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https://www.readbyqxmd.com/read/29099735/effect-of-pharmacogenetic-markers-of-vitamin-d-pathway-on-deferasirox-pharmacokinetics-in-children
#1
Sarah Allegra, Jessica Cusato, Silvia De Francia, Filomena Longo, Elisa Pirro, Davide Massano, Antonio Piga, Antonio D'Avolio
OBJECTIVES: Patients with β-thalassemia major have extremely low vitamin D levels, owing to reduced intestinal absorption, subicteric tint, and/or iron-induced higher pigmentation. We investigated whether some polymorphisms within the VDR, CYP24A1, CYP27B1, and GC genes could play a role in deferasirox pharmacokinetics in a cohort of pediatric patients. PATIENTS AND METHODS: Eighteen children with β-thalassemia were enrolled. Drug plasma concentrations at the end of dosing interval (Ctrough) and after 0, 2, 4, 6, and 24 h of drug administration were measured by a HPLC-UV method...
November 2, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29071014/chelation-of-thallium-iii-in-rats-using-combined-deferasirox-and-deferiprone-therapy
#2
Samie Salehi, Amir Sh Saljooghi, Somayeh Badiee, Mojtaba Mashmool Moqadam
Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days...
October 2017: Toxicological Research
https://www.readbyqxmd.com/read/29069221/protective-effects-of-deferasirox-and-n-acetyl-l-cysteine-on-iron-overload-injured-bone-marrow
#3
J C Shen, Y C Zhang, M F Zhao
Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow...
October 19, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29068574/total-antioxidant-capacity-in-mediterranean-%C3%AE-thalassemic-patients
#4
Ioannis Tsamesidis, Claudio Fozza, Eleni Vagdatli, Anastasia Kalpaka, Carla Cirotto, Maria Carmina Pau, Antonella Panataleo, Francesco Turrini, Elisavet Grigoriou, Eugenia Lymperaki
BACKGROUND: Beta thalassemia major (BT) is an inherited blood disorder caused by reduced or absent synthesis of the hemoglobin beta chains, associated with profound anemia, jaundice, splenomegaly, expanded bone marrow volume, siderosis and cardiomegaly. Because of repeated blood transfusions, BT patients are subjected to peroxidative tissue injury due to secondary iron overload. OBJECTIVES: The aim of the study was to analyze: 1) the total antioxidant capacity (TAC) value in BT patients (study group) and their healthy controls (control group) from Greece (Central Macedonia) and Italy (Sardinia); correlations between 2) the TAC and ferritin levels of BT patients, and 3) the TAC and ferritin values in BT patients with different chelation therapies...
August 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29019038/utilisation-and-safety-of-deferasirox-results-from-an-observational-cohort-study-in-england
#5
Vicki Osborne, Miranda Davies, Deborah Layton, Saad A W Shakir
INTRODUCTION: Deferasirox (EXJADE(®), Novartis, UK) is an oral iron-chelating agent primarily used to reduce chronic iron overload in patients receiving blood transfusions for various chronic anaemias and some non-transfusion dependant anaemias. OBJECTIVE: The aim of this study was to examine the utilisation and safety of deferasirox used in general practice in England. METHOD: A single exposure observational cohort study design was used...
October 10, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28968980/safety-and-tolerability-of-deferasirox-in-pediatric-hematopoietic-stem-cell-transplant-recipients-one-facility-s-five-years-experience-of-chelation-treatment
#6
Natalia Maximova, Massimo Gregori, Roberto Simeone, Aurelio Sonzogni, Giulia Boz, Carmen Fucile, Valeria Marini, Antonietta Martelli, Francesca Mattioli
42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28940159/zinc-status-in-beta-thalassemia-major-patients
#7
Attanayaka Mudiyanselage Dilhara Sewwandi Karunaratna, Jamburagoda Gamage Shirani Ranasingha, Rasnayaka Mudiyanselage Mudiyanse
Beta thalassemia is a common monogenic hereditary hemoglobinopathy which is associated with compound complications. Zinc deficiency, which is commonly observed in thalassemia patients, is also associated with multiple health complications. The objective of this study was to determine the zinc status and its effect on the growth and immune functions of young beta thalassemia major patients. The study included 40 patients in comparison with age- and sex-matched 30 healthy individuals as controls. The patients were interviewed for socio-demographic variables, and their medical histories were obtained from the hospital files...
September 23, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28933303/cardioprotective-potential-of-iron-chelators-and-prochelators
#8
Hana Jansova, Tomas Simunek
Heart is a particularly sensitive organ to iron overload and cardiomyopathy due to the excessive cardiac iron deposition causes most deaths in disorders such as beta-thalassemia major. Free or loosely bound iron ions readily cycle between ferrous and ferric states and catalyze Haber-Weiss reaction that yields highly reactive and toxic hydroxyl radicals. Treatment with iron chelators (desferrioxamine, deferiprone, and deferasirox) substantially improved cardiovascular morbidity and mortality in iron overloaded patients...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28932366/comparison-of-iron-chelation-effects-of-deferoxamine-deferasirox-and-combination-of-deferoxamine-and-deferiprone-on-liver-and-cardiac-t2-mri-in-thalassemia-maior
#9
Shahla Ansari, Azita Azarkeivan, Ghasem Miri-Aliabad, Saeed Yousefian, Tahereh Rostami
BACKGROUND: Cardiac complications due to iron overload are the most common cause of death in patients with thalassemia major. The aim of this study was to compare iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on cardiac and liver iron load measured by T2* MRI. METHODS: In this study, 108 patients with thalassemia major aged over 10 years who had iron overload in cardiac T2* MRI were studied in terms of iron chelators efficacy on the reduction of myocardial siderosis...
2017: Caspian Journal of Internal Medicine
https://www.readbyqxmd.com/read/28930590/chelation-protocols-for-the-elimination-and-prevention-of-iron-overload-in-thalassaemia
#10
Annita Kolnagou, George John Kontoghiorghes
Iron overload toxicity is the main cause of mortality and morbidity in thalassaemia patients. The complete elimination and prevention of iron overload is the main aim of chelation therapy, which can be achieved by chelation protocols that can effectively remove excess iron load and maintain body iron at normal levels. Deferiprone and selected combinations with deferoxamine can be designed, adjusted and used effectively for removing all excess stored iron and for maintaining normal iron stores (NIS) in different categories of thalassaemia patients...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28924413/pseudovitelliform-maculopathy-associated-with-deferoxamine-toxicity-multimodal-imaging-and-electrophysiology-of-a-rare-entity
#11
Kelly M Bui, SriniVas R Sadda, Hani Salehi-Had
Deferoxamine is a commonly used chelating agent for secondary hemochromatosis. We report a rare retinal manifestation of deferoxamine toxicity in a 68-year-old man and provide supporting multimodal imaging and electrophysiology. The patient had iron overload related to transfusion-dependent myelodysplastic syndrome and developed a pseudovitelliform macular lesion related to deferoxamine toxicity. We also describe for the first time the worsening of this maculopathy on deferasirox, an alternative chelating agent...
2017: Digital Journal of Ophthalmology: DJO
https://www.readbyqxmd.com/read/28900315/efficacy-and-safety-of-deferasirox-in-pediatric-patients-of-thalassemia-at-a-tertiary-care-teaching-hospital
#12
Dhaval R Thakor, Chetna K Desai, Jigar D Kapadia, Ram K Dikshit, K M Mehariya
OBJECTIVE: To evaluate efficacy, safety and utilization pattern of deferasirox in paediatric patients of transfusion dependant β Thalassemia Major at a tertiary care teaching hospital in Gujarat. MATERIALS AND METHODS: This observational, prospective-retrospective, single centre, continuous study was conducted in a tertiary care teaching hospital among paediatric patients of transfusion dependent β Thalassemia Major. Patients treated with deferasirox for not more than 12 weeks were enrolled...
April 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28875336/progression-of-liver-fibrosis-can-be-controlled-by-adequate-chelation-in-transfusion-dependent-thalassemia-tdt
#13
D Maira, E Cassinerio, A Marcon, M Mancarella, M Fraquelli, P Pedrotti, M D Cappellini
A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection has been implicated in the development of liver fibrosis. Hepatic siderosis and fibrosis were assessed in 99 transfusion-dependent thalassemia (TDT) patients using transient elastography (TE) and liver iron concentration (LIC) assessed by T2*MRI at baseline and after 4 years. Data were analyzed retrospectively. At baseline, the overall mean liver stiffness measurement (LSM) was 7...
November 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28864815/eltrombopag-a-powerful-chelator-of-cellular-or-extracellular-iron-iii-alone-or-combined-with-a-second-chelator
#14
Evangelia Vlachodimitropoulou, Yu-Lin Chen, Maciej Garbowski, Pimpisid Koonyosying, Bethan Psaila, Martha Sola-Visner, Nichola Cooper, Robert Hider, John Porter
Eltrombopag (ELT) is a thrombopoietin receptor agonist reported to decrease labile iron in leukemia cells. Here we examine the previously undescribed iron(III)-coordinating and cellular iron-mobilizing properties of ELT. We find a high binding constant for iron(III) (log β2=35). Clinically achievable concentrations (1 µM) progressively mobilized cellular iron from hepatocyte, cardiomyocyte, and pancreatic cell lines, rapidly decreasing intracellular reactive oxygen species (ROS) and also restoring insulin secretion in pancreatic cells...
October 26, 2017: Blood
https://www.readbyqxmd.com/read/28820004/drug-induced-liver-injury-in-children-clinical-observations-animal-models-and-regulatory-status
#15
Qiang Shi, Xi Yang, James J Greenhaw, Alec Thomas Salminen, Gary M Russotti, William F Salminen
Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI)...
September 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28818403/heavy-metal-levels-in-patients-with-ineffective-erythropoiesis
#16
Turan Bayhan, Şule Ünal, Eyüp Çırak, Onur Erdem, Cemal Akay, Orhan Gürsel, İbrahim Eker, Erdem Karabulut, Fatma Gümrük
OBJECTIVES: Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS: Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls...
August 2, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28815805/intracellular-iron-overload-leading-to-dna-damage-of-lymphocytes-and-immune-dysfunction-in-thalassemia-major-patients
#17
Jyoti Shaw, Ayan Chakraborty, Arijit Nag, Arnab Chattopadyay, Anjan K Dasgupta, Maitreyee Bhattacharyya
OBJECTIVES: To investigate the cause and effects of intracellular iron overload in lymphocytes of thalassemia major patients. METHODS: Sixty-six thalassemia major patients having iron overload and 10 age-matched controls were chosen for the study. Blood sample was collected, and serum ferritin, oxidative stress; lymphocyte DNA damage were examined, and infective episodes were also counted. RESULTS: Case-control analysis revealed significant oxidative stress, iron overload, DNA damage, and rate of infections in thalassemia cases as compared to controls...
August 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28809446/deferasirox-for-managing-iron-overload-in-people-with-thalassaemia
#18
REVIEW
Claudia Bollig, Lisa K Schell, Gerta Rücker, Roman Allert, Edith Motschall, Charlotte M Niemeyer, Dirk Bassler, Joerg J Meerpohl
BACKGROUND: Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. OBJECTIVES: To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload...
August 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28781827/deferasirox-associated-with-liver-failure-and-death-in-a-sickle-cell-anemia-patient-homozygous-for-the-1774delg-polymorphism-in-the-abcc2-gene
#19
Caroline C B Braga, Bruno Deltreggia Benites, Dulcineia M de Albuquerque, Marisa C Alvarez, Tiago Seva-Pereira, Bruno K L Duarte, Fernando F Costa, Simone C O Gilli, Sara T O Saad
This manuscript describes the case of a patient with sickle cell anemia who died of fulminant hepatitis after therapy with the iron chelator Deferasirox. The patient was homozygous for the -1774delG polymorphism in the Abcc2 gene, which raises the concern about the use of hepatotoxic drugs in this specific context.
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28753129/glomerular-and-tubular-functions-in-children-and-adults-with-transfusion-dependent-thalassemia
#20
Agageldi Annayev, Zeynep Karakaş, Serap Karaman, Altan Yalçıner, Alev Yılmaz, Sevinç Emre
OBJECTIVE: This study aimed at assessing renal functions in patients with transfusion dependent thalassemia (TDT). MATERIALS AND METHODS: Fifty patients and 30 controls were enrolled in this prospective study. Serum levels of electrolytes and albumin were measured by a spectrophotometer. Serum levels of cystatin-C and urinary levels of β2-microglobulin were measured by nephelometric method. Thirty-eight patients were receiving Deferasirox, 8 were on Deferiprone...
July 28, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
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