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https://www.readbyqxmd.com/read/28732253/diminished-ovarian-reserve-in-women-with-transfusion-dependent-beta-thalassemia-major-is-iron-gonadotoxic
#1
Aysel Uysal, Gül Alkan, Ayşegül Kurtoğlu, Onur Erol, Erdal Kurtoğlu
OBJECTIVE: Iron accumulation in the endocrine glands has been implicated in the aetiopathogenesis of decreased reproductive capacity in patients with beta-thalassemia major (β-TM). The aim of the current study was to investigate the serum concentration of anti-Müllerian hormone (AMH), a marker of ovarian reserve, in women with transfusion-dependent β-TM. STUDY DESIGN: In this case-control study, we recruited 43 women with transfusion-dependent TM and 44 age-matched healthy controls...
July 5, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28731917/the-impact-of-iron-overload-in-acute-leukemia-chronic-inflammation-but-not-the-presence-of-nontransferrin-bound-iron-is-a-determinant-of-oxidative-stress
#2
Lale Olcay, Mustafa Serteser, Murat Kolay, Havva F Balci, Ülkü M Yildirim, Sibel A Tekgündüz, Tuncay Hazirolan, Yunus K Terzi
In the literature, studies on the oxidant effects of nontransferrin bound iron [NTBI (eLPI assay)] during chemotherapy of acute lymphoblastic leukemia and acute myeloblastic leukemia are lacking. We established NTBI and oxidative stress determinants (OSD), iron parameters, high-sensitive C-reactive protein (hs-CRP) levels, liver tests, cumulative chemotherapeutic doses, and transfused blood in 36 children with acute leukemia throughout chemotherapy. These parameters were determined at the beginning and end of chemotherapy blocks (11 time points) and in 20 healthy children using enzyme-linked immunosorbent assay, and colorimetric and fluorometric enzymatic methods...
July 20, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28730969/the-battle-for-iron-between-humans-and-microbes
#3
Peggy L Carver
Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment and a complex 'tug of war' has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection...
July 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28727322/hfe-gene-polymorphism-defined-by-sequence-based-typing-of-the-brazilian-population-and-a-standardized-nomenclature-for-hfe-allele-sequences
#4
W N Campos, J D Massaro, A L C Martinelli, J A Halliwell, S G E Marsh, C T Mendes-Junior, E A Donadi
The HFE molecule controls iron uptake from gut, and defects in the molecule have been associated with iron overload, particularly in hereditary hemochromatosis. The HFE gene including both coding and boundary intronic regions were sequenced in 304 Brazilian individuals, encompassing healthy individuals and patients exhibiting hereditary or acquired iron overload. Six sites of variation were detected: i) H63D C > G in exon 2, ii) IVS2 (+4) T > C in intron 2, iii) a C > G transversion in intron 3, iv) C282Y G > A in exon 4, v) IVS4 (-44) T > C in intron 4, and vi) a new Guanine deletion (G > del) in intron 5, which were used for haplotype inference...
July 20, 2017: HLA
https://www.readbyqxmd.com/read/28727296/chitosan-fe-iii-complex-as-a-phosphate-chelator-in-uraemic-rats-a-novel-treatment-option
#5
Wander Barros do Carmo, Bárbara Bruna Abreu Castro, Clóvis Antônio Rodrigues, Melani Ribeiro Custódio, Helady Sanders-Pinheiro
Phosphate retention and hyperphosphataemia are associated with increased mortality in chronic kidney disease (CKD) patients. We tested the use of cross-linked iron chitosan III (CH-FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into 4 groups (control, CKD, CH-FeCl, and CKD/CH-FeCl), over 7 weeks. We induced CKD by feeding animals an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study...
July 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28720890/iron-overload-exacerbates-age-associated-cardiac-hypertrophy-in-a-mouse-model-of-hemochromatosis
#6
Abitha Sukumaran, JuOae Chang, Murui Han, Shrutika Mintri, Ban-An Khaw, Jonghan Kim
Cardiac damage associated with iron overload is the most common cause of morbidity and mortality in patients with hereditary hemochromatosis, but the precise mechanisms leading to disease progression are largely unexplored. Here we investigated the effects of iron overload and age on cardiac hypertrophy using 1-, 5- and 12-month old Hfe-deficient mice, an animal model of hemochromatosis in humans. Cardiac iron levels increased progressively with age, which was exacerbated in Hfe-deficient mice. The heart/body weight ratios were greater in Hfe-deficient mice at 5- and 12-month old, compared with their age-matched wild-type controls...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720846/physiological-stress-induced-corticosterone-increases-heme-uptake-via-klf4-hcp1-signaling-pathway-in-hippocampus-neurons
#7
Hongxia Li, Caixia Zhang, Hui Shen, Zhilei Shen, Lusha Wu, Fengfeng Mo, Min Li
Iron overload has attracted much attention because of its adverse effect in increasing the risk of developing several neurodegenerative disorders. Under various pathologic conditions, a lot of heme are released. The aggregation of heme is more neurotoxic than that of iron released from the heme breakdown. Our previous studies demonstrated that psychological stress (PS) is a risk factor of cerebral iron metabolism disorders, thus causing iron accumulation in rat brains. In the present study, we found PS could increase heme uptake via heme carrier protein 1 (HCP1) in rat brains...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719386/is-there-a-standard-of-care-for-transfusion-therapy-in-thalassemia
#8
Massimo Franchini, Gian L Forni, Giancarlo M Liumbruno
PURPOSE OF REVIEW: Thalassemia is the most common form of inherited anemia, characterized by variable clinical phenotypes. The purpose of this review is to summarize the transfusion support in thalassemia patients and the management of transfusion-related iron overload. RECENT FINDINGS: The most recent evidence on transfusion strategy and iron chelation therapy in thalassemia arising from clinical trials as well as from recommendation guidelines are critically discussed...
July 14, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28714470/essential-role-of-fbxl5-mediated-cellular-iron-homeostasis-in-maintenance-of-hematopoietic-stem-cells
#9
Yoshiharu Muto, Masaaki Nishiyama, Akihiro Nita, Toshiro Moroishi, Keiichi I Nakayama
Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28710073/zinc-mediates-the-srebp-scd-axis-to-regulate-lipid-metabolism-in-caenorhabditis-elegans
#10
Jing-Jing Zhang, Jun-Jun Hao, Yu-Ru Zhang, Yan-Li Wang, Ming-Yi Li, Hui-Lai Miao, Xiao-Ju Zou, Bin Liang
Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBPs transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still less understood. Here, we show that reduction of SBP-1, the only homologue of SREBPs in C. elegans, surprisingly leads to high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restores the fat accumulation and fatty acid profile of sbp-1(ep79) mutant...
July 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28708597/mri-based-evaluation-of-multiorgan-iron-overload-is-a-predictor-of-adverse-outcomes-in-pediatric-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#11
Natalia Maximova, Massimo Gregori, Giulia Boz, Roberto Simeone, Davide Zanon, Giulia Schillani, Floriana Zennaro
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707012/soluble-form-of-transferrin-receptor-1-level-is-associated-with-the-age-at-first-diagnosis-and-the-risk-of-therapeutic-intervention-and-iron-overloading-in-patients-with-non-transfusion-dependent-thalassemia
#12
Paolo Ricchi, Antonella Meloni, Silvia Costantini, Anna Spasiano, Tiziana Di Matola, Alessia Pepe, Patrizia Cinque, Aldo Filosa
We retrospectively evaluated the relationship between serum transferrin receptor-1 (sTfR1) and some fundamental events in the life and the management (the age at diagnosis, the age at the first red blood cells transfusion, the age at splenectomy, and the overall need of chelation therapy) of 111 patients with non-transfusion-dependent thalassemia (NTDT) subdivided in four genetic entities: patients with homozygous or compound heterozygous state for β-thalassemia, patients with triplicated α genotype associated with β heterozygosity, patients with deletional HbH, and patients with the combination of a β defect plus a β chain variant...
July 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28706555/advances-in-iron-chelation-therapy-transitioning-to-a-new-oral-formulation
#13
Nirmish R Shah
Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consideration and may be affected by side effects...
2017: Drugs in Context
https://www.readbyqxmd.com/read/28705058/standardized-approach-for-roi-based-measurements-of-proton-density-fat-fraction-and-r2-in-the-liver
#14
Camilo A Campo, Diego Hernando, Tilman Schubert, Candice A Bookwalter, Andrew J Van Pay, Scott B Reeder
OBJECTIVE: The purpose of this study was to evaluate the reproducibility (interreviewer agreement) and repeatability (intrareviewer agreement) of ROI sampling strategies to measure chemical shift-encoded (CSE) MRI-based liver proton density fat fraction (PDFF) and R2* (1 / T2*). A secondary purpose was to standardize ROI-based liver PDFF and R2* measurements by providing a compromise between measurement reproducibility and repeatability and time burden for image analysts. MATERIALS AND METHODS: CSE data from two cohorts were retrospectively analyzed...
July 13, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28704940/effects-of-protein-iron-complex-concentrate-supplementation-on-iron-metabolism-oxidative-and-immune-status-in-preweaning-calves
#15
Robert Kupczyński, Michał Bednarski, Kinga Śpitalniak, Krystyna Pogoda-Sewerniak
The objective of this study was to determine the effects of feeding protein-iron complex (PIC) on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf's life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast). Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose) 10 g/day calf of protein-iron complex, HFe (height iron dose) 20 g/day calf, and control group...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28700905/chronic-iron-overload-induces-functional-and-structural-vascular-changes-in-small-resistance-arteries-via-nadph-oxidase-dependent-o2-production
#16
Rogério Faustino Ribeiro, Vinicius Bermond Marques, Dieli Oliveira Nunes, Ivanita Stefanon, Leonardo Dos Santos
Iron overload leads to excessive free radical formation and induces cardiovascular dysfunction. Thus, our aim was to investigate the structural and endothelial modulation of vascular tone induced by chronic iron overload in mesenteric arteries. Rats were divided into two groups: the control (vehicle) group and the group treated with iron dextran for 28days (100mg/kg, 5days a week). Chronic iron overload altered the following morpho-physiological parameters of third-order mesenteric resistance arteries: decreased lumen and external diameters; increased wall/lumen ratio and wall thickness; decreased distensibility and increased stiffness; and increased pulse wave velocity...
July 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28699283/prospective-evaluation-of-chronic-organ-damage-in-adult-sickle-cell-patients-a-seven-year-follow-up-study
#17
Charlotte F J van Tuijn, Marein Schimmel, Eduard J van Beers, Erfan Nur, Bart J Biemond
Organ damage in sickle cell disease (SCD) is a crucial determinant for disease severity and prognosis. In a previous study, we analyzed the prevalence of SCD-related organ damage and complications in adult sickle cell patients. We now describe a seven-year follow-up of this cohort. All patients from the primary analysis in 2006 (n=104), were included for follow-up. Patients were screened for SCD-related organ damage and complications (microalbuminuria, renal failure, elevated tricuspid regurgitation flow velocity (TRV) (≥2...
July 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28695675/the-role-of-diffusion-weighted-imaging-in-prediction-liver-iron-concentration-in-beta-thalassaemia-patients
#18
Suha Akpinar, Guliz Yilmaz, Nail Bulakbasi, Murat Kocaoglu
OBJECTIVE: The aim of this study was to analyse the value of diffusion-weighted magnetic resonance imaging (DWI) to determine the liver parenchyma iron concentration in β-thalassaemia major patients. METHODS: Abdominal magnetic resonance (MR) imaging, including gradient echo sequences and DWI sequences, was undertaken of 55 β-thalassaemia major patients. The apparent diffusion coefficient (ADC) values of liver parenchyma were measured in seven regions at the level of the portal bifurcation and compared with liver iron concentration (LIC)...
July 11, 2017: Journal of Medical Imaging and Radiation Oncology
https://www.readbyqxmd.com/read/28695249/first-study-on-iron-complexes-in-blood-and-organ-samples-from-thalassaemic-and-normal-laboratory-mice-using-m%C3%A3-ssbauer-spectroscopy
#19
George Charitou, Vlassis Petousis, Charalambos Tsertos, Yannis Parpottas, Marina Kleanthous, Marios Phylactides, Soteroula Christou
Measurements of iron complexes and iron stores in the body are crucial for evaluation and management of chelation therapy targeted against iron accumulation or overload in blood and organs. In this work, blood and tissue samples from one normal and one thalassaemic laboratory mouse were studied using (57)Fe Mössbauer spectroscopy at 78 K for the first time. In contrast to human patients, these laboratory mice did not receive any medical treatment, thus the iron components present in the samples are not altered from their natural state...
July 10, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28694969/hypogonadotropic-hypogonadism-in-men-with-hereditary-hemochromatosis
#20
Rabih El Osta, Nicolas Grandpre, Nicolas Monnin, Jacques Hubert, Isabelle Koscinski
Hereditary hemochromatosis is a genetic disease that progresses silently. This disease is often diagnosed late when complications appear. Hypogonadotropic hypogonadism (HH) is one of the classical complications of hemochromatosis. Its frequency is declining probably because of earlier diagnosis and better informed physicians. Certain symptoms linked to HH can have an impact on a patient's sexuality, such as decreased libido, erectile dysfunction, and impairment of ejaculation, as well as on his reproductive capacities...
2017: Basic and Clinical Andrology
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