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https://www.readbyqxmd.com/read/28453480/a-multifunctional-biocompatible-drug-candidate-is-highly-effective-in-delaying-pathological-signs-of-alzheimer-s-disease-in-5xfad-mice
#1
Hadar Segal-Gavish, Ortal Danino, Yael Barhum, Tali Ben-Zur, Ella Shai, David Varon, Daniel Offen, Bilha Fischer
BACKGROUND: Metal-ion-chelation was suggested to prevent zinc and copper ions-induced amyloid-β (Aβ) aggregation and oxidative stress, both implicated in the pathophysiology of Alzheimer's disease (AD). In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we previously tested a series of nucleoside 5'-phosphorothioate derivatives as agents for decomposition of Cu(I)/Cu(II)/Zn(II)-Aβ-aggregates, and as inhibitors of OH radicals formation in Cu(I) or Fe(II) /H2O2 solution...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28446716/targeted-alpha-therapy-using-a-novel-cd70-targeted-thorium-227-conjugate-in-in-vitro-and-in-vivo-models-of-renal-cell-carcinoma
#2
Urs B Hagemann, Dessislava Mihaylova, Steinar R Uran, Joergen Borrebaek, Derek Grant, Roger M Bjerke, Jenny Karlsson, Alan S Cuthbertson
The cell surface receptor CD70 has been previously reported as a promising target for B-cell lymphomas and several solid cancers including renal cell carcinoma. We describe herein the characterization and efficacy of a novel CD70 targeted thorium-227 conjugate (CD70-TTC) comprising the combination of the three components, a CD70 targeting antibody, a chelator moiety and the short-range, high-energy alpha-emitting radionuclide thorium-227 (227Th). In vitro analysis demonstrated that the CD70-TTC retained binding affinity to its target and displayed potent and specific cytotoxicity compared to an isotype control-TTC...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443261/diabetes-mellitus-caused-by-secondary-hemochromatosis-after-multiple-blood-transfusions-in-2-patients-with-severe-aplastic-anemia
#3
Hyun Jin Kim, Yoon-Myung Kim, Eungu Kang, Beom Hee Lee, Jin-Ho Choi, Han-Wook Yoo
Hemochromatosis is an inherited or secondary disorder caused by excessive iron storage leading to multiple organ damage. We describe 2 patients with diabetes mellitus caused by hemochromatosis secondary to multiple blood transfusions due to severe aplastic anemia. Subject 1, who was diagnosed with severe aplastic anemia at 15 years of age, received multiple red blood cell transfusions before he underwent autologous peripheral blood stem cell transplantation (PBSCT) at 22 years of age. At 21 years of age, hyperglycemia was detected with increased hemoglobin A1c and serum ferritin levels, 9...
March 2017: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28440111/quality-of-life-outcomes-in-a-pediatric-thalassemia-population-in-egypt
#4
Soheir Adam, Hanan Afifi, Manal Thomas, Phoebe Magdy, Ghada El-Kamah
Thalassemia is a disorder of hemoglobin (Hb) synthesis characterized by chronic hemolysis. In β-thalassemias major (β-TM), patients require regular transfusion at an early age due to severe anemia. Subsequently, intensive chelation therapy is initiated to mitigate the effects of the resultant iron overload. Clinical disease burden and the demanding treatment can affect health-related quality of life (HRQoL) outcomes in this population. The aim of this study was to assess HRQoL outcomes in Egyptian pediatric thalassemia patients...
April 25, 2017: Hemoglobin
https://www.readbyqxmd.com/read/28439915/treatment-of-chronic-hepatitis-c-with-direct-acting-antivirals-in-patients-with-%C3%AE-thalassaemia-major-and-advanced-liver-disease
#5
Emmanouil Sinakos, Dimitrios Kountouras, John Koskinas, Kalliopi Zachou, Stylianos Karatapanis, Christos Triantos, Themistoklis Vassiliadis, Ioannis Goulis, Alexandra Kourakli, Efthymia Vlachaki, Barbara Toli, Maria Tampaki, Pinelopi Arvaniti, Georgios Tsiaoussis, Aristea Bellou, Antonis Kattamis, Konstantinos Maragkos, Foteini Petropoulou, George N Dalekos, Evangelos Akriviadis, George V Papatheodoridis
Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with β-thalasaemia major (β-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with β-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28437627/tumor-acidity-activatable-tat-targeted-nanomedicine-for-enlarged-fluorescence-magnetic-resonance-imaging-guided-photodynamic-therapy
#6
Meng Gao, Feng Fan, Dongdong Li, Yue Yu, Kuirong Mao, Tianmeng Sun, Haisheng Qian, Wei Tao, Xianzhu Yang
Nanoparticles simultaneously integrated the photosensitizers and diagnostic agents represent an emerging approach for imaging-guided photodynamic therapy (PDT). However, the diagnostic sensitivity and therapeutic efficacy of nanoparticles as well as the heterogeneity of tumors pose tremendous challenges for clinical imaging-guided PDT treatment. Herein, a polymeric nanoparticle with tumor acidity (pHe)-activatable TAT targeting ligand that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates contrast agent Gd(3+) is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28435994/thalassemia-minor-and-major-%C3%A2-current-management
#7
REVIEW
Ved Prakash Choudhry
Thalassemia is a common genetic disorder. It has been estimated that in India nearly 5 crore people are thalassemia carriers. They are asymptomatic and are detected on blood tests. These people are at same risk of developing iron deficiency anemia as general population and need iron therapy in the presence of iron deficiency anemia. Nearly 12,000 children with thalassemia major (Homozygous state) are born every year. These children often present with significant anemia along with hepatosplenomegaly during infancy and require early diagnosis and institution of therapy with repeated blood transfusions and chelation therapy...
April 24, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28435466/design-of-tumor-acidity-responsive-sheddable-nanoparticles-for-fluorescence-magnetic-resonance-imaging-guided-photodynamic-therapy
#8
Feng Fan, Yue Yu, Fei Zhong, Meng Gao, Tianmeng Sun, Jiaxin Liu, Huimao Zhang, Haisheng Qian, Wei Tao, Xianzhu Yang
Imaging-guided cancer therapy, which integrates diagnostic and therapeutic functionalities into a single system, holds great promise to enhance the accuracy of diagnosis and improve the efficacy of therapy. Specifically, for photodynamic therapy (PDT), it is highly desirable to precisely focus laser light onto the tumor areas to generate reactive oxygen species (ROS) that are cytotoxic tumor cells and avoid light-associated side effects. Herein, a distinct three-layer nanostructured particle with tumor acidity-responsiveness (S-NP) that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates Gd(3+) is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT...
2017: Theranostics
https://www.readbyqxmd.com/read/28433106/novel-perspectives-on-wilson-disease-treatment
#9
Christian Rupp, Wolfgang Stremmel, Karl-Heinz Weiss
Wilson disease is an autosomal-recessive copper overload disorder causing hepatic and neurologic symptoms. Commonly used medical therapy shows satisfactory results with regard to hepatic disease but only limited effects in neurologically affected patients. In recent years several new therapy options have been developed, showing promising results that might improve the management of Wilson disease in the near future. Optimization of treatment regimens depending on biochemical response pattern seems worthwhile, especially in the decoppering phase of therapy...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28433101/wilson-disease-currently-used-anticopper-therapy
#10
Anna Członkowska, Tomasz Litwin
Wilson disease (WD) is a genetic disorder of copper metabolism that can be treated successfully with pharmacologic treatment. Two groups of drugs are currently used: chelators (e.g., d-penicillamine and trientine), which increase urinary copper excretion, and zinc salts, which inhibit copper absorption in the digestive tract. The mechanisms of action lead to a negative copper balance, stopping pathologic accumulation of copper in the tissues and clearing affected organs of copper overload. Due to a lack of prospective clinical trials, the use of drugs depends mainly on center experience and the accessibility in different countries or regions...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28428704/lead-poisoning-due-to-herbal-medications
#11
Shailja Chambial, Pankaj Bhardwaj, Abbas Ali Mahdi, Praveen Sharma
Lead ranks as one of the most serious environmental poisons all over the world amongst toxic heavy metals with no known biological function useful for the human body. A case of lead toxicity due to consumption of herbal medicine is being discussed. The case presented with gastrointestinal complaints and history of intake of herbal medicines for diabetes control for past 8 months. The analysis of the powdered herbal medicine procured from ayurveda practitioner was found to have high content of lead responsible for the lead toxicity...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28426137/hydroxyurea-hydroxycarbamide-for-sickle-cell-disease
#12
REVIEW
Sarah J Nevitt, Ashley P Jones, Jo Howard
BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting...
April 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28419408/iron-chelating-therapy-with-deferasirox-in-transfusion-dependent-higher-risk-myelodysplastic-syndromes-a-retrospective-multicentre-study
#13
Pellegrino Musto, Luca Maurillo, Vittorio Simeon, Antonella Poloni, Carlo Finelli, Enrico Balleari, Alessandra Ricco, Flavia Rivellini, Agostino Cortelezzi, Giuseppe Tarantini, Oreste Villani, Giovanna Mansueto, Maria R Milella, Daniele Scapicchio, Gioacchino Marziano, Massimo Breccia, Pasquale Niscola, Alessandro Sanna, Cristina Clissa, Maria T Voso, Susanna Fenu, Adriano Venditti, Valeria Santini, Emanuele Angelucci, Alessandro Levis
Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75)...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28409295/metal-chelator-tpen-selectively-induces-apoptosis-in-k562-cells-through-reactive-oxygen-species-signaling-mechanism-implications-for-chronic-myeloid-leukemia
#14
Luisa Rojas-Valencia, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio
Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the constitutive expression of BCR-ABL tyrosine kinase. Although successful implementation of tyrosine kinase inhibitors for the treatment of CML remain a traditional choice for molecularly targeted therapy, some patients present primary or secondary resistance to such therapy. Therefore, alternative therapeutic strategies are required to treat resistant CML cells. Accordingly, new anti-proliferative and/or pro-apoptotic compounds would be needed for clinical treatment...
April 13, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28399703/value-of-speckle-tracking-echocardiography-for-detection-of-clinically-silent-left-ventricular-dysfunction-in-patients-with-%C3%AE-thalassemia
#15
Mozhgan Parsaee, Sedigheh Saedi, Pegah Joghataei, Azita Azarkeivan, Zahra Alizadeh Sani
OBJECTIVE: β-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring chronic transfusion therapy. Cardiac involvement is the main cause of death in patients with thalassemia major. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) dysfunction in patients with thalassemia. Therefore, we need novel parameters in different imaging techniques to discover cardiac involvement in an early and subtle stage...
April 12, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28396543/a-topical-hydrogel-with-deferiprone-and-gallium-protoporphyrin-targets-bacterial-iron-metabolism-and-has-antibiofilm-activity
#16
Katharina Richter, Nicky Thomas, Jolien Claeys, Jonathan McGuane, Clive A Prestidge, Tom Coenye, Peter-John Wormald, Sarah Vreugde
Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. Whilst oral drug-delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection-site while reducing systemic side-effects.This study determined the antibiofilm activity of a surgical wound-gel loaded with the iron-chelator deferiprone (Def) and the heme-analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin...
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28389407/d-penicillamine-combined-with-inhibitors-of-hydroperoxide-metabolism-enhances-lung-and-breast-cancer-cell-responses-to-radiation-and-carboplatin-via-h2o2-mediated-oxidative-stress
#17
Sebastian J Sciegienka, Shane R Solst, Kelly C Falls, Joshua D Schoenfeld, Adrienne R Klinger, Natalie L Ross, Samuel N Rodman, Douglas R Spitz, Melissa A Fath
D-penicillamine (DPEN), a copper chelator, has been used in the treatment of Wilson's disease, cystinuria, and rheumatoid arthritis. Recent evidence suggests that DPEN in combination with biologically relevant copper (Cu) concentrations generates H2O2 in cancer cell cultures, but the effects of this on cancer cell responses to ionizing radiation and chemotherapy are unknown. Increased steady-state levels of H2O2 were detected in MB231 breast and H1299 lung cancer cells following treatment with DPEN (100µM) and copper sulfate (15µM)...
April 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28388554/synergistic-inhibitory-effects-of-deferasirox-in-combination-with-decitabine-on-leukemia-cell-lines-skm-1-thp-1-and-k-562
#18
Nianyi Li, Qinfen Chen, Jingwen Gu, Shuang Li, Guangjie Zhao, Wei Wang, Zhicheng Wang, Xiaoqin Wang
A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388076/immunopet-imaging-of-ctla-4-expression-in-mouse-models-of-non-small-cell-lung-cancer
#19
Emily B Ehlerding, Christopher G England, Rebecca L Majewski, Hector F Valdovinos, Dawei Jiang, Glenn Liu, Douglas G McNeel, Robert J Nickles, Weibo Cai
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is expressed on the surface of activated T cells and some tumor cells, and is the target of the clinically approved monoclonal antibody ipilimumab. In this study, we investigate specific binding of radiolabeled ipilimumab to CTLA-4 expressed by human non-small cell lung cancer cells in vivo using positron emission tomography (PET). Ipilimumab was radiolabeled with (64)Cu (t1/2 = 12.7 h) through the use of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to formulate (64)Cu-DOTA-ipilimumab...
April 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28384880/efficacy-of-deferasirox-as-an-oral-iron-chelator-in-paediatric-thalassaemia-patients
#20
Shikha Jaiswal, Rajesh Hishikar, Onkar Khandwal, Manju Agarwal, Usha Joshi, Ajay Halwai, Basant Maheshwari, Raka Sheohare
INTRODUCTION: Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. AIM: To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
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