Information System (INIS)

    Cardiac hypertrophy (CH) leads to a decrease in creatine kinase (CK) enzymatic activity. To determine if the mRNA for CK also decreases with CH, they performed the following studies. Cardiac RNA was isolated from rats subjected to either abdominal aortic stenosis (AS) or sham surgery. Through Northern blot analysis, total cardiac RNA was quantitated with a CK specific 32P-labelled cDNA clone. At 3 and 8 days post-constriction, the mRNA for CK decreases by 54.6 +/- 7% and 65.3 +/- 18% respectively, whereas the heart weight increases by 19% and 37% relative to controls. Further studies indicate that CK mRNA also decreases by 41.8% in hypothyroid rats (Tx) but decreases by a total of 68.1% in Tx rats subjected to 8 days of AS. Pressure overload stimulated CH leads to a rapid decrease in CK mRNA in normal and Tx rats. This CK mRNA decrease may account for the decreased efficiency of contraction seen in CH

  20. Cardiac Function and Iron Chelation in Thalassemia Major and Intermedia: a Review of the Underlying Pathophysiology and Approach to Chelation Management

    OpenAIRE

    Aessopos, Athanasios; Berdoukas, Vasilios

    2009-01-01

    Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia. The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload. The high output state ...

  1. Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress

    OpenAIRE

    BernardGENY; MichelKINDO; LaurentMONASSIER; FabriceFAVRET

    2012-01-01

    Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced left ventricular hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure...

  2. 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. PMID:23600689

  3. 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 .

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

    International Nuclear Information System (INIS)

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

  5. Iron status in Danes updated 1994. I: prevalence of iron deficiency and iron overload in 1332 men aged 40-70 years. Influence Of blood donation, alcohol intake, and iron supplementation.

    Science.gov (United States)

    Milman, N; Ovesen, L; Byg, K; Graudal, N

    1999-09-01

    Iron status, S-ferritin, and hemoglobin (Hb) were assessed in a population survey in 1994 (DAN-MONICA 10) comprising 1332 Caucasian Danish men equally distributed in age cohorts of 40, 50, 60 and 70 years. Blood donors (n=186) had lower S-ferritin, median 76 microg/l, than nondonors, median 169 microg/l (p300 microg/l) was 20%. S-ferritin in nondonors correlated with body mass index (r(s)=0.19, p=0.0001) and with alcohol intake (r(s)=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14 mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136 microg/l, than nontreated, median 169 microg/l (p<0.001) and those treated with H(2)-receptor antagonists (n=30) had lower S-ferritin, median 142 microg/l, than nontreated, median 171 microg/l (p<0.04). Compared with the DAN-MONICA 1 iron status survey of Danish men in 1984, the prevalences of iron depletion and iron deficiency anemia are unchanged whereas the prevalence of iron overload has increased significantly. In Denmark, iron fortification of flour was abolished in 1987. This apparently had no negative effect on iron status in men. PMID:10525826

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

    Directory of Open Access Journals (Sweden)

    Kristýna Pimková

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    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. Mice lacking functional TRPV1 are protected from pressure overload cardiac hypertrophy

    OpenAIRE

    Buckley, Cadie L; Stokes, Alexander J.

    2011-01-01

    TRPV1 (transient receptor potential cation channel, subfamily V, member 1) is best studied in peripheral sensory neurons as a pain receptor; however TRPV1 is expressed in numerous tissues and cell types including those of the cardiovascular system. TRPV1 expression is upregulated in the hypertrophic heart, and the channel is positioned to receive stimulatory signals in the hypertrophic heart. We hypothesized that TRPV1 has a role in regulating cardiac hypertrophy. Using transverse aortic cons...

  10. Iron status in Danes 1994. II: Prevalence of iron deficiency and iron overload in 1319 Danish women aged 40-70 years. Influence of blood donation, alcohol intake and iron supplementation.

    Science.gov (United States)

    Milman, N; Byg, K E; Ovesen, L

    2000-11-01

    Iron status, i.e. serum ferritin and haemoglobin (Hb) levels, was assessed in a population survey in 1994 (Dan-Monica 10) comprising 1319 Caucasian Danish women in age cohorts of 40, 50, 60 and 70 years. In the entire series, ferritin levels increased significantly from 40 years to 60 years of age. The prevalence of small iron stores (ferritin 16-32 microg/l), depleted iron stores (ferritin 300 microg/l) was 1.54%. Ferritin levels in 60- and 70-year-old non-donors were correlated with the body mass index (r(s) =0.11, P=0.01). Ferritin levels in 50- to 60-year-old non-donors were correlated with alcohol intake (r(s)=0.23, P<0.0001). In the entire series, 37.5% of non-donors took supplemental ferrous iron (median 14 mg iron per day). Iron supplements had a significant positive influence on iron status in 40-year-old premenopausal non-donors but no effect in postmenopausal women or in donors. Non-donors (n = 170) treated with acetylsalicylic acid had lower ferritin levels (median 55 microg/l) than non-treated (n = 1038; median 75 microg/l) (P<0.0001). Compared with the Dan-Monica 1 iron status survey in 1984, the prevalence of iron deficiency and iron deficiency anaemia was unchanged, whereas the prevalence of iron overload displayed a slight increase. The 1987 abolition of the mandatory iron fortification of flour apparently had no negative effect on iron status. PMID:11131920

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

    Science.gov (United States)

    2012-07-16

    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

  12. 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 ...

  13. 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.

  14. Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress

    OpenAIRE

    Kindo, Michel; Gerelli, Sébastien; Bouitbir, Jamal; Charles, Anne-Laure; Zoll, Joffrey; Hoang Minh, Tam; Monassier, Laurent; Favret, Fabrice; Piquard, François; Geny, Bernard

    2012-01-01

    Objective: Increased mechanical stress and contractility characterizes normal left ventricular (LV) subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced LV hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function...

  15. 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.

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

    OpenAIRE

    Ali T Taher; Viprakasit, Vip; Khaled M. Musallam; 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 ...

  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. Heart cells in culture: a model of myocardial iron overload and chelation

    International Nuclear Information System (INIS)

    The effect of iron loading and chelation was studied in heart cell cultures obtained from newborn rats. Radioactive iron uptake per 2 X 10(6) cells/24 hr was 3.8% for 59Fe-transferrin, 15.8% for 59Fe-ferric ammonium citrate (FeAC) at 20 micrograms Fe/ml in 20% serum, and 37.1% for 59FeAC at 20 micrograms Fe/ml in serum-free medium. About one third of the cellular radioactive iron was in ferritin and the rest in an insoluble lysosomal fraction. Iron uptake was almost completely inhibited by reducing the incubation temperature from 37 degrees C to 10 degrees C. Intracellular concentrations of malonyldialdehyde (MDA) were doubled after 15 minutes of iron loading and reached maximal concentrations at 3 hours. Conversely, iron mobilization by deferoxamine at concentrations ranging from 0.025 mmol/L to 0.3 mmol/L resulted in normalization of cellular MDA concentrations, in direct proportion to the amounts of iron removed. These findings indicate that cultured myocardial cells are able to assimilate large amounts of nontransferrin iron and that iron uptake and mobilization are associated with striking changes in lipid peroxidation as manifested by the respective increase and decrease in cellular MDA concentrations

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

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

    Supranee Upanan; Kanjana Pangjit; Chairat Uthaipibull; Suthat Fucharoen; Andrew T McKie; Somdet Srichairatanakool

    2015-01-01

    Objective: To evaluate the efficacy of deferiprone (DFP), 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) or green tea extract (GTE) in enhancing expres-sion of hepatic hepcidin1 (Hamp1) mRNA and relieving iron overload in b-globin knockout thalassemic mice. Methods: The b-globin knockout thalassemic mice were fed with a ferrocene-supplemented diet for 2 months and oral administration of deionized water, DFP (50 mg/kg), CM1 (50 mg/kg), GTE (50 mg epigallocatechin 3-gallate equivalent/kg), GTE along with DFP (50 mg/kg), and GTE along with CM1 (50 mg/kg) every day for 3 months. Levels of hepatic Hamp1 mRNA, plasma non-transferrin bound iron, plasma alanine aminotransferase activity and tissue iron content were determined. Results: All chelation treatments could reduce plasma non-transferrin bound iron con-centrations. Additionally, hepatic Hamp1 mRNA expression was significantly up-regulated in the mice in a GTE+DFP combined treatment, correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition. Conclusions: The GTE + DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-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.

  2. 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

  3. Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress

    Directory of Open Access Journals (Sweden)

    Michel eKINDO

    2012-08-01

    Full Text Available Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi and whether pressure overload-induced left ventricular hypertrophy (LVH might modulate transmural gradients through increased reactive oxygen species (ROS production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group. Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01 and complex IV activity (-57.4%, P<0.05. Mitochondrial hydrogen peroxide (H2O2 production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass, associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%, increased mitochondrial H2O2 production (+86.9 and +73.1%, free radical leak (+27.2% and +36.3% and citrate synthase activity (+27.2% and +36.3% in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02. Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.

  4. Respiratory function in patients with thalassaemia major: relation with iron overload

    OpenAIRE

    Li, A.; Chan, D.; C. Li; Wong, E.; Chan, Y.; Fok, T

    2002-01-01

    Aims: (1) To determine the pattern of respiratory impairment in children with thalassaemia major (TM); (2) to assess the relation between the degree of respiratory impairment and total body iron content.

  5. Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long term survivors after allogeneic hematopoietic stem cell transplantation (HSCT).

    Science.gov (United States)

    Rose, Christian; Ernst, Olivier; Hecquet, Bernard; Maboudou, Patrice; Renom, Pascale; Noel, Marie Pierre; Yakoub-Agha, Ibrahim; Bauters, Francis; Jouet, Jean Pierre

    2007-06-01

    We quantified and studied the impact of post transfusional iron overload alone in post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 mg/L. Liver iron content (LIC) was 117 mmoles/gdw. Correlation RBCs and ferritin was (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal ferritin group in terms of RBCs transfused (p<10(-3)), ALT (p<0.009). But occurrence of liver dysfunction was not significant. Magnitude of iron overload correlates closely to the number of RBCs and is quantified by MRI. Impact on liver dysfunction is moderate in absence of co-morbidity. PMID:17550861

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

    International Nuclear Information System (INIS)

    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.)

  7. 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.)

  8. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    Institute of Scientific and Technical Information of China (English)

    Massimo; Sartori; Silvano; Andorno; Angelo; Rossini; Renzo; Boldorini; Cristina; Bozzola; Stefania; Carmagnola; Mario; Del; Piano; Emanuele; Albano

    2010-01-01

    AIM:To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C(CHC). METHODS:We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to,or unsuitable for,antiviral therapy who underwent mild iron depletion(ferritin≤70 ng/mL) by long-term phlebotomy.Histological improvement,as defined by at least one point reduction in the staging score or,in case...

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

    Institute of Scientific and Technical Information of China (English)

    Katarzyna Sikorska; Piotr Stalke; Tomasz Romanowski

    2013-01-01

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

  10. Molecular responses of ceruloplasmin to Edwardsiella ictaluri infection and iron overload in channel catfish (Ictalurus punctatus)

    Science.gov (United States)

    Ceruloplasmin is a serum ferroxidase that carries more than 90% of the copper in plasma and has documented roles in iron homeostasis as well as antioxidative functions. In our previous studies, it has been shown that the ceruloplasmin gene is strongly up-regulated in catfish during challenge with Ed...

  11. 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.

  12. Hepcidin Expression in Iron Overload Diseases Is Variably Modulated by Circulating Factors

    OpenAIRE

    Ravasi, Giulia; Pelucchi, Sara; Trombini, Paola; Mariani, Raffaella; Tomosugi, Naohisa; Modignani, Giulia Litta; Pozzi, Matteo; Nemeth, Elizabeth; Ganz, Tomas; Hayashi, Hisao; Barisani, Donatella; Piperno, Alberto

    2012-01-01

    Hepcidin is a regulatory hormone that plays a major role in controlling body iron homeostasis. Circulating factors (holotransferrin, cytokines, erythroid regulators) might variably contribute to hepcidin modulation in different pathological conditions. There are few studies analysing the relationship between hepcidin transcript and related protein expression profiles in humans. Our aims were: a. to measure hepcidin expression at either hepatic, serum and urinary level in three paradigmatic ir...

  13. Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

    OpenAIRE

    Neely, Benjamin A.; Kevin P Carlin; Arthur, John M.; McFee, Wayne E.; Janech, Michael G.

    2013-01-01

    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-tran...

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

    Directory of Open Access Journals (Sweden)

    Antonio Fabron Jr

    2003-01-01

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

  15. 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

    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 and...... 70 yr. Results: In the 1984 survey, median ferritin values in the four age cohorts in non-blood-donors were 44, 57, 84 and 80 mug/L, and in the 1994 survey 40, 67, 97 and 95 mug/L, respectively. In 1984, premenopausal women had median ferritin of 43 mug/L and in 1994 of 39 mug/L (NS). In 1984......, postmenopausal women had median ferritin of 75 mug/L and in 1994 of 93 mug/L (P <0.0001). The prevalence of depleted iron stores (ferritin <16 mug/L) was not significantly different in 1984 and 1994 either in premenopausal or in postmenopausal women. The prevalence of small + depleted iron stores (ferritin less...

  16. Is iron overload in alcohol-related cirrhosis mediated by hepcidin?

    Institute of Scientific and Technical Information of China (English)

    Tariq Iqbal; Azzam Diab; Douglas G Ward; Matthew J Brookes; Chris Tselepis; Jim Murray; Elwyn Elias

    2009-01-01

    In this case report we describe the relationship between ferritin levels and hepcidin in a patient with alcohol-related spur cell anemia who underwent liver transplantation. We demonstrate a reciprocal relationship between serum or urinary hepcidin and serum ferritin, which indicates that inadequate hepcidin production by the diseased liver is associated with elevated serum ferritin. The ferritin level falls with increasing hepcidin production after transplantation. Neither inflammatory indices (IL6) nor erythropoietin appear to be related to hepcidin expression in this case. We suggest that inappropriately low hepcidin production by the cirrhotic liver may contribute substantially to elevated tissue iron stores in cirrhosis and speculate that hepcidin replacement in these patients may be of therapeutic benefit in the future.

  17. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    Science.gov (United States)

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID:26677163

  18. 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.)

  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)

    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. Identification of novel mutations in hemochromatosis genes by targeted next generation sequencing in Italian patients with unexplained iron overload.

    Science.gov (United States)

    Badar, Sadaf; Busti, Fabiana; Ferrarini, Alberto; Xumerle, Luciano; Bozzini, Paolo; Capelli, Paola; Pozzi-Mucelli, Roberto; Campostrini, Natascia; De Matteis, Giovanna; Marin Vargas, Sergio; Giorgetti, Alejandro; Delledonne, Massimo; Olivieri, Oliviero; Girelli, Domenico

    2016-06-01

    Hereditary hemochromatosis, one of the commonest genetic disorder in Caucasians, is mainly associated to homozygosity for the C282Y mutation in the HFE gene, which is highly prevalent (allele frequency up to near 10% in Northern Europe) and easily detectable through a widely available "first level" molecular test. However, in certain geographical regions like the Mediterranean area, up to 30% of patients with a HH phenotype has a negative or non-diagnostic (i.e. simple heterozygosity) test, because of a known heterogeneity involving at least four other genes (HAMP, HJV, TFR2, and SLC40A1). Mutations in such genes are generally rare/private, making the diagnosis of atypical HH essentially a matter of exclusion in clinical practice (from here the term of "non-HFE" HH), unless cumbersome traditional sequencing is applied. We developed a Next Generation Sequencing (NGS)-based test targeting the five HH genes, and applied it to patients with clinically relevant iron overload (IO) and a non-diagnostic first level genetic test. We identified several mutations, some of which were novel (i.e. HFE W163X, HAMP R59X, and TFR2 D555N) and allowed molecular reclassification of "non-HFE" HH clinical diagnosis, particularly in some highly selected IO patients without concurring acquired risk factors. This NGS-based "second level" genetic test may represent a useful tool for molecular diagnosis of HH in patients in whom HH phenotype remains unexplained after the search of common HFE mutations. Am. J. Hematol. 91:420-425, 2016. © 2016 Wiley Periodicals, Inc. PMID:26799139

  1. A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload

    Science.gov (United States)

    Kannengiesser, Caroline; Jouanolle, Anne-Marie; Hetet, Gilles; Mosser, Annick; Muzeau, Françoise; Henry, Dominique; Bardou-Jacquet, Edouard; Mornet, Martine; Brissot, Pierre; Deugnier, Yves; Grandchamp, Bernard; Beaumont, Carole

    2009-01-01

    Background Elevated serum ferritin levels are frequently encountered in clinical situations and once iron overload or inflammation has been ruled out, many cases remain unexplained. Genetic causes of hyperferritinemia associated to early cataract include mutations in the iron responsive element in the 5’ untranslated region of the L ferritin mRNA, responsible for the hereditary hyperferritinemia cataract syndrome. Design and Methods We studied 91 probands with hyperferritinemia comprising 25 family cases belonging to families with at least two cases of unexplained hyperferritinemia, and 66 isolated cases. In the families, we also analyzed 30 relatives. Hyperferritinemia was considered as unexplained when transferrin saturation was below 45% and/or serum iron below 25 μmol/L and/or no tissue iron excess was detected, when inflammation had been ruled out and when iron responsive element mutation was absent. We carried out sequencing analysis of the FTL gene coding the L ferritin. Results A novel heterozygous p.Thr30Ile mutation in the NH2 terminus of L ferritin subunit was identified in 17 probands out of the cohort. The mutation was shown to cosegregate with hyperferritinemia in all the 10 families studied. No obvious clinical symptom was found associated with the presence of the mutation. This unique mutation is associated with an unusually high percentage of ferritin glycosylation. Conclusions This missense mutation of FTL represents a new cause of genetic hyperferritinemia without iron overload. We hypothesized that the mutation increases the efficacy of L ferritin secretion by increasing the hydrophobicity of the N terminal “A” α helix. PMID:19176363

  2. Wild Edible Fruit of Prunus nepalensis Ser. (Steud, a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice.

    Directory of Open Access Journals (Sweden)

    Dipankar Chaudhuri

    Full Text Available The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud, a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical (IC50 = 30.92 ± 0.40 μg/ml. PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38. On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.

  3. 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

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

    OpenAIRE

    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...

  5. Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

    Czech Academy of Sciences Publication Activity Database

    Beneš, J.; Kazdová, L.; Drahota, Zdeněk; Houštěk, Josef; Medříková, Daša; Kopecký, Jan; Kovářová, Nikola; Vrbacký, Marek; Sedmera, David; Strnad, Hynek; Kolář, Michal; Petrák, J.; Benada, Oldřich; Škaroupková, P.; Červenka, L.; Melenovský, V.

    2011-01-01

    Roč. 121, č. 1 (2011), s. 29-41. ISSN 0143-5221 R&D Projects: GA MŠk(CZ) 1M0510; GA MZd(CZ) NS9757; GA MŠk(CZ) 1M0520 Grant ostatní: GA MZd(CZ) NS10497; GA ČR(CZ) GA305/09/1390 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : AMP-activated protein kinase * energy metabolism * heart failure * metformin * survival * volume overload Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.317, year: 2011

  6. CARDIAC FUNCTION AND IRON CHELATION IN THALASSEMIA MAJOR AND INTERMEDIA: A REVIEW OF THE UNDERLYING PATHOPHYSIOLOGY AND APPROACH TO CHELATION MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Athanasios Aessopos

    2009-07-01

    Full Text Available Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia.  The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload.  The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype.  Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function.  For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy.  Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients.  If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted.  In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available.  With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with

  7. Exogenous nerve growth factor supplementation elevates myocardial immunoreactivity and attenuates cardiac remodeling in pressure-overload rats

    Institute of Scientific and Technical Information of China (English)

    Bing He; and Yuming Li; Fan Ye; Xin Zhou; He Li; Xiaoqing Xun; Xiaoqing Ma; Xudong Liu; Zhihong Wang; Pengxiao Xu

    2012-01-01

    It is postulated that supplementation of exogenous nerve growth factor (NGF) might mediate improvement of the cardiac sympathetic nerve function in heart failure (HF).Local intramuscular injection of NGF near the cardiac sympathetic ganglia could influence the innervation pattern,norepinephrine transporter (NET) gene expression,and improve the cardiac remodeling in experimental HF animals.In this study,we injected NGF into the scalenus medius muscles of Sprague-Dawley rats with abdominal aortic constriction (AC).The nerve innervated pattern,left ventricular morphology,and function following injection in rats with AC were investigated respectively by immunohistochemistry and echocardiography.Levels of mRNA expression of NET,growth associated protein 43 (GAP 43),NGF and its receptors TrkA and p75NTR,and brain natriuretic peptide (BNP) were measured by realtime polymerase chain reaction.The results showed that myocardial NGF mRNA levels were comparable in rats with AC.Short-term supplementation of exogenous NGF raised the myocardial NGF immunoreactivity,but did not cause hyperinnervation and NET mRNA upregulation in the AC rats.Furthermore,myocardial TrkA mRNA was found to be remarkably decreased and p75NTR mRNA was increased.Myocardial TrkA downregulation may play a beneficial effect for avoiding the hyperinnervation,and it is reasonable to postulate that p75NTR can function as an NGF receptor in the absence of TrkA.Interestingly,local NGF administration into the neck muscles near the ganglia could attenuate cardiac remodeling and downregulate BNP mRNA.These results suggest that exogenous NGF can reach the target tissue along the axons anterogradely,and improve the cardiac remodeling.

  8. The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

    Directory of Open Access Journals (Sweden)

    Jianping Li

    2016-03-01

    Results and conclusion: The results indicate the presence of PAR-2 on MCs and that tryptase inhibition and nedocromil prevented TAC-induced fibrosis and increases in MC density, activation, and chymase release. Tryptase also significantly increased chymase concentration in ventricular slice culture media, which was prevented by the tryptase inhibitor. Hydroxyproline concentration in culture media was significantly increased with tryptase incubation as compared to the control group and the tryptase group incubated with nafamostat mesilate or chymostatin. We conclude that tryptase contributes to TAC-induced cardiac fibrosis primarily via activation of MCs and the amplified release of chymase.

  9. Effects of combination of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in rat cardiac pressure-overload hypertrophy

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Aim: To observe effects of angiotensin (Ang) Ⅱ receptor antagonist (AT1) irbesartan and angiotensin-converting enzyme (ACE) inhibitor perindopril on rat myocardium calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in the model of pressure-overload cardiac hypertrophy. Methods: Forty male adult Sprague Dawley rats were divided into 5 groups.One group was treated by sham operation; four groups were myocardium hypertrophy cases caused by banding aortic above renal artery. Drugs were given one week after operation. Group 1: sham group, rats (n=8) were gavaged with normal saline 2 ml/(kg·d)(ig); Group 2: control group, rats (n=8) were treated with normal saline 2 ml/(kg·d) (ig); Group 3: rats (n=8) were given perindopril 2 mg/(kg·d) (ig); Group 4: rats (n=8) were treated with irbesartan 20 mg/(kg·d) (ig); Group 5: rats (n=8) were given irbesartan 20 mg/(kg·d) plus perindopril 2 mg/(kg·d) (ig). Morphometric determination, calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity were done at the end of 6 week of drug intervention. Expression of calcineurin in myocardium was detected by immunohistochemistry. Results: Left ventricular mass index (LVMI), transverse diameter of myocardial cell (TDM), calcineurin activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination drug therapy group. Sarcoplasmic reticulum Ca2+-ATPase activity was increased after drug intervention, especially in the combined drug therapy group. Calcineurin expression in myocardium was remarkably decreased after drug intervention. LVMI was positively correlated with TDM and calcineurin, negatively correlated with sarcoplasmic reticulum Ca2+-ATPase. Conclusion:These data suggest that irbesartan and perindopril inhibit cardiac hypertrophy through the increased activity of sarcoplasmic reticulum Ca2+-ATPase and decreased expression of calcineurin. Their combination had better effects on regressing of

  10. Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    Xue-Hui Wang; Xiao-Zhen Zhuo; Ya-Juan Ni; Min Gong; Ting-Zhong Wang; Qun Lu; Ai-Qun Ma

    2012-01-01

    Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

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

    OpenAIRE

    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 Pr...

  12. MRI Measurements of Iron Load in Transfusion-Dependent Patients: Implementation, Challenges, and Pitfalls.

    Science.gov (United States)

    Quinn, Charles T; St Pierre, Tim G

    2016-05-01

    Magnetic resonance imaging (MRI) has played a key role in studies of iron overload in transfusion-dependent patients, providing insights into the relations among liver and cardiac iron loading, iron chelator dose, and morbidity. Currently, there is rapid uptake of these methods into routine clinical practice as part of the management strategy for iron overload in regularly transfused patients. Given the manifold methods of data acquisition and analysis, there are several potential pitfalls that may result in inappropriate decision making. Herein, we review the challenges of establishing suitable MRI techniques for tissue iron measurement in regularly transfused patients. PMID:26713769

  13. 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.

  14. Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload

    OpenAIRE

    Trinder, D.; P.; Oates; Thomas, C; Sadleir, J.; Morgan, E.

    2000-01-01

    BACKGROUND—The mechanism of iron absorption by the intestine and its transfer to the main iron storage site, the liver, is poorly understood. Recently an iron carrier was cloned and named DMT1 (divalent metal transporter 1).
AIMS—To determine the level of DMT1 gene expression and protein distribution in duodenum and liver.
METHODS—A DMT1 cRNA and antibody were produced and used in in situ hybridisation and immunohistochemistry, respectively, in rats in which the iron stores were altered by fe...

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

    Science.gov (United States)

    Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della; Fenaux, Pierre; Ganser, Arnold; Guerci-Bresler, Agnes; Schmid, Mathias; Taylor, Kerry; Vassilieff, Dominique; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Rose, Christian

    2010-09-01

    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 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. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p<0.0001). This large dataset prospectively confirms the efficacy and well characterizes the safety profile of deferasirox in MDS. PMID:20451251

  16. 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.

  17. 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....... Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p...

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

    DEFF Research Database (Denmark)

    Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della; Fenaux, Pierre; Ganser, Arnold; Guerci-Bresler, Agnes; Schmid, Mathias; Taylor, Kerry; Vassilieff, Dominique; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Rose, Christian Schack; Kjeldsen, Lars

    2010-01-01

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

  19. 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.

  20. Rapid iron loading in a pregnant woman with transfusion-dependent thalassemia after brief cessation of iron chelation therapy

    OpenAIRE

    Farmaki, Kallistheni; Gotsis, Efstathios; Tzoumari, Ioanna; Berdoukas, Vasilios

    2008-01-01

    In general, in women with transfusion-dependent thalassemia, during pregnancy, iron chelation therapy is ceased. We report a splenectomized patient, who was an excellent complier with chelation therapy, who before embarking on a pregnancy showed no evidence of iron overload, with normal cardiac, thyroid function and glucose metabolism. Laboratory findings showed ferritin 67 μg/L, myocardial T2* of 34 ms and liver magnetic resonance imaging (MRI) liver iron concentration of 1 mg/g dry weight. ...

  1. 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

  2. Coenzyme Q10 Supplementation Prevents Iron Overload While Improving Glycaemic Control and Antioxidant Protection in Insulin-Resistant Psammomys obesus.

    Science.gov (United States)

    Lazourgui, Mohamed Amine; El-Aoufi, Salima; Labsi, Moussa; Maouche, Boubekeur

    2016-09-01

    This study investigated the anti-diabetic preventive activity of coenzyme Q10 (CoQ10) in a murine model of diet-induced insulin resistance (IR), Psammomys obesus (Po). IR was induced by feeding a standard laboratory diet (SD). CoQ10 oil suspension was orally administered at 10 mg/kg body weight (BW)/day along with SD for 9 months. Anthropometric parameters, namely, total body weight gain (BWG) and the relative weight of white adipose tissue (WAT) were determined. Blood glucose, insulin, quantitative insulin sensitivity check index (QUICKI), total antioxidant status (TAS), iron, malondialdehyde (MDA) and nitrite (NO2 (-)) were evaluated. NO2 (-) level was also assessed in peripheral blood mononuclear cells (PBMCs) culture supernatants. Our results show that CoQ10 supplementation significantly improved blood glucose, insulin, QUICKI, TAS, iron and MDA, but influenced neither NO2 (-) levels nor the anthropometric parameters. These findings support the hypothesis that CoQ10 would exert an anti-diabetic activity by improving both glycaemic control and antioxidant protection. The most marked effect of CoQ10 observed in this study concerns the regulation of iron levels, which may carry significant preventive importance. PMID:26779622

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-09-01

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

  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. Iron Therapy for Preterm Infants

    OpenAIRE

    Rao, Raghavendra; Georgieff, Michael K.

    2009-01-01

    Preterm infants are at risk for both iron deficiency and iron overload. The role of iron in multiple organ functions suggests that iron supplementation is essential for the preterm infant. Conversely, the potential for iron overload and the poorly developed anti-oxidant measures in the preterm infant argues against indiscriminate iron supplementation in this population. The purpose of this article is to review the predisposing factors and consequences of iron deficiency and iron overload in t...

  7. Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy A redução da pressão de perfusão coronariana está associada com a fibrose endocárdica no modelo de hipertrofia por sobrecarga de volume em ratos

    OpenAIRE

    Maria Carolina Guido; Márcia Kiyomi Koike; Clovis de Carvalho Frimm

    2004-01-01

    Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To in...

  8. 携带式微量注射泵在血液病中治疗铁过载的护理%Nursing of Portable Syringe Pump Iron Overload in the Treatment of Blood Diseases

    Institute of Scientific and Technical Information of China (English)

    陈为

    2014-01-01

    Objective: using portable micro pump subcutaneous deferoxamine to nursing iron overload of iron treatment, in order to improve the clinical treatment ef ect. Methods:I Division in 2011 January--2013 year in August a total of 31 cases of patients with clinical diagnosis of iron overload, the portable micro pump subcutaneous deferoxamine to iron therapy. Results: Patients with iron overload use portable micro injection pump to iron treatment ef icacy. Conclusion: to increase the safety coef icient and the ef ective concentration of the medication of the patients, improve the therapeutic ef ect, is beneficial to the recovery of patients. Simple operation, easy to use, reduces the burden of nurses, improve the quality of medical care, clinical curative ef ect, is a kind of new technique worthy of popularization and application.%目的:采用携带式微量泵皮下注射去铁胺去铁治疗铁过载的护理,以提高临床治疗效果。方法选择我科于2011年1月~2013年8月共有31例血液病患者符合铁过载的临床诊断,采用携带式微量泵皮下注射去铁胺去铁治疗。结果铁过载患者使用携带式微量注射泵去铁治疗效果肯定。结论增加患者用药安全系数和有效浓度,提高治疗效果,有利于患者早日康复。操作简单,使用方便,减轻了护士负担,提高了医疗护理质量,临床疗效确切,是值得推广应用的一种新技术。

  9. Prevention of Cardiomyopathy in Transfusion-Dependent Homozygous Thalassaemia Today and the Role of Cardiac Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Athanassios Aessopos

    2009-01-01

    Full Text Available Transfusion and iron chelation therapy revolutionised survival and reduced morbidity in patients with transfusion-dependent beta thalassaemia major. Despite these improvements, cardiac disease remained the most common cause of death in those patients. Recently the ability to determine the degree of cardiac iron overload, through cardiac magnetic resonance imaging (CMR has allowed more logical approaches to iron removal, particularly from the heart. The availability of two oral chelators, deferiprone and deferasirox has reduced the need for the injectable chelator deferrioxamine and an additional benefit has been that deferiprone has been shown to be more cardioprotective than deferrioxamine. This review on the prevention of cardiac disease makes recommendations on the chelation regime that would be desirable for patients according to their cardiac iron status as determined by CMR determined by CMR. It also discusses approaches to chelation management should CMR not be available.

  10. 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.

  11. CMR T2* technique for segmental and global quantification of myocardial iron: multi-centre transfereability and healtcare impact evalaution

    OpenAIRE

    Gerardi Calogera; Luciani Antongiulio; Valeri Gianluca; Restaino Gennaro; Cracolici Eliana; Natale Luigi; Mangione Maurizio; Marcheschi Paolo; Salvatori Cristina; Rossi Giuseppe; Pepe Alessia; Meloni Antonella; Ramazzotti Anna; Positano Vincenzo; Lombardi Massimo

    2009-01-01

    The multislice multiecho T2* technique is transferable among scanners with good reproducibility. The network seems to be a robust and scalable system in which T2* CMR based cardiac iron overload assessment is available, accessible and reachable for a significant and increasing number of thalassemia patients, reducing the mean distance from the patients' locations to the CMR sites.

  12. HSF1 and NF-κB p65 participate in the process of exercise preconditioning attenuating pressure overload-induced pathological cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Tongyi [Department of Cardiothoracic Surgery, No. 401 Hospital of PLA, Qingdao (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zhang, Ben [Centre of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Yang, Fan; Cai, Chengliang; Wang, Guokun [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Han, Qingqi, E-mail: handoctor@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zou, Liangjian, E-mail: zouliangjiansh@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2015-05-08

    Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague–Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation. - Highlights: • EP could effectively reduce the cardiac hypertrophic responses induced by TAC. • EP may play a protective role by upregulating the expressions of HSF1 and HSP70 and then activating HSF1. • EP may play a protective role by inhibiting the expression

  13. HSF1 and NF-κB p65 participate in the process of exercise preconditioning attenuating pressure overload-induced pathological cardiac hypertrophy

    International Nuclear Information System (INIS)

    Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague–Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation. - Highlights: • EP could effectively reduce the cardiac hypertrophic responses induced by TAC. • EP may play a protective role by upregulating the expressions of HSF1 and HSP70 and then activating HSF1. • EP may play a protective role by inhibiting the expression

  14. The use of skin Fe levels as a surrogate marker for organ Fe levels, to monitor treatment in cases of iron overload

    Science.gov (United States)

    Farquharson, Michael J.; Bagshaw, Andrew P.; Porter, John B.; Abeysinghe, R. D.

    2000-05-01

    A system based on the detection of K-shell x-ray fluorescence (XRF) has been used to investigate whether a correlation exists between the concentration of iron in the skin and the concentration of iron in the liver, as the degree of iron loading increases. The motivation behind this work is to develop a non-invasive method of determining the extent of the body's iron stores via measurements on the skin, in order to monitor the efficacy of chelation therapy administered to patients with β-thalassaemia. Sprague-Dawley rats were iron loaded via injections of iron dextran and subsequently treated with the iron chelator CP94. The non-haem iron concentrations of the liver, heart and spleen were determined using bathophenanthroline sulphonate as the chromogen reagent. Samples of abdominal skin were taken and the iron concentrations determined using XRF. A strong correlation between the skin iron concentration and the liver iron concentration has been demonstrated (R2 = 0.86). Similar correlations exist for the heart and the spleen. These results show that this method holds great potential as a tool in the diagnosis and treatment of hereditary haemochromatosis and β-thalassaemia.

  15. The use of skin Fe levels as a surrogate marker for organ Fe levels, to monitor treatment in cases of iron overload

    International Nuclear Information System (INIS)

    A system based on the detection of K-shell x-ray fluorescence (XRF) has been used to investigate whether a correlation exists between the concentration of iron in the skin and the concentration of iron in the liver, as the degree of iron loading increases. The motivation behind this work is to develop a non-invasive method of determining the extent of the body's iron stores via measurements on the skin, in order to monitor the efficacy of chelation therapy administered to patients with β-thalassaemia. Sprague-Dawley rats were iron loaded via injections of iron dextran and subsequently treated with the iron chelator CP94. The non-haem iron concentrations of the liver, heart and spleen were determined using bathophenanthroline sulphonate as the chromogen reagent. Samples of abdominal skin were taken and the iron concentrations determined using XRF. A strong correlation between the skin iron concentration and the liver iron concentration has been demonstrated (R2 = 0.86). Similar correlations exist for the heart and the spleen. These results show that this method holds great potential as a tool in the diagnosis and treatment of hereditary haemochromatosis and β-thalassaemia. (author)

  16. The use of skin Fe levels as a surrogate marker for organ Fe levels, to monitor treatment in cases of iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Farquharson, M.J.; Bagshaw, A.P. [Department of Radiography, City University, Rutland Place, Charterhouse Square, London EC1M 6PA (United Kingdom); Porter, J.B.; Abeysinghe, R.D. [Department of Haematology, University College London, 98 Chenies Mews, London WC1E 6HX (United Kingdom)

    2000-05-01

    A system based on the detection of K-shell x-ray fluorescence (XRF) has been used to investigate whether a correlation exists between the concentration of iron in the skin and the concentration of iron in the liver, as the degree of iron loading increases. The motivation behind this work is to develop a non-invasive method of determining the extent of the body's iron stores via measurements on the skin, in order to monitor the efficacy of chelation therapy administered to patients with {beta}-thalassaemia. Sprague-Dawley rats were iron loaded via injections of iron dextran and subsequently treated with the iron chelator CP94. The non-haem iron concentrations of the liver, heart and spleen were determined using bathophenanthroline sulphonate as the chromogen reagent. Samples of abdominal skin were taken and the iron concentrations determined using XRF. A strong correlation between the skin iron concentration and the liver iron concentration has been demonstrated (R{sup 2} = 0.86). Similar correlations exist for the heart and the spleen. These results show that this method holds great potential as a tool in the diagnosis and treatment of hereditary haemochromatosis and {beta}-thalassaemia. (author)

  17. Iron deposition following chronic myocardial infarction as a substrate for cardiac electrical anomalies: initial findings in a canine model.

    Directory of Open Access Journals (Sweden)

    Ivan Cokic

    Full Text Available PURPOSE: Iron deposition has been shown to occur following myocardial infarction (MI. We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. METHODS: Two groups of dogs (ex-vivo (n = 12 and in-vivo (n = 10 were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity ([Formula: see text] and conductivity ([Formula: see text]. Mass spectrometry was used to classify and characterize tissue sections with (IRON+ and without (IRON- iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR for estimation of scar volume (late-gadolinium enhancement, LGE and iron deposition (T2* relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR, QT interval (QT, QT corrected for HR (QTc and QTc dispersion (QTcd. In a fraction of these animals (n = 5, ultra-high resolution electroanatomical mapping (EAM was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs. RESULTS: Compared to IRON- sections, IRON+ sections had higher[Formula: see text], but no difference in[Formula: see text]. A linear relationship was found between iron content and [Formula: see text] (p1.5% with similar scar volumes (7.28% ± 1.02% (Iron (1.5%, p = 0.51 but markedly different iron volumes (1.12% ± 0.64% (Iron (1.5%, p = 0.02, QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05. EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. CONCLUSION: The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may

  18. The Association between Myocardial Iron Load and Ventricular Repolarization Parameters in Asymptomatic Beta-Thalassemia Patients

    Directory of Open Access Journals (Sweden)

    Mehmet Kayrak

    2012-01-01

    Full Text Available Previous studies have demonstrated impaired ventricular repolarization in patients with β-TM. However, the effect of iron overload with cardiac T2* magnetic resonance imaging (MRI on cardiac repolarization remains unclear yet. We aimed to examine relationship between repolarization parameters and iron loading using cardiac T2* MRI in asymptomatic β-TM patients. Twenty-two β-TM patients and 22 age- and gender-matched healthy controls were enrolled to the study. From the 12-lead surface electrocardiography, regional and transmyocardial repolarization parameters were evaluated manually by two experienced cardiologists. All patients were also undergone MRI for cardiac T2* evaluation. Cardiac T2* score <20 msec was considered as iron overload status. Of the QT parameters, QT duration, corrected QT interval, and QT peak duration were significantly longer in the β-TM group compared to the healthy controls. Tp−Te and Tp−Te dispersions were also significantly prolonged in β-TM group compared to healthy controls. (Tp-Te/QT was similar between groups. There was no correlation between repolarization parameters and cardiac T2* MRI values. In conclusion, although repolarization parameters were prolonged in asymptomatic β-TM patients compared with control, we could not find any relation between ECG findings and cardiac iron load.

  19. Iron mobilization using chelation and phlebotomy

    DEFF Research Database (Denmark)

    Flaten, T. P.; Aaseth, J.; Andersen, Ole;

    2012-01-01

    . Iron overload has many different causes, both genetic and environmental. The two most common iron overload disorders are hereditary haemochromatosis and transfusional siderosis, which occurs in thalassaemias and other refractory anaemias. The two most important treatment options for iron overload are...

  20. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Tarp, Sven; Gouws, Rufus H.

    2016-01-01

    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 th...

  1. 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.

  2. METABOLISM OF IRON STORES

    OpenAIRE

    Saito, Hiroshi

    2014-01-01

    ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since th...

  3. 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)

    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)

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

    Science.gov (United States)

    Xu, Qi; Kanthasamy, Anumantha G.; Jin, Huajun; Reddy, Manju B.

    2016-01-01

    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 Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P 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. PMID:27298749

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

    Science.gov (United States)

    Xu, Qi; Kanthasamy, Anumantha G; Jin, Huajun; Reddy, Manju B

    2016-01-01

    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 export mediated by ferroportin 1. PMID:27298749

  6. 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

    2012-03-01

    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

  7. Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

    OpenAIRE

    Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E.; Zhong, Ju-ming

    2015-01-01

    Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- a...

  8. Iron Imports. III. Transfer of iron from the mucosa into circulation

    OpenAIRE

    Wessling-Resnick, Marianne

    2006-01-01

    Transfer of iron from the mucosa is a critical step in dietary iron assimilation that is tightly regulated to ensure the appropriate amount of iron is absorbed to meet the body's demands. Too much iron is highly toxic, and failure to properly control intestinal iron export causes iron overload associated with hereditary forms of hemochromatosis. One form of genetic iron overload, ferroportin disease, originates due to defects in ferroportin, the membrane iron exporter. Ferroportin acts in con...

  9. Electrocardiographic Presentation, Cardiac Arrhythmias, and Their Management in β-Thalassemia Major Patients.

    Science.gov (United States)

    Russo, Vincenzo; Rago, Anna; Papa, Andrea Antonio; Nigro, Gerardo

    2016-07-01

    Beta-thalassemia major (β-TM) is a genetic hemoglobin disorder characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Clinical management of thalassemia major consists in regular long-life red blood cell transfusions and iron chelation therapy to remove iron introduced in excess with transfusions. Iron deposition in combination with inflammatory and immunogenic factors is involved in the pathophysiology of cardiac dysfunction in these patients. Heart failure and arrhythmias, caused by myocardial siderosis, are the most important life-limiting complications of iron overload in beta-thalassemia patients. Cardiac complications are responsible for 71% of global death in the beta-thalassemia major patients. The aim of this review was to describe the most frequent electrocardiographic abnormalities and arrhythmias observed in β-TM patients, analyzing their prognostic impact and current treatment strategies. PMID:27324981

  10. Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice

    Science.gov (United States)

    Sustained pressure overload causes cardiac hypertrophy and the transition to heart failure. We show here that dietary supplementation with physiologically relevant levels of copper (Cu) reverses pre-established hypertrophic cardiomyopathy in the presence of pressure overload induced by ascending aor...

  11. 铁超负荷诱导胰岛细胞凋亡机制的研究%Thestudy of mechanism on iron overload inducing apoptosis of pancreatic islet cells in the wistar rats

    Institute of Scientific and Technical Information of China (English)

    吕雪梅; 高赟; 杨波; 陈涛; 龙洋; 田浩明

    2012-01-01

    Objective To investigate the effect of iron overload on apoptosis of pancreatic islet cells in the Wistar rats. Methods Sixty-five male rats of the Wistar strain were divided randomly into four groups: Group A which received repeated in-traperitoneal injections of ferric nitrilotriacetate (FeNTA) , Group B which received the equivalent dose of disodic nitrilotriacetate, Group C which was injected i. p. Diethylenetriaminepentaacetic acid besides FeNTA and Group D that was untreated controls, respectively. Glucose tolerance tests were performed at the beginning and the 10th week. Serum iron and ferritin were measured after performing the intervention. The protein and mRNA expression of Caspase-3、PPAR-γ and NF-KB in pancreatic islets were assessed by immunohistochemistry and in situ hybridization, respectively. Results At 10 week, both the protein and mRNA expression of Caspase-3 as well as NF-KB were significantly higher in Group A than those of the other groups; the protein and mRNA expression of PPAR-γ in Group A were lower as compared with group B or group D; the apoptotic cells of islets in Group A were more than those in the other groups. Conclusion Iron overload may induce oxidative stress and NF-KB activation, inhibit the expression of PPAR-γ and lead to the increased expression of Caspase-3 in islet cells, which were involved in the apoptosis of islet cells.%目的 观察铁超负荷对Wistar大鼠胰岛细胞凋亡影响.方法 雄性Wistar大鼠65只随机分为四组:A组(铁干预组)、B组(次氮三乙酸二钠对照组)、C组(铁干预加去铁组)和D组(空白对照组).于实验开始、第10周时行腹腔注射葡萄糖耐量试验;10周后采血测血清铁、血清铁蛋白;针对NF-κB、PPAR-γ Caspase-3作免疫组织化学染色及核酸原位杂交.结果 A组胰岛中NF-κB、Caspase-3蛋白、NF-κB和Caspase-3 mRNA较其它三组明显增加(P<0.05);A组胰岛中PPAR-γ蛋白和mRNA较B组和D组明显减低(P<0.05);A组胰岛

  12. Cardiac Failure after Liver Transplantation Requiring a Biventricular Assist Device

    Directory of Open Access Journals (Sweden)

    Rita Jermyn

    2014-01-01

    Full Text Available Increased hepatic iron load in extrahepatic organs of cirrhotic patients with and without hereditary hemochromatosis portends a poorer long term prognosis after liver transplant. Hepatic as well as nonhepatic iron overload is associated with increased infectious and postoperative complications, including cardiac dysfunction. In this case report, we describe a cirrhotic patient with alpha 1 antitrypsin deficiency and nonhereditary hemochromatosis (non-HFE that developed cardiogenic shock requiring mechanical circulatory support for twenty days after liver transplant. Upon further investigation, she was found to have significant iron deposition in both the liver and heart biopsies. Her heart regained complete and sustained recovery following ten days of mechanical biventricular support. This case highlights the importance of preoperatively recognizing extrahepatic iron deposition in patients referred for liver transplantation irrespective of etiology of liver disease as this may prevent postoperative complications.

  13. Non cardiopatic and cardiopatic beta thalassaemic patients: quantitative and qualitative cardiac iron deposition evaluation with MRI; Pazienti {beta} talassemici non cardiopatici e cardiopatici: valutazione quantitativa e qualitativa del deposito di ferro cardiaco con RM

    Energy Technology Data Exchange (ETDEWEB)

    Macarini, Luca; Marini, Stefania; Scardapane, Arnaldo [Bari Univ., Bari (Italy). DIMIMP-Sezione di Diagnostica per Immagini; Pietrapertosa, Anna [Bari Univ., Bari (Italy). MIDIM-Cattedra di Ematologia II; Ettore, Giovanni Carlo [Foggia Univ., Foggia (Italy). Cattedra di Radiologia

    2005-02-01

    Purpose: Cardiomyopathy is one of the major complications of {beta} thalassaemia major as a result of transfusion iron overload. The aim of our study is to evaluate with MR if there is any difference of iron deposition signal intensity (SI) or distribution between non-cardiopatic and cardiopatic thalassaemic patients in order to establish if there is a relationship between cardiopathy and iron deposition. Materials and methods: We studied 20 patients affected by {beta} thalassaemia major, of whom 10 cardiopatic and 10 non-cardiopatic, and 10 healthy volunteers as control group. Serum ferritin and left ventricular ejection fraction were calculated in thalassaemic patients. All patients were examinated using a 1.5 MR unit with ECG-gated GE cine-MR T2*-weighted, SE T1-weighted and GE T2*-weighted sequences. In all cases, using an adequate ROI, the myocardial and skeletal muscle signal intensity (SI), the myocardial/skeletal muscle signal intensity radio (SIR) and the SI average of the myocardium and skeletal muscle were calculated for every study group. The qualitative evaluation of iron deposition distribution was independently performed by three radiologists who analysed the extension, the site and the morphology of iron deposition on the MR images and reported their observations on the basis of a four-level rating scale: 0 (absent), 1 (limited), 2 (partial), 3 (widespread deposition). The results of quantitative and qualitative evaluation were analysed with statistical tests. Results: Cardiac iron deposition was found in 8/10 non-cardiopatic thalassaemic patients and in all cardiopatic thalassaemic patients. We noticed a significant SI difference (p>0.05) between the healthy volunteer control group and the thalassaemic patients with iron deposition, but no significant SI difference in iron deposition between non-cardiopatic thalassaemic patients in the areas evaluated. The qualitative evaluation revealed a different distribution of iron deposition between the two

  14. 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 ...

  15. Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral Deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload.

    Science.gov (United States)

    Nolte, F; Höchsmann, B; Giagounidis, A; Lübbert, M; Platzbecker, U; Haase, D; Lück, A; Gattermann, N; Taupitz, M; Baier, M; Leismann, O; Junkes, A; Schumann, C; Hofmann, W K; Schrezenmeier, H

    2013-01-01

    The majority of patients with myelodysplastic syndrome (MDS) present with anemia and will become dependent on regular transfusions of packed red blood cells (PRBC) with the risk of iron overload (IOL). Liver iron content best reflects the total body iron content, and measurement of liver iron concentration (LIC) by MRI is a validated tool for detection, but data in MDS is rather limited. Here we present the results of a multi-center trial evaluating the efficacy and safety of deferasirox (DFX) in low and intermediate-1 risk MDS patients with transfusion-dependent IOL. Three patients with transfusion frequency of > 4 units PRBC per month were initially treated with 30 mg/kg/day while in 46 patients with a lower transfusion burden deferasirox was initiated at 20 mg/kg/day, due to patient related reasons one patient received DFX in a dose of 6 mg/kg/day only. LIC was measured by MRI at baseline and end of study using the method by St. Pierre et al. The intention to treat population consisted of 50 MDS patients (28 male; 22 female) with a median age of 69 years who were treated with DFX for a median duration of 354 days. Mean daily dose of DFX was 19 mg/kg/day. Median serum ferritin level (SF) at baseline was 2,447 ng/mL and decreased to 1,685 ng/mL (reduction by 31 %) at end of study (p = 0.01). In 7 (13 %) patients the initially chosen dose had to be increased due to unsatisfactory efficacy of chelation therapy. For 21 patients, LIC measurement by liver MRI was performed at baseline and for 19 of these patients at the end of study: mean LIC decreased significantly from 16,8 mg/g dry tissue weight (± 8.3 mg/g dry tissue weight) at study entry to 10,8 mg/g dry tissue weight (± 10.4 mg/g dry tissue weight) at end of study (p = 0.01). Of all patients exposed to the study drug (n = 54), 28 (52 %) did not complete the 12 month study period most commonly due to AEs in 28 % (n = 15) and abnormal laboratory values in 7 % (n = 4

  16. A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload

    Directory of Open Access Journals (Sweden)

    Lacerda Rosa

    2006-03-01

    (p = 0.0009. Conclusion The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH. It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed.

  17. Iron Metabolism in Thalassemia and Sickle Cell Disease.

    OpenAIRE

    Mariani, Raffaella; Trombini, Paola; Pozzi, Matteo; Piperno, Alberto

    2009-01-01

    There are two main mechanisms by which iron overload develops in thalassemias: increased iron absorption due to ineffective erythropoiesis and blood transfusions. In nontransfused patients with severe thalassemia, abnormal dietary iron absorption increases body iron burden between 2 and 5 g per year. If regular transfusions are required, this doubles the rate of iron accumulation leading to earlier massive iron overload and iron-related damage. Iron metabolism largely differs between thalasse...

  18. 长期铅暴露雄性大鼠脑组织铁过载及DNA氧化损伤%Effect of iron overload and DNA oxidative stress in male rats brain exposed to lead

    Institute of Scientific and Technical Information of China (English)

    焦欢; 陈英; 黎砚书; 周繁坤; 杜桂花; 管临福; 王志平; 冯昶; 祝高春

    2013-01-01

    determined by ELISA.The offspring were measured the lead and iron concentration of brain by ICP-AES.Results At the same growth stage,the brain lead,brain iron and 8-OHdG contents were higher in different lead exposure groups compared with the control.Linear regression showed that the brain iron and the 8-OHdG contents of the brain were higher in different lead exposure groups (P<0.05); Brain iron and brain lead could jointly raise the 8-OHdG of brain(P<0.05),whether a synergistic effect between brain iron and brain lead needed to be validated.The 8-OHdG contents increased with lead exposure levels at weaning and the old-age (P<0.05).In control group,the mid-age and old-age groups were higher than the weaning rats (P<0.05).In high lead group,the old-age group was higher than the mid-age and weaning rats (P<0.05).There was no significant difference in mid-aged rats.Conclusion Lead exposure may induce iron overload and DNA damage in rat brain.

  19. Iron

    Science.gov (United States)

    ... seafood, and foods that contain vitamin C , like citrus fruits, strawberries, sweet peppers, tomatoes, and broccoli. What ... diets. What are some effects of iron on health? Scientists are studying iron to understand how it ...

  20. 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...

  1. Pathophysiological and clinical aspects of iron chelation therapy in MDS.

    Science.gov (United States)

    Gattermann, Norbert

    2012-01-01

    The majority of patients with myelodysplastic syndromes (MDS) become transfusion-dependent during the course of disease and may thus develop transfusional iron overload. As a further contributor to iron overload there is increased absorption of dietary iron from the gut, as a consequence of ineffective erythropoiesis. Compared with thalassemia, it is less clear how frequent patients with MDS develop clinical complications of iron overload, and whether the accumulation of iron shortens their survival. This review aims to summarize our current knowledge of the detrimental effects of transfusional iron overload in MDS, point out the risks associated with iron-induced oxidative stress, describe the tools available for diagnosing iron overload, indicate the treatment options with currently available iron chelators, and discuss the measurement of labile plasma iron (LPI) as a tool to monitor the efficacy of iron chelation therapy. PMID:22571702

  2. New developments and controversies in iron metabolism and iron chelation therapy

    OpenAIRE

    Christina N. Kontoghiorghe; Kontoghiorghes, George J.

    2016-01-01

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using ...

  3. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  4. Iron Overload in Sickle Cell Disease

    OpenAIRE

    Little, Jane A.; Deepa Manwani; Radha Raghupathy

    2010-01-01

    In sickle cell disease transfusions improve blood flow by reducing the proportion of red cells capable of forming sickle hemoglobin polymer. This limits hemolysis and the endothelial damage that result from high proportions of sickle polymer-containing red cells. Additionally, transfusions are used to increase blood oxygen carrying capacity in sickle cell patients with severe chronic anemia or with severe anemic episodes. Transfusion is well-defined as prophylaxis (stroke) and as therapy (acu...

  5. Changes of iron overload in children with severe beta-thalassaemia pre- and post-splenectomy%重度β-地中海贫血患儿脾脏切除术前后铁负荷的变化

    Institute of Scientific and Technical Information of China (English)

    金伶; 龙兴江; 袁大华; 杨彤; 黄献文

    2014-01-01

    Objective To explore the changes of iron overload in children with severeβ-thalassemia pre-and post-sple-nectomy. Method The annual amount of blood transfused and serum ferritin (SF) levels of 18 children with severeβ-thalasse-mia before and after splenectomy from January 2003 to December 2012 were retrospectively analyzed. Result The annual amount of blood transfused in children with severeβ-thalassemia at one year and two years after splenectomy were (101.94 ± 30.73) ml/kg and (96.50 ± 34.00) ml/kg respectively, significantly lower than the amount of two years before splenectomy (241.89 ± 73.66) ml/kg and one year before splenectomy (289.22 ± 102.30) ml/kg (P<0.05). The SF levels at 6, 12, 18 and 24 months after splenectomy were (2 410.00 ± 731.77) μg/L, (2 742.78 ± 813.74) μg/L, (2 870.56 ± 740.94) μg/L and (2 886.67 ± 795.34)μg/L, significantly lower than that (4 975.00±1 245.85)μg/L of before splenectomy (P<0.05). Conclusions The serum ferritin level after splenectomy significantly decreases compared with that of before splenectomy, but still remarkably higher than that of normal controls. Monitoring of serum ferritin level and iron-chelating therapy are needed.%目的:探讨重度β-地中海贫血患儿脾脏切除术前后铁负荷状况的变化。方法回顾性分析2003年1月至2012年12月18例重度β-地中海贫血患儿行脾切除术前、后的年输血量及血清铁蛋白水平。结果重度β-地中海贫血患儿脾切除术后第1年和第2年的平均年输血量为(101.94±30.73)ml/kg和(96.50±34.00)ml/kg,均分别低于脾切除术前2年(241.89±73.66)ml/kg和前1年(289.22±102.30)ml/kg的年输血量,差异均有统计学意义(P<0.05)。脾切除术后6、12、18和24个月患儿的血清铁蛋白(SF)水平分别为(2410.00±731.77)μg/L、(2742.78±813.74)μg/L、(2870.56±740.94)μg/L和(2886.67±795.34)μg/L,均低于脾切除术前SF水平[(4975.00±1245.85)

  6. Research Progress of Impact of Pretransplant Iron Overload on Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Hematologic Neoplasms%移植前铁过载对血液肿瘤患者异基因造血干细胞移植预后影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    张潇予; 黄勇

    2014-01-01

    In recent years,a large number of documents have reported that pretransplant iron overload could increase the non-relapsed-related mortality and reduce the overall survival (OS) rate after allogeneic hematopoietic stem cell transplantation (allo-HSCT),especially increased the risk of infection and organ damage and may lead to acute or chronic graft-versus-host disease (GVHD).The main mechanism is related to excessive iron deposition in tissues and activation of oxygen free radicals which could induce apoptosis,tissue disorders and organ dysfunction.Whether pretransplant iron overload can be used to assess the risk factors of allo-HSCT prognosis and whether allo-HSCT patients can benefit from iron chelation therapy still need more researches to prove.%近年来大量文献证明,移植前铁过载可增加异基因造血干细胞移植(allo-HSCT)后患者的非复发相关死亡率,降低移植后总生存(OS)率,尤其增加感染及器官损伤的风险,可能导致急性及慢性移植物抗宿主病(GVHD)的发生.其主要机制涉及过多铁在组织中的沉积,活化氧自由基,进而诱导细胞凋亡及组织和器官功能障碍.移植前铁过载是否可作为评估allo-HSCT预后的危险因素,祛铁治疗是否可使allo-HSCT患者获益,目前仍需进一步研究证实.

  7. High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats.

    Science.gov (United States)

    Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R; Collins, James F

    2016-01-01

    Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

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

    OpenAIRE

    Theil, Elizabeth C.

    2010-01-01

    Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley’s Anemia and other iron overload conditions, a...

  9. 51例重型β珠蛋白生成障碍性贫血患儿长期输血去铁治疗与铁过载的关系研究%Relationship of long-term blood transfusion, iron chelation therapy with iron overload in 51 children with beta-thalassaemia major

    Institute of Scientific and Technical Information of China (English)

    陈光福; 陈娟娟; 高红英; 龙琦; 富国华

    2012-01-01

    Objective To explore the relationship of long-term blood transfusion, iron chelation therapy with iron overload in the patients with beta-thalassaemia major. Methods The serum ferritin (SF) , liver function, renal function, myocardial enzyme, ultrasonograph of liver and spleen, blood glucose and urine glucose were detected in the patients with beta-thalassaemia major in "Friends of thalassemia" and "Service team for thalassemia in Shenzhen" with regular long-term blood transfusion and iron chelation therapy in three months. Left ventricular ejection fraction (LVEF) , myocardial, liver, pancreas and pituitary MR imaging T2* were performed on 51 patients of them. The51 patients were divided into 3 groups. 10 cases with sufficient dose DFO and sufficient dose DFP iron chelation treatment group (sufficient dose joint group) ; 31 cases with insufficient DFO and DFP iron chelation treatment group (insufficient joint group) ; 10 cases with sufficient dose DFX iron chelation treatment group (DFX group). Results There was no difference in myocardial T2*, pituitary T2*, LVEF in every group. (P > 0.05). Liver T2* in sufficient dose joint group was higher than that in insufficient joint group (P 0.05), and there was moderate negative correlation with liver T2*(r = 0.558,P < 0.01). Conclusion The sufficient dose DFO with DFP treatment, and the DFX treatment can effectively reduce SF, compared with that of insufficient DFO with DFP treatment. All iron chelation therapy can alleviate myocardial iron overload.%目的 探讨重型β珠蛋白生成障碍性贫血(beta-thalassaemia,简称β -TM)患儿长期输血、去铁治疗与铁过载的关系.方法 深圳市第二人民医院2001年成立“地贫之友”与“地贫服务队”,对β-TM患儿进行规范性的长期输血和去铁治疗.每3个月监测血清铁蛋白浓度(SF)、肝肾功能、心肌酶谱、心功能、心脏和肝脾B超、血糖和尿糖.2001年2月至2010年6月对其中51例患儿进

  10. Isolation of Related Genes of Cardiac Hypertrophy in Pressure overloaded Rat Models with Subtractive Hybridization%压力负荷型心肌肥厚大鼠心肌组织相关基因的分离

    Institute of Scientific and Technical Information of China (English)

    田靫; 潘德思; 陈兰英

    2000-01-01

    Cardiac hypertrophy is intensively related with the morbidity of heart failure,atherosclerosis and stroke. The rat models of left ventricular hypertrophy caused by abdominal aorta constriction and the method of subtractive hybridization to isolate genes expressing differently were used during cardiac hypertrophy. 24 cDNA segments were isolated and identified by colony and dot hybridization. Sequence homogenous comparison showed that some of them were very similar to known genes or segments, others were limitedly homogenous and the rest were not found to be significantly homogenous.

  11. Quantification of Myocardial Extracellular Volume Fraction with Cardiac MR Imaging in Thalassemia Major.

    Science.gov (United States)

    Hanneman, Kate; Nguyen, Elsie T; Thavendiranathan, Paaladinesh; Ward, Richard; Greiser, Andreas; Jolly, Marie-Pierre; Butany, Jagdish; Yang, Issac Y; Sussman, Marshall S; Wintersperger, Bernd J

    2016-06-01

    Purpose To quantify myocardial extracellular volume (ECV) by using cardiac magnetic resonance (MR) imaging in thalassemia major and to investigate the relationship between ECV and myocardial iron overload. Materials and Methods With institutional review board approval and informed consent, 30 patients with thalassemia major (mean age ± standard deviation, 34.6 years ± 9.5) and 10 healthy control subjects (mean age, 31.5 years ± 4.4) were prospectively recruited (clinicaltrials.gov identification number NCT02090699). Nineteen patients (63.3%) had prior myocardial iron overload (defined as midseptal T2* tracking was assessed with same-day transthoracic echocardiography. Statistical analysis included use of the two-sample t test, Fisher exact test, and Spearman correlation. Results Unenhanced T1 values were significantly lower in patients with prior myocardial iron overload than in control subjects (850.3 ± 115.1 vs 1006.3 ± 35.4, P Online supplemental material is available for this article. PMID:26653680

  12. Safety of deferasirox as an oral iron chelator in thalassemic children

    OpenAIRE

    Shikha Jaiswal; Rajesh Hishikar; Basant Maheshwari; Onkar Khandwal; Raka Sheohare

    2016-01-01

    Background: Thalassemia major patients require frequent blood transfusion leading to iron overload. Iron overload is characterized by excessive iron deposition and consequent injury and dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their coexisting medical conditions. Current prospective, observatio...

  13. Ineffective erythropoiesis and regulation of iron status in iron loading anaemias.

    Science.gov (United States)

    Camaschella, Clara; Nai, Antonella

    2016-02-01

    The definition 'iron loading anaemias' encompasses a group of inherited and acquired anaemias characterized by ineffective erythropoiesis, low hepcidin levels, excessive iron absorption and secondary iron overload. Non-transfusion-dependent β-thalassaemia is the paradigmatic example of these conditions that include dyserythropoietic and sideroblastic anaemias and some forms of myelodysplasia. Interrupting the vicious cycle between ineffective erythropoiesis and iron overload may be of therapeutic benefit in all these diseases. Induction of iron restriction by means of transferrin infusions, minihepcidins or manipulation of the hepcidin pathway prevents iron overload, redistributes iron from parenchymal cells to macrophage stores and partially controls anaemia in β-thalassaemic mice. Inhibition of ineffective erythropoiesis by activin ligand traps improves anaemia and iron overload in the same models. Targeting iron loading or ineffective erythropoiesis shows promise in preclinical studies; activin ligand traps are in clinical trials with promising results and may be useful in patients with ineffective erythropoiesis. PMID:26491866

  14. Iron toxicity in yeast.

    Science.gov (United States)

    Wiśnicka, R; Krzepiłko, A; Wawryn, J; Biliński, T

    1997-01-01

    It has been found that yeast cells are sensitive to iron overload only when grown on glucose as a carbon source. Effective concentration of ferrous iron is much higher than that found in natural environments. Effects of ferrous iron are strictly oxygen dependent, what suggest that the formation of hydroxyl radicals in the Fenton reaction is a cause of the toxicity. Respiratory deficiency and pretreatment of cells with antimycin A prevent toxic effects in the late exponential phase of growth, whereas uncouplers and 2mM magnesium salts completely protect even the most vulnerable exponential cells. Generally, toxic effects correlate with the ability of cells to take up this metal. The results presented suggest that during ferrous iron overload iron is transported through the unspecific divalent cation uptake system which is known in fungi. The data suggest that recently described high and low affinity systems of iron uptake in yeast are the only source of iron in natural environments. PMID:9516981

  15. 铁过载对脐带血来源的造血干祖细胞及造血支持细胞的作用观察%Effect of iron overload on umbilical cord blood derived hematopoietic stem/progenitor cells and hematopoietic supportive cells

    Institute of Scientific and Technical Information of China (English)

    肖霞; 赵明峰; 卢文艺; 柴笑; 穆娟; 邓琦; 李青; 李玉明

    2013-01-01

    目的 探讨铁过载对脐带血(UCB)来源的造血干祖细胞及造血支持细胞,尤其是间充质干细胞(MSCs)的损伤作用.方法 体外培养脐带血单个核细胞(UCB-MNCs)和脐带血间充质干细胞(UCB-MSCs),向培养液中添加200 μmol/L的枸橼酸铁胺(FAC) 24 h建立铁过载模型.分为MNCs-CTL组、MNCs-FAC组、MSCs-CTL组、MSCs-FAC组,每组设3个复孔,实验重复3次.检测细胞内活性氧物质(ROS)水平变化、细胞增殖、分化、凋亡以及造血支持作用.结果 对UCB-MNCs进行铁过载,MNCs-FAC组造血集落形成单位(CFU-E、CFU-GM、BFU-E、CFU-mix)计数显著低于MNCs-CTL组(P<0.05),MNCs-FAC组造血干细胞(CD+34)、髓系造血细胞(CD+33)、红系造血细胞(GlyA+)比例及计数均显著低于MNCs-CTL组(P均<0.05);MNCs-FAC组的凋亡率高于MNCs-CTL组(P<0.05).MSCs-FAC组的群体倍增时间明显长于MSCs-CTL组,且其凋亡率亦高于MSCs-CTL组(P<0.05).结论 铁过载可抑制造血干祖细胞的增殖、分化,诱导其凋亡,也可抑制MSCs的增殖能力,诱导其凋亡,降低其造血支持能力,且此过程中ROS升高.%Objective To explore the detrimental effect of iron overload on umbilical-cord blood (UCB) derived hematopoietic stem/progenitor cells (HSPCs) and hematopoietic supportive cells,especially mesenchymal stem cells (MSCs).Methods Iron overload model of UCB-MNCs and UCB-MSCs was successfully established by adding 200? mol/L FAC into the culture medium for 12h.Then the reactive oxygen species (ROS) level,cell proliferation,cell differentiation,apoptosis and hematopoietic supportive capability were detected respectively.Results Iron overload was conducted on the UCB-MNCs.The hematopoietic colony forming units (CFU-E,CFU-GM,BFU-E,CFU-mix) counts in the MNCs-FAC group were significantly lower than those of MNCs-CTL group (P < 0.05) ; CD+34,CD3+33,GlyA + cell ratio and counts in the MNCs-FAC group were significantly lower than those in the MNCs-CTL (all P

  16. Pregnancy as a cardiac stress model

    OpenAIRE

    Chung, Eunhee; Leinwand, Leslie A.

    2014-01-01

    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women witho...

  17. Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

    Science.gov (United States)

    Westby, Christian M.; Brown, A. K.; Platts, S. H.

    2012-01-01

    The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the

  18. Iron and Ferritin Levels in Saliva of Patients with Thalassemia and Iron Deficiency Anemia

    OpenAIRE

    Canatan, Duran; Akdeniz, Sevgi Kosaci

    2012-01-01

    Most of the techniques for measuring iron stores such as serum iron concentration, iron binding capacity, serum ferritin level, liver biopsy can be troublesome or invasive for patients with thalassemia. The salivary iron measurement could be of potential advantage being an easy and non invasive approach for diagnosis of iron deficiency and iron overload . The aim of this study was to compare the levels of iron and ferritin in saliva and serum of patients affected by thalassemia or iron defici...

  19. Hepcidin: regulation of the master iron regulator

    OpenAIRE

    2015-01-01

    Iron, an essential nutrient, is required for many diverse biological processes. The absence of a defined pathway to excrete excess iron makes it essential for the body to regulate the amount of iron absorbed; a deficiency could lead to iron deficiency and an excess to iron overload and associated disorders such as anaemia and haemochromatosis respectively. This regulation is mediated by the iron-regulatory hormone hepcidin. Hepcidin binds to the only known iron export protein, ferroportin (FP...

  20. Iron regulation by hepatocytes and free radicals

    OpenAIRE

    Takami, Taro; Sakaida, Isao

    2011-01-01

    Iron is an essential metallic microelement for life. However, iron overload is toxic. The liver serves an important role as a storehouse for iron in the body. About 20–25 mg of iron is required each day for hemoglobin synthesis. To maintain iron homeostasis, transferrin and transferrin receptors are primarily involved in the uptake of iron into hepatocytes, ferritin in its storage, and ferroportin in its export. Moreover, hepcidin controls ferroportin and plays a central role in the iron meta...

  1. ANG II is required for optimal overload-induced skeletal muscle hypertrophy

    Science.gov (United States)

    Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

    2001-01-01

    ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

  2. Transient upregulation of protein kinase C in pressure-overloaded neonatal rat myocardium

    Czech Academy of Sciences Publication Activity Database

    Hamplová, B.; Novák, F.; Kolář, František; Nováková, O.

    2010-01-01

    Roč. 59, č. 1 (2010), s. 25-33. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : protein kinase C * cardiac development * pressure overload Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  3. Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload.

    Science.gov (United States)

    Hu, Ping; Zhang, Dongfang; Swenson, LeAnne; Chakrabarti, Gopa; Abel, E Dale; Litwin, Sheldon E

    2003-09-01

    We developed a minimally invasive method for producing left ventricular (LV) pressure overload in mice. With the use of this technique, we quickly and reproducibly banded the transverse aorta with low surgical morbidity and mortality. Minimally invasive transverse aortic banding (MTAB) acutely and chronically increased LV systolic pressure, increased heart weight-to-body weight ratio, and induced myocardial fibrosis. We used this technique to determine whether reduced insulin signaling in the heart altered the cardiac response to pressure overload. Mice with cardiac myocyte-restricted knockout of the insulin receptor (CIRKO) have smaller hearts than wild-type (WT) controls. Four weeks after MTAB, WT and CIRKO mice had comparably increased LV systolic pressure, increased cardiac mass, and induction of mRNA for beta-myosin heavy chain and atrial natriuretic factor. However, CIRKO hearts were more dilated, had depressed LV systolic function by echocardiography, and had greater interstitial fibrosis than WT mice. Expression of connective tissue growth factor was increased in banded CIRKO hearts compared with WT hearts. Thus lack of insulin signaling in the heart accelerates the transition to a more decompensated state during cardiac pressure overload. The use of the MTAB approach should facilitate the study of the pathophysiology and treatment of pressure-overload hypertrophy. PMID:12738623

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

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Carlo, E-mail: c.liguori@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Pitocco, Francesca, E-mail: f.pitocco@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Di Giampietro, Ilenia, E-mail: i.digiampietro@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Vivo, Aldo Eros de, E-mail: devivoeros@gmail.com [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Schena, Emiliano, E-mail: e.schena@unicampus.it [Unit of Measurements and Biomedical Instrumentation, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Cianciulli, Paolo, E-mail: CIANCIULLI.PAOLO@aslrmc.it [Thalassemia Unit, Ospedale Sant Eugenio, Piazzale dell’Umanesimo 10, 00143 Rome (Italy); Zobel, Bruno Beomonte, E-mail: b.zobel@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy)

    2013-09-15

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

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

    International Nuclear Information System (INIS)

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

  6. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  7. Clinical Analysis of Magnetic Resonance Imaging T2* Tests on Iron Overload in Children With β-Thalassemia Major%重型β-地中海贫血患儿体内铁负荷磁共振成像T2*检测的临床分析

    Institute of Scientific and Technical Information of China (English)

    许吕宏; 方建培; 张亚停; 徐宏贵; 翁文骏; 刘勇; 吴佳凯

    2011-01-01

    Objective To investigate the clinical significance of magnetic resonance imaging T2-star (MRI T2 # ) tests on iron overload in children with β-thalassemia major. Methods Nineteen children with |3-thalassemia major were recruited in this study during January to December 2010. Retrospective analytical study on the history of blood transfusion and chelation therapy were recorded. Sera were obtained from the patients and were tested for serum ferritin. MRI T2* tests on iron overload of liver, heart, pancreas and pituitary in these children were performed in Queen Mary Hospital, Hong Kong. The results were evaluated, and the relationships between different values of iron overload were analyzed. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Informed consent was obtained from the parents of each participating child. Results All the patients received irregular blood transfusion and chelation therapy. The value of serum ferritin ranged from 3114 μg/L to 14 550μg/L. The organs of the patients showed different degrees of iron overload by MRI T2* detection. Levels of serum ferritin were negatively correlated with liver MRI T2* , left ventricular ejection fraction, and pancreas MRI T2* O= - 0.569, P = 0. Oil ;r= -0. 633, P = 0. 004 ;r=- 0.592, P = 0. 008). In addition, there were positive correlation between heart MRI T2* and pancreas MRI T2* 0 = 0. 696, P = 0. 001), between pancreas MRI T2* and pituitary MRI T2* 0=0. 491, P=0. 033) as well. Conclusion MRI T2* tests show clinical significance for evaluating iron overload in children with β-thalassemia major.%目的 探讨磁共振成像T2*(MRI T2*)技术检测β-地中海贫血患儿体内铁负荷的应用价值.方法 2010年1月至12月本院儿科共收治19例重型β-地中海贫血患儿,采用回顾性分析方法 记录患儿输血及去铁治疗情况.分离患儿血清,检测血清铁蛋白含量.入组患儿

  8. The relationship between heart and liver iron in thalassemia: a quantitative analysis using MRI

    International Nuclear Information System (INIS)

    Objective: To quantify the heart and liver iron overload in thalassemia patients and discuss the relationship of iron deposition between them, and to evaluate the accuracy of using hepatic iron concentration > 15 mg/g dry tissue as an index to predict heart iron deposition as used in clinical practice. Methods: One hundred and three transfusion-dependent patients with thalassemia, who were older than 5 years, underwent MRI heart and liver measurement to obtain T2* values. The Spearman rank correlation was employed to analyze the relationship between cardiac T2* and liver T2* values. By using liver T2* =0.96 ms as standard setting, patients were divided into two groups, and the differences of cardiac T2* values between the two groups were compared by Wilcoxon rank sum test. Then by using cardiac T2* =10, 20 ms as standard setting, patients were divided into 3 groups, and the differences of liver T2* values among the 3 groups were compared by Wilcoxon rank sum test. The ROC curves were drawn to predict the possibility of using hepatic iron concentration > 15 mg/g dry tissue as an index of cardiac iron deposition. Results: The cardiac and liver T2* values of the 103 thalassemia patients showed low correlation (r=0.453, P=0.000). With the liver T2* value reduced, the cardiac T2* value did not decline proportionally. The cardiac T2* value range and median of 25 patients' group whose liver T2* < 0.96 ms were 4.70 to 41.70 ms and 12.10 ms, respectively. The cardiac T2* value range and the median of 78 patients' group whose liver T2* > 0.96 ms were 4.80 to 51.10 ms and 26.10 ms, respectively. There was statistically significant difference between those of the two groups (Z=-3.566, P=0.000). The liver T2* value range and the median of 20 patients' group whose cardiac T2* < 10 ms was 0.68 to 3.83 ms and 1.06 ms, respectively. The liver T2* value range and the median of 58 patients' group whose cardiac T2* ≥20 ms were 0.74 to 14.80 ms and 1.76 ms

  9. The Role of Hepcidin in Iron Metabolism

    OpenAIRE

    Nemeth, Elizabeta; Ganz, Tomas

    2009-01-01

    Hepcidin is the central regulator of systemic iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemias, and hepatitis C. Hepcidin excess is associated with anemia of inflammation, chronic kidney disease and iron-refractory iron deficiency anemia. Diagnostic and therapeutic applications of this new knowledge are beginning to emerge. Dr. Ernest Beutler play...

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

    OpenAIRE

    Boturão-Neto E.; Marcopito L.F.; Zago M.A.

    2002-01-01

    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 i...

  11. 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

  12. Multi-center transferability of a breath-hold T2 technique for myocardial iron assessment

    Directory of Open Access Journals (Sweden)

    Chan Godfrey CF

    2008-02-01

    Full Text Available Abstract Background Cardiac iron overload is the leading cause of death in thalassemia major and is usually assessed using myocardial T2* measurements. Recently a cardiovascular magnetic resonance (CMR breath-hold T2 sequence has been developed as a possible alternative. This cardiac T2 technique has good interstudy reproducibility, but its transferability to different centres has not yet been investigated. Methods and Results The breath-hold black blood spin echo T2 sequence was installed and validated on 1.5T Siemens MR scanners at 4 different centres across the world. Using this sequence, 5–10 thalassemia patients from each centre were scanned twice locally within a week for local interstudy reproducibility (n = 34 and all were rescanned within one month at the standardization centre in London (intersite reproducibility. The local interstudy reproducibility (coefficient of variance and mean difference were 4.4% and -0.06 ms. The intersite reproducibility and mean difference between scanners were 5.2% and -0.07 ms. Conclusion The breath-hold myocardial T2 technique is transferable between Siemens scanners with good intersite and local interstudy reproducibility. This technique may have value in the diagnosis and management of patients with iron overload conditions such as thalassemia.

  13. Frequency of fluid overload and usefulness of bioimpedance in patients requiring intensive care for sepsis syndromes.

    Science.gov (United States)

    Larsen, Timothy R; Singh, Gurbir; Velocci, Victor; Nasser, Mohamed; McCullough, Peter A

    2016-01-01

    Guideline-directed therapy for sepsis calls for early fluid resuscitation. Often patients receive large volumes of intravenous fluids. Bioimpedance vector analysis (BIVA) is a noninvasive technique useful for measuring total body water. In this prospective observational study, we enrolled 18 patients admitted to the intensive care unit for the treatment of sepsis syndromes. Laboratory data, clinical parameters, and BIVA were recorded daily. All but one patient experienced volume overload during the course of treatment. Two patients had >20 L of excess volume. Volume overload is clinically represented by tissue edema. Edema is not a benign condition, as it impairs tissue oxygenation, obstructs capillary blood flow, disrupts metabolite clearance, and alters cell-to-cell interactions. Specifically, volume overload has been shown to impair pulmonary, cardiac, and renal function. A positive fluid balance is a predictor of hospital mortality. As septic patients recover, volume excess should be aggressively treated with the use of targeted diuretics and renal replacement therapies if necessary. PMID:26722156

  14. Echocardiographic features of right ventricular volume overload

    Directory of Open Access Journals (Sweden)

    Shah Lilam

    1979-01-01

    Full Text Available Interventricular septal motion is studied in sixty tow cases clas-sified into 3 groups; Gr. 1-right ventricular volume overload (RVVO; Gr. II-combined right ventricular volume overload and left ventricular volume overload (RVVO + LVVO; Gr. III-com-bined right ventricular volume overload and right ventricular pres-sure overload (RVVO + RVPO. A linear relationship was obtained between the right ventricu-lar dimension index (RVDI obtained echocardiographically and the magnitude of the left to right shunt at the atrial level (Qn/Qs. Two rare instances of false negatives in a hemodynamically in-significant left to right shunt and in a large ASD are reported. Modification of abnormal septal motion in Gr. II and Gr. III is studied. Lesion specific features of certain anomalies i.e. Ebstein′s ano-maly, total anomalous pulmonary venous return (TAPVR and en-docardial cushion defects (ECD are discussed.

  15. 2型糖尿病患者铁负荷与非酒精性脂肪性肝病的相关性研究%Association of iron overload with non-alcoholic fatty liver disease in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    张林杉; 卞华; 颜红梅; 夏明锋; 常薪霞; 高键; 高鑫

    2014-01-01

    目的 分析2型糖尿病患者铁负荷水平与肝脏脂肪含量(liver fat content,LFC)、肝酶以及肝纤维化的相关性,探讨铁负荷与2型糖尿病肝病状态以及肝病结局的关系.方法 采集530例住院2型糖尿病患者和18例肝穿刺的糖代谢异常患者的病史资料、生化指标、肝脏超声和质子磁共振波谱(1 H-MRS)结果,测定血清铁蛋白(serum ferritin,SF)水平.结果 2型糖尿病合并非酒精性脂肪性肝病(NAFLD)患者的SF水平较单纯2型糖尿病患者显著升高[(328.7±252.2对239.9±171.8)μg/L,P<0.01],SF是NAFLD的独立危险因素(P<0.05);多元线性回归分析显示,校正性别、年龄、糖尿病病程后,SF与LFC线性正相关.伴有肝酶升高的NAFLD患者SF显著高于单纯性NAFLD患者[(429.9±287.4对293.4±233.3) μg/L,P<0.01],SF是NAFLD患者肝酶升高的独立危险因素(P<0.05).进展性纤维化患者的SF较无进展性纤维化的患者显著下降[(246.8±191.2对382.5±253.7)μg/L,P<0.01].肝穿刺患者中,非酒精性脂肪性肝炎(NASH)患者的SF稍高于单纯性脂肪肝,但未达统计学意义;NASH患者是否伴有进展性纤维化其SF差异无统计学意义.结论 2型糖尿病患者体内铁负荷水平增高可能是发生NAFLD及其肝酶升高的独立危险因素,进展性纤维化患者的铁负荷水平显著下降.%Objective To analyze the association of fat content,enzymes,and fibrosis in liver with iron overload in patients with type 2 diabetes,and to explore the relationship between iron overload and severity of nonalcoholic fatty liver disease (NAFLD) in these patients.Methods Five hundred and thirty hospitalized patients with type 2 diabetes and 18 patients with abnormal glucose metabolism undergoing liver biopsy were recruited.History data,results of laboratory tests,liver ultrasound,hepatic 1 H-MRS were collected and serum ferritin level was determined.Results The serum ferritin level was significantly higher in patients with

  16. 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; Nick, Hanspeter; Wood, John C

    2012-01-01

    Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated that ...

  17. PPAR-γ expression in animals subjected to volume overload and chronic Urotensin II administration

    OpenAIRE

    Harris, Gregory S.; Lust, Robert M; DeAntonio, Jonathan H.; Katwa, Laxmansa C

    2008-01-01

    Activation of PPAR-γ through the administration of glitazones has shown promise in preserving function following cardiac injury, although recent evidence has suggested their use may be contraindicated in the case of severe heart failure. This study tested the hypothesis that PPAR-γ expression increases in a time dependent manner in response to chronic volume overload (VO) induced heart failure. Additionally, we attempted to determine what effect 4 week administration of Urotensin II (UTII) ma...

  18. Perceived tiredness and heart rate variability in relation to overload during a field hockey World Cup.

    Science.gov (United States)

    Parrado, Eva; Cervantes, Julio; Pintanel, Monica; Rodas, Gil; Capdevila, Lluís

    2010-06-01

    The aim of the study was to examine the utility of perceived tiredness to predict cardiac autonomic response to overload among field hockey players during the 2006 World Cup. The French Society for Sports Medicine (SFMS) questionnaire was administered at the start of the Cup to evaluate perception of tiredness. Autonomic function was assessed nine days later at the semifinal match by time and frequency domain analysis of heart rate variability. An anxiety questionnaire was administered so that the effect of precompetitive anxiety on heart rate variability could be controlled. Results showed a negative correlation between perceived tiredness scores and time domain indexes, and a positive correlation of perceived tiredness scores and the high frequency component ratio (LF/HF ratio) of heart rate variability. Anxiety did not influence the precompetitive cardiac response despite somatic anxiety's correlation with sympathetic response (LF/HF ratio) and tiredness scores. Perceived tiredness predicted the autonomic cardiac response to competitive overload. Thus, the perceived tiredness assessment would be a good early marker of fatigue and overload states during competition. PMID:20681325

  19. Overload Control for the Wireless Intelligent Network

    Directory of Open Access Journals (Sweden)

    Zuojie Deng

    2014-02-01

    Full Text Available Wireless intelligent network (WIN is a network in the mobile environment that supports the use of intelligent network capabilities which is mainly made up of a service control point (SCP and some mobile switching centers (MSCs. When there are too more incoming services to SCP and MSCs in the WIN simultaneously than they can handle will cause the SCP or MSCs overload and degrades the performance of the WIN. To resolve this problem, we introduce a queue model, design an overload control model and put forward a two-level overload control algorithm for the WIN. The results of our analysis and experiments show that our overload control algorithm is effective

  20. The membrane proteins of the overloaded and senescent heart.

    Science.gov (United States)

    Chevalier, B; Charlemagne, D; Callens-el Amrani, F; Carre, F; Moalic, J M; Delcayre, C; Mansier, P; Swynghedauw, B

    1992-01-01

    Cardiac hypertrophy which occurs during chronic mechanical overload is one of the numerous examples of biological adaptation to environmental requirements. As such, it is obtained at random by trial and error, and adaptation represents the sum of various modifications in gene expression, including the shift in isoform of myosin or in iso Na+, K+ ATPase, the decrease in beta-adrenergic and muscarinic receptors, ryanodine channels or SR Ca2+ ATPase densities and the unchanged density in Ca2+ current. Some of these changes are beneficial at the cellular level, but are finally detrimental for the organism as a whole, as is the slowing of Vmax. It was suggested that the calcium homeostasis of the hypertrophied cardiocyte was fragile and that this modified cell was less able to buffer the changes in the intracellular calcium, thus providing a biological basis for the arrhythmogenicity of the hypertrophied heart. These various modifications may provide a new key for future pharmaceutical research. PMID:1323260

  1. Mitochondria in cardiac hypertrophy and heart failure

    OpenAIRE

    Rosca, Mariana G.; Tandler, Bernard; Hoppel, Charles L.

    2012-01-01

    Heart failure (HF) frequently is the unfavorable outcome of pathological heart hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in response to exercise and leads to full adaptation of contractility to the increased wall stress, pathological hypertrophy occurs in response to volume or pressure overload, ultimately leading to contractile dysfunction and HF. Because cardiac hypertrophy impairs the relationship between ATP demand and production, mitochondrial bioenerget...

  2. Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

    International Nuclear Information System (INIS)

    Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection

  3. Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Penno, E.; Johnsson, C.; Johansson, L.; Ahlstroem, H. [Uppsala Univ. Hospital (Sweden). Depts. of Diagnostic Radiology and of Transplantation Surgery

    2006-04-15

    Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection.

  4. Correlation between Heart and Liver Iron Levels Measured by MRI T2* and Serum Ferritin in Patients with β-thalassemia Major

    Directory of Open Access Journals (Sweden)

    Razieh Taghizadeh Sarvestani

    2016-03-01

    Full Text Available Background Transfusion-induced iron overload leads to many complications in patients with β-thalassemia major. This study aimed to compare the level of iron stored in the liver and heart measured by MRI T2 * with ferritin levels in these patients. Materials and Methods This study was done on 52 patients with β-thalassemia major aged 7 to 29 years. Serum ferritin level was checked and heart and liver MRI T2* operation was performed, then the liver and heart iron level measured by MRI T2 * was compared with serum ferritin levels. Results 150-180 cc/kg packed cells were received on average. The mean ± SD serum ferritin level was 2644.8±1988.3 ng/mL. The mean ± SD relaxation times in liver and heart MRI T2* were 4.39±5.8 and 26.59±10.62 millisecond, respectively. A negative significant correlation was found between serum ferritin levels and liver MRI T2* (P0.05. Conclusion Since there was no correlation between serum ferritin levels and cardiac iron levels, accurate assessment of cardiac iron load using MRI T2* is necessary in patients with β-thalassemia major. Serum ferritin level is reliable for assessing liver iron levels.

  5. Intestinal Iron Homeostasis and Colon Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yatrik M. Shah

    2013-06-01

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

  6. Iron Chelation Therapy in Myelodysplastic Syndromes

    OpenAIRE

    Giuseppe Saglio; Daniela Cilloni; Emanuela Messa

    2010-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous disorder of the hematopoietic stem cells, frequently characterized by anemia and transfusion dependency. In low-risk patients, transfusion dependency can be long lasting, leading to iron overload. Iron chelation therapy may be a therapeutic option for these patients, especially since the approval of oral iron chelators, which are easier to use and better accepted by the patients. The usefulness of iron chelation in MDS patients is still unde...

  7. Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle.

    Science.gov (United States)

    Tsika, R W; Herrick, R E; Baldwin, K M

    1987-11-01

    The purpose of this study was to ascertain whether anabolic steroids act synergistically with functional overload in terms of increasing muscle weight and subcellular protein content of normal overloaded and suspended overloaded rodent plantaris muscle. Female rats were randomly assigned to six groups (7 rats/group) for 6 wk: 1) normal control (NC), 2) overload (OV), 3) overload steroid (OV-S), 4) normal suspended (N-SUS), 5) overload suspended (OV-SUS), and 6) overload suspended steroid (OV-SUS-S). Rats receiving anabolic steroid were administered 0.3 mg nandrolone decanoate (Deca-Durabolin) per day. Relative to control values, overload induced 1) sparing of muscle weight of the OV-SUS group as well as larger absolute and normalized (mg muscle/g body wt) muscle weight of the OV group (P less than 0.05), 2) greater protein content (mg/muscle, P less than 0.05), and 3) an increased relative expression of slow myosin in both the OV and OV-SUS groups (P less than 0.05). Although anabolic steroid treatment of overload animals (OV-S) did not alter further the pattern of response of any parameter analyzed for the OV group, it did induce larger absolute and normalized muscle weight (P less than 0.05) as well as a greater protein content (mg/muscle, P less than 0.05) of the OV-SUS-S group compared with control values. However, anabolic steroid treatment did not alter the pattern of isomyosin expression observed in the overload (OV-S vs. OV) or overload suspended (OV-SUS-S vs. OV-SUS) groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3693242

  8. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

  9. Impact of Retransmission Mechanism on SIP Overload: Stability Condition and Overload Control

    Directory of Open Access Journals (Sweden)

    Yang Hong

    2012-01-01

    Full Text Available SIP (Session Initiation Protocol has been widely adopted as a signaling protocol to establish, modify and terminate media sessions between end-users in the Internet. SIP introduces a retransmission mechanism to ensure the reliability of its real-time message delivery. However, retransmission can make server overload worse, leading to server crashes in SIP-based carrier networks (e.g. Skype. In order to study the impact of retransmission mechanism on SIP overload, in this paper, we create a discrete time fluid model to describe the queuing dynamics of an overloaded SIP server. Then we derive a sufficient stability condition that a SIP server can handle the overload effectively under the retransmission mechanism. Fluid model allows us to run fluid-based Matlab simulation directly to evaluate the overload performance. Event-driven OPNET simulation was also conducted to validate our fluid model. Our simulation results demonstrate that: (1 the sufficient stability bound is quite tight. The bound indicates that effective CPU utilization as low as 20% can still lead to an unstable system after a short period of demand burst or a temporary server slowdown. Resource over-provisioning is not a viable solution to the server crash problem; (2 by satisfying the stability condition, the initial queue size introduced by a transient overload can avoid a system crash. Such stability condition can help the operator to determine whether and when to activate overload control mechanism in case of heavy load. A simple overload control solution is also proposed.

  10. Ly6C(low and not Ly6C(high macrophages accumulate first in the heart in a model of murine pressure-overload.

    Directory of Open Access Journals (Sweden)

    Christina Weisheit

    Full Text Available Cardiac tissue remodeling in the course of chronic left ventricular hypertrophy requires phagocytes which degrade cellular debris, initiate and maintain tissue inflammation and reorganization. The dynamics of phagocytes in left ventricular hypertrophy have not been systematically studied. Here, we characterized the temporal accumulation of leukocytes in the cardiac immune response by flow cytometry and fluorescence microscopy at day 3, 6 and 21 following transverse aortic constriction (TAC. Cardiac hypertrophy due to chronic pressure overload causes cardiac immune response and inflammation represented by an increase of immune cells at all three time points among which neutrophils reached their maximum at day 3 and macrophages at day 6. The cardiac macrophage population consisted of both Ly6C(low and Ly6C(high macrophages. Ly6C(low macrophages were more abundant peaking at day 6 in response to pressure overload. During the development of cardiac hypertrophy the expression pattern of adhesion molecules was investigated by qRT-PCR and flow cytometry. CD11b, CX3CR1 and ICAM-1 determined by qRT-PCR in whole cardiac tissue were up-regulated in response to pressure overload at day 3 and 6. CD11b and CX3CR1 were significantly increased by TAC on the surface of Ly6C(low but not on Ly6C(high macrophages. Furthermore, ICAM-1 was up-regulated on cardiac endothelial cells. In fluorescence microscopy Ly6C(low macrophages could be observed attached to the intra- and extra-vascular vessel-wall. Taken together, TAC induced the expression of adhesion molecules, which may explain the accumulation of Ly6C(low macrophages in the cardiac tissue, where these cells might contribute to cardiac inflammation and remodeling in response to pressure overload.

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-15

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

  13. APJ ACTS AS A DUAL RECEPTOR IN CARDIAC HYPERTROPHY

    OpenAIRE

    Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Metzler, Scott; Wei, Ke; Wang, Jianming; Woods, Chris E.; Purcell, Nicole H.; Catalucci, Daniele; Akasaka, Takashi; Bueno, Orlando F.; Vlasuk, George P.; Kaliman, Perla; Bodmer, Rolf; Smith, Layton H.

    2012-01-01

    Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues 1 . Here we report that genetic loss of APJ confers resistance to chronic pressure overload by dramatically reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to s...

  14. Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD(+) protects the heart against pressure overload.

    Science.gov (United States)

    Yano, Masamichi; Akazawa, Hiroshi; Oka, Toru; Yabumoto, Chizuru; Kudo-Sakamoto, Yoko; Kamo, Takehiro; Shimizu, Yu; Yagi, Hiroki; Naito, Atsuhiko T; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Komuro, Issei

    2015-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD(+) by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD(+) concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD(+), were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD(+) levels and NAD(+)-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD(+) against heart failure. PMID:26522369

  15. Iron Supplementation and Altitude: Decision Making Using a Regression Tree

    OpenAIRE

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

    2016-01-01

    Altitude exposure increases the body’s need for iron (Gassmann and Muckenthaler, 2015), primarily to support accelerated erythropoiesis, yet clear supplementation guidelines do not exist. Athletes are typically recommended to ingest a daily oral iron supplement to facilitate altitude adaptations, and to help maintain iron balance. However, there is some debate as to whether athletes with otherwise healthy iron stores should be supplemented, due in part to concerns of iron overload. Excess iro...

  16. Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in long-term iron loadingβ-thalassemic mice

    Institute of Scientific and Technical Information of China (English)

    Kanokwan Kulprachakarn; Nittaya Chansiw; Kanjana Pangjit; Chada Phisalaphong; Suthat Fucharoen; Robert C Hider; Sineenart Santitherakul; Somdet Srichairatanakool

    2014-01-01

    Objective:To evaluate the iron-chelating properties and free-radical scavenging activities of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) treatment in chronic iron-loadedβ-thalassemic (BKO) mice. Methods:The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1 [50 mg/(kg.day)] for 6 months. Blood levels of non-transferrin bound iron, labile plasma iron, ferritin (Ft) and malondialdehyde were determined. Results:The BKO mice were fed with an iron diet for 8 months which resulted in iron overload. Interestingly, the mice showed a decrease in the non-transferrin bound iron, labile plasma iron and malondialdehyde levels, but not the Ft levels after continuous CM1 treatment. Conclusions:CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overloadβ-thalassemic mice.

  17. 丹参多酚对铁过载引起的脐血造血细胞氧化应激损伤的抑制作用%Inhibitory effect of salvianolate on iron overload-derived oxidative stress injury of hematopoietic cells of umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    穆娟; 赵明峰; 李玉明; 张宇辰; 曹小立; 李青

    2015-01-01

    目的:探讨丹参多酚对铁过载引起的脐血造血细胞氧化应激损伤的保护作用。方法分离脐血单个核细胞,分为对照组、模型组、丹参多酚低、中、高剂量组。模型组及丹参多酚低、中、高剂量组以400μmol/L浓度的枸橼酸铁胺( FAC)建立铁过载细胞模型,丹参多酚低、中、高剂量组于培养第3天分别加入18、50、160μg/mL丹参多酚培养24 h;对照组不加FAC及丹参多酚。采用流式细胞术检测各组细胞的活性氧( ROS)水平、细胞凋亡率,计数各组细胞集落形成数量。结果模型组ROS水平高于对照组及丹参多酚各剂量组( P均<0.05)。模型组细胞凋亡率高于对照组及丹参多酚高剂量组(P<0.05)。模型组红系祖细胞集落形成单位(CFU-E)、粒—单核系祖细胞集落形成单位( CFU-GM)、爆式红系祖细胞集落形成单位( BFU-E)和混合祖细胞集落形成单位( CFU-mix)数量均低于对照组及丹参多酚高剂量组(P均<0.05)。结论丹参多酚可减轻氧化应激引起的细胞凋亡及其对造血细胞增殖、分化功能的抑制作用。%Objective To investigate the protective effect of salvianolate on the iron overload-derived oxidative stress injury of mononuclear cells of umbilical cord blood (UC-MNCs).Methods The UC-MNCs were divided into the control group, FAC group, low-dose salvianolate group, medium-dose salvianolate group, and high-dose salvianolate group.The control group received normal culture .The iron overload cell models in the FAC and salvianolate groups were established by adding 400 μmol/L FAC into the culture medium for 24 h on the second day.Then the low-dose, medium-dose and high-dose salvianolate groups were received 18, 50 and 160μg/mL salvianolate for 24 h, respectively on the third day .Then the levels of reactive oxygen species ( ROS) , apoptosis rate and LIP level were detected by flow cytometry

  18. 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.

  19. Cardiac magnetic resonance angiography using blood-pool contrast agents. Comparison of citrate-coated very small superparamagnetic iron oxide particles with gadofosveset trisodium in pigs

    International Nuclear Information System (INIS)

    Purpose: To compare citrate-coated very small superparamagnetic iron oxide particles (VSOP) with gadofosveset trisodium as blood pool contrast agents for cardiac magnetic resonance angiography (CMRA) in pigs. Materials and Methods: Animal experiments were approved by the responsible authority. 10 CMRA-like examinations were performed at 1.5 T after administration of VSOP (0.06 mmol Fe/kg; 5 examinations) and gadofosveset trisodium (0.03 mmol Gd/kg; 5 examinations). The CMRA protocol included ECG-gated inversion-recovery-prepared T1-weighted gradient echo imaging (IR-GRE; one slice) and ECG-gated inversion recovery prepared steady state free precession imaging (IR SSFP; one slice) before and 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, and 60 min after injection. At each time point, three different inversion times (TI; 200 msec, 300 msec, and 400 msec) were applied. Contrast-to-noise ratios (CNR) between blood and myocardium were calculated and compared using mixed linear models. Results: No significant differences of CNR were found between IR-GRE and IR SSFP. At 3 and 5 min after contrast agent administration, VSOP showed a significantly higher CNR than gadofosveset trisodium when TI of 200 msec and 300 msec were applied (TI of 200 msec at 3 min: 8.2 ± 0.7 vs. 5.4 ± 0.7; TI of 200 msec at 5 min: 7.9 ± 0.7 vs. 3.5 ± 0.8; TI of 300 msec at 3 min: 11.7 ± 0.7 vs. 8.8 ± 0.8; TI of 300 msec at 5 min: 11.4 ± 0.7 vs. 8.0 ± 0.8; p < 0.05). Moreover, significant differences in favor of VSOP were found for all time points from 10 to 40 min irrespective of TI (p < 0.05). Conclusion: VSOP has superior blood-pool properties compared to gadofosveset trisodium resulting in prolonged improvement of CNR on CMRA. (orig.)

  20. Cardiac magnetic resonance angiography using blood-pool contrast agents. Comparison of citrate-coated very small superparamagnetic iron oxide particles with gadofosveset trisodium in pigs

    Energy Technology Data Exchange (ETDEWEB)

    Schnorr, J.; Taupitz, M.; Schellenberger, E.A.; Warmuth, C.; Wagner, S.; Kaufels, N.; Wagner, M. [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie; Fahlenkamp, U.L. [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie; Universitaetsklinikum Bonn (Germany). Radiologische Klinik

    2012-02-15

    Purpose: To compare citrate-coated very small superparamagnetic iron oxide particles (VSOP) with gadofosveset trisodium as blood pool contrast agents for cardiac magnetic resonance angiography (CMRA) in pigs. Materials and Methods: Animal experiments were approved by the responsible authority. 10 CMRA-like examinations were performed at 1.5 T after administration of VSOP (0.06 mmol Fe/kg; 5 examinations) and gadofosveset trisodium (0.03 mmol Gd/kg; 5 examinations). The CMRA protocol included ECG-gated inversion-recovery-prepared T1-weighted gradient echo imaging (IR-GRE; one slice) and ECG-gated inversion recovery prepared steady state free precession imaging (IR SSFP; one slice) before and 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, and 60 min after injection. At each time point, three different inversion times (TI; 200 msec, 300 msec, and 400 msec) were applied. Contrast-to-noise ratios (CNR) between blood and myocardium were calculated and compared using mixed linear models. Results: No significant differences of CNR were found between IR-GRE and IR SSFP. At 3 and 5 min after contrast agent administration, VSOP showed a significantly higher CNR than gadofosveset trisodium when TI of 200 msec and 300 msec were applied (TI of 200 msec at 3 min: 8.2 {+-} 0.7 vs. 5.4 {+-} 0.7; TI of 200 msec at 5 min: 7.9 {+-} 0.7 vs. 3.5 {+-} 0.8; TI of 300 msec at 3 min: 11.7 {+-} 0.7 vs. 8.8 {+-} 0.8; TI of 300 msec at 5 min: 11.4 {+-} 0.7 vs. 8.0 {+-} 0.8; p < 0.05). Moreover, significant differences in favor of VSOP were found for all time points from 10 to 40 min irrespective of TI (p < 0.05). Conclusion: VSOP has superior blood-pool properties compared to gadofosveset trisodium resulting in prolonged improvement of CNR on CMRA. (orig.)

  1. Iron in haemoglobinopathies and rare anaemias

    Directory of Open Access Journals (Sweden)

    John Porter

    2014-12-01

    Full Text Available Iron overload in haemoglobinopathies and rare anaemias may develop from increased iron absorption secondary to hepcidin suppression, and/or from repeated blood transfusions. While the accumulation of body iron load from blood transfusion is inevitable and predictable from the variable rates of transfusion in the different conditions, there are some important differences in the distribution of iron overload and its consequences between these. Transfusion-dependent thalassaemia (TDT is the best described condition in which transfusional overload occurs. Initially iron loads into macrophages, subsquently hepatocytes, and then the endocrine system including the anterior pituiatry and finally the myocardium. The propensity to extrahepatic iron spread increases with rapid transfusion and with inadequate chelation therapy but there is considerable interpatient and interpopulation variability in this tendency. The conduits though which iron is delivered to tissues is through non transferrin iron species (NTBI which are taken into liver, endocrine tissues and myocardium through L-type calcium channells and possibly through other channells. Recent work by the MSCIO group1 suggests that levels of NTBI are determined by three mechanisms: i increasing with iron overload; ii increasing with ineffective erythropoieis; iii and decreasing when level of transferrin iron utilisation is high. In TDT all three mechanisms increase NTBI levels because transferrin iron utilisation is suppressed by hypertransfusion. It is hypothesized that the transfusion regimen and target mean Hb may have a key impact on NTBI levels because high transfusion regimes may suppress the ‘sink’ effect of the erythron though decreased clearance of transferrin iron. In sickle cell disease (SCD without blood transfusion the anaemia results mainly from haemolysis rather than from ineffective erythropoiesis.2 Thus there is a tendency to iron depletion because of urinary iron loss from

  2. The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling*

    OpenAIRE

    Skurk, Carsten; Izumiya, Yasuhiro; Maatz, Henrike; Razeghi, Peter; Shiojima, Ichiro; Sandri, Marco; Sato, Kaori; Zeng, Ling; Schiekofer, Stephan; Pimentel, David; Lecker, Stewart; Taegtmeyer, Heinrich; Goldberg, Alfred L.; Walsh, Kenneth

    2005-01-01

    Although signaling mechanisms inducing cardiac hypertrophy have been extensively studied, little is known about the mechanisms that reverse cardiac hypertrophy. Here, we describe the existence of a similar Akt/forkhead signaling axis in cardiac myocytes in vitro and in vivo, which is regulated by insulin, insulin-like growth factor (IGF), stretch, pressure overload, and angiotensin II stimulation. FOXO3a gene transfer prevented both IGF and stretch-induced hypertrophy in rat neonatal cardiac ...

  3. Session Initiation Protocol (SIP) Server Overload Control: Design and Evaluation

    OpenAIRE

    Shen, Charles; Schulzrinne, Henning; Nahum, Erich

    2008-01-01

    A Session Initiation Protocol (SIP) server may be overloaded by emergency-induced call volume, ``American Idol'' style flash crowd effects or denial of service attacks. The SIP server overload problem is interesting especially because the costs of serving or rejecting a SIP session can be similar. For this reason, the built-in SIP overload control mechanism based on generating rejection messages cannot prevent the server from entering congestion collapse under heavy load. The SIP overload pro...

  4. 30 CFR 56.12001 - Circuit overload protection.

    Science.gov (United States)

    2010-07-01

    ... § 56.12001 Circuit overload protection. Circuits shall be protected against excessive overload by fuses or circuit breakers of the correct type and capacity. ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 56.12001...

  5. 30 CFR 57.12001 - Circuit overload protection.

    Science.gov (United States)

    2010-07-01

    ... Electricity Surface and Underground § 57.12001 Circuit overload protection. Circuits shall be protected against excessive overloads by fuses or circuit breakers of the correct type and capacity. ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 57.12001...

  6. 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.

  7. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model

    Directory of Open Access Journals (Sweden)

    Qifeng Zhou

    2015-01-01

    Full Text Available Mutations in the giant sarcomeric protein titin (TTN are a major cause for inherited forms of dilated cardiomyopathy (DCM. We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC in heterozygous (Het Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction (p<0.05, while wild-type (WT TAC mice did not. Het mice also trended toward increased ventricular end diastolic pressure and volume compared to WT littermates. We found an increase in histologically diffuse cardiac fibrosis in Het compared to WT in TAC mice. This study shows that a pattern of DCM can be induced by TAC-mediated pressure overload in a TTN-truncated mouse model. This model enlarges our arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure.

  8. Noninvasive assessment of filling pressure and left atrial pressure overload in severe aortic valve stenosis: relation to ventricular remodeling and clinical outcome after aortic valve replacement

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbæk, Lars; Poulsen, Mikael K;

    2011-01-01

    One of the hemodynamic consequences of aortic valve stenosis is pressure overload leading to left atrial dilatation. Left atrial size is a known risk factor providing prognostic information in several cardiac conditions. It is not known if this is also the case in patients with aortic valve steno...

  9. On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

    Directory of Open Access Journals (Sweden)

    Carpenter JP

    2011-09-01

    Full Text Available Abstract Background Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM patients. Treatment effects with improved left ventricular (LV ejection fraction (EF have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR to the relative risk (RR of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM and 63-70% (lower half of the normal range for TM. Results A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p Conclusion These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

  10. Low-grade haemolysis and assessment of iron status during the steady state in G6PD-deficient subjects.

    Science.gov (United States)

    Ragusa, R; Di Cataldo, A; Gangarossa, S; Lo Nigro, L; Schilirò, G

    1993-01-01

    We evaluated the iron status of 50 Sicilian patients with G6PD deficiency under steady-state conditions and compared our results with those for 50 control patients. We studied haemolysis and iron indices to evaluate the iron balance. These patients could be considered to be at risk of iron overload as a result of increased bone marrow activity. Reticulocytosis and macrocytosis with reduced levels of haptoglobin were found in the G6PD-deficient subjects, both of which are evidence of a moderate haemolysis. Iron status within the normal range, without iron overload or iron deficiency, was found. PMID:8237270

  11. Measurement of Liver Iron Concentration by MRI Is Reproducible

    Directory of Open Access Journals (Sweden)

    José María Alústiza

    2015-01-01

    Full Text Available Purpose. The objectives were (i construction of a phantom to reproduce the behavior of iron overload in the liver by MRI and (ii assessment of the variability of a previously validated method to quantify liver iron concentration between different MRI devices using the phantom and patients. Materials and Methods. A phantom reproducing the liver/muscle ratios of two patients with intermediate and high iron overload. Nine patients with different levels of iron overload were studied in 4 multivendor devices and 8 of them were studied twice in the machine where the model was developed. The phantom was analysed in the same equipment and 14 times in the reference machine. Results. FeCl3 solutions containing 0.3, 0.5, 0.6, and 1.2 mg Fe/mL were chosen to generate the phantom. The average of the intramachine variability for patients was 10% and for the intermachines 8%. For the phantom the intramachine coefficient of variation was always below 0.1 and the average of intermachine variability was 10% for moderate and 5% for high iron overload. Conclusion. The phantom reproduces the behavior of patients with moderate or high iron overload. The proposed method of calculating liver iron concentration is reproducible in several different 1.5 T systems.

  12. 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.

  13. Oligopolistic Competition with Choice-Overloaded Consumers

    OpenAIRE

    Gerasimou, Georgios; Papi, Mauro

    2015-01-01

    A large body of experimental work has suggested the existence of a "choice overload" effect in consumer decision making: Faced with large menus of choice options, decision makers often defer or avoid choice. A suggested reason for the occurrence of this effect is that the agents attempt to avoid the cognitive effort that is associated with choosing from larger menus. Building on this explanation, we propose and analyse a model of duopolistic competition where firms compete in menu design in t...

  14. Dietary fat overload reprograms brown fat mitochondria

    OpenAIRE

    Lettieri Barbato, Daniele; Tatulli, Giuseppe; Vegliante, Rolando; Cannata, Stefano M.; Bernardini, Sergio; Ciriolo, Maria R.; Aquilano, Katia

    2015-01-01

    Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD) at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were stron...

  15. Java Modular Extension for Operator Overloading

    OpenAIRE

    Melentyev, Artem

    2014-01-01

    The paper introduces a modular extension (plugin) for Java language compilers and Integrated Development Environments (IDE) which adds operator overloading feature to Java language while preserving backward compatibility. The extension use the idea of library-based language extensibility similar to SugarJ. But unlike most language extensions, it works directly inside the compiler and does not have any external preprocessors. This gives much faster compilation, better language compatibility an...

  16. Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients

    International Nuclear Information System (INIS)

    Purpose: To assess the correlation between MRI findings of the pancreas with those of the heart and liver in patients with beta thalassemia; to compare the pancreas T2* MRI results with glucose and ferritin levels and labile plasma iron (LPI). Materials and methods: We retrospectively evaluated chronically transfused patients, testing glucose with enzymatic tests, serum ferritin with chemiluminescence, LPI with cellular fluorescence, and T2* MRI to assess iron content in the heart, liver, and pancreas. MRI results were compared with one another and with serum glucose, ferritin, and LPI. Liver iron concentration (LIC) was determined in 11 patients’ liver biopsies by atomic absorption spectrometry. Results: 289 MRI studies were available from 115 patients during the period studied. 9.4% of patients had overt diabetes and an additional 16% of patients had impaired fasting glucose. Both pancreatic and cardiac R2* had predictive power (p 2 = 0.20, p 2 = 0.09, p 2 = 0.14, p 2 = 0.03, p 2 of 0.91. Conclusions: Pancreatic iron overload can be assessed by MRI, but siderosis in other organs did not correlate significantly with pancreatic hemosiderosis.

  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......-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ...... 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. Liver iron content determination by magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Konstantinos; Tziomalos; Vassilios; Perifanis

    2010-01-01

    Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potenti...

  19. New developments and controversies in iron metabolism and iron chelation therapy

    Science.gov (United States)

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients’ therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic

  20. New developments and controversies in iron metabolism and iron chelation therapy.

    Science.gov (United States)

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-03-26

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic

  1. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

    OpenAIRE

    Harris, Brett S.; Zhang, Yuhua; Card, Lauren; Rivera, Lee B.; Brekken, Rolf A.; Bradshaw, Amy D.

    2011-01-01

    Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associa...

  2. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model.

    Science.gov (United States)

    Zhou, Qifeng; Kesteven, Scott; Wu, Jianxin; Aidery, Parwez; Gawaz, Meinrad; Gramlich, Michael; Feneley, Michael P; Harvey, Richard P

    2015-01-01

    Mutations in the giant sarcomeric protein titin (TTN) are a major cause for inherited forms of dilated cardiomyopathy (DCM). We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC) in heterozygous (Het) Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction (p arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure. PMID:26504781

  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. Iron and Iron Metabolism

    OpenAIRE

    Melike Sezgin Evim; Birol Baytan; Adalet Meral Güneş

    2012-01-01

    Iron is an essential element for almost all living organisms except some bacteria. A great number of new articles related to the iron metabolism have been published in recent years explaining new findings. Hepsidine, a peptide hormon, that is recently found, regulates iron methabolism by effecting iron absorbsion from gut, secreting iron from hepatic store and flows iron from macrophages. Hepsidin blockes to effluxe iron from cells by bounding to ferroportin and by inducing ferroportin destru...

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

    Science.gov (United States)

    Porter, John B; de Witte, Theo; Cappellini, M Domenica; Gattermann, Norbert

    2016-03-01

    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 best described in thalassemia major and related inherited anemias, they are increasingly recognized in acquired conditions, such as myelodysplastic syndromes (MDS). Iron overload in MDS not only impacts on certain tissues, but may affect the clonal evolution of MDS through generation of reactive oxygen species. Iron overload may also influence hematopoietic-stem-cell-transplantation outcomes. Novel MRI methods for assessing body iron have impacted significantly on outcome in inherited anemias by allowing monitoring of iron burden and iron chelation therapy. This approach is increasingly being used in MDS and stem-cell-transplant procedures. Knowledge gained from managing transfusional iron overload in inherited anemias may be translated to general oncology, with potential for improved patient outcomes. PMID:26806144

  6. FORMULATION OF ORAL IRON CHELATOR DEFERASIROX IN A NEW STABLE AND SUITABLE DOSAGE FORM WITH OPTIMUM RELEASE PARAMETERS

    OpenAIRE

    Yugandhar KM, Vasanth PM, Suresh K, Ramesh T, Ramesh Malothu*

    2013-01-01

    Regular blood transfusions for patients with chronic anemia inevitably lead to iron overload in the blood. The cumulative effect of iron overload may cause morbidity and mortality if not treated with chelator. Oral iron chelator, Deferasirox used in the treatment of β-thalessemia is designed and developed into a stable solid oral dispersion dosage form to deliver with optimum concentration of the drug at desired site at specific time comparable to the innovator product. The excipients were fo...

  7. Significance of assess the iron reserves of severe renal anemia patients before and after blood transfusion

    Institute of Scientific and Technical Information of China (English)

    Gui-Fen Zhang

    2015-01-01

    Objective:To study the significance of evaluating hemoglobin and iron reserves in the severe renal anemia patient before and after blood transfusion, to guide clinical treatment.Methods:Simple randomly selected 120 patients in phase 5 of chronic renal failure from the department of nephrology, who are regular dialysis with severe renal anemia, according to the situation of iron reserves before blood transfusion, patients will be divided into its reserves of iron deficiency and iron overload group and normal group, and the three groups were divided into 1 U and 2 U group. Comparing the change of different unit quantity of hemoglobin, serum iron, iron, protein and total iron binding force before and after blood transfusion and variation is compared between groups.Results: Three groups of patients with 1U blood transfusion ,Hemoglobin, serum iron and ferritin, total iron binding force, transferrin saturation are higher before a blood transfusion,The differences were statistically significant; before and after blood transfusion hemoglobin, serum iron and ferritin, total iron binding force, transferrin saturation change in 1 U group normal iron reserves compared with Insufficient iron reserves 1 U group has no statistically significant difference, iron overload 1 U group before and after blood transfusion hemoglobin, serum iron and ferritin, total iron binding force, transferrin saturation change significantly greater than Insufficient iron reserves 1 U group and 1U with normal iron reserves group, the differences were statistically significant; Three groups of patients blood transfusion after 2 U, hemoglobin, serum iron and ferritin, total iron binding force, transferrin saturation were higher before a blood transfusion, differences were statistically significant; iron overload 2 U group before and after blood transfusion hemoglobin, serum iron and ferritin, total iron binding force, transferrin saturation change significantly greater than Insufficient iron reserves 2

  8. A Comparative Study of SIP Overload Control Algorithms

    OpenAIRE

    Hong, Yang; Huang, Changcheng; Yan, James

    2012-01-01

    Recent collapses of SIP servers in the carrier networks indicates two potential problems of SIP: (1) the current SIP design does not easily scale up to large network sizes, and (2) the built-in SIP overload control mechanism cannot handle overload conditions effectively. In order to help carriers prevent widespread SIP network failure effectively, this chapter presents a systematic investigation of current state-of-the-art overload control algorithms. To achieve this goal, this chapter first ...

  9. Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    Full Text Available BACKGROUND: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3 is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. METHODS AND RESULTS: PTX3 systemic knockout (PTX3-KO mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG, and the respective wild-type (WT littermate mice were subjected to transverse aortic constriction (TAC or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2 in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. CONCLUSION: The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

  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. Res...

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

    International Nuclear Information System (INIS)

    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 Ca2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca2+ 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 Ca2+ handling proteins demonstrated that aconitine promoted Ca2+ overload through the expression regulation of Ca2+ 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 Ca2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca2+ overload causes arrhythmia in rats.

  12. Haemochromatosis presenting as congestive cardiac failure.

    OpenAIRE

    Porter, J; Cary, N; Schofield, P

    1995-01-01

    A 24 year old man with congestive cardiac failure was found to have grossly increased transferrin saturations, raised serum ferritin, and an iron-laden myocardium on biopsy. Initial treatment with the iron chelator desferrioxamine was replaced by weekly venesection. He was placed on the cardiac transplant list because of severe left ventricular dysfunction but was later removed because his symptoms and function improved. He remains well with few symptoms and is maintained on regular venesecti...

  13. Iron disorders of genetic origin: a changing world.

    Science.gov (United States)

    Brissot, Pierre; Bardou-Jacquet, Edouard; Jouanolle, Anne-Marie; Loréal, Olivier

    2011-12-01

    Iron disorders of genetic origin are mainly composed of iron overload diseases, the most frequent being HFE-related hemochromatosis. Hepcidin deficiency underlies iron overload in HFE-hemochromatosis as well as in several other genetic iron excess disorders, such as hemojuvelin or hepcidin-related hemochromatosis and transferrin receptor 2-related hemochromatosis. Deficiency of ferroportin, the only known cellular protein iron exporter, produces iron overload in the typical form of ferroportin disease. By contrast, genetically enhanced hepcidin production, as observed in matriptase-2 deficiency, generates iron-refractory iron deficiency anemia. Diagnosis of these iron storage disorders is usually established noninvasively through combined biochemical, imaging and genetic approaches. Moreover, improved knowledge of the molecular mechanisms accounting for the variations of iron stores opens the way of novel therapeutic approaches aiming to restore normal iron homeostasis. In this review, we will summarize recent findings about these various genetic entities that have been identified owing to an exemplary interplay between clinicians and basic scientists. PMID:21862411

  14. Regional Cardiac Dysfunction and Dyssynchrony in a Murine Model of Afterload Stress

    OpenAIRE

    Bauer, Michael; Cheng, Susan; Unno, Kazumasa; Lin, Fen-Chiung; Liao, Ronglih

    2013-01-01

    Small animal models of afterload stress have contributed much to our present understanding of the progression from hypertension to heart failure. High-sensitivity methods for phenotyping cardiac function in vivo, particular in the setting of compensated cardiac hypertrophy, may add new information regarding alterations in cardiac performance that can occur even during the earliest stages of exposure to pressure overload. We have developed an echocardiographic analytical method, based on speck...

  15. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

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

  16. State of the Art: Clinical Applications of Cardiac T1 Mapping.

    Science.gov (United States)

    Schelbert, Erik B; Messroghli, Daniel R

    2016-03-01

    While cardiovascular magnetic resonance (MR) has become the noninvasive tool of choice for the assessment of myocardial viability and for the detection of acute myocardial edema, cardiac T1 mapping is believed to further extend the ability of cardiovascular MR to characterize the myocardium. Fundamentally, cardiovascular MR can improve diagnosis of disease that historically has been challenging to establish with other imaging modalities. For example, decreased native T1 values appear highly specific to detect and quantify disease severity related to myocardial iron overload states or glycosphingolipid accumulation in Anderson-Fabry disease, whereas high native T1 values are observed with edema, amyloid, and other conditions. Cardiovascular MR can also improve the assessment of prognosis with parameters that relate to myocardial structure and composition that complement the familiar functional parameters around which contemporary cardiology decision making revolves. In large cohorts, extracellular volume fraction (ECV) has been shown to quantify the full extent of myocardial fibrosis in noninfarcted myocardium. ECV may predict outcomes at least as effectively as left ventricular ejection fraction. This uncommon statistical observation (of potentially being more strongly associated with outcomes than ejection fraction) suggests prime biologic importance for the cardiac interstitium that may rank highly in the hierarchy of vast myocardial changes occurring in cardiac pathophysiology. This article presents current and developing clinical applications of cardiac T1 mapping and reviews the existing evidence on their diagnostic and prognostic value in various clinical conditions. This article also contextualizes these advances and explores how T1 mapping and ECV may affect major "global" issues such as diagnosis of disease, risk stratification, and paradigms of disease, and ultimately how we conceptualize patient vulnerability. PMID:26885733

  17. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  18. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

    Science.gov (United States)

    Zhang, Ji; Qiao, Congzhen; Chang, Lin; Guo, Yanhong; Fan, Yanbo; Villacorta, Luis; Chen, Y Eugene; Zhang, Jifeng

    2016-01-01

    Fatty acid binding protein 4 (FABP4) is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG) mice using α myosin-heavy chain (α-MHC) promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC) procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway. PMID:27294862

  19. Role of alcohol in the regulation of iron metabolism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis,an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.

  20. Session Initiation Protocol (SIP) Server Overload Control: Design and Evaluation

    CERN Document Server

    Shen, Charles; Nahum, Erich

    2008-01-01

    A Session Initiation Protocol (SIP) server may be overloaded by emergency-induced call volume, ``American Idol'' style flash crowd effects or denial of service attacks. The SIP server overload problem is interesting especially because the costs of serving or rejecting a SIP session can be similar. For this reason, the built-in SIP overload control mechanism based on generating rejection messages cannot prevent the server from entering congestion collapse under heavy load. The SIP overload problem calls for a pushback control solution in which the potentially overloaded receiving server may notify its upstream sending servers to have them send only the amount of load within the receiving server's processing capacity. The pushback framework can be achieved by either a rate-based feedback or a window-based feedback. The centerpiece of the feedback mechanism is the algorithm used to generate load regulation information. We propose three new window-based feedback algorithms and evaluate them together with two exis...

  1. Spatio-temporal propagation of cascading overload failures

    CERN Document Server

    Zhao, Jichang; Sanhedrai, Hillel; Cohen, Reuven; Havlin, Shlomo

    2015-01-01

    Different from the direct contact in epidemics spread, overload failures propagate through hidden functional dependencies. Many studies focused on the critical conditions and catastrophic consequences of cascading failures. However, to understand the network vulnerability and mitigate the cascading overload failures, the knowledge of how the failures propagate in time and space is essential but still missing. Here we study the spatio-temporal propagation behavior of cascading overload failures analytically and numerically. The cascading overload failures are found to spread radially from the center of the initial failure with an approximately constant velocity. The propagation velocity decreases with increasing tolerance, and can be well predicted by our theoretical framework with one single correction for all the tolerance values. This propagation velocity is found similar in various model networks and real network structures. Our findings may help to predict and mitigate the dynamics of cascading overload f...

  2. Evaluation of thermal overload in boiler operators.

    Science.gov (United States)

    Braga, Camila Soares; Rodrigues, Valéria Antônia Justino; Campos, Julio César Costa; de Souza, Amaury Paulo; Minette, Luciano José; de Moraes, Angêlo Casali; Sensato, Guilherme Luciano

    2012-01-01

    The Brazilians educational institutions need a large energy demand for the operation of laundries, restaurants and accommodation of students. Much of that energy comes from steam generated in boilers with wood fuel. The laboral activity in boiler may present problems for the operator's health due to exposure to excessive heat, and its operation has a high degree of risk. This paper describes an analysis made the conditions of thermal environment in the operation of a B category boiler, located at a Higher Education Institution, located in the Zona da Mata Mineira The equipments used to collect data were Meter WBGT of the Heat Index; Meter of Wet Bulb Index and Globe Thermometer (WBGT); Politeste Instruments, an anemometer and an Infrared Thermometer. By the application of questionnaires, the second phase consisted of collecting data on environmental factors (temperature natural environment, globe temperature, relative humidity and air velocity). The study concluded that during the period evaluated, the activity had thermal overload. PMID:22316768

  3. 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.

  4. Urinary iron excretion induced by intravenous infusion of deferoxamine in beta-thalassemia homozygous patients.

    Science.gov (United States)

    Boturao-Neto, E; Marcopito, L F; Zago, M A

    2002-11-01

    The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent beta-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 beta-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. PMID:12426631

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

    Directory of Open Access Journals (Sweden)

    JosephineAnneWright

    2014-07-01

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

  6. Bioimpedance can solve problems of fluid overload.

    Science.gov (United States)

    Abbas, Samer R; Zhu, Fansan; Levin, Nathan W

    2015-03-01

    Bioimpedance (BI) techniques for measuring normal hydration status (NHS) can be generally classified as (1) by frequency as single frequency at 50 kHz, BI analysis, and multifrequency BI spectroscopy and (2) by method as whole body (wrist to ankle) measurement and calf BI spectroscopy. The aim of this article was to review current BI methods for clinical practice in patients with end-stage of kidney disease. BI vector analysis using whole-body single-frequency BI at 50 kHz may be useful for population studies to indicate a range of degree of fluid loading and of nutritional status. Whole body multifrequency BI spectroscopy is used to estimate extracellular (ECV), intracellular fluid volume, and total body water in dialysis patients. The whole-body BI model is used in the body composition monitor (BCM). The whole-body BI model is established with ECV, intracellular fluid volume, and body weight based on parameters from regression analysis in healthy subjects to calculate fluid overload in dialysis patients. Calf BI methods have been developed to measure NHS by 2 ways: (1) continuous measurement of the intradialytic resistance curve until flattening occurs; (2) calf normalized resistivity in the range of healthy subjects (18.5 × 10(-2) Ω m(3)/kg in male and 19.1 × 10(-2) Ω m(3)/kg in female). In general, for population studies, BI vector analysis or ECV/total body water may be useful; BCM is a commercially available device that can certainly guide volume reduction safely over time. For more exact measure of fluid overload, calf BI methods appear to be most accurate, but these are at present research tools. BI techniques are not only useful in assessing NHS but also in the study of nutrition and body composition. PMID:25556307

  7. Identification of genes regulated during mechanical load-induced cardiac hypertrophy

    Science.gov (United States)

    Johnatty, S. E.; Dyck, J. R.; Michael, L. H.; Olson, E. N.; Abdellatif, M.; Schneider, M. (Principal Investigator)

    2000-01-01

    Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

  8. 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...

  9. The effect of iron on the biodistribution of bone scanning agents in humans

    International Nuclear Information System (INIS)

    Nine patients with chronic iron overload, resulting from either repeated transfusions or hemochromatosis, had bone scans that were characterized by a reduction of bony uptake, marked increase in renal activity, and a significant increase in soft-tissue accumulation of 99mTc-labeled bone-seeking agents. These findings were supported by semiquantitative computer analysis. The probable mechanisms of altered biodistribution and the possible role of serum ferritin are discussed. The importance of realizing the effect of excess iron on skeletal scintigraphy is further emphasized by the results of bone scanning in another patient in whom acute iron overload following infusion of iron-dextran resulted in excessive blood pool labeling

  10. Penetrating cardiac injury by a metallic fragment

    International Nuclear Information System (INIS)

    An adult male had a penetrating injury of the chest resulting in cardiac tamponade. The injury resulted as a consequence of a detached iron piece from an iron bar in a steel mill. Emergency sternotomy and percardiotomy revealed blood in the pericardial cavity and full thickness penetration of the right ventricle. The defect was repaired following the removal of the iron fragment. Postoperative recovery was uneventful. (author)

  11. MRI Detects Myocardial Iron in the Human Heart

    OpenAIRE

    Ghugre, Nilesh R; Enriquez, Cathleen M.; Gonzalez, Ignacio; Nelson, Marvin D.; Coates, Thomas D.; Wood, John C.

    2006-01-01

    Iron-induced cardiac dysfunction is a leading cause of death in transfusion-dependent anemia. MRI relaxation rates R2(1/T2) and R2∗(1∕T2∗) accurately predict liver iron concentration, but their ability to predict cardiac iron has been challenged by some investigators. Studies in animal models support similar R2 and R2∗ behavior with heart and liver iron, but human studies are lacking. To determine the relationship between MRI relaxivities and cardiac iron, regional variations in R2 and R2∗ we...

  12. Fatigue crack growth with single overload - Measurement and modeling

    Science.gov (United States)

    Davidson, D. L.; Hudak, S. J., Jr.; Dexter, R. J.

    1987-01-01

    This paper compares experiments with an analytical model of fatigue crack growth under variable amplitude. The stereoimaging technique was used to measure displacements near the tips of fatigue cracks undergoing simple variations in load amplitude-single overloads and overload/underload combinations. Measured displacements were used to compute strains, and stresses were determined from the strains. Local values of crack driving force (Delta-K effective) were determined using both locally measured opening loads and crack tip opening displacements. Experimental results were compared with simulations made for the same load variation conditions using Newman's FAST-2 model. Residual stresses caused by overloads, crack opening loads, and growth retardation periods were compared.

  13. Overloaded phase-code multiplexing for volume holographic storage.

    Science.gov (United States)

    Berger, Gernot; Dietz, Mathias; Denz, Cornelia

    2008-06-01

    Overloaded phase codes for volume holographic data storage are introduced. In contrast to any previous phase-code design, overloaded phase codes enable multiplexing of a number of data pages that exceeds the number of utilized reference beams. In this way the achievable data capacity can be augmented. Overloaded codes are generated by extending multilevel phase codes based on the discrete Fourier transform. We demonstrate multiplexing of 70 analog pages by means of 64 reference beams. The analysis of reconstructed digital data pages suggests that a capacity gain of up to 15% is reasonable. PMID:18516191

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

    Directory of Open Access Journals (Sweden)

    Konstantinos Gkouvatsos

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

  15. 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 c

  16. Dietary ω-3 Fatty Acids Alter Cardiac Mitochondrial Phospholipid Composition and Delay Ca2+-Induced Permeability Transition

    OpenAIRE

    O’Shea, Karen M.; Khairallah, Ramzi J.; Sparagna, Genevieve C.; Xu, Wenhong; Hecker, Peter A; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Kristian, Tibor; Robert C. Murphy; Fiskum, Gary; Stanley, William C.

    2009-01-01

    Consumption of ω-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA+DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA+DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospho...

  17. [Navigation aid through the information overload].

    Science.gov (United States)

    Günther, Judith; Schindler, Birgit; Suter, Katja

    2014-10-01

    We live in the modern information society. "To be informed" has a crucial impact on the personal, professional, economic and social development. The knowledge of things and their relationships is essential for acute decisions as well as for long-term planning. And at no time it was easier to get the information required within shorter time periods--no matter to whatsoever. The offer of information of the World Wide Web is inexhaustible. This also applies to information about all possible therapeutic and pharmaceutical issues. But is the information found reliable, too? And are easily accessible sources credible? Can we deal with the information overload at these days or do we actually risk paddling only on the surface of the "information-sea", without ever perceiving the actual information depth and width, less to use it? How can we protect being taken in by marketing strategies? The present article describes a structured proceed when seeking literature to find useful medical and pharmaceutical information in a time saving manner. PMID:25632609

  18. 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.

  19. A RETROSPECTIVE STUDY OF THE LESIONS ASSOCIATED WITH IRON STORAGE DISEASE IN CAPTIVE EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

    Science.gov (United States)

    Leone, Angelique M; Crawshaw, Graham J; Garner, Michael M; Frasca, Salvatore; Stasiak, Iga; Rose, Karrie; Neal, Dan; Farina, Lisa L

    2016-03-01

    Egyptian fruit bats (Rousettus aegyptiacus) are one of many species within zoologic collections that frequently develop iron storage disease. The goals of this retrospective multi-institutional study were to determine the tissue distribution of iron storage in captive adult Egyptian fruit bats and the incidence of intercurrent neoplasia and infection, which may be directly or indirectly related to iron overload. Tissue sections from 83 adult Egyptian fruit bats were histologically evaluated by using tissue sections stained with hematoxylin and eosin, trichrome, and Prussian blue techniques. The liver and spleen consistently had the largest amount of iron, but significant amounts of iron were also detected in the pancreas, kidney, skeletal muscle, and lung. Hepatocellular carcinoma (HCC; 11) was the most common neoplasm, followed by cholangiocarcinoma (4). Extrahepatic neoplasms included bronchioloalveolar adenoma (3), pulmonary carcinosarcoma (1), oral sarcoma (1), renal adenocarcinoma (1), transitional cell carcinoma of the urinary bladder (1), mammary gland adenoma (1), and parathyroid adenoma (1). There were also metastatic neoplasms of undetermined primary origin that included three poorly differentiated carcinomas, a poorly differentiated sarcoma, and a neuroendocrine tumor. Bats with hemochromatosis were significantly more likely to have HCC than bats with hemosiderosis (P = 0.032). Cardiomyopathy was identified in 35/77 bats with evaluable heart tissue, but no direct association was found between cardiac damage and the amount of iron observed within the liver or heart. Hepatic abscesses occurred in multiple bats, although a significant association was not observed between hemochromatosis and bacterial infection. To the authors' knowledge, this is the first publication providing evidence of a positive correlation between hemochromatosis and HCC in any species other than humans. PMID:27010264

  20. Risk factors and outcomes in transfusion-associated circulatory overload

    OpenAIRE

    Murphy, EL; Kwaan, N; Looney, MR; Gajic, O; Hubmayr, RD; Gropper, MA; Koenigsberg, M; Wilson, G.; Matthay, M; Bacchetti, P.; Toy, P

    2013-01-01

    Background: Transfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized. Methods: Using a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic ...

  1. Probablistic Power Flow Simulations Allowing Temporary Current Overloading

    OpenAIRE

    Wadman, W; Bloemhof, G.; Crommelin, D.; Frank, J.

    2012-01-01

    This paper presents a probabilistic power flow model subject to connection temperature constraints. Renewable power generation is included and modelled stochastically in order to reflect its intermittent nature. In contrast to conventional models that enforce connection current constraints, short-term current overloading is allowed. Temperature constraints are weaker than current constraints, and hence the proposed model quantifies the overload risk more realistically. Using such a constraint...

  2. Biliary excretion of iron and ferritin in idiopathic hemochromatosis

    International Nuclear Information System (INIS)

    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

  3. 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.

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

    OpenAIRE

    Monica Pinheiro de Almeida Verissimo; Sandra Regina Loggetto; Antonio Fabron Junior; Giorgio Roberto Baldanzi; Nelson Hamerschlak; Juliano de Lara Fernandes; Aderson da Silva Araujo; Clarisse Lopes de Castro Lobo; Kleber Yotsumoto Fertrin; Vasilios Antonios Berdoukas; Renzo Galanello

    2013-01-01

    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 red...

  5. Magnetic resonance imaging repercussions of intravenous iron products used for iron-deficiency anemia and dialysis-associated anemia.

    Science.gov (United States)

    Rostoker, Guy; Cohen, Yves

    2014-01-01

    During the past 2 decades, routine use of recombinant erythropoiesis-stimulating agents (ESAs) has enabled anemia to be corrected in dialysis patients, thereby improving their quality of life and permitting better outcomes. As successful use of ESA requires sufficient available iron, almost all end-stage renal disease patients on ESA now receive concomitant parenteral iron therapy. Radiologists must be aware that iron overload among dialysis patients is now an increasingly recognized clinical situation in the ESA era yet was previously considered rare. The KDIGO Controversies Conference on Iron Management in Chronic Kidney Disease, which took place in San Francisco on March 27 to 30, 2014, recognized the entity of iron overload in hemodialysis patients and called for an agenda of research on this topic, especially by means of magnetic resonance imaging (MRI).It is therefore very likely that radiologists will be heavily solicited in the future by nephrology teams requesting quantitative hepatic MRI in dialysis patients, both for research purposes and for diagnosis and follow-up of iron overload. Radiologists should be aware of the marked differences in the pharmacological properties of available intravenous iron products and their potential interference with MRI. Specific MRI protocols need to be established in radiology divisions for each pharmaceutical iron product, especially for treated dialysis patients. PMID:25229202

  6. Protective Effect of Quercetin on Posttraumatic Cardiac Injury.

    Science.gov (United States)

    Jing, Zehao; Wang, Zhuorun; Li, Xiujie; Li, Xintao; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Chen, Xu; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

    2016-01-01

    Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca(2+)]i of H9c2 cells were detected using an MTT assay, ELISA, and 2',7'-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 μM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca(2+)]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca(2+) overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma. PMID:27470932

  7. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    JonasSDe Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  8. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  9. Cardiac Rehabilitation

    Science.gov (United States)

    Cardiac rehabilitation (rehab) is a medically supervised program to help people who have A heart attack Angioplasty or coronary artery bypass grafting for coronary heart disease A heart valve repair or replacement A ...

  10. Cardiac sarcoidosis

    OpenAIRE

    Costello BT; Nadel J.; Taylor AJ

    2016-01-01

    Benedict T Costello,1,2 James Nadel,3 Andrew J Taylor,1,21Department of Cardiovascular Medicine, The Alfred Hospital, 2Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC, 3School of Medicine, University of Notre Dame, Sydney, NSW, Australia Abstract: Cardiac sarcoidosis is a rare but life-threatening condition, requiring a high degree of clinical suspicion and low threshold for investigation to make the diagnosis. The cardiac manifestations include heart failure, conducting syst...

  11. Mapping and characterization of iron compounds in Alzheimer's tissue

    International Nuclear Information System (INIS)

    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.

  12. 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

  13. 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.)

  14. Identifying non-technical skills and barriers for improvement of teamwork in cardiac arrest teams

    DEFF Research Database (Denmark)

    Andersen, P.O.; Jensen, Michael Kammer; Lippert, A.;

    2010-01-01

    2006 to November 2006. Interviews were focussed on barriers and recommendations for teamwork in the cardiac arrest team, optimal policy for improvement of resuscitation training and clinical practice, use of cognitive aids and adoption of European Resuscitation Council (ERC) Guidelines 2005. Interviews...... task management. Important barriers that were identified were inexperienced team leaders, task overload and hierarchic structure in the teams' inability to maintain focus on chest compressions. Conclusion: Interview participants pointed out that NTSs of teams could improve the treatment of cardiac...

  15. 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.

  16. Iron and genome stability: An update

    International Nuclear Information System (INIS)

    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.

  17. Fat overload syndrome after the rapid infusion of SMOFlipid emulsion.

    Science.gov (United States)

    Hojsak, Iva; Kolaček, Sanja

    2014-01-01

    Fat overload syndrome is a well-known complication of intravenous lipid emulsion therapy. It is characterized by headaches, fever, jaundice, hepatosplenomegaly, respiratory distress, and spontaneous hemorrhage. Other symptoms include anemia, leukopenia, thrombocytopenia, low fibrinogen levels, and coagulopathy. Several reports in the literature describe fat overload syndrome caused by rapid infusion of lipid emulsions, all with soybean-based lipid emulsions. We report fat overload syndrome in a 2-year-old girl with short bowel syndrome on home parenteral nutrition. Fat overload syndrome occurred as a result of accidental, very rapid infusion of a 20% soy oil, medium-chain triglyceride, olive and fish oil-based lipid emulsion (SMOFlipid) that showed the same complications seen with an earlier lipid emulsion (Intralipid). The patient was successfully treated with supportive care combining fluid infusion, transfusion of platelets, and substitution of serum albumin (0.5 g/kg/d) and fresh-frozen plasma (10 mL/kg). In the next couple of days, she received extra platelets, erythrocyte transfusion, and filgrastim (Neupogen; 5 µg/kg/d) due to a very low leukocyte count. To the best of our knowledge, this is the first case of fat overload syndrome caused by SMOFlipid emulsion described in the literature. PMID:23520135

  18. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism. PMID:26463975

  19. Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Hu, Jin; Zhang, Qiang; Liu, Bo [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo, E-mail: xhb_6505@163.com [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)

    2014-08-15

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 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{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 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{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca

  20. Clinical studies on myocardial perfusion imaging in patients with right ventricular overload

    International Nuclear Information System (INIS)

    Patients with heart disease which had been clinically diagnosed underwent 201Tl myocardial perfusion imaging. The thickness of right ventricular wall measured from original images was directly proportional to systolic pressure of the right ventricle measured by cardiac catheterization, and 201Tl activity in the right ventricle was more directly proportional to systolic pressure of the right ventricle. Imaging patterns of various diseases were also described. Images of patients with hypertrophic cardiomyopathy revealed that right ventricular wall was thin and right ventricular cavity was small, but the thickness of septal wall and left ventricular wall were maximal. Images of patients with mitral insufficiency revealed that the thickness of right ventricular wall, septal wall, and left ventricular wall was medium, and the right ventricular cavity was smaller than the left ventricular cavity. Images of patients with congestive cardiomyopathy and congestive cardiac failure showed that enlargement of both ventricular cavities was disproportionate to the thickness of each wall. Images of patients with arterial septal defect revealed that the thickness of each wall was comparatively normal, the right ventricular cavity was maximal, and the left ventricular cavity was minimal. Images of patients with primary pulmonary hypertention, pulmonary stenosis and tetralogy of Fallot in whom pressure overload was recognized revealed severe thickenings of right ventricular wall, moderate enlargement of the right ventricle, small left ventricle, and thin left ventricular wall. (Tsunoda, M.)

  1. Salvaging transient data with overloads and zero offsets

    Energy Technology Data Exchange (ETDEWEB)

    Smallwood, D.O.; Cap, J.S. [Sandia National Labs., Albuquerque, NM (United States). Mechanical and Thermal Environments Dept.

    1997-10-21

    The authors are sometimes presented with data with serious flaws, like overloads, zero shifts, and impulse noise, including much of the available pyrotechnic data. Obviously, these data should not be used if at all possible. However, they are sometimes forced to use these data as the only data available. Methods to salvage these data are discussed. Using the methods requires judgment, and the results must be accepted with the understanding that the answers are credible, not necessarily correct. None of the methods will recover information lost due to overloads or non-linearities of the data system. The best that can be accomplished is the recovery of data, after the data system has recovered from the overload. Several correction methods are discussed: high pass filtering of the data, correction with two forms of an exponential function, and a correction with the form t exp({minus}{alpha}t). Examples showing the results of the methods will be given using flawed pyrotechnic data.

  2. Handling Overload Conditions In High Performance Trustworthy Information Retrieval Systems

    CERN Document Server

    Ramachandran, Sumalatha; Paulraj, Sujaya; Ramaraj, Vetriselvi

    2010-01-01

    Web search engines retrieve a vast amount of information for a given search query. But the user needs only trustworthy and high-quality information from this vast retrieved data. The response time of the search engine must be a minimum value in order to satisfy the user. An optimum level of response time should be maintained even when the system is overloaded. This paper proposes an optimal Load Shedding algorithm which is used to handle overload conditions in real-time data stream applications and is adapted to the Information Retrieval System of a web search engine. Experiment results show that the proposed algorithm enables a web search engine to provide trustworthy search results to the user within an optimum response time, even during overload conditions.

  3. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  4. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  5. Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2007-10-01

    Full Text Available Abstract Background Hereditary hemochromatosis (HH encompasses genetic disorders of iron overload characterized by deficient expression or function of the iron-regulatory hormone hepcidin. Mutations in 5 genes have been linked to this disease: HFE, TFR2 (encoding transferrin receptor 2, HAMP (encoding hepcidin, SLC40A1 (encoding ferroportin and HJV (encoding hemojuvelin. Hepcidin inhibits iron export from cells into plasma. Hemojuvelin, an upstream regulator of hepcidin expression, is expressed in mice mainly in the heart and skeletal muscle. It has been suggested that soluble hemojuvelin shed by the muscle might reach the liver to influence hepcidin expression. Heart muscle is one of the target tissues affected by iron overload, with resultant cardiomyopathy in some HH patients. Therefore, we investigated the effect of iron overload on gene expression in skeletal muscle and heart using Illumina™ arrays containing over 47,000 probes. The most apparent changes in gene expression were confirmed using real-time RT-PCR. Results Genes with up-regulated expression after iron overload in both skeletal and heart muscle included angiopoietin-like 4, pyruvate dehydrogenase kinase 4 and calgranulin A and B. The expression of transferrin receptor, heat shock protein 1B and DnaJ homolog B1 were down-regulated by iron in both muscle types. Two potential hepcidin regulatory genes, hemojuvelin and neogenin, showed no clear change in expression after iron overload. Conclusion Microarray analysis revealed iron-induced changes in the expression of several genes involved in the regulation of glucose and lipid metabolism, transcription and cellular stress responses. These may represent novel connections between iron overload and pathological manifestations of HH such as cardiomyopathy and diabetes.

  6. Cardiac sarcoidosis

    Science.gov (United States)

    Smedema, J.P.; Zondervan, P.E.; van Hagen, P.; ten Cate, F.J.; Bresser, P.; Doubell, A.F.; Pattynama, P.; Hoogsteden, H.C.; Balk, A.H.M.M.

    2002-01-01

    Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696121

  7. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  8. Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice.

    Science.gov (United States)

    Viatte, Lydie; Lesbordes-Brion, Jeanne-Claire; Lou, Dan-Qing; Bennoun, Myriam; Nicolas, Gaël; Kahn, Axel; Canonne-Hergaux, François; Vaulont, Sophie

    2005-06-15

    Evidence is accumulating that hepcidin, a liver regulatory peptide, could be the common pathogenetic denominator of all forms of iron overload syndromes including HFE-related hemochromatosis, the most prevalent genetic disorder characterized by inappropriate iron absorption. To understand the mechanisms whereby hepcidin controls iron homeostasis in vivo, we have analyzed the level of iron-related proteins by Western blot and immunohistochemistry in hepcidin-deficient mice, a mouse model of severe hemochromatosis. These mice showed important increased levels of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), and ferroportin compared with control mice. Interestingly, the level of ferroportin was coordinately up-regulated in the duodenum, the spleen, and the liver (predominantly in the Kupffer cells). Finally, we also evidenced a decrease of ceruloplasmin in the liver of hepcidin-deficient mice. We hypothesized that the deregulation of these proteins might be central in the pathogenesis of iron overload, providing key therapeutic targets for iron disorders. PMID:15713792

  9. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  10. 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.

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

    International Nuclear Information System (INIS)

    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 55Fe-NTBI. Methods: Biliary iron kinetics of plasma 55Fe-labeled NTBI and cumulative recoveries of 55Fe 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 55Fe 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

  12. 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.

  13. 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.

  14. New Power Estimation Methods for Highly Overloaded Synchronous CDMA Systems

    CERN Document Server

    Nashtaali, Damoun; Pad, Pedram; Moghadasi, Seyed Reza; Marvasti, Farokh

    2011-01-01

    In CDMA systems, the received user powers vary due to moving distance of users. Thus, the CDMA receivers consist of two stages. The first stage is the power estimator and the second one is a Multi-User Detector (MUD). Conventional methods for estimating the user powers are suitable for underor fully-loaded cases (when the number of users is less than or equal to the spreading gain). These methods fail to work for overloaded CDMA systems because of high interference among the users. Since the bandwidth is becoming more and more valuable, it is worth considering overloaded CDMA systems. In this paper, an optimum user power estimation for over-loaded CDMA systems with Gaussian inputs is proposed. We also introduce a suboptimum method with lower complexity whose performance is very close to the optimum one. We shall show that the proposed methods work for highly over-loaded systems (up to m(m + 1) =2 users for a system with only m chips). The performance of the proposed methods is demonstrated by simulations. In ...

  15. Effects of Information Overload on Brazilian E-Consumers

    Directory of Open Access Journals (Sweden)

    Rafael Lucian

    2009-01-01

    Full Text Available Problem statement: E-commerce is a reality; Companies must consider this media as an important trade channel without distances between products and consumers. A key issue of e-commerce is how companies are disclosing information to its customers. This study aims to measure if there is relationship between the information overload in the virtual environment and the response of satisfaction and confusion of consumers. Approach: Research had exploratory-experimental character and it was used a quasi-experiment. Due to the methodology adopted, two samples were obtained, the first of control with 114 respondents and the second of experiment with 178 cases reported. Data analysis was made though descriptive statistics (central tendency and dispersion, multivariate (factor analysis and non-parametric (Mann-Whitney U test. Results: A factorial matrix was built and it was found that information overload relates to the responses of satisfaction and confusion in the environment of e-commerce. There was a statistical significance level supporting these relationships. Conclusion/Recommendation: The main implication of information load was the feeling of not having done the best buy, generating a possible repentance. Related to the feeling of confusion generated by the large amount of information, the physical and virtual environment has the same properties. The performed analyses in this study indicated that there is a relationship between the e-commerce consumer satisfaction and the experience of information overload. Future studies might investigate the relationship between information overload and other responses.

  16. Functional hallux limitus and lesser-metatarsal overload.

    Science.gov (United States)

    Clough, James G

    2005-01-01

    The implications of functional hallux limitus for lesser-metatarsal overload are discussed. A new method of treating functional hallux limitus is proposed, and three case histories are reviewed showing adequate resolution of symptoms using the proposed method of treatment. A proposed mechanism for the development of functional hallux limitus is discussed, and different methods of identification are illustrated. PMID:16291854

  17. 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.

  18. Probe-based end-to-end overload control for networks of SIP servers

    OpenAIRE

    Wang, Jinzhu; Liao, Jianxin; Li, Tonghong; Jing WANG; Wang, Jingyu; Qi, Qi

    2013-01-01

    The Session Initiation Protocol (SIP) has been adopted by the IETF as the control protocol for creating, modifying and terminating multimedia sessions. Overload occurs in SIP networks when SIP servers have insufficient resources to handle received messages. Under overload, SIP networks may suffer from congestion collapse due to current ineffective SIP overload control mechanisms. This paper introduces a probe-based end-to-end overload control (PEOC) mechanism, which is deployed at the edge se...

  19. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice

    DEFF Research Database (Denmark)

    Patrick, David M; Montgomery, Rusty L; Qi, Xiaoxia;

    2010-01-01

    cardiac hypertrophy and fibrosis in rodents in response to pressure overload. In contrast, we have shown here that miR-21-null mice are normal and, in response to a variety of cardiac stresses, display cardiac hypertrophy, fibrosis, upregulation of stress-responsive cardiac genes, and loss of cardiac......MicroRNAs inhibit mRNA translation or promote mRNA degradation by binding complementary sequences in 3' untranslated regions of target mRNAs. MicroRNA-21 (miR-21) is upregulated in response to cardiac stress, and its inhibition by a cholesterol-modified antagomir has been reported to prevent...... contractility comparable to wild. type littermates. Similarly, inhibition of miR-21 through intravenous delivery of a locked nucleic acid-modified (LNA-modified) antimiR oligonucleotide also failed to block the remodeling response of the heart to stress. We therefore conclude that miR-21 is not essential for...

  20. Hepatocyte divalent metal-ion transporter-1 is dispensable for hepatic iron accumulation and non-transferrin-bound iron uptake in mice

    OpenAIRE

    Wang, Chia-Yu; Knutson, Mitchell D.

    2013-01-01

    Divalent metal-ion transporter-1 (DMT1) is required for iron uptake by the intestine and developing erythroid cells. DMT1 is also present in the liver, where it has been implicated in the uptake of transferrin-bound iron (TBI) and non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. To test the hypothesis that DMT1 is required for hepatic iron uptake, we examined mice with the Dmt1 gene selectively inactivated in hepatocytes (Dmt1liv/liv). We found that Dmt1liv...

  1. Iron overdose

    Science.gov (United States)

    Iron is a mineral found in many over-the-counter supplements. Iron overdose occurs when someone takes more than the ... This can be by accident or on purpose. Iron overdose is especially dangerous for children. A severe ...

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

    OpenAIRE

    Saliba AN; Harb AR; Taher AT

    2015-01-01

    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, def...

  3. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation

    OpenAIRE

    Nicolas, Gaël; Chauvet, Caroline; Viatte, Lydie; Danan, Jean Louis; Bigard, Xavier; Devaux, Isabelle; Beaumont, Carole; Kahn, Axel; Vaulont, Sophie

    2002-01-01

    The present study was aimed at determining whether hepcidin, a recently identified peptide involved in iron metabolism, plays a role in conditions associated with both iron overload and iron deficiency. Hepcidin mRNA levels were assessed in two models of anemia, acute hemolysis provoked by phenylhydrazine and bleeding provoked by repeated phlebotomies. Hepcidin response to hypoxia was also studied, both ex vivo, in human hepatoma cells, and in vivo. Anemia and hypoxia were associated with a d...

  4. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  5. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  6. Parenteral iron sucrose in iron deficiency anaemia of paediatric chronic kidney disease

    International Nuclear Information System (INIS)

    Background: Erythropoietin (Epo) and iron therapy plays a major role in the management of renal anaemia. Iron sucrose (IS) has been used to treat iron deficiency anaemia (IDA) and to maintain adequate iron store in chronic kidney disease (CKD). The objective of the study was to determine the response and safety of IS in the treatment of IDA. Methods: This retrospective study was carried out in the Department of Nephrology, National Institute of Child Health, Karachi from Dec 2008 to Dec 2010. Children aged 6 months to 14 years, CKD-stage 2-5, and IDA were included. Pertinent data including age, gender, serum creatinine (SCr), CKD-stage, aetiology, treatment mode, IS dose, pre- and post-treatment parameters and side effects were collected and analysed. Results: Among 35, majority (66%) were boys. Mean age was 6.97+-4.13 years and mean SCr was 3.78+-3.1 mg/dl. Majority were in CKD-stage 4-5 and treated conservatively. Major aetiologies were hypoplasia-dysplasia (40%), juvenile nephronophthiasis (17.14%), posterior urethral valves, and stones. Baseline mean Hb and Transferrin Saturation (TS) was 7.38+-1.38 g/dl and 11.19+-5.28% respectively. Mean Hb increased to 9.22+-16.32 g/dl with correction of iron deficit (p<0.001) and a sustained rise in Hb was observed after Epo and maintenance iron sucrose. Mean TS% increased to 49.13+-18% (p<0.001). No major side effects were observed except iron overload. Conclusion: Iron sucrose was effective in improving IDA in CKD without significant side effects. Iron sucrose may be used to treat IDA with monitoring for iron overload. (author)

  7. The Cardiac Ventricular 5-HT4 Receptor Is Functional in Late Foetal Development and Is Reactivated in Heart Failure

    OpenAIRE

    Brattelid, Trond; Qvigstad, Eirik; Moltzau, Lise R; Bekkevold, Silje V. S.; Sandnes, Dagny L; Birkeland, Jon Arne K.; Skomedal, Tor; Osnes, Jan-Bjørn; Sjaastad, Ivar; Levy, Finn Olav

    2012-01-01

    A positive inotropic responsiveness to serotonin, mediated by 5-HT4 and 5-HT2A receptors, appears in the ventricle of rats with post-infarction congestive heart failure (HF) and pressure overload-induced hypertrophy. A hallmark of HF is a transition towards a foetal genotype which correlates with loss of cardiac functions. Thus, we wanted to investigate whether the foetal and neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts were collected day 3 and 1 before expe...

  8. Thermal Aging Characteristics of Insulation Paper in Mineral Oil under Overloaded Operating Transformers

    Science.gov (United States)

    Miyagi, Katsunori; Oe, Etsuo; Yamagata, Naoki; Miyahara, Hideyuki

    A sudden capacity increase in demand during the summer peak, or in contingencies such as malfunctioning transformers, may cause overload for normal transformers. In this paper, on the basis of examples of overloaded transformer operation in distributing substations, thermal aging testing in oil was carried out under various overload patterns, such as short time overload and long time overload, but with the winding insulation paper's life loss kept constant. From the results, various characteristics such as mean degree of polymerization and productions of furfural and (CO2+CO), and their effects on the life loss of the insulation paper were obtained.

  9. Cardiac Hypertrophy: A Review on Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Ankur Rohilla

    2012-07-01

    Full Text Available Cardiac hypertrophy has been considered as an important risk factor for cardiac morbidity and mortality whose prevalence has increased during the last few decades. Cardiac hypertrophy, a disease associated with the myocardium, is characterized by thickening of ventricle wall of heart and consequent reduction in the contracting ability of heart to pump the blood. Cardiac hypertrophy has been divided into two types, i.e. physiological and pathological hypertrophy. The exercise-induced increase in the ability of pumping blood leads to thickening of ventricle wall, referred to as physiological hypertrophy. On the other hand, reduced ability of pumping blood as a result of hypertension and volume overload on heart denotes pathological hypertrophy. Numerous mediators have been found to be involved in the pathogenesis of cardiac hypertrophy that include mitogen-activated protein kinase (MAPK, protein kinase C (PKC insulin-like growth factor-I (IGF-I, phosphatidylinositol 3-kinase (PI3K-AKT/PKB, calcinurin-nuclear factor of activated T cells (NFAT and mammalian target of rapamycin (mTOR. The prevention strategy for cardiac hypertrophy involve thiazide diuretics, angiotensin-converting enzyme (ACE inhibitors, angiotensin (Ang II receptor blockers, beta blockers and calcium channel blockers. The present review article highlights the signaling mechanisms involved and the approaches required in the treatment of cardiac hypertrophy.

  10. Effect of matrine and carvedilol on collagen and MMPs activity of hypertrophy myocardium induced by pressure overload

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore the effect and mechanism of matrine (Mt.) on myocardial interstitial fibrosis induced by pressure overload. Methods: Pressure overloaded myocardial hypertrophy was produced by banding of aorta abdominalis in 67 male Sprague-Dawley rats weighing (200± 15) g. The rats were assigned into one of the following groups: sham-operation control,operation control, operation group treated with matrine (15 mg/(kg.d)) and treated with carvedilol (Car.) (3.6 mg/(kg.d)) group.The rats were given drugs one day after operation. Five weeks after treatment, the left ventricular weight (LVW) was measured and the volume of myocardial cells was detected with Hematoxylin-Eosin (H-E) stain and Masson stain was used to assess the level of fibrosis of the myocardial matrix. Myocardial metalloproteinase activity was quantified with zymography, and survival rate was calculated. Results: Survival rate significantly decreased (P<0.05), LVW/BW (body weight), MMP-2 (matrix metalloproteinase-2)activity (P<0.05), size of cardiomyocytes and interstitial fibrosis obviously increased in the operation group compared with sham control group. Mt. and Car. treatment can significantly increase survival rate (P<0.05), decrease LVW/BW (P<0.05) and MMP-2 activity (P<0.05), decrease size of cardiomyocytes and interstitial fibrosis compared with operation group. But there was difference compared with sham group. Conclusion: Matrine was shown to be able to prevent cardiac remodelling of hypertrophy cardium induced by pressure overload including myocardial hypertrophy and fibrosis which may be associated with the decrease in MMP-2 activity of heart.

  11. Lipocalin 2 alleviates iron toxicity by facilitating hypoferremia of inflammation and limiting catalytic iron generation.

    Science.gov (United States)

    Xiao, Xia; Yeoh, Beng San; Saha, Piu; Olvera, Rodrigo Aguilera; Singh, Vishal; Vijay-Kumar, Matam

    2016-06-01

    Iron is an essential transition metal ion for virtually all aerobic organisms, yet its dysregulation (iron overload or anemia) is a harbinger of many pathologic conditions. Hence, iron homeostasis is tightly regulated to prevent the generation of catalytic iron (CI) which can damage cellular biomolecules. In this study, we investigated the role of iron-binding/trafficking innate immune protein, lipocalin 2 (Lcn2, aka siderocalin) on iron and CI homeostasis using Lcn2 knockout (KO) mice and their WT littermates. Administration of iron either systemically or via dietary intake strikingly upregulated Lcn2 in the serum, urine, feces, and liver of WT mice. However, similarly-treated Lcn2KO mice displayed elevated CI, augmented lipid peroxidation and other indices of organ damage markers, implicating that Lcn2 responses may be protective against iron-induced toxicity. Herein, we also show a negative association between serum Lcn2 and CI in the murine model of dextran sodium sulfate (DSS)-induced colitis. The inability of DSS-treated Lcn2KO mice to elicit hypoferremic response to acute colitis, implicates the involvement of Lcn2 in iron homeostasis during inflammation. Using bone marrow chimeras, we further show that Lcn2 derived from both immune and non-immune cells participates in CI regulation. Remarkably, exogenous rec-Lcn2 supplementation suppressed CI levels in Lcn2KO serum and urine. Collectively, our results suggest that Lcn2 may facilitate hypoferremia, suppress CI generation and prevent iron-mediated adverse effects. PMID:27007712

  12. Competition of dipositive metal ions for Fe (III) binding sites in chelation therapy of Iron Load

    International Nuclear Information System (INIS)

    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)

  13. Cardiac conduction system

    Science.gov (United States)

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  14. Stress 2.0 : Social Media Overload among Swiss Teenagers

    OpenAIRE

    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 understudied, even more so when social network sites are concerned. Our study explores how feelings of overexposure and stress relate to the self-expressive needs of teenagers, made explicit through ...

  15. Overload syndromes of the knee in adolescents: Sonographic findings

    OpenAIRE

    Draghi, F.; Danesino, G.M.; Coscia, D.; Precerutti, M.; Pagani, C.

    2008-01-01

    Overload syndromes are caused by repetitive microtrauma, and the knee joint is most frequently affected in adolescents. The reason for this is that the knee joint is engaged in almost all sports activities. Pathologies related to the anterior aspect of the knee are: femoropatellar pain, jumper's knee syndromes, Osgood–Schlatter disease, Sinding-Larsen–Johansson syndrome and patellar stress fractures; to the medial aspect: semimembranous tendon enthesopathy and pes anserinus bursitis; to the l...

  16. Fluid models of congestion collapse in overloaded switched networks

    OpenAIRE

    Shah, Devavrat; Wischik, Damon

    2010-01-01

    We consider a switched network (i.e. a queueing network in which there are constraints on which queues may be served simultaneously), in a state of overload. We analyse the behaviour of two scheduling algorithms for multihop switched networks: a generalized version of max-weight, and the α-fair policy. We show that queue sizes grow linearly with time, under either algorithm, and we characterize the growth rates. We use this characterization to demonstrate examples of congestion collapse, i...

  17. JOB SATISFACTION, ROLE OVERLOAD AND GENDER IN TURKEY

    OpenAIRE

    BOZKURT, Veysel; AYTAÇ, Serpil; Bondy, Jules; Emirgil, Faik

    2011-01-01

    ABSTRACTJob satisfaction is widely studied in academic literature but there are still limited studies about the relationship between job satisfaction with the role overload in Turkey, especially in the context of gender.Working women's lives in contemporary Turkey are divided between home and work.Women are faced with a wide range of competing demands like being in paid employment, familial duties as wives and mothers, and other gendered roles and tasks more broadly within the community.The i...

  18. 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

  19. 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.

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

    OpenAIRE

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

    2011-01-01

    Ferritin is a multisubunit protein that is responsible for storing and detoxifying cytosolic iron. Ferritin can be found in serum but is relatively iron poor. Serum ferritin occurs in iron overload disorders, inflammation and in the genetic disorder hyperferritinemia with cataracts. We show that ferritin secretion results when cellular ferritin synthesis occurs in the relative absence of free cytosolic iron. In yeast and mammalian cells, newly synthesized ferritin monomers can be translocated...

  1. 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.

  2. ω-3 Polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin

    Directory of Open Access Journals (Sweden)

    O'Shea Karen M

    2010-09-01

    Full Text Available Abstract Background Pathological left ventricular (LV hypertrophy frequently progresses to dilated heart failure with suppressed mitochondrial oxidative capacity. Dietary marine ω-3 polyunsaturated fatty acids (ω-3 PUFA up-regulate adiponectin and prevent LV dilation in rats subjected to pressure overload. This study 1 assessed the effects of ω-3 PUFA on LV dilation and down-regulation of mitochondrial enzymes in response to pressure overload; and 2 evaluated the role of adiponectin in mediating the effects of ω-3 PUFA in heart. Methods Wild type (WT and adiponectin-/- mice underwent transverse aortic constriction (TAC and were fed standard chow ± ω-3 PUFA for 6 weeks. At 6 weeks, echocardiography was performed to assess LV function, mice were terminated, and mitochondrial enzyme activities were evaluated. Results TAC induced similar pathological LV hypertrophy compared to sham mice in both strains on both diets. In WT mice TAC increased LV systolic and diastolic volumes and reduced mitochondrial enzyme activities, which were attenuated by ω-3 PUFA without increasing adiponectin. In contrast, adiponectin-/- mice displayed no increase in LV end diastolic and systolic volumes or decrease in mitochondrial enzymes with TAC, and did not respond to ω-3 PUFA. Conclusion These findings suggest ω-3 PUFA attenuates cardiac pathology in response to pressure overload independent of an elevation in adiponectin.

  3. 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.

  4. Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse

    OpenAIRE

    Britton Robert S; Fleming Robert E; Kytömäki Leena; Hilvo Mika; Rodriguez Alejandra; Bacon Bruce R; Parkkila Seppo

    2007-01-01

    Abstract Background Hereditary hemochromatosis (HH) encompasses genetic disorders of iron overload characterized by deficient expression or function of the iron-regulatory hormone hepcidin. Mutations in 5 genes have been linked to this disease: HFE, TFR2 (encoding transferrin receptor 2), HAMP (encoding hepcidin), SLC40A1 (encoding ferroportin) and HJV (encoding hemojuvelin). Hepcidin inhibits iron export from cells into plasma. Hemojuvelin, an upstream regulator of hepcidin expression, is ex...

  5. Mapping and characterization of iron compounds in Alzheimer's tissue

    Energy Technology Data Exchange (ETDEWEB)

    Collingwood, Joanna; Dobson, Jon [Keele

    2008-06-16

    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.

  6. Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation

    Directory of Open Access Journals (Sweden)

    HelenePuccio

    2014-06-01

    Full Text Available Friedreich ataxia (FRDA is the most common recessive ataxia in the Caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia frequently associating cardiomyopathy. The disease results from decreased expression of the FXN gene coding for the mitochondrial protein frataxin. Early histological and biochemical study of the pathophysiology in patient’s samples revealed that dysregulation of iron metabolism is a key feature of the disease, mainly characterized by mitochondrial iron accumulation and by decreased activity of iron-sulfur cluster enzymes. In the recent past years, considerable progress in understanding the function of frataxin has been provided through cellular and biochemical approaches, pointing to the primary role of frataxin in iron-sulfur cluster biogenesis. However, why and how the impact of frataxin deficiency on this essential biosynthetic pathway leads to mitochondrial iron accumulation is still poorly understood. Herein, we review data on both the primary function of frataxin and the nature of the iron metabolism dysregulation in FRDA. To date, the pathophysiological implication of the mitochondrial iron overload in FRDA remains to be clarified.

  7. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  8. On TCP-based Session Initiation Protocol (SIP) Server Overload Control

    CERN Document Server

    Shen, Charles

    2010-01-01

    The Session Initiation Protocol (SIP) server overload management has attracted interest since SIP is being widely deployed in the Next Generation Networks (NGN) as a core signaling protocol. Yet all existing SIP overload control work is focused on SIP-over-UDP, despite the fact that TCP is increasingly seen as the more viable choice of SIP transport. This paper answers the following questions: is the existing TCP flow control capable of handling the SIP overload problem? If not, why and how can we make it work? We provide a comprehensive explanation of the default SIP-over-TCP overload behavior through server instrumentation. We also propose and implement novel but simple overload control algorithms without any kernel or protocol level modification. Experimental evaluation shows that with our mechanism the overload performance improves from its original zero throughput to nearly full capacity. Our work leads to the important general insight that the traditional notion of TCP flow control alone is incapable of...

  9. Effect of band-overload on fatigue crack growth rate of HSLA steel

    Science.gov (United States)

    Abhinay, S. V.; Tenduwe, Om Prakash; Kumar, Ajit; Dutta, K.; Verma, B. B.; Ray, P. K.

    2015-02-01

    Fatigue crack growth behavior is important parameter of structural materials. This parameters can be used to predict their life, service reliability and operational safety in different conditions. The material used in this investigation is an HSLA steel. In this investigation effect of single overload and band-overload on fatigue crack growth of same steel are studied using compact tension (CT) specimens under mode-I condition and R=0.3. It is observed that overload and band-overload applications resulted retardation on the fatigue crack growth rate in most of the cases. It is also noticed that maximum retardation took place on application of seven successive overload cycles. Application of ten and more overload cycles caused no crack growth retardation.

  10. Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes.

    Science.gov (United States)

    Yan, Xinhua; Schuldt, Adam J T; Price, Robert L; Amende, Ivo; Liu, Fen-Fen; Okoshi, Katashi; Ho, Kalon K L; Pope, Adèle J; Borg, Thomas K; Lorell, Beverly H; Morgan, James P

    2008-03-01

    The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice. PMID:18178728

  11. NCOA4 Deficiency Impairs Systemic Iron Homeostasis

    Directory of Open Access Journals (Sweden)

    Roberto Bellelli

    2016-01-01

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

  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. Improved survival in MDS patients receiving iron chelation therapy - a matched pair analysis of 188 patients from the Düsseldorf MDS registry.

    Science.gov (United States)

    Neukirchen, Judith; Fox, Frank; Kündgen, Andrea; Nachtkamp, Kathrin; Strupp, Corinna; Haas, Rainer; Germing, Ulrich; Gattermann, Norbert

    2012-08-01

    MDS patients are prone to develop transfusional iron overload. Iron overload may partly explain why transfusion dependency is associated with a decreased likelihood of survival. Our matched-pair analysis included 94 patients on long-term chelation therapy and 94 matched patients without it. All patients had iron overload, defined as serum ferritin (SF) above 1000 ng/ml or a history of multiple transfusions and SF ≥ 500 ng/ml. Median SF was 1954 ng/ml in chelated and 875 ng/ml in non-chelated patients. The difference in median survival (74 vs. 49 months, respectively; p=0.002) supports the idea that iron chelation therapy is beneficial for MDS patients. PMID:22564985

  14. On TCP-based Session Initiation Protocol (SIP) Server Overload Control

    OpenAIRE

    Shen, Charles; Schulzrinne, Henning

    2010-01-01

    The Session Initiation Protocol (SIP) server overload management has attracted interest since SIP is being widely deployed in the Next Generation Networks (NGN) as a core signaling protocol. Yet all existing SIP overload control work is focused on SIP-over-UDP, despite the fact that TCP is increasingly seen as the more viable choice of SIP transport. This paper answers the following questions: is the existing TCP flow control capable of handling the SIP overload problem? If not, why and how c...

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

    OpenAIRE

    Pradana, Andika; Salehudin, Imam

    2013-01-01

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

  16. Heat Shock Transcription Factor 1-Deficiency Attenuates Overloading-Associated Hypertrophy of Mouse Soleus Muscle

    OpenAIRE

    Tomoyuki Koya; Sono Nishizawa; Yoshitaka Ohno; Ayumi Goto; Akihiro Ikuta; Miho Suzuki; Tomotaka Ohira; Tatsuro Egawa; Akira Nakai; Takao Sugiura; Yoshinobu Ohira; Toshitada Yoshioka; Moroe Beppu; Katsumasa Goto

    2013-01-01

    Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on t...

  17. [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients].

    Science.gov (United States)

    Zhang, Yao; Xiao, Chao; Gu, Shu-Cheng; Chang, Chun-Kang

    2014-08-01

    This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPO<1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P < 0.05). Obviously, the level of EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance

  18. Salt overload damages the glycocalyx sodium barrier of vascular endothelium

    OpenAIRE

    Oberleithner, Hans; Peters, Wladimir; Kusche-Vihrog, Kristina; Korte, Stefanie; Schillers, Hermann; Kliche, Katrin; Oberleithner, Kilian

    2011-01-01

    Sodium overload stiffens vascular endothelial cells in vitro and promotes arterial hypertension in vivo. The hypothesis was tested that the endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the surface of the endothelium, participates in the stiffening process. By using a mechanical nanosensor, mounted on an atomic force microscope, height (∼400 nm) and stiffness (∼0.25 pN/nm) of the eGC on the luminal endothelial surface of split-open human umbilical arteries were quantifi...

  19. Aeronautical Magnetic Torque Limiter for Passive Protection against Overloads

    Directory of Open Access Journals (Sweden)

    Cristian Cristache

    2016-09-01

    Full Text Available Actual aerospace and defense technologies present multiple limitations that need to be overcome in order to evolve to less contaminating and more efficient aircraft solutions. Contactless technologies come with essential advantages such as the absence of wear and friction. This work describes the design, prototype, and performance test according to RTCA-DO-160 of an aeronautical magnetic torque limiter. The results show correct continuous transmission operation (2250 rpm and 24 Nm from −50 °C to +90 °C. Moreover, overload protection has been demonstrated for more than 200 jamming events without damage or required maintenance to the device.

  20. Quantum Overloading Cryptography Using Single-Photon Nonlocality

    Institute of Scientific and Technical Information of China (English)

    TAN Yong-Gang; CAI Qing-Yu; SHI Ting-Yun

    2007-01-01

    @@ Using the single-photon nonlocality, we propose a quantum novel overloading cryptography scheme, in which a single photon carries two bits information in one-way quantum channel. Two commutative modes of the single photon, the polarization mode and the spatial mode, are used to encode secret information. Strict time windows are set to detect the impersonation attack. The spatial mode which denotes the existence of photons is noncommutative with the phase of the photon, so that our scheme is secure against photon-number-splitting attack. Our protocol may be secure against individual attack.

  1. Blood Transfusion, Serum Ferritin, and Iron in Hemodialysis Patients in Africa

    Directory of Open Access Journals (Sweden)

    Leonard Kouegnigan Rerambiah

    2015-01-01

    Full Text Available 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.

  2. Effect of chronic ethanol administration on iron metabolism in the rat

    International Nuclear Information System (INIS)

    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)

  3. Iron Homeostasis and Nutritional Iron Deficiency123

    OpenAIRE

    Theil, Elizabeth C.

    2011-01-01

    Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins enc...

  4. Effect of iron on the biodistribution of bone scanning agents in humans

    International Nuclear Information System (INIS)

    Nine patients with chronic iron overload, resulting from either repeated transfusions or hemochromatosis, had bone scans that were characterized by a reduction of bony uptake, marked increase in renal activity, and a significant increase in soft-tissue accumulation of /sup 99m/Tc-labeled bone-seeking agents. These findings were supported by semiquantitative computer analysis. The probable mechanisms of altered biodistribution and the possible role of serum ferritin are discussed. The importance of realizing the effect of excess iron on skeletal scintigraphy is further emphasized by the results of bone scanning in another patient in whom acute iron overload following infusion of iron-dextran resulted in excessive blood pool labeling

  5. Protective Effect of Qiliqiangxin Capsule on Energy Metabolism and Myocardial Mitochondria in Pressure Overload Heart Failure Rats

    Directory of Open Access Journals (Sweden)

    Junfang Zhang

    2013-01-01

    Full Text Available Qiliqiangxin capsule (QL was developed under the guidance of TCM theory of collateral disease and had been shown to be effective and safe for the treatment of heart failure. The present study explored the role of and mechanism by which the herbal compounds QL act on energy metabolism, in vivo, in pressure overload heart failure. SD rats received ascending aorta constriction (TAC to establish a model of myocardial hypertrophy. The animals were treated orally for a period of six weeks. QL significantly inhibited cardiac hypertrophy due to ascending aortic constriction and improved hemodynamics. This effect was linked to the expression levels of the signaling factors in connection with upregulated energy and the regulation of glucose and lipid substrate metabolism and with a decrease in metabolic intermediate products and the protection of mitochondrial function. It is concluded that QL may regulate the glycolipid substrate metabolism by activating AMPK/PGC-1α axis and reduce the accumulation of free fatty acids and lactic acid, to protect cardiac myocytes and mitochondrial function.

  6. Autoimmune Hepatitis: Diagnostic Dilemma in the Setting of Suspected Iron Overload

    OpenAIRE

    In Chul An; Tiwari, Ashish K.; Srujan Ameda; Laird-Fick, Heather S.

    2013-01-01

    Autoimmune hepatitis (AIH) is an inflammatory condition of the liver that has a multitude of clinical presentations from chronic hepatitis to acute fulminant hepatitis. AIH diagnosis is typically suspected after ruling out other causes of hepatitis (such as vial hepatitis, hemochromatosis, Wilson's disease, and primary biliary cirrhosis) through serological tests and by findings of high titers of certain autoantibodies (ANA and anti-SMA for type 1 AIH and anti-LKM-1 for type 2 AIH). AIH like ...

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

    Science.gov (United States)

    2014-12-09

    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

  8. Is iron overload in alcohol-related cirrhosis mediated by hepcidin?

    OpenAIRE

    Iqbal, Tariq; Diab, Azzam; Ward, Douglas G.; Brookes, Matthew J; Tselepis, Chris; Murray, Jim; Elias, Elwyn

    2009-01-01

    In this case report we describe the relationship between ferritin levels and hepcidin in a patient with alcohol-related spur cell anemia who underwent liver transplantation. We demonstrate a reciprocal relationship between serum or urinary hepcidin and serum ferritin, which indicates that inadequate hepcidin production by the diseased liver is associated with elevated serum ferritin. The ferritin level falls with increasing hepcidin production after transplantation. Neither inflammatory indic...

  9. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  10. 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. PMID:25642927

  11. 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. PMID:25891399

  12. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle.

    Science.gov (United States)

    Fujimaki, Shin; Machida, Masanao; Wakabayashi, Tamami; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

    2016-01-01

    Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise. PMID:26779264

  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. 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. PMID:21538152

  15. Myocardial stress and hypertrophy: a complex interface between biophysics and cardiac remodeling

    OpenAIRE

    Grossman, William; Paulus, Walter J.

    2013-01-01

    Pressure and volume overload results in concentric and eccentric hypertrophy of cardiac ventricular chambers with, respectively, parallel and series replication of sarcomeres. These divergent patterns of hypertrophy were related 40 years ago to disparate wall stresses in both conditions, with systolic wall stress eliciting parallel replication of sarcomeres and diastolic wall stress, series replication. These observations are relevant to clinical practice, as they relate to the excessive hype...

  16. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    OpenAIRE

    Leitch, Heather A.; Vickars, Linda M.; Chase, Jocelyn M.; Badawi, Maha A.

    2010-01-01

    Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC). A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the ...

  17. Blood Transfusion, Serum Ferritin, and Iron in Hemodialysis Patients in Africa

    OpenAIRE

    Leonard Kouegnigan Rerambiah; Laurence Essola Rerambiah; Armel Mbourou Etomba; Rose Marlène Mouguiama; Phanie Brunelle Issanga; Axel Sydney Biyoghe; Batchelili Batchilili; Sylvestre Akone Assembe; Joel Fleury Djoba Siawaya

    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. Co...

  18. The HLA linked iron loading gene in an Afrikaner population.

    OpenAIRE

    Meyer, T.E.; Ballot, D; Bothwell, T. H.; Green, A; Derman, D P; Baynes, R D; Jenkins, T.; Jooste, P. L.; du Toit, E D; Jacobs, P J

    1987-01-01

    The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of seru...

  19. Dietary glutamine supplementation partly reverses impaired macrophage function resulting from overload training in rats.

    Science.gov (United States)

    Xiao, Weihua; Chen, Peijie; Dong, Jingmei; Wang, Ru; Luo, Beibei

    2015-04-01

    The aim of this study was to evaluate the effect of overload training on the function of peritoneal macrophages in rats, and to test the hypothesis that glutamine in vivo supplementation would partly reverse the eventual functional alterations induced by overload training in these cells. Forty male Wistar rats were randomly divided into 5 groups: control group (C), overload training group (E1), overload training and restore one week group (E2), glutamine-supplementation group (EG1), and glutamine-supplementation and restore 1-week group (EG2). All rats, except those placed on sedentary control were subjected to 11 weeks of overload training protocol. Blood hemoglobin, serum testosterone, and corticosterone of rats were measured. Moreover, the functions (chemotaxis, phagocytosis, cytokines synthesis, reactive oxygen species generation) of peritoneal macrophages were determined. Data showed that blood hemoglobin, serum testosterone, corticosterone and body weight in the overload training group decreased significantly as compared with the control group. Meanwhile, the chemotaxis capacity (decreased by 31%, p = .003), the phagocytosis capacity (decreased by 27%, p = .005), the reactive oxygen species (ROS) generation (decreased by 35%, p = .003) and the cytokines response capability of macrophages were inhibited by overload training. However, the hindering of phagocytosis and the cytokines response capability of macrophages induced by overload training could be ameliorated and reversed respectively, by dietary glutamine supplementation. These results suggest that overload training impairs the function of peritoneal macrophages, which is essential for the microbicidal actions of macrophages. This may represent a novel mechanism of immunodepression induced by overload training. Nonetheless, dietary glutamine supplementation could partly reverse the impaired macrophage function resulting from overload training. PMID:25028814

  20. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  1. Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6-18 years with transfusion-dependent β-thalassemia major, with an emphasis on the impact of cardiac iron load.

    Science.gov (United States)

    Uçar, Ahmet; Öner, Nergiz; Özek, Gülcihan; Çetinçakmak, Mehmet Güli; Abuhandan, Mahmut; Yıldırım, Ali; Kaya, Cemil; Ünverdi, Sena; Emeksiz, Hamdi Cihan; Yılmaz, Yasin; Yetim, Aylin

    2016-07-01

    The variable presence of adrenal insufficiency (AI) due to hypocortisolemia (HC) in patients with thalassemia is well established; however, the prevalence of adrenocortical hypofunction (ACH) in the zona glomerulosa and zona reticularis of the adrenal cortex is unknown. To establish the prevalence of ACH, we examined the cortisol response to 1-µg and 250-µg ACTH tests, plasma aldosterone (A)/plasma renin activity (PRA) ratio, and serum dehydroepiandrosterone sulfate (DHEAS) levels in a large cohort of patients with thalassemia, and to investigate the impact of total body iron load (TBIL) on adrenocortical function. The setting used was University hospital and government-based tertiary care center. One hundred twenty-one (52 females) patients with β-thalassemia major (β-TM) and 72 healthy peers (38 females) were enrolled. The patients underwent a 250-µg cosyntropin test if their peak cortisol was AI due to HC and zona glomerulosa and zona reticularis hypofunction. TBIL surrogates can predict ACH, but cardiac iron was the only surrogate that was adequately sensitive to predict the severity of ACH. PMID:26839091

  2. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  3. Abundance and Significance of Iron, Zinc, Copper, and Calcium in the Hearts of Patients With Friedreich Ataxia.

    Science.gov (United States)

    Kruger, Pamela C; Yang, Karl X; Parsons, Patrick J; Becker, Alyssa B; Feustel, Paul J; Koeppen, Arnulf H

    2016-07-01

    Cardiomyopathy is a frequent cause of death in patients with Friedreich ataxia (FA), and a characteristic pathological feature is the focal accumulation of iron (Fe) in cardiomyocytes. This restricted localization of the metal contrasts with the diffuse cardiac Fe overload in hemochromatosis and transfusion siderosis. Nevertheless, heart Fe in FA contributes to cardiomyocyte necrosis, inflammation, and scarring as the disease progresses. A putative mechanism of cardiomyopathy in FA is Fe-mediated oxidative damage. Two other transition metals zinc (Zn) and copper (Cu), are diffusely distributed throughout normal hearts and the hearts of patients with FA. The myocardium in FA is also prone to deposits of calcium in the form of scattered concretions. In this study, heart tissues (left and right ventricular walls and ventricular septum) of 23 patients with genetically confirmed FA and 8 normal controls were obtained at autopsy and analyzed for Fe, Zn, Cu, and calcium. The principal assay methods were inductively coupled plasma optical emission spectrometry and plasma mass spectrometry. Total levels of Fe in bulk extracts were not significantly higher than normal, and the concentrations of Zn also remained in the normal range. Cu levels, however, were significantly lower in FA. In conclusion, the decrease of Cu may be important in consideration of the potential benefit of Cu supplements in FA cardiomyopathy. PMID:27189813

  4. Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

    Directory of Open Access Journals (Sweden)

    Bernardo A. Petriz

    2014-01-01

    Full Text Available Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.

  5. 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.

  6. Atherogenesis and iron: from epidemiology to cellular level

    Directory of Open Access Journals (Sweden)

    ViktóriaJeney

    2014-05-01

    Full Text Available Iron accumulates in human atherosclerotic lesions but whether it is a cause or simply a downstream consequence of the atheroma formation has been an open question for decades. According to the so called “iron hypothesis”, iron is believed to be detrimental for the cardiovascular system, thus promoting atherosclerosis development and progression. Iron, in its catalytically active form, can participate in the generation of reactive oxygen species and induce lipid-peroxidation, triggering endothelial activation, smooth muscle cell proliferation and macrophage activation; all of these processes are considered to be proatherogenic. On the other hand, the observation that hemochromatotic patients, affected by life-long iron overload, do not show any increased incidence of atherosclerosis is perceived as the most convincing evidence against the “iron hypothesis”. Epidemiological studies and data from animal models provided conflicting evidences about the role of iron in atherogenesis. Therefore more careful studies are needed in which issues like the source and the compartmentalization of iron will be addressed. This review article summarizes what we have learnt about iron and atherosclerosis from epidemiological studies, animal models and cellular systems and highlights the rather contributory than innocent role of iron in atherogenesis.

  7. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short circuit protection. 75.518 Section 75.518 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection....

  8. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the...

  9. Data Overload Impact on Project Management: How Knowledge Management Systems Can Improve Federal Agencies Effectiveness

    Science.gov (United States)

    Rodriguez, Jacinto

    2013-01-01

    This mixed method exploratory case study was used to explore the effect data overload has on project management, how data overload affects project management effectiveness, how prepared program office staff is to manage multiple projects effectively, and how the program office's organizational structure and data management systems affect project…

  10. Eccentric overload training in patients with a chronic Achilles tendinopathy: a systematic review.

    NARCIS (Netherlands)

    Kingma, J.J.; Knikker, R. de; Wittink, H.M.; Takken, T.

    2007-01-01

    Background: Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear. Study design: Systematic review of the

  11. A combined LIFO-priority algorithm for overload control of SIP server

    OpenAIRE

    Kuzminykh, Ievgeniia

    2012-01-01

    In this paper a simulation model of message service procedure in SIP server in the normal conditions and in the congestion state is represented. The paper proposes local overload control for SIP server applied FIFO discipline in normal state and LIFO discipline with priority service model during overload.

  12. Coping with Overload and Stress: Men and Women in Dual-Earner Families

    Science.gov (United States)

    Higgins, Chris A.; Duxbury, Linda E.; Lyons, Sean T.

    2010-01-01

    This study tested gender differences in a model positing relationships between work and family demands, overload, 4 coping mechanisms, and stress. The coping mechanisms were hypothesized to moderate the relationship between overload and stress. The sample consisted of 1,404 men and 1,623 women in dual-earner families. Respondents relied on 2…

  13. Reliability Analysis and Overload Capability Assessment of Oil-Immersed Power Transformers

    Directory of Open Access Journals (Sweden)

    Chen Wang

    2016-01-01

    Full Text Available Smart grids have been constructed so as to guarantee the security and stability of the power grid in recent years. Power transformers are a most vital component in the complicated smart grid network. Any transformer failure can cause damage of the whole power system, within which the failures caused by overloading cannot be ignored. This research gives a new insight into overload capability assessment of transformers. The hot-spot temperature of the winding is the most critical factor in measuring the overload capacity of power transformers. Thus, the hot-spot temperature is calculated to obtain the duration running time of the power transformers under overloading conditions. Then the overloading probability is fitted with the mature and widely accepted Weibull probability density function. To guarantee the accuracy of this fitting, a new objective function is proposed to obtain the desired parameters in the Weibull distributions. In addition, ten different mutation scenarios are adopted in the differential evolutionary algorithm to optimize the parameter in the Weibull distribution. The final comprehensive overload capability of the power transformer is assessed by the duration running time as well as the overloading probability. Compared with the previous studies that take no account of the overloading probability, the assessment results obtained in this research are much more reliable.

  14. "Something's Gotta Give:" Advanced-Degree Seeking Women's Experiences of Sexism, Role Overload, and Psychological Distress

    Science.gov (United States)

    West, Lindsey M.

    2014-01-01

    With the rise in advanced-degree seeking women and the minimal research on the dual impact of sexism and role overload, the current study aims to better understand the impact of sexism and role overload on psychological distress in a particular sample of advanced-degree seeking women. Seventy-six female medical student participants (mean age 24.7)…

  15. APJ acts as a dual receptor in cardiac hypertrophy.

    Science.gov (United States)

    Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Metzler, Scott; Wei, Ke; Wang, Jianming; Woods, Chris E; Purcell, Nicole H; Catalucci, Daniele; Akasaka, Takeshi; Bueno, Orlando F; Vlasuk, George P; Kaliman, Perla; Bodmer, Rolf; Smith, Layton H; Ashley, Euan; Mercola, Mark; Brown, Joan Heller; Ruiz-Lozano, Pilar

    2012-08-16

    Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy. PMID:22810587

  16. New Insights on Iron Study in Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Noha M. El Husseiny

    2014-12-01

    Full Text Available OBJECTIVE: Hepcidin plays a pivotal role in iron homeostasis. It is predominantly produced by hepatocytes and inhibits iron release from macrophages and iron uptake by intestinal epithelial cells. Competitive ELISA is the current method of choice for the quantification of serum hepcidin because of its lower detection limit, low costs, and high throughput. This study aims to discuss the role of hepcidin in the pathogenesis of iron overload in recently diagnosed myelodysplasia (MDS cases. METHODS: The study included 21 recently diagnosed MDS patients and 13 healthy controls. Ferritin, hepcidin, and soluble transferrin receptor (sTFR were measured in all subjects. RESULTS: There were 7 cases of hypocellular MDS, 8 cases of refractory cytopenia with multilineage dysplasia, and 6 cases of refractory anemia with excess blasts. No difference was observed among the 3 MDS subtypes in terms of hepcidin, sTFR, and ferritin levels (p>0.05. Mean hepcidin levels in the MDS and control groups were 55.8±21.5 ng/mL and 19.9±2.6 ng/ mL, respectively. Mean sTFR was 45.7±8.8 nmol/L in MDS patients and 31.1±5.6 nmol/L in the controls. Mean ferritin levels were significantly higher in MDS patients than in controls (539.14±83.5 ng/mL vs. 104.6±42.9 ng/mL, p0.05. CONCLUSION: Hepcidin may not be the main cause of iron overload in MDS. Further studies are required to test failure of production or peripheral unresponsiveness to hepcidin in MDS cases.

  17. 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.

  18. Functional overload attenuates plantaris atrophy in tumor-bearing rats

    International Nuclear Information System (INIS)

    Late stage cancer malignancies may result in severe skeletal muscle wasting, fatigue and reduced quality of life. Resistance training may attenuate these derangements in cancer patients, but how this hypertrophic response relates to normal muscle adaptations in healthy subjects is unknown. Here, we determined the effect of resistance training on muscle mass and myosin heavy chain (MHC) isoform composition in plantaris muscles from tumor-bearing (TB) rats. Age- and gender-matched Buffalo rats were used for all studies (n = 6/group). Suspensions of Morris Hepatoma MH7777 cells or normal saline were injected subcutaneously into the dorsum. Six weeks after cell implantation, muscles from TB rats were harvested, weighed and processed for ATP-independent proteasome activity assays. Once tumor-induced atrophy had been established, subgroups of TB rats underwent unilateral, functional overload (FO). Healthy, sham-operated rats served as controls. After six weeks, the extent of plantaris hypertrophy was calculated and MHC isoform compositions were determined by gel electrophoresis. Six weeks of tumor growth reduced body mass and the relative masses of gastrocnemius, plantaris, tibialis anterior, extensor digitorum longus, and diaphragm muscles (p ≤ 0.05). Percent reductions in body mass had a strong, negative correlation to final tumor size (r = -0.78). ATP-independent proteasome activity was increased in plantaris muscles from TB rats (p ≤ 0.05). In healthy rats, functional overload (FO) increased plantaris mass ~44% compared to the contralateral control muscle, and increased the relative percentage of MHC type I and decreased the relative percentage of MHC type IIb compared to the sham-operated controls (p ≤ 0.05). Importantly, plantaris mass was increased ~24% in TB-FO rats and adaptations to MHC isoform composition were consistent with normal, resistance-trained muscles. Despite significant skeletal muscle derangements due to cancer, muscle retains the capacity to

  19. Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload-induced triggered arrhythmias

    Science.gov (United States)

    Nagy, Norbert; Kormos, Anita; Kohajda, Zsófia; Szebeni, Áron; Szepesi, Judit; Pollesello, Piero; Levijoki, Jouko; Acsai, Károly; Virág, László; Nánási, Péter P; Papp, Julius Gy; Varró, András; Tóth, András

    2014-01-01

    Background and Purpose Augmented Na+/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti-arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca2+i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca2+i rise in conditions when [Ca2+]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na+/K+ pump. Experimental Approach Action potentials (APs) were recorded from canine papillary muscles and Purkinje fibres by microelectrodes. NCX current (INCX) was determined in ventricular cardiomyocytes utilizing the whole-cell patch clamp technique. Ca2+i transients (CaTs) were monitored with a Ca2+-sensitive fluorescent dye, Fluo-4. Key Results Enhanced INaL increased the Ca2+ load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and prevented/reversed the anemone toxin II (ATX-II)-induced [Ca2+]i rise without influencing APD, CaT or cell shortening, or affecting the ATX-II-induced increased APD. ORM10103 significantly decreased the number of strophanthidin-induced spontaneous diastolic Ca2+ release events; however, SEA0400 failed to restrict the veratridine-induced augmentation in Purkinje-ventricle APD dispersion. Conclusions and Implications Selective NCX inhibition – presumably by blocking revINCX (reverse mode NCX current) – is effective against arrhythmogenesis caused by [Na+]i-induced [Ca2+]i elevation, without influencing the AP waveform. Therefore, selective INCX inhibition, by significantly reducing the arrhythmogenic trigger activity caused by the perturbed Ca2+i handling, should be considered as a promising anti-arrhythmic therapeutic strategy. PMID:25073832

  20. Research on the overload protection reliability of moulded case circuit-breakers and its test device

    Institute of Scientific and Technical Information of China (English)

    LI Kui; LU Jian-guo; WU Yi; QIN Zhi-jun; YAO Dong-mei

    2007-01-01

    This paper analyzed the reliability and put forward the reliability index of overload protection for moulded case circuit breaker. The success rate was adopted as its reliability index of overload protection. Based on the reliability index and the reliability level, the reliability examination plan was analyzed and a test device for the overload protection of moulded case circuit-breaker was developed. In the reliability test of overload protection, two power sources were used, which reduced the time of conversion and regulation between two different test currents in the overload protection test, which made the characteristic test more accurate. The test device was designed on the base of a Windows system, which made its operation simple and friendly.