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Iron overload

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https://www.readbyqxmd.com/read/28335084/identification-of-new-bmp6-pro-peptide-mutations-in-patients-with-iron-overload
#1
Chiara Piubelli, Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Sadaf Badar, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Eda Suku, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least 5 different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28334935/genome-wide-association-study-of-iron-traits-and-relation-to-diabetes-in-the-hispanic-community-health-study-study-of-latinos-hchs-sol-potential-genomic-intersection-of-iron-and-glucose-regulation
#2
Laura M Raffield, Tin Louie, Tamar Sofer, Deepti Jain, Eli Ipp, Kent D Taylor, George J Papanicolaou, Larissa Avilés-Santa, Leslie A Lange, Cathy C Laurie, Matthew P Conomos, Timothy A Thornton, Yii-Der Ida Chen, Qibin Qi, Scott Cotler, Bharat Thyagarajan, Neil Schneiderman, Jerome I Rotter, Alex P Reiner, Henry J Lin
Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study (GWAS) of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; >12,000 participants) and also assessed the generalization of previously known loci to this population...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334149/higher-striatal-iron-concentration-is-linked-to-frontostriatal-underactivation-and-poorer-memory-in-normal-aging
#3
Grégoria Kalpouzos, Benjamín Garzón, Rouslan Sitnikov, Carmel Heiland, Alireza Salami, Jonas Persson, Lars Bäckman
In the brain, intracellular iron is essential for cellular metabolism. However, an overload of free iron is toxic, inducing oxidative stress and cell death. Although an increase of striatal iron has been related to atrophy and impaired cognitive performance, the link between elevated iron and altered brain activity in aging remains unexplored. In a sample of 37 younger and older adults, we examined whether higher striatal iron concentration could underlie age-related differences in frontostriatal activity induced by mental imagery of motor and non-motor scenes, and poorer recall of the scenes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28332306/impact-of-iatrogenic-iron-overload-on-the-course-of-hepatitis-c-in-dialysis-population-a-plea-for-caution
#4
Guy Rostoker, Nosratola D Vaziri
About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population...
March 23, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28331855/diabetes-in-hfe-hemochromatosis
#5
REVIEW
James C Barton, Ronald T Acton
Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28328144/diagnosing-and-preventing-iron-overload
#6
Ganesh Ramanathan, John K Olynyk, Paolo Ferrari
Absolute or functional iron (Fe) deficiency is an important determinant of anemia in hemodialysis patients and parenteral Fe is routinely used to treat this condition in conjunction with erythropoiesis stimulating agents. While restoration of hemoglobin toward the target range is a good outcome of Fe replacement, it is well known that Fe overload and toxicity may be adverse consequences of this therapy. Dialysis clinical practice guidelines recommend tailoring Fe therapy based on transferrin saturation and serum ferritin levels...
March 22, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28320343/targets-for-adapting-intravenous-iron-dose-in-hemodialysis-a-proof-of-concept-study
#7
N O Peters, N Jay, J Cridlig, G Rostoker, L Frimat
BACKGROUND: Intravenous iron is widely used to control anemia in dialysis patients and limits costs related to erythropoiesis-stimulating agents (ESA). Current guidelines do not clearly set upper limits for serum ferritin (SF) and transferrin saturation (TSAT). International surveys such as the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed that this lack of upper limits potentially led nephrologists to prescribe iron infusions even for patients with a high SF. Recent publications have suggested a risk of short- and long-term adverse effects related to iron overload...
March 20, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28320102/evaluation-of-iron-chelating-and-antioxidant-potential-of-epilobium-hirsutum-for-the-management-of-iron-overload-disease
#8
N A Sheikh, T R Desai, P R Tirgar
The present study deals with the investigation of iron chelating and antioxidant potential of Epilobium hirsutum in iron-overloaded rats. Iron overload was induced by 6 IP injections of Iron dextran (12.5mg/100g) administered uniformly over a period of 30 days. Different fractions of E. hirsutum were given orally and deferoxamine (DFO) subcutaneously for 30 days. The extent of iron chelation and various biochemical parameters were estimated on 15th and 30th day of treatment. In-vitro study was assessed by EDTA and DFO method; the results exhibited a dose-dependant iron chelation...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320041/prevention-of-iron-overload-and-long-term-maintenance-of-normal-iron-stores-in-thalassaemia-major-patients-using-deferiprone-or-deferiprone-deferoxamine-combination
#9
Annita Kolnagou, Christina N Kontoghiorghe, George J Kontoghiorghes
Decrease in mortality and morbidity is observed in thalassaemia major patients with reduced iron load in comparison to heavy iron loaded patients. Effective and complete treatment of transfusional iron overload can be achieved by chelation protocols that can eliminate excess iron and maintain normal iron stores (NIS). The maintenance of NIS, i. e., serum ferritin (350 μg/L >), MRI T2* cardiac (>20 ms) and liver (>6.3 ms) relaxation time levels was monitored in 16 thalassaemia major patients (32-53 years, 12 splenectomized, 10 male, erythrocyte transfusions 120-323 ml/kg/year) for about 90 patient years...
March 20, 2017: Drug Research
https://www.readbyqxmd.com/read/28317795/iron-overload-in-hematopoietic-stem-cell-transplantation
#10
Sora Yasri, Viroj Wiwanitkit
No abstract text is available yet for this article.
March 1, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28316434/comparison-of-deferasirox-and-deferoxamine-effects-on-iron-overload-and-immunological-changes-in-patients-with-blood-transfusion-dependent-%C3%AE-thalassemia
#11
Hayder M Al-Kuraishy, Ali I Al-Gareeb
INTRODUCTION: Beta-thalassemias are a cluster of inherited (autosomal recessive) hematological disorders prevalent in the Mediterranean area due to defects in synthesis of β chains of hemoglobin. The aim of present study was to compare the effects of deferasirox and deferoxamine on iron overload and immunological changes in patients with blood transfusion-dependent β-thalassemia major and intermedia. PATIENTS AND METHODS: This study involved 64 patients with known cases of β-thalassemia major or intermedia that has been treated with blood transfusion and iron chelators...
January 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28303071/the-regulation-of-iron-absorption-and-homeostasis
#12
REVIEW
Daniel F Wallace
Iron is an essential element in biology, required for numerous cellular processes. Either too much or too little iron can be detrimental, and organisms have developed mechanisms for balancing iron within safe limits. In mammals there are no controlled mechanisms for the excretion of excess iron, hence body iron homeostasis is regulated at the sites of absorption, utilisation and recycling. This review will discuss the discoveries that have been made in the past 20 years into advancing our understanding of iron homeostasis and its regulation...
May 2016: Clinical Biochemist. Reviews
https://www.readbyqxmd.com/read/28301910/soluble-fms-like-tyrosine-kinase-1-as-a-link-between-angiogenesis-and-endothelial-dysfunction-in-pediatric-patients-with-%C3%AE-thalassemia-intermedia
#13
Azza Abdel Gawad Tantawy, Amira Abdel Moneam Adly, Eman Abdel Rahman Ismail, Omneya Ibrahim Youssef, Mohamed ElSayed Ali
Endothelial damage has been implicated in the pathogenesis of vascular complications in β-thalassemia intermedia (β-TI). Soluble fms-like tyrosine kinase 1 (sFLT-1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. Soluble fms-like tyrosine kinase 1 is an antiangiogenic protein that induces endothelial dysfunction by adhering to and inhibiting VEGF and placenta growth factor. The aim of this study was to assess the level of sFLT-1 in 35 children and adolescents with β-TI, correlating it with markers of hemolysis and iron overload as well as cardiopulmonary complications...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28300826/astrocyte-hepcidin-is-a-key-factor-in-lps-induced-neuronal-apoptosis
#14
Lin-Hao You, Cai-Zhen Yan, Bing-Jie Zheng, Yun-Zhe Ci, Shi-Yang Chang, Peng Yu, Guo-Fen Gao, Hai-Yan Li, Tian-Yu Dong, Yan-Zhong Chang
Inflammatory responses involving microglia and astrocytes contribute to the pathogenesis of neurodegenerative diseases (NDs). In addition, inflammation is tightly linked to iron metabolism dysregulation. However, it is not clear whether the brain inflammation-induced iron metabolism dysregulation contributes to the NDs pathogenesis. Herein, we demonstrate that the expression of the systemic iron regulatory hormone, hepcidin, is induced by lipopolysaccharide (LPS) through the IL-6/STAT3 pathway in the cortex and hippocampus...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28296163/long-term-safety-and-efficacy-of-deferasirox-in-young-pediatric-patients-with-transfusional-hemosiderosis-results-from-a-5-year-observational-study-entrust
#15
Elliott Vichinsky, Amal El-Beshlawy, Azzam Al Zoebie, Annie Kamdem, Suzanne Koussa, Thirachit Chotsampancharoen, Andreas Bruederle, Geralyn Gilotti, Jackie Han, Mohsen Elalfy
BACKGROUND: Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years. PROCEDURE: Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28295188/how-we-manage-iron-overload-in-sickle-cell-patients
#16
REVIEW
Thomas D Coates, John C Wood
Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28293409/myelodysplastic-syndromes-and-iron-chelation-therapy
#17
REVIEW
Emanuele Angelucci, Silvana Anna Maria Urru, Federica Pilo, Alberto Piperno
Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We're therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28292647/transfusion-transmitted-infections-in-frequently-transfused-thalassemic-children-living-in-fayoum-governorate-egypt-current-prevalence-and-risk-factors
#18
Zeze Th Atwa, Wafaa Y Abdel Wahed
Regular blood transfusion therapy remains the primary treatment in thalassemia major (TM). Transfusion-transmitted infections (TTIs) and iron overload are considered to be the major drawbacks of this therapy. This cross-sectional study aimed to update the prevalence of the hepatitis C virus (HCV) antibody, PCR-confirmed HCV, hepatitis B surface antigen (HBsAg), and human immunodeficiency virus (HIV) antibody among TM children. Clinical and epidemiological factors that can affect HCV infection prevalence rate were studied...
March 11, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28287621/restoring-the-impaired-cardiac-calcium-homeostasis-and-cardiac-function-in-iron-overload-rats-by-the-combined-deferiprone-and-n-acetyl-cysteine
#19
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Siriporn C Chattipakorn, Nipon Chattipakorn
Intracellular calcium [Ca(2+)]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28280078/pathophysiological-consequences-and-benefits-of-hfe-mutations-20-years-of-research
#20
Ina Hollerer, André Bachmann, Martina U Muckenthaler
Mutations in the HFE (hemochromatosis) gene cause hereditary hemochromatosis, an iron overload disorder that is hallmarked by excessive accumulation of iron in parenchymal organs. The HFE mutation p.Cys282Tyr is pathologically most relevant and occurs in the Caucasian population with a carrier frequency of up to 1 in 8 in specific European regions. Despite this high prevalence, the mutation causes a clinically relevant phenotype only in a minority of cases. In this review, we summarize historical facts and recent research findings about hereditary hemochromatosis and outline the pathological consequences of the associated gene defects...
March 9, 2017: Haematologica
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