Targeted EDTA Chelation Therapy with Albumin Nanoparticles To
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Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus
The Journal of Neuroscience, October 2, 2013 • 33(40):15675–15685 • 15675 Cellular/Molecular Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus Andrea Rahel Sieber,1 Rogier Min,1 and Thomas Nevian1,2 1Department of Physiology and 2Center for Cognition, Learning and Memory, University of Bern, 3012 Bern, Switzerland The thalamus integrates and transmits sensory information to the neocortex. The activity of thalamocortical relay (TC) cells is modulated by specific inhibitory circuits. Although this inhibition plays a crucial role in regulating thalamic activity, little is known about long-term changes in synaptic strength at these inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory inputs to TC cells in the posterior medial nucleus of the thalamus by combining patch-clamp recordings with two-photon fluorescence microscopy in rat brain slices.WefoundthatspecificactivitypatternsinthepostsynapticTCcellinducedinhibitorylong-termpotentiation(iLTP).ThisiLTPwas non-Hebbian because it did not depend on the timing between presynaptic and postsynaptic activity, but it could be induced by postsyn- aptic burst activity alone. iLTP required postsynaptic dendritic Ca 2ϩ influx evoked by low-threshold Ca 2ϩ spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane potential (Ϫ50 mV), which suppressed these low-threshold Ca 2ϩ spikes, induced no plasticity. The postsynaptic dendritic Ca 2ϩ increase triggered the synthesis of nitric oxide that retrogradely activated presynaptic guanylylcyclase,resultinginthepresynapticexpressionofiLTP.ThedependenceofiLTPonthemembranepotentialandthereforeonthe -
Deferasirox (Exjade, Jadenu) Reference Number: CP.PHAR.145 Effective Date: 11.15 Last Review Date: 11.17 Line of Business: Medicaid Revision Log
Clinical Policy: Deferasirox (Exjade, Jadenu) Reference Number: CP.PHAR.145 Effective Date: 11.15 Last Review Date: 11.17 Line of Business: Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Deferasirox (Exjade®, Jadenu®) is an iron chelator. FDA Approved Indication(s) Exjade and Jadenu are indicated: For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. For the treatment of chronic iron overload in patients 10 years of age and older with non- transfusion-dependent thalassemia syndromes and with a liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L. Limitation of use: Controlled clinical trials of Exjade/Jadenu with myelodysplastic syndromes and chronic iron overload due to blood transfusions have not been performed. The safety and efficacy of Exjade/Jadenu when administered with other iron chelation therapy have not been established. Policy/Criteria Provider must submit documentation (including office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation® that Exjade and Jadenu are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Chronic Iron Overload Due to Blood Transfusions (must meet all): 1. Diagnosis of chronic iron overload due to blood transfusions as may occur in the treatment of chronic anemia, including thalassemia; 2. Age ≥ 2 years old; 3. -
Chelation Therapy
Corporate Medical Policy Chelation Therapy File Name: chelation_therapy Origination: 12/1995 Last CAP Review: 2/2021 Next CAP Review: 2/2022 Last Review: 2/2021 Description of Procedure or Service Chelation therapy is an established treatment for the removal of metal toxins by converting them to a chemically inert form that can be excreted in the urine. Chelation therapy comprises intravenous or oral administration of chelating agents that remove metal ions such as lead, aluminum, mercury, arsenic, zinc, iron, copper, and calcium from the body. Specific chelating agents are used for particular heavy metal toxicities. For example, desferroxamine (not Food and Drug Administration [FDA] approved) is used for patients with iron toxicity, and calcium-ethylenediaminetetraacetic acid (EDTA) is used for patients with lead poisoning. Note that disodium-EDTA is not recommended for acute lead poisoning due to the increased risk of death from hypocalcemia. Another class of chelating agents, called metal protein attenuating compounds (MPACs), is under investigation for the treatment of Alzheimer’s disease, which is associated with the disequilibrium of cerebral metals. Unlike traditional systemic chelators that bind and remove metals from tissues systemically, MPACs have subtle effects on metal homeostasis and abnormal metal interactions. In animal models of Alzheimer’s disease, they promote the solubilization and clearance of β-amyloid protein by binding to its metal-ion complex and also inhibit redox reactions that generate neurotoxic free radicals. MPACs therefore interrupt two putative pathogenic processes of Alzheimer’s disease. However, no MPACs have received FDA approval for treating Alzheimer’s disease. Chelation therapy has also been investigated as a treatment for other indications including atherosclerosis and autism spectrum disorder. -
Review of Oral Iron Chelators (Deferiprone and Deferasirox) for the Treatment of Iron Overload in Pediatric Patients
Review of Oral Iron Chelators (Deferiprone and Deferasirox) for the Treatment of Iron Overload in Pediatric Patients D. Adam Algren, MD Assistant Professor of Pediatrics and Emergency Medicine Division of Pediatric Pharmacology and Medical Toxicology Departments of Pediatrics and Emergency Medicine Children’s Mercy Hospitals and Clinics/Truman Medical Center University of Missouri-Kansas City School of Medicine 1 PROPOSAL The World Health Organization Model List of Essential Medicines and Model Formulary 2010 list deferoxamine (DFO) as the treatment of choice for both acute and chronic iron poisoning. The Model Formulary currently does not designate any orally administered agents for the chelation of iron. It is proposed that deferasirox be considered the oral chelator of choice in the treatment of chronic iron overload. Deferasirox is widely available recent evidence support that it is both safe and efficacious. INTRODUCTION Acute iron poisoning and chronic iron overload result in significant morbidity and mortality worldwide. Treatment of acute iron poisoning and chronic iron overload can be challenging and care providers are often confronted with management dilemmas. Oral iron supplements are commonly prescribed for patients with iron deficiency anemia. The wide availability of iron supplements and iron-containing multivitamins provide easy accessibility for both adults and children. The approach to treatment of acute iron toxicity involves providing adequate supportive care, optimizing hemodynamic status and antidotal therapy with IV deferoxamine, when indicated.1 Early following an acute ingestion gastrointestinal (GI) decontamination can be potentially beneficial. Multiple options exist including: syrup of ipecac, gastric lavage, and whole bowel irrigation (WBI). Although definitive evidence that GI decontamination decreases morbidity and mortality is lacking it is often considered to be beneficial. -
Iron Chelating Agents
Pharmacy Benefit Coverage Criteria Effective Date ............................................ 1/1/2021 Next Review Date… ..................................... 1/1/2022 Coverage Policy Number ................................ P0090 Iron Chelating Agents Table of Contents Related Coverage Resources Medical Necessity Criteria ................................... 1 Dimercaprol and Edetate Calcium Disodium FDA Approved Indications ................................... 3 Penicillamine and trientene hydrochloride Recommended Dosing ........................................ 4 Background .......................................................... 8 References ........................................................ 11 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may -
Upfront Dexrazoxane for the Reduction of Anthracycline-Induced
Ganatra et al. Cardio-Oncology (2019) 5:1 https://doi.org/10.1186/s40959-019-0036-7 RESEARCH Open Access Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series Sarju Ganatra1,2,3*, Anju Nohria3, Sachin Shah2, John D. Groarke3, Ajay Sharma2, David Venesy2, Richard Patten2, Krishna Gunturu4,5, Corrine Zarwan4, Tomas G. Neilan6, Ana Barac7, Salim S. Hayek8, Sourbha Dani9, Shantanu Solanki10, Syed Saad Mahmood11 and Steven E. Lipshultz12 Abstract Background: Cardiotoxicity associated with anthracycline-based chemotherapies has limited their use in patients with preexisting cardiomyopathy or heart failure. Dexrazoxane protects against the cardiotoxic effects of anthracyclines, but in the USA and some European countries, its use had been restricted to adults with advanced breast cancer receiving a cumulative doxorubicin (an anthracycline) dose > 300 mg/m2. We evaluated the off-label use of dexrazoxane as a cardioprotectant in adult patients with preexisting cardiomyopathy, undergoing anthracycline chemotherapy. Methods: Between July 2015 and June 2017, five consecutive patients, with preexisting, asymptomatic, systolic left ventricular (LV) dysfunction who required anthracycline-based chemotherapy, were concomitantly treated with off-label dexrazoxane, administered 30 min before each anthracycline dose, regardless of cancer type or stage. Demographic, cardiovascular, and cancer-related outcomes were compared to those of three consecutive patients with asymptomatic cardiomyopathy treated earlier at the same hospital without dexrazoxane. Results: Mean age of the five dexrazoxane-treated patients and three patients treated without dexrazoxane was 70.6 and 72.6 years, respectively. All five dexrazoxane-treated patients successfully completed their planned chemotherapy (doxorubicin, 280 to 300 mg/m2). -
(12) Patent Application Publication (10) Pub. No.: US 2010/0222294 A1 Pele (43) Pub
US 2010O222294A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0222294 A1 Pele (43) Pub. Date: Sep. 2,9 2010 (54) FORMULATIONS OF ATP AND ANALOGS OF Publication Classification ATP (51) Int. Cl. A 6LX 3L/7076 (2006.01) (75) Inventor: Amir Pelleg, Haverford, PA (US) A6IP35/00 (2006.01) Correspondence Address: 39t. 87, C FSH & RICHARDSON P.C. (2006.01) P.O. BOX 1022 A6IP 9/00 308: MNNEAPOLIS. MN 55440-1022 US A6IP II/06 2006.O1 9 (US) A6IP II/08 (2006.01) (73) Assignee: DUSKA SCIENTIFIC CO., CI2N 5/02 (2006.01) Philadelphia, PA (US) AOIN I/02 (2006.01) (52) U.S. Cl. ................................ 514/47; 435/375; 435/2 (21) Appl. No.: 12/715,170 (57) ABSTRACT (22) Filed: Mar. 1, 2010 This disclosure provides solutions and compositions (e.g., O O pharmaceutical solutions and compositions) containing Related U.S. Application Data adenosine 5'-triphosphate (ATP) or an analog thereof. In (60) Provisional application No. 61/156.263, filed on Feb. addition, it features methods of making and using the solu 27, 2009. tions and compositions. Patent Application Publication Sep. 2, 2010 US 2010/0222294 A1 Figure , NH N O O. O. a'rn HO-P-O-PYo-E-40. O-P-O- o, 's-slNYN Ohi Oi O US 2010/0222294 A1 Sep. 2, 2010 FORMULATIONS OF ATP AND ANALOGS OF N-Tris(hydroxymethyl)methylglycine (Tricine); glycine; ATP Diglycine (Gly-Gly); N,N-Bis(2-hydroxyethyl)glycine (Bi cine); N-(2-Hydroxyethyl)piperazine-N'-(4-butanesulfonic acid) (HEPBS); N-Tris(hydroxymethyl)methyl-3-amino 0001. -
Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases
cells Review Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases George J. Kontoghiorghes * and Christina N. Kontoghiorghe Postgraduate Research Institute of Science, Technology, Environment and Medicine, CY-3021 Limassol, Cyprus * Correspondence: [email protected]; Tel./Fax: +357-2627-2076 Received: 7 May 2020; Accepted: 5 June 2020; Published: 12 June 2020 Abstract: Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology. -
Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems
Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 640754, 26 pages http://dx.doi.org/10.1155/2014/640754 Review Article Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems Bechan Sharma,1 Shweta Singh,2 and Nikhat J. Siddiqi3 1 Department of Biochemistry, University of Allahabad, Allahabad 211002, India 2 Department of Genetics, SGPGIMS, Lucknow 226014, India 3 Department of Biochemistry, King Saud University, Riyadh 11451, Saudi Arabia Correspondence should be addressed to Bechan Sharma; [email protected] Received 28 February 2014; Revised 28 May 2014; Accepted 10 July 2014; Published 12 August 2014 Academic Editor: Hartmut Jaeschke Copyright © 2014 Bechan Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Several workers have extensively worked out the metal induced toxicity and have reported the toxic and carcinogenic effects of metals in human and animals. It is well known that these metals play a crucial role in facilitating normal biological functions of cells as well. One of the major mechanisms associated with heavy metal toxicity has been attributed to generation of reactive oxygen and nitrogen species, which develops imbalance between the prooxidant elements and the antioxidants (reducing elements) in the body. In this process, a shift to the former is termed as oxidative stress. The oxidative stress mediated toxicity of heavy metals involves damage primarily to liver (hepatotoxicity), central nervous system (neurotoxicity), DNA (genotoxicity), and kidney (nephrotoxicity) in animals and humans. Heavy metals are reported to impact signaling cascade and associated factors leading to apoptosis. -
Spectrophotometric Determination of Ethylenediaminetetraacetic Acid and Its Related Compounds with P-Carboxyphenylfluorone, Titanium(IV) and Hydrogen Peroxide1
ANALYTICAL SCIENCES DECEMBER 1998, VOL. 14 1157 1998 © The Japan Society for Analytical Chemistry Notes Spectrophotometric Determination of Ethylenediaminetetraacetic Acid and Its Related Compounds with p-Carboxyphenylfluorone, Titanium(IV) and Hydrogen Peroxide1 Yoshikazu FUJITA, Itsuo MORI and Takako MATSUO Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka 569–1094, Japan Keywords Ethylenediaminetetraacetic acid and its related compounds, spectrophotometry, p-carboxyphenylfluorone- titanium(IV) complex, hydrogen peroxide Ethylenediaminetetraacetic acid (EDTA), an (polyethylene glycol-p-nonylphenylether, Nakarai aminopolycarboxylic acid, is widely used in industry, Tesque) and 0.8% Amphitol 24B (betaine lauryldimethyl- detergents and foods. Recently, environmental pollu- aminoacetate, Kao Chem.) in the final concentration. tion by EDTA is getting more and more serious due to A buffer solution of pH 5.5 was prepared by mixing a its strong affinity with highly toxic heavy metals and its 0.2 M disodium hydrogenphosphate solution and a 0.1 resistance to biodegradation. Thus, it is imperative that M citric acid solution. Reagent-grade chemicals were sensitive and selective means of analysis are available. used throughout. Pure water was prepared by purifying We have reported some sensitive spectrophotometric deionized water with a Milli-Q Labo system just before methods2,3 for the determination of hydrogen peroxide use. (H2O2) based on fading of a dye-titanium(IV) complex A Shimadzu spectrophotometer (Model UV-160) with in the presence of EDTA. We speculated that a method 1.0-cm matched silica cells was used for an absorbance which would utilize fading of a dye-titanium(IV) com- measurement. The pH measurements were made with a plex in the presence of H2O2 would serve as a sensitive Horiba (F-11) pH meter in combination with a calomel determination for EDTA. -
Transcriptomic Analysis of Synergy Between Antifungal Drugs and Iron Chelators for Alternative Antifungal Therapies
Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies Yu-Wen Lai School of Life and Environmental Sciences (SoLES) Faculty of Science The University of Sydney 2017 A thesis submitted in fulfilment of the requirements of the degree of Doctor of Philosophy. Declaration of originality I certify that this thesis contains no materials which have been accepted for award of any other degree or diploma at any other university. To the best of my knowledge, this thesis is original and contains no material previously published or written by any other person, except where due reference has been made in the text. Yu-Wen Lai August 2016 i Acknowledgements This whole thesis and the years spent into completing it would not have been possible without the help and support of a lot of people. I am thankful and grateful to my supervisor Dee Carter and also to my co-supervisor Sharon Chen for giving me the opportunity to work on this project. I am also thankful to our collaborator Marc Wilkins and his team. This project has been very challenging and your inputs and advice have really helped immensely. A big thank you goes to past and present honours students, PhD candidates and post-docs. Your prep talks, stimulating discussions, humour, baked goods and cider making sessions were my staples for keeping me mostly sane. To Kate Weatherby and Sam Cheung, we started honours and PhDs together and even travelled together in Europe. There were major ups and downs during the course of our projects, but were finally getting to the end! Thank you Katherine Pan and Mia Zeric for always offering chocolate and snacks, I swear I mostly go over to your side of the office just to eat your food. -
Mechanisms and Effects of Intracellular Calcium Buffering on Neuronal Survival in Organotypic Hippocampal Cultures Exposed to Anoxia/Aglycemia Or to Excitotoxins
The Journal of Neuroscience, May 15, 1997, 17(10):3538–3553 Mechanisms and Effects of Intracellular Calcium Buffering on Neuronal Survival in Organotypic Hippocampal Cultures Exposed to Anoxia/Aglycemia or to Excitotoxins Khaled M. Abdel-Hamid1 and Michael Tymianski1,2 1Playfair Neuroscience Unit and 2Division of Neurosurgery, University of Toronto, Toronto, Ontario M5T-2S8, Canada Neuronal calcium loading attributable to hypoxic/ischemic in- survival after OGD were identical, indicating that increased jury is believed to trigger neurotoxicity. We examined in orga- buffer content is necessary for the observed protective effect. notypic hippocampal slice cultures whether artificially and re- Protection by Ca21 buffering originated presynaptically be- versibly enhancing the Ca21 buffering capacity of neurons cause BAPTA-AM was ineffective when endogenous transmit- reduces the neurotoxic sequelae of oxygen–glucose depriva- ter release was bypassed by directly applying NMDA to the tion (OGD), whether such manipulation has neurotoxic poten- cultures, and because pretreatment with the low Ca21 affinity tial, and whether the mechanism underlying these effects is pre- buffer 2-aminophenol-N,N,O-triacetic acid acetoxymethyl es- or postsynaptic. Neurodegeneration caused over 24 hr by 60 ter, which attenuates excitatory transmitter release, attenuated min of OGD was triggered largely by NMDA receptor activation neurodegeneration. Thus, in cultured hippocampal slices, en- and was attenuated temporarily by pretreating the slices with hancing neuronal Ca21 buffering unequivocally attenuates or cell-permeant Ca21 buffers such as 1,2 bis(2- delays the onset of anoxic neurodegeneration, likely by atten- aminophenoxy)ethane-N,N,N9,N9-tetra-acetic acid acetoxym- uating the synaptic release of endogenous excitatory neuro- ethyl ester (BAPTA-AM).