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Sample records for dietary iron overload

  1. Pathology of dietary carbonyl iron overload in rats.

    PubMed

    Park, C H; Bacon, B R; Brittenham, G M; Tavill, A S

    1987-11-01

    Serial light microscopic and ultrastructural studies were performed in rats with experimental iron overload produced by dietary supplementation with carbonyl (elemental) iron over a 12-month period. Hepatic iron increased rapidly to concentrations approximately 40 to 90 times those of control rats by 3 months. Within the liver, iron deposition was initially confined to periportal (zone 1) hepatocytes but subsequently extended to midzonal (zone 2) and centrilobular (zone 3) hepatocytes. Reticuloendothelial cell deposits of iron increased gradually and became prominent after 3 months. At this time, morphologic evidence of hepatocellular injury was mild and subtle with occasional foci of spotty necrosis and ultrastructural subcellular organelle damage. By 8 months, iron deposition was massive. Portal areas were enlarged with collections of iron-loaded macrophages and increased collagenous tissue. This portal fibrous tissue extended between periportal (zone 1) hepatocytes at sites of maximal iron deposition and around iron-loaded Kupffer cells and macrophages. At 12 months, the periportal (zone 1) fibrosis was more pronounced. These serial morphologic studies are the first to demonstrate the production of hepatic fibrosis by chronic dietary iron overload. This experimental model may reproduce important components of the pathophysiologic sequence of chronic liver damage seen in iron overload states in humans.

  2. Dietary iron overload in southern African rural blacks.

    PubMed

    Friedman, B M; Baynes, R D; Bothwell, T H; Gordeuk, V R; Macfarlane, B J; Lamparelli, R D; Robinson, E J; Sher, R; Hamberg, S

    1990-09-15

    A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Genome-linked toxic responses to dietary iron overload.

    PubMed

    Whittaker, P; Dunkel, V C; Bucci, T J; Kusewitt, D F; Thurman, J D; Warbritton, A; Wolff, G L

    1997-01-01

    Genome-related differences to Fe overload between and within rodent species were evaluated in the present study. Male B6C3F1 mice, yellow and black C5YSF1 mice, and Fischer 344 (F344) rats were fed AIN-76A diets containing 35 (control), 1,500, 3,500, 5,000, or 10,000 micrograms carbonyl Fe/g for 12 wk. No effects on body weight gain were observed in the B6C3F1 and black C5YSF1 mice, whereas at all doses of Fe above the control, weight gain was reduced in yellow C5YSF1 mice and F344 rats. At the 10,000 micrograms Fe/g dose, 9 of 12 rats died, but there was no mortality among the mice. In all animals, there was a dose-related increase in liver nonheme Fe, and the Fe was stored in hepatocytes predominantly in the periportal region. There was significant hypertrophy of the hepatocytes in both B6C3F1 mice and F344 rats fed the 10,000 micrograms Fe/g diet. PCNA assays showed significant stimulatory effects of the high dose of Fe on hepatocyte proliferation in the F344 rats and the C5YSF1 mice but not in the B6C3F1 mice. In the rat, there was pancreatic atrophy with loss of both endocrine and exocrine tissue. Morphometric evaluation of pancreas showed fewer beta cells in B6C3F1 and yellow C5YSF1 mice but not in the black C5YSF1 mice. There were fewer islets in the yellow C5YSF1 mice, and total and mean islet areas were smaller than in the control mice. Rats in the 10,000 micrograms Fe/g dose group had markedly exacerbated dose-dependent nephropathy and changes in glomerular and tubular epithelium associated with Fe accumulation. The rats also showed degeneration of the germinal epithelium of the testis, formation of multinucleated giant cells, and lack of mature sperm. PMID:9437799

  4. Insulin resistance due to dietary iron overload disrupts inner hair cell ribbon synapse plasticity in male mice.

    PubMed

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Rui; Zhang, Wenyue; Yang, Jun; Chen, Jie

    2015-06-15

    To evaluate whether cochlear inner hair cells (IHCs) ribbon synapse plasticity would be interrupted by insulin resistance (IR) due to dietary iron overload, we established an IR model in C57Bl/6 male mice with an iron-enriched diet for 16 weeks. Glucose levels were measured at weeks 4, 8, 12, 16. Glucose tolerance test and insulin tolerance test were performed at week 16 after overnight fasting. Then, auditory brainstem responses (ABRs) measurements were performed for hearing threshold shifts. After ABR measurements, cochleae were harvested for assessment of the number of IHC ribbon synapses by immunostaining, the morphology of cochlear hair cells and spiral ganglion neurons (SGNs) by transmission electron microscopy or immunostaining. Here, we show that IR due to dietary iron overload decreased the number of ribbon synapses, and induced moderate ABR threshold elevations. Besides, additional components including outer hair cells (OHCs), IHCs, and SGNs were unaffected. Moreover, IR did not disrupt the expression of vesicular glutamate transporter 3 (VGLUT3), myosin VIIa and prestin in hair cells. These results indicate that IHC ribbon synapses may be more susceptible to IR due to dietary iron overload.

  5. Insulin resistance due to dietary iron overload disrupts inner hair cell ribbon synapse plasticity in male mice.

    PubMed

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Rui; Zhang, Wenyue; Yang, Jun; Chen, Jie

    2015-06-15

    To evaluate whether cochlear inner hair cells (IHCs) ribbon synapse plasticity would be interrupted by insulin resistance (IR) due to dietary iron overload, we established an IR model in C57Bl/6 male mice with an iron-enriched diet for 16 weeks. Glucose levels were measured at weeks 4, 8, 12, 16. Glucose tolerance test and insulin tolerance test were performed at week 16 after overnight fasting. Then, auditory brainstem responses (ABRs) measurements were performed for hearing threshold shifts. After ABR measurements, cochleae were harvested for assessment of the number of IHC ribbon synapses by immunostaining, the morphology of cochlear hair cells and spiral ganglion neurons (SGNs) by transmission electron microscopy or immunostaining. Here, we show that IR due to dietary iron overload decreased the number of ribbon synapses, and induced moderate ABR threshold elevations. Besides, additional components including outer hair cells (OHCs), IHCs, and SGNs were unaffected. Moreover, IR did not disrupt the expression of vesicular glutamate transporter 3 (VGLUT3), myosin VIIa and prestin in hair cells. These results indicate that IHC ribbon synapses may be more susceptible to IR due to dietary iron overload. PMID:25956034

  6. Iron overload and hematologic malignancies.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2004-01-01

    Although iron is essential for cell replication and survival, an increase of body iron stores has been implicated in the development of cancer. However, while the association between iron overload and hepatocellular carcinoma is well documented, the relationship with nonhepatocellular malignancies remains ill-defined. In this review, we briefly report the present knowledge regarding the association between iron overload and hematologic malignancies.

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

    PubMed

    Espinoza, A; Morales, S; Arredondo, M

    2014-06-01

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

  8. Genetics Home Reference: African iron overload

    MedlinePlus

    ... of a genetic condition? Genetic and Rare Diseases Information Center Frequency African iron overload is common in rural areas of central and ... more about the gene associated with African iron overload SLC40A1 Related Information What is a gene? What is a gene ...

  9. Hepatocellular carcinoma and African iron overload.

    PubMed Central

    Gangaidzo, I T; Gordeuk, V R

    1995-01-01

    Both hepatocellular carcinoma (HCC) and iron overload are important health problems in Africa. Chronic hepatitis B virus (HBV) infection is recognised as a major risk factor for HCC, but iron overload in Africans has not been considered in pathogenesis. Up to half the patients with HCC in Africa do not have any recognised risk factors such as preceding chronic HBV infection, and other risk factors remain unidentified. HCC is an important complication of HLA-linked haemochromatosis, an iron loading disorder found in Europeans. It is proposed that African iron overload might also be a risk factor for HCC. PMID:8549953

  10. [IRON OVERLOAD: BETTER UNDERSTANDING, BETTER CARE].

    PubMed

    Brissot, Pierre

    2015-12-01

    Chronic iron overload, either of genetic (hemochromatoses) or acquired (transfusions) origin, leads to frequent disorders, affecting both the quality of life and life expectancy. Major recent advances in the knowledge of iron metabolism, together with advances in biology, imaging and drug design have already significantly improved the diagnostic and therapeutic approaches. These conceptual and technological ameliorations should, in the near future, continue to benefit the clinical management of iron overloaded patients. PMID:26979029

  11. Iron overload in hematopoietic cell transplantation.

    PubMed

    Majhail, N S; Lazarus, H M; Burns, L J

    2008-06-01

    Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic cell transplant (HCT) recipients. Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction post transplant. Elevated pretransplant ferritin levels have been reported to increase the risk of nonrelapse mortality following HCT and might influence the risk of acute and chronic GVHD. Serum ferritin is sensitive but not specific for iron overload and is a poor predictor of body iron burden. Estimation of hepatic iron content with a liver biopsy or magnetic resonance imaging should be considered prior to initiating therapy for post transplant iron overload. A subgroup of transplant survivors with mild iron overload and no end-organ damage may not need therapy. Phlebotomy is the treatment of choice with iron-chelation therapy reserved for patients not eligible for phlebotomy. Natural history, evolution and treatment of iron overload in transplant survivors have not been adequately investigated and more studies are needed to determine its impact on short-term and long-term morbidity and mortality. PMID:18438425

  12. [Iron deficiency and overload. Implications in oxidative stress and cardiovascular health].

    PubMed

    Toxqui, L; De Piero, A; Courtois, V; Bastida, S; Sánchez-Muniz, F J; Vaquero, Ma P

    2010-01-01

    Although iron is an essential mineral for maintaining good health, excessive amounts are toxic. Nowadays, much interest is focused on the mechanisms and regulation of iron metabolism by down-regulation of the hormone hepcidin. The HAMP gene encodes for hepcidin appears to be exceptionally preserved. Disorders of iron metabolism could lead to iron overload, mainly causing the rare disease hereditary hemochromatosis, or on the other hand, iron deficiency and iron deficiency anaemia. Currently, these alterations constitute an important problem of public health. The genetic variation implicated in iron overload and iron deficiency anaemia, involves mutations in several genes such as HFE, TFR2,HAMP, HJV, Tf and TMPRSS6. Iron has the capacity to accept and donate electrons easily and can catalyze reactions of free radicals production. Therefore, iron overload causes lipid peroxidation and increases cardiovascular risk. Recently, a relationship between iron metabolism and insulin resistance and obesity has been described. In contrast, regarding a possible relationship between iron deficiency anaemia and cardiovascular disease, many aspects remain controversial. This review presents an overview of the most recent information concerning iron metabolism, iron bioavailability and iron overload/deficiency related diseases. The relation between iron and cardiovascular risk, in iron overload and in iron deficiency situations, is also examined. Finally, strategies to modify dietary iron bioavailability in order to prevent iron deficiency or alleviate iron overload are suggested.

  13. Iron overload in cultured rat myocardial cells

    NASA Astrophysics Data System (ADS)

    Bauminger, E. R.; Iancu, T. C.; Link, G.; Pinson, A.; Hershko, C.

    1987-03-01

    In order to characterize the nature of iron deposits associated with iron overload in heart cells, Mössbauer spectroscopy and ultrastructural studies were performed in iron loaded heart cell cultures obtained from newborn rats grown in a medium containing 20 μg iron/ml. Maximal uptake of iron after 24 hrs was about 15%. Not more than 20% of the iron in these cells was stored in ferritin and the rest was found in smaller trivalent iron aggregates. With time there was a shift from smaller to larger aggregates. In chase samples there was only a very limited spontaneous release of iron from heart cells. Desferrioxamine, an iron chelating drug, removed a major part of the smaller aggregates, but did not remove ferritin iron.

  14. Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

    PubMed

    Sebastiani, Giada; Pantopoulos, Kostas

    2011-10-01

    In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references).

  15. Orally active iron chelators in the treatment of iron overload.

    PubMed

    Olivieri, N F

    1996-03-01

    Data from several trials have provided evidence for the efficacy of deferiprone in the treatment of iron overload in thalassemia major. Deferiprone has now been shown to induce sustained decreases in tissue iron to concentrations that are associated with survival free of the complications of iron overload in deferoxamine-treated patients. Despite this evidence of efficacy, the risk of agranulocytosis mandates a careful evaluation of the risk of this drug in patients willing and able to use deferoxamine. The incidence of agranulocytosis associated with deferiprone is under study in a prospective multicenter trial in Canada, Italy, and the United States, under corporate sponsorship by Apotex Research in Canada. The results of this study should determine the risk associated with the use of this agent and may provide the data required for a US Food and Drug Administration decision regarding licensing of this agent for the treatment of iron overload, a goal supported by investigators worldwide.

  16. Dietary fat overload reprograms brown fat mitochondria

    PubMed Central

    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 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 modulate health and lifespan. PMID:26483700

  17. Liver toxicity of thioacetamide is increased by hepatocellular iron overload.

    PubMed

    Ackerman, Zvi; Pappo, Orit; Link, Gabriela; Glazer, Maya; Grozovski, Maria

    2015-02-01

    An increase in hepatic iron concentration might exacerbate liver injury. However, it is unknown whether hepatic iron overload may exacerbate acute liver injury from various toxins. Therefore, we evaluated how manipulations to increase hepatic iron concentration affected the extent of acute liver injury from thioacetamide. In this study, we used rats with either "normal" or increased hepatic iron concentration. Iron overload was induced by either providing excess iron in the diet or by injecting iron subcutaneously. Both routes of providing excess iron induced an increase in hepatic iron overload. Meanwhile, the subcutaneous route induced both hepatocellular and sinusoidal cell iron deposition; the oral route induced lesser degree of hepatic iron concentration and only hepatocellular iron overload. Thioacetamide administration to the rats with "normal" hepatic iron concentration induced hepatic cell necrosis and apoptosis associated with a remarkable increase in serum aminotransaminases and depletion of hepatic glutathione and other antioxidative indices. Thioacetamide administration to the iron-overloaded rats exacerbated the extent of liver injury only in the rats orally induced with iron overload. In the rats subcutaneously induced with iron overload, the extent of liver injury from thioacetamide was not different from that observed in the rats with "normal" iron overload. It was concluded that the outcome of thioacetamide-induced acute liver injury may depend on both the level of hepatic iron concentration and on the cellular distribution of iron. While isolated hepatocellular iron overload may exacerbate thioacetamide-induced acute liver injury, a combined hepatocellular and sinusoidal cell iron deposition, even at high hepatic iron concentration, had no such an effect. PMID:25161090

  18. Iron excretion in iron dextran-overloaded mice

    PubMed Central

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-01-01

    Background Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Materials and methods Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. Results In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (p<0.01). The iron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. Conclusions This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion. PMID:24960657

  19. Health implications of iron overload: the role of diet and genotype.

    PubMed

    Heath, Anne-Louise M; Fairweather-Tait, Susan J

    2003-02-01

    The relationship between high dietary iron intake, mutations of the HFE gene, and iron status, and their effects on human health are reviewed. Prolonged high dietary intakes of iron are unlikely to result in iron overload in the general population. Homozygotes for the C282Y mutation of the HFE gene have elevated body iron levels. Heterozygotes have normal iron stores but some may be at increased risk for cardiovascular disease. There is no convincing evidence that elevated iron status increases the risk of coronary heart disease or type 2 diabetes, but high iron intakes may increase the risk of colorectal cancer. The dietary levels of iron associated with health risks in different HFE genotypes must be determined.

  20. Iron deficiency and iron overload: effects of diet and genes.

    PubMed

    Burke, W; Imperatore, G; Reyes, M

    2001-02-01

    Like most essential nutrients, Fe needs to be maintained in the body at a defined level for optimal health, with appropriate adaptation to varying Fe needs and supply. The primary mechanism for controlling Fe level is the regulation of Fe absorption. Several different proteins have been identified as contributors to the process. Despite a complex regulatory system, Fe disorders (both Fe deficiency and Fe overload) occur. Fe deficiency is a common problem worldwide, resulting from inadequate dietary Fe and blood loss. Complications include pre-term labour, developmental delay, and impaired work efficiency. No specific genetic syndromes causing isolated Fe deficiency have been described, but animal studies and clinical observations suggest that such a relationship may be a possibility. Conversely, the known causes of Fe overload are genetic. Fe overload is less common than Fe deficiency, but can result in serious medical complications, including cirrhosis, primary liver cancer, diabetes, cardiomyopathy and arthritis. The most common and best characterized syndrome of Fe overload is hereditary haemochromatosis (HHC), an autosomal recessive disorder. Mutations in the HFE protein cause HHC, but the clinical presentation is variable. Of particular interest is the factor that some FIFE genotypes appear to be associated with protection from Fe deficiency. Other genetic variants in the regulatory pathway may influence the likelihood of Fe deficiency and Fe overload. Studies of genetic variants in HFE and other regulatory proteins provide important tools for studying the biological processes in Fe regulation. This work is likely to lead to new insights into Fe disorders and potentially to new therapeutic approaches. It will not be complete, however, until coordinated study of both genetic and nutritional factors is undertaken. PMID:11310426

  1. Associations between Lifestyle Factors and Iron Overload in Korean Adults

    PubMed Central

    2016-01-01

    It has been suggested that iron overload, which indicates the accumulation of iron, generates cellular reactive oxygens and causes peroxide damages to the body. Such oxidative stresses, in a broader context, are also caused by lifestyles such as alcohol consumption and smoking. However, there are limited data on the association between these lifestyle factors and internal iron overload. In present study, we evaluated associations between lifestyle factors, such as smoking status, alcohol consumption, and physical activity, and serum markers of iron overload. In a population-based cross-sectional study including 2,347 Korean men and women aged 49–79 years, we assessed serum transferrin saturation (TSAT) levels and defined iron overload as TSAT levels > 50% for men and > 45% for women. After excluding persons with chronic diseases and iron deficiency, multivariate odds ratio (OR) and its 95% confidence interval (CI) were estimated to evaluate associations between lifestyle factors and iron overload in 1,973 participants. In all participants, we examined a significantly positive association between heavy alcohol consumption (> 30 g/day) and iron overload; heavy drinkers showed 1.6-fold higher OR (95% CI, 1.11–2.36) than non-drinkers. Stratified analysis by sex showed that this association was significant only among men. In addition, we observed a potential association between heavy smoking > 10 cigarettes/day and iron overload (p = 0.07). In stratified analysis by sex, we examined a significant association between smoking and iron overload only among women; former or current smokers had 1.9-fold higher OR (95% CI, 1.01–3.63) than never-smoker. Our findings suggest that heavy alcohol consumption and smoking may worsen iron accumulation in the body. PMID:27812516

  2. High Fat Diet Subverts Hepatocellular Iron Uptake Determining Dysmetabolic Iron Overload

    PubMed Central

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

    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 characterize the effect of free fatty acids on iron metabolism in HepG2 hepatocytes in vitro, and to assess the translational relevance in patients with fatty liver with and without iron accumulation. Despite decreased uptake of dietary iron, rats fed HFD accumulated more hepatic iron than those fed regular diet, which was associated with steatosis development. Hepatic iron accumulation was paralleled by induction of ferritin, in the presence of preserved upregulation of hepcidin, recapitulating the features of DIOS. HFD was associated with increased expression of the major iron uptake protein Transferrin receptor-1 (TfR-1), consistently with upregulation of the intracellular iron sensor Iron regulated protein-1 (IRP1). Supplementation with fatty acids induced TfR-1 and IRP1 in HepG2 hepatocytes, favoring intracellular iron accumulation following exposure to iron salts. IRP1 silencing completely abrogated TfR-1 induction and the facilitation of intracellular iron accumulation induced by fatty acids. Hepatic TfR-1 mRNA levels were upregulated in patients with fatty liver and DIOS, whereas they were not associated with liver fat nor with inflammation. In conclusion, increased exposure to fatty acids subverts hepatic iron metabolism, favoring the induction of an iron uptake program despite hepatocellular iron accumulation. PMID:25647178

  3. Use of magnetic resonance imaging to monitor iron overload.

    PubMed

    Wood, John C

    2014-08-01

    Treatment of iron overload requires robust estimates of total-body iron burden and its response to iron chelation therapy. Compliance with chelation therapy varies considerably among patients, and individual reporting is notoriously unreliable. Even with perfect compliance, intersubject variability in chelator effectiveness is extremely high, necessitating reliable iron estimates to guide dose titration. In addition, each chelator has a unique profile with respect to clearing iron stores from different organs. This article presents the tools available to clinicians to monitor their patients, focusing on noninvasive magnetic resonance imaging methods because they have become the de facto standard of care.

  4. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy

    PubMed Central

    Das, Subhash K.; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B.; Hajjar, Roger J.; Dyck, Jason R. B.; Kassiri, Zamaneh; Oudit, Gavin Y.

    2015-01-01

    Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca2+ homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca2+ homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload. PMID:26638758

  5. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy.

    PubMed

    Das, Subhash K; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B; Hajjar, Roger J; Dyck, Jason R B; Kassiri, Zamaneh; Oudit, Gavin Y

    2015-12-07

    Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca(2+) homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload.

  6. Plant phenolics and their potential role in mitigating iron overload disorder in wild animals.

    PubMed

    Lavin, Shana R

    2012-09-01

    Phenolic compounds are bioactive chemicals found in all vascular plants but are difficult to characterize and quantify, and comparative analyses on these compounds are challenging due to chemical structure complexity and inconsistent laboratory methodologies employed historically. These chemicals can elicit beneficial or toxic effects in consumers, depending on the compound, dose and the species of the consumer. In particular, plant phenolic compounds such as tannins can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo-managed wild animal species are sensitive to iron overload, and these species tend to be offered diets higher in iron than most of the plant browse consumed by these animals in the wild and in captivity. Furthermore, these animals likely consume diets higher in polyphenols in the wild as compared with in managed settings. Thus, in addition to reducing dietary iron concentrations in captivity, supplementing diets with phenolic compounds capable of safely chelating iron in the intestinal lumen may reduce the incidence of iron overload in these animal species. It is recommended to investigate various sources and types of phenolic compounds for use in diets intended for iron-sensitive species. Candidate compounds should be screened both in vitro and in vivo using model species to reduce the risk of toxicity in target species. In particular, it would be important to assess potential compounds in terms of 1) biological activity including iron-binding capacity, 2) accessibility, 3) palatability, and 4) physiological effects on the consumer, including changes in nutritional and antioxidant statuses.

  7. Plant phenolics and their potential role in mitigating iron overload disorder in wild animals.

    PubMed

    Lavin, Shana R

    2012-09-01

    Phenolic compounds are bioactive chemicals found in all vascular plants but are difficult to characterize and quantify, and comparative analyses on these compounds are challenging due to chemical structure complexity and inconsistent laboratory methodologies employed historically. These chemicals can elicit beneficial or toxic effects in consumers, depending on the compound, dose and the species of the consumer. In particular, plant phenolic compounds such as tannins can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo-managed wild animal species are sensitive to iron overload, and these species tend to be offered diets higher in iron than most of the plant browse consumed by these animals in the wild and in captivity. Furthermore, these animals likely consume diets higher in polyphenols in the wild as compared with in managed settings. Thus, in addition to reducing dietary iron concentrations in captivity, supplementing diets with phenolic compounds capable of safely chelating iron in the intestinal lumen may reduce the incidence of iron overload in these animal species. It is recommended to investigate various sources and types of phenolic compounds for use in diets intended for iron-sensitive species. Candidate compounds should be screened both in vitro and in vivo using model species to reduce the risk of toxicity in target species. In particular, it would be important to assess potential compounds in terms of 1) biological activity including iron-binding capacity, 2) accessibility, 3) palatability, and 4) physiological effects on the consumer, including changes in nutritional and antioxidant statuses. PMID:23156709

  8. Epidemiology and diagnostic testing for hemochromatosis and iron overload.

    PubMed

    Adams, P C

    2015-05-01

    Hemochromatosis is the most common genetic disease in northern European populations. Body iron stores progressively increase in most patients, which can lead to cirrhosis of the liver, hepatocellular carcinoma, heart failure, arthritis, and pigmentation. Simple blood tests such as the serum ferritin and transferrin saturation are useful to suggest the diagnosis which can be confirmed in most cases with a simple genetic test for the C282Y mutation of the HFE gene. However, these blood tests are often misinterpreted and there are rare patients with iron overload without HFE mutations. A diagnostic approach is presented based on a large referral practice and a population-based study (HEIRS) which screened for iron overload in 101,168 participants.

  9. Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload.

    PubMed

    Altamura, Sandro; Kessler, Regina; Gröne, Hermann-Josef; Gretz, Norbert; Hentze, Matthias W; Galy, Bruno; Muckenthaler, Martina U

    2014-08-01

    The regulatory axis between the iron hormone hepcidin and its receptor, the iron exporter ferroportin (FPN), is central to iron homeostasis. Mutations preventing hepcidin-mediated degradation of FPN cause systemic iron overload. We have introduced a point mutation (C326S) into the murine Fpn locus, resembling human hereditary hemochromatosis type 4, including elevated plasma iron and ferritin levels, high transferrin saturation, hepatic iron overload, and iron depletion of duodenal enterocytes and reticuloendothelial macrophages. Unlike other mouse models of iron overload, homozygous C326S mice die between 7 and 14 months of age. Pancreatic acinar cells display marked iron accumulation, oxidative damage and degeneration, associated with failure of the exocrine pancreas and severe body weight loss. Rescue experiments reveal iron overload and exocrine pancreatic failure as leading causes of death. This work uncovers the critical importance of the hepcidin-ferroportin regulatory axis for life and unveils the sensitivity of the exocrine pancreas to iron overload.

  10. Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application

    PubMed Central

    van Velden, DP; van Rensburg, SJ; Erasmus, R

    2009-01-01

    Iron uptake, utilisation, release and storage occur at the gene level. Individuals with variant forms of genes involved in iron metabolism may have different requirements for iron and are likely to respond differently to the same amount of iron in the diet, a concept termed nutrigenetics. Iron deficiency, iron overload and the anemia of inflammation are the commonest iron-related disorders. While at least four types of hereditary iron overload have been identified to date, our knowledge of the genetic basis and consequences of inherited iron deficiency remain limited. The importance of genetic risk factors in relation to iron overload was highlighted with the identification of the HFE gene in 1996. Deleterious mutations in this gene account for 80-90% of inherited iron overload and are associated with loss of iron homeostasis, alterations in inflammatory responses, oxidative stress and in its most severe form, the disorder hereditary haemochromatosis (HH). Elucidation of the genetic basis of HH has led to rapid clinical benefit through drastic reduction in liver biopsies performed as part of the diagnostic work-up of affected patients. Today, detection of a genetic predisposition in the presence of high serum ferritin and transferrin saturation levels is usually sufficient to diagnose HH, thereby addressing the potential danger of inherited iron overload which starts with the same symptoms as iron deficiency, namely chronic fatigue. This review provides the scientific back-up for application of pathology supported genetic testing, a new test concept that is well placed for optimizing clinical benefit to patients with regard to iron status.

  11. The C57BL/6 genetic background confers cardioprotection in iron-overloaded mice

    PubMed Central

    Musumeci, Marco; Maccari, Sonia; Sestili, Paola; Massimi, Alessia; Corritore, Elisa; Marano, Giuseppe; Catalano, Liviana

    2013-01-01

    Background Chronic transfusion therapy causes a progressive iron overload that damages many organs including the heart. Recent evidence suggests that L-type calcium channels play an important role in iron uptake by cardiomyocytes under conditions of iron overload. Given that beta-adrenergic stimulation significantly enhances L-type calcium current, we hypothesised that beta-adrenergic blocking drugs could reduce the deleterious effects of iron overload on the heart. Methods Iron overload was generated by intraperitoneal injections of iron dextran (1g/kg) administered once a week for 8 weeks in male C57bl/6 mice, while propranolol was administered in drinking water at the dose of 40 mg/kg/day. Cardiac function and ventricular remodelling were evaluated by echocardiography and histological methods. Results As compared to placebo, iron injection caused cardiac iron deposition. Surprisingly, despite iron overload, myocardial function and ventricular geometry in the iron-treated mice resulted unchanged as compared to those in the placebo-treated mice. Administration of propranolol increased cardiac performance in iron-overloaded mice. Specifically, as compared to the values in the iron-overloaded group, in iron-overloaded animals treated with propranolol left ventricular fractional shortening increased (from 31.6% to 44.2%, P =0.01) whereas left ventricular end-diastolic diameter decreased (from 4.1±0.1 mm to 3.5±0.1 mm, P =0.03). Propranolol did not alter cardiac systolic function or left ventricular sizes in the placebo group. Conclusions These results demonstrate that C57bl/6 mice are resistant to iron overload-induced myocardial injury and that treatment with propranolol is able to increase cardiac performance in iron-overloaded mice. However, since C57bl/6 mice were resistant to iron-induced injury, it remains to be evaluated further whether propranolol could prevent iron-overload cardiomyopathy. PMID:22790263

  12. Myocardial iron overload in thalassaemia major. How early to check?

    PubMed

    Borgna-Pignatti, Caterina; Meloni, Antonella; Guerrini, Giulia; Gulino, Letizia; Filosa, Aldo; Ruffo, Giovan B; Casini, Tommaso; Chiodi, Elisabetta; Lombardi, Massimo; Pepe, Alessia

    2014-02-01

    The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients' age ranged from 4·2 to 9·7 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value <20 ms and two patients showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction and the iron transfused was <35 g in all cases. Cardiac iron loading can occur much earlier than previously described. The first cardiac T2* assessment should be performed as early as feasible without sedation, especially if chelation is started late or if poor compliance is suspected.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed Central

    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

  15. Curcumin Attenuates Iron Accumulation and Oxidative Stress in the Liver and Spleen of Chronic Iron-Overloaded Rats

    PubMed Central

    Badria, Farid A.; Ibrahim, Ahmed S.; Badria, Adel F.; Elmarakby, Ahmed A.

    2015-01-01

    Objectives Iron overload is now recognized as a health problem in industrialized countries, as excessive iron is highly toxic for liver and spleen. The potential use of curcumin as an iron chelator has not been clearly identified experimentally in iron overload condition. Here, we evaluate the efficacy of curcumin to alleviate iron overload-induced hepatic and splenic abnormalities and to gain insight into the underlying mechanisms. Design and Methods Three groups of male adult rats were treated as follows: control rats, rats treated with iron in a drinking water for 2 months followed by either vehicle or curcumin treatment for 2 more months. Thereafter, we studied the effects of curcumin on iron overload-induced lipid peroxidation and anti-oxidant depletion. Results Treatment of iron-overloaded rats with curcumin resulted in marked decreases in iron accumulation within liver and spleen. Iron-overloaded rats had significant increases in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver and spleen when compared to control group. The effects of iron overload on lipid peroxidation and NO levels were significantly reduced by the intervention treatment with curcumin (P<0.05). Furthermore, the endogenous anti-oxidant activities/levels in liver and spleen were also significantly decreased in chronic iron overload and administration of curcumin restored the decrease in the hepatic and splenic antioxidant activities/levels. Conclusion Our study suggests that curcumin may represent a new horizon in managing iron overload-induced toxicity as well as in pathological diseases characterized by hepatic iron accumulation such as thalassemia, sickle cell anemia, and myelodysplastic syndromes possibly via iron chelation, reduced oxidative stress derived lipid peroxidation and improving the body endogenous antioxidant defense mechanism. PMID:26230491

  16. Bmp6 Expression in Murine Liver Non Parenchymal Cells: A Mechanism to Control their High Iron Exporter Activity and Protect Hepatocytes from Iron Overload?

    PubMed Central

    Rausa, Marco; Pagani, Alessia; Nai, Antonella; Campanella, Alessandro; Gilberti, Maria Enrica; Apostoli, Pietro; Camaschella, Clara; Silvestri, Laura

    2015-01-01

    Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production. PMID:25860887

  17. Bmp6 expression in murine liver non parenchymal cells: a mechanism to control their high iron exporter activity and protect hepatocytes from iron overload?

    PubMed

    Rausa, Marco; Pagani, Alessia; Nai, Antonella; Campanella, Alessandro; Gilberti, Maria Enrica; Apostoli, Pietro; Camaschella, Clara; Silvestri, Laura

    2015-01-01

    Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production.

  18. Measurement of liver iron overload: noninvasive calibration of MRI-R2* by magnetic iron detector susceptometer.

    PubMed

    Gianesin, B; Zefiro, D; Musso, M; Rosa, A; Bruzzone, C; Balocco, M; Carrara, P; Bacigalupo, L; Banderali, S; Rollandi, G A; Gambaro, M; Marinelli, M; Forni, G L

    2012-06-01

    An accurate assessment of body iron accumulation is essential for the diagnosis and therapy of iron overload in diseases such as thalassemia or hemochromatosis. Magnetic iron detector susceptometry and MRI are noninvasive techniques capable of detecting iron overload in the liver. Although the transverse relaxation rate measured by MRI can be correlated with the presence of iron, a calibration step is needed to obtain the liver iron concentration. Magnetic iron detector provides an evaluation of the iron overload in the whole liver. In this article, we describe a retrospective observational study comparing magnetic iron detector and MRI examinations performed on the same group of 97 patients with transfusional or congenital iron overload. A biopsy-free linear calibration to convert the average transverse relaxation rate in iron overload (R(2) = 0.72), or in liver iron concentration evaluated in wet tissue (R(2) = 0.68), is presented. This article also compares liver iron concentrations calculated in dry tissue using MRI and the existing biopsy calibration with liver iron concentrations evaluated in wet tissue by magnetic iron detector to obtain an estimate of the wet-to-dry conversion factor of 6.7 ± 0.8 (95% confidence level).

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

    PubMed

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

    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 gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  20. Dietary glutamine supplementation partly reverses impaired macrophage function resulting from overload training in rats.

    PubMed

    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

  1. Dietary glutamine supplementation partly reverses impaired macrophage function resulting from overload training in rats.

    PubMed

    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.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    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 found that iron overload resulted in liver dysfunction, increased apoptosis and elevated oxidative stress. Taurine supplementation increased liver taurine levels by 40% and led to improved liver function, as well as a reduction in apoptosis, ROS formation and mitochondrial swelling and an attenuation in the loss of the mitochondrial membrane potential. Treatment with taurine mediated a reduction in oxidative stress in iron-overloaded mice, attenuated liver lipid peroxidation, elevated antioxidant enzyme activities and maintained reduced glutathione levels. These results indicate that taurine reduces iron-induced hepatic oxidative stress, preserves liver function and inhibits hepatocyte apoptosis. Therefore, taurine may be a potential therapeutic drug to reduce liver damage caused by iron overload. PMID:25201602

  4. [Non-transferrin-bound iron: a promising biomarker in iron overload disorders].

    PubMed

    Maas, Roderick P P W M; Voets, Philip J G M; de Swart, Louise; Swinkels, Dorine W

    2013-01-01

    Iron overload disorders are common and, if left untreated, severe systemic diseases that can have both genetic and acquired causes. Hereditary haemochromatosis, β-thalassaemia, myelodysplastic syndromes and sickle cell disease are among the most important examples. Iron that is not bound to transferrin, haem or ferritin (non-transferrin-bound iron, NTBI) seems to play a key role in the pathophysiology of these disorders. NTBI is a heterogeneous group of potentially toxic iron complexes in plasma which are generated almost exclusively under pathological conditions. Cellular uptake of NTBI contributes to its toxicity and is mediated by several organ-specific transporters and receptors. NTBI-induced toxicity is the result of oxidative damage to various macromolecules by reactive oxygen species (ROS). In the near future, we hypothesize that NTBI will have important implications for both diagnosis and treatment of iron overload disorders. However, before NTBI can be applied to patient care, the currently available assays need further clinical and analytical validation. PMID:24299624

  5. Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats.

    PubMed

    Whittaker, P; Hines, F A; Robl, M G; Dunkel, V C

    1996-01-01

    The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 micrograms Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 micrograms Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.

  6. Dietary phosphorus overload aggravates the phenotype of the dystrophin-deficient mdx mouse.

    PubMed

    Wada, Eiji; Yoshida, Mizuko; Kojima, Yoriko; Nonaka, Ikuya; Ohashi, Kazuya; Nagata, Yosuke; Shiozuka, Masataka; Date, Munehiro; Higashi, Tetsuo; Nishino, Ichizo; Matsuda, Ryoichi

    2014-11-01

    Duchenne muscular dystrophy is a lethal X-linked disease with no effective treatment. Progressive muscle degeneration, increased macrophage infiltration, and ectopic calcification are characteristic features of the mdx mouse, a murine model of Duchenne muscular dystrophy. Because dietary phosphorus/phosphate consumption is increasing and adverse effects of phosphate overloading have been reported in several disease conditions, we examined the effects of dietary phosphorus intake in mdx mice phenotypes. On weaning, control and mdx mice were fed diets containing 0.7, 1.0, or 2.0 g phosphorus per 100 g until they were 90 days old. Dystrophic phenotypes were evaluated in cryosections of quadriceps and tibialis anterior muscles, and maximal forces and voluntary activity were measured. Ectopic calcification was analyzed by electron microscopy to determine the cells initially responsible for calcium deposition in skeletal muscle. Dietary phosphorus overload dramatically exacerbated the dystrophic phenotypes of mdx mice by increasing inflammation associated with infiltration of M1 macrophages. In contrast, minimal muscle necrosis and inflammation were observed in exercised mdx mice fed a low-phosphorus diet, suggesting potential beneficial therapeutic effects of lowering dietary phosphorus intake on disease progression. To our knowledge, this is the first report showing that dietary phosphorus intake directly affects muscle pathological characteristics of mdx mice. Dietary phosphorus overloading promoted dystrophic disease progression in mdx mice, whereas restricting dietary phosphorus intake improved muscle pathological characteristics and function.

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

    PubMed

    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

  8. Kinetics of iron removal by phlebotomy in patients with iron overload after allogeneic hematopoietic cell transplantation

    PubMed Central

    Eisfeld, Ann-Kathrin; Krahl, Rainer; Jaekel, Nadja; Niederwieser, Dietger; Al-Ali, Haifa Kathrin

    2012-01-01

    Excess body iron could persist for years after allogeneic hematopoietic cell transplantation (HCT) with possible deleterious sequels. An iron depletive therapy with phlebotomy seems rational. Kinetics of iron removal by phlebotomy without erythropoietin support in non-thalassemic adult patients with iron overload after HCT and the impact of pre- and post-HCT hemochromatosis (HFE) genotype on iron mobilization were investigated. Patients and methods: Phlebotomy was initiated in 61 recipients of allografts due to hematologic malignancies (median age 48 years) after a median of 18 months. The prephlebotomy median serum ferritin (SF) was 1697ng/ml and the median number of blood transfusions 28 units. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST), alkaline phosphates (AP), and bilirubin were elevated in 55.7%, 64% and 11.5% patients respectively. HFE-genotype was elucidated by polymerase chain reaction using hybridization probes and melting curve analysis. Results: Phlebotomy was well-tolerated irrespective of age or conditioning. A negative iron balance in 80% of patients (median SF 1086 ng/ml) and a rise in hemoglobin were observed (p<0.0001). Higher transfusional burden and SF were associated with a greater iron mobilization per session (p=0.02). In 58% of patients, a plateau after an initial steady decline in SF was followed by a second decline under further phlebotomy. The improvement in ALT (p=0.002), AST (p=0.03), AP (p=0.01), and bilirubin (p<0.0001) did not correlate with the decline in SF. Mutant HFE-gene variants were detected in 14/55 (25%) pre-HCT and 22/55 (40%) patients post-HCT. Overall, dissimilar pre- and posttransplantational HFE-genotypes were detected in 20/55 (40%) patients. Posttransplantational mutant HFE variants correlated with a slower decline in SF (p=0.007). Conclusions: Phlebotomy is a convenient therapy of iron overload in survivors of HCT. A negative iron balance and a rise in hemoglobin were observed in the majority of

  9. Oral exfoliative cytology as a screening tool for iron overload in β-thalassemia patients

    PubMed Central

    Rathore, Ajit Singh; Keshri, Neha; Shetty, Devi Charan; Juneja, Saurabh

    2016-01-01

    Background: Increased iron overload is frequent problem in thalassemia patients, and this is monitored by serum ferritin levels or chemical assessment of the iron levels in liver tissue. However, repeated monitoring of serum ferritin levels to assess the iron overload is an invasive procedure associated with practical problems. Aims: To use Perl's Prussian blue reaction to evaluate the iron overload in beta-thalassemia patients by staining the oral cytosmears. Materials and Methods: The study comprised 35 patients diagnosed with beta-thalassemia. Cytosmears were prepared from exfoliated oral epithelial cells, fixed in 70% ethanol and stained with Perl's Prussian blue stain for detection of blue colored granules in the cytoplasm. Results: 29/35 (82.9%) cases showed a positive reaction for Perl's Prussian blue reaction while 6/35 (17%) cases did not show the presence of blue colored granules in the oral cytosmears. The presence of iron detected by Perl's Prussian blue reaction correlated with serum ferritin level (P < 0.05). Conclusion: Perl's Prussian blue reaction can be used to evaluate the iron overload in beta-thalassemia patients by staining the oral cytosmears. It is a simple and noninvasive method for assessment of iron overload in such patients. PMID:26958519

  10. Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing.

    PubMed

    Daba, Alina; Gkouvatsos, Konstantinos; Sebastiani, Giada; Pantopoulos, Kostas

    2013-01-01

    The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

  11. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload.

    PubMed Central

    Houglum, K; Filip, M; Witztum, J L; Chojkier, M

    1990-01-01

    In hepatic iron overload, iron-catalyzed lipid peroxidation has been implicated in the mechanisms of hepatocellular injury. Lipid peroxidation may produce reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which may form aldehyde-protein adducts. We investigated whether lipid peroxidation occurred in rats fed a diet containing 3% carbonyl iron for 5-13 wk, and if this resulted in the formation of MDA- and 4-HNE- protein adducts. Chronic iron feeding resulted in hepatic iron overload (greater than 10-fold) and concomitantly induced a 2-fold increase in hepatic lipid peroxidation. Using an antiserum specific for MDA-lysine protein adducts, we demonstrated by immunohistochemistry the presence of aldehyde-protein adducts in the cytosol of periportal hepatocytes, which co-localized with iron. In addition, MDA- and 4-HNE-lysine adducts were found in plasma proteins of animals with iron overload. Only MDA adducts were detected in albumin, while other plasma proteins including a approximately 120-kD protein had both MDA and 4-HNE adducts. In this animal model of hepatic iron overload, injury occurs primarily in periportal hepatocytes, where MDA-lysine protein adducts and excess iron co-localized. Images PMID:2123889

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

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

  13. Iron overload impairs proliferation of erythroid progenitors cells (BFU-E) from patients with myelodysplastic syndromes.

    PubMed

    Hartmann, Julia; Braulke, Friederike; Sinzig, Ursula; Wulf, Gerald; Maas, Jens Holger; Konietschke, Frank; Haase, Detlef

    2013-03-01

    In patients with myelodysplastic syndromes (MDS) iron overload caused by long-term red blood cell transfusions is an important factor for comorbidity especially in low-risk MDS. In this report we present the results of a comparative study based on colony formation assays of hematopoietic cells in MDS patients with and without iron overload. We demonstrate that iron overload suppresses the proliferation of erythroid progenitors cells (BFU-E), while the myeloid compartment (CFU-GM) was not found to be affected. Even patients with slightly elevated ferritin values show an impaired proliferation capacity in comparison to patients with normal ferritin levels. Furthermore, we show that this negative impact is reversible by sufficient iron chelation therapy.

  14. Effect of mild iron overload on liver and kidney lipid peroxidation.

    PubMed

    Galleano, M; Puntarulo, S

    1994-10-01

    1. Hepatotoxicity is the most common finding in patients with iron overload since the liver is the major recipient of iron excess, even though the kidney could be a target of iron toxicity. The effect of iron overload was studied in the early stages after iron-dextran injection in rats, as a model for secondary hemocromatosis. 2. Total hepatic and kidney iron content was markedly elevated over control values 20 h after the iron administration. Plasma GOT, GPT and LDH activities were not affected, suggesting that liver cell permeability was not affected by necrosis. 3. Spontaneous liver chemiluminescence was measured as an indicator of oxidative stress and lipid peroxidation. Light emission was increased four-fold 6 h after iron supplementation. 4. Increases in the generation of thiobarbituric acid reactive substances (TBARS in liver and kidney homogenates were detected after iron administration. 5. The activities of catalase, SOD and glutathione peroxidase were determined. Enzymatic activities declined in liver homogenates by 25, 36 and 32%, respectively, 20 h after iron injection. These activities were not affected in kidney as compared to control values, except for SOD activity that was decreased by 26%. 6. The content of alpha-tocopherol was decreased by 31% in whole kidney homogenates and by 40% in plasma. 7. Our data indicate that lipid peroxidation occurs after mild iron overload both in liver and kidney. Enzymatic antioxidants are consumed significantly in liver and alpha-tocopherol content decreases in kidney, suggesting an organ-specific antioxidant effect.

  15. Estimation of iron overloads using oral exfoliative cytology in beta-thalassemia major patients

    PubMed Central

    Leekha, Swati; Nayar, Amit Kumar; Bakshi, Preeti; Sharma, Aman; Parhar, Swati; Soni, Sugandhi

    2016-01-01

    Background: Iron overload is a medical condition that occurs when too much of the mineral iron builds up inside the body and produces a toxic reaction. Thalassemia is a genetic disorder of hemoglobin synthesis, which requires regular blood transfusion therapy, and the lack of specific excretory pathways for iron in humans leads to iron overload in the body tissues. It is a major cause of morbidity and mortality in these patients. The estimation of iron levels in exfoliated buccal mucosal cells may provide a simple, noninvasive, and a safe procedure for estimating the iron overload by using the Perls’ Prussian blue stain. Methods: Smears were obtained from buccal mucosa of 40 randomly selected beta-thalassemia major patients and 40 healthy subjects as controls. Smears were stained with Perls’ Prussian blue method. Blood samples were taken for estimation of serum ferritin levels. Images of smears were analyzed using the software image J software version 1.47v and correlated with serum ferritin. Results: Perls’ positivity was observed in 87.5% of thalassemic patients with a positive correlation to serum ferritin levels. Conclusion: The use of exfoliative buccal mucosal cells for the evaluation of iron overloads in the body provides us with a diagnostic medium that is noninvasive, easy to collect, store, and transport, cost effective, and above all reliable. PMID:27081394

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

    PubMed Central

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

    2015-01-01

    Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. PMID:26190429

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    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.

  19. Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice.

    PubMed

    Patchen, Bonnie; Koppe, Tiago; Cheng, Aaron; Seo, Young Ah; Wessling-Resnick, Marianne; Fraenkel, Paula G

    2016-09-01

    Hepcidin, a peptide produced in the liver, decreases intestinal iron absorption and macrophage iron release by causing degradation of the iron exporter, ferroportin. Because its levels are inappropriately low in patients with iron overload syndromes, hepcidin is a potential drug target. We previously conducted a chemical screen that revealed ipriflavone, an orally available small molecule, as a potent inducer of hepcidin expression. To evaluate ipriflavone's effect on iron homeostasis, we placed groups of 5-week old wild type or thalassemia intermedia (Hbb(Th3+/-)) mice on a soy-free, iron-sufficient diet, AIN-93G containing 220mg iron and 0-750mgipriflavone/kg of food for 50days. Ipriflavone 500mg/kg significantly reduced liver iron stores and intestinal ferroportin expression in WT mice, while increasing the ratio of hepcidin transcript levels to liver iron stores. Ipriflavone supplementation in Hbb(Th3+/-) mice failed to alleviate iron overload and was associated with a milder reduction in intestinal ferroportin and a failure to alter the ratio of hepcidin transcript levels to liver iron stores or splenic expression of the hepcidin-regulatory hormone, erythroferrone. These data suggest that dietary supplementation with ipriflavone alone would not be sufficient to treat iron overload in thalassemia intermedia. PMID:27519943

  20. Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes.

    PubMed

    Ono, Yukiya; Ishigami, Masatoshi; Hayashi, Kazuhiko; Wakusawa, Shinya; Hayashi, Hisao; Kumagai, Kotaro; Morotomi, Natsuko; Yamashita, Tetsuji; Kawanaka, Miwa; Watanabe, Minemori; Ozawa, Hiroaki; Tai, Mayumi; Miyajima, Hiroaki; Yoshioka, Kentarou; Hirooka, Yoshiki; Goto, Hidemi

    2015-06-28

    In biology, redox reactions are essential and sometimes harmful, and therefore, iron metabolism is tightly regulated by cuproproteins. Since the state of copper in iron overload syndromes remains unclear, we investigated whether copper metabolism is altered in these syndromes. Eleven patients with iron overload syndromes participated in this study. The clinical diagnoses were aceruloplasminemia (n=2), hemochromatosis (n=5), ferroportin disease (n=2), and receiving excess intravenous iron supplementation (n=2). Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray analyzer. In addition to a large amount of iron associated with oxygen and phosphorus, the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur, regardless of disease etiology. Two-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within hemosiderins. Copper stasis was unlikely in noncirrhotic patients. The enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in hemosiderins. In conclusion, we have demonstrated that copper accumulates in hemosiderins in iron overload conditions, perhaps due to alterations in copper metabolism. PMID:26356991

  1. [The clinical significance of glycosylated ferritin in iron overloads and hematopoietic malignancies].

    PubMed

    Takakuwa, Y; Miyazawa, K; Yoshikawa, O; Toyama, K

    1994-08-01

    Serum ferritin concentration had been known to represent the amount of total body iron and has been clinically used as a parameter to evaluate the iron storage pool in a whole body. Glycosylated (secreted) and non-glycosylated (non-secreted) forms of serum ferritin (sFt) have been reported by others based on the difference in their affinity to concanavalin-A binding. In this report, we assessed the amount of glycosylated serum ferritin (Glyco-sFt) and the ratio (%) of Glyco-sFt/in hematopoietic disorders including iron overloads (n = 10), leukemias (n = 36), malignant lymphomas (n = 10), multiple myelomas (n = 3) and myelodysplastic syndromes (n = 12). A high percentage of Glyco-sFt was observed in normal healthy controls (n = 18, 78.1 +/- 7.4%) and iron-overloads (61.1 +/- 17.8%) as compared with that in hematopoietic malignancies (43.8 +/- 23.4%, p < 0.001). The amount of Glyco-sFt in iron-overloads was higher than that in hematopoietic malignancies with hyperferritinemia (p < 0.005). These data demonstrated that the same part of serum ferritin in hematopoietic malignancies was the non-secreted form and appeared to be derived from tumor cell lysis. We conclude that assessment of Glyco-Ft is a useful parameter to distinguish iron-overloads from malignant hematopoietic disorders both displaying hyperferritinemia.

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

    PubMed

    Refaat, Marwan M; El Hage, Lea; Steffensen, Annette Buur; Hotait, Mostafa; Schmitt, Nicole; Scheinman, Melvin; Badhwar, Nitish

    2016-03-01

    The authors present a unique case of torsades de pointes in a β-thalassemia patient with early iron overload in the absence of any structural abnormalities as seen in hemochromatosis. Genetic testing showed a novel KCNQ1 gene mutation 1591C>T [Gln531Ter(X)]. Testing of the gene mutation in Xenopus laevis oocytes showed loss of function of the IKs current. The authors hypothesize that iron overload combined with the KCNQ1 gene mutation leads to prolongation of QTc and torsades de pointes. PMID:26920202

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

    PubMed Central

    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

  4. Chronic iron overload in rats induces oval cells in the liver.

    PubMed Central

    Smith, P. G.; Yeoh, G. C.

    1996-01-01

    Liver damage induced by a variety of agents including hepatocarcinogens, alcohol, and virus induces proliferation of oval cells. In this study, iron overloading of the liver is used as a means of inducing liver damage over an extended period to ascertain whether it promotes the appearance of oval cells. Rats were fed a 2% carbonyl-iron-supplemented diet for 3 or 6 months. Extensive iron deposits appeared periportally in hepatocytes and some Kupffer cells. Iron deposition was less pronounced pericentrally. Small oval-like cells, morphologically and immunocytochemically similar to CDE-derived oval cells, were identified and quantified. They first emerged periportally and subsequently in small tracts or foci nearer central regions and stained positively for alpha-fetoprotein, pi-class glutathione S-transferase, and the embryonic form of pyruvate kinase. They contained very few iron deposits and were classified as iron free. The major difference between CDE- and iron-overload-derived oval cells was that the latter were negative for transferrin. This study shows that cellular changes occurring in iron-overloaded rat liver are similar to those observed in rats placed on a hepatocarcinogenic diet and in rats chronically exposed to alcohol. Images Figure 1 Figure 2 Figure 3 PMID:8701979

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

    PubMed

    Zhang, Ying; Wang, Hao; Cui, Lijing; Zhang, Yuanyuan; Liu, Yang; Chu, Xi; Liu, Zhenyi; Zhang, Jianping; Chu, Li

    2015-01-01

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

  6. The effect of iron overload on rat plasma and liver oxidant status in vivo.

    PubMed Central

    Dabbagh, A J; Mannion, T; Lynch, S M; Frei, B

    1994-01-01

    There is ample evidence implicating reactive oxygen species in a number of human degenerative diseases such as atherosclerosis and haemochromatosis. Although lipid peroxidation underlies many of the toxic effects of oxidative stress, there is a lack of a sensitive and reliable method for its assessment in vivo. To understand the implications of oxidative stress in vivo, we have used dietary iron overload (IO) in the rat. Oxidant status in these animals was determined by assessing depletion of endogenous antioxidants and formation of various lipid peroxidation products, including acylated F2-isoprostanes, a novel class of free-radical-derived prostaglandin-F2-like compounds. IO led to a significant decrease in the concentration of the antioxidants alpha-tocopherol and ascorbic acid in plasma, and alpha-tocopherol, beta-carotene and ubiquinol-10 in liver. Whereas there was no significant lipid peroxidation in plasma, hepatic F2-isoprostane levels were moderately but significantly increased in IO. In addition, IO caused a significant increase in plasma total and high-density lipoprotein cholesterol levels, an effect that was correlated with depletion of plasma ascorbic acid but not alpha-tocopherol. The data demonstrate that IO causes lipid metabolism disturbances and oxidative stress which is associated with substantial depletion of endogenous antioxidants and moderate lipid peroxidative damage. PMID:8010963

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

    PubMed Central

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

    2013-01-01

    ABSTRACT To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions. PMID:24488397

  8. Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major.

    PubMed

    Angelucci, Emanuele; Pilo, Federica

    2016-03-01

    Solid evidence has established the negative impact of high iron burden and related tissue damage on the outcome of hemopoietic stem cell transplantation for thalassemia major. Recent improvements in our knowledge of iron metabolism have been focused on elevated non-transferrin-bound iron and labile plasma iron levels in the peritransplantation period as potential contributors to tissue toxicity and subsequent adverse transplant outcome. As mouse models have shown, iron overload can injure bone marrow hematopoiesis by increasing reactive oxygen species. The Pesaro experience, conducted in the deferoxamine-only era, clearly defined three iron-related factors (liver fibrosis, hepatomegaly, and quality of lifelong chelation) as significantly affecting transplant outcome. The detrimental effect of iron has only been clarified in recent years. Active interventional strategies are ongoing. Although successful hematopoietic stem cell transplantation clinically resolves the thalassemia marrow defect, patients still remain carriers of iron overload and of all the clinical complications acquired during prior years of transfusion therapy. Therefore, adequate "iron diagnosis" and management is mandatory after hemopoietic stem cell transplantation. In transplanted thalassemia patients, body iron should be returned to within the normal range. Phlebotomy is the gold standard to reduce iron burden; though deferoxamine is a proven, acceptable alternative, clinical investigations on deferasirox are ongoing. PMID:26999450

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

    PubMed

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

    2008-05-21

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

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

    PubMed Central

    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

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

    PubMed

    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.

  12. Differential expression of stress-inducible proteins in chronic hepatic iron overload

    SciTech Connect

    Brown, Kyle E. Broadhurst, Kimberly A.; Mathahs, M. Meleah; Weydert, Jamie

    2007-09-01

    Introduction:: Oxidative stress can trigger a cellular stress response characterized by induction of antioxidants, acute phase reactants (APRs) and heat shock proteins (HSPs), which are presumed to play a role in limiting tissue damage. In rodents, hepatic iron overload causes oxidative stress that results in upregulation of antioxidant defenses with minimal progressive liver injury. The aim of this study was to determine whether iron overload modulates expression of other stress-responsive proteins such as APRs and HSPs that may confer protection against iron-induced damage in rodent liver. Methods:: Male rats received repeated injections of iron dextran or dextran alone over a 6-month period. Hepatic transcript levels for a panel of APRs and HSPs were quantitated by real-time PCR and protein expression was evaluated by Western blot and immunohistochemistry. Results:: Hepatic iron concentrations were increased > 50-fold in the iron-loaded rats compared to controls. Iron loading resulted in striking increases in mRNAs for Hsp32 (heme oxygenase-1; 12-fold increase vs. controls) and metallothionein-1 and -2 (both increased {approx} 6-fold). Transcripts for {alpha}1-acid glycoprotein, the major rat APR, were increased {approx} 3-fold, while expression of other classical APRs was unaltered. Surprisingly, although mRNA levels for the HSPs were not altered by iron, the abundance of Hsp25, Hsp70 and Hsp90 proteins was uniformly reduced in the iron-loaded livers, as were levels of NAD(P)H:quinone oxidoreductase 1, an Hsp70 client protein. Conclusions:: Chronic iron administration elicits a unique pattern of stress protein expression. These alterations may modulate hepatic responses to iron overload, as well as other injury processes.

  13. Effects of iron and copper overload on the human liver: an ultrastructural study.

    PubMed

    Fanni, D; Fanos, V; Gerosa, C; Piras, M; Dessi, A; Atzei, A; Van, Eyken P; Gibo, Y; Faa, G

    2014-01-01

    Iron and copper ions play important roles in many physiological functions of our body, even though the exact mechanisms regulating their absorption, distribution and excretion are not fully understood. Metal-related human pathology may be observed in two different clinical settings: deficiency or overload. The overload in liver cells of both trace elements leads to multiple cellular lesions. Here we report the main pathological changes observed at transmission electron microscopy in the liver of subjects affected by Beta-thalassemia and by Wilson's disease. The hepatic iron overload in beta-thalassemia patients is associated with haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes. Haemosiderin granules are grouped inside voluminous lysosomes, also called siderosomes. Other ultrastructural changes are fat droplets, proliferation of the smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and infiltration of sinusoids by polymorphonucleates is also detected in beta-thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease patients are characterized by severe mitochondrial changes, associated with an increased number of perossisomes, cytoplasmic lipid droplets and the presence of lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles surrounded by electron-dense lysosomes. In patients affected by Wilson's disease, nuclei are frequently involved, with disorganization of the nucleoplasm and with glycogen inclusions. On the contrary, no significant changes are detected in Kupffer cells. Our data show that iron and copper, even though are both transition metals, are responsible of different pathological changes at ultrastructural level. In particular, copper overload is associated with mitochondrial damage, whereas iron overload only rarely may cause severe mitochondrial changes. These differences underlay the need for further studies in which biochemical analyses should be associated with

  14. Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: A pilot study.

    PubMed

    Ghavamzadeh, Ardeshir; Mirzania, Mehrzad; Kamalian, Naser; Sedighi, Nahid; Azimi, Parisima

    2015-04-01

    Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta-thalassemia major, but liver iron overload in these patients will not decrease and hepatic fibrosis may still progress despite successful HSCT. Liver biopsy samples were taken from 14 patients (Out of 25 patients) who underwent HSCT. All patients met three criteria: negative HCV antibody, liver fibrosis in samples before HSCT and lack of regular treatment for iron overload after HSCT (Because patients did not consent to phlebotomy or they had not regular follow-up). We evaluated liver fibrosis and liver iron overload by a semi quantitative method, Perls' Prussian blue staining, before and after HSCT. HSCT was successful in all the patients. Liver iron overload did not change after transplant (P=0.61), but hepatic fibrosis progressed after transplant (P=0.01). In patients with beta thalassemia major who previously had some degree of liver fibrosis, HSCT alone cannot reduce liver iron overload and liver fibrosis will increase. We recommend that regardless of the amount of iron overload in patients with beta thalassemia major that have shown some degree of fibrosis in their liver biopsy before transplantation, appropriate steps should be taken to reduce iron overload as soon as possible after successful transplantation.

  15. Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: A pilot study

    PubMed Central

    Ghavamzadeh, Ardeshir; Mirzania, Mehrzad; Kamalian, Naser; Sedighi, Nahid; Azimi, Parisima

    2015-01-01

    Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta-thalassemia major, but liver iron overload in these patients will not decrease and hepatic fibrosis may still progress despite successful HSCT. Liver biopsy samples were taken from 14 patients (Out of 25 patients) who underwent HSCT. All patients met three criteria: negative HCV antibody, liver fibrosis in samples before HSCT and lack of regular treatment for iron overload after HSCT (Because patients did not consent to phlebotomy or they had not regular follow-up). We evaluated liver fibrosis and liver iron overload by a semi quantitative method, Perls’ Prussian blue staining, before and after HSCT. HSCT was successful in all the patients. Liver iron overload did not change after transplant (P=0.61), but hepatic fibrosis progressed after transplant (P=0.01). In patients with beta thalassemia major who previously had some degree of liver fibrosis, HSCT alone cannot reduce liver iron overload and liver fibrosis will increase. We recommend that regardless of the amount of iron overload in patients with beta thalassemia major that have shown some degree of fibrosis in their liver biopsy before transplantation, appropriate steps should be taken to reduce iron overload as soon as possible after successful transplantation. PMID:25922644

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

    PubMed Central

    Barbosa, Maritza Cavalcante; dos Santos, Talyta Ellen Jesus; de Souza, Geane Félix; de Assis, Lívia Coêlho; Freitas, Max Victor Carioca; Gonçalves, Romélia Pinheiro

    2013-01-01

    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. PMID:23580881

  17. Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

    PubMed

    McLaren, Gordon D; Gordeuk, Victor R

    2009-01-01

    Hemochromatosis comprises a group of inherited disorders resulting from mutations of genes involved in regulating iron metabolism. The multicenter, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study screened approximately 100,000 participants in the US and Canada, testing for HFE mutations, serum ferritin and transferrin saturation. As in other studies, HFE C282Y homozygosity was common in Caucasians but rare in other ethnic groups, and there was a marked heterogeneity of disease expression in C282Y homozygotes. Nevertheless, this genotype was often associated with elevations of serum ferritin and transferrin saturation and with iron stores of more than four grams in men but not in women. If liver biopsy was performed, in some cases because of evidence of hepatic dysfunction, fibrosis or cirrhosis was often found. Combined elevations of serum ferritin and transferrin saturation were observed in non-C282Y homozygotes of all ethnic groups, most prominently Asians, but not often with iron stores of more than four grams. Future studies to discover modifier genes that affect phenotypic expression in C282Y hemochromatosis should help identify patients who are at greatest risk of developing iron overload and who may benefit from continued monitoring of iron status to detect progressive iron loading.

  18. Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Morgan, Jennifer L. L.; Quiriarte, Heather A.; Sams, Clarence F.; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of: (1) peripheral leukocyte distribution, (2) plasma cytokine levels and (3) cytokine production profiles following whole blood mitogenic stimulation

  19. Iron overload, cardiac and other factors affecting pregnancy in thalassemia major.

    PubMed

    Tsironi, Maria; Karagiorga, Markissia; Aessopos, Athanasios

    2010-06-01

    The reproductive thalassemic population is growing older and doctors confront the challenge of the thalassemic pregnancy. Pregnancy is characterized by dynamic multiple system changes, resulting in increased basal oxygen consumption, changes in energy substrate use by different organs and increased susceptibility to oxidative stress, while homozygous transfusion-dependent beta-thalassemia (beta-thal) patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Pregnant thalassemic patients require significantly larger amount of total blood transfusion during pregnancy and iron overload increases the oxidative stress of pregnancy, while the risk for cardiovascular events, in a high cardiac output state, is augmented and chelation treatment is generally avoided due to the potential teratogenicity. Pregnancy in thalassemia major should be considered high risk, and be cared for by an expert team with special caution and sensitivity.

  20. Synthesis of polymers containing 3-hydroxypyridin-4-one bidentate ligands for treatment of iron overload

    PubMed Central

    Saghaie, Lotfollah; Liu, Dy; Hider, Robert C

    2015-01-01

    Iron overload is a clinical problem which can be prevented by using iron chelating agents. An alternative method of relieving iron overload is to reduce iron absorption from the intestine by administering specific iron chelating agents, which can bind iron to form nonabsorbable complexes. Based on this strategy, a series of polymeric ligands containing the chelating moiety 3-hydroxypyridin-4-ones (HPOs) were synthesized. The synthetic route involves the benzylation of hydroxyl group of (2-methyl-3-hydroxypyran-4-one (maltol) and conversion of benzylated maltol to 3-benzyloxypyridin-4-one derivatives by using three suitable primary amines (2,6-diaminohexanoic acid (lysine) and 1,6-diaminohexane and 5-aminopentanol). The resulted compounds incorporated into polymer by copolymerization with acryloyl chloride using 2, 2’-azobisisobutyronitrile (AIBN) as the initiator. Finally, the benzyl groups of polymers were removed by catalytic hydrogenation (Pd/C). In this work, three final polymers of HPO derivatives namely poly-2-propylamido-6-(3- hydroxy -1,4-dihydro-2-methy-4-oxopyrid-1-yl) hexanoic acid, 6-(3-hydroxy-1, 4-dihydro-2-methyl-4-oxopyrid-1-yl) hexyl-1-polypropylamide and 5-(3-hydroxy-1-,4-dihydro-2-methyl-4-oxopyrid-1-yl)-1-polyacrylate pentane were synthesized. Identification and structural elucidation of compounds were achieved by proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR) and infrared (IR) spectroscopy. PMID:26600863

  1. Changes in transferrin saturation after treatment with the oral iron chelator deferiprone in patients with iron overload.

    PubMed Central

    al-Refaie, F N; De Silva, C E; Wonke, B; Hoffbrand, A V

    1995-01-01

    AIMS--To evaluate the changes in transferrin saturation in patients with iron overload following the oral administration of the iron chelator deferiprone; to assess the correlation between the degree of transferrin desaturation, the deferiprone dose, and urinary iron excretion. METHODS--Serum samples were obtained from 16 patients with iron overload at different time intervals following the oral administration of deferiprone (50 mg/kg). These samples were analysed using 6M urea/polyacrylamide gel electrophoresis (UPAGE). This method is able to resolve serum transferrin into four different forms (free iron, two forms of monoferric, and diferric). The deferiprone concentration in these samples was estimated using high pressure liquid chromatography (HPLC). Zero time samples (t0) from 10 patients were incubated with 150 microM deferiprone or normal saline either at room temperature or at 37 degrees C for 30 minutes and 24 hours, and also at -20 degrees C for six weeks. Samples were then analysed using UPAGE. RESULTS--A maximum decrease in transferrin saturation from (mean (SD)) 93.0 (10.6)% to 54.5 (17.2)% was observed 72.5 (50.0) minutes after deferiprone administration and in most of the patients coincided with peak deferiprone concentration. This was associated with a maximum rise in the percentage of iron free transferrin (apotransferrin) from 2.9 (7.0)% to 27.3 (17.8)%. The total amount of iron estimated to be removed from transferrin constituted 21.3 (20.2)% of the 24 hour urinary iron excretion measured during the study. When deferiprone (150 mumol/l) was incubated in vitro with t0 samples from 10 patients for 30 minutes and 24 hours at room temperature, 37 degrees C, and at -20 degrees C for six weeks, deferiprone was more efficient at removing iron from transferrin at 37 degrees C, with maximum transferrin desaturation accomplished within 30 minutes compared with 24 hours at room temperature. CONCLUSIONS--The results confirm that deferiprone can remove iron

  2. mRNA regulation of cardiac iron transporters and ferritin subunits in a mouse model of iron overload.

    PubMed

    Brewer, Casey J; Wood, Ruth I; Wood, John C

    2014-12-01

    Iron cardiomyopathy is the leading cause of death in iron overload. Men have twice the mortality rate of women, though the cause is unknown. In hemojuvelin-knockout mice, a model of the disease, males load more cardiac iron than females. We postulated that sex differences in cardiac iron import cause differences in cardiac iron concentration. Reverse transcription polymerase chain reaction was used to measure mRNA of cardiac iron transporters in hemojuvelin-knockout mice. No sex differences were discovered among putative importers of nontransferrin-bound iron (L-type and T-type calcium channels, ZRT/IRT-like protein 14 zinc channels). Transferrin-bound iron transporters were also analyzed; these are controlled by the iron regulatory element/iron regulatory protein (IRE/IRP) system. There was a positive relationship between cardiac iron and ferroportin mRNA in both sexes, but it was significantly steeper in females (p < 0.05). Transferrin receptor 1 and divalent metal transporter 1 were more highly expressed in females than males (p < 0.01 and p < 0.0001, respectively), consistent with their lower cardiac iron levels, as predicted by IRE/IRP regulatory pathways. Light-chain ferritin showed a positive correlation with cardiac iron that was nearly identical in males and females (R(2) = 0.41, p < 0.01; R(2) = 0.56, p < 0.05, respectively), whereas heavy-chain ferritin was constitutively expressed in both sexes. This represents the first report of IRE/IRP regulatory pathways in the heart. Transcriptional regulation of ferroportin was suggested in both sexes, creating a potential mechanism for differential set points for iron export. Constitutive heavy-chain-ferritin expression suggests a logical limit to cardiac iron buffering capacity at levels known to produce heart failure in humans. PMID:25220979

  3. Antioxidative effects of lactic acid bacteria on the colonic mucosa of iron-overloaded mice.

    PubMed

    Ito, Masahiko; Ohishi, Kenji; Yoshida, Yasuto; Yokoi, Wakae; Sawada, Haruji

    2003-07-16

    The antioxidative effects of lactic acid bacteria on lipid peroxidation in the colonic mucosa were investigated. Among 49 strains of lactic acid bacteria, Streptococcus thermophilus YIT 2001 showed the highest inhibitory activity against lipid peroxidation in liposomes induced by ferrous iron. Feeding a diet containing 0.4% St. thermophilus YIT 2001 (2 x 10(8) colony-forming units per mouse per day) for 2 weeks caused a significant decrease of lipid peroxide (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overloaded mice (0.07% Fe in the diet). The mucosal lipid peroxide level did not correlate with the soluble iron concentration of the cecal contents. Therefore, it is suggested that the antioxidative effect of St. thermophilus YIT 2001 in the colonic mucosa was not due to the removal of ferrous iron from the reaction system of lipid peroxidation. PMID:12848525

  4. Iron Overload Causes Alterations of E-Cadherin in the Liver.

    PubMed

    Fujikura, Y; Krijt, J; Povýšil, C; Mělková, Z; Přikryl, P; Vokurka, M; Nečas, E

    2016-01-01

    Iron overload causes tissue damage in the liver, but its initial effects at the molecular and cellular level are not well understood. Epithelial cadherin (E-cad) is a major adhesion protein in adherens junctions and is associated with several signal transduction pathways. Dysfunction of E-cad causes instability of adherens junctions, which leads to cell invasion, cell migration, and carcinogenesis. We found in liver samples from iron-overloaded mice that the apparent molecular mass of E-cad was reduced from 125 to 115 kDa in sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and immunoblotting, and that the cellular expression of E-cad was decreased in immunohistochemistry. The mRNA level of E-cad, however, did not change significantly, suggesting that the alterations are posttranslational. Interestingly, incubation of control liver extracts with Fe2+ alone also produced the same mobility shift. Neither an oxidant nor an antioxidant influenced this shift in vitro, suggesting that reactive oxygen species, which are generated by iron and known to cause damage to macromolecules, are not involved. Treatment of the 115 kDa E-cad with deferoxamine, an iron chelator, thus removing Fe2+, shifted the molecular mass back to 125 kDa, demonstrating that the shift is reversible. The observation also implies that the alteration that causes the mobility shift is not due to transcriptional control, deglycosylation, and proteolysis. This reversible mobility shift of E-cad has not been previously known. The alteration of E-cad that causes the mobility shift might be an initial step to liver diseases by iron overload. PMID:27516188

  5. Duodenal Absorption and Tissue Utilization of Dietary Heme and Nonheme Iron Differ in Rats123

    PubMed Central

    Cao, Chang; Thomas, Carrie E.; Insogna, Karl L.; O'Brien, Kimberly O.

    2014-01-01

    Background: Dietary heme contributes to iron intake, yet regulation of heme absorption and tissue utilization of absorbed heme remains undefined. Objectives: In a rat model of iron overload, we used stable iron isotopes to examine heme- and nonheme-iron absorption in relation to liver hepcidin and to compare relative utilization of absorbed heme and nonheme iron by erythroid (RBC) and iron storage tissues (liver and spleen). Methods: Twelve male Sprague-Dawley rats were randomly assigned to groups for injections of either saline or iron dextran (16 or 48 mg Fe over 2 wk). After iron loading, rats were administered oral stable iron in the forms of 57Fe-ferrous sulfate and 58Fe-labeled hemoglobin. Expression of liver hepcidin and duodenal iron transporters and tissue stable iron enrichment was determined 10 d postdosing. Results: High iron loading increased hepatic hepcidin by 3-fold and reduced duodenal expression of divalent metal transporter 1 (DMT1) by 76%. Nonheme-iron absorption was 2.5 times higher than heme-iron absorption (P = 0.0008). Absorption of both forms of iron was inversely correlated with hepatic hepcidin expression (heme-iron absorption: r = −0.77, P = 0.003; nonheme-iron absorption: r = −0.80, P = 0.002), but hepcidin had a stronger impact on nonheme-iron absorption (P = 0.04). Significantly more 57Fe was recovered in RBCs (P = 0.02), and more 58Fe was recovered in the spleen (P = 0.01). Conclusions: Elevated hepcidin significantly decreased heme- and nonheme-iron absorption but had a greater impact on nonheme-iron absorption. Differential tissue utilization of heme vs. nonheme iron was evident between erythroid and iron storage tissues, suggesting that some heme may be exported into the circulation in a form different from that of nonheme iron. PMID:25332470

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

    SciTech Connect

    Smith, A.G.; Carthew, P.; Francis, J.E.; Edwards, R.E.; Dinsdale, D. )

    1990-12-01

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

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

    PubMed Central

    Sousa, Leilismara; Garcia, Israel J. P.; Costa, Tamara G. F.; Silva, Lilian N. D.; Renó, Cristiane O.; Oliveira, Eneida S.; Tilelli, Cristiane Q.; Santos, Luciana L.; Cortes, Vanessa F.; Santos, Herica L.; Barbosa, Leandro A.

    2015-01-01

    Iron is an essential chemical element for human life. However, in some pathological conditions, such as hereditary hemochromatosis type 1 (HH1), iron overload induces the production of reactive oxygen species that may lead to lipid peroxidation and a change in the plasma-membrane lipid profile. In this study, we investigated whether iron overload interferes with the Na,K-ATPase activity of the plasma membrane by studying erythrocytes that were obtained from the whole blood of patients suffering from iron overload. Additionally, we treated erythrocytes of normal subjects with 0.8 mM H2O2 and 1 μM FeCl3 for 24 h. We then analyzed the lipid profile, lipid peroxidation and Na,K-ATPase activity of plasma membranes derived from these cells. Iron overload was more frequent in men (87.5%) than in women and was associated with an increase (446%) in lipid peroxidation, as indicated by the amount of the thiobarbituric acid reactive substances (TBARS) and an increase (327%) in the Na,K-ATPase activity in the plasma membrane of erythrocytes. Erythrocytes treated with 1 μM FeCl3 for 24 h showed an increase (132%) in the Na,K-ATPase activity but no change in the TBARS levels. Iron treatment also decreased the cholesterol and phospholipid content of the erythrocyte membranes and similar decreases were observed in iron overload patients. In contrast, erythrocytes treated with 0.8 mM H2O2 for 24 h showed no change in the measured parameters. These results indicate that erythrocytes from patients with iron overload exhibit higher Na,K-ATPase activity compared with normal subjects and that this effect is specifically associated with altered iron levels. PMID:26197432

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

    PubMed

    Sousa, Leilismara; Garcia, Israel J P; Costa, Tamara G F; Silva, Lilian N D; Renó, Cristiane O; Oliveira, Eneida S; Tilelli, Cristiane Q; Santos, Luciana L; Cortes, Vanessa F; Santos, Herica L; Barbosa, Leandro A

    2015-01-01

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

  9. Iron overload-related heart failure in a patient with transfusion-dependent myelodysplastic syndrome reversed by intensive combined chelation therapy.

    PubMed

    Pinto, Valeria; Balocco, Manuela; Ambaglio, Ilaria; Derchi, Giorgio; Malcovati, Luca; Forni, Gian Luca

    2015-11-01

    Patients with transfusion-dependent myelodysplastic syndromes (MDS) have an increased risk of cardiac events, due to both chronic anemia and iron overload. Here, we report the recovery of cardiac function after an intensive iron chelation therapy in a MDS patient who had developed heart failure due to iron overload.

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

    PubMed Central

    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

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

    PubMed Central

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

    2016-01-01

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

  12. Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

    PubMed Central

    Hernández Vázquez, Wendy Ivett; Solorio-Meza, Sergio; Albarrán-Tamayo, Froylán; Ramos-Rodríguez, Edna; Benítez- Bribiesca, Luis

    2016-01-01

    Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length. PMID:27800120

  13. Suppressive effects of bifidobacteria on lipid peroxidation in the colonic mucosa of iron-overloaded mice.

    PubMed

    Ito, M; Sawada, H; Ohishi, K; Yoshida, Y; Yokoi, W; Watanabe, T; Yokokura, T

    2001-07-01

    The antioxidative effects of live bifidobacteria on lipid peroxidation in the colonic mucosa were investigated. Bifidobacterium bifidum strain Yakult, which has been used for production of fermented milk, most effectively inhibited lipid peroxidation catalyzed by ferrous iron in liposomes among 10 species of bifidobacteria from human intestinal flora. Oral administration of B. bifidum strain Yakult for 2 wk significantly decreased the level of lipid peroxide (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overload mice (Fe 0.07% in diet). The iron concentrations in plasma and cecum contents were not affected by administration of B. bifidum strain Yakult. Bifidobacterium bifidum strain Yakult had no chelating or incorporating activity for ferrous iron in vitro. Therefore, the antioxidative effect of B. bifidum strain Yakult in the colonic mucosa was not thought to be based on the removal of ferrous iron from the reaction system of lipid peroxidation. These results suggested that B. bifidum strain Yakult protected the colonic mucosa from oxidative injury without inhibiting iron absorption. PMID:11467806

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

    PubMed

    Berdoukas, Vasilios; Farmaki, Kallistheni; Carson, Susan; Wood, John; Coates, Thomas

    2012-01-01

    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 use of other combinations in chelation treatment, some of which have been used only in a very limited fashion to date. All these advances in management require absolute cooperation and understanding of parents, children, and, subsequently, the patients themselves. Only with such cooperation can normal long-term survival be achieved, as

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

    PubMed Central

    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

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

    PubMed

    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

  17. Evolution of iron overload in patients with low-risk myelodysplastic syndrome: iron chelation therapy and organ complications.

    PubMed

    Remacha, Ángel F; Arrizabalaga, Beatriz; Villegas, Ana; Durán, María Soledad; Hermosín, Lourdes; de Paz, Raquel; Garcia, Marta; Diez Campelo, Maria; Sanz, Guillermo

    2015-05-01

    This study aimed to evaluate the evolution of iron overload, assessed by serum ferritin (SF), in transfusion-dependent lower risk patients with myelodysplastic syndrome (MDS), as well as to describe the occurrence of organ complications, and to analyze its relationship with iron chelation therapy. This observational retrospective study was conducted from March 2010 to March 2011 in 47 Spanish hospitals. A total of 263 patients with lower risk MDS (International Prognostic Scoring System [IPSS] low/intermediate-1 risk or Spanish Prognostic Index [SPI] 0-1 risk), transfusion-dependent, and who had received ≥10 packed red blood cells (PRBC) were included. At MDS diagnosis, patients received a mean of 2.8 ± 3.9 PRBC/month, and 8.7% of patients showed SF ≥1000 μg/L. Over the course of the disease, patients received a mean of 83.4 ± 83.3 PRBC, and 36.1% of patients presented SF ≥2500 μg/L. Cardiac, hepatic, endocrine, or arthropathy complications appeared/worsened in 20.2, 11.4, 9.9, and 3.8% of patients, respectively. According to investigator, iron overload was a main cause of hepatic (70.0%) and endocrine (26.9%) complications. A total of 96 (36.5%) patients received iron chelation therapy for ≥6 months, being deferasirox the most frequent first chelation treatment (71.9%). Chelation-treated patients showed longer overall survival (p < 0.001), leukemia-free survival (p = 0.007), and cardiac event-free survival (p = 0.017) than non-chelated patients. In multivariable analyses, age (p = 0.011), IPSS (p < 0.001), and chelation treatment (p = 0.015) were predictors for overall survival; IPSS (p = 0.014) and transfusion frequency (p = 0.001) for leukemia-free survival; and chelation treatment (p = 0.040) and Sorror comorbidity index (p = 0.039) for cardiac event-free survival. In conclusion, these results confirm the potential survival benefit of iron chelation therapy and provide additional evidence on the

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

    PubMed Central

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

    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 of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

  19. MicroRNAs and liver cancer associated with iron overload: therapeutic targets unravelled.

    PubMed

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

    2013-08-28

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

  20. Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone.

    PubMed

    Yatmark, Paranee; Morales, Noppawan Phumala; Chaisri, Urai; Wichaiyo, Surasak; Hemstapat, Warinkarn; Srichairatanakool, Somdet; Svasti, Saovaros; Fucharoen, Suthat

    2014-09-01

    The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180 mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygous β-globin knockout mice ((mu)β(th-3/+), BKO). The effects of deferiprone and deferoxamine in this model were investigated. The iron was distributed homogenously throughout the 4 liver lobes (left, caudate, right and median) and was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and nucleus membrane degeneration were observed as a result of iron overload in the WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis was observed only in the BKO mice with iron overload. In the heart, the iron accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of the myocardial fibers and cardiac myocyte degeneration were observed. Although the total liver iron was not significantly altered by iron chelation therapy, image analysis demonstrated a difference in the efficacies of two iron chelators. The major site of chelation was the extracellular compartment, but treatment with deferiprone also resulted in intracellular iron chelation. Interestingly, iron chelators reversed the pathological changes resulting from iron overload in WT and BKO mice despite being used for only a short treatment period. We suggest that some of these effects may be secondary to the anti-inflammatory activity of the chelators.

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

    PubMed

    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 pH<4. In a small survey that I made in dental practice, patients (patients did not report taking any medication; had no frequent gingival bleeding) that had extrinsic black 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.

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

    PubMed

    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 pH<4. In a small survey that I made in dental practice, patients (patients did not report taking any medication; had no frequent gingival bleeding) that had extrinsic black 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

  3. Effect of co-inheritance of β-thalassemia and hemochromatosis mutations on iron overload.

    PubMed

    López-Escribano, Herminio; Ferragut, Joana F; Parera, Maria M; Guix, Pilar; Castro, José A; Ramon, M Misericòrdia; Picornell, Antònia

    2012-01-01

    Co-inheritance of mutations in the HFE gene underlying hereditary hemocromatosis (HH) may play a role in the variability of iron status in patients with β-thalassemia (β-thal) minor. Different studies have yielded conflicting results: some suggest iron overload might arise from the interaction of the β-thal trait with homozygosity or even heterozygosity for HFE mutations and others that it was unrelated to the HFE genotype. Because of the high frequency of HFE mutations in the Balearic Islands, where the β-thal trait is also moderately common, it is of interest to evaluate the effect of the co-inheritance of mutations in both genes on the severity of iron loading. A retrospective analysis of 142 individuals heterozygous for β-thal was performed to investigate the effect of HFE mutations on iron status of these patients. No significant differences were detected between β-thal carriers with and without HFE mutations. These results suggest that in the Balearic population the β-thal trait does not tend to be aggravated by the co-inheritance of HFE mutations.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    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; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2* >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.

  6. The role of S-methylisothiourea hemisulfate as inducible nitric oxide synthase inhibitor against kidney iron deposition in iron overload rats

    PubMed Central

    Maleki, Maryam; Samadi, Melika; Khanmoradi, Mehrangiz; Nematbakhsh, Mehdi; Talebi, Ardeshir; Nasri, Hamid

    2016-01-01

    Background: Iron dextran is in common use to maintain iron stores. However, it is potentially toxic and may lead to iron deposition (ID) and impair functions of organs. Iron overload can regulate the expression of inducible nitric oxide synthase (iNOS) in some cells that has an important role in tissue destruction. S-methylisothiourea hemisulfate (SMT) is a direct inhibitor of iNOS, and this study was designed to investigate the effect of SMT against kidney ID in iron overload rats. Materials and Methods: 24 Wistar rats (male and female) were randomly assigned to two groups. Iron overloading was performed by iron dextran 100 mg/kg/day every other day for 2 weeks. In addition, during the study, groups 1 and 2 received vehicle and SMT (10 mg/kg, ip), respectively. Finally, blood samples were obtained, and the kidneys were prepared for histopathological procedures. Results: SMT significantly reduced the serum levels of creatinine and blood urea nitrogen. However, SMT did not alter the serum levels of iron and nitrite, and the kidney tissue level of nitrite. Co-administration of SMT with iron dextran did not attenuate the ID in the kidney. Conclusion: SMT, as a specific iNOS inhibitor, could not protect the kidney from ID while it attenuated the serum levels of kidney function biomarkers. PMID:27308268

  7. Estimation of dietary iron bioavailability from food iron intake and iron status.

    PubMed

    Dainty, Jack R; Berry, Rachel; Lynch, Sean R; Harvey, Linda J; Fairweather-Tait, Susan J

    2014-01-01

    Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000-2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19-64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1-40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration. PMID:25356629

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

    EPA Science Inventory

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

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

    PubMed

    Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

    2013-02-01

    In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload. PMID:23923610

  10. Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias.

    PubMed

    Di Tucci, Anna Angela; Matta, Gildo; Deplano, Simona; Gabbas, Attilio; Depau, Cristina; Derudas, Daniele; Caocci, Giovanni; Agus, Annalisa; Angelucci, Emanuele

    2008-09-01

    Only limited data are available regarding myocardial iron overload in adult patients with transfusion dependent acquired anemias. To address this topic using MRI T2* we studied 27 consecutive chronic transfusion dependent patients with acquired anemias: (22 myelodysplastic syndrome, 5 primary myelofibrosis). Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 39.8) milliseconds. Of the 24 analyzable patients, cardiac T2* correlated with transfusion burden (p=0.0002). No patient who had received less than 290 mL/kg of packed red blood cells (101 units=20 grams of iron) had a pathological cardiac T2* value (< 20 ms). All patients who had received at least 24 PRBC units showed MRI T2* detectable hepatic iron (liver T2* value iron overload (T2* <1.4 ms) showed cardiac T2* value indicative of dangerous myocardial iron deposition. Serum ferritin was not significantly correlated with cardiac T2* (p=0.24). Gradient echo T2* magnetic resonance imaging provides a rapid and reproducible method for detecting myocardial iron overload which developed after a heavy transfusion burden equal to or greater than 290 mL/kg of packed red blood cell units. PMID:18603557

  11. SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis.

    PubMed

    Jenkitkasemwong, Supak; Wang, Chia-Yu; Coffey, Richard; Zhang, Wei; Chan, Alan; Biel, Thomas; Kim, Jae-Sung; Hojyo, Shintaro; Fukada, Toshiyuki; Knutson, Mitchell D

    2015-07-01

    Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14(-/-) mice with Hfe(-/-) and Hfe2(-/-) mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.

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

    PubMed

    Frýdlová, Jana; Přikryl, Petr; Truksa, Jaroslav; Falke, Lucas L; Du, Xin; Gurieva, Iuliia; Vokurka, Martin; Krijt, Jan

    2016-01-01

    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.

  13. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders.

    PubMed

    Angelucci, Emanuele; Barosi, Giovanni; Camaschella, Clara; Cappellini, Maria Domenica; Cazzola, Mario; Galanello, Renzo; Marchetti, Monia; Piga, Antonio; Tura, Sante

    2008-05-01

    New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy. PMID:18413891

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

    PubMed

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

    2014-12-01

    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 demonstrates that, in thalassemic-derived osteoclasts, tartrate-resistant acid phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration. The vanilloid agonist resiniferatoxin dramatically reduces cathepsin K levels and osteoclast numbers in vitro, without affecting tartrate-resistant acid phosphatase expression. The iron chelators deferoxamine, deferiprone and deferasirox decrease both tartrate-resistant acid phosphatase and cathepsin K expression, as well as osteoclast activity. Taken together, these data show that transient receptor potential vanilloid type 1 activation/desensitization influences tartrate-resistant acid phosphatase expression and activity, and this effect is dependent on iron, suggesting a pivotal role for iron overload in the dysregulation of bone metabolism in patients with thalassemia major. Our applied pharmacology provides evidence for the potential of iron chelators to abrogate these effects by reducing osteoclast activity. Whether iron chelation therapy is capable of restoring bone health in humans requires further study, but the potential to provide dual benefits for patients with β-thalassemia major -preventing iron-overload and alleviating associated osteoporotic changes - is exciting.

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

    PubMed Central

    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 demonstrates that, in thalassemic-derived osteoclasts, tartrate-resistant acid phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration. The vanilloid agonist resiniferatoxin dramatically reduces cathepsin K levels and osteoclast numbers in vitro, without affecting tartrate-resistant acid phosphatase expression. The iron chelators deferoxamine, deferiprone and deferasirox decrease both tartrate-resistant acid phosphatase and cathepsin K expression, as well as osteoclast activity. Taken together, these data show that transient receptor potential vanilloid type 1 activation/desensitization influences tartrate-resistant acid phosphatase expression and activity, and this effect is dependent on iron, suggesting a pivotal role for iron overload in the dysregulation of bone metabolism in patients with thalassemia major. Our applied pharmacology provides evidence for the potential of iron chelators to abrogate these effects by reducing osteoclast activity. Whether iron chelation therapy is capable of restoring bone health in humans requires further study, but the potential to provide dual benefits for patients with β-thalassemia major –preventing iron-overload and alleviating associated osteoporotic changes – is exciting. PMID:25216685

  16. Decitabine treatment could ameliorate primary iron-overload in myelodysplastic syndrome patients.

    PubMed

    Shucheng, Gu; Chunkang, Chang; Youshan, Zhao; Juan, Guo; Chengming, Fei; Xi, Zhang; Chao, Xiao; Xiao, Li

    2015-04-01

    In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 μg/L to 366.77 ± 21.90 μg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.

  17. Determination of Serum Ferritin Glycosylation in Hyperferritinemia Associated to Iron Overload and Inflammation.

    PubMed Central

    Gasser, Bethina Isasi

    2009-01-01

    Background Serum ferritin is a commonly used clinical biochemical parameter and hyperferritinemia is used as a surrogate marker for iron overload, acute or chronic inflammation, malignancy or cell death. The aim of the present study was to develop purification strategies of ferritin from sera to determine if micro-heterogeneity of serum ferritin can be used to differentiate the underlying cause of the hyperferritinemia. Patients, Materials and Methods Sera from patients with hemochromatosis, rheumatologic diseases, aceruloplasminemia, ferroportin disease or iron loading anemia have been collected and stored and ferritin purified by negative affinity followed by ion exchange and size exclusion chromatography. Purified serum ferritin was analyzed by western blotting and MALDI TOF mass spectrometry and the spectra compared with the results from ferritin isolated from human liver, spleen and placenta. Results By Western blotting a major band of 19kD has been found in most sera, suggesting that the L-ferritin is the predominant isoform present in serum regardless of the cause of hyperferritinemia. Multistep chromatography can be used for significant enrichment and purification of ferritin from serum, which can be further analyzed by MALDI TOF MS. Tryptic digestion and peptide mass finger-printing by MALDI TOF MS of ferritin purified from human tissues shows differential spectra. Discussion and conclusions Analysis of ferritin micro-heterogeneity by MALDI TOF allows determination of the tissue origin of ferritin, which could be applied in the differential diagnostic workup of hyperferritinemia.

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

    PubMed

    Qiao, Yang; He, Huan; Zhang, Zeyu; Liao, Zhangping; Yin, Dong; Liu, Dan; Yi, Bo; He, Ming

    2016-01-01

    Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU). We determined the protective role of SF against liver injury by examining liver-to-body ratio (%), transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection. In addition, antioxidative enzymes activities, ROS formation, mitochondrial swelling, and mitochondrial membrane potential (MMP) were all evaluated to clarify the mechanism of protective effect of SF associated with oxidative stress. After 15 weeks of SF treatment, we found a significant reduction in liver-to-body weight radio and elevation in both transaminase and hepatocyte apoptosis associated with iron-injected to levels comparable to those achieved with TAU. Both SF and TAU significantly attenuated the impaired liver function associated with iron-overloaded in mice, whereas neither showed any significant effect on the iron uptake. Furthermore, treatment with either SF or TAU in iron-overloaded mice attenuated oxidative stress, associated with elevated oxidant enzymes activities, decreased ROS production, prevented mitochondrial swelling and dissipation of MMP and then inhibited hepatic apoptosis. Taken together, the current study shows that, SF alleviated oxidative stress and liver damage associated with iron-overload conditions compared to the standard ROS scavenger (TAU), and potentially could encourage higher consumption and utilization as healthy and sustainable ingredients by the food and drink. PMID:27649133

  19. Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity.

    PubMed

    Bernhardt, Paul V; Chin, Piao; Sharpe, Philip C; Richardson, Des R

    2007-08-14

    The potentially tridentate ligand 2-pyridinecarbaldehyde isonicotinoyl hydrazone (HPCIH) and its analogues are an emerging class of orally effective Fe chelators that show great promise for the treatment of Fe overload diseases. Herein, we present an extensive study of the Fe coordination chemistry of the HPCIH analogues including the first crystallographically characterised Fe(II) complex of these chelators. Unlike most other clinically effective Fe chelators, the HPCIH analogues bind Fe(II) and not Fe(III). In fact, these chelators form low-spin bis-ligand Fe(II) complexes, although NMR suggests that the complexes are close to the high-spin/low-spin crossover. All the Fe complexes show a high potential Fe(III/II) redox couple (> 500 mV vs. NHE) and cyclic voltammetry in aqueous or mixed aqueous/organic solvents is irreversible as a consequence of a rapid hydration reaction that occurs upon oxidation. A number of the HPCIH analogues show high activity at inducing Fe efflux from cells and also at preventing Fe uptake by cells from the serum Fe transport protein transferrin. As a class of ligands, these chelators are more effective at reducing Fe uptake from transferrin than inducing Fe mobilisation from cells. This may be related to their ability to intercept Fe(II) after its release from transferrin within the cell. Our studies indicate that their Fe chelation efficacy is due, at least in part, to the fact that these ligands and their Fe(II) complexes are neutral at physiological pH (7.4) and sufficiently lipophilic to permeate cell membranes. PMID:17893768

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

    PubMed

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

    2014-01-01

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

  1. Dietary protein alters tubular iron accumulation after partial nephrectomy.

    PubMed

    Nankivell, B J; Tay, Y C; Boadle, R A; Harris, D C

    1994-04-01

    Reactive oxygen species (ROS) have been implicated in progression of disease in the rat remnant kidney (RK) model of chronic renal failure. Substantial amounts of iron accumulate in proximal tubular lysosomes of RK and could damage tubules by ROS generation. The effect of dietary protein intake on ROS, tubular damage and iron accumulation assessed by energy dispersive analysis was determined in RK (5/6 nephrectomy, N = 12) and sham-operated kidneys (SO, N = 10). In RK, mean lysosomal iron concentration, urinary iron and protein excretion and morphological damage were increased and GFR decreased. Dietary protein loading (40% vs. 12%) increased the number of iron-containing lysosomes (P < 0.05) and the mean lysosomal iron (P < 0.02) in proximal tubular cells after four weeks. In RK, high protein diet increased renal weight (P < 0.01), numerical density of iron-containing lysosomes and tubular damage (both P < 0.05). ROS generation, assessed by tissue and plasma malondialdehyde (MDA), was also increased (both P < 0.05). Plasma MDA correlated with tubular iron accumulation (r = 0.75). In RK fed a high protein diet (N = 18) treatment with the iron-chelator desferrioxamine reduced serum iron, urinary volume, and tubular iron accumulation and damage compared to controls (P < 0.01). In summary, in RK dietary protein manipulation altered urinary iron and protein excretion, proximal tubular iron accumulation, renal cortical ROS generation and ultrastructural damage. Desferrioxamine treatment reduced tubular lysosomal iron and ultrastructural damage. These results suggest a role for tubular iron as a determinant of tubular injury associated with dietary protein loading in rats with partial nephrectomy.

  2. Iron Chelation

    MedlinePlus

    ... iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you have ... may want to perform: How quickly does iron overload happen? This is different for each person. It ...

  3. Variations in dietary iron alter behavior in developing rats.

    PubMed

    Piñero, D; Jones, B; Beard, J

    2001-02-01

    Iron deficiency in children is associated with retardation in growth and cognitive development, and the effects on cognition may be irreversible, even with treatment. Excessive iron has also been associated with neurological disease, especially in reference to the increased iron content in the brains of Alzheimer's disease and Parkinson's disease patients. This study evaluated the effects of dietary iron deficiency and excess iron on physical activity in rats. The animal model used is developmentally sensitive and permits control of the timing as well as the duration of the nutritional insult. Hence, to study the effects of early, late and long-term iron deficiency or excess iron (supplementation), rats were either made iron deficient or supplemented on postnatal day (PND) 10-21, PND 21-35 and PND 10-35. Some iron-deficient rats were iron repleted between PND 21-35. Different measures of motor activity were taken at PND 14, 17, 20, 27 and 34. Iron-deficient and iron-supplemented rats showed decreased activity and stereotypic behavior; this was apparent for any onset and duration of the nutritional insult. Recovery from iron deficiency did not normalize these functional variables, showing that the deleterious effects of early iron deficiency persist despite subsequent adequate treatment. This study demonstrates that iron deficiency in early life leads to irreversible behavioral changes. The biological bases for these behavioral alterations are not readily apparent, because iron therapy rapidly reverses the iron losses in all brain regions.

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

    PubMed

    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 < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain 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

  5. Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload.

    PubMed

    Montaldo, Claudia; Mattei, Simone; Baiocchini, Andrea; Rotiroti, Nicolina; Del Nonno, Franca; Pucillo, Leopoldo Paolo; Cozzolino, Angela Maria; Battistelli, Cecilia; Amicone, Laura; Ippolito, Giuseppe; van Noort, Vera; Conigliaro, Alice; Alonzi, Tonino; Tripodi, Marco; Mancone, Carmine

    2014-05-01

    Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighted the hepatocytic vitronectin expression as the most promising specific biomarker for iron-associated fibrogenesis in HCV infections. Next, the robustness of our in vitro findings was challenged in human liver biopsies by immunohistochemistry and yielded two major results: (i) hepatocytic vitronectin expression is associated to liver fibrogenesis in HCV-infected patients with iron overload; (ii) hepatic vitronectin expression was found to discriminate also the transition between mild to moderate fibrosis in HCV-infected patients without iron overload.

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

    PubMed

    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

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

    PubMed Central

    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

  8. Serum ferritin concentrations in Africans with low dietary iron.

    PubMed

    Moyo, Victor M; Mvundura, Elisha; Khumalo, Hlosukwazi; Gangaidzo, Innocent T; Saungweme, Thokozile; Nouraie, Mehdi; Rouault, Tracey A; Gomo, Zvenyika A R; Gordeuk, Victor R

    2009-11-01

    In the setting of high dietary, several studies have provided evidence for a strong effect of both high dietary iron and an unidentified genetic locus on iron stores in Africans. To investigate whether these effects are discernible in the setting of low dietary iron, serum ferritin concentrations were measured in 194 Zimbabwean men >30 years of age and 299 postmenopausal women who consumed a non-iron-fortified diet and who did not drink iron-rich traditional beer or other alcoholic beverages. Comparisons were made with non-alcohol drinking African-Americans studied in the third National Health and Nutritional Examination Survey (NHANES III) who consume an iron-fortified diet. As stratified by age and sex, serum ferritin concentrations were significantly lower in the 493 Zimbabweans studied than in 1,380 comparable African-Americans (P < 0.0005). Nevertheless, nine Zimbabwean subjects (1.8% of all cases) had modestly elevated serum ferritin concentrations not associated with evidence of inflammation or hepatic dysfunction. These data suggest that mild serum ferritin concentration elevations may occur among Zimbabweans not exposed to high dietary iron and that iron fortification of the diet may have substantial effects on serum ferritin concentration.

  9. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    PubMed

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling.

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

    NASA Technical Reports Server (NTRS)

    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

  11. En Route to New Therapeutic Options for Iron Overload Diseases: Matriptase-2 as a Target for Kunitz-Type Inhibitors.

    PubMed

    Beckmann, Anna-Madeleine; Maurer, Eva; Lülsdorff, Verena; Wilms, Annika; Furtmann, Norbert; Bajorath, Jürgen; Gütschow, Michael; Stirnberg, Marit

    2016-04-01

    The cell-surface serine protease matriptase-2 is a critical stimulator of iron absorption by negatively regulating hepcidin, the key hormone of iron homeostasis. Thus, it has attracted much attention as a target in primary and secondary iron overload diseases. Here, we have characterised Kunitz-type inhibitors hepatocyte growth factor activator inhibitor 1 (HAI-1) and HAI-2 as powerful, slow-binding matriptase-2 inhibitors. The binding modes of the matriptase-2-HAI complexes were suggested by molecular modelling. Different assays, including cell-free and cell-based measurements of matriptase-2 activity, determination of inhibition constants and evaluation of matriptase-2 inhibition by analysis of downstream effects in human liver cells, demonstrated that matriptase-2 is an excellent target for Kunitz inhibitors. In particular, HAI-2 is considered a promising scaffold for the design of potent and selective matriptase-2 inhibitors.

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

    SciTech Connect

    Guenancia, Charles; Li, Na; Hachet, Olivier; Rigal, Eve; Cottin, Yves; Dutartre, Patrick; Rochette, Luc; Vergely, Catherine

    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

  13. A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload.

    PubMed

    Sripetchwandee, Jirapas; Wongjaikam, Suwakon; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-09-22

    Iron-overload can cause cognitive impairment due to blood-brain barrier (BBB) breakdown and brain mitochondrial dysfunction. Although deferiprone (DFP) has been shown to exert neuroprotection, the head-to-head comparison among iron chelators used clinically on brain iron-overload has not been investigated. Moreover, since antioxidant has been shown to be beneficial in iron-overload condition, its combined effect with iron chelator has not been tested. Therefore, the hypothesis is that all chelators provide neuroprotection under iron-overload condition, and that a combination of an iron chelator with an antioxidant has greater efficacy than monotherapy. Male Wistar rats (n=42) were assigned to receive a normal diet (ND) or a high-iron diet (HFe) for 4months. At the 2nd month, HFe-fed rats were treated with a vehicle, deferoxamine (DFO), DFP, deferasirox (DFX), n-acetyl cysteine (NAC) or a combination of DFP with NAC, while ND-fed rats received vehicle. At the end of the experiment, rats were decapitated and brains were removed to determine brain iron level and deposition, brain mitochondrial function, BBB protein expression, brain mitochondrial dynamic, brain apoptosis, tau-hyperphosphorylation, amyloid-β (Aβ) accumulation and dendritic spine density. The results showed that iron-overload induced BBB breakdown, brain iron accumulation, brain mitochondrial dysfunction, impaired brain mitochondrial dynamics, tau-hyperphosphorylation, Aβ accumulation and dendritic spine reduction. All treatments, except DFX, attenuated these impairments. Moreover, combined therapy provided a greater efficacy than monotherapy. These findings suggested that iron-overload induced brain iron toxicity and a combination of an iron chelator with an antioxidant provided a greatest efficacy for neuroprotection than monotherapy.

  14. A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload.

    PubMed

    Sripetchwandee, Jirapas; Wongjaikam, Suwakon; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-09-22

    Iron-overload can cause cognitive impairment due to blood-brain barrier (BBB) breakdown and brain mitochondrial dysfunction. Although deferiprone (DFP) has been shown to exert neuroprotection, the head-to-head comparison among iron chelators used clinically on brain iron-overload has not been investigated. Moreover, since antioxidant has been shown to be beneficial in iron-overload condition, its combined effect with iron chelator has not been tested. Therefore, the hypothesis is that all chelators provide neuroprotection under iron-overload condition, and that a combination of an iron chelator with an antioxidant has greater efficacy than monotherapy. Male Wistar rats (n=42) were assigned to receive a normal diet (ND) or a high-iron diet (HFe) for 4months. At the 2nd month, HFe-fed rats were treated with a vehicle, deferoxamine (DFO), DFP, deferasirox (DFX), n-acetyl cysteine (NAC) or a combination of DFP with NAC, while ND-fed rats received vehicle. At the end of the experiment, rats were decapitated and brains were removed to determine brain iron level and deposition, brain mitochondrial function, BBB protein expression, brain mitochondrial dynamic, brain apoptosis, tau-hyperphosphorylation, amyloid-β (Aβ) accumulation and dendritic spine density. The results showed that iron-overload induced BBB breakdown, brain iron accumulation, brain mitochondrial dysfunction, impaired brain mitochondrial dynamics, tau-hyperphosphorylation, Aβ accumulation and dendritic spine reduction. All treatments, except DFX, attenuated these impairments. Moreover, combined therapy provided a greater efficacy than monotherapy. These findings suggested that iron-overload induced brain iron toxicity and a combination of an iron chelator with an antioxidant provided a greatest efficacy for neuroprotection than monotherapy. PMID:27403880

  15. Longitudinal MRI and Ferritin Monitoring of Iron Overload in Chronically Transfused and Chelated Children With Sickle Cell Anemia and Thalassemia Major.

    PubMed

    Aubart, Mélodie; Ou, Phalla; Elie, Caroline; Canniffe, Carla; Kutty, Shelby; Delos, Vincent; Graffigne, Christine; de Montalembert, Mariane; Brousse, Valentine

    2016-10-01

    Iron overload is an ineluctable complication in chronically transfused children warranting accurate assessment to avoid related morbidity. We investigated longitudinally the relationships between ferritin levels and hepatic and cardiac T2* magnetic resonance imaging (MRI) in a cohort of chronically transfused children receiving chelation therapy. Thirty children with sickle cell anemia (SCA) and 7 with thalassemia major (TM) chelated similarly by deferasirox were analyzed. Sex ratio, age, median duration of transfusion programs (5 y; range, 2 to 14 y), median transfusion iron intake 0.54 mg/kg/d (range, 0.27 to 0.74 mg/kg/d), and median ferritin level (1550 mg/L; range, 184 to 6204 mg/L) were comparable in TM and SCA. A significant relation was found between ferritin level and transfusion iron intake (P<0.001) despite chelation therapy. Analysis of 73 hepatic T2* MRI performed yearly demonstrated severe hepatic iron overload (≥14 mg/g) in 38.3% cases and a strong relationship between serum ferritin level and liver iron content both in SCA and TM (P<0.001). Analysis of 55 cardiac T2* MRI measurements found no cardiac overload in patients with SCA. Cardiac iron overload was moderate in 4 cases and severe in 1 case of TM. In almost half the cases, ferritin trend correctly predicted hepatic iron trend, both in patients with SCA and TM but failed to predict cardiac iron trend, notably in TM patients. Despite chelation therapy, iron burden in chronically transfused patients remains a threat. Ferritin levels are associated with liver iron overload in chelated children with SCA and TM, but iron burden should be best monitored with MRI whenever the setting allows it. PMID:27548334

  16. Effects of Dietary Iron and Gamma Radiation on the Rat Retina

    NASA Technical Reports Server (NTRS)

    Morgan, Jennifer; Marshall, Grace; Theriot, Corey A.; Chacon, Natalia; Zwart, Sara; Zanello, Susana B.

    2012-01-01

    A health risk of concern for NASA relates to radiation exposure and its synergistic effects with other space environmental factors, includi ng nutritional status of the crew. Astronauts consume almost three times the recommended daily allowance of iron due to the use of fortifie d foods aboard the International Space Station, with iron intake occa sionally exceeding six times the recommended values. Recently, NASA has become concerned with visual changes associated with spaceflight, a nd research is being conducted to elucidate the etiology of eye structure alterations in the spaceflight environment. Terrestrially, iron o verload is also associated with certain optic neuropathies. In additi on, due to its role in Fenton reactions, iron can potentiate oxidative stress, which is a recognized cause of cataract formation. As part o f a study investigating the combined effects of radiation exposure an d iron overload on multiple physiological systems, we focused on defining the effects of both treatments on eye biology. In this study, 12- week-old Sprague-Dawley rats were assigned to one of four experimental groups: normal iron/no radiation (Control/Sham), high iron/no radiat ion (Fe/Sham), normal iron/gamma radiation (3 Gy cumulative dose, fra ctionated at 0.375 Gy/d every other day for 16 d) (Control/Rad), and high iron/gamma radiation (Fe/Rad). Oxidative stress-induced DNA damag e, measured as concentration of the marker 8-hydroxy-2'-deoxyguanosine (8OHdG) in eye retinal tissue by enzyme-immunoanalysis did not show significant changes among treatments. However, there was an overall i ncrease in 8OHdG immunostaining density in retina sections due to radiation exposure (P = 0.05). Increased dietary iron and radiation expos ure had an interactive effect (P = 0.02) on 8OHdG immunostaining of t he retinal ganglion cell layer with iron diet increasing the signal in the group not exposed to radiation (P = 0.05). qPCR gene expression profiling of relevant target genes

  17. Dietary Omega-3 Polyunsaturated Fatty Acids Suppress NHE-1 Upregulation in a Rabbit Model of Volume- and Pressure-Overload

    PubMed Central

    van Borren, Marcel M. G. J.; den Ruijter, Hester M.; Baartscheer, Antonius; Ravesloot, Jan H.; Coronel, Ruben; Verkerk, Arie O.

    2012-01-01

    . Conclusion: Dietary ω3-PUFAs from FO suppress upregulation of the NHE-1 activity and lower the incidence of DADs in our rabbit model of volume- and pressure-overload. PMID:22485092

  18. Evaluation of the Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Morgan, Jennifer L. L.; Quiriarte, Heather A.; Sams, Clarence F.; Smith, Scott M.; Zwart, Sara R.

    2011-01-01

    NASA is concerned with the health risks to astronauts, particularly those risks related to radiation exposure. Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of (A) peripheral leukocyte distribution; (B) plasma cytokine levels; (C) cytokine production profiles following whole blood stimulation of either T cells or monocytes.

  19. Dietary phosphate supplementation delays the onset of iron deficiency anemia and affects iron status in rats.

    PubMed

    Nakao, Mari; Yamamoto, Hironori; Nakahashi, Otoki; Ikeda, Shoko; Abe, Kotaro; Masuda, Masashi; Ishiguro, Mariko; Iwano, Masayuki; Takeda, Eiji; Taketani, Yutaka

    2015-11-01

    Inorganic phosphate (Pi) plays critical roles in bone metabolism and is an essential component of 2,3-diphosphoglycerate (2,3-DPG). It has been reported that animals fed a low-iron diet modulate Pi metabolism, whereas the effect of dietary Pi on iron metabolism, particularly in iron deficiency anemia (IDA), is not fully understood. In this study, we hypothesized the presence of a link between Pi and iron metabolism and tested the hypothesis by investigating the effects of dietary Pi on iron status and IDA. Wistar rats aged 4 weeks were randomly assigned to 1 of 4 experimental dietary groups: normal iron content (Con Fe)+0.5% Pi, low-iron (Low Fe)+0.5% Pi, Con Fe+1.5% Pi, and Low Fe+1.5% Pi. Rats fed the 1.5% Pi diet for 14 days, but not for 28 days, maintained their anemia state and plasma erythropoietin concentrations within the reference range, even under conditions of low iron. In addition, plasma concentrations of 2,3-DPG were significantly increased by the 1.5% Pi diets and were positively correlated with plasma Pi concentration (r=0.779; P<.001). Dietary Pi regulated the messenger RNA expression of iron-regulated genes, including divalent metal transporter 1, duodenal cytochrome B, and hepcidin. Furthermore, iron concentration in liver tissues was increased by the 1.5% Pi in Con Fe diet. These results suggest that dietary Pi supplementation delays the onset of IDA and increases plasma 2,3-DPG concentration, followed by modulation of the expression of iron-regulated genes.

  20. Interactions among dietary manganese, heme iron, and nonheme iron in women.

    PubMed

    Davis, C D; Malecki, E A; Greger, J L

    1992-11-01

    The relationship among dietary intake of heme iron, nonheme iron, and manganese on indexes of hematological and nutritional status in regard to manganese of 47 women consuming their typical diets was investigated. Increasing dietary iron intake, by consuming more nonheme iron in the diet, had questionable effects on hematological status (hematocrit values and ferritin and transferrin concentrations) and negative effects on nutritional status in regard to manganese (serum manganese, urine manganese, and lymphocyte manganese-dependent superoxide dismutase activity). In contrast, heme-iron intake was positively correlated with hematological status and had no consistent effect on nutritional status in regard to manganese. Differences in dietary manganese intake had no consistent effect on indices of manganese or iron status, possibly because foods that contain significant amounts of manganese (green vegetables, breads, and cereals) often contain significant amounts of nonheme iron. Thus, increasing dietary manganese intake by consuming these foods is apt to have limited impact on manganese status because of the interaction between nonheme iron and manganese. PMID:1415012

  1. Glutathione synthesis inhibitor butathione sulfoximine regulates ceruloplasmin by dual but opposite mechanism: Implication in hepatic iron overload.

    PubMed

    Tapryal, Nisha; Mukhopadhyay, Chaitali; Mishra, Manoj Kumar; Das, Dola; Biswas, Sudipta; Mukhopadhyay, Chinmay K

    2010-06-01

    Glutathione (GSH) depletion is often detected in chronic pathological conditions like hepatitis C infection, alcohol consumption or xenobiotic assault with simultaneous reactive oxygen species (ROS) generation and hepatic iron overload. However, relation between GSH depletion and regulators of iron homeostasis is not clear so far. To determine that hepatic HepG2 cells were treated with GSH synthesis inhibitor butathione sulfoximine (BSO) and a dual regulation of ceruloplasmin (Cp) that involves in hepatic iron release was detected unlike other iron homeostasis regulators. BSO treatment that caused marginal GSH deficiency increased Cp synthesis due to increased transcription mediated by activator protein (AP)-1-binding site. In higher GSH deficiency (> 40 %) with increased ROS generation, Cp expression was decreased due to promotion of Cp mRNA decay mediated by 3'untranslated region (3'UTR) as found by transfecting chimera of chloramphenicol acetyl transferase (CAT) gene with Cp 3'UTR. RNA gel shift assay showed significant reduction in 3'UTR binding protein complex in similar condition. Decreased CAT expression and RNA-protein complex binding are reversed by pretreatment with antioxidant N-acetyl cysteine suggesting 3'UTR binding protein complex is redox-sensitive. This unique and opposite regulation of Cp provides a mechanism of hepatic iron-deposition during glutathione deficiency detected in chronic pathological conditions.

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

    SciTech Connect

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

    1988-12-01

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

  3. Iron Test

    MedlinePlus

    ... detect and help diagnose iron deficiency or iron overload. In people with anemia , these tests can help ... also be ordered when iron deficiency or iron overload is suspected. Early iron deficiency often goes unnoticed. ...

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

    ClinicalTrials.gov

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Guenancia, Charles; Li, Na; Hachet, Olivier; Rigal, Eve; Cottin, Yves; Dutartre, Patrick; Rochette, Luc; Vergely, Catherine

    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 (15mg/kg) for 3weeks (D0-D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran-iron (125-1000μg/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.

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

    PubMed

    Guenancia, Charles; Li, Na; Hachet, Olivier; Rigal, Eve; Cottin, Yves; Dutartre, Patrick; Rochette, Luc; Vergely, Catherine

    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 (15mg/kg) for 3weeks (D0-D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran-iron (125-1000μg/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. PMID:25711856

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

    PubMed Central

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

    2016-01-01

    AIM: This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status. SUBJECTS AND METHODS: The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing. RESULTS: Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001). CONCLUSION: Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients. PMID:27335591

  9. Iron and the female athlete: a review of dietary treatment methods for improving iron status and exercise performance.

    PubMed

    Alaunyte, Ieva; Stojceska, Valentina; Plunkett, Andrew

    2015-01-01

    Iron is a functional component of oxygen transport and energy production in humans and therefore is a critically important micronutrient for sport and exercise performance. Athletes, particularly female athletes participating in endurance sport, are at increased risk of compromised iron status due to heightened iron losses through menstruation and exercise-induced mechanisms associated with endurance activity. Conventionally oral iron supplementation is used in prevention or/and treatment of iron deficiency. However, this approach has been criticised because of the side effects and increased risk of iron toxicity associated with the use of supplements. Thus, more recently there has been a growing interest in using dietary modification rather than the use of supplements to improve iron status of athletes. Dietary iron treatment methods include the prescription of an iron-rich diet, or/and haem iron-based diet, dietary advice counselling and inclusion of novel iron-rich products into the daily diet. Although studies using dietary modification are still scarce, current literature suggests that dietary iron interventions can assist in maintaining iron status in female athletes, especially during intensive training and competition. Future research should focus on the most efficient method(s) of dietary modification for improvement of iron status and whether these approaches can have a favourable impact on sports and exercise performance. PMID:26448737

  10. Iron uptake and homeostasis related genes in potato cultivated in vitro under iron deficiency and overload.

    PubMed

    Legay, Sylvain; Guignard, Cédric; Ziebel, Johanna; Evers, Danièle

    2012-11-01

    Potato is one of the most important staple food in the world because it is a good source of vitamin C, vitamin B6 but also an interesting source of minerals including mainly potassium, but also magnesium, phosphorus, manganese, zinc and iron to a lesser extent. The lack of iron constitutes the main form of micronutrient deficiency in the world, namely iron deficiency anemia, which strongly affects pregnant women and children from developing countries. Iron biofortification of major staple food such as potato is thus a crucial issue for populations from these countries. To better understand mechanisms leading to iron accumulation in potato, we followed in an in vitro culture experiment, by qPCR, in the cultivar Désirée, the influence of media iron content on the expression of genes related to iron uptake, transport and homeostasis. As expected, plantlets grown in a low iron medium (1 mg L(-1) FeNaEDTA) displayed a decreased iron content, a strong induction of iron deficiency-related genes and a decreased expression of ferritins. Inversely, plantlets grown in a high iron medium (120 mg L(-1) FeNaEDTA) strongly accumulated iron in roots; however, no significant change in the expression of our set of genes was observed compared to control (40 mg L(-1) FeNaEDTA).

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

    PubMed

    Link, G; Pinson, A; Hershko, C

    1985-08-01

    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.

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

    SciTech Connect

    Link, G.; Pinson, A.; Hershko, C.

    1985-08-01

    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 /sup 59/Fe-transferrin, 15.8% for /sup 59/Fe-ferric ammonium citrate (FeAC) at 20 micrograms Fe/ml in 20% serum, and 37.1% for /sup 59/FeAC 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.

  13. Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis.

    PubMed

    Ye, Qi; Kim, Jonghan

    2015-07-01

    Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe(-/-) mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe(-/-) mice. Compared with manganese-instilled wild-type mice, Hfe(-/-) mice showed decreased manganese accumulation in the cerebellum. Hfe(-/-) mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation.

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

    PubMed

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

    2015-12-01

    This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.

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

    PubMed

    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, P<0.001). Male sex (estimate, -0.28; 95% CI, -0.43 to -0.14; P<0.001), mean 3-year hemoglobin level ≤8 g/dL (estimate, -0.36; 95% CI, -0.53 to -0.19; P<0.001), mean 3-year ferritin 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

  16. Transferrin receptor 1 (TfR1) and putative stimulator of Fe transport (SFT) expression in iron deficiency and overload: an overview.

    PubMed

    Barisani, Donatella; Conte, Dario

    2002-01-01

    Transferrin Receptor 1 (TfR1) and putative Stimulator of Fe Transport (SFT) represent two different proteins involved in iron metabolism in mammalian cells. The expression of TfR1 in the duodenum of subjects with normal body iron stores has been mainly localized in the basolateral portion of the cytoplasm of crypt cells, supporting the idea that this molecule may be involved in the sensing of body iron stores. In iron deficiency anemia TfR1 expression demonstrated an inverse relationship with body iron stores as assessed by immunohistochemistry with anti-TfR1 antibodies. In iron overload, TfR1 expression in the duodenum differed according to the presence or absence of the C282Y mutation in the HFE gene, being increased in HFE-related hemochromatosis and similar to controls in non-HFE-related iron overload. SFT is characterized by its ability to increase iron transport both through the transferrin dependent and independent uptake, and could thus affect iron absorption in the intestine. Immunohistochemistry using anti-SFT antibodies which recognize a putative stimulator of Fe transport of approximately 80 KDa revealed a localization of this protein in the apical part of the cytoplasm of enterocytes localized at the tip of the villi. The expression of the protein recognized by these antibodies was increased in iron deficiency, as well as in patients carrying the C282Y HFE mutation. Thus, the increased expression of both proteins only in patients with HFE-related hemochromatosis suggests that other factors should be involved in determining non-HFE-related iron overload.

  17. Associations between dietary iron and zinc intakes, and between biochemical iron and zinc status in women.

    PubMed

    Lim, Karen; Booth, Alison; Szymlek-Gay, Ewa A; Gibson, Rosalind S; Bailey, Karl B; Irving, David; Nowson, Caryl; Riddell, Lynn

    2015-04-20

    Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18-50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12-38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort.

  18. Circulating Retinol-Binding Protein-4 Concentration Might Reflect Insulin Resistance–Associated Iron Overload

    PubMed Central

    Fernández-Real, José Manuel; Moreno, José María; Ricart, Wifredo

    2008-01-01

    OBJECTIVES—The mechanisms behind the association between retinol-binding protein-4 (RBP4) and insulin resistance are not well understood. An interaction between iron and vitamin A status, of which RBP4 is a surrogate, has long been recognized. We hypothesized that iron-associated insulin resistance could be behind the impaired insulin action caused by RBP4. RESEARCH DESIGN AND METHODS—Serum ferritin and RBP4 concentration and insulin resistance were evaluated in a sample of middle-aged men (n = 132) and in a replication independent study. Serum RBP4 was also studied before and after iron depletion in patients with type 2 diabetes. Finally, the effect of iron on RBP4 release was evaluated in vitro in adipose tissue. RESULTS—A positive correlation between circulating RBP4 and log serum ferritin (r = 0.35 and r = 0.61, respectively; P < 0.0001) was observed in both independent studies. Serum RBP4 concentration was higher in men than women in parallel to increased ferritin levels. On multiple regression analyses to predict serum RBP4, log serum ferritin contributed significantly to RBP4 variance after controlling for BMI, age, and homeostasis model assessment value. Serum RBP4 concentration decreased after iron depletion in type 2 diabetic patients (percent mean difference −13.7 [95% CI −25.4 to −2.04]; P = 0.024). The iron donor lactoferrin led to increased dose-dependent adipose tissue release of RBP4 (2.4-fold, P = 0.005) and increased RBP4 expression, while apotransferrin and deferoxamine led to decreased RBP4 release. CONCLUSIONS—The relationship between circulating RBP4 and iron stores, both cross-sectional and after iron depletion, and in vitro findings suggest that iron could play a role in the RBP4–insulin resistance relationship. PMID:18426863

  19. Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant.

    PubMed

    Yuki, Kyoko E; Eva, Megan M; Richer, Etienne; Chung, Dudley; Paquet, Marilène; Cellier, Mathieu; Canonne-Hergaux, François; Vaulont, Sophie; Vidal, Silvia M; Malo, Danielle

    2013-01-01

    Salmonella, a ubiquitous Gram-negative intracellular bacterium, is a food borne pathogen that infects a broad range of hosts. Infection with Salmonella Typhimurium in mice is a broadly recognized experimental model resembling typhoid fever in humans. Using a N-ethyl-N-nitrosurea (ENU) mutagenesis recessive screen, we report the identification of Ity16 (Immunity to Typhimurium locus 16), a locus responsible for increased susceptibility to infection. The position of Ity16 was refined on chromosome 8 and a nonsense mutation was identified in the ankyrin 1 (Ank1) gene. ANK1 plays an important role in the formation and stabilization of the red cell cytoskeleton. The Ank1(Ity16/Ity16) mutation causes severe hemolytic anemia in uninfected mice resulting in splenomegaly, hyperbilirubinemia, jaundice, extramedullary erythropoiesis and iron overload in liver and kidneys. Ank1(Ity16/Ity16) mutant mice demonstrated low levels of hepcidin (Hamp) expression and significant increases in the expression of the growth differentiation factor 15 (Gdf15), erythropoietin (Epo) and heme oxygenase 1 (Hmox1) exacerbating extramedullary erythropoiesis, tissue iron deposition and splenomegaly. As the infection progresses in Ank1(Ity16/Ity16), the anemia worsens and bacterial load were high in liver and kidneys compared to wild type mice. Heterozygous Ank1(+/Ity16) mice were also more susceptible to Salmonella infection although to a lesser extent than Ank1(Ity16/Ity16) and they did not inherently present anemia and splenomegaly. During infection, iron accumulated in the kidneys of Ank1(+/Ity16) mice where bacterial loads were high compared to littermate controls. The critical role of HAMP in the host response to Salmonella infection was validated by showing increased susceptibility to infection in Hamp-deficient mice and significant survival benefits in Ank1(+/Ity16) heterozygous mice treated with HAMP peptide. This study illustrates that the regulation of Hamp and iron balance are crucial

  20. Chelation of dietary iron prevents iron accumulation and macrophage infiltration in the type I diabetic kidney

    PubMed Central

    Morita, Tatsuyori; Nakano, Daisuke; Kitada, Kento; Morimoto, Satoshi; Ichihara, Atsuhiro; Hitomi, Hirofumi; Kobori, Hiroyuki; Shiojima, Ichiro; Nishiyama, Akira

    2015-01-01

    We previously reported that the functional deletion of p21, a cyclin-dependent kinase inhibitor, in mice attenuated renal cell senescence in streptozotocin (STZ)-induced type 1 diabetic mice. In the present study, we investigated the effect of iron chelation on renal cell senescence and inflammation in the type 1 diabetic kidney. STZ-treated mice showed increase in iron accumulation, tubular cell senescence and macrophage infiltration at week 28 in the kidney. Administering deferasirox, which removes only dietary iron, significantly attenuated iron accumulation in proximal tubules and the number of infiltrating F4/80-positive cells without effecting blood glucose, hematocrit or hemoglobin levels. In contrast however, deferasirox did not influence renal cell senescence. The lack of p21 decreased the renal tubular iron accumulation and did not change tubular cell senescence. Interestingly, the STZ-treated animals showed an increase in p16, another cyclin-dependent kinase inhibitor. The results suggest that type 1 diabetes increases renal tubular iron accumulation and macrophage infiltration through a p21-dependent mechanism, and that the chelation of dietary iron attenuates these responses. PMID:25820160

  1. Protective effects of naringenin on iron-overload-induced cerebral cortex neurotoxicity correlated with oxidative stress.

    PubMed

    Chtourou, Yassine; Fetoui, Hamadi; Gdoura, Radhouane

    2014-06-01

    Iron is a component of several metalloproteins involved in crucial metabolic processes such as oxygen sensing and transport, energy metabolism, and DNA synthesis. This metal progressively accumulates in the pathogenesis of Alzheimer's (AD) and Parkinson's (PD) diseases. Naringenin (NGEN), a natural flavonoid compound, has been reported to possess neuroprotective effect against PD-related pathology, however, the mechanisms underlying its beneficial effects are poorly defined. Thus, the aim of this study is to investigate the potential mechanism involved in the cytoprotection of NGEN against iron-induced neurotoxicity in the cerebral cortex of Wistar rats. Animals that were given repetitive injections of iron dextran for a total of 4 weeks showed a significant increase in lipid and protein markers such as thiobarbituric reactive acid substances, protein carbonyl product content levels, and DNA apoptosis in the cerebral cortex. These changes were accompanied by a decrease of enzymatic antioxidants like superoxide dismutase and catalase and in the levels of nonenzymatic antioxidants like total thiols and ascorbic acid. The activity of glutathione peroxidase remained unchanged in rats. A significant decrease in acetylcholinesterase and Na(+)/K(+)-ATPase activities was also shown, with a substantial rise in the nitric oxide levels. Coadministration of NGEN to iron-treated rats significantly improved antioxidant enzyme activities and attenuated oxidative damages observed in the cerebral cortex. The potential effect of NGEN to prevent iron-induced neurotoxicity was also reflected by the microscopic study, indicative of its neuroprotective effects. PMID:24682942

  2. Iron status and dietary iron intake of adolescents from a rural community in Sabah, Malaysia.

    PubMed

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

    2004-01-01

    Iron deficiency anaemia (IDA) is the most prevalent micronutrient deficiency in the world affecting the general health and wellbeing of millions. In Malaysia, moderately high prevalences of anaemia have been reported amongst infants, young children and women of childbearing age. Data is scant for the adolescents. This study was undertaken to assess the iron status and dietary intake of 165 adolescents, comprising 74 male and 91 female subjects, aged 12 to 19 years, from the rural communities in Tuaran District of Sabah, Malaysia. Convenience sampling was used for the selection of study subjects. Multiple iron status indicators namely, serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV) and haemoglobin (Hb) were determined for the study. The mean age of the subjects was 15.2 +/-2.1 years. While the majority of the subjects (77.6%) had normal body mass index (BMI) values, 17.6% were underweight and 4.8% overweight. About 35% to 40% of the subjects showed deficient values for haematocrit, serum ferritin, serum iron, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and transferrin saturation (TS), and 20% were anaemic (Hb <12 g/L). Using the multiple criteria of iron status indicators, the prevalence of iron depletion, iron deficiency and IDA in the male and female adolescents were 5.4% vs. 6.6%, 18.9% vs. 26.4% and 5.4% vs. 26.4%, respectively. Iron deficiency anaemia (85.0%) contributed largely to the prevalence of anaemia. The dietary iron intake of the adolescents was unsatisfactory, with approximately 98% of subjects failing to meet the Malaysian RDA level. Almost all the female subjects (91%) had dietary iron intake below two-thirds of the RDA level compared with a much smaller proportion for the male adolescents (68%). The prevalence of IDA in the present study population, especially in the female adolescents, appears to be a significant public health problem. Priority should therefore be given to the eradication of

  3. Association of hepcidin promoter c.-582 A>G variant and iron overload in thalassemia major

    PubMed Central

    Andreani, Marco; Radio, Francesca Clementina; Testi, Manuela; De Bernardo, Carmelilia; Troiano, Maria; Majore, Silvia; Bertucci, Pierfrancesco; Polchi, Paola; Rosati, Renata; Grammatico, Paola

    2009-01-01

    Hepcidin is a 25-amino acid peptide, derived from cleavage of an 84 amino acid pro-peptide produced predominantly by hepatocytes. This molecule, encoded by the hepcidin antimicrobial peptide (HAMP) gene shows structural and functional properties consistent with a role in innate immunity. Moreover, as demonstrated in mice and humans, hepcidin is a major regulator of iron metabolism, and acts by binding to ferroportin and controlling its concentration and trafficking. In this study we investigated the influence that mutations in HAMP and/or hemocromatosis (HFE) genes might exert on iron metabolism in a group of poly-transfused thalassemic patients in preparation for bone marrow transplantation. Our results showed that the presence of the c.-582 A>G polymorphism (rs10421768) placed in HAMP promoter (HAMP-P) might play a role in iron metabolism, perhaps varying the transcriptional activation that occurs through E-boxes located within the promoter. PMID:19734422

  4. Association of hepcidin promoter c.-582 A>G variant and iron overload in thalassemia major.

    PubMed

    Andreani, Marco; Radio, Francesca Clementina; Testi, Manuela; De Bernardo, Carmelilia; Troiano, Maria; Majore, Silvia; Bertucci, Pierfrancesco; Polchi, Paola; Rosati, Renata; Grammatico, Paola

    2009-09-01

    Hepcidin is a 25-amino acid peptide, derived from cleavage of an 84 amino acid pro-peptide produced predominantly by hepatocytes. This molecule, encoded by the hepcidin antimicrobial peptide (HAMP) gene shows structural and functional properties consistent with a role in innate immunity. Moreover, as demonstrated in mice and humans, hepcidin is a major regulator of iron metabolism, and acts by binding to ferroportin and controlling its concentration and trafficking. In this study we investigated the influence that mutations in HAMP and/or hemocromatosis (HFE) genes might exert on iron metabolism in a group of poly-transfused thalassemic patients in preparation for bone marrow transplantation. Our results showed that the presence of the c.-582 A>G polymorphism (rs10421768) placed in HAMP promoter (HAMP-P) might play a role in iron metabolism, perhaps varying the transcriptional activation that occurs through E-boxes located within the promoter.

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

    PubMed

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

    2014-01-01

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

  6. Iron containing vitamins and dietary supplements: control of the iron state using Mössbauer spectroscopy with high velocity resolution

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Semionkin, V. A.; Milder, O. B.; Novikov, E. G.

    2009-04-01

    Control of the iron state in iron containing vitamins and dietary supplements using Mössbauer spectroscopy with high velocity resolution was done. An improvement of velocity resolution appeared to be useful in determination of impurities and analysis of the main components in iron containing pharmaceuticals with better quality.

  7. Protective value of dietary copper and iron against some toxic effects of lead in rats.

    PubMed Central

    Klauder, D S; Petering, H G

    1975-01-01

    Both dietary iron and copper were inversely related to lead absorption as indicated by erythrocyte and kidney lead levels, dietary iron having the greatest effect. Kidney copper values were depressed when dietary iron was low, a condition which was worsened by lead. Lead tended to lower heart cytochrome c oxidase especially when dietary copper was low, but also when dietary copper and zinc were high. Lead interfered with hematopoiesis when dietary copper and/or iron were low, the effect being expecially severe when both essential nutrients were low. These results show the importance of copper and iron nutriture and metabolism as factors which reduce lead toxicity, and emphasize the necessity of considering nutritional status in evaluating lead toxicity. PMID:179804

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

    PubMed Central

    Panja, Sourav; Das, Abhishek; Mandal, Nripendranath

    2015-01-01

    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. PMID:26633891

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

    PubMed

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

    2015-01-01

    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.

  10. Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

    PubMed Central

    Ye, Qi; Kim, Jonghan

    2015-01-01

    Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe−/− mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe−/− mice. Compared with manganese-instilled wild-type mice, Hfe−/− mice showed decreased manganese accumulation in the cerebellum. Hfe−/− mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation. PMID:26189056

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

    PubMed

    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.

  12. Association between vitamin D levels and left ventricular function and NT-proBNP levels among thalassemia major children with iron overload

    PubMed Central

    Ambarwati, Leny; Rahayuningsih, Sri Endah; Setiabudiawan, Budi

    2016-01-01

    Background: Heart disease is the major cause of death in thalassemia patients. Repeated blood transfusions and hemolysis cause iron overload and also disrupts the hydroxylation and synthesis of vitamin D, causing vitamin D deficiency. Vitamin D deficiency is associated with cardiac dysfunction. Objective: The purpose of this study was to determine the association between vitamin D levels and left ventricular function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in thalassemia major children with iron overload. Patients and Methods: A cross-sectional study was conducted in March-April 2015 in the thalassemia clinic, Department of Child Health, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Thirty-four children with thalassemia were enrolled consecutively. Serum vitamin D and NT-proBNP levels were measured with electrochemiluminescence (ECLIA) method and echocardiography was performed to assess ventricular function. Results: Significant correlations were found between vitamin D levels and left ventricular ejection fraction (LVEF) (r = 0.399, P = 0.019) and fractional shortening (FS) (r = 0.394, P = 0.021). There was also significant correlation between vitamin D and NT-proBNP levels (r = -0.444, P = 0.008). Chi-square analysis also showed a relationship between vitamin D and NT-proBNP (P = 0.019) levels. There was a difference in NT-proBNP levels among thalassemia major children with iron overload (P = 0.020). Post hoc analysis showed that there was a significant difference in NT-proBNP levels between those with vitamin D deficiency and those with normal vitamin D levels (P = 0.012). Conclusion: There is an association between vitamin D and left ventricular function and NT-proBNP levels in children with thalassemia major and iron overload. Vitamin D can be considered in patients with thalassemia having vitamin D deficiency. PMID:27212846

  13. Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload.

    PubMed Central

    Smith, A G; Francis, J E

    1987-01-01

    An inhibitor of hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was demonstrated in heat-treated extracts of livers from C57BL/10ScSn mice with iron overload after a single dose (100 mg/kg; 350 mumol/kg) of hexachlorobenzene (HCB). Inhibition was not due to accumulated uroporphyrin since this could be removed by a SEP-PAK C18 cartridge without affecting inhibitor activity. The presence of the inhibitor could be first demonstrated 2 weeks after mice received HCB and before major elevation of hepatic porphyrin levels. Maximum inhibitory potential was reached at about 8 weeks and was still detected 25 weeks after the chemical, thus paralleling the depression of enzyme activity reported previously [Smith, Francis, Kay, Greig & Stewart (1986) Biochem. J. 238, 871-878]. The inhibitor was not detected following treatment of mice with either iron or HCB alone or after the decarboxylase activity was destroyed in vitro by the combination of uroporphyrin and light. The formation of the inhibitor by inbred mouse strains nominally Ah-responsive (C57BL/6J, C57BL/10ScSn, BALB/c, C3H/HeJ, CBA/J and A/J) and Ah-nonresponsive (SWR, AKR, 129, SJL, LP and DBA/2) did not correlate fully with their reported Ah-phenotype. There was a correlation amongst the Ah-responsive strains only, with hepatic ethoxyphenoxazone de-ethylase activity induced in parallel experiments by treatment with beta-naphthoflavone. De-ethylase activity induced by HCB, however, was considerably less than that with beta-naphthoflavone, which has not been reported as porphyrogenic. Other polyhalogenated chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,2',3',4'-hexachlorobiphenyl and hexabromobenzene, also caused the formation of the inhibitor of uroporphyrinogen decarboxylase. PMID:3675556

  14. Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A.

    PubMed

    Glei, Michael; Latunde-Dada, Gladys O; Klinder, Annett; Becker, Thomas W; Hermann, Uta; Voigt, Klaus; Pool-Zobel, Beatrice L

    2002-08-26

    Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS). The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H(2)O(2) (75microM) and quercetin (25-100microM) treatment. Analytic detection of iron in cell cultures, treated with 250microM Fe-NTA for 15 min to 24h, showed that 48.02+/-5.14 to 68.31+/-2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000microM) induced DNA breaks and oxidised bases, which were enhanced by subsequent H(2)O(2) exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H(2)O(2) for 15 min, 37 degrees C did not change the effect of H(2)O(2) alone. The impact of Fe-NTA and H(2)O(2)-induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H(2)O(2)-control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor.

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

    PubMed

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

    2016-09-01

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

  16. Positive association between dietary iron intake and iron status in HIV-infected children in Johannesburg, South Africa.

    PubMed

    Kruger, Herculina S; Balk, Lisanne J; Viljoen, Michelle; Meyers, Tammy M

    2013-01-01

    Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy. In this prospective study, the difference between dietary intakes of iron-deficient children (soluble transferrin receptor >9.4 mg/L) and iron-sufficient children after 18 months on highly active antiretroviral therapy was examined. The association between iron intake and hemoglobin (Hb) concentration was also assessed. Longitudinal data collected for 18 months from 58 HIV-infected African children were assessed by generalized estimation equations, with adjustment for demographic information, dietary intakes, growth parameters, and CD4%. After adjustment for covariates, the longitudinal association between dietary iron intake and Hb concentration remained significant. This association shows that for every 1-mg increase in iron intake per day, Hb increases by 1.1 g/L (P < .001). Mean Hb increased significantly after 18 months of follow-up (106 ± 14 to 129 ± 14 g/L, P < .01), but soluble transferrin receptor also increased (7.7 ± 2.7 to 8.9 ± 3.0 mg/L, P < .01). The incidence of ID increased from 15.2% at baseline to 37.2% after 18 months. Children with animal protein intakes greater than >20 g/d had significantly lower odds for ID at 18 months than did children with lower intakes (odds ratio, 0.40; 95% confidence interval, 0.21-0.77). Dietary iron intake was insufficient to protect against ID, pointing to a need for low-dose iron supplementation for iron-deficient HIV-infected children and interventions to increase the consumption of animal protein.

  17. N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration.

    PubMed

    Voloboueva, Ludmila A; Killilea, David W; Atamna, Hani; Ames, Bruce N

    2007-12-01

    Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have elevated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochondria, disruption of retinal metabolism, and vision impairment or loss. As a possible model for iron-induced AMD, we investigated the effects of excess iron in cultured human fetal RPE cells on oxidant levels and mitochondrial cytochrome c oxidase (complex IV) function and tested for protection by N-tert-butyl hydroxylamine (NtBHA), a known mitochondrial antioxidant. RPE exposure to ferric ammonium citrate resulted in a time- and dose-dependent increase in intracellular iron, which increased oxidant production and decreased glutathione (GSH) levels and mitochondrial complex IV activity. NtBHA addition to iron-overloaded RPE cells led to a reduction of intracellular iron content, oxidative stress, and partial restoration of complex IV activity and GSH content. NtBHA might be useful in AMD due to its potential to reduce oxidative stress, mitochondrial damage, and age-related iron accumulation, which may damage normal RPE function and lead to loss of vision.

  18. Influence of high dietary iron as ferrous carbonate and ferrous sulfate on iron metabolism in young calves.

    PubMed

    McGuire, S O; Miller, W J; Gentry, R P; Neathery, M W; Ho, S Y; Blackmon, D M

    1985-10-01

    Twelve intact male Holstein calves averaging 90 kg and 12 wk of age were fed one of three dietary treatments for 28 d. The diets were A) control, B) control plus 1000 ppm iron as ferrous carbonate, and C) control plus 1000 ppm iron as ferrous sulfate monohydrate. Calves were dosed orally on d 15 of the treatment period with 1 mCi of iron-59. Neither source of added iron had a significant effect on weight gains, feed consumption, hemoglobin, packed cell volume, serum total iron, serum total iron-binding capacity, unbound iron-binding capacity, serum copper, tissue copper, fecal dry matter, or a consistent effect on fecal pH. The ferrous carbonate had no significant effect on stable zinc or stable iron in any tissue studied. Calves fed ferrous sulfate had higher average stable iron in most tissues and significantly more in the small intestine. Tissue zinc was lower in spleen and pancreas of ferrous sulfate-fed calves. Both sources of added iron sharply reduced iron-59 in serum, whole blood, and body tissues. The reduction was substantially greater in calves fed the ferrous sulfate iron. Iron in ferrous sulfate had a higher biological availability than that in the ferrous carbonate; however, bioavailability of the ferrous carbonate iron appeared to be substantial and considerably more than that noted in previous studies in which a different source of ferrous carbonate was used. The maximum safe level of dietary iron is materially influenced by the source of iron with a higher tolerance indicated for ferrous carbonated than ferrous sulfate monohydrate.

  19. Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A

    PubMed Central

    Fernández, Belén; Fdez, Elena; Gómez-Suaga, Patricia; Gil, Fernando; Molina-Villalba, Isabel; Ferrer, Isidro; Patel, Sandip; Churchill, Grant C.; Hilfiker, Sabine

    2016-01-01

    ABSTRACT Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load. PMID:27383256

  20. Community-based dietary phytate reduction and its effect on iron status in Malawian children.

    PubMed

    Manary, Mark J; Krebs, Nancy F; Gibson, Rosalind S; Broadhead, Robin L; Hambidge, K Michael

    2002-06-01

    This study describes a community-based method used in rural Malawi to remove dietary phytate, an inhibitor of iron absorption, and notes an improvement in the iron status of ten children who participated in the trial. Phytate was removed by soaking maize flour in excess water with phytase and decanting the water before cooking the flour. Iron status, as measured by soluble transferrin receptor and zinc protoporphyrin, was improved but not normal.

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

    PubMed

    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 <2500 ng/ml was a risk factor for never having liver iron concentration (LIC) measurement, while absence of cardiac disease and siderosis were risk factors for a delay in LIC measurement >2 years. Patients who never had a cardiac MRI (CMR) T2* measurement were <18 years, had iron intake ≤0·4 mg/kg per day, or a serum ferritin <2500 ng/ml. A history of normal CMR T2* was the main risk factor for a delay in subsequent assessment of >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.

  2. The effects of dietary iron supplementation on the toxicity of piroctone olamine in the growing rat.

    PubMed

    Nolen, G A; Baines, D; Poynter, J I; Weaver, J E; Slough, C L

    1989-06-01

    Weanling Charles River CD rats of both sexes were fed 300 mg/kg/day of Piroctone Olamine, an anti-bacterial agent, and were supplemented with 0, 50, 100 or 200 ppm dietary iron as FeSO4.7H2O for six weeks. However, analytical data indicated that Piroctone was degraded in the diet so that the rats received only 225 mg/kg/day. The rats given Piroctone Olamine without iron gained significantly less body weight and ate significantly less feed than controls, with the effect being more pronounced in the males. They also developed severe microcytic, hypochromic anemia. The rats supplemented with all three levels of dietary iron grew at a rate similar to controls. The rats supplemented with 50 ppm dietary iron had anemia with all of the hematological iron-associated factors being significantly depressed. The 100 ppm supplement restored all hematologic factors to normal in the females, but slight reductions remained in the males. The 200 ppm supplement of iron restored all parameters to values similar to the controls in both sexes. These results suggest that the mechanism of the toxicity of Piroctone Olamine is the prevention of dietary iron absorption by in situ chelation. PMID:2598828

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

    PubMed Central

    Neely, Benjamin A.; Carlin, Kevin P.; 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-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 ± SD) at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to 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

  4. Relationship of dietary factors with dialyzable iron and in vitro iron bioavailability in the meals of farm women.

    PubMed

    Singh, Anamika; Bains, Kiran; Kaur, Hapreet

    2016-04-01

    Sixty rural women with age varying between 25 and 35 were selected randomly to determine the role of dietary factors on bioavailability of iron in their diets. Food samples of selected subjects were collected for three major meals i.e. breakfast, lunch and dinner for three consecutive days. The samples were analyzed for meal constituents associated with iron absorption as well as for total and dialyzable iron. Based on dietary characteristics, the diets of the farm women were in the class of intermediate diets as per FAO/WHO classification with iron bioavailability of 8.11 %. The statistical analysis revealed that the meal constituents which were found to influence iron absorption positively were ascorbic acid and β-carotene in breakfast and only β-carotene in dinner. The meal constituents which affected iron absorption negatively were zinc and calcium in breakfast as well as lunch and phytates and NDF in dinner, however, polyphenols present in the meals of the subjects did not show any relationship with iron absorption. PMID:27413227

  5. Optimal management of iron deficiency anemia due to poor dietary intake

    PubMed Central

    Aspuru, Kattalin; Villa, Carlos; Bermejo, Fernando; Herrero, Pilar; López, Santiago García

    2011-01-01

    Iron is necessary for the normal development of multiple vital processes. Iron deficiency (ID) may be caused by several diseases, even by physiological situations that increase requirements for this mineral. One of its possible causes is a poor dietary iron intake, which is infrequent in developed countries, but quite common in developing areas. In these countries, dietary ID is highly prevalent and comprises a real public health problem and a challenge for health authorities. ID, with or without anemia, can cause important symptoms that are not only physical, but can also include a decreased intellectual performance. All this, together with a high prevalence, can even have negative implications for a community’s economic and social development. Treatment consists of iron supplements. Prevention of ID obviously lies in increasing the dietary intake of iron, which can be difficult in developing countries. In these regions, foods with greater iron content are scarce, and attempts are made to compensate this by fortifying staple foods with iron. The effectiveness of this strategy is endorsed by multiple studies. On the other hand, in developed countries, ID with or without anemia is nearly always associated with diseases that trigger a negative balance between iron absorption and loss. Its management will be based on the treatment of underlying diseases, as well as on oral iron supplements, although these latter are limited by their tolerance and low potency, which on occasions may compel a change to intravenous administration. Iron deficiency has a series of peculiarities in pediatric patients, in the elderly, in pregnant women, and in patients with dietary restrictions, such as celiac disease. PMID:22114518

  6. Retention of iron by rat intestine in vivo as affected by dietary fiber, ascorbate and citrate.

    PubMed

    Reinhold, J G; Garcia Estrada, J; Garcia, P M; Garzon, P

    1986-06-01

    The effects of pH, ascorbate, citrate and dietary fiber on retention of ferrous and ferric iron by jejuno-ileal segments of rat intestine were examined in vivo. Iron was introduced in an isosmotic solution of sodium chloride and dextrose buffered by 2-[bis(2-hydroxyethyl)amino]ethanesulfonic acid (BES) and acetate. Stabilization of the iron solutions was aided by use of iron concentrations less than or equal to 1 microgram/ml injected into the intestine for 10-min periods. Iron retention was optimal over a broad pH range from 5 to 7.8. Inclusion of ascorbic acid in the solution injected (5, 25 or 75 micrograms/ml) did not increase retention of iron in either valence state. A low concentration of sodium citrate (2 mM) had no effect on iron retention, but increasing the concentration to 5 mM released iron from the mucosa. Maize and wheat fibers decreased the retention of ferrous iron by binding and by promoting autoxidation and formation of poorly soluble iron polymers. Bound ferrous iron was released completely at pH below 5. Retention of ferric iron was also lowered in the presence of fiber, presumably as a result of polymerization. Retention of iron by the rat in the absence of ligands was independent of valence state.

  7. Hepcidin is a Better Predictor of Iron Stores in Premenopausal Women than Blood Loss or Dietary Intake

    PubMed Central

    Lim, Karen H. C.; Booth, Alison O.; Nowson, Caryl A.; Szymlek-Gay, Ewa A.; Irving, David O.; Riddell, Lynn J.

    2016-01-01

    The relationship between dietary intake, circulating hepcidin and iron status in free-living premenopausal women has not been explored. This cross-sectional study aimed to identify dietary determinants of iron stores after accounting for blood loss and to determine whether iron intake predicts iron stores independently of hepcidin in a sample of Australian women. Three hundred thirty eight women aged 18–50 years were recruited. Total intake and food sources of iron were determined via food frequency questionnaire; the magnitude of menstrual losses was estimated by self-report; and blood donation volume was quantified using blood donation records and self-reported donation frequency. Serum samples were analysed for ferritin, hepcidin and C-reactive protein concentrations. Linear regression was used to investigate associations. Accounting for blood loss, each 1 mg/day increase in dietary iron was associated with a 3% increase in iron stores (p = 0.027); this association was not independent of hepcidin. Hepcidin was a more influential determinant of iron stores than blood loss and dietary factors combined (R2 of model including hepcidin = 0.65; R2 of model excluding hepcidin = 0.17, p for difference <0.001), and increased hepcidin diminished the positive association between iron intake and iron stores. Despite not being the biggest contributor to dietary iron intake, unprocessed meat was positively associated with iron stores, and each 10% increase in consumption was associated with a 1% increase in iron stores (p = 0.006). No other dietary factors were associated with iron stores. Interventions that reduce hepcidin production combined with dietary strategies to increase iron intake may be important means of improving iron status in women with depleted iron stores. PMID:27598194

  8. Hepcidin is a Better Predictor of Iron Stores in Premenopausal Women than Blood Loss or Dietary Intake.

    PubMed

    Lim, Karen H C; Booth, Alison O; Nowson, Caryl A; Szymlek-Gay, Ewa A; Irving, David O; Riddell, Lynn J

    2016-01-01

    The relationship between dietary intake, circulating hepcidin and iron status in free-living premenopausal women has not been explored. This cross-sectional study aimed to identify dietary determinants of iron stores after accounting for blood loss and to determine whether iron intake predicts iron stores independently of hepcidin in a sample of Australian women. Three hundred thirty eight women aged 18-50 years were recruited. Total intake and food sources of iron were determined via food frequency questionnaire; the magnitude of menstrual losses was estimated by self-report; and blood donation volume was quantified using blood donation records and self-reported donation frequency. Serum samples were analysed for ferritin, hepcidin and C-reactive protein concentrations. Linear regression was used to investigate associations. Accounting for blood loss, each 1 mg/day increase in dietary iron was associated with a 3% increase in iron stores (p = 0.027); this association was not independent of hepcidin. Hepcidin was a more influential determinant of iron stores than blood loss and dietary factors combined (R² of model including hepcidin = 0.65; R² of model excluding hepcidin = 0.17, p for difference <0.001), and increased hepcidin diminished the positive association between iron intake and iron stores. Despite not being the biggest contributor to dietary iron intake, unprocessed meat was positively associated with iron stores, and each 10% increase in consumption was associated with a 1% increase in iron stores (p = 0.006). No other dietary factors were associated with iron stores. Interventions that reduce hepcidin production combined with dietary strategies to increase iron intake may be important means of improving iron status in women with depleted iron stores. PMID:27598194

  9. Hepcidin is a Better Predictor of Iron Stores in Premenopausal Women than Blood Loss or Dietary Intake.

    PubMed

    Lim, Karen H C; Booth, Alison O; Nowson, Caryl A; Szymlek-Gay, Ewa A; Irving, David O; Riddell, Lynn J

    2016-09-02

    The relationship between dietary intake, circulating hepcidin and iron status in free-living premenopausal women has not been explored. This cross-sectional study aimed to identify dietary determinants of iron stores after accounting for blood loss and to determine whether iron intake predicts iron stores independently of hepcidin in a sample of Australian women. Three hundred thirty eight women aged 18-50 years were recruited. Total intake and food sources of iron were determined via food frequency questionnaire; the magnitude of menstrual losses was estimated by self-report; and blood donation volume was quantified using blood donation records and self-reported donation frequency. Serum samples were analysed for ferritin, hepcidin and C-reactive protein concentrations. Linear regression was used to investigate associations. Accounting for blood loss, each 1 mg/day increase in dietary iron was associated with a 3% increase in iron stores (p = 0.027); this association was not independent of hepcidin. Hepcidin was a more influential determinant of iron stores than blood loss and dietary factors combined (R² of model including hepcidin = 0.65; R² of model excluding hepcidin = 0.17, p for difference <0.001), and increased hepcidin diminished the positive association between iron intake and iron stores. Despite not being the biggest contributor to dietary iron intake, unprocessed meat was positively associated with iron stores, and each 10% increase in consumption was associated with a 1% increase in iron stores (p = 0.006). No other dietary factors were associated with iron stores. Interventions that reduce hepcidin production combined with dietary strategies to increase iron intake may be important means of improving iron status in women with depleted iron stores.

  10. Dietary Determinants of and Possible Solutions to Iron Deficiency for Young Women Living in Industrialized Countries: A Review

    PubMed Central

    Beck, Kathryn L.; Conlon, Cathryn A.; Kruger, Rozanne; Coad, Jane

    2014-01-01

    Iron deficiency is a concern in both developing and developed (industrialized) countries; and young women are particularly vulnerable. This review investigates dietary determinants of and possible solutions to iron deficiency in young women living in industrialized countries. Dietary factors including ascorbic acid and an elusive factor in animal protein foods (meat; fish and poultry) enhance iron absorption; while phytic acid; soy protein; calcium and polyphenols inhibit iron absorption. However; the effects of these dietary factors on iron absorption do not necessarily translate into an association with iron status and iron stores (serum ferritin concentration). In cross-sectional studies; only meat intake has consistently (positively) been associated with higher serum ferritin concentrations. The enhancing effects of ascorbic acid and meat on iron absorption may be negated by the simultaneous consumption of foods and nutrients which are inhibitory. Recent cross-sectional studies have considered the combination and timing of foods consumed; with mixed results. Dietary interventions using a range of focused dietary measures to improve iron status appear to be more effective than dietary approaches that focus on single nutrients or foods. Further research is needed to determine optimal dietary recommendations for both the prevention and treatment of iron deficiency. PMID:25244367

  11. Enzymatic degradation of phytate, polyphenols and dietary fibers in Ethiopian injera flours: effect on iron bioaccessibility.

    PubMed

    Baye, Kaleab; Guyot, Jean-Pierre; Icard-Vernière, Christèle; Rochette, Isabelle; Mouquet-Rivier, Claire

    2015-05-01

    The effect of removing phytate (IP6), iron-binding polyphenols, and dietary fibers on iron bioaccessibility in wheat-red sorghum (WrS) and teff-white sorghum (TwS) flour blends used in Ethiopia to make injera, a fermented pancake, was evaluated through the application of exogenous enzymes. Phytase treatment led to >90% reduction in IP6 and to an IP6:Fe molar ratio <1, but iron bioaccessibility was not improved (P > 0.05). Phytase + xylanase + cellulase (P + X + C) treatment increased iron bioaccessibility in TwS (non-detectableto1.6%) and WrS (1.9-3.2%), whereas phytase + polyphenol oxidase (P + PPO) treatment only showed improvement in the TwS blend. P + X + C + PPO treatment of the WrS blend increased the soluble non-dialysable iron fraction (6.7%) more than P + PPO treatment (3.9%). Although responses to enzyme treatments and iron bioaccessibility were matrix dependent, a positive effect of dietary fiber hydrolysis with X + C was obtained, irrespective of the blend. Dietary fibers had a negative effect on iron bioaccessibility independent of phytates.

  12. Dietary iron-deficiency up-regulates hephaestin mRNA level in small intestine of rats.

    PubMed

    Sakakibara, Shoji; Aoyama, Yoritaka

    2002-05-17

    Hephaestin is a protein, recently found from the study of sla (sex-linked anemia) mouse. Hephaestin is suggested to transport iron from intestinal enterocytes into the circulation. Iron is essential for living and for humans to maintain a constant total iron concentration in whole body. In this study, it was found that dietary iron-deficiency up-regulated hephaestin mRNA level in the proximal small intestine of rats. Therefore, it is suggested that in dietary iron-deficiency, hephaestin gene expression in proximal small intestine is up-regulated to absorb more iron from diet.

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

    PubMed

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

    2014-01-01

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

  14. Mössbauer Spectroscopy of Iron Containing Vitamins and Dietary Supplements

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.

    2004-12-01

    Mössbauer spectroscopy was used to study various industrial samples of vitamins containing ferrous fumarate and ferrous bisglycinate chelate (Ferrochel®) and dietary supplements containing ferrous sulfate. The presence of small quantities of various ferric impurities was found. Two vitamins contained major iron compounds that did not correspond to ferrous fumarate and ferrous bisglycinate chelate.

  15. Effect of dietary protein and iron on the fractional turnover rate of rat liver xanthine oxidase

    SciTech Connect

    Cherry, D.M.; Amy, N.K.

    1987-12-01

    Rat liver xanthine oxidase activity is regulated in response to dietary protein and iron. To investigate whether the change in activity was mediated by a change in the rate of protein degradation, we measured the fractional turnover rate using the double-isotope technique with (/sup 3/H)- and (/sup 14/C)leucine and calculated the apparent half-life of xanthine oxidase in rats fed diets containing either 20 or 5% casein with either 35 or 5 mg iron/kg diet. Under control conditions, xanthine oxidase had an apparent half-life of 4.8 d and approximately 65% of the enzyme subunits were active. Rats fed diets with low dietary protein had lower xanthine oxidase activity, but the enzyme had a slower fractional turnover rate, resulting in an apparent half-life of 6.4 d, and only 15-20% of the enzyme was active. The apparent half-life of xanthine oxidase increased to 7.5 d in rats fed diets with low dietary iron, but dietary iron did not affect the specific activity of the enzyme or the percentage of active subunits. These results suggest that the loss of enzyme activity is not due to loss of enzyme protein by increased degradation, but rather to inactivation of the enzyme.

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

    EPA Science Inventory

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

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

    PubMed Central

    Bulhões, Sara; Brilhante, Maria José; Pereirinha, Tânia; Cabral, Rita; Rego, Ana Catarina; Fraga, Cristina; Miguel, António G.; Brasil, Gracinda; Macedo, Paula; Mota-Vieira, Luisa

    2015-01-01

    Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations– c.845G>A [p.Cys282Tyr], c.187C>G [p.His63Asp], and c.193A>T [p.Ser65Cys]. Results revealed that the family’s HH pseudodominant pattern is due to consanguineous marriage of HFE-c.845G>A carriers, and to marriage with a genetically unrelated spouse that is a -c.187G carrier. Regarding unrelated patients, six were homozygous for c.845A, and three were c.845A/c.187G compound heterozygous. We then performed sequencing of HFE exons 2, 4, 5 and their intron-flanking regions. No other mutations were observed, but we identified the -c.340+4C [IVS2+4C] splice variant in 26 (74.3%) patients. Functionally, the c.340+4C may generate alternative splicing by HFE exon 2 skipping and consequently, a protein missing the α1-domain essential for HFE/ transferrin receptor-1 interactions. Finally, we investigated HFE mutations configuration with iron overload by determining haplotypes and genotypic profiles. Results evidenced that carriers of HFE-c.187G allele also carry -c.340+4C, suggesting in-cis configuration. This data is corroborated by the association analysis where carriers of the complex allele HFE-c.[187C>G;340+4T>C] have an increased iron overload risk (RR = 2.08, 95% CI = 1.40−2.94, p<0.001). Therefore, homozygous for this complex allele are at risk of having iron overload because they will produce two altered proteins—the p.63Asp [c.187G], and the protein lacking 88 amino acids encoded by exon 2. In summary, we provide evidence that the complex allele HFE-c.[187C

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

    PubMed

    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

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

    PubMed

    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.

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

    SciTech Connect

    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.

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

    PubMed

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

    2003-01-01

    =-0.477, p < 0.0001), while stepwise multiple regression analysis, IRI showed a positive correlation with fibrinogen (b=0.64, t=3.746, p<0.001), triglycerides (b=0.37, t=2.619, p<0.01) and ferritin (b=0.20, t=1.827, p=0.05). No correlation of IRI, with any of the above parameters was seen in the offspring of normal parents. By logistic regression analysis the parameters characterizing the offspring of parents with DM2 were IRI (OR 14.9 CI 2.4-91.0) serum iron (OR 44.2 CI 6.9-281), TIBC (OR 6.1 CI 1.01-37.0 and gamma-GT (OR 29.6 CI 5.0-174). In conclusion, the data indicate that the iron load, is significantly increased in offspring of DM2 subjects with unaffected glucose tolerance. Furthermore, ferritin concentration is related to insulin resistance. Hence, the relative iron "overload" in offspring of type 2 diabetics is present along with insulin resistance and might worsen the hepatic insulin insensitivity already present in these patients. PMID:17003017

  2. Dietary iron supplements and Moringa oleifera leaves influence the liver hepcidin messenger RNA expression and biochemical indices of iron status in rats.

    PubMed

    Saini, R K; Manoj, P; Shetty, N P; Srinivasan, K; Giridhar, P

    2014-07-01

    In this study, the effects of iron depletion and repletion on biochemical and molecular indices of iron status were investigated in growing male Wistar rats. We hypothesized that iron from Moringa leaves could overcome the effects of iron deficiency and modulate the expression of iron-responsive genes better than conventional iron supplements. Iron deficiency was induced by feeding rats an iron-deficient diet for 10 weeks, whereas control rats were maintained on an iron-sufficient diet (35.0-mg Fe/kg diet). After the depletion period, animals were repleted with different source of iron, in combination with ascorbic acid. Iron deficiency caused a significant (P < .05) decrease in serum iron and ferritin levels by 57% and 40%, respectively, as compared with nondepleted control animals. Significant changes in the expression (0.5- to100-fold) of liver hepcidin (HAMP), transferrin, transferrin receptor-2, hemochromatosis type 2, ferroportin 1, ceruloplasmin, and ferritin-H were recorded in iron-depleted and iron-repleted rats, as compared with nondepleted rats (P < .05). Dietary iron from Moringa leaf was found to be superior compared with ferric citrate in overcoming the effects of iron deficiency in rats. These results suggest that changes in the relative expression of liver hepcidin messenger RNA can be used as a sensitive molecular marker for iron deficiency. PMID:25150122

  3. Dietary iron supplements and Moringa oleifera leaves influence the liver hepcidin messenger RNA expression and biochemical indices of iron status in rats.

    PubMed

    Saini, R K; Manoj, P; Shetty, N P; Srinivasan, K; Giridhar, P

    2014-07-01

    In this study, the effects of iron depletion and repletion on biochemical and molecular indices of iron status were investigated in growing male Wistar rats. We hypothesized that iron from Moringa leaves could overcome the effects of iron deficiency and modulate the expression of iron-responsive genes better than conventional iron supplements. Iron deficiency was induced by feeding rats an iron-deficient diet for 10 weeks, whereas control rats were maintained on an iron-sufficient diet (35.0-mg Fe/kg diet). After the depletion period, animals were repleted with different source of iron, in combination with ascorbic acid. Iron deficiency caused a significant (P < .05) decrease in serum iron and ferritin levels by 57% and 40%, respectively, as compared with nondepleted control animals. Significant changes in the expression (0.5- to100-fold) of liver hepcidin (HAMP), transferrin, transferrin receptor-2, hemochromatosis type 2, ferroportin 1, ceruloplasmin, and ferritin-H were recorded in iron-depleted and iron-repleted rats, as compared with nondepleted rats (P < .05). Dietary iron from Moringa leaf was found to be superior compared with ferric citrate in overcoming the effects of iron deficiency in rats. These results suggest that changes in the relative expression of liver hepcidin messenger RNA can be used as a sensitive molecular marker for iron deficiency.

  4. Blood donation, being Asian, and a history of iron deficiency are stronger predictors of iron deficiency than dietary patterns in premenopausal women.

    PubMed

    Beck, Kathryn L; Conlon, Cathryn A; Kruger, Rozanne; Heath, Anne-Louise M; Matthys, Christophe; Coad, Jane; Jones, Beatrix; Stonehouse, Welma

    2014-01-01

    This study investigated dietary patterns and nondietary determinants of suboptimal iron status (serum ferritin < 20 μg/L) in 375 premenopausal women. Using multiple logistic regression analysis, determinants were blood donation in the past year [OR: 6.00 (95% CI: 2.81, 12.82); P < 0.001], being Asian [OR: 4.84 (95% CI: 2.29, 10.20); P < 0.001], previous iron deficiency [OR: 2.19 (95% CI: 1.16, 4.13); P = 0.016], a "milk and yoghurt" dietary pattern [one SD higher score, OR: 1.44 (95% CI: 1.08, 1.93); P = 0.012], and longer duration of menstruation [days, OR: 1.38 (95% CI: 1.12, 1.68); P = 0.002]. A one SD change in the factor score above the mean for a "meat and vegetable" dietary pattern reduced the odds of suboptimal iron status by 79.0% [OR: 0.21 (95% CI: 0.08, 0.50); P = 0.001] in women with children. Blood donation, Asian ethnicity, and previous iron deficiency were the strongest predictors, substantially increasing the odds of suboptimal iron status. Following a "milk and yoghurt" dietary pattern and a longer duration of menstruation moderately increased the odds of suboptimal iron status, while a "meat and vegetable" dietary pattern reduced the odds of suboptimal iron status in women with children.

  5. The dietary significance of adventitious iron, zinc, copper and lead in domestically prepared food.

    PubMed

    Reilly, C

    1985-01-01

    The uptake of iron, zinc, copper and lead by food cooked under domestic conditions in utensils made of different metals (cast iron, aluminium, plain and tinned copper) was investigated. It was found that the metal content of the food was generally related to the metal in immediate contact with the food during cooking. Daily dietary intake could vary from 11 to 6 mg of iron, 11 to 9 mg of zinc, 2 to 1 mg of copper and 0.4 to 0.1 mg of lead, depending on the cooking utensils used. Dietary intake of the metals was also related to sources and domestic practices regarding water supply. Consistent use of municipal water from a domestic hot water system could contribute a daily intake of 32 mg iron, 29 mg zinc and 12 mg copper. Rainwater stored in a galvanized iron tank could provide 23 mg of zinc per day when used for domestic purposes. The nutritional and toxicological significance of such adventitious sources of metals in the diet are discussed. The need to consider them when investigating the metal intake of individuals is stressed.

  6. 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

    PubMed Central

    Porter, John; Bowden, Donald K.; Economou, Marina; Troncy, Jacques; Ganser, Arnold; Habr, Dany; Martin, Nicolas; Gater, Adam; Rofail, Diana; Abetz-Webb, Linda; Lau, Helen; Cappellini, Maria Domenica

    2012-01-01

    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. PMID:22924125

  7. Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food-borne bacterial pathogens.

    PubMed

    Kortman, Guus A M; Mulder, Michelle L M; Richters, Thijs J W; Shanmugam, Nanda K N; Trebicka, Estela; Boekhorst, Jos; Timmerman, Harro M; Roelofs, Rian; Wiegerinck, Erwin T; Laarakkers, Coby M; Swinkels, Dorine W; Bolhuis, Albert; Cherayil, Bobby J; Tjalsma, Harold

    2015-09-01

    Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.

  8. Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food-borne bacterial pathogens.

    PubMed

    Kortman, Guus A M; Mulder, Michelle L M; Richters, Thijs J W; Shanmugam, Nanda K N; Trebicka, Estela; Boekhorst, Jos; Timmerman, Harro M; Roelofs, Rian; Wiegerinck, Erwin T; Laarakkers, Coby M; Swinkels, Dorine W; Bolhuis, Albert; Cherayil, Bobby J; Tjalsma, Harold

    2015-09-01

    Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition. PMID:26046550

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  11. Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis.

    PubMed

    Muñoz, Manuel; García-Erce, José Antonio; Remacha, Angel Francisco

    2011-04-01

    IRON FUNCTIONS: Iron is an essential micronutrient, as it is required for satisfactory erythropoietic function, oxidative metabolism and cellular immune response. IRON PHYSIOLOGY: Absorption of dietary iron (1-2 mg/day) is tightly regulated and just balanced against iron loss because there are no active iron excretory mechanisms. Dietary iron is found in haem (10%) and non-haem (ionic, 90%) forms, and their absorption occurs at the apical surface of duodenal enterocytes via different mechanisms. Iron is exported by ferroportin 1 (the only putative iron exporter) across the basolateral membrane of the enterocyte into the circulation (absorbed iron), where it binds to transferrin and is transported to sites of use and storage. Transferrin-bound iron enters target cells-mainly erythroid cells, but also immune and hepatic cells-via receptor-mediated endocytosis. Senescent erythrocytes are phagocytosed by reticuloendothelial system macrophages, haem is metabolised by haem oxygenase, and the released iron is stored as ferritin. Iron will be later exported from macrophages to transferrin. This internal turnover of iron is essential to meet the requirements of erythropoiesis (20-30 mg/day). As transferrin becomes saturated in iron-overload states, excess iron is transported to the liver, the other main storage organ for iron, carrying the risk of free radical formation and tissue damage. REGULATION OF IRON HOMOEOSTASIS: Hepcidin, synthesised by hepatocytes in response to iron concentrations, inflammation, hypoxia and erythropoiesis, is the main iron-regulatory hormone. It binds ferroportin on enterocytes, macrophages and hepatocytes triggering its internalisation and lysosomal degradation. Inappropriate hepcidin secretion may lead to either iron deficiency or iron overload.

  12. HEPCIDIN AND IRON HOMEOSTASIS

    PubMed Central

    Ganz, Tomas; Nemeth, Elizabeta

    2014-01-01

    Despite fluctuations in dietary iron intake and intermittent losses through bleeding, the plasma iron concentrations in humans remain stable at 10–30 μM. While most of the iron entering blood plasma comes from recycling, appropriate amount of iron is absorbed from the diet to compensate for losses and maintain nontoxic amounts in stores. Plasma iron concentration and iron distribution are similarly regulated in laboratory rodents. The hepatic peptide hepcidin was identified as the systemic iron-regulatory hormone. In the efferent arc, hepcidin regulates intestinal iron absorption, plasma iron concentrations, and tissue iron distribution by inducing degradation of its receptor, the cellular iron exporter ferroportin. Ferroportin exports iron into plasma from absorptive enterocytes, from macrophages that recycle the iron of senescent erythrocytes, and from hepatocytes that store iron. In the more complex and less well understood afferent arc, hepatic hepcidin synthesis is transcriptionally regulated by extracellular and intracellular iron concentrations through a molecular complex of bone morphogenetic protein receptors and their iron-specific ligands, modulators and iron sensors. Through as yet undefined pathways, hepcidin is also homeostatically regulated by the iron requirements of erythroid precursors for hemoglobin synthesis. In accordance with the role of hepcidin-mediated iron redistribution in host defense, hepcidin production is regulated by inflammation as well. Increased hepcidin concentrations in plasma are pathogenic in iron-restrictive anemias including anemias associated with inflammation, chronic kidney disease and some cancers. Hepcidin deficiency causes iron overload in hereditary hemochromatosis and ineffective erythropoiesis. Hepcidin, ferroportin and their regulators represent potential targets for the diagnosis and treatment of iron disorders and anemias. PMID:22306005

  13. The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents and Stereotypical Behaviors in Male C57BL/6J Mice

    PubMed Central

    Liu, Lumei; Byrd, Aria; Plummer, Justin; Erikson, Keith M.; Harrison, Scott H.; Han, Jian

    2016-01-01

    Adequate brain iron levels are essential for enzyme activities, myelination, and neurotransmitter synthesis in the brain. Although systemic iron deficiency has been found in genetically or dietary-induced obese subjects, the effects of obesity-associated iron dysregulation in brain regions have not been examined. The objective of this study was to examine the effect of dietary fat and iron interaction on brain regional iron contents and regional-associated behavior patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly assigned to six dietary treatment groups (n = 5) with varying fat (control/high) and iron (control/high/low) contents. The stereotypical behaviors were measured during the 24th week. Blood, liver, and brain tissues were collected at the end of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum, and thalamus regions. Iron contents and ferritin heavy chain (FtH) protein and mRNA expressions in these regions were measured. Correlations between stereotypical behaviors and brain regional iron contents were analyzed at the 5% significance level. Results showed that high-fat diet altered the stereotypical behaviors such as inactivity and total distance traveled (P < 0.05). The high-fat diet altered brain iron contents and FtH protein and mRNA expressions in a regional-specific manner: (1) high-fat diet significantly decreased the brain iron content in the striatum (P < 0.05), but not other regions, and (2) thalamus has a more distinct change in FtH mRNA expression compared with other regions. Furthermore, high-fat diet resulted in a significant decreased total distance traveled and a significant correlation between iron content and sleeping in midbrain (P < 0.05). Dietary iron also decreased brain iron content and FtH protein expression in a regionally specific manner. The effect of interaction between dietary fat and iron was observed in brain iron content and behaviors. All these findings

  14. The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents and Stereotypical Behaviors in Male C57BL/6J Mice.

    PubMed

    Liu, Lumei; Byrd, Aria; Plummer, Justin; Erikson, Keith M; Harrison, Scott H; Han, Jian

    2016-01-01

    Adequate brain iron levels are essential for enzyme activities, myelination, and neurotransmitter synthesis in the brain. Although systemic iron deficiency has been found in genetically or dietary-induced obese subjects, the effects of obesity-associated iron dysregulation in brain regions have not been examined. The objective of this study was to examine the effect of dietary fat and iron interaction on brain regional iron contents and regional-associated behavior patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly assigned to six dietary treatment groups (n = 5) with varying fat (control/high) and iron (control/high/low) contents. The stereotypical behaviors were measured during the 24th week. Blood, liver, and brain tissues were collected at the end of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum, and thalamus regions. Iron contents and ferritin heavy chain (FtH) protein and mRNA expressions in these regions were measured. Correlations between stereotypical behaviors and brain regional iron contents were analyzed at the 5% significance level. Results showed that high-fat diet altered the stereotypical behaviors such as inactivity and total distance traveled (P < 0.05). The high-fat diet altered brain iron contents and FtH protein and mRNA expressions in a regional-specific manner: (1) high-fat diet significantly decreased the brain iron content in the striatum (P < 0.05), but not other regions, and (2) thalamus has a more distinct change in FtH mRNA expression compared with other regions. Furthermore, high-fat diet resulted in a significant decreased total distance traveled and a significant correlation between iron content and sleeping in midbrain (P < 0.05). Dietary iron also decreased brain iron content and FtH protein expression in a regionally specific manner. The effect of interaction between dietary fat and iron was observed in brain iron content and behaviors. All these findings

  15. Effects of low levels of dietary lead and iron on hepatic RNA, protein, and minerals in young Japanese quail

    SciTech Connect

    Stone, C.L.; Fox, M.R.S.

    1984-04-01

    Day-old Japanese quail were fed purified diets containing either 0.2 (control), 5.4, or 16.2 ppm lead as the acetate with either 25 (deficient) or 100 ppm (adequate control) iron for 2 weeks. Iron deficiency caused decreases in hemoglobin, iron, and manganese concentrations in the liver, and hepatic RNA synthesis. Iron deficiency also caused increased concentrations of lead, calcium, and molybdenum in the liver. Lead supplements caused increased concentrations of lead in the liver, and with adequate dietary iron, each supplemental lead level caused a slight decrease in the concentration of RNA in the liver. Treatment had no effect on DNA or protein synthesis, body weight, or liver weight in relation to body weight. These low levels of dietary lead did not cause the same adverse metabolic effects observed by others with higher levels of lead; however, iron deficiency increased lead uptake by the liver and affected RNA synthesis. 44 references.

  16. Hepcidin: A Promising Therapeutic Target for Iron Disorders

    PubMed Central

    Liu, Jing; Sun, Bingbing; Yin, Huijun; Liu, Sijin

    2016-01-01

    Abstract Iron is required for most forms of organisms, and it is the most essential element for the functions of many iron-containing proteins involved in oxygen transport, cellular respiration, DNA replication, and so on. Disorders of iron metabolism are associated with diverse diseases, including anemias (e.g., iron-deficiency anemia and anemia of chronic diseases) and iron overload diseases, such as hereditary hemochromatosis and β-thalassemia. Hepcidin (encoded by Hamp gene) is a peptide hormone synthesized by hepatocytes, and it plays an important role in regulating the systematic iron homeostasis. As the systemic iron regulator, hepcidin, not only controls dietary iron absorption and iron egress out of iron storage cells, but also induces iron redistribution in various organs. Deregulated hepcidin is often seen in a variety of iron-related diseases including anemias and iron overload disorders. In the case of iron overload disorders (e.g., hereditary hemochromatosis and β-thalassemia), hepatic hepcidin concentration is significantly reduced. Since hepcidin deregulation is responsible for iron disorder-associated diseases, the purpose of this review is to summarize the recent findings on therapeutics targeting hepcidin. Continuous efforts have been made to search for hepcidin mimics and chemical compounds that could be used to increase hepcidin level. Here, a literature search was conducted in PubMed, and research papers relevant to hepcidin regulation or hepcidin-centered therapeutic work were reviewed. On the basis of literature search, we recapitulated recent findings on therapeutic studies targeting hepcidin, including agonists and antagonists to modulate hepcidin expression or its downstream signaling. We also discussed the molecular mechanisms by which hepcidin level and iron metabolism are modulated. Elevating hepcidin concentration is an optimal strategy to ameliorate iron overload diseases, and also to relieve β-thalassemia phenotypes by improving

  17. Effects of dietary cottonseed meal and iron-treated cottonseed meal in different laying hen genotypes.

    PubMed

    Panigrahi, S; Morris, T R

    1991-03-01

    The effects of dietary screw-pressed cottonseed meal (CSM) and iron-treated CSM on laying performance and discolourations in eggs were examined in a range of hen genotypes. In experiment 1, six genotypes, obtained at point-of-lay from various sources, were fed on a non-CSM diet, a diet with 300 g CSM/kg, and a diet containing iron-treated CSM at 300 g/kg. In experiment 2, two of these genotypes were reared together from day-old and were fed from 10 to 18 weeks on a non-CSM diet or a diet containing iron-treated CSM at 250 g/kg. They were then fed on a non-CSM layer diet or a diet containing iron-treated CSM at 300 g/kg, in a 2 x 2 x 2 factorial design that also examined the effects of the rearing diet. 2. The effects on food intakes and egg production of including CSM and iron-treated CSM in layer diets depended on the genotype of the hens. The strongest interaction between breed and diet was on food intake, the breed Hubbard Golden Comet (HGC) being the least tolerant of CSM and iron-treated CSM. 3. Inclusion of iron-treated CSM in the rearer diet to supply approximately 70% of the dietary protein had no adverse effects on growth or age at first egg. Food intake and egg production between 18 and 26 weeks were affected by the iron-treated CSM layer diet, but there were no carry-over effects attributable to the rearing diets. 4. Genotype was not a factor in the development of the gossypol-related brown yolk discolouration in fresh or warm-stored eggs of hens fed on a CSM-based diet containing 197 mg free gossypol/kg and 52 mg cyclopropenoid fatty acids (CPFA)/kg (experiment 1). 5. In both experiments, the susceptibility of eggs to the CPFA-related cold storage effects depended on the genotype of the hen, eggs from hens of the HCG breed being more affected than those of ISA hens. 6. Treatment of CSM with crystalline ferrous sulphate heptahydrate, at a 4:1 weight ratio of iron to free gossypol, prevented brown yolk discolourations in all genotypes tested, as assessed

  18. Intra-amniotic administration and dietary inulin affect the iron status and intestinal functionality of iron-deficient broiler chickens.

    PubMed

    Tako, E; Glahn, R P

    2012-06-01

    Inulin, a linear β-fructan, is present in a variety of plants, with relatively high levels of up to 20% in chicory root. It exhibits prebiotic properties and was shown to enhance mineral absorption. Our objectives were to assess the effect of intra-amniotic administration of inulin at 17 d of incubation on the iron status of broiler chicks (at hatch, 21 d) and to continue to monitor iron status with and without dietary inulin on these hatchlings for 42 d. The study included 3 prehatch treatment groups (n = 30): 1) inulin, inulin solution (4% inulin/0.85% saline); 2) control 1, untreated eggs; and 3) control 2, saline solution (0.85% saline). Solutions were injected into the naturally consumed amniotic fluid of 17-d-old chicken embryos (groups 1, 3). Upon hatch (93% hatchability), and from each group, 10 chicks were killed and their small intestine, liver, and cecum were removed for mRNA abundance of intestinal iron-related transporters, liver ferritin amounts, and bacterial analysis of cecal content, respectively. From the remaining chicks of each group, chicks were allocated to a standard corn-based diet (± 4% inulin, n = 10). During the trial, hemoglobin concentrations and body hemoglobin-Fe values were higher in the inulin group versus controls (P < 0.05). On d 42, birds were anesthetized and their duodenal loops were exposed. A nonocclusive catheter was inserted into the duodenal vein for blood sampling. A solution containing ⁵⁸Fe (0.1 mg of Fe/10 mM ascorbic acid) added to the digested diet sample was injected into the loop. Blood samples were collected every 5 min and for 90 min postinjection and analyzed by inductively coupled argon-plasma mass spectrometry for ⁵⁸Fe concentrations. At the end of the procedure, animals were killed and cecum contents and sections of the duodenum and liver were removed. Results showed that ⁵⁸Fe absorption rates were at times higher in the inulin group versus the other groups. Also, mRNA abundance of DMT1 (an Fe

  19. Synthetic and natural iron chelators: therapeutic potential and clinical use

    PubMed Central

    Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

    2013-01-01

    Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

  20. Clinical implications of changes in the modern diet: iron intake, absorption and status.

    PubMed

    Heath, Anne-Louise M; Fairweather-Tait, Susan J

    2002-06-01

    The modern British diet contains less red meat and is lower in iron than that consumed 30 years ago. This is in spite of the fact that fortification of foods, particularly breakfast cereals, with iron has become more widespread. Although there is no clear relationship between dietary iron intake and iron status, isotope studies have identified multiple dietary factors that influence iron absorption, such as ascorbic acid, animal tissue, phytates and polyphenols. There is no evidence to suggest that current dietary changes will have a major impact on iron status in the general population; however, effects on the incidence of iron overload in individuals with HFE mutations and iron deficiency in children and premenopausal women remain to be determined.

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

    PubMed

    Gkouvatsos, Konstantinos; Fillebeen, Carine; Daba, Alina; Wagner, John; Sebastiani, Giada; Pantopoulos, Kostas

    2014-01-01

    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.

  2. Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure

    PubMed Central

    Węglewska-Jurkiewicz, Anna; Taybert, Joanna; Pronicki, Maciej; Szymańska-Dębińska, Tamara; Karkucińska-Więckowska, Agnieszka; Jakóbkiewicz-Banecka, Joanna; Kowalski, Paweł; Piekutowska-Abramczuk, Dorota; Pajdowska, Magdalena; Socha, Piotr; Sykut-Cegielska, Jolanta; Węgrzyn, Grzegorz

    2010-01-01

    ) iron overload may additionally damage mtDNA-depleted tissues; (iii) low birth weight, adaptation trouble, and abnormal amino acids in newborn screening are frequent in dGK-deficient neonates. PMID:21107780

  3. Bioactive Dietary Polyphenols Inhibit Heme Iron Absorption in A Dose-Dependent Manner in Human Intestinal Caco-2 cells

    PubMed Central

    Ma, Qianyi; Kim, Eun-Young; Lindsay, Elizabeth Ann; Han, Okhee

    2011-01-01

    Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous work revealed that (−)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco-2 cells. The aims of this study were to examine whether small amounts of EGCG, GSE and green tea extract (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme-55Fe absorption study was conducted by adding various concentrations of EGCG, GSE and GT to Caco-2 cells in the absence and presence of ascorbic acid. Polyphenolic compounds significantly inhibited heme-55Fe absorption in a dose-dependent manner. The addition of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concentration of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compounds when lower concentrations of polyphenols were added (≤ 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metabolism and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of 55Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concentrations of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concentrations of polyphenols. PMID:22417433

  4. Comparison effects of dietary iron dextran and bacterial-iron supplementation on growth performance, fecal microbial flora, and blood profiles in sows and their litters.

    PubMed

    Zhao, Pinyao; Upadhaya, Santi Devi; Li, Jian; Kim, Inho

    2015-11-01

    This study was conducted to compare effects of dietary administration of iron dextran and bacterial-iron on growth performance, fecal microbial flora, and blood profiles in sows and their litters. A total of 20 multiparous sows (Landrace × Yorkshire) were randomly allotted into two treatments: (i) ID (basal diet, piglets were injected with iron dextran); (ii) BR (basal diet + bacterial-iron; bacterial-iron was given to sows, piglets were not injected with iron dextran). There were five replicates per treatment with two sows per replicate. No differences were observed on sow and piglet growth performance, fecal microbial flora as well as sow blood profiles between ID and BR treatments. In piglets, blood iron, red blood cell and hemoglobin concentrations in ID treatment were higher (P < 0.05) on days 12 and 24. Furthermore, concentration of white blood cells in BR treatment was lower (P < 0.05) on day 12. However, the percentage of lymphocytes on day 12 was increased (P < 0.05) in BR treatment. In conclusion, effect of iron dextran and bacterial-iron has no difference on growth performance in lactating sows and piglets, but iron dextran injection has higher blood iron, white blood cell, red blood cell and hemoglobin concentrations in piglets.

  5. Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort.

    PubMed

    Molina-Montes, Esther; Wark, Petra A; Sánchez, María-José; Norat, Teresa; Jakszyn, Paula; Luján-Barroso, Leila; Michaud, Dominique S; Crowe, Francesca; Allen, Naomi; Khaw, Kay-Tee; Wareham, Nicholas; Trichopoulou, Antonia; Adarakis, George; Katarachia, Helen; Skeie, Guri; Henningsen, Maria; Broderstad, Ann Ragnhild; Berrino, Franco; Tumino, Rosario; Palli, Domenico; Mattiello, Amalia; Vineis, Paolo; Amiano, Pilar; Barricarte, Aurelio; Huerta, José-María; Duell, Eric J; Quirós, José-Ramón; Ye, Weimin; Sund, Malin; Lindkvist, Björn; Johansen, Dorthe; Overvad, Kim; Tjønneland, Anne; Roswall, Nina; Li, Kuanrong; Grote, Verena A; Steffen, Annika; Boeing, Heiner; Racine, Antoine; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Peeters, Petra H M; Siersema, Peter D; Fedirko, Veronika; Jenab, Mazda; Riboli, Elio; Bueno-de-Mesquita, Bas

    2012-10-01

    Several studies support a protective effect of dietary magnesium against type 2 diabetes, but a harmful effect for iron. As diabetes has been linked to pancreatic cancer, intake of these nutrients may be also associated with this cancer. We examined the association between dietary intake of magnesium, total iron and heme-iron and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In total, 142,203 men and 334,999 women, recruited between 1992 and 2000, were included. After an average follow-up of 11.3 years, 396 men and 469 women developed exocrine pancreatic cancer. Hazard ratios and 95% confidence intervals (CIs) were obtained using Cox regression stratified by age and center, and adjusted for energy intake, smoking status, height, weight, and self-reported diabetes status. Neither intake of magnesium, total iron nor heme-iron was associated with pancreatic cancer risk. In stratified analyses, a borderline inverse association was observed among overweight men (body mass index, ≥ 25 kg/m(2) ) with magnesium (HR(per 100 mg/day increase) = 0.79, 95% CI = 0.63-1.01) although this was less apparent using calibrated intake. In female smokers, a higher intake of heme-iron was associated with a higher pancreatic cancer risk (HR (per 1 mg/day increase) = 1.38, 95% CI = 1.10-1.74). After calibration, this risk increased significantly to 2.5-fold (95% CI = 1.22-5.28). Overall, dietary magnesium, total iron and heme-iron were not associated with pancreatic cancer risk during the follow-up period. Our observation that heme-iron was associated with increased pancreatic cancer risk in female smokers warrants replication in additional study populations.

  6. Dietary intake and thiamin, iron, and zinc status in elite Nordic skiers during different training periods.

    PubMed

    Fogelholm, M; Rehunen, S; Gref, C G; Laakso, J T; Lehto, J; Ruokonen, I; Himberg, J J

    1992-12-01

    This study evaluated how different training periods affect dietary intake and biochemical indices of thiamin, iron, and zinc status in elite Nordic skiers. Subjects were 17 skiers and 39 controls, ages 18-38 yrs. Dietary data were collected by 7-day food records at 3-month intervals. Coefficient of variation (CV) was used to indicate magnitude of seasonal changes. Energy intake for the year (28 food record days) was 3,802 kcal/day (CV 19.1%) in male skiers, 2,754 kcal/day (CV 3.7%) in male controls, 2,812 kcal/day (CV 9.1%) in female skiers, and 2,013 kcal/day (CV 5.9%) in female controls. CVs for thiamin, riboflavin, vitamin C, calcium, magnesium, iron, and zinc intake were 14.1-23.9% (male skiers), 2.9-15.0% (male controls), 4.8-24.5% (female skiers), and 4.3-11.5% (female controls). Seasonal changes in energy, carbohydrate, and micronutrient intakes reflected energy expenditure in male endurance athletes particularly. Erythrocyte transketolase activation coefficients and serum ferritin and zinc concentrations did not differ between skiers and controls. Seasonal variations in these biochemical indices of nutritional status were of the same magnitude in skiers and controls, despite large changes in skiers' physical activity.

  7. Effects of dietary manganese and iron on manganese and iron metabolism during infancy

    SciTech Connect

    Kiehl, H.; Loennerdal, B. )

    1991-03-15

    To derive a better understanding of the metabolism of Mn during infancy, infant formulas with different levels of Mn and Fe were labeled with {sup 54}Mn and {sup 59}Fe and administered orally to suckling rats: control low-Fe formula; control with 100-times Mn; and control with 100-times Fe. Another group received 200 {mu}g MnCl{sub 2} daily during infancy. 12 hr post-dosing, the pattern of {sup 54}Mn distribution in the tissues paralleled that of {sup 59}Fe. An excess of either mineral decreased overall retention but led to higher recoveries of both elements in the proximal intestine and liver. Conversely, these recoveries in pups given Mn from birth were lower than in controls. Analysis of the cytosolic fractions from intestine and liver using FPLC gel filtration demonstrated the impact of the mineral loads on protein profiles. In all cases except the high-Mn dose, dietary manipulations resulted in greater relative levels of a high molecular weight protein with MW similar to ferritin. The high-Mn formula seemed to induce in the hepatocyte a lower MW protein with which most of the {sup 54}Mn and {sup 59}Fe was associated. These results suggest a possible role of Mn as a regulator in the synthesis of cytosolic proteins of the enterocyte and hepatocyte in infants.

  8. Iron absorption and transport-an update.

    PubMed

    Conrad, M E; Umbreit, J N

    2000-08-01

    Iron is vital for all living organisms. However, excess iron is hazardous because it produces free radical formation. Therefore, iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss of iron. In countries where heme is a significant part of the diet, most body iron is derived from dietary heme iron because heme binds few of the luminal intestinal iron chelators that inhibit absorption of non-heme iron. Uptake of luminal heme into enterocytes occurs as a metalloporphyrin. Intracellularly, iron is released from heme by heme oxygenase so that iron leaves the enterocyte to enter the plasma as non-heme iron. Ferric iron is absorbed via a beta(3) integrin and mobilferrin (IMP) pathway that is not shared with other nutritional metals. Ferrous iron uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with manganese. Other proteins were recently described which are believed to play a role in iron absorption. SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from enterocytes into the plasma. The iron concentration within enterocytes reflects the total body iron and either upregulates or satiates iron-binding sites on regulatory proteins. Enterocytes of hemochromatotics are iron-depleted similarly to the absorptive cells of iron-deficient subjects. Iron depletion, hemolysis, and hypoxia each can stimulate iron absorption. In non-intestinal cells most iron uptake occurs via either the classical clathrin-coated pathway utilizing transferrin receptors or the poorly defined transferrin receptor independent pathway. Non-intestinal cells possess the IMP and DMT-1 pathways though their role in the absence of iron overload is unclear. This suggests that these pathways have intracellular functions in addition to facilitating iron uptake.

  9. Volumetric Titrations Using Electrolytically Generated Reagents for the Determination of Ascorbic Acid and Iron in Dietary Supplement Tablets: An Undergraduate Laboratory Experiment

    ERIC Educational Resources Information Center

    Scanlon, Christopher; Gebeyehu, Zewdu; Griffin, Kameron; Dabke, Rajeev B.

    2014-01-01

    An undergraduate laboratory experiment for the volumetric quantitative analysis of ascorbic acid and iron in dietary supplement tablets is presented. Powdered samples of the dietary supplement tablets were volumetrically titrated against electrolytically generated reagents, and the mass of dietary reagent in the tablet was determined from the…

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed

    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

  13. Dietary Iron Intake and Body Iron Stores Are Associated with Risk of Coronary Heart Disease in a Meta-Analysis of Prospective Cohort Studies123

    PubMed Central

    Hunnicutt, Jacob; He, Ka; Xun, Pengcheng

    2014-01-01

    The link between iron intake as well as body iron stores and coronary heart disease (CHD) has been contentiously debated, and the epidemiologic evidence is inconsistent. We aimed to quantitatively summarize the literature on the association between dietary iron intake/body iron stores and CHD risk by conducting a meta-analysis of prospective cohort studies. PubMed was used to find studies published through June 2013 in peer-reviewed journals. Embase or a hand search of relevant articles was used to obtain additional articles. The pooled RRs of CHD incidence and mortality with 95% CIs were calculated by using either a random-effects or fixed-effects model, as appropriate. Twenty-one eligible studies (32 cohorts) including 292,454 participants with an average of 10.2 y of follow-up were included. Heme iron was found to be positively associated with CHD incidence (RR: 1.57; 95% CI: 1.28, 1.94), whereas total iron was inversely associated (RR: 0.85; 95% CI: 0.73, 0.999). Neither heme-iron nor total iron intakes were significantly associated with CHD mortality. Both transferrin saturation and serum iron were inversely related to CHD incidence [RR (95% CI): 0.76 (0.66, 0.88) and 0.68 (0.56, 0.82), respectively], but only transferrin saturation was inversely associated with CHD mortality (RR: 0.85; 95% CI: 0.73, 0.99). In conclusion, total iron intake and serum iron concentrations were inversely associated with CHD incidence, but heme iron intake was positively related to CHD incidence. Elevated serum transferrin saturation concentration was inversely associated with both CHD incidence and mortality. Future research is needed to establish the causal relation and to elucidate potential mechanisms. PMID:24401818

  14. Association of iron depletion with menstruation and dietary intake indices in pubertal girls: the healthy growth study.

    PubMed

    Moschonis, George; Papandreou, Dimitrios; Mavrogianni, Christina; Giannopoulou, Angeliki; Damianidi, Louisa; Malindretos, Pavlos; Lionis, Christos; Chrousos, George P; Manios, Yannis

    2013-01-01

    The aim of the present study was to investigate the associations of iron depletion (ID) with menstrual blood losses, lifestyle, and dietary habits, in pubertal girls. The study sample comprised 1222 girls aged 9-13 years old. Biochemical, anthropometrical, dietary, clinical, and physical activity data were collected. Out of 274 adolescent girls with menses, 33.5% were found to be iron depleted (defined as serum ferritin < 12 μg/L) compared to 15.9% out of 948 girls without menses. Iron-depleted girls without menses were found to have lower consumption of poultry (P = 0.017) and higher consumption of fruits (P = 0.044) and fast food (P = 0.041) compared to their peers having normal iron status. Multivariate logistic regression analysis showed that girls with menses were 2.57 (95% CI: 1.37, 4.81) times more likely of being iron depleted compared to girls with no menses. Iron depletion was found to be associated with high calcium intake, high consumption of fast foods, and low consumption of poultry and fruits. Menses was the only factor that was found to significantly increase the likelihood of ID in these girls. More future research is probably needed in order to better understand the role of diet and menses in iron depletion.

  15. Effect of dietary phytic acid and cadmium on the availability of cadmium, zinc, copper, iron, and manganese to rats

    SciTech Connect

    Turecki, T.; Ewan, R.C.; Stahr, H.M.

    1995-05-01

    The main route of cadmium intake for general population, both human and animal, is via ingestion. The intestinal absorption of cadmium is relatively low, 6% of a single oral dose for humans and less than 2% for various animal species. However, due to poor excretion, accumulation of cadmium occurs, primarily in kidney. The chronic exposure even to low levels of dietary cadmium can lead to the development of renal disturbances. Fox (1988) suggests that phytic acid might be a dietary component capable to influence the intestinal absorption of cadmium. Phytic acid naturally occurs as the major phosphorus storage constituent of most cereals, legumes, and oilseeds. At physiological pH, phytic acid is ionized and has a strong affinity for divalent cations. The potential of phytic acid to decrease the availability of Zn has been for long time of concern for nutritionists. Phytic acid has also been reported to decrease the availability of other trace metals. For nonessential elements, reduced availability of lead has been observed. The experimental data concerning the effect of dietary phytic acid on the availability of dietary cadmium are limited to the work of Rose and Quarterman (1984). The objective of this experiment was to examine: (1) the effect of dietary phytic acid on the availability of cadmium under conditions of chronic dietary exposure of rats to cadmium, and (2) the effect of dietary phytic acid and of chronic dietary exposure to cadmium on the availability of zinc, copper, iron, and manganese to rats. 19 refs., 4 tabs.

  16. Dietary intervention with iron and black tea infusion in reducing cytotoxicity of arsenic.

    PubMed

    Poddar, Sandeep

    2004-09-01

    The relative efficacy of infusion of black tea leaf, Camellia sinensis (Linn.) O. Kuntze, (Theaceae), and iron as freshly prepared aqueous solution of ferrous sulphate in reducing the cytotoxic effects of arsenic, was tested in bone marrow cells of laboratory bred Swiss albino mice. Ferrous sulphate and tea given alone did not induce chromosomal breakage to any appreciable extent. Tea decreased chromosome damage induced by arsenic to a significant extent, while the addition of ferrous sulphate did not alter the protective action of tea against arsenic. Such protection against arsenic cytotoxicity by prolonged dietary administration of black tea infusion--a common routine beverage--is of importance in view of widespread exposure of human populations to arsenic damage through drinking water from tubewells in Eastern India and Bangladesh.

  17. Dietary energy nutrient distribution, calcium, iron and zinc in young and old Asians

    SciTech Connect

    Wu-Tso, P.; Fuentes-Cano, M.; Tam, C.F. )

    1992-02-26

    The objective of this study is to examine whether ethnic eating patterns influence dietary nutrient intakes in young and old Asians. The authors experimental groups included young CSLA Asian students and their parents or close relatives. Most of them lived in the same households. Three-day dietary records were analyzed for protein, fat, carbohydrate, calcium, iron, and zinc by the Nutritionist III computer program and statistically analyzed using Mustat. No statistical difference was observed in the KCAL distribution of protein, fat, and carbohydrate and both groups met the guidelines of 20%, 30%, and 50%, respectively. However, mean KCAL intakes of both groups were found to be about 79% of NRC-RDA. No statistical difference was found in % RDA for Ca and Zn between groups, except % RDA for Fe. With respect to RDA, the older Asians consumed more Fe than the younger Asians. It is noteworthy that they did not meet the RDA requirements for Ca and Zn. Since recent Asian immigrants and refugees often suffer from a high incidence of infectious disease such as tuberculosis, these observations of low intakes of KCAL, Ca, and Zn, may, at least in part, contribute to disease.

  18. [Prevalence of deficiency and dietary intake of iron, zinc and copper in Chilean childbearing age women].

    PubMed

    Mujica-Coopman, María F; Borja, Angélica; Pizarro, Fernando; Olivares, Manuel

    2014-03-01

    The aim of the present study was to evaluate anemia, the biochemical status and dietary adequacy of iron (Fe), zinc (Zn) and copper (Cu), in Chilean childbearing age women. We studied a convenience sample of 86 women aged 18 to 48 years from Santiago, Chile. We determined anemia and the micronutrient status through hemoglobin (Hb) mean corpuscular volume, transferrin saturation, zinc protoporphyrin, serum ferritin (SF), serum Zn and Cu. Dietary adequacy was estimated using a food frequency questionnaire. Of all women, 4.7% had Fe deficiency (ID) anemia, 21 % ID without anemia, 26 % depleted Fe stores and 48.3% normal Fe status. Obese women had higher SF (p<0.01) compared with those classified as having normal BMI. Also, showed higher Hb (p<0.05) concentrations compared with overweight and normal weight women. Partidipants showed 3.5 % and 2.3 % of Zn and Cu deficiency, respectively. Also, 95 %, 94 % and 99 % had adequate intake of Fe, Zn and Cu respectively, according to EAR cut points. There were no significant differences in micronutrients intake across different nutritional status. There was a low prevalence of anemia, Fe, Zn and Cu deficiency. A high percentage of women reached micronutrient adequacy. However, 47% of women had ID without anemia and Fe depleted stores.

  19. Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets

    PubMed Central

    Antonides, Alexandra; Schoonderwoerd, Anne C.; Scholz, Gabi; Berg, Brian M.; Nordquist, Rebecca E.; van der Staay, Franz Josef

    2015-01-01

    Iron deficiency is the most common nutritional deficiency in humans, affecting more than two billion people worldwide. Early-life iron deficiency can lead to irreversible deficits in learning and memory. The pig represents a promising model animal for studying such deficits, because of its similarities to humans during early development. We investigated the effects of pre-weaning dietary iron deficiency in piglets on growth, blood parameters, cognitive performance, and brain histology later in life. Four to six days after birth, 10 male sibling pairs of piglets were taken from 10 different sows. One piglet of each pair was given a 200 mg iron dextran injection and fed a control milk diet for 28 days (88 mg Fe/kg), whereas the other sibling was given a saline injection and fed an iron deficient (ID) milk diet (21 mg Fe/kg). Due to severely retarded growth of two of the ID piglets, only eight ID piglets were tested behaviorally. After dietary treatment, all piglets were fed a balanced commercial pig diet (190–240 mg Fe/kg). Starting at 7.5 weeks of age, piglets were tested in a spatial cognitive holeboard task. In this task, 4 of 16 holes contain a hidden food reward, allowing measurement of working (short-term) memory and reference (long-term) memory (RM) simultaneously. All piglets received 40–60 acquisition trials, followed by a 16-trial reversal phase. ID piglets showed permanently retarded growth and a strong decrease in blood iron parameters during dietary treatment. After treatment, ID piglets' blood iron values restored to normal levels. In the holeboard task, ID piglets showed impaired RM learning during acquisition and reversal. Iron staining at necropsy at 12 weeks of age showed that ID piglets had fewer iron-containing cells in hippocampal regions CA1 and dentate gyrus (DG). The number of iron-containing cells in CA3 correlated positively with the average RM score during acquisition across all animals. Our results support the hypothesis that early

  20. Transcriptional up-regulation of a novel ferritin homolog in abalone Haliotis discus hannai Ino by dietary iron.

    PubMed

    Wu, Chenglong; Zhang, Wenbing; Mai, Kangsen; Xu, Wei; Wang, Xiaojie; Ma, Hongming; Liufu, Zhiguo

    2010-11-01

    A novel cDNA encoding ferritin (HdhNFT) was cloned from the hepatopancreas of abalone, Haliotis discus hannai Ino. The deduced protein contains 171 amino acid residues with a predicted molecular mass (MW) about 19.8 kDa and theoretical isoelectric point (pI) of 4.792. Amino acid alignment revealed that HdhNFT shared high similarity with other known ferritins. The HdhNFT contained a highly conserved motif for the ferroxidase center, which consists of seven residues of a typical vertebrate heavy-chain ferritin with a typical stem-loop structure. HdhNFT mRNA contains a 27 bp iron-responsive element (IRE) in the 5'-untranslated region. This IRE exhibited 82.14% similarity with abalone H. discus discus and 78.57% similarity with Pacific oyster Crassostrea gigas IREs. By real-time PCR assays, the mRNA transcripts of HdhNFT were found to be higher expressed in kidney, hepatopancreas, gill, mantle and muscle than in haemocytes and gonad. Moreover, mRNA expression levels of HdhNFT in the hepatopancreas and haemocytes were measured by real-time PCR in abalone fed with graded levels of dietary iron (29.2, 65.7, 1267.2 and 6264.7 mg/kg). Results showed that the expression of the HdhNFT mRNA increased with dietary iron contents. Furthermore, the maximum value of the HdhNFT mRNA was found in the treatment with 6264.7 mg/kg of dietary iron. These data indicated that dietary iron can up-regulate HdhNFT at transcriptional level in abalone.

  1. Uses and limitations of serum ferritin, magnetic resonance imaging T2 and T2* in the diagnosis of iron overload and in the ferrikinetics of normalization of the iron stores in thalassemia using the International Committee on Chelation deferiprone/deferoxamine combination protocol.

    PubMed

    Kolnagou, Anita; Yazman, Dilek; Economides, Charalambos; Eracleous, Eleni; Kontoghiorghes, George J

    2009-01-01

    Excess cardiac iron deposition leads to congestive cardiac failure and accounts for more than 70% of deaths in thalassemia major patients. In three separate studies involving 145 thalassemia patients, serum ferritin and magnetic resonance imaging (MRI) relaxation times T2 and T2* have been compared for assessing iron load levels during chelation treatment. In two studies, variable levels of cardiac iron load have been detected by T2 and T2* in patients treated with deferoxamine (DFO), which, however, were unrelated to serum ferritin. In most cases, similar range levels from normal to severe cardiac iron load could be identified by both the T2 and T2* methods. However, in a few cases there were substantial differences in the levels detected between the two methods. In the third study, the ferrikinetics of the normalization of the iron stores during the International Committee on Chelation (ICOC) deferiprone (L1)/DFO combination protocol was followed up using T2 and T2* and serum ferritin. Iron deposits were found not to be proportionally distributed between the liver and the heart or uniformly distributed within each organ. Iron mobilization in each patient varied and iron deposits in each organ were cleared at different rates. Despite some limitations, the application of the MRI relaxation times T2 and T2* offers the best diagnostic methods for iron overload estimations in most organs and especially the heart. These MRI methods and serum ferritin could also be used for the ferrikinetics of iron mobilization and removal during chelation therapy and the normalization of the iron stores during the ICOC L1/DFO combination protocol. There is a need to standardize the two MRI relaxation times T2 and T2* methods and identify the factors causing the differences between them.

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

    PubMed Central

    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 < 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. PMID:27298749

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

    PubMed

    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 < 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. PMID:27298749

  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.

    PubMed

    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 < 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.

  5. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake.

    PubMed Central

    Berglund, M; Akesson, A; Nermell, B; Vahter, M

    1994-01-01

    Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. Figure 3. A Figure 3. B Figure 4. Figure 5. PMID:7713018

  6. Association between Plasma Endothelin-1, Transforming Growth Factor-β, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation.

    PubMed

    Akı, Şahika Zeynep; Suyanı, Elif; Cengiz, Mustafa; Özenirler, Seren; Elbeğ, Şehri; Paşaoğlu, Hatice; Sucak, Gülsan Türköz

    2015-05-01

    Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-β, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-β, and FGF were 81.54 ± 21.62 μmol/mL, 31.82 ± 26.42 μmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-β, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-β, and

  7. Signs of Overload

    MedlinePlus

    ... Listen Text Size Email Print Share Signs of Overload Page Content Article Body Although stress is a ... 12 (Copyright © 2004 American Academy of Pediatrics) The information contained on this Web site should not be ...

  8. Effect of dietary alpha-tocopherol, ascorbic acid, selenium, and iron on oxidative stress in sub-yearling Chinook salmon (Oncorhynchus tshawytscha)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A three-variable central composite design coupled with surface-response analysis was used to examine the effects of dietary alpha-tocopherol + ascorbic acid (TOCAA), selenium (Se), and iron (Fe) on indices of oxidative stress in juvenile spring Chinook salmon. Each dietary factor was tested at five ...

  9. High Dietary Iron and Radiation Exposure Increase Biomarkers of Oxidative Stress in Blood and Liver of Rats

    NASA Technical Reports Server (NTRS)

    Morgan, Jennifer L. L.; Theriot, Corey A.; Wu, Honglu; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs-137 every other day for 16 days for a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet compared to 45 mg Fe/kg for controls) in Sprague-Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation treatment increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. We thus found preliminary indications of synergistic effects of radiation exposure and increased dietary Fe, warranting further study. This study was funded by the NASA Human Research Project.

  10. Serum iron test

    MedlinePlus

    ... of iron homeostasis: iron deficiency and overload. In: Hoffman R, Benz EJ Jr, Silberstein LE, et al, ... EJ, Gardner LB. Anemia of chronic diseases. In: Hoffman R, Benz EJ Jr, Silberstein LE, et al, ...

  11. Total iron binding capacity

    MedlinePlus

    ... GM. Disorders of iron homeostasis: iron deficiency and overload. In: Hoffman R, Benz EJ Jr, Silberstein LE, ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  12. Effects of Radiation and Dietary Iron on Expression of Genes and Proteins Involved in Drug Metabolism

    NASA Technical Reports Server (NTRS)

    Faust, K. M.; Wotring, V. E.

    2014-01-01

    Liver function, especially the rate of metabolic enzyme activities, determines the concentration of circulating drugs and the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Dietary factors and exposure to radiation are aspects of spaceflight that are potential oxidative stressors and both can be modeled in ground experiments. In this experiment, we examined the effects of high dietary iron and low dose gamma radiation (individually and combined) on the gene expression of enzymes involved in drug metabolism, redox homeostasis, and DNA repair. METHODS All procedures were approved by the JSC Animal Care and Use Committee. Male Sprague-Dawley rats were divided into 4 groups (n=8); control, high Fe diet (650 mg iron/kg), radiation (fractionated 3 Gy exposure from a Cs- 137 source) and combined high Fe diet + radiation exposure. Animals were euthanized 24h after the last treatment of radiation; livers were removed immediately and flash -frozen in liquid nitrogen. Expression of genes thought to be involved in redox homeostasis, drug metabolism and DNA damage repair was measured by RT-qPCR. Where possible, protein expression of the same genes was measured by western blotting. All data are expressed as % change in expression normalized to reference gene expression; comparisons were then made of each treatment group to the sham exposed/ normal diet control group. Data was considered significant at p< 0

  13. Common Bean Leaves as a Source of Dietary Iron: Functional Test in an Iron-Deficient Rat Model.

    PubMed

    Martínez-Zavala, Mauricio; Mora-Avilés, María Alejandra; Anaya-Loyola, Miriam Aracely; Guzmán-Maldonado, Horacio; Aguilera-Barreyro, Araceli; Blanco-Labra, Alejandro; García-Gasca, Teresa

    2016-09-01

    Recent findings made by our group indicate that the iron content in Phaseolus vulgaris leaves is at least four times greater than in grains therefore, we evaluated the effect of supplementation with bean leaf (iron content of 275 mg/kg on a dry basis) in iron-deficient rats. Anemia was induced by feeding rats with an iron-deficient diet (IDD) for 11 days and iron-recovery diets were subsequently tested for 14 days using a normal diet, a 10 % bean leaf-supplemented IDD (BLSD) or a ferrous sulfate-supplemented IDD. Decreased levels of leukocytes (64 %), erythrocytes (30 %), lymphocytes (62 %), granulocytes (72 %), hematocrit (34 %), hemoglobin (35 %), and ferritin (34 %) were observed in the iron-deficient rats compared to the control rats. BLSD supplementation showed the highest recovery values relative to those recorded for control rats: leukocytes (40 %), erythrocytes (24 %), lymphocytes (33 %), granulocytes (88 %), hematocrit (17 %), and hemoglobin (18 %), suggesting that common bean leaves could be a good source of bioavailable iron with possible immunomodulatory effects. PMID:27319012

  14. Effective use of tea to limit dietary iron available to starlings (Sturnus vulgaris).

    PubMed

    Seibels, Bob; Lamberski, Nadine; Gregory, Christopher R; Slifka, Kerri; Hagerman, Ann E

    2003-09-01

    Wild-caught starlings (Sturnus vulgaris) were fed an iron-enriched diet, with or without supplemental black tea leaves, to determine whether tea-derived tannins would prevent intestinal iron absorption. Hepatic biopsies were obtained to determine hepatic iron concentrations by atomic absorption spectroscopy. Hepatic iron concentrations increased significantly (P = 0.04) in 21 birds that consumed only the iron-enriched diet for 6 mo but not in the 20 birds that consumed the iron-enriched diet with tea leaf supplementation for the same time period. PMID:14582799

  15. Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study.

    PubMed

    Jakszyn, Paula; Agudo, Antonio; Lujan-Barroso, Leila; Bueno-de-Mesquita, H Bas; Jenab, Mazda; Navarro, Carmen; Palli, Domenico; Boeing, Heiner; Manjer, Jonas; Numans, Mattijs E; Igali, Laszlo; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Morois, Sophie; Grioni, Sara; Panico, cSalvatore; Tumino, Rosario; Sacerdote, Carlotta; Quirós, J Ramon; Molina-Montes, Esther; Huerta Castaño, Jose Ma; Barricarte, Aurelio; Amiano, Pilar; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi E; Key, Timothy J; Jeurnink, Suzanne M; Peeters, Petra H M; Bamia, Christina; Valanou, Elisabeth; Trichopoulou, Antonia; Kaaks, Rudolf; Lukanova, Annekatrin; Bergmann, Manuela M; Lindkvist, Björn; Stenling, Roger; Johansson, Ingegerd; Dahm, Christina C; Overvad, Kim; Olsen, Anja; Tjonneland, Anne; Skeie, Guri; Broderstad, Ann Ragnhild; Lund, Eiliv; Michaud, Dominique S; Mouw, Traci; Riboli, Elio; González, Carlos A

    2012-06-01

    Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.01-1.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01-2.35). We found a positive association between heme iron intake and gastric cancer risk. PMID:21717452

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

    PubMed

    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

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

    PubMed Central

    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

  18. Dietary inulin supplementation does not promote colonic iron absorption in a porcine model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prebiotics may enhance iron bioavailability by increasing iron absorption in the colon. Anemic pigs fitted with cecal cannulas were fed a low-iron diet with or without 4% inulin. Over 7 days, pigs were administered 1 mg 54 Fe in the morning feed followed by cannula infusion of 0.5 mg 58 Fe to measu...

  19. Potential of common bean to enhance dietary iron availability in humans: Germplasm diversity and QTL analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We are interested in the improvement of iron nutritional status of humans living in developing world countries where iron deficiency anemia is quite severe. We also wish to promote the use of plant-based food sources to improve human iron status, and thus are focusing on staple food crops like comm...

  20. Overloading the Competent Reader.

    ERIC Educational Resources Information Center

    Smith, Frank

    Two sources of information are involved in reading; the visual information picked up by the eyes from the printed page and the nonvisual information, or prior knowledge, that the reader possesses. An overreliance on visual information leads to an overloading of the cognitive process involved in reading and loss in comprehension. Overreliance on…

  1. Interdisciplinary Research and Information Overload.

    ERIC Educational Resources Information Center

    Wilson, Patrick

    1996-01-01

    Discusses information overload and examines several ways in which actual and potential overload affects research choices for the solo researcher in interdisciplinary areas. Topics include information overload and teamwork; entry barriers to certain specialties, including necessary background knowledge; and information utilization and knowledge…

  2. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats

    PubMed Central

    Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I.; Cruzblanca, Humberto; Mancilla, Evelyn

    2016-01-01

    Objective Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Materials and Methods Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Results Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable

  3. METABOLISM OF IRON STORES

    PubMed Central

    SAITO, HIROSHI

    2014-01-01

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

  4. Mathematical model of zinc absorption: effects of dietary calcium, protein and iron on zinc absorption.

    PubMed

    Miller, Leland V; Krebs, Nancy F; Hambidge, K Michael

    2013-02-28

    A previously described mathematical model of Zn absorption as a function of total daily dietary Zn and phytate was fitted to data from studies in which dietary Ca, Fe and protein were also measured. An analysis of regression residuals indicated statistically significant positive relationships between the residuals and Ca, Fe and protein, suggesting that the presence of any of these dietary components enhances Zn absorption. Based on the hypotheses that (1) Ca and Fe both promote Zn absorption by binding with phytate and thereby making it unavailable for binding Zn and (2) protein enhances the availability of Zn for transporter binding, the model was modified to incorporate these effects. The new model of Zn absorption as a function of dietary Zn, phytate, Ca, Fe and protein was then fitted to the data. The proportion of variation in absorbed Zn explained by the new model was 0·88, an increase from 0·82 with the original model. A reduced version of the model without Fe produced an equally good fit to the data and an improved value for the model selection criterion, demonstrating that when dietary Ca and protein are controlled for, there is no evidence that dietary Fe influences Zn absorption. Regression residuals and testing with additional data supported the validity of the new model. It was concluded that dietary Ca and protein modestly enhanced Zn absorption and Fe had no statistically discernable effect. Furthermore, the model provides a meaningful foundation for efforts to model nutrient interactions in mineral absorption.

  5. Iron

    MedlinePlus

    ... cereals and breads. White beans, lentils, spinach, kidney beans, and peas. Nuts and some dried fruits, such as raisins. Iron in food comes in two forms: heme iron and nonheme iron. Nonheme iron is found in plant foods and iron-fortified food products. Meat, seafood, ...

  6. Iron

    MedlinePlus

    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 ...

  7. Influence of dietary protein type and iron source on the absorption of amino acids and minerals.

    PubMed

    Pérez-Llamas, F; Garaulet, M; Martínez, J A; Marín, J F; Larqué, E; Zamora, S

    2001-12-01

    The apparent digestibility coefficient (ADC) of amino acids and the balance of minerals (calcium, phosphorus, magnesium and iron) has been determined in rats fed four diets differing in the protein type (casein or soy protein) and iron source (ferrous sulphate or lactate) in order to study the possible interactions of these nutrients. The availability of amino acids, especially essential amino acids, was greater in the diet made with animal protein (casein). The iron source also affected the absorption of most amino acids in all the diets assayed with ferrous sulphate being greater. The balance of iron, magnesium and phosphorus was higher in the diets containing animal protein. The retention of calcium and magnesium was significantly greater when ferrous sulphate was used as iron source. These results demonstrate the important interaction between amino acids and minerals and between the minerals themselves, which must be carefully studied when selecting different types of protein or mineral sources in human or animal nutrition.

  8. Biological Status and Dietary Intakes of Iron, Zinc and Vitamin A among Women and Preschool Children in Rural Burkina Faso

    PubMed Central

    Martin-Prevel, Yves; Allemand, Pauline; Nikiema, Laetitia; Ayassou, Kossiwavi A.; Ouedraogo, Henri Gautier; Moursi, Mourad; De Moura, Fabiana F.

    2016-01-01

    Background Food-based approaches such as biofortification are meant to sustainably address micronutrient deficiencies in poor settings. Knowing more about micronutrient intakes and deficiencies is a prerequisite to designing and evaluating interventions. Objective The objectives of the study were to assess biological status and dietary intakes of iron, zinc and vitamin A among women and children aged 36–59 months in rural Burkina Faso and to study relationships between intake and status to better inform future food-based interventions. Design A cross-sectional survey was carried out in two rural provinces of Burkina Faso on a random cluster sample of 480 mother-child pairs. Dietary data was obtained by 24-hour recalls repeated on a random sub-selection of 37.5% of subjects to allow calculation of nutrient’s probability of adequacy (PA). Biomarkers were measured on a sub-sample of 180 mother-child pairs. Blood samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptors (sTfR), C-reactive protein, alpha-1-glycoprotein, serum zinc concentration (SZnC) and retinol. For each micronutrient the relationship between biomarker and dietary intake was investigated by multiple linear regression models accounting for inflammatory biomarkers. Results Mean PA for iron, zinc and vitamin A was 0.49, 0.87 and 0.21 among women and 0.61, 0.95 and 0.33 among children, respectively. Prevalence of anemia, corrected low serum ferritin and high sTfR was 37.6%, 4.0% and 77.5% among women and 72.1%, 1.5% and 87.6% among children, respectively. Prevalence of low SZnC and corrected low serum retinol was 39.4% and 12.0% among women and 63.7% and 24.8% among children, respectively. There was a tendency for a positive relationship between vitamin A intakes and serum retinol among women (β = 0.0003, P = 0.06). Otherwise, no link was found between micronutrients biomarkers and intakes. Conclusion Our study depicted different images of micronutrient deficiencies when

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

    PubMed

    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

  10. Iron, oxidative stress, and redox signaling in the cardiovascular system.

    PubMed

    Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine; Rochette, Luc

    2014-08-01

    The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are involved in maintaining iron homeostasis. These include its storage at the intracellular and extracellular level. Control of iron balance in the whole organism requires communication between sites of uptake, utilization, and storage. Key protein transporters and the molecules that regulate their activities have been identified. In this field, ferritins and hepcidin are the major regulator proteins. A variety of transcription factors may be activated depending on the level of oxidative stress, leading to the expression of different genes. Major preclinical and clinical trials have shown advances in iron-chelation therapy for the treatment of iron-overload disease as well as cardiovascular and chronic inflammatory diseases.

  11. Iron, oxidative stress, and redox signaling in the cardiovascular system.

    PubMed

    Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine; Rochette, Luc

    2014-08-01

    The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are involved in maintaining iron homeostasis. These include its storage at the intracellular and extracellular level. Control of iron balance in the whole organism requires communication between sites of uptake, utilization, and storage. Key protein transporters and the molecules that regulate their activities have been identified. In this field, ferritins and hepcidin are the major regulator proteins. A variety of transcription factors may be activated depending on the level of oxidative stress, leading to the expression of different genes. Major preclinical and clinical trials have shown advances in iron-chelation therapy for the treatment of iron-overload disease as well as cardiovascular and chronic inflammatory diseases. PMID:24888568

  12. How to Avoid Fluid Overload

    PubMed Central

    Ogbu, Ogbonna C.; Murphy, David J.; Martin, Greg S.

    2015-01-01

    Purpose of the review This review highlights recent evidence describing the outcomes associated with fluid overload in critically ill patients and provides an overview of fluid management strategies aimed at preventing fluid overload during the resuscitation of patients with shock. Recent findings Fluid overload is a common complication of fluid resuscitation and is associated with increased hospital costs, morbidity and mortality. Summary Fluid management goals differ during the resuscitation, optimization, stabilization and evacuation phases of fluid resuscitation. To prevent fluid overload, strategies that reduce excessive fluid infusions and emphasize the removal of accumulated fluids should be implemented. PMID:26103147

  13. Ascorbic Acid Offsets the Inhibitory Effect of Bioactive Dietary Polyphenolic Compounds on Transepithelial Iron Transport in Caco-2 Intestinal Cells12

    PubMed Central

    Kim, Eun-Young; Ham, Soo-Kyung; Bradke, Daniel; Ma, Qianyi; Han, Okhee

    2011-01-01

    We previously reported that (-)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) at high concentration nearly blocked intestinal iron transport across the enterocyte. In this study, we aimed to determine whether small amounts of EGCG, GSE, and green tea extract (GT) are capable of inhibiting iron absorption, to examine if ascorbic acid counteracts the inhibitory action of polyphenols on iron absorption, and to explore the mechanisms of polyphenol-mediated apical iron uptake and basolateral iron release. An55Fe absorption study was conducted by adding various concentrations of EGCG, GSE, and GT using Caco-2 intestinal cells. Polyphenols were found to inhibit the transepithelial 55Fe transport in a dose-dependent manner. The addition of ascorbic acid offset the inhibitory effects of polyphenols on iron transport. Ascorbic acid modulated the transepithelial iron transport without changing the apical iron uptake and the expression of ferroportin-1 protein in the presence of EGCG. The polyphenol-mediated apical iron uptake was inhibited by membrane impermeable Fe2+ chelators (P < 0.001), but at a low temperature (4°C), the apical iron uptake was still higher than the control values at 37°C (P < 0.001). These results suggest that polyphenols enhance the apical iron uptake partially by reducing the conversion of ferric to ferrous ions and possibly by increasing the uptake of polyphenol-iron complexes via the energy-independent pathway. The present results indicate that the inhibitory effects of dietary polyphenols on iron absorption can be offset by ascorbic acid. Further studies are needed to confirm the current findings in vivo. PMID:21430251

  14. Dietary assessment methods for intakes of iron, calcium, selenium, zinc and iodine.

    PubMed

    Serra-Majem, Lluis; Pfrimer, Karina; Doreste-Alonso, Jorge; Ribas-Barba, Lourdes; Sánchez-Villegas, Almudena; Ortiz-Andrellucchi, Adriana; Henríquez-Sánchez, Patricia

    2009-12-01

    The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence is working towards developing aligned micronutrient recommendations across Europe. The purpose of the present study was to conduct a review of methods used in validation studies carried out in adults assessing dietary intake of EURRECA priority minerals. A search strategy and inclusion criteria were defined and a scoring system was developed to rate the quality of each validation study that produced a quality index with possible scores obtained ranging from 0.5 to 7. A MEDLINE and EMBASE literature review was conducted. Articles/validation studies meeting the inclusion criteria included: 79/88 for Fe; 95/104 for Ca; 13/15 for Se; 29/30 for Zn; 7/9 for iodine. The most frequently used method to ascertain dietary intake was the Food Frequency Questionnaire (FFQ), whereas dietary records (DR) and 24 h recalls were the most used reference methods. The correlation coefficients (CC) between study mineral intakes estimated by FFQ and the reference method were weighted according to the study's quality index and obtained acceptable to good ratings, ranging from 0.36 to 0.60 when the reference method was DR and from 0.41 to 0.58 when the reference was 24 h recalls. A minority of studies (n 9) used biomarkers for validation and among these, five included iodine obtaining a CC of 0.47. The FFQ was seen as a valid method for assessing mineral intake, particularly for Ca and, to a lower extent, for iodine and Zn. Se and Fe showed only acceptable correlations. The present review provides new insights regarding the characteristics that assessment methods for dietary mineral intakes should fulfil.

  15. Biofortified indica rice attains iron and zinc nutrition dietary targets in the field

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Iron (Fe) and zinc (Zn) deficiencies are the most prevalent micronutrient malnutrition globally1. Fe in rice has proven efficacious in improving serum ferritin concentration and body Fe levels2. Rapid progress in biofortification demonstrates the feasibility to enhance Fe in polished rice by expre...

  16. The Mythology of Information Overload.

    ERIC Educational Resources Information Center

    Tidline, Tonyia J.

    1999-01-01

    Combines ideas from mythology, folklore, and library and information science to conclude that information overload is a myth of modern culture. Reports results of a pilot project intended to describe information overload experienced by a particular folk group composed of future library and information professionals. (Author/LRW)

  17. Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

    PubMed Central

    Aigner, Elmar; Weiss, Günter; Datz, Christian

    2015-01-01

    Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxyl-radicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications. PMID:25729473

  18. Pharmacology of Iron Transport

    PubMed Central

    Byrne, Shaina L.; Krishnamurthy, Divya; Wessling-Resnick, Marianne

    2013-01-01

    Elucidating the molecular basis for the regulation of iron uptake, storage, and distribution is necessary to understand iron homeostasis. Pharmacological tools are emerging to identify and distinguish among different iron transport pathways. Stimulatory or inhibitory small molecules with effects on iron uptake can help characterize the mechanistic elements of iron transport and the roles of the transporters involved in these processes. In particular, iron chelators can serve as potential pharmacological tools to alleviate diseases of iron overload. This review focuses on the pharmacology of iron transport, introducing iron transport membrane proteins and known inhibitors. PMID:23020294

  19. Effects of dietary restriction and metal supplementation on the accumulation of iron-laden glial inclusions in the aging rat hippocampus.

    PubMed

    Borten, O; Liberman, A; Tuchweber, B; Chevalier, S; Ferland, G; Schipper, H M

    2004-01-01

    The mechanisms responsible for the pathological deposition of iron and other redox-active metals in the aging and degenerating mammalian CNS remain poorly understood. We previously demonstrated that normal aging and pharmacological (oxidative) stressors promote the transformation of astroglial mitochondria to iron-laden, diaminobenzidine (DAB)-positive cytoplasmic inclusions in sub-cortical regions of the rat brain. In the current study, we demonstrate that (1) numbers of DAB-positive glial granules in the rat dorsal hippocampus, an area implicated in learning and memory, progressively increase between 3, 12 and 22 months of age; (2) dietary restriction (40%), a manipulation that attenuates many mammalian aging processes, has no effect on the age-related accumulation of these gliosomes in the rat hippocampus; and (3) the latter can be accelerated by dietary supplementation of iron and copper. Our data support the view that dietary exposure to iron and/or copper in adult life can impact the sequestration of redox-active metals in aging hippocampal astroglia.

  20. Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats.

    PubMed

    Guéraud, Françoise; Taché, Sylviane; Steghens, Jean-Paul; Milkovic, Lidija; Borovic-Sunjic, Suzana; Zarkovic, Neven; Gaultier, Eric; Naud, Nathalie; Héliès-Toussaint, Cécile; Pierre, Fabrice; Priymenko, Nathalie

    2015-06-01

    The end products of polyunsaturated fatty acid (PUFA) peroxidation, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and isoprostanes (8-iso-PGF2α), are widely used as systemic lipid oxidation/oxidative stress biomarkers. However, some of these compounds have also a dietary origin. Thus, replacing dietary saturated fat by PUFAs would improve health but could also increase the formation of such compounds, especially in the case of a pro-oxidant/antioxidant imbalanced diet. Hence, the possible impact of dietary fatty acids and pro-oxidant compounds was studied in rats given diets allowing comparison of the effects of heme iron vs. ferric citrate and of ω-6- vs. ω-3-rich oil on the level of lipid peroxidation/oxidative stress biomarkers. Rats given a heme iron-rich diet without PUFA were used as controls. The results obtained have shown that MDA and the major urinary metabolite of HNE (the mercapturic acid of dihydroxynonane, DHN-MA) were highly dependent on the dietary factors tested, while 8-iso-PGF2α was modestly but significantly affected. Intestinal inflammation and tissue fatty acid composition were checked in parallel and could only explain the differences we observed to a limited extent. Thus, the differences in biomarkers were attributed to the formation of lipid oxidation compounds in food or during digestion, their intestinal absorption, and their excretion into urine. Moreover, fecal extracts from the rats fed the heme iron or fish oil diets were highly toxic for immortalized mouse colon cells. Such toxicity can eventually lead to promotion of colorectal carcinogenesis, supporting the epidemiological findings between red meat intake and colorectal cancer risk. Therefore, the analysis of these biomarkers of lipid peroxidation/oxidative stress in urine should be used with caution when dietary factors are not well controlled, while control of their possible dietary intake is needed also because of their pro-inflammatory, toxic, and even

  1. Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption

    PubMed Central

    Bayele, Henry K.; Balesaria, Sara; Srai, Surjit K.S.

    2015-01-01

    Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis. PMID:26546695

  2. Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption.

    PubMed

    Bayele, Henry K; Balesaria, Sara; Srai, Surjit K S

    2015-12-01

    Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis.

  3. The effect of dietary cadmium on zinc, copper and iron levels in the bone of rats.

    PubMed

    Bonner, F W; King, L J; Parke, D V

    1980-02-01

    The effect of continuous oral administration of cadium (Cd) (75 ppm) on the concentrations of zinc (ZN), Copper (CU) and iron (Fe) in the bone of rats was investigated. Accumulation of Cd in the femur was low but increased with time. After 8 weeks of Cd exposure, femur Zn and Fe levels were significantly decreased and remained low throughout the period of cadmium treatment. After 48 weeks, Cd exposed animals had Zn and Fe concentrations in the femur of 63% and 51% of controls, respectively. The femur Cu concentration was unchanged at 36 weeks but at 48 weeks it was 76% of control animals.

  4. Inhibitory effect of dietary iron deficiency on the induction of putative preneoplastic foci in rat liver initiated with diethylnitrosamine and promoted by phenobarbital.

    PubMed Central

    Yoshiji, H.; Nakae, D.; Kinugasa, T.; Matsuzaki, M.; Denda, A.; Tsujii, T.; Konishi, Y.

    1991-01-01

    The effects of dietary iron deficiency on induction of putative preneoplastic, gamma-glutamyltransferase (GGT)-positive hepatocyte focal lesions in the liver of rats treated with diethylnitrosamine (DEN) followed by phenobarbital (PB) were investigated. Male Fischer 344 rats of 4 weeks old were placed on an iron deficient (ID) diet containing less than 5 p.p.m. of iron or an iron supplemented (IS) diet containing 180 p.p.m. of iron throughout experimental period of 12 weeks. Both groups of rats were administered 200 mg kg-1 body weight of DEN by a single intraperitoneal injection at Week 4 followed by PB mixed into each diet at a concentration of 0.05% from Week 6 to the final sacrifice at Week 12 when induction of GGT-positive foci was quantitatively analysed. On the ID and IS diets, respective numbers of GGT-positive foci were 6.3 and 14.2 cm-2. The sizes of foci were not altered by the iron content of the diet. The present results indicate that iron plays a role in the development of preneoplastic foci in the livers of rats initiated with DEN and promoted by PB especially in the initiation phase. PMID:1681886

  5. Death by information overload.

    PubMed

    Hemp, Paul

    2009-09-01

    The value of information in the knowledge economy is indisputable, but so is its capacity to overwhelm consumers of it. HBR contributing editor Hemp reports on practical ways for individuals and organizations to avoid getting too much of a good thing. Ready access to useful information comes at a cost: As the volume increases, the line between the worthwhile and the distracting starts to blur. And ready access to you--via e-mail, social networking, and so on--exacerbates the situation: On average, Intel executives get 300 e-mails a day, and Microsoft workers need 24 minutes to return to work after each e-mail interruption. Clearly, productivity is taking a hit. Technological aids can help, such as e-mail management software for you, a message-volume regulation system for your organization, or even more-sophisticated solutions being developed by Microsoft, IBM, and others. Yet, battling technological interruptions on their own turf only goes so far. You also need to change your mind-set, perhaps by seeking help from personal-productivity experts or by simply accepting that you can't respond to every distraction that flits across your screen. Similarly, organizations must change their cultures, for instance by establishing clear e-communication protocols. In the end, only a multipronged approach will help you and your organization subdue the multiheaded monster of information overload. The secret is to manage the beast while still respecting it for the beautiful creature it is.

  6. Ethnic studies of dietary intakes of zinc, copper, iron, and calcium

    SciTech Connect

    Matthews, C.; Figueroa, M.; Tam, C.F.

    1986-01-01

    Immigrants, such as S.E. Asians who live in the L.A. area, often suffer high incidences of diseases. It is of interest to examine ethnic eating patterns whether they influence dietary Zn, Cu, Fe, Ca, protein and Kcal, which are essential for proper immune functions. Three-day dietary intake of adult ethnic groups, Asian(A)(N=18), Caucasian(C)(26), Black(B)(7), Latino(L)(12), Middle Easterner(ME)(9) and Filipino(F)(6) were analyzed for Zn, Cu, Fe, Ca, protein and Kcal by Ohio Data Base Foods II(ODBF) then statistically compared by PROPHET. Zn and Cu were also analyzed by hand calculation(HC). No statistical differences were observed for mean Zn between groups analyzed by ODBF whereas HC of mean Zn between A vs C (A=11.3 +/- S.D.2.9 mg vs C=8.8 +/- 2.8, P<0.01) and A vs L (11.3+/-2.9 vs L=8.9+/-2.2, P<0.05) were statistically different. No differences were found for Cu between the groups. By ODBF, none of mean Cu or Zn met 2/3 RDA for any of the groups. For Fe, no differences were found between groups and only 50% of the subjects met 2/3 RDA. Significant differences were observed for Ca only between A vs C and B vs C. Both A and B had lower mean Ca than C. All groups had adequate protein. Mean Kcal of all groups were found to be at or about 2/3 RDA. Both insufficient Kcal and eating patterns contribute to inadequate Cu, Zn, and Fe intakes and hence may affect immune competency.

  7. Biofortified indica rice attains iron and zinc nutrition dietary targets in the field.

    PubMed

    Trijatmiko, Kurniawan R; Dueñas, Conrado; Tsakirpaloglou, Nikolaos; Torrizo, Lina; Arines, Felichi Mae; Adeva, Cheryl; Balindong, Jeanette; Oliva, Norman; Sapasap, Maria V; Borrero, Jaime; Rey, Jessica; Francisco, Perigio; Nelson, Andy; Nakanishi, Hiromi; Lombi, Enzo; Tako, Elad; Glahn, Raymond P; Stangoulis, James; Chadha-Mohanty, Prabhjit; Johnson, Alexander A T; Tohme, Joe; Barry, Gerard; Slamet-Loedin, Inez H

    2016-01-01

    More than two billion people are micronutrient deficient. Polished grains of popular rice varieties have concentration of approximately 2 μg g(-1) iron (Fe) and 16 μg g(-1) zinc (Zn). The HarvestPlus breeding programs for biofortified rice target 13 μg g(-1) Fe and 28 μg g(-1) Zn to reach approximately 30% of the estimated average requirement (EAR). Reports on engineering Fe content in rice have shown an increase up to 18 μg g(-1) in glasshouse settings; in contrast, under field conditions, 4 μg g(-1) was the highest reported concentration. Here, we report on selected transgenic events, field evaluated in two countries, showing 15 μg g(-1) Fe and 45.7 μg g(-1) Zn in polished grain. Rigorous selection was applied to 1,689 IR64 transgenic events for insert cleanliness and, trait and agronomic performances. Event NASFer-274 containing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes showed a single locus insertion without a yield penalty or altered grain quality. Endosperm Fe and Zn enrichment was visualized by X-ray fluorescence imaging. The Caco-2 cell assay indicated that Fe is bioavailable. No harmful heavy metals were detected in the grain. The trait remained stable in different genotype backgrounds. PMID:26806528

  8. Biofortified indica rice attains iron and zinc nutrition dietary targets in the field

    PubMed Central

    Trijatmiko, Kurniawan R.; Dueñas, Conrado; Tsakirpaloglou, Nikolaos; Torrizo, Lina; Arines, Felichi Mae; Adeva, Cheryl; Balindong, Jeanette; Oliva, Norman; Sapasap, Maria V.; Borrero, Jaime; Rey, Jessica; Francisco, Perigio; Nelson, Andy; Nakanishi, Hiromi; Lombi, Enzo; Tako, Elad; Glahn, Raymond P.; Stangoulis, James; Chadha-Mohanty, Prabhjit; Johnson, Alexander A. T.; Tohme, Joe; Barry, Gerard; Slamet-Loedin, Inez H.

    2016-01-01

    More than two billion people are micronutrient deficient. Polished grains of popular rice varieties have concentration of approximately 2 μg g−1 iron (Fe) and 16 μg g−1 zinc (Zn). The HarvestPlus breeding programs for biofortified rice target 13 μg g−1 Fe and 28 μg g−1 Zn to reach approximately 30% of the estimated average requirement (EAR). Reports on engineering Fe content in rice have shown an increase up to 18 μg g−1 in glasshouse settings; in contrast, under field conditions, 4 μg g−1 was the highest reported concentration. Here, we report on selected transgenic events, field evaluated in two countries, showing 15 μg g−1 Fe and 45.7 μg g−1 Zn in polished grain. Rigorous selection was applied to 1,689 IR64 transgenic events for insert cleanliness and, trait and agronomic performances. Event NASFer-274 containing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes showed a single locus insertion without a yield penalty or altered grain quality. Endosperm Fe and Zn enrichment was visualized by X-ray fluorescence imaging. The Caco-2 cell assay indicated that Fe is bioavailable. No harmful heavy metals were detected in the grain. The trait remained stable in different genotype backgrounds. PMID:26806528

  9. Dose titration of deferasirox iron chelation therapy by magnetic resonance imaging for chronic iron storage disease in three adult red bald-headed uakari (Cacajao calvus rubicundus).

    PubMed

    Brewer, Casey; Tyszka, J Michael; Stadler, Cynthia K; Garner, Michael; Baer, Janet; Wood, John C

    2014-06-01

    Iron overload is common in lemurs and some New World nonhuman primates raised in captivity, but there is no such documentation in the red bald-headed uakari (Cacajao calvus rubicundus). This study describes postmortem documentation of severe iron storage disease in one red bald-headed uakari and the use of iron chelation with oral deferasirox in the three surviving members of the colony. Magnetic resonance imaging was used to quantify pretreatment iron burden and to follow the response to therapy in two females, 22 and 28 yr of age, and one male 33 yr of age. Baseline liver iron concentrations ranged from 16 to 23 mg/g dry weight. In humans, a liver iron concentration greater than 15 mg/g is considered severe and associated with endocrine and cardiac toxicity. The uakaris were otherwise asymptomatic, generally healthy, nonpregnant, and on a stable, low-iron diet. Quantitative magnetic resonance imaging indicated that dosage escalations up to 100 mg/kg were needed to produce meaningful reductions in iron stores. After 5 yr of therapy, two animals continue at a dosage of 100 mg/kg per day, and the third was transitioned to twice-weekly maintenance dosing because of successful de-ironing. The animals tolerated iron chelation therapy well, having stable hematologic, renal, and hepatic function profiles before, during, and after treatment. Deferasirox monotherapy may represent a therapeutic option in primates with iron storage disease when dietary measures are ineffective and phlebotomy is logistically challenging.

  10. Brain iron homeostasis.

    PubMed

    Moos, Torben

    2002-11-01

    transferrin were, however, restricted to areas situated in close proximity to the ventricular and pial surfaces. In particular, transferrin injected into the ventricles was never observed in regions distant from the CSF. It was concluded that choroid plexus-derived transferrin is not likely to play a significant role for binding and transporting iron in the brain interstitium. Transferrin secretion from oligodendrocytes probably plays the key role in this process. In the third part of the thesis, the uptake of iron by neurons devoid of projections beyond the blood-brain barrier and glia is addressed. Given the fact that the demonstration of plasma proteins in brain sections can be hampered by several methodological factors, a mapping of the cellular distribution of transferrin in the brain was performed employing extensive use of tissue-processing and staining protocols. In order to aid in the understanding of cellular iron uptake in the intact brain, attempts were made to identify iron, transferrin, and transferrin receptors at the light microscopic level. Consistent with the widespread distribution of transferrin receptors in neurons, the ligand transferrin was also found in neurons throughout the CNS. When examined at high resolution, transferrin was found to be distributed to the cytoplasm of neurons, exhibiting a dotted appearance, which is probably consistent with a distribution in the endosomallysosomal system. In contrast to the consistent presence of transferrin receptors on neurons, it was not possible to detect transferrin receptors on glial cells. Related to these observations, the presence of non-transferrin-bound iron in the brain suggests that glial cells may take it up by a mechanism that does not involve the transferrin receptor. The widespread distribution of ferritin in glial cells clearly indicates that the glial cells acquire iron. Dietary iron-overload did not change the distribution of transferrin receptors or ferritin in the brain. By contrast, iron

  11. Nutrient and plant secondary compound composition and iron-binding capacity in leaves and green stems of commonly used plant browse (Carolina willow; Salix caroliniana) fed to zoo-managed browsing herbivores.

    PubMed

    Lavin, S R; Sullivan, K E; Wooley, S C; Robinson, R; Singh, S; Stone, K; Russell, S; Valdes, E V

    2015-11-01

    Plant secondary compounds are diverse structurally, and associated biological effects can vary depending on multiple factors including chemical structure and reaction conditions. Phenolic compounds such as tannins can chelate dietary iron, and supplementation of animal species sensitive to iron overload with tannins may prevent/treat iron overload disorder. We assessed the nutrient and phenolic composition and iron-binding capacity of Carolina willow (Salix caroliniana), a plant fed to zoo-managed browsing herbivores. Based on studies in other plant species and the chemical structures of phenolic compounds, we hypothesized that the concentration of condensed tannins in willow would be inversely related to the concentration of phenolic glycosides and directly related to iron-binding capacity. Our results indicated that willow nutrient composition varied by year, season, and plant part, which could be taken into consideration when formulating animal diets. We also found that the predominant plant secondary compounds were condensed tannins with minimal phenolic glycosides. Instead of binding to iron, the willow leaf extracts reduced iron from the ferric to ferrous form, which may have prooxidative effects and increase the bioavailability of iron depending on animal species, gastrointestinal conditions, and whole animal processes. We recommend identifying alternative compounds that effectively chelate iron in vitro and conducting chelation therapy trials in vivo to assess potential effects on iron balance and overall animal health.

  12. Stability of bacterial carotenoids in the presence of iron in a model of the gastric compartment - comparison with dietary reference carotenoids.

    PubMed

    Sy, Charlotte; Dangles, Olivier; Borel, Patrick; Caris-Veyrat, Catherine

    2015-04-15

    Recently isolated spore-forming pigmented marine bacteria, Bacillus indicus HU36 and Bacillus firmus GB1 are sources of carotenoids (∼fifteen distinct yellow and orange pigments and ∼thirteen distinct pink pigments, respectively). They are glycosides of oxygenated lycopene derivatives (apo-lycopenoids) and are assumed to be more heat- and gastric-stable than common carotenoids. In this study, the oxidation by O2 of the bacterial carotenoids was initiated by free iron (Fe(II) and Fe(III)) or by heme iron (metmyoglobin) in a mildly acidic aqueous solution mimicking the gastro-intestinal compartment and compared to the oxidation of the common dietary carotenoids β-carotene, lycopene and astaxanthin. Under these conditions, all bacterial carotenoids appear more stable in the presence of heme iron vs. free iron. Carotenoid autoxidation initiated by Fe(II) is relatively fast and likely involves reactive oxygen-iron species derived from Fe(II) and O2. By contrast, the corresponding reaction with Fe(III) is kinetically blocked by the slow preliminary reduction of Fe(III) into Fe(II) by the carotenoids. The stability of carotenoids toward autoxidation increases as follows: β-caroteneiron-induced autoxidation of astaxanthin and HU36 carotenoids has been performed and gives insights in the underlying mechanisms. PMID:25595845

  13. Effect of dietary α-tocopherol + ascorbic acid, selenium, and iron on oxidative stress in sub-yearling Chinook salmon (Oncorhynchus tshawytscha Walbaum)

    USGS Publications Warehouse

    Welker, T.L.; Congleton, J.L.

    2009-01-01

    A three-variable central composite design coupled with surface-response analysis was used to examine the effects of dietary ??-tocopherol + ascorbic acid (TOCAA), selenium (Se), and iron (Fe) on indices of oxidative stress in juvenile spring Chinook salmon. Each dietary factor was tested at five levels for a total of fifteen dietary combinations (diets). Oxidative damage in liver and kidney (lipid peroxidation, protein carbonyls) and erythrocytes (erythrocyte resistance to peroxidative lysis, ERPL) was determined after feeding experimental diets for 16 (early December) and 28 (early March) weeks. Only TOCAA influenced oxidative stress in this study, with most measures of oxidative damage decreasing (liver lipid peroxidation in December and March; ERPL in December; liver protein carbonyl in March) with increasing levels of TOCAA. We also observed a TOCAA-stimulated increase in susceptibility of erythrocytes to peroxidative lysis in March at the highest levels of TOCAA. The data suggest that under most circumstances a progressive decrease in oxidative stress occurs as dietary TOCAA increases, but higher TOCAA concentrations can stimulate oxidative damage in some situations. Higher levels of TOCAA in the diet were required in March than in December to achieve comparable levels of protection against oxidative damage, which may have been due to physiological changes associated with the parr-smolt transformation. Erythrocytes appeared to be more sensitive to variation in dietary levels of TOCAA than liver and kidney tissues. Using the March ERPL assay results as a baseline, a TOCAA level of approximately 350-600 mg/kg diet would provide adequate protection against lipid peroxidation under most circumstances in juvenile Chinook salmon. ?? 2008 The Authors.

  14. Hepcidin: an emerging biomarker for iron disorders, inflammatory diseases, and infections

    NASA Astrophysics Data System (ADS)

    Westerman, Mark E.; Olbina, Gordana; Ostland, Vaughn E.; Nemeth, Elizabeta; Ganz, Tomas

    2010-04-01

    The peptide hormone hepcidin, has emerged as the master regulator of iron homeostasis. Dysregulation of hepcidin is a principal or contributing factor in most genetic and acquired systemic iron disorders, including anemia of inflammation (anemia of chronic disease). Hepcidin maintains healthy blood iron levels by regulating dietary iron absorption and transport from body iron stores to plasma. High serum hepcidin levels observed in chronic and acute inflammatory conditions can cause anemia by limiting plasma iron available for erythropoiesis. Chronically low serum hepcidin levels cause iron-overload and ultimately, accumulation of iron in liver and heart. We recently validated the first immunoassay for serum hepcidin and established the normal ranges in adults. Hepcidin has excellent potential as a biomarker and has a known mechanism of action, good stability, and rapid response to iron stores, inflammatory stimuli, and bacterial infections. Hepcidin can be measured in blood, urine, and saliva, and is generally not measurable in iron deficient/anemic patients and highly elevated in inflammatory diseases and infections. Intrinsic LifeSciences (ILS) is developing second generation hepcidin immunoassays and lateral-flow POC devices for hepcidin, a well characterized multi-purpose biomarker with applications in global health security.

  15. Contribution of meat to vitamin B-12, iron, and zinc intakes in five ethnic groups in the U.S.: Implications for developing food-based dietary guidelines

    PubMed Central

    Sharma, Sangita; Sheehy, Tony; Kolonel, Laurence N

    2016-01-01

    Background To describe the sources of meat and their contributions to vitamin B-12, iron, and zinc in five ethnic groups in the USA. Methods Dietary data for the Multiethnic Cohort, established in Hawaii and Los Angeles, were collected using a quantitative food frequency questionnaire from more than 215,000 subjects aged 45–75 years at baseline (1993–1996). Participants included African American, Latino, Japanese American (JpAm), Native Hawaiian (NH) and Caucasian men and women. Servings of meat items were calculated based on the USDA recommendations and their contributions to intakes of total meat, red meat, vitamin B-12, iron, and zinc were determined. Results Of all types of meat, poultry contributed the most to meat consumption, followed by red meat and fish among all ethnicities, except for Latino (born in Mexico and Central/South America) men who consumed more beef. Lean beef was the most commonly consumed red meat for all ethnic-sex groups (9.3–14.3%), except for NH and JpAm men, and JpAm women whose top contributor was stew/curry with beef/lamb and stir-fried beef/pork with vegetables respectively. The contribution of meat was most substantial for zinc (11.1–29.3%) and vitamin B-12 (19.7–40%), and to a lesser extent for iron (4.3–14.2%). Conclusions This is the first large multiethnic cohort study to describe meat sources and their contributions to selected nutrients among ethnic minorities in the U.S. These findings may be used to develop ethnic-specific recommendations for meat consumption to improve dietary quality among these groups. PMID:23398393

  16. Iron and the liver.

    PubMed

    Pietrangelo, Antonello

    2016-01-01

    Humans have evolved to retain iron in the body and are exposed to a high risk of iron overload and iron-related toxicity. Excess iron in the blood, in the absence of increased erythropoietic needs, can saturate the buffering capacity of serum transferrin and result in non-transferrin-bound highly reactive forms of iron that can cause damage, as well as promote fibrogenesis and carcinogenesis in the parenchymatous organs. A number of hereditary or acquired diseases are associated with systemic or local iron deposition or iron misdistribution in organs or cells. Two of these, the HFE- and non-HFE hemochromatosis syndromes represent the paradigms of genetic iron overload. They share common clinical features and the same pathogenic basis, in particular, a lack of synthesis or activity of hepcidin, the iron hormone. Before hepcidin was discovered, the liver was simply regarded as the main site of iron storage and, as such, the main target of iron toxicity. Now, as the main source of hepcidin, it appears that the loss of the hepcidin-producing liver mass or genetic and acquired factors that repress hepcidin synthesis in the liver may also lead to iron overload. Usually, there is low-grade excess iron which, through oxidative stress, is sufficient to worsen the course of the underlying liver disease or other chronic diseases that are apparently unrelated to iron, such as chronic metabolic and cardiovascular diseases. In the future, modulation of hepcidin synthesis and activity or hepcidin hormone-replacing strategies may become therapeutic options to cure iron-related disorders.

  17. Iron status and cellular immune competence.

    PubMed

    Good, M F; Powell, L W; Halliday, J W

    1988-03-01

    There is increasing evidence that both iron overload and iron deficiency are associated with significant abnormalities of immune function. In diseases associated with iron overload there is increased susceptibility to both infection and neoplasia. The precise mechanisms are still being unravelled but iron overload has been shown to impair antigen-specific immune responses and to reduce the number of functional helper precursor cells. Similarly, iron in vitro in concentrations reported to be present in the serum of patients with iron overload impairs the generation of cytotoxic T-cells, enhances suppressor T-cell activity and reduces the proliferative capacity of helper T-cells. The predominant tumor seen in iron overload is primary hepatocellular carcinoma; however other aetiological factors appear to be involved in addition to iron overload, especially hepatic cirrhosis. Nevertheless, primary liver cancer occurs much more frequently in hemochromatosis than in other forms of cirrhosis. Iron deficiency is associated with an altered response to infection but the relationship is again a complex one. The cellular mechanisms involved have yet to be clearly defined, although impaired T and B cell function have been demonstrated.

  18. Epigallocatechin-3-Gallate Inhibition of Myeloperoxidase and Its Counter-Regulation by Dietary Iron and Lipocalin 2 in Murine Model of Gut Inflammation.

    PubMed

    Yeoh, Beng San; Aguilera Olvera, Rodrigo; Singh, Vishal; Xiao, Xia; Kennett, Mary J; Joe, Bina; Lambert, Joshua D; Vijay-Kumar, Matam

    2016-04-01

    Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment. PMID:26968114

  19. Ferritin as a reporter gene for MRI: chronic liver over expression of H-ferritin during dietary iron supplementation and aging.

    PubMed

    Ziv, Keren; Meir, Gila; Harmelin, Alon; Shimoni, Eyal; Klein, Eugenia; Neeman, Michal

    2010-06-01

    The iron storage protein, ferritin, provides an important endogenous MRI contrast that can be used to determine the level of tissue iron. In recent years the impact of modulating ferritin expression on MRI contrast and relaxation rates was evaluated by several groups, using genetically modified cells, viral gene transfer and transgenic animals. This paper reports the follow-up of transgenic mice that chronically over-expressed the heavy chain of ferritin (h-ferritin) in liver hepatocytes (liver-hfer mice) over a period of 2 years, with the aim of investigating the long-term effects of elevated level of h-ferritin on MR signal and on the well-being of the mice. Analysis revealed that aging liver-hfer mice, exposed to chronic elevated expression of h-ferritin, have increased R(2) values compared to WT. As expected for ferritin, R(2) difference was strongly enhanced at high magnetic field. Histological analysis of these mice did not reveal liver changes with prolonged over expression of ferritin, and no differences could be detected in other organs. Furthermore, dietary iron supplementation significantly affected MRI contrast, without affecting animal wellbeing, for both wildtype and ferritin over expressing transgenic mice. These results suggest the safety of ferritin over-expression, and support the use of h-ferritin as a reporter gene for MRI.

  20. Bioavailability of iron in geophagic earths and clay minerals, and their effect on dietary iron absorption using an in vitro digestion/Caco-2 cell model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Geophagy, the deliberate consumption of earth, is strongly associated with iron (Fe) deficiency. It has been proposed that geophagy may be practiced as a means to improve Fe status by increasing Fe intakes and, conversely, that geophagy may cause Fe deficiency by inhibiting Fe absorption. We tested ...

  1. Effects of Selected Dietary Secondary Metabolites on Reactive Oxygen Species Production Caused by Iron(II) Autoxidation

    PubMed Central

    Chobot, Vladimir; Hadacek, Franz; Kubicova, Lenka

    2015-01-01

    Iron is an essential co-factor for many enzymes that catalyze electron transfer reactions. It is well known that so-called “poorly liganded” iron can increase ROS concentrations and trigger oxidative stress that is capable of initiating apoptosis. Conversely, controlled ROS production has been recognized as an integral part of cellular signaling. Elevated ROS concentrations are associated with aging, inflammatory and degenerative diseases. Anti-aging properties have been attributed especially to antioxidant phenolic plant metabolites that represent food additives in our diet. Consequently, this study explores the effects of flavonoids (quercetin and rutin), several phenolic acids (caffeic, chlorogenic, and protocatechuic acid), and the alkaloid caffeine on iron(II) autoxidation and ROS production in comparison to the standard antioxidants ascorbic acid and Trolox. The iron(II) autoxidation assay was carried out in pH 6.0 (plant apoplast and inflamed human tissue) and 7.4 (cell cytoplasm and human blood plasma). The obtained results accentuate phenolic acids as the more specific antioxidants compared to ascorbic acid and Trolox. Flavonoid redox chemistry depends more on the chemical milieu, specifically on pH. In vivo, the presence of iron cannot be ruled out and “wrongly” or “poorly” complexed iron has been pointed out as causative agent of various age-related diseases. PMID:25470272

  2. Trials of Improved Practices (TIPs) to Enhance the Dietary and Iron-Folate Intake during Pregnancy- A Quasi Experimental Study among Rural Pregnant Women of Varanasi, India

    PubMed Central

    Shivalli, Siddharudha; Srivastava, Ratan Kumar; Singh, Gyan Prakash

    2015-01-01

    Background Behavior Change Communications (BCC) play a decisive role in modifying socio-cultural norms affecting the perception and nutritional practices during pregnancy. Objective To examine the effectiveness of ‘Trials of Improved Practices’ (TIPs) on dietary and iron-folate intake during pregnancy. Design Community based quasi experimental study with a control group Setting Four villages of Chiraigaon Community Development Block of Varanasi, India from May 2010 and recruited from August 2010. End line assessment, after 12 weeks of intervention, was completed in April 2011. Participants Pregnant women in 13–28 weeks of gestation Intervention TIPs was implemented in addition to ongoing essential obstetric care services in two villages through 3 home (assessment, negotiation and evaluation) visits and only assessment and evaluation visits in the other two control villages. Interpersonal communication, endorsing the active participation of family members and home based reminder materials were the TIPs based strategies. The effect of TIPs was assessed by comparing key outcome variables at baseline and after 12 weeks of intervention. Outcome Measures Hemoglobin%, anemia prevalence, weight gain, compliance for iron-folate supplementation and dietary intake of calorie, protein, calcium and iron. Results A total of 86 participants completed the study. At the end, mean hemoglobin levels were 11.5±1.24 g/dl and 10.37±1.38 g/dl in the TIPs and control groups, respectively. The prevalence of anemia reduced by half in TIPs group and increased by 2.4% in the control group. Weight gain (grams/week) was significantly (p<0.01) higher in TIPs group (326.9±91.8 vs. 244.6±97.4). More than 85% of the PW in TIPs group were compliant for Iron-folate and only 38% were compliant among controls. The mean intake of protein increased by 1.78gm in intervention group and decreased by 1.81 gm in controls (p<0.05). More than two thirds of PW in TIPs group were taking one extra meal

  3. Influence of dietary iron level and form on biochemical, hematological, and immunological changes in copper deficient rats

    SciTech Connect

    Leu, H.; Gallaher, D.D.; Kramer, T.R.

    1986-03-01

    Weanling male Lewis rats (N = 10/group) were fed ad-libitum for 42 days diets based on AIN standards containing 21% casein, 5% safflower oil, deficient (0.6 ..mu..g/g) or adequate (5.6 ..mu..g/g) levels of Cu, and adequate (50 ..mu..g/g) or high (300 ..mu..g/g) levels of Fe/sup +2/ or Fe/sup +3/. Cu-deficient rats, regardless of Fe level or form, exhibited depressed (p < 0.05) serum Cu, Fe and ceruloplasmin activity, and hemoglobin levels; and elevated (p < 0.05) unsaturated serum Fe binding capacity. Except for high Fe/sup +3/ fed rats, Cu-deficient rats showed decreased hematocrits. Decreased proliferation was exhibited by concanavalin-A (Con-A) stimulated spleen lymphoid cells (SLC) of Cu-deficient rats fed adequate dietary Fe, but not by SLC of Cu-deficient rats fed high dietary Fe. High Fe fed rats exhibited reduced proliferation and increased variability in proliferation by Con-A stimulated SLC, which apparently caused a lack of difference in proliferation by SLC of Cu-deficient and Cu-adequate rats fed high Fe. Thus, high dietary Fe did not correct biochemical and hematological parameters in Cu-deficient rats, but because of lowered proliferation and increased variability of SLC proliferation, high dietary Fe did alleviate suppressed Con-A stimulated SLC proliferation in Cu-deficiency.

  4. Chitosan Interaction with Iron from Yoghurt Using an In Vitro Digestive Model: Comparative Study with Plant Dietary Fibers

    PubMed Central

    Staffolo, Marina Dello; Martino, Miriam; Bevilacqua, Alicia; Montero, Mirta; Rodríguez, María Susana; Albertengo, Liliana

    2011-01-01

    The objective of this work was to investigate the interaction of chitosan with iron from yoghurt by an in vitro gastrointestinal tract model. Taking into account that chitosan is a polysaccharide included in fiber definition by Codex Alimentarius; chitosan behavior was studied and compared with different plant fiber (wheat, bamboo, apple, psyllium and inulin) behaviors, in the same in vitro conditions. Ferrous sulfate was added to yoghurts with each type of fiber. The gastric environment was simulated with HCl (pH 1.0–2.0). The duodenal environment was simulated with NaHCO3 (pH 6.8–7.2) and a dialysis tubing cellulose membrane. Results showed that chitosan had the highest iron retention percentages (53.2% at 30 min; 56.8% at 60 min) interacting in a more pronounced manner with iron than the plant fibers used in this work. PMID:21845102

  5. Dietary iron intake in the first 4 months of infancy and the development of type 1 diabetes: a pilot study

    PubMed Central

    2010-01-01

    Aims To investigate the impact of iron intake on the development of type 1 diabetes (T1DM). Methods Case-control study with self-administered questionnaire among families of children with T1DM who were less than 10 years old at the time of the survey and developed diabetes between age 1 and 6 years. Data on the types of infant feeding in the first 4 months of life was collected from parents of children with T1DM (n = 128) and controls (n = 67) <10 years old. Because some cases had sibling controls, we used conditional logistic regression models to analyze the data in two ways. First we performed a case-control analysis of all 128 cases and 67 controls. Next, we performed a case-control analysis restricted to cases (n = 59) that had a sibling without diabetes (n = 59). Total iron intake was modeled as one standard deviation (SD) increase in iron intake. The SD for iron intake was 540 mg in the total sample and 539 mg in the restricted sample as defined above. Results The median (min, max) total iron intake in the first 4 months of life was 1159 (50, 2399) mg in T1DM cases and 466 (50, 1224) mg among controls (P < 0.001). For each one standard deviation increase in iron intake, the odds ratio (95% confidence interval) for type 1 diabetes was 2.01 (1.183, 3.41) among all participants (128 cases and 67 controls) while it was 2.26 (1.27, 4.03) in a restricted sample of T1 D cases with a control sibling (59 cases and 59 controls) in models adjusted for birth weight, age at the time of the survey, and birth order. Conclusion In this pilot study, high iron intake in the first 4 months of infancy is associated with T1DM. Whether iron intake is causal or a marker of another risk factor warrants further investigation. PMID:20854668

  6. Molecular evidence and physiological characterization of iron absorption in isolated enterocytes of rainbow trout (Oncorhynchus mykiss): implications for dietary cadmium and lead absorption.

    PubMed

    Kwong, Raymond W M; Andrés, Jose A; Niyogi, Som

    2010-09-01

    Recent studies suggested the probable involvement of an apical iron (Fe(2+)) transporter, the divalent metal transporter-1 (DMT1), in the uptake of several divalent metals in fish. The present study examined the gastrointestinal expression of the DMT1 gene, and investigated the kinetics of Fe(2+) uptake and its interactions with cadmium and lead in isolated enterocytes of freshwater rainbow trout (Oncorhynchus mykiss). The expressions of two DMT1 isoforms (Nramp-beta and -gamma) were recorded along the entire gastrointestinal tract of fish as well as in the enterocytes. Fe(2+) uptake in isolated enterocytes was saturable and sensitive to the proton gradient and membrane potential, suggesting DMT1-mediated transport. Both cadmium and lead inhibited Fe(2+) uptake in isolated enterocytes in a concentration-dependent manner, and lead appeared to be a stronger inhibitor than cadmium. The kinetic characterization of Fe(2+) uptake revealed that the apparent affinity of uptake was significantly decreased (increased K(m)) in the presence of either cadmium or lead, whereas the maximum uptake rate (J(max)) remained unchanged-indicating that the interaction between Fe(2+) and cadmium or lead is competitive in nature. Overall, our study suggests that the uptake of dietary cadmium and lead may occur via the iron-transporting pathway in fish.

  7. Lipid peroxidation by "free" iron ions and myoglobin as affected by dietary antioxidants in simulated gastric fluids.

    PubMed

    Lapidot, Tair; Granit, Rina; Kanner, Joseph

    2005-05-01

    Grilled red turkey muscle (Doner Kabab) is a real "fast food" containing approximately 200 microM hydroperoxides, homogenized in simulated gastric fluid and oxidized more rapidly at pH 3.0 than at pH 5.0, after 180 min, producing 1200 and 600 microM hydroperoxides, respectively. The effects of "free" iron ions and metmyoglobin, two potential catalyzers of lipid peroxidation in muscle foods, were evaluated for linoleic acid peroxidation at pH 3.0 of simulated gastric fluid. The prooxidant effects of free iron ions on linoleic acid peroxidation in simulated gastric fluid was evaluated in the presence of ascorbic acid. At low concentrations of ascorbic acid, the effects were prooxidative, which was reversed at high concentrations. In the presence of metmyoglobin, ascorbic acid with or without free iron enhanced the antioxidative effect. Lipid peroxidation by an iron-ascorbic acid system was inhibited totally by 250-500 microM catechin at pH 3.0. The catechin antioxidant effect was determined also in the iron-ascorbic acid system containing metmyoglobin. In this system, catechin totally inhibited lipid peroxidation at a concentration 20-fold lower than without metmyoglobin. The ability of catechin to inhibit lipid peroxidation was also determined at a low pH with beta-carotene as a sensitive target molecule for oxidation. The results show that a significant protection was achieved only with almost 100-fold higher antioxidant concentration. Polyphenols from different groups were determined for the antioxidant activity at pH 3.0. The results show a high antioxidant activity of polyphenols with orthodihydroxylated groups at the B ring, unsaturation, and the presence of a 4-oxo group in the heterocyclic ring, as demonstrated by quercetin. PMID:15853376

  8. Lipid peroxidation by "free" iron ions and myoglobin as affected by dietary antioxidants in simulated gastric fluids.

    PubMed

    Lapidot, Tair; Granit, Rina; Kanner, Joseph

    2005-05-01

    Grilled red turkey muscle (Doner Kabab) is a real "fast food" containing approximately 200 microM hydroperoxides, homogenized in simulated gastric fluid and oxidized more rapidly at pH 3.0 than at pH 5.0, after 180 min, producing 1200 and 600 microM hydroperoxides, respectively. The effects of "free" iron ions and metmyoglobin, two potential catalyzers of lipid peroxidation in muscle foods, were evaluated for linoleic acid peroxidation at pH 3.0 of simulated gastric fluid. The prooxidant effects of free iron ions on linoleic acid peroxidation in simulated gastric fluid was evaluated in the presence of ascorbic acid. At low concentrations of ascorbic acid, the effects were prooxidative, which was reversed at high concentrations. In the presence of metmyoglobin, ascorbic acid with or without free iron enhanced the antioxidative effect. Lipid peroxidation by an iron-ascorbic acid system was inhibited totally by 250-500 microM catechin at pH 3.0. The catechin antioxidant effect was determined also in the iron-ascorbic acid system containing metmyoglobin. In this system, catechin totally inhibited lipid peroxidation at a concentration 20-fold lower than without metmyoglobin. The ability of catechin to inhibit lipid peroxidation was also determined at a low pH with beta-carotene as a sensitive target molecule for oxidation. The results show that a significant protection was achieved only with almost 100-fold higher antioxidant concentration. Polyphenols from different groups were determined for the antioxidant activity at pH 3.0. The results show a high antioxidant activity of polyphenols with orthodihydroxylated groups at the B ring, unsaturation, and the presence of a 4-oxo group in the heterocyclic ring, as demonstrated by quercetin.

  9. Erythrocyte membrane fatty acid composition is related to overloaded plasma ferritin in Chinese males with angiographic coronary artery disease.

    PubMed

    Li, Zhongxia; Li, Xinrui; Zhang, Yuan; Feng, Xiang; Yang, Fang; Su, Dongfang; Qiu, Jian; Ling, Wenhua; Yang, Yan

    2013-10-01

    Not only is iron deficiency an abnormal iron status, but iron overload is also harmful for human health. It has been reported that overloaded iron stores are positively associated with increased coronary artery disease (CAD) risk, which is called the "iron-heart hypothesis". Previous studies evaluating the relationships between fatty acids (FAs) and body iron status only focused on participants with iron deficiency. However, whether FA composition is related to overloaded iron remains unclear. Therefore, this study was designed to investigate the relationships between erythrocyte membrane FA (Ery-FA) composition and overloaded body iron status as measured by plasma ferritin levels in Chinese CAD patients. A total of 446 subjects with angiographically identified CAD (mean age 63.1 years, 76.9% males) were recruited in a hospital between 2009 and 2010. Ery-FAs were measured by gas chromatography and the activities of FA desaturases, which are involved in the de novo synthesis of unsaturated FAs, were evaluated by using FA product-to-precursor ratios. Results showed that the average iron status was a bit overloaded in the population (median ferritin levels of 234.1 ng mL(-1) and 40.4% males of overload). Moreover, in males, saturated FAs (SFAs) were positively correlated (22 : 0, r = 0.182, p = 0.001; 24 : 0, r = 0.214, p < 0.001), whereas monounsaturated FAs (MUFAs) and n-6 polyunsaturated FAs (PUFAs) were negatively correlated (18 : 1n-9, r = -0.120, p = 0.028; 18 : 2n-6, r = -0.216, p < 0.001) with plasma ferritin levels. A negative correlation (r < 0, p < 0.05) between stearoyl-CoA desaturase (SCD) activity and ferritin levels was also found in males. However, all the significant associations above were not observed in females. In conclusion, the Ery-FA composition was related to overloaded plasma ferritin levels only in Chinese males with angiographic CAD, which might be linked to the change of SCD activity. The results may contribute to the understanding of the

  10. Dietary Intake, Anthropometric Characteristics, and Iron and Vitamin D Status of Female Adolescent Ballet Dancers Living in New Zealand.

    PubMed

    Beck, Kathryn L; Mitchell, Sarah; Foskett, Andrew; Conlon, Cathryn A; von Hurst, Pamela R

    2015-08-01

    Ballet dancing is a multifaceted activity requiring muscular power, strength, endurance, flexibility, and agility; necessitating demanding training schedules. Furthermore dancers may be under aesthetic pressure to maintain a lean physique, and adolescent dancers require extra nutrients for growth and development. This cross-sectional study investigated the nutritional status of 47 female adolescent ballet dancers (13-18 years) living in Auckland, New Zealand. Participants who danced at least 1 hr per day 5 days per week completed a 4-day estimated food record, anthropometric measurements (Dual-energy X-ray Absorptiometry) and hematological analysis (iron and vitamin D). Mean BMI was 19.7 ± 2.4 kg/m2 and percentage body fat, 23.5 ± 4.1%. The majority (89.4%) of dancers had a healthy weight (5th-85th percentile) using BMI-for-age growth charts. Food records showed a mean energy intake of 8097.3 ± 2155.6 kJ/day (48.9% carbohydrate, 16.9% protein, 33.8% fat, 14.0% saturated fat). Mean carbohydrate and protein intakes were 4.8 ± 1.4 and 1.6 ± 0.5 g/kg/day respectively. Over half (54.8%) of dancers consumed less than 5 g carbohydrate/kg/day, and 10 (23.8%) less than 1.2 g protein/kg/day. Over 60% consumed less than the estimated average requirement for calcium, folate, magnesium and selenium. Thirteen (28.3%) dancers had suboptimal iron status (serum ferritin (SF) < 20 μg/L). Of these, four had iron deficiency (SF < 12 μg/L, hemoglobin (Hb) ≥ 120 g/L) and one iron deficiency anemia (SF < 12 μg/L, Hb < 120 g/L). Mean serum 25-hydroxy vitamin D was 75.1 ± 18.6 nmol/L, 41 (91.1%) had concentrations above 50 nmol/L. Female adolescent ballet dancers are at risk for iron deficiency, and possibly inadequate nutrient intakes. PMID:25386731

  11. Dietary Intake, Anthropometric Characteristics, and Iron and Vitamin D Status of Female Adolescent Ballet Dancers Living in New Zealand.

    PubMed

    Beck, Kathryn L; Mitchell, Sarah; Foskett, Andrew; Conlon, Cathryn A; von Hurst, Pamela R

    2015-08-01

    Ballet dancing is a multifaceted activity requiring muscular power, strength, endurance, flexibility, and agility; necessitating demanding training schedules. Furthermore dancers may be under aesthetic pressure to maintain a lean physique, and adolescent dancers require extra nutrients for growth and development. This cross-sectional study investigated the nutritional status of 47 female adolescent ballet dancers (13-18 years) living in Auckland, New Zealand. Participants who danced at least 1 hr per day 5 days per week completed a 4-day estimated food record, anthropometric measurements (Dual-energy X-ray Absorptiometry) and hematological analysis (iron and vitamin D). Mean BMI was 19.7 ± 2.4 kg/m2 and percentage body fat, 23.5 ± 4.1%. The majority (89.4%) of dancers had a healthy weight (5th-85th percentile) using BMI-for-age growth charts. Food records showed a mean energy intake of 8097.3 ± 2155.6 kJ/day (48.9% carbohydrate, 16.9% protein, 33.8% fat, 14.0% saturated fat). Mean carbohydrate and protein intakes were 4.8 ± 1.4 and 1.6 ± 0.5 g/kg/day respectively. Over half (54.8%) of dancers consumed less than 5 g carbohydrate/kg/day, and 10 (23.8%) less than 1.2 g protein/kg/day. Over 60% consumed less than the estimated average requirement for calcium, folate, magnesium and selenium. Thirteen (28.3%) dancers had suboptimal iron status (serum ferritin (SF) < 20 μg/L). Of these, four had iron deficiency (SF < 12 μg/L, hemoglobin (Hb) ≥ 120 g/L) and one iron deficiency anemia (SF < 12 μg/L, Hb < 120 g/L). Mean serum 25-hydroxy vitamin D was 75.1 ± 18.6 nmol/L, 41 (91.1%) had concentrations above 50 nmol/L. Female adolescent ballet dancers are at risk for iron deficiency, and possibly inadequate nutrient intakes.

  12. [Iron function and carcinogenesis].

    PubMed

    Akatsuka, Shinya; Toyokuni, Shinya

    2016-07-01

    Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models.

  13. [Iron function and carcinogenesis].

    PubMed

    Akatsuka, Shinya; Toyokuni, Shinya

    2016-07-01

    Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models. PMID:27455808

  14. Adequately Diversified Dietary Intake and Iron and Folic Acid Supplementation during Pregnancy Is Associated with Reduced Occurrence of Symptoms Suggestive of Pre-Eclampsia or Eclampsia in Indian Women

    PubMed Central

    Agrawal, Sutapa; Fledderjohann, Jasmine; Vellakkal, Sukumar; Stuckler, David

    2015-01-01

    Background/Objective Pre-eclampsia or Eclampsia (PE or E) accounts for 25% of cases of maternal mortality worldwide. There is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. We examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E in Indian women. Methods Cross-sectional data from India’s third National Family Health Survey (NFHS-3, 2005-06) was used for this study. Self-reported symptoms suggestive of PE or E during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. Multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother. Results In their most recent pregnancy, 1.2% (n=456) of the study sample experienced symptoms suggestive of PE or E. Mothers who consumed an adequately diversified diet were 34% less likely (OR: 0.66; 95% CI: 0.51-0.87) to report PE or E symptoms than mothers with inadequately diversified dietary intake. The likelihood of reporting PE or E symptoms was also 36% lower (OR: 0.64; 95% CI: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. As a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. Our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of PE or E symptoms. Conclusion Having a adequately diversified dietary

  15. Dietary protection by iron against clastogenic effects of short-term exposure to arsenic in mice in vivo.

    PubMed

    Poddar, S; Mukherjee, P; Talukder, G; Sharma, A

    2000-08-01

    Iron, as freshly prepared aqueous solution of ferrous sulfate, was administered by gavage to laboratory bred Swiss albino mice. The concentration used was 152 mg/kg body weight (1/10 of the LD(50)). While screening for protection against arsenic, in one set of experiment exposure to iron was followed after 2 hr by gavaging with 2.5 mg/kg body weight (1/10 of the LD(50)) of arsenic as sodium (III) meta arsenite in distilled water. In another set, equal amounts (1:1) of ferrous sulfate and sodium arsenite were administered simultaneously. Control sets were given sodium m-arsenite alone and distilled water (vehicle). After exposure for 24 hr in all experiments, mice were sacrificed and chromosome preparations were made from bone marrow according to a colchicine-hypotonic-fixation-air-drying-Giemsa schedule. Cytogenetic endpoints screened were chromosome aberrations and divisional frequencies. Sodium arsenite alone was highly clastogenic. Ferrous sulfate, whether given together with or before exposure to sodium arsenite, reduced the clastogenic effects of the latter to a significant extent.

  16. Action of dietary trypsin, pressed coffee oil, silymarin and iron salt on 1,2-dimethylhydrazine tumorigenesis by gavage.

    PubMed

    Gershbein, L L

    1994-01-01

    Sprague-Dawley male rats, 24 days of age, were placed on diets based on a balanced ration as such and supplemented with Brazilian A rabica green coffee bean oil (0.10%), silymarin flavonolignans (0.10%), porcine trypsin (2429 mu/g ration) and ferrous sulfate (0.24% Fe) for a period of 32 weeks. A portion of the controls was switched to the iron salt diet at day 37 when 1,2-dimethylhydrazine was administered by gavage at a dosage of 20 mg/kg (base) and continued weekly for a total of 15 weeks. The colon and small intestinal adenocarcinoma numbers were determined for each group of rats surviving the carcinogen treatment and compared with the respective controls by a statistical design based on Poisson distribution. The results indicate that the adenocarcinoma frequencies of the colon, both total and occurrence in the proximal and distal portions were significantly decreased in the groups fed coffee oil, silymarin group and trypsin. The colon tumor numbers for the iron salt-fed were in the control range except for a decrement in the distal colon for rats on the diet from the start. Small intestinal adenocarcinoma scores with all supplemented diets did not differ significantly from the controls.

  17. Bioavailability of iron in geophagic earths and clay minerals, and their effect on dietary iron absorption using an in vitro digestion/Caco-2 cell model.

    PubMed

    Seim, Gretchen L; Ahn, Cedric I; Bodis, Mary S; Luwedde, Flavia; Miller, Dennis D; Hillier, Stephen; Tako, Elad; Glahn, Raymond P; Young, Sera L

    2013-08-01

    Geophagy, the deliberate consumption of earth, is strongly associated with iron (Fe) deficiency. It has been proposed that geophagy may be practiced as a means to improve Fe status by increasing Fe intakes and, conversely, that geophagy may cause Fe deficiency by inhibiting Fe absorption. We tested these hypotheses by measuring Fe concentration and relative bioavailable Fe content of 12 samples of geophagic earth and 4 samples of pure clay minerals. Further, we assessed the impact of these samples on the bioavailability of Fe from an Fe-rich test meal (cooked white beans, WB). Fe concentrations were measured with inductively coupled plasma atomic emission spectroscopy. Fe bioavailability was determined using an in vitro digestion/Caco-2 cell model in which ferritin formation was used as an index of Fe bioavailability. Geophagic earth and clay mineral samples were evaluated with this model, both alone and in combination with WB (1 : 16 ratio, sample : WB). Median Fe concentration of the geophagic earth was 3485 (IQR 2462, 14 ,571) μg g⁻¹ and mean Fe concentration in the clay minerals was 2791 (±1782) μg g⁻¹. All specimens had Fe concentrations significantly higher (p ≤ 0.005) than the Fe concentration of WB (77 μg g⁻¹). Ferritin formation (i.e. Fe uptake) in cells exposed to geophagic earths and clay minerals was significantly lower than in cells exposed to WB (p ≤ 0.05) and Fe uptake responses of 11 of the 16 samples were not significantly different from the blank, indicating no bioavailable Fe. When samples were combined with WB, 5 of 16 had mean ferritin levels that were significantly lower (p ≤ 0.05, one tail) than the WB alone, indicating that the samples inhibited Fe uptake from the WB. None of the ferritin responses of cells exposed to both WB and earth/clay were significantly higher than WB alone. Thus, although geophagic earths and mineral clays are high in total Fe, very little of this Fe is bioavailable. Further, some

  18. Dietary iron concentration influences serum concentrations of manganese in rats consuming organic or inorganic sources of manganese.

    PubMed

    Zhang, Huaiyong; Gilbert, Elizabeth R; Pan, Shuqin; Zhang, Keying; Ding, Xuemei; Wang, Jianping; Zeng, Qiufeng; Bai, Shiping

    2016-02-28

    To determine the effects of dietary Fe concentration on Mn bioavailability in rats fed inorganic or organic Mn sources, fifty-four 22-d-old male rats were randomly assigned and fed a basal diet (2·63 mg Fe/kg) supplemented with 0 (low Fe (L-Fe)), 35 (adequate Fe (A-Fe)) or 175 (high Fe (H-Fe)) mg Fe/kg with 10 mg Mn/kg from MnSO4 or Mn-lysine chelate (MnLys). Tissues were harvested after 21 d of feeding. Serum Mn was greater (P<0·05) in MnLys rats than in MnSO4 rats, and in L-Fe rats than in A-Fe or H-Fe rats. Duodenal divalent metal transporter-1 (DMT1) mRNA was lower (P<0·05) in H-Fe rats than in A-Fe rats for the MnSO4 treatment; however, no significant difference was observed between them for MnLys. Liver DMT1 mRNA abundance was greater (P<0·05) in MnSO4 than in the MnLys group for H-Fe rats. The DMT1 protein in duodenum and liver and ferroportin 1 (FPN1) protein in liver was greater (P<0·05) in the MnSO4 group than in the MnLys group, and in L-Fe rats than in H-Fe rats. Duodenal FPN1 protein was greater (P<0·05) in L-Fe rats than in A-Fe rats for the MnLys treatment, but it was not different between them for the MnSO4 treatment. Results suggest that MnLys increased serum Mn concentration as compared with MnSO4 in rats irrespective of dietary Fe concentration, which was not because of the difference in DMT1 and FPN1 expression in the intestine and liver.

  19. Thyroid hormone-dependent formation of a subcortical band heterotopia (SBH) in the neonatal brain is not exacerbated under conditions of low dietary iron (FeD).

    PubMed

    Spring, S R; Bastian, T W; Wang, Y; Kosian, P; Anderson, G W; Gilbert, M E

    2016-01-01

    Thyroid hormones (TH) are critical for brain development and insufficiencies can lead to structural abnormalities in specific brain regions. Administration of the goitrogen propylthiouracil (PTU) reduces TH production by inhibiting thyroperoxidase (TPO), an enzyme that oxidizes iodide for the synthesis of TH. TPO activity is iron (Fe)-dependent and dietary iron deficiency (FeD) also reduces circulating levels of TH. We have previously shown that modest degrees of TH insufficiency induced in pregnant rat dams alters the expression of TH-responsive genes in the cortex and hippocampus of the neonate, and results in the formation of a subcortical band heterotopia (SBH) in the corpus callosum (Royland et al., 2008, Bastian et al., 2014, Gilbert et al., 2014). The present experiment investigated if FeD alone was sufficient to induce a SBH or if FeD would augment SBH formation at lower doses of PTU. One set of pregnant rats was administered 0, 1, 3, or 10ppm of PTU via drinking water starting on gestational day (GD) 6. FeD was induced in a 2nd set of dams beginning on GD2. A third set of dams received the FeD diet from GD2 paired with either 1ppm or 3ppm PTU beginning on GD6. All treatments continued until the time of sacrifice. On PN18, one female pup from each litter was sacrificed and the brain examined for SBH. We observed lower maternal, PN2 and PN18 pup serum T4 in response to PTU. FeD reduced serum T4 in pups on PN16, but did not affect serum T4 in dams or PN2 pups. Neither did FeD in combination with PTU alter T4 levels in dams on PN18 or pups on PN2 compared to PTU treatment alone. By PN16, however more severe T4 reductions were observed in pups when FeD was combined with PTU. SBH increased with increasing dosage of PTU, but counter to our hypothesis, no SBH was detected in the offspring of FeD dams. As such, T4 levels in dams and newborn pups rather than older neonates appear to be a better predictor SBH associated with TH insufficiency. These data indirectly

  20. Thyroid hormone-dependent formation of a subcortical band heterotopia (SBH) in the neonatal brain is not exacerbated under conditions of low dietary iron (FeD).

    PubMed

    Spring, S R; Bastian, T W; Wang, Y; Kosian, P; Anderson, G W; Gilbert, M E

    2016-01-01

    Thyroid hormones (TH) are critical for brain development and insufficiencies can lead to structural abnormalities in specific brain regions. Administration of the goitrogen propylthiouracil (PTU) reduces TH production by inhibiting thyroperoxidase (TPO), an enzyme that oxidizes iodide for the synthesis of TH. TPO activity is iron (Fe)-dependent and dietary iron deficiency (FeD) also reduces circulating levels of TH. We have previously shown that modest degrees of TH insufficiency induced in pregnant rat dams alters the expression of TH-responsive genes in the cortex and hippocampus of the neonate, and results in the formation of a subcortical band heterotopia (SBH) in the corpus callosum (Royland et al., 2008, Bastian et al., 2014, Gilbert et al., 2014). The present experiment investigated if FeD alone was sufficient to induce a SBH or if FeD would augment SBH formation at lower doses of PTU. One set of pregnant rats was administered 0, 1, 3, or 10ppm of PTU via drinking water starting on gestational day (GD) 6. FeD was induced in a 2nd set of dams beginning on GD2. A third set of dams received the FeD diet from GD2 paired with either 1ppm or 3ppm PTU beginning on GD6. All treatments continued until the time of sacrifice. On PN18, one female pup from each litter was sacrificed and the brain examined for SBH. We observed lower maternal, PN2 and PN18 pup serum T4 in response to PTU. FeD reduced serum T4 in pups on PN16, but did not affect serum T4 in dams or PN2 pups. Neither did FeD in combination with PTU alter T4 levels in dams on PN18 or pups on PN2 compared to PTU treatment alone. By PN16, however more severe T4 reductions were observed in pups when FeD was combined with PTU. SBH increased with increasing dosage of PTU, but counter to our hypothesis, no SBH was detected in the offspring of FeD dams. As such, T4 levels in dams and newborn pups rather than older neonates appear to be a better predictor SBH associated with TH insufficiency. These data indirectly

  1. Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Tatsumoto, Narihito; Taniguchi, Masatomo; Noguchi, Hideko; Nakano, Toshiaki; Masutani, Kosuke; Ooboshi, Hiroaki; Tsuruya, Kazuhiko; Kitazono, Takanari

    2014-06-15

    Hyperphosphatemia contributes to increased cardiovascular mortality through vascular calcification (VC) in patients with chronic kidney disease (CKD). Malnutrition and inflammation are also closely linked to an increased risk of cardiovascular death in CKD. However, the effects of Pi overload on inflammation and malnutrition remain to be elucidated. The aim of the present study was to investigate the effects of dietary Pi loading on the interactions among inflammation, malnutrition, and VC in CKD. We used control rats fed normal diets and adenine-induced CKD rats fed diets with different Pi concentrations ranging from 0.3% to 1.2% for 8 wk. CKD rats showed dietary Pi concentration-dependent increases in serum and tissue levels of TNF-α and urinary and tissue levels of oxidative stress markers and developed malnutrition (decrease in body weight, serum albumin, and urinary creatinine excretion), VC, and premature death without affecting kidney function. Treatment with 6% lanthanum carbonate blunted almost all changes induced by Pi overload. Regression analysis showed that serum Pi levels closely correlated with the extent of inflammation, malnutrition, and VC. Also, in cultured human vascular smooth muscle cells, high-Pi medium directly increased the expression of TNF-α in advance of the increase in osteochondrogenic markers. Our data suggest that dietary Pi overload induces systemic inflammation and malnutrition, accompanied by VC and premature death in CKD, and that inhibition of Pi loading through dietary or pharmacological interventions or anti-inflammatory therapy may be a promising treatment for the prevention of malnutrition-inflammation-atherosclerosis syndrome.

  2. Drugs preventing Na+ and Ca2+ overload.

    PubMed

    Ravens, U; Himmel, H M

    1999-03-01

    Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by increased intracellular Na+concentration leads to cellular Ca2+overload resulting in arrhythmias and contractile dysfunction. Na+and Ca2+overload-associated arrhythmias can be produced experimentally by inhibition of Na+efflux (digitalis-induced intoxication) and by abnormal Na+influx via modulated Na+channels (veratridine, DPI 201-106; hypoxia) or via the Na+, H+exchanger. Theoretically, blockers of Na+and Ca2+channels, inhibitors of abnormal oscillatory release of Ca2+from internal stores or modulators of the Na+, Ca2+and Na+, H+exchanger activities could protect against cellular Na+and Ca2+overload. Three exemplary drugs that prevent Na+and Ca2+overload, i.e. the benzothiazolamine R56865, the methylenephenoxydioxy-derivative CP-060S, and the benzoyl-guanidine Hoe 642, a Na+, H+exchange blocker, are briefly reviewed with respect to their efficacy on digitalis-, veratridine- and ischaemia/reperfusion-induced arrhythmias. PMID:10094840

  3. [Bruxism and overload of periodontium and implants].

    PubMed

    Jacobs, R; De Laat, A

    2000-07-01

    Bruxism is responsible for occlusal tooth wear but can not induce nor aggravate gingivitis or periodontitis. Bruxism induces jiggling forces, which cause a clinical tooth hypermobility, radiologically seen as a widened periodontal space. Although there is no direct causal relation between bruxism and implant failure, implant overload may lead to fractures of the components and bone loss. PMID:11385782

  4. Performance During the Stress of Processing Overload.

    ERIC Educational Resources Information Center

    Martin, David W.

    Performance becomes degraded when the human processing system undergoes the stress of processing overload. Information processing models are often used to predict how performance will be affected. Single channel models hypothesize that information will either be lost in the queue or processed with delay. Single capacity models predict that for a…

  5. Shock absorber protects motive components against overloads

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Shock absorber with an output shaft, hollow gear, and a pair of springs forming a resilient driving connection between shaft and gear, operates when abnormally high torques are applied. This simple durable frictional device is valuable in rotating mechanisms subject to sudden overloads.

  6. Formulas providing adequate pantothenic acid, vitamin D, manganese, iron and vitamin A for infants fed with mother's milk (aged 6-11 months) according to the Japanese Dietary Reference Intakes prepared by the Ministry of Health, Labour and Welfare (2005 edition).

    PubMed

    Tsutie, Setsuko; Kurihara, Nobutaka; Sasaki, Aki; Takagi, Arisa; Seguti, Harumiti; Inatome, Tetsuya

    2010-04-01

    Weaning formulas served in hospitals and care facilities in Japan should conform to dietary reference intakes (DRIs). We examined whether the DRI for breastfed infants aged 6-11 months can be satisfied in dietary practice, with a particular focus on the fulfilment rates for vitamins, minerals, trace elements and electrolytes in weaning formulas containing energy and protein at levels either greater than or equal to the DRIs, as well as on the dietary profiles of weaning formulas to achieve the DRI for every nutrient. The results showed that no weaning formulas examined in this study fulfilled the DRI for pantothenic acid (5 mg), vitamin D (4 microg), manganese (1.2 mg) or iron (5.5 mg). Furthermore, their vitamin A content exceeded the DRI (350 microg RE). The discrepancy between the guidelines and actual dietary practice is probably because of the fact that the estimated reference values poorly reflect the actual dietary intake in the target population; for example, the pantothenic acid and manganese DRIs for breastfed infants aged 6-11 months were set based on the breast milk intake of younger infants (0-5 months) in combination with the breast milk contents. Our results suggest that dietary guidance for infants should include information to promote proper intakes of vitamins A and D, and iron by reducing the amount of vitamin A-rich foods and utilizing dietary vitamin D and iron supplements including government-approved specified health foods.

  7. 30 CFR 57.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cable overload protection. 57.12003... Electricity Surface and Underground § 57.12003 Trailing cable overload protection. Individual overload protection or short circuit protection shall be provided for the trailing cables of mobile equipment....

  8. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Circuit overload protection. 57.12001 Section... 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....

  9. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Circuit overload protection. 57.12001 Section... 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....

  10. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 57.12001 Section... 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....

  11. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Circuit overload protection. 57.12001 Section... 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....

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

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

    The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

  13. Current approach to iron chelation in children.

    PubMed

    Aydinok, Yesim; Kattamis, Antonis; Viprakasit, Vip

    2014-06-01

    Transfusion-dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non-transfusion-dependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron-induced end-organ complications, in order to achieve a normal pattern of complication-free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores' depletion.

  14. Toward resolving the unsettled role of iron chelation therapy in myelodysplastic syndromes.

    PubMed

    Merkel, Drorit G; Nagler, Arnon

    2014-07-01

    Transfusion dependent low risk myelodysplastic syndromes (MDS) patients, eventually develop iron overload. Iron toxicity, via oxidative stress, can damage cellular components and impact organ function. In thalassemia major patients, iron chelation therapy lowered iron levels with recovery of cardiac and liver functions and significant improvement in survival. Several noncontrolled studies show inferior survival in MDS patients with iron overload, including an increase in transplant-related mortality and infection risk while iron chelation appears to improve survival in both lower risk MDS patients and in stem cell transplant settings. Collated data are presented on the pathophysiological impact of iron overload; measuring techniques and chelating agents' therapy positive impact on hematological status and overall survival are discussed. Although suggested by retrospective analyses, the lack of clear prospective data of the beneficial effects of iron chelation on morbidity and survival, the role of iron chelation therapy in MDS patients remains controversial.

  15. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use....

  16. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use....

  17. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use....

  18. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use....

  19. Iron Chelation Therapy in Myelodysplastic Syndromes

    PubMed Central

    Messa, Emanuela; Cilloni, Daniela; Saglio, Giuseppe

    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 under debate, mainly because of the lack of solid prospective clinical trials that should take place in the future. This review aims to summarize what is currently known about the incidence and clinical consequences of iron overload in MDS patients and the state-of the-art of iron chelation therapy in this setting. We also give an overview of clinical guidelines for chelation in MDS published to date and some perspectives for the future. PMID:20672005

  20. Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

    PubMed Central

    Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

    2011-01-01

    Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

  1. Valgus Extension Overload in Baseball Players.

    PubMed

    Paulino, Franklin E; Villacis, Diego C; Ahmad, Christopher S

    2016-01-01

    Repetitive throwing, such as in baseball pitching, applies massive stress on the elbow. This can often lead to a predictable constellation of elbow injuries, such as valgus extension overload syndrome (VEO). The following review of VEO provides an understanding of relevant anatomy, explanation of pathomechanics, key aspects to clinical evaluation, effective treatment options, and indications for surgery. In addition, we provide the senior author's (CSA) preferred arthroscopic technique for cases of VEO refractory to conservative management.

  2. Valgus Extension Overload in Baseball Players.

    PubMed

    Paulino, Franklin E; Villacis, Diego C; Ahmad, Christopher S

    2016-01-01

    Repetitive throwing, such as in baseball pitching, applies massive stress on the elbow. This can often lead to a predictable constellation of elbow injuries, such as valgus extension overload syndrome (VEO). The following review of VEO provides an understanding of relevant anatomy, explanation of pathomechanics, key aspects to clinical evaluation, effective treatment options, and indications for surgery. In addition, we provide the senior author's (CSA) preferred arthroscopic technique for cases of VEO refractory to conservative management. PMID:26991567

  3. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex.

    PubMed

    Suh, Jung H; Moreau, Régis; Heath, Shi-Hua D; Hagen, Tory M

    2005-01-01

    Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders. To understand the extent of iron accumulation and its effect on antioxidant status, we monitored iron content in the cerebral cortex of F344 rats by inductively coupled plasma atomic emission spectrometry (ICP-AES) and found that the cerebral iron levels in 24-28-month-old rats were increased by 80% (p<0.01) relative to 3-month-old rats. Iron accumulation correlated with a decline in glutathione (GSH) and the GSH/GSSG ratio, indicating that iron accumulation altered antioxidant capacity and thiol redox state in aged animals. Because (R)-alpha-Lipoic acid (LA) is a potent chelator of divalent metal ions in vitro and also regenerates other antioxidants, we monitored whether feeding LA (0.2% [w/w]; 2 weeks) could lower cortical iron and improve antioxidant status. Results show that cerebral iron levels in old LA-fed animals were lower when compared to controls and were similar to levels seen in young rats. Antioxidant status and thiol redox state also improved markedly in old LA-fed rats versus controls. These results thus show that LA supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging.

  4. Dietary Assessment

    Cancer.gov

    The Epidemiology and Genomics Research Program's goals in Dietary Assessment are to increase the precision of dietary intake estimates by improving self-report of dietary intake and the analytic procedures for processing reported information.

  5. Sequestration and Scavenging of Iron in Infection

    PubMed Central

    Parrow, Nermi L.; Fleming, Robert E.

    2013-01-01

    The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen. PMID:23836822

  6. Acceleration of Fatigue Crack Growth after Overload in Carbon Steel

    NASA Astrophysics Data System (ADS)

    Yamauchi, A.; Miyahara, H.; Makabe, C.; Miyazaki, T.

    The effects of an overload on fatigue crack growth behavior have been investigated by using carbon steel. Delayed retardation and acceleration of crack growth were both observed. These phenomena depended not only on overload conditions but also on the baseline stress conditions. Moreover, the mechanical properties of the materials affected the crack growth rate after overload. It was found that crack growth accelerated when tensile residual stress was distributed in front of the crack tip. The residual stress distribution is related to the crack opening geometry at the overload stage.

  7. Iron-based phosphate binders: do they offer advantages over currently available phosphate binders?

    PubMed Central

    Negri, Armando Luis; Ureña Torres, Pablo Antonio

    2015-01-01

    Increased cardiovascular morbidity and mortality has been associated with the hyperphosphatemia seen in patients with end-stage chronic kidney disease (CKD). Oral phosphate binders are prescribed in these patients to prevent intestinal absorption of dietary phosphate and reduce serum phosphate. In prospective observational cohorts they have shown to decrease all-cause and cardiovascular mortality risk. Different problems have been associated with currently available phosphate binders as positive calcium balance and impaired outcomes with calcium-based phosphate binders or increased costs with non-calcium-based phosphate binders. Iron-based phosphate binders represent a new class of phosphate binders. Several iron-based phosphate binders have undergone testing in clinical trials. Ferric citrate (JTT-751) and sucroferric oxyhydroxide (PA21) are the two iron-based binders that have passed to the clinical field after being found safe and effective in decreasing serum phosphate. Iron from ferric citrate is partially absorbed compared to sucroferric oxyhydroxide. Ferric citrate usage could result in an important reduction in erythropoiesis-stimulating agent (ESA) and IV iron usage, resulting in significant cost savings. Sucroferric oxyhydroxide was effective in lowering serum phosphorus in dialysis patients with similar efficacy to sevelamer carbonate, but with lower pill burden, and better adherence. Ferric citrate may be more suited for the treatment of chronic hyperphosphatemia in CKD patients requiring iron supplements but its use may have been hampered by potential aluminum overload, as citrate facilitates its absorption; sucroferric oxyhydroxide may be more suited for hyperphosphatemic CKD patients not requiring iron supplementation, with low pill burden. PMID:25815172

  8. [Chronic nicotinamide overload and type 2 diabetes].

    PubMed

    Zhou, Shi-Sheng; Li, Da; Zhou, Yi-Ming; Sun, Wu-Ping; Liu, Xing-Xing; Lun, Yong-Zhi

    2010-02-25

    Type 2 diabetes is a major global health problem. It is generally accepted that type 2 diabetes is the result of gene-environmental interaction. However, the mechanism underlying the interaction is unclear. Diet change is known to play an important role in type 2 diabetes. The fact that the global high prevalence of type 2 diabetes has occurred following the spread of food fortification worldwide suggests a possible involvement of excess niacin intake. Our recent study found that nicotinamide overload and low nicotinamide detoxification may induce oxidative stress associated with insulin resistance. Based on the relevant facts, this review briefly summarized the relationship between the prevalence of type 2 diabetes and the nicotinamide metabolism changes induced by excess niacin intake, aldehyde oxidase inhibitors, liver diseases and functional defects of skin. We speculate that the gene-environmental interaction in type 2 diabetes may be a reflection of the outcome of the association of chronic nicotinamide overload-induced toxicity and the relatively low detoxification/excretion capacity of the body. Reducing the content of niacin in foods may be a promising strategy for the control of type 2 diabetes.

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

    PubMed Central

    St Pierre, Tim G.

    2015-01-01

    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

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

    PubMed

    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.

  11. Dietary inulin affects the expression of intestinal enterocyte iron transporters, receptors and storage protein and alters the microbiota in the pig intestine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inulin, a linear beta fructan, is present in a variety of plants including chicory root and wheat. It exhibits prebiotic properties and was shown to enhance mineral absorption and increase beneficial bacteria in the colon. The aim of this study was to assess the effect of dietary inulin on selected...

  12. Iron status in the elderly.

    PubMed

    Fairweather-Tait, Susan J; Wawer, Anna A; Gillings, Rachel; Jennings, Amy; Myint, Phyo K

    2014-01-01

    Iron deficiency anaemia is prevalent in older age, particularly after the age of 80. Serum ferritin concentrations also decline, although there is no evidence to suggest that changes in iron stores are an inevitable consequence of ageing. Chronic inflammation is a common condition in older people, making the measurement of iron status difficult, and it is likely that elevated levels of circulating hepcidin are responsible for changes in iron metabolism that result in systemic iron depletion. Other contributory factors are poor diet and some medications, such as aspirin. Anaemia in older age has undesirable health outcomes, including increased susceptibility to falling and depression. However, there are concerns about possible adverse effects of iron supplements, either in relation to pro-inflammatory effects in the gut or inappropriate tissue iron deposition. Brain iron levels are increased with age-related degenerative diseases, but it is not known if this is the cause or a consequence of the disease, and genetic factors are likely to play a role. In order to maintain body iron within the normal range a personalised approach is required, taking into account all of the factors that may affect iron metabolism and the available strategies for preventing iron deficiency or overload.

  13. Aluminium toxicity and iron homeostasis.

    PubMed

    Ward, R J; Zhang, Y; Crichton, R R

    2001-11-01

    In an animal model of aluminum overload, (aluminium gluconate), the increases in tissue aluminium content were paralleled by elevations of tissue iron in the kidney, liver heart and spleen as well as in various brain regions, frontal, temporal and parietal cortex and hippocampus. Despite such increases in iron content there were no significant changes in the activities of a wide range of cytoprotective enzymes apart from an increase in superoxide dismutase in the frontal cortex of the aluminium loaded rats. Such increases in tissue iron content may be attributed to the stabilisation of IRP-2 by aluminium thereby promoting transferrin receptor synthesis while blocking ferritin synthesis. Using the radioactive tracer (26)Al less than 1% of the injected dose was recovered in isolated ferritin, supporting previous studies which also found little evidence for aluminium storage within ferritin. The increases in brain iron may well be contributory to neurodegeneration, although the pathogenesis by which iron exerts such an effect is unclear.

  14. Risk of Oxidative Damage to Bone from Increased Iron Stores During Space Flight

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Smith, S. M.

    2014-01-01

    Iron stores are increased secondary to neocytolysis of red blood cells and a high dietary intake of iron during space flight. This raises concerns about the risk of excess iron causing oxidative damage in many tissues, including bone. Biomarkers of iron status, oxidative damage, and bone resorption during space flight were analyzed for 23 (16 M/7 F) International Space Station crewmembers as part of the Nutrition SMO project. Up to 5 in-flight blood samples and 24-h urine pools were collected over the course of the 4-6 month missions. Serum iron increased slightly during space flight and was decreased at landing (P < 0.0004). An increase in serum ferritin early in flight (217% in women and 68% in men, P < 0.0004), returning to preflight concentrations at landing, and a decrease in transferrin and transferrin receptors during flight indicated that a transient increase in iron stores occurred. No inflammatory response was observed during flight. The oxidative damage markers 8-hydroxy-2'-deoxyguanosine and prostaglandin F(sub 2(alpha)) were positively correlated (both P < 0.001) with serum ferritin. A greater area under the curve for ferritin during flight was correlated with greater changes in bone mineral density of several bone regions after flight (1). In a separate study (2), a ground-based investigation was conducted that examined the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in several physiological systems in 12-wk male Sprague-Dawley rats. The rats were acclimated to an adequate iron diet (45 mg iron (ferric citrate)/kg diet) for 3 wk and then assigned to one of four groups: adequate iron (Fe) diet/no radiation, adequate Fe diet/ radiation, moderately high Fe diet (650 mg Fe (ferric citrate)/kg diet)/no radiation, and moderately high Fe diet/radiation. Animals remained on the assigned diet for 4 wk. Starting on day 14 of experimental diet treatment, animals were exposed to a fractionated dose (0.375 Gy) of Cs

  15. Engineering and the problem of moral overload.

    PubMed

    Van den Hoven, Jeroen; Lokhorst, Gert-Jan; Van de Poel, Ibo

    2012-03-01

    When thinking about ethics, technology is often only mentioned as the source of our problems, not as a potential solution to our moral dilemmas. When thinking about technology, ethics is often only mentioned as a constraint on developments, not as a source and spring of innovation. In this paper, we argue that ethics can be the source of technological development rather than just a constraint and technological progress can create moral progress rather than just moral problems. We show this by an analysis of how technology can contribute to the solution of so-called moral overload or moral dilemmas. Such dilemmas typically create a moral residue that is the basis of a second-order principle that tells us to reshape the world so that we can meet all our moral obligations. We can do so, among other things, through guided technological innovation. PMID:21533834

  16. Evaluation of thermal overload in boiler operators.

    PubMed

    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

  17. Avoiding Program-Induced Cumulative Overload (PICO).

    PubMed

    Orr, Robin; Knapik, Joseph J; Pope, Rodney

    2016-01-01

    This article defines the concept of program-induced cumulative overload (PICO), provides examples, and advises ways to mitigate the adverse effects. PICO is the excessive cumulative physical workload that can be imparted to military personnel by a military training program with an embedded physical training component. PICO can be acute (accumulating within a single day) or chronic (accumulating across the entirety of the program) and results in adverse outcomes for affected personnel, including detrimental fatigue, performance degradation, injuries, or illness. Strategies to mitigate PICO include focusing administration and logistic practices during the development and ongoing management of a trainee program and implementing known musculoskeletal injury prevention strategies. More training is not always better, and trainers need to consider the total amount of physical activity that military personnel experience across both operational training and physical training if PICO is to be mitigated. PMID:27450610

  18. Evaluation of thermal overload in boiler operators.

    PubMed

    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.

  19. Correlates of anaemia in pregnant urban South Indian women: a possible role of dietary intake of nutrients that inhibit iron absorption

    PubMed Central

    Samuel, Tinu Mary; Thomas, Tinku; Finkelstein, Julia; Bosch, Ronald; Rajendran, Ramya; Virtanen, Suvi M; Srinivasan, Krishnamachari; Kurpad, Anura V; Duggan, Christopher

    2013-01-01

    Objective To identify correlates of anaemia during the first trimester of pregnancy among 366 urban South Indian pregnant women. Design Cross-sectional study evaluating demographic, socio-economic, anthropometric and dietary intake data on haematological outcomes. Setting A government maternity health-care centre catering predominantly to the needs of pregnant women from the lower socio-economic strata of urban Bangalore. Subjects Pregnant women (n 366) aged ≥18 and ≤40 years, who registered for antenatal screening at ≤14 weeks of gestation. Results Mean age was 22.6 (SD 3.4) years, mean BMI was 20.4 (SD 3.3) kg/m2 and 236 (64.5%) of the pregnant women were primiparous. The prevalence of anaemia (Hb <11.0g/dl) was 30.3% and of microcytic anaemia (anaemia with mean corpuscular volume <80fl) 20.2%. Mean dietary intakes of energy, Ca, Fe and folate were well below the Indian RDA. In multivariable log-binomial regression analysis, anaemia was independently associated with high dietary intakes of Ca (relative risk; 95% CI: 1.79; 1.16, 2.76) and P (1.96; 1.31, 2.96) and high intake of meat, fish and poultry (1.94; 1.29, 2.91). Conclusions Low dietary intake of multiple micronutrients, but higher intakes of nutrients that inhibit Fe absorption such as Ca and P, may help explain high rates of maternal anaemia in India. PMID:22575487

  20. Dietary effects on breast cancer

    SciTech Connect

    Stevens, R.G. )

    1991-07-20

    Professor Lee and colleagues show a significant effect of dietary red meat intake, no effect of fat, and a protective effect of soya protein on the risk of breast cancer in young women in Singapore. They do not ascribe the red-meat effect to fat in the meat, and offer no alternative explanation. Red meat contains the most readily absorbed form of dietary iron, and there is evidence that increased body iron stores raise cancer risk, perhaps by one or both of two possible mechanisms: (1) boosting the availability of an essential nutrient for cancer cells, and (2) increasing the production of oxygen radicals. In addition, there is some evidence from studies in animals for a role for iron in mammary-tumor induction. Thompson et al administered 1-methyl-1-nitrosourea to groups of rats receiving normal rat chow, a low-iron diet, or an iron-supplemented diet. The group receiving dietary iron supplementation had the greatest mammary-tumor burden, whereas that receiving an iron-restricted diet had fewer tumors than the group on the normal diet (although this latter effect may have resulted merely from reduced body weight in the rats on an iron-restricted diet). The protective effect of soya protein seen by Lee et al may also be related to iron metabolism. Soy beans are a source of phytate, a constituent of most cereals, nuts, and legumes, that avidly binds iron in such a way that it is incapable of catalyzing the production of oxygen radicals. The protective effect of soya protein may be shared by increased intakes of other plant products that are high in phytate but either not consumed in quantity in Singapore or not assessed in the questionnaire Lee et al administered.

  1. Contribution of leafy vegetable sauces to dietary iron, zinc, vitamin A and energy requirements in children and their mothers in Burkina Faso.

    PubMed

    Icard-Vernière, Christèle; Olive, Fanny; Picq, Christian; Mouquet-Rivier, Claire

    2015-03-01

    Improved leafy vegetable (LV) sauces, with amaranth, sorrel, and Ceylon spinach/spider plant leaves were formulated from traditional recipes to assess their potential use for food-to-food fortification in iron, zinc and vitamin A in the diet of young children and their mothers in Burkina Faso. Improvement was based on an increase in LV proportion and a decrease in mineral absorption inhibitors. An increase in iron content of up to 3 mg/100 g was obtained in some improved sauces in which dried fish was replaced by chicken liver, and vitamin A content was about 40 times higher than in traditional sauces. Fractional dialyzable iron was low in all sauces. Intakes of sauce were measured to assess their acceptability and no significant difference was found between traditional and improved formulations. The mean intakes of sauces were 66 ± 40 g for young children and 166 ± 65 g for their mothers. Amaranth or Ceylon spinach/spider plant sauces, consumed with the cereal based paste "tô" twice a day, would contribute 80 to 86% of children's estimated average requirement (EAR) of iron and to 90 to 170% of EAR of vitamin A but their contribution to zinc and energy needs would remain low.

  2. Pleiotropic actions of iron balance in diabetes mellitus.

    PubMed

    Wang, Xinhui; Fang, Xuexian; Wang, Fudi

    2015-03-01

    As an essential element, iron plays a central role in many physiological processes, including redox balance, inflammation, energy metabolism, and environment sensing. Perturbations in iron homeostasis are associated with several conditions, including hyperglycemia and diabetes, both of which have been studied in patients and animal models. To clarify the pleiotropic role of iron homeostasis in diabetes development, the early studies on diseases with iron-overload, studies on clinical iron depletion therapies, associations between iron-related genetic polymorphisms and diabetes, and etiological mechanisms underlying iron perturbations-impaired insulin secretion and insulin sensitivity were carefully reviewed and discussed. Hereditary hemochromatosis, transfusion-dependent thalassemia, and excess heme iron intake can increase the risk of developing diabetes. Genetically modified mice and mice fed a high-iron diet present with discrepant phenotypes due to differences in tissue iron distribution. Moreover, several genetic polymorphisms related to iron homeostasis have been associated with the risk of developing diabetes. Tightly controlled iron metabolism is essential for insulin secretion and insulin sensitivity, and iron overload in pancreatic islets alters reactive oxygen species (ROS) generation, as well as hypoxia-inducible factor-1α (HIF-1α) stability and adenosine triphosphate (ATP) synthesis, thereby impairing the function and viability of β-cells. Decreased levels of adiponectin, macrophage-mediated inflammation, and ROS-mediated liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) activation can contribute to iron overload-induced insulin resistance, whereas iron deficiency could also participate in obesity-related inflammation, hypoxia, and insulin resistance. Because iron homeostasis is closely correlated with many metabolic processes, future studies are needed in order to elucidate the finely tuned network among iron

  3. Dietary Supplements

    MedlinePlus

    Dietary supplements are vitamins, minerals, herbs, and many other products. They can come as pills, capsules, powders, drinks, ... possible Tell your health care provider about any dietary supplements you use Do not take a bigger dose ...

  4. Iron deficiency and cardiovascular disease.

    PubMed

    von Haehling, Stephan; Jankowska, Ewa A; van Veldhuisen, Dirk J; Ponikowski, Piotr; Anker, Stefan D

    2015-11-01

    Iron deficiency affects up to one-third of the world's population, and is particularly common in elderly individuals and those with certain chronic diseases. Iron excess can be detrimental in cardiovascular illness, and research has now also brought anaemia and iron deficiency into the focus of cardiovascular medicine. Data indicate that iron deficiency has detrimental effects in patients with coronary artery disease, heart failure (HF), and pulmonary hypertension, and possibly in patients undergoing cardiac surgery. Around one-third of all patients with HF, and more than one-half of patients with pulmonary hypertension, are affected by iron deficiency. Patients with HF and iron deficiency have shown symptomatic improvements from intravenous iron administration, and some evidence suggests that these improvements occur irrespective of the presence of anaemia. Improved exercise capacity has been demonstrated after iron administration in patients with pulmonary hypertension. However, to avoid iron overload and T-cell activation, it seems that recipients of cardiac transplantations should not be treated with intravenous iron preparations.

  5. Effect of ferroportin polymorphism on iron homeostasis and infection.

    PubMed

    Kasvosve, Ishmael

    2013-02-01

    Ferroportin (FPN) is the sole iron export membrane protein identified in mammals that is abundantly expressed on absorptive enterocytes and macrophages, and is essential for physiological regulation of cellular iron. The expression of FPN is positively induced by cellular iron and is suppressed by liver hepcidin in response to either increased systemic iron or inflammatory stimuli. Hepcidin binds to cell surface FPN inducing FPN internalization followed by lysosomal degradation of the protein and consequently iron efflux from macrophages is blocked and there is suboptimal iron absorption by duodenal enterocytes. Dozens of FPN gene mutations have been identified in different ethnic populations and some of the mutations are associated with autosomal dominant iron overload disorder described as FPN disease or hemochromatosis type 4 that is distinct from hereditary hemochromatosis due to HFE mutations. Clinical manifestations of iron overload FPN disease can be classified into two groups according to whether there is selective macrophage iron loading or parenchymal and reticuloendothelial iron accumulation. There is evidence suggesting that altered hepcidin-FPN interaction can modulate host's response to infection. Resistance to hepcidin promotes iron egress from cells and this inhibits growth of intracellular pathogens. Conversely, iron retention due to loss of iron export activity by mutated FPN results in intracellular iron accumulation and a permissive environment for intracellular pathogens.

  6. Bioaugmentation of overloaded anaerobic digesters restores function and archaeal community.

    PubMed

    Tale, V P; Maki, J S; Zitomer, D H

    2015-03-01

    Adding beneficial microorganisms to anaerobic digesters for improved performance (i.e. bioaugmentation) has been shown to decrease recovery time after organic overload or toxicity upset. Compared to strictly anaerobic cultures, adding aerotolerant methanogenic cultures may be more practical since they exhibit higher methanogenic activity and can be easily dried and stored in ambient air for future shipping and use. In this study, anaerobic digesters were bioaugmented with both anaerobic and aerated, methanogenic propionate enrichment cultures after a transient organic overload. Digesters bioaugmented with anaerobic and moderately aerated cultures recovered 25 and 100 days before non-bioaugmented digesters, respectively. Increased methane production due to bioaugmentation continued a long time, with 50-120% increases 6 to 12 SRTs (60-120 days) after overload. In contrast to the anaerobic enrichment, the aerated enrichments were more effective as bioaugmentation cultures, resulting in faster recovery of upset digester methane and COD removal rates. Sixty days after overload, the bioaugmented digester archaeal community was not shifted, but was restored to one similar to the pre-overload community. In contrast, non-bioaugmented digester archaeal communities before and after overload were significantly different. Organisms most similar to Methanospirillum hungatei had higher relative abundance in well-operating, undisturbed and bioaugmented digesters, whereas organisms similar to Methanolinea tarda were more abundant in upset, non-bioaugmented digesters. Bioaugmentation is a beneficial approach to increase digester recovery rate after transient organic overload events. Moderately aerated, methanogenic propionate enrichment cultures were more beneficial augments than a strictly anaerobic enrichment. PMID:25528544

  7. Bioaugmentation of overloaded anaerobic digesters restores function and archaeal community.

    PubMed

    Tale, V P; Maki, J S; Zitomer, D H

    2015-03-01

    Adding beneficial microorganisms to anaerobic digesters for improved performance (i.e. bioaugmentation) has been shown to decrease recovery time after organic overload or toxicity upset. Compared to strictly anaerobic cultures, adding aerotolerant methanogenic cultures may be more practical since they exhibit higher methanogenic activity and can be easily dried and stored in ambient air for future shipping and use. In this study, anaerobic digesters were bioaugmented with both anaerobic and aerated, methanogenic propionate enrichment cultures after a transient organic overload. Digesters bioaugmented with anaerobic and moderately aerated cultures recovered 25 and 100 days before non-bioaugmented digesters, respectively. Increased methane production due to bioaugmentation continued a long time, with 50-120% increases 6 to 12 SRTs (60-120 days) after overload. In contrast to the anaerobic enrichment, the aerated enrichments were more effective as bioaugmentation cultures, resulting in faster recovery of upset digester methane and COD removal rates. Sixty days after overload, the bioaugmented digester archaeal community was not shifted, but was restored to one similar to the pre-overload community. In contrast, non-bioaugmented digester archaeal communities before and after overload were significantly different. Organisms most similar to Methanospirillum hungatei had higher relative abundance in well-operating, undisturbed and bioaugmented digesters, whereas organisms similar to Methanolinea tarda were more abundant in upset, non-bioaugmented digesters. Bioaugmentation is a beneficial approach to increase digester recovery rate after transient organic overload events. Moderately aerated, methanogenic propionate enrichment cultures were more beneficial augments than a strictly anaerobic enrichment.

  8. Dietary exposure and trends of exposure to nutrient elements iodine, iron, selenium and sodium from the 2003-4 New Zealand Total Diet Survey.

    PubMed

    Thomson, Barbara M; Vannoort, Richard W; Haslemore, Roger M

    2008-03-01

    The mean dietary exposure to the nutrient elements iodine, Fe, Se and Na by eight age-sex groups of the New Zealand population was estimated from foods purchased and prepared as for consumption. A total of 968 samples comprising 121 foods were collected and analysed. Mean daily exposures were calculated from mean concentration levels of the selected nutrients in each food combined with simulated diets for a 25+-year-old male and female, a 19-24-year-old male, a 11-14-year-old boy and girl, a 5-6-year-old child, a 1-3-year-old toddler and a 6-12-month-old infant. Food concentrations and dietary exposures are reported and compared with nutrient reference values (for example, recommended daily intakes, adequate intakes or upper limits). Dietary iodine exposures for all age-sex groups were well below recommended levels and have steadily decreased since 1982, raising concern especially for the physical and mental development of infants and young children. Fe exposures meet the recommended daily intake for the average male and 11-14 year olds but are only about half that recommended for adult females. Se exposure is about 20 % less than optimal for females. Na exposures, excluding discretionary salt, are above the acceptable exposure level for all age-sex groups, and exceed the upper intake limits for 25+-year-old males, 19-24-year-old young males, and 11-14-year-old boys and girls by up to 125 % for an average consumer. PMID:17925056

  9. Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice.

    PubMed

    Das, Abhishek; Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Chatterjee, Anupam; Mandal, Nripendranath

    2015-05-01

    Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases. PMID:26040025

  10. Dietary uptake of Cu sorbed to hydrous iron oxide is linked to cellular toxicity and feeding inhibition in a benthic grazer

    USGS Publications Warehouse

    Cain, Daniel J.; Croteau, Marie-Noele; Fuller, Christopher C.; Ringwood, Amy H.

    2016-01-01

    Whereas feeding inhibition caused by exposure to contaminants has been extensively documented, the underlying mechanism(s) are less well understood. For this study, the behavior of several key feeding processes, including ingestion rate and assimilation efficiency, that affect the dietary uptake of Cu were evaluated in the benthic grazer Lymnaea stagnalis following 4–5 h exposures to Cu adsorbed to synthetic hydrous ferric oxide (Cu–HFO). The particles were mixed with a cultured alga to create algal mats with Cu exposures spanning nearly 3 orders of magnitude at variable or constant Fe concentrations, thereby allowing first order and interactive effects of Cu and Fe to be evaluated. Results showed that Cu influx rates and ingestion rates decreased as Cu exposures of the algal mat mixture exceeded 104 nmol/g. Ingestion rate appeared to exert primary control on the Cu influx rate. Lysosomal destabilization rates increased directly with Cu influx rates. At the highest Cu exposure where the incidence of lysosomal membrane damage was greatest (51%), the ingestion rate was suppressed 80%. The findings suggested that feeding inhibition was a stress response emanating from excessive uptake of dietary Cu and cellular toxicity.

  11. High hepcidin level accounts for the nigral iron accumulation in acute peripheral iron intoxication rats.

    PubMed

    Sun, Chao; Song, Ning; Xie, Anmu; Xie, Junxia; Jiang, Hong

    2012-08-01

    Hepcidin is considered to be a circulatory hormone and a major mechanism regulating iron homeostasis. Our previous publication revealed that acute iron intoxication induced iron deposit and dopaminergic neuron degeneration in the substantia nigra (SN) of a rat model. However, whether and how hepcidin functions in this nigral iron accumulation has not been elucidated. In the present study, we observed a decreased of FPN1 protein level in the SN triggered by peripheral iron overload within 4 h, which correlated with a high hepcidin level. To further investigate the role of intracellular hepcidin under iron overload circumstances, we assessed the expression of hepcidin mRNA and FPN1 protein in vitro. We observed that hepcidin mRNA level was up-regulated and FPN1 protein level was down-regulated in MES23.5 dopaminergic cells in a period of 4h incubation with iron. Both in pCMV-XL4-hepcidin transfected and hepcidin-treated cells, decreased FPN1 protein levels were observed. Our data provide direct evidence that the role for intracellular hepcidin generated in the SN is particularly relevant to restrict iron release by down-regulation FPN1 expression in this region, thus an important contributor to the abnormal iron deposit occurred at an early stage in conditions of peripheral iron intoxication. PMID:22659129

  12. Endoplasmic reticulum stress involved in heart and liver injury in iron-loaded rats.

    PubMed

    Lou, Li-Xia; Geng, Bin; Chen, Yu; Yu, Fang; Zhao, Jing; Tang, Chao-Shu

    2009-07-01

    1. Iron overload contributes to the pathogenesis of various diseases and directly induces tissue injury. In the present study, we investigated the relationship between heart and liver injury induced by iron overload and cellular endoplasmic reticulum (ER) stress to explore the molecular mechanism of iron overload-induced cellular injury. 2. Iron overload in rats was generated by intraperitoneal injection of iron-dextran chronically (30 mg/kg per day for 9 weeks) or acutely (300 mg/kg once). Tissue injury was assessed by determining serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as malondialdehyde (MDA) content in the heart and liver. The ER stress response was analysed by expression of glucose-response protein 78 (GRP78) and activation of caspase 12. 3. In chronic iron-loaded rats, iron levels in the heart and liver were higher, by approximately 2- and 7.8-fold, respectively (P < 0.01), compared with control. Serum LDH, ALT and AST activity, as well as MDA content, GRP78 expression and caspase 12 activity in the heart and liver, were upregulated in chronically iron-loaded rats. In acute iron-loaded rats, iron content in the heart and liver was 51% and 63% higher than in controls (both P < 0.01). Serum LDH, ALT and AST activity, MDA content in the heart and liver and levels of ER stress markers were all increased in acute iron-loaded rats. N-Acetylcysteine (150 mg/kg, s.c.) lowered the levels of these parameters in acute iron-loaded rats. 4. The results of the present study indicate that ER stress may play an important role in iron-induced tissue injury and that reactive oxygen species may mediate the ER stress response in the pathogenesis of iron-overload cellular injury. PMID:19594550

  13. Obesity versus osteoarthritis: beyond the mechanical overload

    PubMed Central

    Sartori-Cintra, Angélica Rossi; Aikawa, Priscila; Cintra, Dennys Esper Correa

    2014-01-01

    Obesity is currently considered a major public health problem in the world, already reaching epidemic characteristics, according to the World Health Organization. Excess weight is the major risk factor associated with various diseases, such as type 2 diabetes mellitus, hypertension, dyslipidemia and osteometabolic diseases, including osteoporosis and osteoarthritis. Osteoarthritis is the most prevalent rheumatic disease and the leading cause of physical disability and reduced quality of life of the population over 65 years. It mainly involves the joints that bear weight - knees and hips. However, along with the cases of obesity, its prevalence is increasing, and even in other joints, such as hands. Thus, it is assumed that the influence of obesity on the development of OA is beyond mechanical overload. The purpose of this review was to correlate the possible mechanisms underlying the genesis and development of these two diseases. Increased fat mass is directly proportional to excessive consumption of saturated fatty acids, responsible for systemic low-grade inflammation condition and insulin and leptin resistance. At high levels, leptin assumes inflammatory characteristics and acts in the articular cartilage, triggering the inflammatory process and changing homeostasis this tissue with consequent degeneration. We conclude that obesity is a risk factor for osteoarthritis and that physical activity and changes in diet composition can reverse the inflammatory and leptin resistance, reducing progression or preventing the onset of osteoarthritis. PMID:25184806

  14. Iron Metabolism in Field Hockey Players During an Annual Training Cycle

    PubMed Central

    Podgórski, Tomasz; Kryściak, Jakub; Konarski, Jan; Domaszewska, Katarzyna; Durkalec-Michalski, Krzysztof; Strzelczyk, Ryszard; Pawlak, Maciej

    2015-01-01

    Post-physical training changes in iron metabolism in the human body often occur. To fully describe these processes, fifteen male Polish National Team field hockey players (age 27.7 ± 5.2 years, body mass 72.8 ± 7.6 kg and body height 177.1 ± 5.7 cm) were examined in three phases of an annual training cycle: preparatory (T1), competitive (T2) and transition (T3). To assess aerobic fitness, maximal oxygen uptake (VO2max) was evaluated. Based on the iron concentration, the changes in total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and other selected haematological indicators (haemoglobin, erythrocytes, mean corpuscular haemoglobin - MCH) in iron metabolism were estimated. The average values of maximum oxygen uptake increased from 54.97 ± 3.62 ml·kg−1·min−1 in T1 to 59.93 ± 3.55 ml·kg−1·min−1 in T2 (p<0.05) and then decreased to 56.21 ± 4.56 ml·kg−1·min−1 in T3 (p<0.05). No statistically significant changes in the erythrocyte count were noted. The MCH and haemoglobin concentration decreased between T1 and T2. The maximal exercise test caused a significant (p<0.05) increase in the plasma iron concentration during the competition and transition phases. Progressive but non-significant increases in resting iron concentration, TIBC and UIBC in the analysed annual training cycle were noted. To show global changes in iron metabolism in the human body, it is necessary to determine additional variables, i.e. UIBC, TIBC, haemoglobin, MCH or the erythrocyte count. The direction of changes in iron metabolism depends on both the duration and intensity of the physical activity and the fitness level of the subjects. Dietary intake of iron increases the level of this trace element and prevents anaemia associated with training overloads. PMID:26557195

  15. Mammalian target of rapamycin coordinates iron metabolism with iron-sulfur cluster assembly enzyme and tristetraprolin.

    PubMed

    Guan, Peng; Wang, Na

    2014-09-01

    Both iron deficiency and excess are relatively common health concerns. Maintaining the body's levels of iron within precise boundaries is critical for cell functions. However, the difference between iron deficiency and overload is often a question of a scant few milligrams of iron. The mammalian target of rapamycin (mTOR), an atypical Ser/Thr protein kinase, is attracting significant amounts of interest due to its recently described role in iron homeostasis. Despite extensive study, a complete understanding of mTOR function has remained elusive. mTOR can form two multiprotein complexes that consist of mTOR complex 1 (mTORC1) and mTOR complex 2. Recent advances clearly demonstrate that mTORC1 can phosphorylate iron-sulfur cluster assembly enzyme ISCU and affect iron-sulfur clusters assembly. Moreover, mTOR is reported to control iron metabolism through modulation of tristetraprolin expression. It is now well appreciated that the hormonal hepcidin-ferroportin system and the cellular iron-responsive element/iron-regulatory protein regulatory network play important regulatory roles for systemic iron metabolism. Sustained ISCU protein levels enhanced by mTORC1 can inhibit iron-responsive element and iron-regulatory protein binding activities. In this study, hepcidin gene and protein expression in the livers of tristetraprolin knockout mice were dramatically reduced. Here, we highlight and summarize the current understanding of how mTOR pathways serve to modulate iron metabolism and homeostasis as the third iron-regulatory system.

  16. Fob1 and Fob2 proteins are virulence determinants of Rhizopus oryzae via facilitating iron uptake from ferrioxamine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis. Although not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we de...

  17. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Iron-choline citrate complex. 172.370 Section 172... Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline citrate complex made by reacting... source of iron in foods for special dietary use....

  18. Multimedia reviews: multimedia overload produces "symplexity".

    PubMed

    Zingrone, Frank

    2003-03-01

    We humans "know" from information mediated through our "natural senses." All outside signals come to us through some medium-sound waves, pressure and touch, light waves, radio and television waves, and so forth. McLuhan's famous mantra "The medium is the message" paradoxically highlighted the critical transformation of meaning when each type of medium-radio, television, drums, hand signals-by its very nature modifies the message it is transmitting. In this month's column Dr. Zingrone brings challenging new ideas to the field of human communication and vividly describes the communication distortions that occur when the overload of increasingly complex modern media results in a paradoxical diminution of meaning itself. He has coined a term for this unintended consequence and given it to his exciting new book, The Media Symplex: At the Edge of Meaning in the Age of Chaos (1). Many of us may recognize the effect created by this accelerating phenomenon-our stupefaction as we experience the onslaught of sound and visual signals produced by a television news screen, where an avalanche of rapidly changing, overlapping, and distorted visual images flash at our eyes while screeching, undulating synthetic "music" crashes about our ears. And in that chaos we struggle to find meaning,Dr. Zingrone, who worked with McLuhan and who has written extensively about his work (2,3), has succeeded in his new book to move the pioneering work of human communication scientists forward and thereby help us all to understand the developing paradox and danger of more communication yet less meaning. PMID:12610237

  19. Multimedia reviews: multimedia overload produces "symplexity".

    PubMed

    Zingrone, Frank

    2003-03-01

    We humans "know" from information mediated through our "natural senses." All outside signals come to us through some medium-sound waves, pressure and touch, light waves, radio and television waves, and so forth. McLuhan's famous mantra "The medium is the message" paradoxically highlighted the critical transformation of meaning when each type of medium-radio, television, drums, hand signals-by its very nature modifies the message it is transmitting. In this month's column Dr. Zingrone brings challenging new ideas to the field of human communication and vividly describes the communication distortions that occur when the overload of increasingly complex modern media results in a paradoxical diminution of meaning itself. He has coined a term for this unintended consequence and given it to his exciting new book, The Media Symplex: At the Edge of Meaning in the Age of Chaos (1). Many of us may recognize the effect created by this accelerating phenomenon-our stupefaction as we experience the onslaught of sound and visual signals produced by a television news screen, where an avalanche of rapidly changing, overlapping, and distorted visual images flash at our eyes while screeching, undulating synthetic "music" crashes about our ears. And in that chaos we struggle to find meaning,Dr. Zingrone, who worked with McLuhan and who has written extensively about his work (2,3), has succeeded in his new book to move the pioneering work of human communication scientists forward and thereby help us all to understand the developing paradox and danger of more communication yet less meaning.

  20. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    PubMed

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload.

  1. Adipocyte iron regulates leptin and food intake

    PubMed Central

    Gao, Yan; Li, Zhonggang; Gabrielsen, J. Scott; Simcox, Judith A.; Lee, Soh-hyun; Jones, Deborah; Cooksey, Bob; Stoddard, Gregory; Cefalu, William T.; McClain, Donald A.

    2015-01-01

    Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression. PMID:26301810

  2. Iron nutrition in adolescence.

    PubMed

    Mesías, Marta; Seiquer, Isabel; Navarro, M Pilar

    2013-01-01

    Adolescence is an important period of nutritional vulnerability due to increased dietary requirements for growth and development. Iron needs are elevated as a result of intensive growth and muscular development, which implies an increase in blood volume; thus, it is extremely important for the adolescent's iron requirements to be met. Diet, therefore, must provide enough iron and, moreover, nutrients producing adequate iron bioavailability to favor element utilization and thus be sufficient for needs at this stage of life. Currently, many adolescents consume monotonous and unbalanced diets which may limit mineral intake and/or bioavailability, leading to iron deficiency and, consequently, to ferropenic anemia, a nutritional deficit of worldwide prevalence. Iron deficiency, apart from provoking important physiological repercussions, can adversely affect adolescents' cognitive ability and behavior. Accordingly, promoting the consumption of a varied, adjusted, and balanced diet by adolescents will facilitate iron utilization, benefiting their health both at present and in adulthood. This review discusses how physiological changes during adolescence can cause iron requirements to increase. Consequently, it is important that diet should contribute an appropriate amount of this mineral and, moreover, with an adequate bioavailability to satisfy needs during this special period of life.

  3. Quenching-Chemiluminescence Determination of Trace Amounts of l-Tyrosine Contained in Dietary Supplement by Chemiluminescence Reaction of an Iron-Phthalocyanine Complex

    PubMed Central

    Ohtomo, Takao; Igarashi, Shukuro; Takagai, Yoshitaka; Ohno, Osamu

    2012-01-01

    The chemiluminescence (CL) signal immediately appeared when a hydrogen peroxide solution was injected into an iron-phthalocyanine tetrasulfonic acid (Fe-PTS) aqueous solution. Moreover, the CL intensity of Fe-PTS decreased by adding l-tyrosine. Based on these results, the determination of trace amounts of l-tyrosine was developed using the quenching-chemiluminescence. The calibration curve of l-tyrosine was obtained in the concentration range of 2.0 × 10−7 M to 2.0 × 10−5 M. Moreover, the relative standard deviation (RSD) was 1.63 % (n = 5) for 2.0 × 10−6 M l-tyrosine, and its detection limits (3σ) were 1.81 × 10−7 M. The spike and recovery experiments for l-tyrosine were performed using a soft drink. Furthermore, the determination of l-tyrosine was applied to supplements containing various kinds of amino acids. Each satisfactory relative recovery was obtained at 98 to 102%. PMID:22567562

  4. Dietary Deficiency of Calcium and/or Iron, an Age-Related Risk Factor for Renal Accumulation of Cadmium in Mice.

    PubMed

    Min, Kyong-Son; Sano, Erika; Ueda, Hidenori; Sakazaki, Fumitoshi; Yamada, Keita; Takano, Masaoki; Tanaka, Keiichi

    2015-01-01

    The major route of cadmium (Cd) intake by non-smokers is through food ingestion. Cd is a non-essential metal absorbed through one or more transporters of essential metal ions. Expression of these transporters is affected by nutritional status. To investigate the risk factors for Cd toxicity, the effects of deficiency of essential metals on hepatic and renal accumulation of Cd were studied in mice of different ages. Mice were administered a control diet or one of the essential metal-deficient diets, administered Cd by gavage for 6 weeks, and killed; then, Cd accumulation was evaluated. Iron deficiency (FeDF) or calcium deficiency (CaDF) resulted in remarkable increases in hepatic and renal Cd accumulation compared with control-diet mice and other essential metal-deficient mice. Cd accumulation in hepatic and renal tissue was increased significantly at all ages tested in FeDF and CaDF mice. Renal Cd concentrations were higher in 4-week-old mice than in 8- and 25-week-old mice. Increase in intestinal mRNA expression of calcium transporter (CaT)1, divalent metal ion transporter-1, and metallothionein (MT)1 was also higher in 4-week-old mice than in other mice. Renal accumulation of Cd showed strong correlation with intestinal mRNA expression of CaT1 and MT1. These data suggest that CaDF and FeDF at younger ages can be a risk factor for Cd toxicity.

  5. Protein adducts of malondialdehyde and 4-hydroxynonenal in livers of iron loaded rats: quantitation and localization.

    PubMed

    Khan, M Firoze; Wu, Xiaohong; Tipnis, Ulka R; Ansari, G A S; Boor, Paul J

    2002-05-01

    Pathophysiological mechanisms for hepatocellular injury, fibrosis and/or cirrhosis in hepatic iron overload are poorly understood. An increase in intracellular transit pool of iron can catalyze peroxidation of lipids to produce reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE). Covalent binding of such lipid aldehydes with proteins may cause impairment in cellular function and integrity. This investigation was focused on quantitative determination of MDA and HNE-protein adducts, and to establish a correlation between iron deposition and formation and localization of MDA and HNE-protein adducts, using immunohistochemistry. To achieve iron overload, male SD rats were fed a 2.5% carbonyl iron-supplemented diet for six weeks, while control animals received standard diet. Total iron as well as low molecular weight chelatable iron (LMWC-Fe) in the hepatic tissue of rats fed the iron supplemented diet increased significantly ( approximately 14- and approximately 15-fold, respectively). Quantitative ELISA for MDA-and HNE-protein adducts showed remarkable increases of 186 and 149%, respectively, in the liver homogenates of rats fed the iron-supplemented diet. Sections of liver stained for iron showed striking iron deposits in periportal (zone 1) hepatocytes, which was less dramatic in midzonal (zone 2) cells. Livers from iron-loaded rats showed strong, diffuse staining for both MDA and HNE adducts, which was highly pronounced in centrilobular (zone 3) hepatocytes, but was also evident in midzonal cells (zone 2). The demonstration of greater formation of both MDA and HNE-protein adducts provides evidence of iron-catalyzed lipid peroxidation in vivo. Although in this model of iron overload there was no evidence of tissue injury, our results provide an account of some of the initiating factors or early molecular events in hepatocellular damage that may lead to the pathological manifestations seen in chronic iron overload.

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

    SciTech Connect

    Collingwood, Joanna; Dobson, Jon

    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.

  7. Distribution and quantitation of skin iron in primary haemochromatosis: correlation with total body iron stores in patients undergoing phlebotomy.

    PubMed

    Pinheiro, Teresa; Silva, Raquel; Fleming, Rita; Gonçalves, Afonso; Barreiros, Maria A; Silva, João N; Morlière, Patrice; Santus, René; Filipe, Paulo

    2014-01-01

    Measurement of the concentration of iron in the skin, if correlated with total body iron stores, may enable better informed decisions on when to initiate, change or stop therapy in hereditary heamochromatosis. Naïve haemochromatosis patients with iron overload and with C282Y and/or H63D HFE mutations were evaluated at the following time-points: disease diagnosis, end of the therapy programme, and 6 months after the end of therapy. The distribution and concentration of iron in the skin were assessed by quantitative nuclear microscopy methods, in parallel with serum and plasma iron concentration. Iron content in the liver was determined by nuclear magnetic resonance. Iron accumulated in the epidermis; its concentration increased from outer to inner layers, being maximal in the basal layer (7.33 ± 0.98 µmol/g). At all 3 time-points, most of the iron was associated with the extracellular space. During the phlebotomy programme the iron content of the skin and the liver decreased by a factor of 2. These data suggest that measurements of iron concentration in the epidermis, which is a readily accessible tissue, reflect iron overload in the liver.

  8. Cadmium in blood and urine--impact of sex, age, dietary intake, iron status, and former smoking--association of renal effects.

    PubMed Central

    Olsson, Ing-Marie; Bensryd, Inger; Lundh, Thomas; Ottosson, Helena; Skerfving, Staffan; Oskarsson, Agneta

    2002-01-01

    We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinary Cd (UCd) was 0.23 nmol/mmol creatinine (range, 0.065-0.99). The intake of Cd per kilogram body weight did not significantly differ between sexes and did not correlate with BCd or UCd, which may be explained by a low and varying bioavailibility of Cd from food items. However, when a subgroup of the study population, couples of never-smoking men and women, were compared, a lower intake per kilogram body weight was found in the women, but the women had a 1.8 times higher BCd and a 1.4 times higher UCd. The higher female BCd and UCd may be explained by higher absorption due to low iron status. BCd and UCd both increased with age and were higher in the ex-smokers, who had stopped smoking more than 5 years before the study, compared to never-smokers. The contribution of locally produced food to the total Cd intake was relatively low and varied. Males living in areas with low soil Cd had lower UCd than the others. However, Cd levels in kidneys from pigs, fed locally produced cereals, did not predict BCd or UCd in humans at the same farms. The kidney function parameter ss2-microglobulin-creatinine clearance was related to UCd, whereas urinary protein-HC, N-acetyl-ss-glucoseaminidase or albumin-creatinine clearance was not when age was accounted for. Hence, even at the low exposure levels in this study population, there was an indication of effect on biochemical markers of renal function. PMID:12460796

  9. Salvaging transient data with overloads and zero offsets

    SciTech Connect

    Smallwood, D.O.; Cap, J.S.

    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.

  10. Cancer Cells with Irons in the Fire

    PubMed Central

    Bystrom, Laura M.; Rivella, Stefano

    2014-01-01

    Iron is essential for the growth and proliferation of cells, as well as for many biological processes that are important for the maintenance and survival of the human body. However, excess iron is associated with the development of cancer and other pathological conditions, due in part to the pro-oxidative nature of iron and its damaging effects on DNA. Current studies suggest that iron depletion may be beneficial for patients that have diseases associated with iron overload or other iron metabolism disorders that may increase the risk for cancer. On the other hand, studies suggest that cancer cells are more vulnerable to the effects of iron depletion and oxidative stress in comparison to normal cells. Therefore, cancer patients might benefit from treatments that alter both iron metabolism and oxidative stress. This review highlights the pro-oxidant effects of iron, the relationship between iron and cancer development, the vulnerabilities of iron-dependent cancer phenotype, and how these characteristics may be exploited to prevent or treat cancer. PMID:24835768

  11. Iron sufficient to cause hepatic fibrosis and ascites does not cause cardiac arrhythmias in the gerbil.

    PubMed

    Kaiser, Lana; Davis, John M; Patterson, Jon; Johnson, Abby L; Bohart, George; Olivier, N Bari; Schwartz, Kenneth A

    2009-10-01

    Chronic iron overload associated with hereditary hemochromatosis or repeated red cell transfusions is known to cause cardiac failure. Cardiac arrhythmias have been incidentally noted in patients with iron overload, but they are often dismissed as being related to comorbid conditions. Studies with anesthetized iron-loaded gerbils using short recordings suggest a role for iron in the development of arrhythmias. Our goal was to characterize iron-induced arrhythmias in the chronically instrumented, untethered, telemetered gerbil. Electrocardiograms were recorded for 10 s every 30 min for approximately 6 months in iron-loaded (n=23) and control (n=8) gerbils. All gerbils in both groups showed evidence of frequent sinus arrhythmia. There was no difference in heart rate, electrocardiographic parameters, or number of arrhythmias per minute between groups. Gerbils rarely showed significant arrhythmias. Body weight and heart weight were not significantly different between groups, whereas liver weight increased with increasing iron dose in the treated group. Cardiac and hepatic iron concentrations were significantly increased in iron-loaded gerbils. Eight of 14 gerbils loaded to 6.2 g/kg body weight developed ascites. We conclude that an iron load sufficient to cause clinical liver disease does not cause cardiac arrhythmias in the gerbil model of iron overload.

  12. Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling.

    PubMed

    Zhang, Miao; Liu, Jing; Guo, Wenli; Liu, Xin; Liu, Sijin; Yin, Huijun

    2016-05-01

    Systemic iron homeostasis is strictly controlled under normal conditions to ensure a balance between the absorption, utilization, storage and recycling of iron. The hepcidin-ferroportin (FPN) axis is of critical importance in the maintenance of iron homeostasis. Hepcidin deficiency gives rise to enhanced dietary iron absorption, as well as to increased iron release from macrophages, and this in turn results in iron accumulation in the plasma and organs, and is associated with a range of tissue pathologies. Low hepcidin levels have been demonstrated in most forms of hereditary hemochromatosis (HH), as well as in β-thalassemia. Therapies that increase hepcidin concentrations may potentially play a role in the treatment of these iron overload-related diseases. To date, natural compounds have not been extensively investigated for this purpose, to the best of our knowledge. Thus, in the present study, we screened natural compounds that have the potential to regulate hepcidin expression. By performing hepcidin promoter-luciferase assay, RT-qPCR and animal experiments, we demonstrated that icariin and berberine were potent stimulators of hepcidin transcription. Mechanistic experiments indicated that icariin and berberine increased hepcidin expression by activating the signal transducer and activator of transcription 3 (Stat3) and Smad1/5/8 signaling pathways. The induction of hepcidin was confirmed in mice following icariin administration, coupled with associated changes in serum and tissue iron concentrations. In support of these findings, the icariin analogues, epimedin A, B and C, also increased hepatic hepcidin expression. However, these changes were not observed in hepcidin-deficient [Hamp1-/- or Hamp1‑knockout (KO)] mice following icariin administration, thereby verifying hepatic hepcidin as the target of icariin. Although berberine exhibited a robust capacity to promote hepcidin expression in vitro, it failed to alter hepcidin expression in mice. Taken together

  13. Iron-chelation therapy: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2004-01-01

    Chronically transfused patients develop iron overload that leads to organ damage and ultimately to death. The introduction of the iron-chelating agent, desferrioxamine mesylate, dramatically improved the life expectancy of these patients. However, the very demanding nature of this treatment (subcutaneous continuous infusion via a battery-operated portable pump) has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. In this review, we describe the most important advances in iron-chelating therapy. In particular, we analyze a new method of administering desferrioxamine mesylate (twice daily subcutaneous bolus injections) and a novel, orally active iron chelator (ICL670A). We also present a meta-analysis of the largest trials on the oral iron chelator deferiprone and the results of combined therapy (deferiprone and desferrioxamine).

  14. Iron Homeostasis in Health and Disease

    PubMed Central

    Gozzelino, Raffaella; Arosio, Paolo

    2016-01-01

    Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload. PMID:26805813

  15. Nuclear resonance scattering measurement of human iron stores

    SciTech Connect

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

    1985-07-01

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

  16. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test

    PubMed Central

    2012-01-01

    Background Dietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20 g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1 ± 5.8 years old) immediately before and 5 and 60 min after the exhaustive Wingate test. Results Maximum anaerobic power was improved by acute creatine supplementation (10.5 %), but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP), leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects. Conclusions Our data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent) and inherent antioxidant activity of creatine. PMID:22691230

  17. Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

    PubMed

    Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

    2015-09-01

    The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and

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

    PubMed

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

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

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

    PubMed Central

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

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

  20. Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

    PubMed

    Macdougall, Iain C; Bircher, Andreas J; Eckardt, Kai-Uwe; Obrador, Gregorio T; Pollock, Carol A; Stenvinkel, Peter; Swinkels, Dorine W; Wanner, Christoph; Weiss, Günter; Chertow, Glenn M

    2016-01-01

    Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

  1. Obesity Alters Adipose Tissue Macrophage Iron Content and Tissue Iron Distribution

    PubMed Central

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

    2014-01-01

    Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFehi, and the remaining ATMs are referred to as MFelo. In lean mice, ~25% of the ATMs are MFehi; this percentage decreases in obesity owing to the recruitment of MFelo macrophages. Similar to MFelo cells, MFehi ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFehi ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFehi iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFehi ATM phenotype and their reduced capacity to handle iron. PMID:24130337

  2. Nondestructive test determines overload destruction characteristics of current limiter fuses

    NASA Technical Reports Server (NTRS)

    Swartz, G. A.

    1968-01-01

    Nondestructive test predicts the time required for current limiters to blow /open the circuit/ when subjected to a given overload. The test method is based on an empirical relationship between the voltage rise across a current limiter for a fixed time interval and the time to blow.

  3. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  4. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  5. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  6. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  7. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  8. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  9. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  10. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  11. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  12. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  13. Shift Work, Role Overload, and the Transition to Parenthood

    ERIC Educational Resources Information Center

    Perry-Jenkins, Maureen; Goldberg, Abbie E.; Pierce, Courtney P.; Sayer, Aline G.

    2007-01-01

    This article examines how the work hours, work schedules, and role overload of working-class couples are related to depressive symptoms and relationship conflict across the transition to parenthood. Data are from 132 dual-earner couples interviewed 5 times across the transition. Multilevel modeling analyses revealed that working evening or night…

  14. Information Overload and Viral Marketing: Countermeasures and Strategies

    NASA Astrophysics Data System (ADS)

    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.

  15. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    NASA Technical Reports Server (NTRS)

    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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. PMID:27540317

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

    PubMed

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. PMID:27540317

  19. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection. Automatic... electric equipment and circuits against short circuit and overloads. Three-phase motors on all electric... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electric equipment and circuits; overload...

  20. The role of iron in the skin and cutaneous wound healing

    PubMed Central

    Wright, Josephine A.; Richards, Toby; Srai, Surjit K. S.

    2014-01-01

    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 UVA spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anemia on wound healing using a variety of experimental methodology to establish anemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialization. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localized iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary hemochromatosis. Iron plays a key role in chronic ulceration and conditions such as rheumatoid arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic disease and dysregulation of local cutaneous iron hemostasis. 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. PMID:25071575

  1. Iron homeostasis: a new job for macrophages in adipose tissue?

    PubMed

    Hubler, Merla J; Peterson, Kristin R; Hasty, Alyssa H

    2015-02-01

    Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron-handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity.

  2. Iron homeostasis: a new job for macrophages in adipose tissue?

    PubMed Central

    Hubler, Merla J.; Peterson, Kristin R.; Hasty, Alyssa H.

    2015-01-01

    Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity. PMID:25600948

  3. [Iron stores status at early pregnancy].

    PubMed

    Barón, María Adela; Solano, Liseti; Peña, Evelyn; Del Real, Sara

    2005-06-01

    Iron deficiency is the most common cause of nutritional anemia. During pregnancy there is a high risk of developing it, due to the increase of iron requirements for fetal and maternal tissues growth. The objective of this study was to determine the iron nutritional status in early pregnancy and to determine its relationship with the dietary intake. The study applied a cross-sectional and descriptive design in 419 pregnant women (13-41 y) from Valencia, Carabobo, Venezuela. Serum ferritin was determined by enzimoinmunoassay and hemoglobin by a semi-automated method. Dietary iron intake was assessed through two non-consecutive 24 hours recalls. Statistical analysis included basic descriptives, Fisher exact test, Chi-square, and Mann-Whitney tests; with a statistical significance of p < 0.05. The iron deficiency and anemia prevalence were 16.2% and 14.4%, respectively; corresponding 36.6% to ferropenic anemia. 10.4%, 29.0% and 24.2% of the women had deficient intake for iron, vitamin C and A, respectively. There were no significant differences by age. A nutritional risk was observed regarding the iron status, demonstrated by the percentage of ferropenic anemia and because the main dietary contribution came from non-heme iron, which has low bioavailability. Additionally, there was an important percentage of inadequate vitamin C and A intakes; hence, their contribution to iron absorption was limited.

  4. Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and reactive oxygen species (ROS) production.

    PubMed

    Wu, Zhihao; Du, Yumei; Xue, Hua; Wu, Yongsheng; Zhou, Bing

    2012-01-01

    The neurotoxicity of aluminum (Al) - the most abundant metal element on earth - has been known for years. However, the mechanism of Al-induced neurodegeneration and its relationship to Alzheimer's disease are still controversial. In particular, in vivo functional data are lacking. In a Drosophila model with chronic dietary Al overloading, general neurodegeneration and several behavioral changes were observed. Al-induced neurodegeneration is independent of β-amyloid or tau-associated toxicity, suggesting they act in different molecular pathways. Interestingly, Drosophila frataxin (dfh), which causes Friedreich's ataxia if mutated in humans, displayed an interacting effect with Al, suggesting Friedreich's ataxia patients might be more susceptible to Al toxicity. Al-treated flies accumulated large amount of iron and reactive oxygen species (ROS), and exhibited elevated SOD2 activity. Genetic and pharmacological efforts to reduce ROS or chelate excess Fe significantly mitigated Al toxicity. Our results indicate that Al toxicity is mediated through ROS production and iron accumulation and suggest a remedial route to reduce toxicity due to Al exposure.

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.

    PubMed

    Sangokoya, Carolyn; Doss, Jennifer F; Chi, Jen-Tsan

    2013-04-01

    Ferroportin (FPN) is the only known cellular iron exporter in mammalian cells and plays a critical role in the maintenance of both cellular and systemic iron balance. During iron deprivation, the translation of FPN is repressed by iron regulatory proteins (IRPs), which bind to the 5' untranslated region (UTR), to reduce iron export and preserve cellular iron. Here, we report a novel iron-responsive mechanism for the post-transcriptional regulation of FPN, mediated by miR-485-3p, which is induced during iron deficiency and represses FPN expression by directly targeting the FPN 3'UTR. The overexpression of miR-485-3p represses FPN expression and leads to increased cellular ferritin levels, consistent with increased cellular iron. Conversely, both inhibition of miR-485-3p activity and mutation of the miR-485-3p target sites on the FPN 3'UTR are able to relieve FPN repression and lead to decreased cellular iron levels. Together, these findings support a model that includes both IRPs and microRNAs as iron-responsive post-transcriptional regulators of FPN. The involvement of microRNA in the iron-responsive regulation of FPN offers additional stability and fine-tuning of iron homeostasis within different cellular contexts. MiR-485-3p-mediated repression of FPN may also offer a novel potential therapeutic mechanism for circumventing hepcidin-resistant mechanisms responsible for some iron overload diseases.

  7. PfeT, a P1B4 -type ATPase, effluxes ferrous iron and protects Bacillus subtilis against iron intoxication.

    PubMed

    Guan, Guohua; Pinochet-Barros, Azul; Gaballa, Ahmed; Patel, Sarju J; Argüello, José M; Helmann, John D

    2015-11-01

    Iron is an essential element for nearly all cells and limited iron availability often restricts growth. However, excess iron can also be deleterious, particularly when cells expressing high affinity iron uptake systems transition to iron rich environments. Bacillus subtilis expresses numerous iron importers, but iron efflux has not been reported. Here, we describe the B. subtilis PfeT protein (formerly YkvW/ZosA) as a P1B4 -type ATPase in the PerR regulon that serves as an Fe(II) efflux pump and protects cells against iron intoxication. Iron and manganese homeostasis in B. subtilis are closely intertwined: a pfeT mutant is iron sensitive, and this sensitivity can be suppressed by low levels of Mn(II). Conversely, a pfeT mutant is more resistant to Mn(II) overload. In vitro, the PfeT ATPase is activated by both Fe(II) and Co(II), although only Fe(II) efflux is physiologically relevant in wild-type cells, and null mutants accumulate elevated levels of intracellular iron. Genetic studies indicate that PfeT together with the ferric uptake repressor (Fur) cooperate to prevent iron intoxication, with iron sequestration by the MrgA mini-ferritin playing a secondary role. Protection against iron toxicity may also be a key role for related P1B4 -type ATPases previously implicated in bacterial pathogenesis. PMID:26261021

  8. A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv⁻/⁻ mice.

    PubMed

    Padda, Ranjit Singh; Gkouvatsos, Konstantinos; Guido, Maria; Mui, Jeannie; Vali, Hojatollah; Pantopoulos, Kostas

    2015-02-15

    Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv(-/-) mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv(-/-) mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv(-/-) mice. Notably, steatosis was attenuated in Hjv(-/-) mice on the HFD+Fe regimen. Hjv(-/-) animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice.

  9. A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv⁻/⁻ mice.

    PubMed

    Padda, Ranjit Singh; Gkouvatsos, Konstantinos; Guido, Maria; Mui, Jeannie; Vali, Hojatollah; Pantopoulos, Kostas

    2015-02-15

    Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv(-/-) mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv(-/-) mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv(-/-) mice. Notably, steatosis was attenuated in Hjv(-/-) mice on the HFD+Fe regimen. Hjv(-/-) animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice. PMID:25501544

  10. Early postnatal iron repletion overcomes lasting effects of gestational iron deficiency in rats.

    PubMed

    Beard, John L; Unger, Erica L; Bianco, Laura E; Paul, Tessy; Rundle, Sarah E; Jones, Byron C

    2007-05-01

    Iron deficiency anemia in early childhood causes developmental delays and, very likely, irreversible alterations in neurological functioning. One primary goal for the present study was to determine whether the effects of late gestational iron deficiency on brain monoamine metabolism, iron content, and behavioral phenotypes could be repaired with iron intervention in early lactation. Young pregnant rats were provided iron-deficient or control diets from mid-gestation (G15). At postnatal d 4 (P4), pups from iron-deficient dams were out-fostered either to other ID dams or control dams while pups of control dams were similarly fostered to other control dams. Dietary treatments continued to adulthood (P65) when brain iron and regional monoamines were evaluated. P4 iron repletion normalized body iron status, brain iron concentrations, monoamine concentrations, and monoamine transporter and receptor densities in most brain regions. Dopamine transporter densities in caudate and substantia nigra were lower in ID rats but were normalized with iron repletion. Serotonin transporter levels in most brain regions and open-field exploration were also normalized with iron repletion. The success of this approach of early postnatal iron intervention following iron deficiency in utero contrasts to a relative lack of success when the intervention is performed at weaning. These data suggest that a window of opportunity exists for reversing the detrimental effects of iron deficiency in utero in rats and provides strong support of intervention approaches in humans with iron deficiency during pregnancy.

  11. CXCR4 gene transfer prevents pressure overload induced heart failure

    PubMed Central

    LaRocca, Thomas J.; Jeong, Dongtak; Kohlbrenner, Erik; Lee, Ahyoung; Chen, JiQiu; Hajjar, Roger J.; Tarzami, Sima T.

    2012-01-01

    Stem cell and gene therapies are being pursued as strategies for repairing damaged cardiac tissue following myocardial infarction in an attempt to prevent heart failure. The chemokine receptor-4 (CXCR4) and its ligand, CXCL12, play a critical role in stem cell recruitment post-acute myocardial infarction. Whereas progenitor cell migration via the CXCL12/CXCR4 axis is well characterized, little is known about the molecular mechanisms of CXCR4 mediated modulation of cardiac hypertrophy and failure. We used gene therapy to test the effects of CXCR4 gene delivery on adverse ventricular remodeling due to pressure overload. We assessed the effect of cardiac overexpression of CXCR4 during trans-aortic constriction (TAC) using a cardiotropic adeno-associated viral vector (AAV9) carrying the CXCR4 gene. Cardiac overexpression of CXCR4 in mice with pressure overload prevented ventricular remodeling, preserved capillary density and maintained function as determined by echocardiography and in vivo hemodynamics. In isolated adult rat cardiac myocytes, CXCL12 treatment prevented isoproterenol induced hypertrophy and interrupted the calcineurin/NFAT pathway. Finally, a complex involving the L-type calcium channel, β2-adenoreceptor, and CXCR4 (Cav1.2/β2AR/CXCR4) was identified in healthy cardiac myocytes and was shown to dissociate as a consequence of heart failure. CXCR4 administered to the heart via gene transfer prevents pressure overload induced heart failure. The identification of CXCR4 participation in a Cav1.2-β2AR regulatory complex provides further insight into the mechanism by which CXCR4 modulates calcium homeostasis and chronic pressure overload responses in the cardiac myocyte. Together these results suggest AAV9.CXCR4 gene therapy is a potential therapeutic approach for congestive heart failure. PMID:22668785

  12. Oleanolic acid alleviated pressure overload-induced cardiac remodeling.

    PubMed

    Liao, Hai-Han; Zhang, Nan; Feng, Hong; Zhang, Ning; Ma, Zhen-Guo; Yang, Zheng; Yuan, Yuan; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-11-01

    Previous study has demonstrated that oleanolic acid (OA) possessing the anti-inflammatory and anti-oxidant properties blunted high-glucose-induced diabetic cardiomyopathy and ameliorated experimental autoimmune myocarditis in mice. However, little is known about its effects on pressure overload-induced cardiac remodeling. Herein, we investigated the effect of OA on cardiac remodeling and underlying mechanism. Mice, subjected to aortic banding (AB), were randomly assigned into control group and experimental group. OA premixed in diets was administered to mice after 3 days of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed after 8 weeks' treatment of OA. Histologic examination and molecular analyses were used to assess cardiac hypertrophy and tissue fibrosis. In addition, the inhibitory effects of OA on H9c2 cardiomyocytes and cardiac primary fibroblast responded to the stimulation of AngII were also investigated. OA ameliorated the systolic and diastolic dysfunction induced by pressure overload evidenced by echocardiography and catheter-based measurements. OA also decreased the mRNA expression of cardiac hypertrophy and fibrosis markers evidenced by RT-PCR. It has been shown in our study that pressure overload activated the phosphorylations of Akt, mTOR, p70s6k, S6, GSK3β, and FoxO3a, and treatment of OA attenuated the phosphorylation of these proteins. In addition, hypertrophy of cardiomyocytes and fibrosis markers induced by AngII was inhibited by OA in vitro. Our findings uncover that OA suppressed AB-induced cardiac hypertrophy, partly by inhibiting the activity of Akt/mTOR pathway, and suggest that treatment of OA may have a benefit on retarding the progress of cardiac remodeling under long terms of pressure overload. PMID:26215454

  13. Natural history and information overload: The case of Linnaeus.

    PubMed

    Müller-Wille, Staffan; Charmantier, Isabelle

    2012-03-01

    Natural History can be seen as a discipline paradigmatically engaged in 'data-driven research.' Historians of early modern science have begun to emphasize its crucial role in the Scientific Revolution, and some observers of present day genomics see it as engaged in a return to natural history practices. A key concept that was developed to understand the dynamics of early modern natural history is that of 'information overload.' Taxonomic systems, rules of nomenclature, and technical terminologies were developed in botany and zoology to catch up with the ever increasing amount of information on hitherto unknown plant and animal species. In our contribution, we want to expand on this concept. After all, the same people who complain about information overload are usually the ones who contribute to it most significantly. In order to understand this complex relationship, we will turn to the annotation practices of the Swedish naturalist Carl Linnaeus (1707-1778). The very tools that Linnaeus developed to contain and reduce information overload, as we aim to demonstrate, facilitated a veritable information explosion that led to the emergence of a new research object in botany: the so-called 'natural' system.

  14. Influence, information overload, and information technology in health care.

    PubMed

    Rebitzer, James B; Rege, Mari; Shepard, Christopher

    2008-01-01

    We investigate whether information technology (IT) can help physicians more efficiently acquire new knowledge in a clinical environment characterized by information overload. We combine analysis of data from a randomized trial with a theoretical model of the influence that IT has on the acquisition of new medical knowledge. Although the theoretical framework we develop is conventionally microeconomic, the model highlights the non-market and non-pecuniary influence activities that have been emphasized in the sociological literature on technology diffusion. We report three findings. First, empirical evidence and theoretical reasoning suggests that computer-based decision support will speed the diffusion of new medical knowledge when physicians are coping with information overload. Second, spillover effects will likely lead to "underinvestment" in this decision support technology. Third, alternative financing strategies common to new IT, such as the use of marketing dollars to pay for the decision support systems, may lead to undesirable outcomes if physician information overload is sufficiently severe and if there is significant ambiguity in how best to respond to the clinical issues identified by the computer. This is the first paper to analyze empirically and theoretically how computer-based decision support influences the acquisition of new knowledge by physicians. PMID:19548513

  15. Natural history and information overload: The case of Linnaeus

    PubMed Central

    Müller-Wille, Staffan; Charmantier, Isabelle

    2012-01-01

    Natural History can be seen as a discipline paradigmatically engaged in ‘data-driven research.’ Historians of early modern science have begun to emphasize its crucial role in the Scientific Revolution, and some observers of present day genomics see it as engaged in a return to natural history practices. A key concept that was developed to understand the dynamics of early modern natural history is that of ‘information overload.’ Taxonomic systems, rules of nomenclature, and technical terminologies were developed in botany and zoology to catch up with the ever increasing amount of information on hitherto unknown plant and animal species. In our contribution, we want to expand on this concept. After all, the same people who complain about information overload are usually the ones who contribute to it most significantly. In order to understand this complex relationship, we will turn to the annotation practices of the Swedish naturalist Carl Linnaeus (1707–1778). The very tools that Linnaeus developed to contain and reduce information overload, as we aim to demonstrate, facilitated a veritable information explosion that led to the emergence of a new research object in botany: the so-called ‘natural’ system. PMID:22326068

  16. Yersiniae and iron. A study in host-parasite relationships.

    PubMed

    Robins-Browne, R M; Prpic, J K; Stuart, S J

    1987-01-01

    Most enterobacteria obtain the iron they require for growth by producing low-molecular-weight high-affinity iron ligands known as siderophores. These substances chelate and solubilize iron making it available to bacteria. The pathogenic Yersiniae produce no detectable siderophores; thus, they proliferate poorly or not at all under conditions of iron limitation. Most systemic infections with Yersinia enterocolitica occur in patients who are overloaded with iron. This may be due to the presence of excess iron in the tissues of such patients, but the adverse effects of excess iron on immune responsiveness may also be partly responsible. Many patients with iron overload receive treatment with desferrioxamine B, a bacterial siderophore which promotes growth of Y. enterocolitica in vitro and in vivo. Thus, desferrioxamine B may add to the risk of systemic yersiniosis developing in patients with siderosis. Some strains of Yersinia frederiksenii, Yersinia intermedia and Yersinia kristensenii produce the hydroxamate siderophore aerobactin, but, paradoxically, they appear to be unable to proliferate in tissues.

  17. Dietary assessment methods: dietary records.

    PubMed

    Ortega, Rosa M; Pérez-Rodrigo, Carmen; López-Sobaler, Ana M

    2015-02-26

    Dietary records or food diaries can be highlighted among dietary assessment methods of the current diet for their interest and validity. It is a prospective, open-ended survey method collecting data about the foods and beverages consumed over a previously specified period of time. Dietary records can be used to estimate current diet of individuals and population groups, as well as to identify groups at risk of inadequacy. It is a dietary assessment method interesting for its use in epidemiological or in clinical studies. High validity and precision has been reported for the method when used following adequate procedures and considering the sufficient number of days. Thus, dietary records are often considered as a reference method in validation studies. Nevertheless, the method is affected by error and has limitations due mainly to the tendency of subjects to report food consumption close to those socially desirable. Additional problems are related to the high burden posed on respondents. The method can also influence food behavior in respondents in order to simplify the registration of food intake and some subjects can experience difficulties in writing down the foods and beverages consumed or in describing the portion sizes. Increasing the number of days observed reduces the quality of completed diet records. It should also be considered the high cost of coding and processing information collected in diet records. One of the main advantages of the method is the registration of the foods and beverages as consumed, thus reducing the problem of food omissions due to memory failure. Weighted food records provide more precise estimates of consumed portions. New Technologies can be helpful to improve and ease collaboration of respondents, as well as precision of the estimates, although it would be desirable to evaluate the advantages and limitations in order to optimize the implementation.

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

    PubMed Central

    Saliba, Antoine N; Harb, Afif R; Taher, Ali T

    2015-01-01

    Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT) and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. PMID:26124688

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

    PubMed

    Saliba, Antoine N; Harb, Afif R; Taher, Ali T

    2015-01-01

    Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT) and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence.

  20. New strategies to target iron metabolism for the treatment of beta thalassemia.

    PubMed

    Oikonomidou, Paraskevi Rea; Casu, Carla; Rivella, Stefano

    2016-03-01

    Iron is one of the most abundant elements in the Earth and a fundamental component of enzymes and other proteins that participate in a wide range of biological processes. As the human body has no mechanisms to eliminate the excess of iron, its metabolism needs to be tightly controlled in order to avoid all the sequelae associated with high iron levels. Iron overload is the main cause of morbidity and mortality in beta thalassemia. The master regulator of iron homeostasis, hepcidin, is chronically repressed in this disorder, leading to increased intestinal iron absorption and consequent iron overload. Many groups have focused on obtaining a better understanding of the pathways involved in iron regulation. New molecules have recently been synthesized and used in animal models of dysregulated iron metabolism, demonstrating their ability to target and reduce iron load. Antisense oligonucleotides, as well as lipid nanoparticle-formulated small interfering RNAs and minihepcidins peptides, are novel agents that have already proved to be efficient in modulating iron metabolism in mouse models and are therefore promising candidates for the treatment of patients affected by iron disorders. PMID:26919168

  1. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice.

    PubMed

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J; Marin, Jose J G; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U; Bucio, Leticia; Montalvo-Jave, Eduardo E; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen; Fernández-Checa, José C; Gomez-Quiroz, Luis Enrique

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. PMID:27635189

  2. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

    PubMed Central

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J.; Marin, Jose J. G.; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U.; Bucio, Leticia; Montalvo-Jave, Eduardo E.; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. PMID:27635189

  3. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

    PubMed Central

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J.; Marin, Jose J. G.; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U.; Bucio, Leticia; Montalvo-Jave, Eduardo E.; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  4. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice.

    PubMed

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J; Marin, Jose J G; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U; Bucio, Leticia; Montalvo-Jave, Eduardo E; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen; Fernández-Checa, José C; Gomez-Quiroz, Luis Enrique

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  5. Iron deficiency.

    PubMed

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  6. The perinatal thyroid in iodine deficient regions: risks of radioiodines--hazards of stable iodine overload. A study in the newborn rat.

    PubMed

    Hindié, E; Walker, F; Petiet, A; Bourahla, K; Galle, P; Colas-Linhart, N

    2001-05-01

    Administration of large quantities of stable iodine is an effective means of reducing the radiation burden on the thyroid in the event of a nuclear power-plant accident. Such administration may involve countries with low baseline dietary iodine intake. It is questioned whether stable iodine overload is safe, and in particular, what are its effects in newborn infants? Iodine-deficient newborn rats were submitted to a single acute administration of stable iodine (100 microg) on the second day of life. The effects on thyroid structure were studied, after 24 hr and after 7 days, using light microscopy. Compared to controls, the thyroids of animals submitted to stable iodine overload showed, 7 days after treatment, signs of acute toxicity including marked desquamation of epithelial cells and rupture of a large number of thyroid follicles. Our findings in iodine deficient newborn rats suggest that stable iodine overload may have side effects during perinatal life. This prophylactic measure should, therefore, be accompanied by follow-up of thyroid function. Thyroid hormones are critical for brain development, during the first period of life. PMID:11441946

  7. Tenellin acts as an iron chelator to prevent iron-generated reactive oxygen species toxicity in the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Jirakkakul, Jiraporn; Cheevadhanarak, Supapon; Punya, Juntira; Chutrakul, Chanikul; Senachak, Jittisak; Buajarern, Taridaporn; Tanticharoen, Morakot; Amnuaykanjanasin, Alongkorn

    2015-01-01

    Iron is an essential element for life. However, the iron overload can be toxic. Here, we investigated the significant increase of tenellin and iron-tenellin complex production in ferricrocin-deficient mutants of Beauveria bassiana. Our chemical analysis indicated that the ferricrocin-deficient mutants T1, T3 and T5 nearly abolished ferricrocin production. In turn, these mutants had significant accumulation of iron-tenellin complex in their mycelia at 247-289 mg g(-1) cell dry weight under iron-replete condition. Both tenellin and iron-tenellin complex were not detected in the wild-type under such condition. Mass analysis of the mutants' crude extracts demonstrated that tenellin formed a 3:1 complex with iron in the absence of ferricrocin. The unexpected link between ferricrocin and tenellin biosynthesis in ferricrocin-deficient mutants could be a survival strategy during iron-mediated oxidative stress. PMID:25670702

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Pulmonary macrophages: Phenomena associated with the particle ``overload`` condition

    SciTech Connect

    Lehnert, B.E.; Sebring, R.J.; Oberdoerster, G.

    1993-05-01

    Numerous lines of evidence support the generalization that alveolar macrophage (AM)-mediated particle clearance, or the transport of particle-containing AM from the alveoli out of the lung via the mucociliary apparatus, is a prominent mechanism that determines the pulmonary retention characteristics of relatively insoluble particles. Studies have also shown that the alveolar deposition of excessive burdens of particles with even low intrinsic cytotoxicity can result in impairments of the AM-mediated panicle clearance mechanism and the development of pathologic disorders including pulmonary fibrosis and lung cancer, at least in the lungs of rats. We briefly review evidence consistent with the idea that the high volumetric loads of particles contained in AM during particle overload conditions underlies their inabilities to translocate from the lung. Using a condition of particle overload brought about by subchronic exposure of rats to ultra-fine titanium dioxide as an experimental model, we have obtained ultrastructural and other evidence that indicates an association between particle overload and: The occurrence of aggregates of particle-containing AM in alveoli, Type II cell hyperplasia in alveoli that contain the AM aggregates, a loss in patent pores of Kohn in alveoli that contain the AM aggregates and show Type II cell hyperplasia, the interstitialization of particles at the sites where these phenomena collectively occur, and the development of fibrosis in alveolar regions where particle interstitialization occurs. The loss of pores of Kohn in the alveoli that contain aggregates of particle-laden AM suggests that these interalveolar pores normally serve as passageways through which AM may migrate to neighboring alveoli as they perform their function of phagocytizing particles that have deposited on the alveolar surface. The pores of Kohn also serve as short-cut pathways for AM to reach the mucociliary apparatus from more distal alveoli.

  10. Pulmonary macrophages: Phenomena associated with the particle overload'' condition

    SciTech Connect

    Lehnert, B.E.; Sebring, R.J. ); Oberdoerster, G. )

    1993-01-01

    Numerous lines of evidence support the generalization that alveolar macrophage (AM)-mediated particle clearance, or the transport of particle-containing AM from the alveoli out of the lung via the mucociliary apparatus, is a prominent mechanism that determines the pulmonary retention characteristics of relatively insoluble particles. Studies have also shown that the alveolar deposition of excessive burdens of particles with even low intrinsic cytotoxicity can result in impairments of the AM-mediated panicle clearance mechanism and the development of pathologic disorders including pulmonary fibrosis and lung cancer, at least in the lungs of rats. We briefly review evidence consistent with the idea that the high volumetric loads of particles contained in AM during particle overload conditions underlies their inabilities to translocate from the lung. Using a condition of particle overload brought about by subchronic exposure of rats to ultra-fine titanium dioxide as an experimental model, we have obtained ultrastructural and other evidence that indicates an association between particle overload and: The occurrence of aggregates of particle-containing AM in alveoli, Type II cell hyperplasia in alveoli that contain the AM aggregates, a loss in patent pores of Kohn in alveoli that contain the AM aggregates and show Type II cell hyperplasia, the interstitialization of particles at the sites where these phenomena collectively occur, and the development of fibrosis in alveolar regions where particle interstitialization occurs. The loss of pores of Kohn in the alveoli that contain aggregates of particle-laden AM suggests that these interalveolar pores normally serve as passageways through which AM may migrate to neighboring alveoli as they perform their function of phagocytizing particles that have deposited on the alveolar surface. The pores of Kohn also serve as short-cut pathways for AM to reach the mucociliary apparatus from more distal alveoli.

  11. Mitochondrial calcium overload is a key determinant in heart failure.

    PubMed

    Santulli, Gaetano; Xie, Wenjun; Reiken, Steven R; Marks, Andrew R

    2015-09-01

    Calcium (Ca2+) released from the sarcoplasmic reticulum (SR) is crucial for excitation-contraction (E-C) coupling. Mitochondria, the major source of energy, in the form of ATP, required for cardiac contractility, are closely interconnected with the SR, and Ca2+ is essential for optimal function of these organelles. However, Ca2+ accumulation can impair mitochondrial function, leading to reduced ATP production and increased release of reactive oxygen species (ROS). Oxidative stress contributes to heart failure (HF), but whether mitochondrial Ca2+ plays a mechanistic role in HF remains unresolved. Here, we show for the first time, to our knowledge, that diastolic SR Ca2+ leak causes mitochondrial Ca2+ overload and dysfunction in a murine model of postmyocardial infarction HF. There are two forms of Ca2+ release channels on cardiac SR: type 2 ryanodine receptors (RyR2s) and type 2 inositol 1,4,5-trisphosphate receptors (IP3R2s). Using murine models harboring RyR2 mutations that either cause or inhibit SR Ca2+ leak, we found that leaky RyR2 channels result in mitochondrial Ca2+ overload, dysmorphology, and malfunction. In contrast, cardiac-specific deletion of IP3R2 had no major effect on mitochondrial fitness in HF. Moreover, genetic enhancement of mitochondrial antioxidant activity improved mitochondrial function and reduced posttranslational modifications of RyR2 macromolecular complex. Our data demonstrate that leaky RyR2, but not IP3R2, channels cause mitochondrial Ca2+ overload and dysfunction in HF. PMID:26217001

  12. Dietary inadequacy in El Salvador.

    PubMed

    Marroquin, C G; Hernandez, M I; Hernandez, B M; Mancia, I Y

    1992-01-01

    Researchers conducted a dietary survey of 59 households selected at random in the marginal community of Peralta in San Salvador, El Salvador to ascertain nutritional needs of the families and identify factors which affect intrafamilial distribution and consumption of food. A nutritionist weighed all the food consumed by each family member in 1 day. 50% of the family members consumed just grain, sugar, oil, and/or beans. 93% of the people ate 90% of the required quantity of vitamin A. 88% ate inadequate amounts of riboflavin, 77% iron, and 40% protein. Moreover 58% of the households spent 61-100% of their income on food. No association occurred between caloric sufficiency and family size and between age and dietary adequacy. Therefore each family evenly distributed food among family members. Further poorer families consumed less food than the families of the higher socioeconomic group.

  13. Inherent overload protection for the series resonant converter

    NASA Technical Reports Server (NTRS)

    King, R. J.; Stuart, T. A.

    1983-01-01

    The overload characteristics of the full bridge series resonant power converter are considered. This includes analyses of the two most common control methods presently in use. The first of these uses a current zero crossing detector to synchronize the control signals and is referred to as the alpha controller. The second is driven by a voltage controlled oscillator and is referred to as the gamma controller. It is shown that the gamma controller has certain reliability advantages in that it can be designed with inherent short circuit protection. Experimental results are included for an 86 kHz converter using power metal-oxide-semiconductor field-effect transistors (MOSFETs).

  14. Noninvasive assessment of skin iron content in hemodialysis patients. An index of parenchymal tissue iron content

    SciTech Connect

    Friedlaender, M.M.; Kaufman, B.; Rubinger, D.; Moreb, J.; Popovtzer, M.M.; Goredetsky, R.

    1988-07-01

    Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was significant positive correlation between individual skin iron determinations with the total number of blood transfusions received, the rate of blood transfusion, and with serum ferritin levels. Bone marrow hemosiderin was examined in six patients and showed a similar trend. Despite correlation only with indirect indices of tissue iron, our findings suggest that DXS may serve as a reliable quick method for noninvasive estimation of nonreticuloendothelial tissue iron deposition in hemodialysis patients suspected of having transfusional iron overload. The method may be valuable in monitoring the effects of chelation therapy.

  15. When enough is not enough: Information overload and metacognitive decisions to stop studying information.

    PubMed

    Murayama, Kou; Blake, Adam B; Kerr, Tyson; Castel, Alan D

    2016-06-01

    People are often exposed to more information than they can actually remember. Despite this frequent form of information overload, little is known about how much information people choose to remember. Using a novel "stop" paradigm, the current research examined whether and how people choose to stop receiving new-possibly overwhelming-information with the intent to maximize memory performance. Participants were presented with a long list of items and were rewarded for the number of correctly remembered words in a following free recall test. Critically, participants in a stop condition were provided with the option to stop the presentation of the remaining words at any time during the list, whereas participants in a control condition were presented with all items. Across 5 experiments, the authors found that participants tended to stop the presentation of the items to maximize the number of recalled items, but this decision ironically led to decreased memory performance relative to the control group. This pattern was consistent even after controlling for possible confounding factors (e.g., task demands). The results indicated a general, false belief that we can remember a larger number of items if we restrict the quantity of learning materials. These findings suggest people have an incomplete understanding of how we remember excessive amounts of information. (PsycINFO Database Record PMID:26595067

  16. Iron Meteorite

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    A meteorite composed mainly of nickel-iron, with traces of other metals; also referred to simply as an iron, and formerly known as a siderite. Irons account for over 6% of all known meteorite specimens. They are the easiest type to identify, being heavy, magnetic and rust-colored; their metallic sheen tarnishes quickly on the Earth's surface, but otherwise irons show better resistance to weatheri...

  17. Mechanisms of plasma non-transferrin bound iron generation: insights from comparing transfused diamond blackfan anaemia with sickle cell and thalassaemia patients.

    PubMed

    Porter, John B; Walter, Patrick B; Neumayr, Lynne D; Evans, Patricia; Bansal, Sukhvinder; Garbowski, Maciej; Weyhmiller, Marcela G; Harmatz, Paul R; Wood, John C; Miller, Jeffery L; Byrnes, Colleen; Weiss, Guenter; Seifert, Markus; Grosse, Regine; Grabowski, Dagmar; Schmidt, Angelica; Fischer, Roland; Nielsen, Peter; Niemeyer, Charlotte; Vichinsky, Elliott

    2014-12-01

    In transfusional iron overload, extra-hepatic iron distribution differs, depending on the underlying condition. Relative mechanisms of plasma non-transferrin bound iron (NTBI) generation may account for these differences. Markers of iron metabolism (plasma NTBI, labile iron, hepcidin, transferrin, monocyte SLC40A1 [ferroportin]), erythropoiesis (growth differentiation factor 15, soluble transferrin receptor) and tissue hypoxia (erythropoietin) were compared in patients with Thalassaemia Major (TM), Sickle Cell Disease and Diamond-Blackfan Anaemia (DBA), with matched transfusion histories. The most striking differences between these conditions were relationships of NTBI to erythropoietic markers, leading us to propose three mechanisms of NTBI generation: iron overload (all), ineffective erythropoiesis (predominantly TM) and low transferrin-iron utilization (DBA).

  18. Information overload in healthcare: too much of a good thing?

    PubMed

    Klerings, Irma; Weinhandl, Alexandra S; Thaler, Kylie J

    2015-01-01

    The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy. PMID:26354128

  19. Information overload in healthcare: too much of a good thing?

    PubMed

    Klerings, Irma; Weinhandl, Alexandra S; Thaler, Kylie J

    2015-01-01

    The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy.

  20. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle.

    PubMed

    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.

  1. Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria.

    PubMed

    Thomas, Mark E; Harris, Kevin P G; Walls, John; Furness, Peter N; Brunskill, Nigel J

    2002-10-01

    The role of the albumin-carried fatty acids in the induction of tubulointerstitial injury was studied in protein-overload proteinuria. Rats were injected with fatty acid-carrying BSA [FA(+)BSA], fatty acid-depleted BSA [FA(-)BSA], or saline. Macrophage infiltration was measured by immunohistochemical staining, apoptotic cells were detec