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Liver iron

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https://www.readbyqxmd.com/read/28231420/serum-ferritin-concentration-predicts-hepatic-fibrosis-better-than-hepatic-iron-concentration-in-human-hfe-hemochromatosis
#1
Marnie J Wood, Darrell H G Crawford, Leesa F Wockner, Lawrie W Powell, Grant A Ramm
BACKGROUND & AIMS: Ferritin is purported to have proinflammatory and profibrogenic effects on hepatic stellate cells. Thus, rather than acting as a passive indicator of hepatic iron concentration (HIC) in hemochromatosis, ferritin may directly influence fibrosis. This study evaluated whether serum ferritin is a better predictor of hepatic fibrosis compared to variables previously associated with increased fibrosis risk in hemochromatosis. METHODS: We identified 291 C282Y HFE-homozygous patients who had undergone liver biopsy for histological fibrosis staging and measurement of HIC...
February 23, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28230720/role-of-vitamin-a-retinoic-acid-in-regulation-of-embryonic-and-adult-hematopoiesis
#2
REVIEW
Ana Cañete, Elena Cano, Ramón Muñoz-Chápuli, Rita Carmona
Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality...
February 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28228829/hepatic-iron-storage-is-related-to-body-adiposity-and-hepatic-inflammation
#3
Chan Yoon Park, Jayong Chung, Kyung-Ok Koo, Min Soo Kim, Sung Nim Han
BACKGROUND: Obesity has been reported to be associated with iron deficiency. However, few studies have investigated iron status in low adiposity. To investigate whether body adiposity was associated with altered hepatic iron status, we compared liver iron levels and markers involved in inflammation and iron absorption in obese, control, and mildly calorie restricted mice. METHODS: Seven week old C57BL/6 mice were fed control (10% kcal fat, Control) or high fat (60% kcal fat, HFD) diets, or reduced amount of control diet to achieve 15% calorie restriction (CR) for 16 weeks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28225576/3d-multiecho-dixon-for-the-evaluation-of-hepatic-iron-and-fat-in-a-clinical-setting
#4
Benjamin Henninger, Heinz Zoller, Stephan Kannengiesser, Xiaodong Zhong, Werner Jaschke, Christian Kremser
PURPOSE: To prospectively evaluate a new 3D-multiecho-Dixon (3D-ME-Dixon) sequence for the quantification of hepatic iron and fat in a clinical setting. MATERIALS AND METHODS: In all, 120 patients underwent 1.5T magnetic resonance imaging of the liver between December 2013 and June 2015 including the following three sequences: 3D-ME-Dixon with inline calculation of R2* and proton-density fat-fraction (PDFF) maps, single-voxel-spectroscopy (SVS), 2D multigradient-echo sequence (2D-ME-GRE)...
February 22, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28224171/assessment-of-liver-iron-overload-by-3%C3%A2-t-mri
#5
A Paisant, A Boulic, E Bardou-Jacquet, E Bannier, G d'Assignies, F Lainé, B Turlin, Y Gandon
PURPOSE: To evaluate the performance and limitations of the signal intensity ratio method for quantifying liver iron overload at 3 T. METHODS: Institutional review board approval and written informed consent from all participants were obtained. One hundred and five patients were included prospectively. All patients underwent a liver biopsy with biochemical assessment of hepatic iron concentration and a 3 T MRI scan with 5 breath-hold single-echo gradient-echo sequences...
February 21, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28221264/efficacy-and-safety-of-combined-oral-chelation-with-deferiprone-and-deferasirox-in-children-with-%C3%AE-thalassemia-major-an-experience-from-north-india
#6
Nupur Parakh, Jagdish Chandra, Sunita Sharma, Bhavna Dhingra, Rajesh Jain, DeoNath Mahto
OBJECTIVE: A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. METHODS: A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years...
February 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28219768/copper-therapy-reduces-intravascular-hemolysis-and-derepresses-ferroportin-in-mice-with-mosaic-mutation-atp7a-mo-ms-an-implication-for-copper-mediated-regulation-of-the-slc40a1-gene-expression
#7
Małgorzata Lenartowicz, Rafał R Starzyński, Aneta Jończy, Robert Staroń, Justyna Antoniuk, Wojciech Krzeptowski, Paweł Grzmil, Aleksandra Bednarz, Olga Pierzchała, Mateusz Ogórek, Zenon Rajfur, Zbigniew Baster, Paweł Lipiński
Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28219045/modulating-the-selectivity-of-matriptase-2-inhibitors-with-unnatural-amino-acids
#8
Catherine St-Georges, Antoine Désilets, François Béliveau, Mariana Ghinet, Sébastien P Dion, Éloic Colombo, Pierre-Luc Boudreault, Rafael J Najmanovich, Richard Leduc, Éric Marsault
Matriptase-2, a type II transmembrane serine protease (TTSP), is expressed in the liver and regulates iron homeostasis via the cleavage of hemojuvelin. Matriptase-2 emerges as an attractive target for the treatment of conditions associated with iron overload, such as hemochromatosis or beta-thalassemia. Starting from the crystal structure of its closest homolog matriptase, we constructed a homology model of matriptase-2 in order to further optimize the selectivity of serine trap peptidomimetic inhibitors for matriptase-2 vs matriptase...
February 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28218005/evaluation-of-cardiac-and-hepatic-iron-overload-in-thalassemia-major-patients-with-t2-magnetic-resonance-imaging
#9
Pustika Amalia Wahidiyat, Felix Liauw, Damayanti Sekarsari, Siti Ayu Putriasih, Vasili Berdoukas, Dudley J Pennell
OBJECTIVES: Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy. METHODS: This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy...
February 20, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28216891/effects-of-potassium-sulfate-k2so4-on-the-element-contents-polyphenol-content-antioxidant-and-antimicrobial-activities-of-milk-thistle-silybum-marianum
#10
Gulsum Yaldiz
BACKGROUND: Silybum marianum L. (Milk thistle) is native to the Mediterranean basin and is now widespread throughout the world. It's sprout is used as a herbal medicine for the treatment of liver disease for centuries. The seeds of milk thistle contain silymarin, an isomeric mixture of flavonolignans [silybin, silychristin, and silydianin]. Silymarin acts as a strong anti-hepatotoxic. OBJECTIVES: The objective of this study was to evaluate the influences of potassium sulfate [K2SO4] fertilizer doses on polyphenol content, some nutrient elements, antioxidant and antimicrobial activities of milk thistle at experimental fields of Ordu University in Turkey...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28214127/functionalized-superparamagnetic-iron-oxide-nanoparticles-provide-highly-efficient-iron-labeling-in-macrophages-for-magnetic-resonance-based-detection-in-vivo
#11
Jack Sharkey, Philip J Starkey Lewis, Michael Barrow, Salamah M Alwahsh, June Noble, Eilidh Livingstone, Ross J Lennen, Maurits A Jansen, Jaime Garcia Carrion, Neill Liptrott, Shareen Forbes, Dave J Adams, Amy E Chadwick, Stuart J Forbes, Patricia Murray, Matthew J Rosseinsky, Christopher E Goldring, B Kevin Park
BACKGROUND AIMS: Tracking cells during regenerative cytotherapy is crucial for monitoring their safety and efficacy. Macrophages are an emerging cell-based regenerative therapy for liver disease and can be readily labeled for medical imaging. A reliable, clinically applicable cell-tracking agent would be a powerful tool to study cell biodistribution. METHODS: Using a recently described chemical design, we set out to functionalize, optimize and characterize a new set of superparamagnetic iron oxide nanoparticles (SPIONs) to efficiently label macrophages for magnetic resonance imaging-based cell tracking in vivo...
February 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28213093/enhanced-effect-of-geldanamycin-nanocomposite-against-breast-cancer-cells-growing-in-vitro-and-as-xenograft-with-vanquished-normal-cell-toxicity
#12
Suma Prabhu, Preeta Ananthanarayanan, Kannangar Aziz Sajida, Sharada Rai, Srinivas Mutalik, Satish Rao Bola Sadashiva
Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28211259/liver-transplantation-from-a-deceased-donor-with-%C3%AE-thalassemia-intermedia-is-not-contraindicated-a-case-report
#13
Ersin Gumus, Osman Abbasoglu, Cahit Tanyel, Fatma Gumruk, Hasan Ozen, Aysel Yuce
The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with β-thalassemia intermedia. A patient, 6-year-old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver...
February 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28204974/lipid-peroxidation-dependent-cell-death-regulated-by-gpx4-and-ferroptosis
#14
Hirotaka Imai, Masaki Matsuoka, Takeshi Kumagai, Taro Sakamoto, Tomoko Koumura
Glutathione peroxidase 4 (Phospholipid hydroperoxide glutathione peroxidase, PHGPx) can directly reduce phospholipid hydroperoxide. Depletion of GPx4 induces lipid peroxidation-dependent cell death in embryo, testis, brain, liver, heart, and photoreceptor cells of mice. Administration of vitamin E in tissue specific GPx4 KO mice restored tissue damage in testis, liver, and heart. These results indicate that suppression of phospholipid peroxidation is essential for cell survival in normal tissues in mice. Ferroptosis is an iron-dependent non-apoptotic cell death that can elicited by pharmacological inhibiting the cystine/glutamate antiporter, system Xc(-) (type I) or directly binding and loss of activity of GPx4 (Type II) in cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression, but not in normal cells...
February 16, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28203549/microbiological-and-clinical-characteristics-of-hypermucoviscous-klebsiella-pneumoniae-isolates-associated-with-invasive-infections-in-china
#15
Yinjuan Guo, Shanshan Wang, Lingling Zhan, Ye Jin, Jingjing Duan, Zhihao Hao, Jingnan Lv, Xiuqin Qi, Liang Chen, Barry N Kreiswirth, Liangxing Wang, Fangyou Yu
A distinctive syndrome caused by hypermucoviscous Klebsiella pneumoniae (HMKP) including pyogenic liver abscess (PLA) is now becoming a globally emerging disease. In the present study, 22.8% (84/369) of K. pneumoniae clinical isolates associated with various types of invasive infections were identified as HMKP, with 45.2% associated with PLA. Multivariate regression analysis showed that male patients with 41-50 years, PLA, diabetes mellitus, and hypertension were independent risk factors for HMKP infections...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28203489/effects-of-anti-repulsive-guidance-molecule-c-rgmc-hemojuvelin-antibody-on-hepcidin-and-iron-in-mouse-liver-and-tumor-xenografts
#16
S V Torti, E Lemler, B K Mueller, A Popp, F M Torti
OBJECTIVE: Hepcidin is a peptide hormone produced by the liver that regulates systemic iron homeostasis. Hepcidin is also synthesized by tumors, where it contributes to tumor growth by increasing the tumoral retention of iron. Targeted reduction of hepcidin may therefore be useful in reducing tumor growth. H5F9-AM8 is an antibody in preclinical development for the anemia of chronic disease that reduces hepcidin synthesis by binding to RGMc, a co-receptor involved in the transcriptional induction of hepcidin by BMP6...
November 2016: Clinical & Experimental Pharmacology
https://www.readbyqxmd.com/read/28202542/m%C3%A3-ssbauer-spectra-of-mouse-hearts-reveal-age-dependent-changes-in-mitochondrial-and-ferritin-iron-levels
#17
Joshua D Wofford, Mrinmoy Chakrabarti, Paul Alan Lindahl
Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from (57)Fe-enriched mice were evaluated by Mossbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood while the other was due to [Fe4S4](2+) clusters and Fe(II) hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28198362/covalent-assembly-of-nanoparticles-as-a-peptidase-degradable-platform-for-molecular-mri
#18
Francisco Perez-Balderas, Sander I van Kasteren, Alaa A A Aljabali, Kim Wals, Sébastien Serres, Andrew Jefferson, Manuel Sarmiento Soto, Alexandre A Khrapitchev, James R Larkin, Claire Bristow, Seung Seo Lee, Guillaume Bort, Filippo De Simone, Sandra J Campbell, Robin P Choudhury, Daniel C Anthony, Nicola R Sibson, Benjamin G Davis
Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers that are designed to be cleaved by intracellular macrophage proteases...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28197411/toxicity-studies-of-ethyl-maltol-and-iron-complexes-in-mice
#19
Zhen Li, Jieli Lu, Chonghui Wu, Quanhai Pang, Zhiwei Zhu, Ruipeng Nan, Ruochen Du, Jia Chen
Ethyl maltol and iron complexes are products of ethyl maltol and the iron found in the cooking pots used to prepare the Chinese dish, hot-pot. Because their safety is undocumented, the toxicity study of ethyl maltol and iron complexes was conducted in male and female Kunming (KM) mice. The animal study was designed based on the preliminary study conducted to determine the median lethal dose (LD50). The doses used in the study were 0, 1/81, 1/27, 1/9, and 1/3 of the LD50 (mg kg body weight (BW)(-1) day(-1)) dissolved in the water...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28195347/characterization-of-ferroptosis-in-murine-models-of-hemochromatosis
#20
Hao Wang, Peng An, Enjun Xie, Qian Wu, Xuexian Fang, Hong Gao, Zhuzhen Zhang, Yuzhu Li, Xudong Wang, Jiaying Zhang, Guoli Li, Lei Yang, Wei Liu, Junxia Min, Fudi Wang
Ferroptosis is a recently identified iron-dependent form of non-apoptotic cell death implicated in brain, kidney, and heart pathology. However, the biological roles of iron and iron metabolism in ferroptosis remain poorly understood. Here, we studied the functional role of iron and iron metabolism in the pathogenesis of ferroptosis. We found that ferric citrate potently induces ferroptosis in murine primary hepatocytes and bone marrow-derived macrophages (BMDMs). Next, we screened for ferroptosis in mice fed a high-iron diet and in mouse models of hereditary hemochromatosis with iron overload...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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