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https://www.readbyqxmd.com/read/29328981/a-simple-lc-ms-ms-method-for-determination-of-deferasirox-in-human-plasma-troubleshooting-of-interference-from-ferric-ion-in-method-development-and-its-application
#1
Tengfei Li, Zhimin Cui, Yan Wang, Wen Yang, Duo Li, QinXin Song, Luning Sun, Li Ding
As an orally active iron chelator, deferasirox forms its ion complexes in the prepared plasma samples and LC-MS mobile phase where ferric ion exists, and then comparing with the nominal concentration level, a lower detected concentration level of deferasirox would be obtained after LC-MS analysis, if no proper treatment was adopted. Meanwhile, the phenomenon would be observed that multiple repeat injections of the same deferasirox plasma sample in the same tube would show the lower and lower detected concentration levels of deferasirox, which caused by more and more ferric ions from the injection needle dissolved in the sample solution as multiple repeated injections...
December 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29319328/deferasirox-decreases-busulfan-clearance
#2
Jennifer Kwiatkowski, Ulrich Duffner, Aly Abdel-Mageed
No abstract text is available yet for this article.
January 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29305770/deferasirox-for-the-treatment-of-iron-overload-after-allogeneic-hematopoietic-cell-transplantation-multicenter-phase-i-study-ksgct1302
#3
Takayoshi Tachibana, Junya Kanda, Shinichiro Machida, Takeshi Saito, Masatsugu Tanaka, Yuho Najima, Satoshi Koyama, Takuya Miyazaki, Eri Yamamoto, Masahiro Takeuchi, Satoshi Morita, Yoshinobu Kanda, Heiwa Kanamori, Shinichiro Okamoto
The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22-68). Median time from HCT to deferasirox administration was 9 months (range 6-84)...
January 5, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29289598/why-should-neuroscientists-worry-about-iron-the-emerging-role-of-ferroptosis-in-the-pathophysiology-of-neuroprogressive-diseases
#4
REVIEW
Gerwyn Morris, Michael Berk, André F Carvalho, Michael Maes, Adam J Walker, Basant K Puri
Ferroptosis is a unique form of programmed death, characterised by cytosolic accumulation of iron, lipid hydroperoxides and their metabolites, and effected by the fatal peroxidation of polyunsaturated fatty acids in the plasma membrane. It is a major driver of cell death in neurodegenerative neurological diseases. Moreover, cascades underpinning ferroptosis could be active drivers of neuropathology in major psychiatric disorders. Oxidative and nitrosative stress can adversely affect mechanisms and proteins governing cellular iron homeostasis, such as the iron regulatory protein/iron response element system, and can ultimately be a source of abnormally high levels of iron and a source of lethal levels of lipid membrane peroxidation...
December 28, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29285268/reactive-oxygen-species-levels-control-nf-%C3%AE%C2%BAb-activation-by-low-dose-deferasirox-in-erythroid-progenitors-of-low-risk-myelodysplastic-syndromes
#5
Mathieu Meunier, Sarah Ancelet, Christine Lefebvre, Josiane Arnaud, Catherine Garrel, Mylène Pezet, Yan Wang, Patrice Faure, Gautier Szymanski, Nicolas Duployez, Claude Preudhomme, Denis Biard, Benoit Polack, Jean-Yves Cahn, Jean Marc Moulis, Sophie Park
Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228699/iron-depletion-is-a-novel-therapeutic-strategy-to-target-cancer-stem-cells
#6
Takayuki Ninomiya, Toshiaki Ohara, Kazuhiro Noma, Yuki Katsura, Ryoichi Katsube, Hajime Kashima, Takuya Kato, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki Kimura, Ling Chen, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara
Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases. In the present study, we investigated the role of iron in the proliferation and stemness of CSCs, using the miPS-LLCcm cell model. Although the anti-cancer agents fluorouracil and cisplatin suppressed the proliferation of miPS-LLCcm cells, these drugs did not alter the expression of stemness markers, including Nanog, SOX2, c-Myc, Oct3/4 and Klf4...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222265/iron-overload-in-thalassemia-different-organs-at-different-rates
#7
REVIEW
Ali T Taher, Antoine N Saliba
Thalassemic disorders lie on a phenotypic spectrum of clinical severity that depends on the severity of the globin gene mutation and coinheritance of other genetic determinants. Iron overload is associated with increased morbidity in both patients with transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The predominant mechanisms driving the process of iron loading include increased iron burden secondary to transfusion therapy in TDT and enhanced intestinal absorption secondary to ineffective erythropoiesis and hepcidin suppression in NTDT...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29199112/-management-of-patients-with-major-beta-thalassemia-in-a-paediatric-department-in-the-south-of-tunisia-about-26-cases
#8
I Maaloul, O Laaroussi, I Jedidi, L Sfaihi, S Kmiha, T Kamoun, H Aloulou, M Hachicha
AIM: Our objectives were to assess the management of patients with major thalassemia and identify the various complications and monitoring means. PATIENTS AND METHODS: A retrospective study was conducted on 26 β-thalassemic patients in the department of paediatrics, Hédi Chaker hospital, Sfax, Tunisia during a period of 25 years (from 1 January 1990 to 31 December 2014). RESULTS: The mean age of the beginning of transfusion was 11.5 months...
November 30, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/29193587/phlebotomy-as-a-preventive-measure-for-crocidolite-induced-mesothelioma-in-male-rats
#9
Yuuki Ohara, Shan-Hwu Chew, Takahiro Shibata, Yasumasa Okazaki, Kyoko Yamashita, Shinya Toyokuni
Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. While MM is difficult to diagnose at an early stage, there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses...
November 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29177643/iron-overload-in-myelodysplastic-syndromes-mds
#10
REVIEW
Norbert Gattermann
Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS...
November 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29160302/role-of-cyp24a1-vdr-and-gc-gene-polymorphisms-on-deferasirox-pharmacokinetics-and-clinical-outcomes
#11
S Allegra, J Cusato, S De Francia, A Arduino, F Longo, E Pirro, D Massano, A De Nicolò, A Piga, A D'Avolio
β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (Ctrough) and the area under the curve (AUC) cutoffs of 20 μg ml(-1) and 360 μg ml(-1) h(-1), respectively; nonresponse AUC limit of 250 μg ml(-1) h(-1)). Ninety-nine β-thalassemic patients were enrolled...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29155313/a-phase-ii-multicenter-single-arm-study-to-evaluate-the-safety-and-efficacy-of-deferasirox-after-hematopoietic-stem-cell-transplantation-in-children-with-%C3%AE-thalassemia-major
#12
Mehmet Akif Yesilipek, Gulsun Karasu, Zuhre Kaya, Baris B Kuskonmaz, Vedat Uygun, Ilkiz Dag, Onur Ozudogru, Mehmet Ertem
We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients (aged >2 to <18 years) with β-thalassemia major (TM) who have undergone hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 µg/L, cardiac MRI T2* <20 ms, or liver iron concentration [LIC; by MRI R2] ≥5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29099735/effect-of-pharmacogenetic-markers-of-vitamin-d-pathway-on-deferasirox-pharmacokinetics-in-children
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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