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Iron chelation

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https://www.readbyqxmd.com/read/28544309/increased-complications-of-chronic-erythrocytapheresis-compared-with-manual-exchange-transfusions-in-children-and-adolescents-with-sickle-cell-disease
#1
Deborah Woods, Robert J Hayashi, Michael M Binkley, Gianna W Sparks, Monica L Hulbert
BACKGROUND: Children and adolescents with sickle cell disease (SCD) are at high risk of strokes and are frequently treated with red blood cell (RBC) transfusions. The goal is to suppress hemoglobin (Hb) S while minimizing transfusion-induced iron overload. RBCs may be given via simple transfusion, manual exchange transfusion (MET), or erythrocytapheresis (aRBCX). Chronic transfusion practices vary among institutions. METHODS: This single-institution, retrospective cohort study compares Hb S control and therapy complication rates between MET and aRBCX in a cohort of children and adolescents with SCD and stroke during a 5-year period from 2008 through 2012...
May 19, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28544032/prevalence-of-diabetes-mellitus-in-chinese-children-with-thalassaemia-major
#2
Yuzhen Liang, Rekha Bajoria, Yan Jiang, Hongwei Su, Hongfei Pan, Ning Xia, Ratna Chatterjee, Yongrong Lai
OBJECTIVE: Diabetes mellitus is a common endocrinopathy in patients with β-thalassaemia major (β-TM), which is high prevalent in southern China. This study aimed to determine the cause and prevalence of glycaemic disorders in Chinese children with β-TM. METHODS: In this prospective study, fasting glucose and insulin (FINS) levels were assessed in 267 β-TM and 80 non-TM control children. Homeostatic model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI) were evaluated...
May 22, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28542352/preconditioning-of-adipose-tissue-derived-mesenchymal-stem-cells-with-deferoxamine-increases-the-production-of-pro-angiogenic-neuroprotective-and-anti-inflammatory-factors-potential-application-in-the-treatment-of-diabetic-neuropathy
#3
Carolina Oses, Belén Olivares, Marcelo Ezquer, Cristian Acosta, Paul Bosch, Macarena Donoso, Patricio Léniz, Fernando Ezquer
Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors...
2017: PloS One
https://www.readbyqxmd.com/read/28540737/investigational-drugs-in-phase-i-and-phase-ii-clinical-trials-for-thalassemia
#4
Irene Motta, Natalia Scaramellini, Maria Domenica Cappellini
Regular transfusion and iron chelation are the current treatment of severe forms of thalassemia. As a result of this demanding supportive treatment, there are several unmet therapeutic needs. Due to a deeper understanding in the pathophysiology of thalassemia, new therapeutic strategies have been developed that are now in pre-clinical and clinical trials. Areas covered: Activin receptor ligand traps (luspatercept and sotatercept), drugs targeting ineffective erythropoiesis, showed encouraging results in Phase I and II clinical trials...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28537266/natural-allelic-variation-of-fro2-modulates-arabidopsis-root-growth-under-iron-deficiency
#5
Santosh B Satbhai, Claudia Setzer, Florentina Freynschlag, Radka Slovak, Envel Kerdaffrec, Wolfgang Busch
Low availability of Fe significantly limits crop yields in many parts of the world. However, it is largely unknown which genes and alleles adjust plant growth in Fe limited environments. Using natural variation of a geographically restricted panel of Arabidopsis thaliana accessions, we identify allelic variation at the FRO2 locus associated with root length under iron deficiency. We show that non-coding sequence variation at the FRO2 locus leads to variation of FRO2 transcript levels, as well as ferric chelate reductase activity, and is causal for a portion of the observed root length variation...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534662/neuroprotection-of-brain-permeable-iron-chelator-vk-28-against-intracerebral-hemorrhage-in-mice
#6
Qian Li, Jieru Wan, Xi Lan, Xiaoning Han, Zhongyu Wang, Jian Wang
Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28533366/mechanism-of-h2s-mediated-protection-against-oxidative-stress-in-escherichia-coli
#7
Alexander Mironov, Tatyana Seregina, Maxim Nagornykh, Lyly G Luhachack, Natalya Korolkova, Liubov Errais Lopes, Vera Kotova, Gennady Zavilgelsky, Rustem Shakulov, Konstantin Shatalin, Evgeny Nudler
Endogenous hydrogen sulfide (H2S) renders bacteria highly resistant to oxidative stress, but its mechanism remains poorly understood. Here, we report that 3-mercaptopyruvate sulfurtransferase (3MST) is the major source of endogenous H2S in Escherichia coli Cellular resistance to H2O2 strongly depends on the activity of mstA, a gene that encodes 3MST. Deletion of the ferric uptake regulator (Fur) renders ∆mstA cells hypersensitive to H2O2 Conversely, induction of chromosomal mstA from a strong pLtetO-1 promoter (P tet -mstA) renders ∆fur cells fully resistant to H2O2 Furthermore, the endogenous level of H2S is reduced in ∆fur or ∆sodA ∆sodB cells but restored after the addition of an iron chelator dipyridyl...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533164/a-novel-iron-ii-preferring-dopamine-agonist-chelator-d-607-significantly-suppresses-%C3%AE-syn-and-mptp-induced-toxicities-in-vivo
#8
Banibrata Das, Subramanian Rajagopalan, Gnanada S Joshi, Liping Xu, Dan Luo, Julie K Andersen, Sokol V Todi, Aloke K Dutta
Here, we report the characterization of a novel hybrid D2/D3 agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D2/D3 receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28532285/utility-of-transient-elastography-in-estimating-hepatic-iron-concentration-in-comparison-to-magnetic-resonance-imaging-in-patients-who-are-transfusion-dependent-a-canadian-center-experience
#9
George Ou, Hin Hin Ko, Pari Tiwari, Navdeep Sandhu, Cherry Galorport, Terry Lee, Hatoon Ezzat
Transfusion-dependent hereditary anemias such as β-thalassemia (β-thal), predispose patients to iron overload and its numerous clinical sequelae. Accurate assessment of overall iron status and prompt initiation of chelation therapy to prevent irreversible end-organ damage can be achieved using magnetic resonance imaging (MRI) to measure liver iron concentration (LIC) as a surrogate marker of total body iron; however, its access may be associated with long wait times and delay in treatment. We report an observational cohort study at a single tertiary care center assessing the theoretical role of transient elastography (TE), which measures liver stiffness, in estimating LIC compared to other established diagnostic measures...
January 2017: Hemoglobin
https://www.readbyqxmd.com/read/28524209/understanding-the-biomimetic-properties-of-gallium-in-pseudomonas-aeruginosa-an-xas-and-xps-study
#10
F Porcaro, C Bonchi, A Ugolini, E Frangipani, G Polzonetti, P Visca, C Meneghini, C Battocchio
Pyochelin (PCH) is a siderophore (extracellular chelator) produced by the pathogenic bacterium Pseudomonas aeruginosa (PAO). PCH is implicated in iron (Fe(3+)) transport to PAO, and is crucial for its metabolism and pathogenicity. Due to the chemical similarity with Fe(3+), gallium (Ga(3+)) interferes with vital iron-dependent processes in bacterial cells, thereby opening new perspectives for the design of specific metal-based antibacterial drugs. However, the structural basis for the Fe(3+)-mimetic properties of Ga(3+) complexed with the PCH siderophore is still lacking...
May 19, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28521818/in-vivo-evaluation-of-microglia-activation-by-intracranial-iron-overload-in-central-pain-after-spinal-cord-injury
#11
Fan Xing Meng, Jing Ming Hou, Tian Sheng Sun
BACKGROUND: Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent microglia activate in the remodeling of the brain after SCI. METHODS: An SCI-induced CP model was established in Sprague-Dawley rats that were randomly assigned to SCI, sham operation, deferoxamine (DFX), minocycline, and nitric oxide synthase inhibitor treatment groups...
May 18, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/28521682/repurposing-of-copper-ii-chelating-drugs-for-the-treatment-of-neurodegenerative-diseases
#12
Valeria Lanza, Danilo Milardi, Giuseppe Di Natale, Giuseppe Pappalardo
BACKGROUND: There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews has exhaustively described either the molecular or clinical aspects of neurodegenerative diseases as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can be also effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) interacting molecules as potential drug candidates in neurodegeneration...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28515762/biochemical-and-histopathological-effects-of-green-tea-nanoparticles-in-ironized-mouse-model
#13
Hidayat Sulistyo, Dhadhang Wahyu Kurniawan, Lantip Rujito
Transfusion in the treatment of thalassemia gives rise to iron deposits in many organs. Since there are many obstacles in the use of deferoxamin (DFO) as an iron chelating agent, it is important to find another alternative therapy that can act as iron chelation. The study aims to compare the histopathological pictures of the heart and spleen in iron-induced rats after administration of DFO and nanoparticles of green tea extract. The research used experimental research design with a post-test only control group...
April 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28515648/evaluation-of-antioxidative-activity-of-various-levels-of-ethanol-extracted-tomato-powder-and-application-to-pork-patties
#14
Hyeong Sang Kim, Koo Bok Chin
This study was performed to evaluate antioxidant activity of tomato powder extracted by various concentrations of ethanol (0, 25, 50, 75, 100%) and to evaluate the physicochemical properties and antioxidant activities of pork patties with ethanol extracted tomato (EET) powder. No differences in the contents of total of individual phenolic compounds including gallic acid and catechin, were observed among the treatments (p>0.05). Among the various concentrations, 50% and 75% EET powder showed the highest free radical scavenging and iron chelating activities (p<0...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/28515173/heme-oxygenase-1-mitigates-ferroptosis-in-renal-proximal-tubule-cells
#15
Oreoluwa Adedoyin, Ravindra Boddu, Amie M Traylor, Jeremie M Lever, Subhashini Bolisetty, James George, Anupam Agarwal
Ferroptosis is an iron-dependent form of regulated, non-apoptotic cell death, which contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1 (HO-1) is a cytoprotective enzyme induced in response to cellular stress, and is protective against AKI due to its anti-apoptotic and anti-inflammatory properties. However, the role of HO-1 in regulating ferroptosis is unclear. The purpose of this study was to elucidate the role of HO-1 in regulating ferroptotic cell death in renal proximal tubule cells (PTCs)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28514101/rearrangement-of-a-p4-butterfly-complex-the-formation-of-a-homoleptic-phosphorus-iron-sandwich-complex
#16
Julian Müller, Sebastian Heinl, Christoph Schwarzmaier, Gábor Balázs, Martin Keilwerth, Karsten Meyer, Manfred Scheer
The versatile coordination behavior of the P4 butterfly complex [{Cp'''Fe(CO)2 }2 (μ,η(1:1) -P4 )] (1, Cp'''=η(5) -C5 H2(t) Bu3 ) towards different iron(II) compounds is presented. The reaction of 1 with [FeBr2 ⋅dme] (dme=dimethoxyethane) leads to the chelate complex [{Cp'''Fe(CO)2 }2 (μ3 ,η(1:1:2) -P4 ){FeBr2 }] (2), whereas, in the reaction with [Fe(CH3 CN)6 ][PF6 ]2 , an unprecedented rearrangement of the P4 butterfly structural motif leads to the cyclo-P4 moiety in {(Cp'''Fe(CO)2 )2 (μ3 ,η(1:1:4) -P4 )}2 Fe][PF6 ]2 (3)...
May 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28512090/the-vibrio-cholerae-vexgh-rnd-efflux-system-maintains-cellular-homeostasis-by-effluxing-vibriobactin
#17
Dillon E Kunkle, X Renee Bina, James E Bina
Resistance-nodulation-division (RND) superfamily efflux systems have been widely studied for their role in antibiotic resistance, but their native biological functions remain poorly understood. We previously showed that loss of RND-mediated efflux in Vibrio cholerae resulted in activation of the Cpx two-component regulatory system, which mediates adaptation to stress resulting from misfolded membrane proteins. Here, we investigated the mechanism linking RND-mediated efflux to the Cpx response. We performed transposon mutagenesis screening of RND-deficient V...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28512001/low-dose-inflammatory-potential-of-silica-particles-in-human-derived-thp-1-macrophage-cell-culture-studies-mechanism-and-effects-of-particle-size-and-iron
#18
Premshekharan Gayatri, Hongqiao Zhang, Kennedy Nguyen, Henry Jay Forman, Valerie Jean Leppert
Silica and iron are major constituents in ambient particulate matter, and iron is a common impurity in many engineered nanomaterials. The purpose of this work was to determine the pro-inflammatory and other biological effects and mechanism of particle size and iron presence under low dose, non-cytotoxic conditions that are likely to approximate actual exposure levels, in contrast with higher dose studies in which cytotoxicity occurs. Specifically, human-derived THP-1 macrophages were exposed to 1 μg/ml of pristine and iron-coated 50 nm and 2 μm engineered silica nanoparticles...
May 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28511780/anti-mycobacterium-avium-complex-activity-of-clarithromycin-rifampin-rifabutin-and-ethambutol-in-combination-with-adenosine-5-triphosphate
#19
Yutaka Tatano, Seiko Yamabe, Chiaki Sano, Haruaki Tomioka
We previously reported that adenosine 5'-triphosphate (ATP) inhibited the growth of various bacteria, including mycobacteria, Staphylococcus, and Pseudomonas, without damaging bacterial surface structures. Notably, ATP's antibacterial activity was found to be attributable to its iron-chelating ability. ATP exhibited combined effects with some antimicrobials against Mycobacterium intracellulare and methicillin-resistant S. aureus, suggesting its usefulness as an adjunctive drug in the chemotherapy against certain intractable infections...
May 2, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28505405/structural-basis-for-xenosiderophore-utilization-by-the-human-pathogen-staphylococcus-aureus
#20
Nathaniel P Endicott, Eries Lee, Timothy Adam Wencewicz
Staphylococcus aureus produces a cocktail of metallophores (staphylopine, staphyloferrin A, and staphyloferrin B) to scavenge transition metals during infection of a host. In addition, S. aureus displays the extracellular surface lipoproteins FhuD1 and FhuD2 along with the ABC transporter complex FhuCBG to facilitate the use of hydroxamate xenosiderophores such as desferrioxamine B (DFOB) for iron acquisition. DFOB is used as a chelation therapy to treat human iron overload diseases and has been linked to an increased risk of S...
May 15, 2017: ACS Infectious Diseases
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