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Management of Hyperkalemia in Heart Failure.
Altay, H, Çavuşoğlu, Y, Çelik, A, Demir, Ş, Kılıçarslan, B, Nalbantgil, S, Temizhan, A, Tokgöz, B, Ural, D, Yeşilbursa, D, et al
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2021;(Supp1):1-32
Abstract
Hyperkalemia is a common electrolyte abnormality in heart failure (HF) that can cause potentially life-threatening cardiac arrhythmias and sudden cardiac death. HF patients with diabetes, chronic kidney disease and older age are at higher risk of hyperkalemia. Moreover, hyperkalemia is also often associated with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and sacubitril-valsartan. In clinical practice, the occurrence of hyperkalemia is a major concern among the clinicians and often limits RAASi use and/or lead to dose reduction or discontinuation, thereby reducing their potential benefits for HF. Furthermore, recurrent hyperkalemia is frequent in the long-term and is associated with an increase in hyperkalemia-related hospitalizations. Therefore, management of hyperkalemia has a special importance in HF patients. However, treatment options in chronic management are currently limited. Dietary restriction of potassium is usually ineffective with variable adherence. Sodium polystyrene sulfonate is commonly used, but its effectiveness is uncertain and reported to be associated with intestinal toxicity. New therapeutic options such as potassium binders have been suggested as potentially beneficial agents in the management of hyperkalemia. This document discusses prevalence, predictors and management of hyperkalemia in HF, emphasizing the importance of careful patient selection for medical treatment, uptitration of the doses of RAASi, regular surveillance of potassium and treatment options of hyperkalemia.
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Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract.
Biruete, A, Hill Gallant, KM, Lindemann, SR, Wiese, GN, Chen, NX, Moe, SM
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(1):4-10
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Abstract
Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.
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Benefits and Detriments of Gadolinium from Medical Advances to Health and Ecological Risks.
Unruh, C, Van Bavel, N, Anikovskiy, M, Prenner, EJ
Molecules (Basel, Switzerland). 2020;(23)
Abstract
Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data shows that metal may accumulate in the human body and its deposition has been detected in organs such as brain and liver. Moreover, the disease nephrogenic systemic fibrosis has been linked to increased Gd3+ levels. Investigation of Gd3+ effects at the cellular and molecular levels mostly revolves around calcium-dependent proteins, since Gd3+ competes with calcium due to their similar size; other reports focus on interaction of Gd3+ with nucleic acids and carbohydrates. However, little is known about Gd3+ effects on membranes; yet some results suggest that Gd3+ interacts strongly with biologically-relevant lipids (e.g., brain membrane constituents) and causes serious structural changes including enhanced membrane rigidity and propensity for lipid fusion and aggregation at much lower concentrations than other ions, both toxic and essential. This review surveys the impact of the anthropogenic use of Gd emphasizing health risks and discussing debilitating effects of Gd3+ on cell membrane organization that may lead to deleterious health consequences.
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Copper Depletion as a Therapeutic Strategy in Cancer.
Lopez, J, Ramchandani, D, Vahdat, L
Metal ions in life sciences. 2019
Abstract
Copper is an essential trace element that plays a critical role in a variety of basic biological functions, and serves as a key component in a number of copper-dependent enzymes that regulate such processes as cell proliferation, angiogenesis, and motility. A growing body of preclinical work has demonstrated that copper is essential to metastatic cancer progression, and may have a role in tumor growth, epithelial-mesenchymal transition, and the formation of the tumor microenvironment and pre-metastatic niche. As a result, copper depletion has emerged as a novel therapeutic strategy in the treatment of metastatic cancer. We present a review of the physiologic role of copper with a discussion of relevant enzymes of the copper proteome in both normal tissue and in cancer. We conducted a comprehensive review of the available preclinical data of several copper chelation agents, including penicillamine, trientine, disulfiram, clioquinol, and tetrathiomolybdate (TM), across a variety of tumor types. We also present the existing early phase clinical trial data for the use of the copper chelator TM in the treatment of breast cancer and other malignancies.
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Successful Treatment of Single Infected Calciphylaxis Lesion With Intralesional Injection of Sodium Thiosulfate at High Concentration.
Zuhaili, B, Al-Talib, K
Wounds : a compendium of clinical research and practice. 2019;(8):E54-E57
Abstract
INTRODUCTION Calciphylaxis is a very complicated disease that usually presents in patients with end-stage renal disease (ESRD). Treatment for calciphylaxis is not well standardized and typically involves a multidisciplinary approach. One of the common medications used in calciphylaxis treatment is sodium thiosulfate (STS). However, its intravenous injection is associated with multiple side effects. CASE REPORT The authors present a case report of an intralesional injection of STS followed by a literature review of the common treatment modalities and possible further use of intralesional injections. A 51-year-old man with ESRD on peritoneal dialysis presented with a right calf biopsy-proven calciphylaxis lesion measuring 3.1 cm x 3.9 cm. About the same time, he had Pseudomonas-associated peritoneal catheter peritonitis. The calciphylaxis lesion was treated with bimonthly intralesional injections of STS. The lesion had a complete resolution by week 9. CONCLUSIONS The authors believe a higher local concentration of STS leading to a faster resolution and requiring less frequent injections needs to be further evaluated. Following additional studies, they also propose a greater use of intralesional STS injections in a select set of patients in the future.
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Site-specific chelator-antibody conjugation for PET and SPECT imaging with radiometals.
Morais, M, Ma, MT
Drug discovery today. Technologies. 2018;:91-104
Abstract
Antibodies and their derivatives radiolabelled with positron- and gamma-emitting radiometals enable sensitive and quantitative molecular Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging of antibody distribution in vivo. Chelators that are covalently attached to antibodies allow radiolabelling with metallic PET and SPECT radioisotopes. Conventional strategies for chelator-protein conjugation generate heterogeneous mixtures of bioconjugates that can exhibit reduced affinity for their receptor targets, and undesirable biodistribution and pharmacokinetics. Recent advances in bioconjugation technology enable site-specific modification to generate well-defined constructs with superior properties. Herein we survey existing site-specific chelator-protein conjugation methods. These include chelator attachment to cysteines/disulfide bonds or the glycan region of the antibody, enzyme-mediated chelator conjugation, and incorporation of sequences of amino acids that chelate the radiometal. Such technology will allow better use of PET and SPECT imaging in the development of antibody-based therapies.
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Phosphorus binders: The new and the old, and how to choose.
Sekar, A, Kaur, T, Nally, JV, Rincon-Choles, H, Jolly, S, Nakhoul, GN
Cleveland Clinic journal of medicine. 2018;(8):629-638
Abstract
In caring for patients with chronic kidney disease, it is important to prevent and treat hyperphosphatemia with a combination of dietary restrictions and phosphorus binders. This review describes the pathophysiology and control of hyperphosphatemia and the different classes of phosphorus binders with respect to their availability, cost, side effects, and scenarios in which one class of binder may be more beneficial than another.
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Synthesis, nature and utility of universal iron chelator - Siderophore: A review.
Khan, A, Singh, P, Srivastava, A
Microbiological research. 2018;:103-111
Abstract
Siderophores, the secondary metabolite of various microorganisms are ferric ion specific chelators secreted under iron stressed condition. These non-ribosomal peptides have been classified as catecholate, hydroxamate, carboxylate and mixed types. Recent studies focus on discovery of possible mammalian siderophores. The biosynthesis pathway including non-ribosomal dependent as well as non-ribosomal independent pathways are of great interest now a days. Many significant roles of siderophores such as virulence in pathogens, oxidative stress tolerance, classification of organisms etc. are being discovered. Studies on siderophore utilization in bioremediation and other heavy metal chelation have increased in past decade. The iron chelation ability of siderophores is being recently studied with regards to malignant cancerous cells. Not only this, it has been found that they possess antimicrobial properties which can be utilized against number of microbes. This review covers all recent aspects of siderophore and its applications.
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Evidence basis for integrated management of mineral metabolism in patients with end-stage renal disease.
Scialla, JJ
Current opinion in nephrology and hypertension. 2018;(4):258-267
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Abstract
PURPOSE OF REVIEW Treatment of mineral metabolism is a mainstay of dialysis care including some of its most widely used and costly pharmaceuticals. Although many mineral metabolites are associated with increased risk of mortality, cardiovascular disease, and other morbidities, few clinical trials are available to guide therapy and most focus on single drug approaches. In practice, providers manage many aspects of mineral metabolism simultaneously in integrated treatment approaches that incorporate multiple agents and changes in the dialysis prescription. The present review discusses the rationale and existing evidence for evaluating integrated, as opposed to single drug, approaches in mineral metabolism. RECENT FINDINGS Drugs used to treat mineral metabolism have numerous, and sometimes, opposing effects on biochemical risk factors, such as fibroblast growth factor 23 (FGF23), calcium, and phosphorus. Although vitamin D sterols raise these risk markers when lowering parathyroid hormone (PTH), calcimimetics lower them. Trials demonstrate that combined approaches best 'normalize' the mineral metabolism axis in end-stage renal disease (ESRD). Observations embedded within major trials of calcimimetics reveal that adjustment of calcium-based binders and dialysate calcium is a common approach to adverse effects of these drugs with some initial, but inconclusive, evidence that these co-interventions may impact outcomes. SUMMARY The multiple, and often opposing, biochemical effects of many mineral metabolism drugs provides a strong rationale for studying integrated management strategies that consider combinations of drugs and co-interventions as a whole. This remains a current gap in the field with opportunities for clinical trials.
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Metal homeostasis in infectious disease: recent advances in bacterial metallophores and the human metal-withholding response.
Neumann, W, Gulati, A, Nolan, EM
Current opinion in chemical biology. 2017;:10-18
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Abstract
A tug-of-war between the mammalian host and bacterial pathogen for nutrients, including first-row transition metals (e.g. Mn, Fe, Zn), occurs during infection. Here we present recent advances about three metal-chelating metabolites that bacterial pathogens deploy when invading the host: staphylopine, staphyloferrin B, and enterobactin. These highlights provide new insights into the mechanisms of bacterial metal acquisition and regulation, as well as the contributions of host-defense proteins during the human innate immune response. The studies also underscore that the chemical composition of the microenvironment at an infection site can influence bacterial pathogenesis and the innate immune system.