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https://www.readbyqxmd.com/read/27917462/iron-overload-across-the-spectrum-of-non-transfusion-dependent-thalassaemias-role-of-erythropoiesis-splenectomy-and-transfusions
#1
John B Porter, Maria Domenica Cappellini, Antonis Kattamis, Vip Viprakasit, Khaled M Musallam, Zewen Zhu, Ali T Taher
Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups...
December 5, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27915113/white-blood-cells-and-subtypes-in-hfe-p-c282y-and-wild-type-homozygotes-in-the-hemochromatosis-and-iron-overload-screening-study
#2
James C Barton, J Clayborn Barton, Ronald T Acton
The major histocompatibility complex is linked to white blood cell (WBC) and lymphocyte counts in subjects unselected for HFE genotypes. We compared age, sex, body mass index, total WBC and subtypes (neutrophils, lymphocytes, monocytes, eosinophils, basophils) (Beckman Coulter® Gen-S), transferrin saturation, and serum ferritin of HFE p.C282Y and wild-type (p.C282Y, p.H63D negative) homozygotes without acquired conditions that influence WBC counts. We performed regressions on WBC and subtypes. There were 161 p...
November 12, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27911488/hepatocellular-carcinoma-as-an-emerging-morbidity-in-the-thalassemia-syndromes-a-comprehensive-review
#3
REVIEW
Hassan M Moukhadder, Racha Halawi, Maria Domenica Cappellini, Ali T Taher
The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27905193/high-pretransplant-hepcidin-levels-are-associated-with-poor-overall-survival-and-delayed-platelet-engraftment-after-allogeneic-hematopoietic-stem-cell-transplantation
#4
Soichiro Sakamoto, Hiroshi Kawabata, Junya Kanda, Tatsuki Uchiyama, Chisaki Mizumoto, Toshiyuki Kitano, Tadakazu Kondo, Masakatsu Hishizawa, Naohisa Tomosugi, Akifumi Takaori-Kondo
Iron overload is considered a risk factor for mortality in patients with hematopoietic malignancies. Hepcidin is a key regulator of systemic iron balance. We previously reported dynamic changes of serum hepcidin-25 levels in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we retrospectively analyzed the association of pretransplant hepcidin-25 levels with overall survival (OS), engraftment, and other clinical outcomes of allo-HSCT in patients with hematologic malignancies...
December 1, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27903581/the-plasma-membrane-metal-ion-transporter-zip14-contributes-to-non-transferrin-bound-iron-uptake-by-human-%C3%AE-cells
#5
Richard Coffey, Mitchell D Knutson
The relationship between iron and β cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZIP14, ZIP8, and DMT1 to iron uptake by human β cells...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903529/angiocrine-bmp2-signaling-in-murine-liver-controls-normal-iron-homeostasis
#6
Philipp-Sebastian Koch, Victor Olsavszky, Friederike Ulbrich, Carsten Sticht, Alexandra Demory, Thomas Leibing, Thomas Henzler, Mathias Meyer, Johanna Zierow, Sven Schneider, Katja Breitkopf-Heinlein, Haristi Gaitantzi, Bradley Spencer-Dene, Bernd Arnold, Kay Klapproth, Kai Schledzewski, Sergij Goerdt, Cyrill Géraud
Microvascular endothelial cells (EC) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific EC control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal EC (LSEC) are uniquely differentiated to fulfil important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSEC. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSEC using EC subtype-specific Stab2-Cre mice...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27900772/hematopoietic-stem-cell-transplantation-for-people-with-%C3%A3-thalassaemia-major
#7
REVIEW
Vanitha A Jagannath, Zbys Fedorowicz, Amani Al Hajeri, Akshay Sharma
BACKGROUND: Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis...
November 30, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27897970/an-essential-cell-autonomous-role-for-hepcidin-in-cardiac-iron-homeostasis
#8
Samira Lakhal-Littleton, Magda Wolna, Yu Jin Chung, Helen C Christian, Lisa C Heather, Marcella Brescia, Vicky Ball, Rebeca Diaz, Ana Santos, Daniel Biggs, Kieran Clarke, Benjamin Davies, Peter A Robbins
Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27896572/identification-of-novel-mutations-in-hfe-hfe2-tfr2-and-slc40a1-genes-in-chinese-patients-affected-by-hereditary-hemochromatosis
#9
Yongwei Wang, Yali Du, Gang Liu, Shanshan Guo, Bo Hou, Xianyong Jiang, Bing Han, Yanzhong Chang, Guangjun Nie
Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups...
November 28, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27893351/management-of-iron-overload-in-myelodysplastic-syndromes-combined-deferasirox-and-deferoxamine-in-a-patient-with-liver-disease
#10
Claudio Cerchione, Giuseppe Cerciello, Simona Avilia, Roberta Della Pepa, Novella Pugliese, Marco Picardi, Lucio Catalano, Fabrizio Pane
No abstract text is available yet for this article.
October 24, 2016: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/27892944/veno-occlusive-disease-sinusoidal-obstruction-syndrome-after-haematopoietic-stem-cell-transplantation-middle-east-north-africa-regional-consensus-on-prevention-diagnosis-and-management
#11
A H Al Jefri, H Abujazar, A Al-Ahmari, A Al Rawas, Z Al Zahrani, A Alhejazi, M A Bekadja, A Ibrahim, M Lahoucine, S Ousia, A Bazarbachi
Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) of the liver is a serious, early complication of haematopoietic stem cell transplantation (HSCT), severe and very severe forms of which are associated with a high mortality rate. A wide variety of patient, disease and treatment-related risk factors for VOD/SOS have been identified. Several bodies have published recommendations for the diagnosis, prevention and management of VOD/SOS following HSCT. A group of regional experts have developed a consensus statement on the diagnosis, prevention and management of VOD/SOS in the Middle East and North Africa region to help in the management of HSCT patients in the region...
November 28, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27890361/iron-dysregulation-in-beta-thalassemia
#12
REVIEW
Kamonlak Leecharoenkiat, Pathrapol Lithanatudom, Wannapa Sornjai, Duncan R Smith
Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis. Ferroportin is the sole cellular iron export protein, and its expression is regulated transcriptionally, post-transcriptionally and post-translationally. Hepcidin, a hormone produced by liver cells, post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes...
November 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27881236/deferasirox-pharmacokinetics-evaluation-in-a-woman-with-hereditary-haemochromatosis-and-heterozygous-%C3%AE-thalassaemia
#13
Sarah Allegra, Silvia De Francia, Filomena Longo, Davide Massano, Jessica Cusato, Arianna Arduino, Elisa Pirro, Antonio Piga, Antonio D'Avolio
We present the deferasirox pharmacokinetics evaluation of a female patient on iron chelation, for the interesting findings from her genetic background (hereditary haemochromatosis and heterozygous β-thalassaemia) and clinical history (ileostomy; iron overload from transfusions). Drug plasma concentrations were measured by an HPLC-UV validated method, before and after ileum resection. Area under deferasirox concentration curve over 24h (AUC) values were determined by the mixed log-linear rule, using Kinetica software...
November 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27872738/the-icet-a-recommendations-for-the-diagnosis-and-management-of-disturbances-of-glucose-homeostasis-in-thalassemia-major-patients
#14
Vincenzo De Sanctis, Ashraf T Soliman, Heba Elsedfy, Saif Al Yaarubi, Nicos Skordis, Doaa Khater, Mohamed El Kholy, Iva Stoeva, Bernadette Fiscina, Michael Angastiniotis, Shahina Daar, Christos Kattamis
Iron overload in patients with thalassemia major (TM) affects glucose regulation and is mediated by several mechanisms. The pathogenesis of glycaemic abnormalities in TM is complex and multifactorial. It has been predominantly attributed to a combination of reduced insulin secretory capacity and insulin resistance. The exact mechanisms responsible for progression from norm glycaemia to overt diabetes in these patients are still poorly understood but are attributed mainly to insulin deficiency resulting from the toxic effects of iron deposited in the pancreas and insulin resistance...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27864463/increased-brain-hemopexin-levels-improve-outcomes-after-intracerebral-hemorrhage
#15
Jenna L Leclerc, Juan Santiago-Moreno, Alex Dang, Andrew S Lampert, Pedro E Cruz, Awilda M Rosario, Todd E Golde, Sylvain Doré
Following intracerebral hemorrhage (ICH), extracellular heme precipitates secondary brain injury, which results in irreversible brain damage and enduring neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory properties. Although Hpx is present in the brain, the endogenous levels are insufficient to combat the massive heme overload following ICH. We hypothesized that increasing brain Hpx levels would improve ICH outcomes...
November 18, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27859814/black-rhinoceros-diceros-bicornis-and-domestic-horse-equus-caballus-hindgut-microflora-demonstrate-similar-fermentation-responses-to-grape-seed-extract-supplementation-in%C3%A2-vitro
#16
N F Huntley, H D Naumann, A L Kenny, M S Kerley
The domestic horse is used as a nutritional model for rhinoceros maintained under human care. The validity of this model for browsing rhinoceros has been questioned due to high prevalence of iron overload disorder (IOD) in captive black rhinoceros (Diceros bicornis), which is associated with high morbidity and mortality. Iron chelators, such as tannins, are under investigation as dietary supplements to ameliorate or prevent IOD in prone species. Polyphenolic compounds variably affect microbial fermentation, so the first objective of this experiment was to evaluate the effects of grape seed extract (GSE; a concentrated source of condensed tannins; CT) on black rhinoceros hindgut fermentation...
November 13, 2016: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/27853903/does-any-drug-to-treat-cancer-target-mtor-and-iron-hemostasis-in-neurodegenerative-disorders
#17
REVIEW
Mohammad Jodeiri Farshbaf, Kamran Ghaedi
The prevalence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease are increased by age. Alleviation of their symptoms and protection of normal neurons against degeneration are the main aspects of the research to establish novel therapeutic strategies. Iron as the one of most important cation not only play important role in the structure of electron transport chain proteins but also has pivotal duties in cellular activities. But disruption in iron hemostasis can make it toxin to neurons which causes lipid peroxidation, DNA damage and etc...
November 16, 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/27848180/iron-overload-patients-with-unknown-etiology-from-national-survey-in-japan
#18
Katsuya Ikuta, Mayumi Hatayama, Lynda Addo, Yasumichi Toki, Katsunori Sasaki, Yasuaki Tatsumi, Ai Hattori, Ayako Kato, Koichi Kato, Hisao Hayashi, Takahiro Suzuki, Masayoshi Kobune, Miyuki Tsutsui, Akihiko Gotoh, Yasuo Aota, Motoo Matsuura, Yuzuru Hamada, Takahiro Tokuda, Norio Komatsu, Yutaka Kohgo
Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27843752/thalassemia-major-how-do-we-improve-quality-of-life
#19
Nonita Dhirar, Jyoti Khandekar, Damodar Bachani, Deonath Mahto
BACKGROUND: Thalassemia Major is a preventable genetic disorder characterized by abnormal hemoglobin synthesis and lifelong blood transfusions. The children suffering from Thalassemia Major have poor quality of life. This study was conducted to assess the factors influencing quality of life of these children and how it can be improved. METHODS: A descriptive cross sectional study was conducted in 2014 at Thalassemia Day Care Centre of a tertiary level children's hospital in Delhi, to assess quality of life of children suffering from Thalassemia Major...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27843711/iron-overload-induced-death-of-osteoblasts-in-vitro-involvement-of-the-mitochondrial-apoptotic-pathway
#20
Qing Tian, Shilei Wu, Zhipeng Dai, Jingjing Yang, Jin Zheng, Qixin Zheng, Yong Liu
BACKGROUND: Iron overload is recognized as a new pathogenfor osteoporosis. Various studies demonstrated that iron overload could induce apoptosis in osteoblasts and osteoporosis in vivo. However, the exact molecular mechanisms involved in the iron overload-mediated induction of apoptosis in osteoblasts has not been explored. PURPOSE: In this study, we attempted to determine whether the mitochondrial apoptotic pathway is involved in iron-induced osteoblastic cell death and to investigate the beneficial effect of N-acetyl-cysteine (NAC) in iron-induced cytotoxicity...
2016: PeerJ
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