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[Hyperkalemia in heart failure: new solutions for an old problem].
Romani, S, Porcari, A, Fabris, E, Sinagra, G
Giornale italiano di cardiologia (2006). 2019;(10):543-551
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Abstract
Potassium is the main intracellular ion and its homeostasis is finely regulated by the renal and gastrointestinal tract. Renal failure and hyperkalemia are conditions commonly found in patients with heart failure, the result of a complex interaction between heart and kidney (e.g. cardio-renal syndrome) and the side effects of drugs commonly used for treating heart disease (e.g. renin-angiotensin-aldosterone system inhibitors). Although hyperkalemia increases the risk of heart conduction disorders and life-threatening arrhythmias, its prognostic significance in heart failure is uncertain. Hyperkalemia and progression of renal damage are the main limitations to the introduction and titration of heart failure therapies. New drugs for the prevention and chronic treatment of hyperkalemia allow the introduction and modulation of anti-neurohormonal therapies in patients with heart failure otherwise excluded from these treatments due to excessively high serum potassium levels.This review illustrates the pathophysiological, epidemiological and prognostic aspects of hyperkalemia and analyses the possible treatments for this condition in heart failure patients.
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Potassium-lowering agents for the treatment of nonemergent hyperkalemia: pharmacology, dosing and comparative efficacy.
Bridgeman, MB, Shah, M, Foote, E
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(Suppl 3):iii45-iii50
Abstract
Hyperkalemia represents a common and potentially life-threating electrolyte abnormality, a complication frequently observed in patients with heart failure, kidney disease, diabetes or in those receiving drug therapies influencing the renin-angiotensin-aldosterone system. Elevated serum potassium levels are often the result of impaired urinary potassium elimination, inadequate or reduced cellular potassium uptake, severe heart failure, use of medications influencing potassium levels in the circulation, or, more commonly, a combination of these factors. Strategies for the treatment of nonemergent hyperkalemia include the use of cation-exchange resins, polymers or other novel mechanisms of potassium trapping, including sodium polystyrene sulfonate, patiromer and sodium zirconium cyclosilicate. These agents differ in their pharmacology and mechanism of action, clinical efficacy, including onset and extent of potassium-lowering effect, dosage and administration, and potential safety and adverse effect profiles. In this review, an evaluation of these characteristics, including clinical evidence and safety concerns, in the management of nonemergent hyperkalemia will be explored.
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Boosting the Limited Use of Mineralocorticoid Receptor Antagonists Through New Agents for Hyperkalemia.
Athyros, VG, Sachinidis, AG, Zografou, I, Simoulidou, E, Piperidou, A, Stavropoulos, N, Karagiannis, A
Current pharmaceutical design. 2018;(46):5542-5547
Abstract
BACKGROUND Hyperkalemia is an important clinical problem that is associated with significant lifethreatening complications. Several conditions are associated with increased risk for hyperkalemia such as chronic kidney disease, diabetes mellitus, heart failure, and the use of renin-angiotensin-aldosterone system (RAAS) inhibitors. OBJECTIVE The purpose of this review is to present and critically discuss treatment options for the management of hyperkalemia. METHOD A comprehensive review of the literature was performed to identify studies assessing the drug-induced management of hyperkalemia. RESULTS The management of chronic hyperkalemia seems to be challenging and includes a variety of traditional interventions, such as restriction in the intake of the dietary potassium, loop diuretics or sodium polystyrene sulfonate. In the last few years, several new agents have emerged as promising options to reduce potassium levels in hyperkalemic patients. Patiromer and sodium zirconium cyclosilicate 9 (ZS-9) have been examined in hyperkalemic patients and were found to be efficient and safe. Importantly, the efficacy of these novel drugs might allow the continuation of the use of RAAS inhibitors, morbidity- and mortality-wise beneficial class of drugs in the setting of chronic kidney disease and heart failure. CONCLUSION Data support that the recently emerged patiromer and ZS-9 offer significant hyperkalemia-related benefits. Larger trials are needed to unveil the impact of these drugs in other patients' subpopulations, as well.
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Effect of root canal irrigation protocols on the dislocation resistance of mineral trioxide aggregate-based materials: A systematic review of laboratory studies.
Neelakantan, P, Ahmed, HMA, Wong, MCM, Matinlinna, JP, Cheung, GSP
International endodontic journal. 2018;(8):847-861
Abstract
The aim of this systematic review was to address the question: Do different irrigating protocols have an impact on the dislocation resistance of mineral trioxide aggregate (MTA)-based materials? The review was performed using a well-defined search strategy in three databases (PubMed, Scopus, Web of Science) to include laboratory studies performed between January 1995 and May 2017, in accordance with PRISMA guidelines. Two reviewers analysed the papers, assessed the risk of bias and extracted data on teeth used, sample size, size of root canal preparation, type of MTA-based material, irrigants, canal filling method, storage method and duration, region of roots and the parameters of push-out testing (slice thickness, plunger dimensions and plunger loading direction), the main results and dislocation resistance values (in MPa). From 255 studies, 27 were included for full-text analysis. Eight papers that met the inclusion criteria were included in this review. There was a wide variation in dislocation resistance due to differences in irrigation sequence, time and concentration of irrigants, storage method and duration, and the parameters of push-out bond strength testing. A meta-analysis was not done but qualitative synthesis of the included studies was performed. No definitive conclusion could be drawn to evaluate the effect of irrigation protocols on dislocation resistance of MTA-based materials. Recommendations have been provided for standardized testing methods and reporting of future studies, so as to obtain clinically relevant information and to understand the effects of irrigating protocols on root canal sealers and their interactions with the dentine walls of root canals.
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Sodium zirconium cyclosilicate: a new potassium binder for the treatment of hyperkalemia.
Cases, A, Gorriz, JL
Drugs of today (Barcelona, Spain : 1998). 2018;(10):601-613
Abstract
Hyperkalemia is one of the most common electrolyte disturbances, especially among some groups of patients, such as in those with chronic kidney disease, diabetes or heart failure. Hyperkalemia has been associated with increased risks of mortality, arrhythmias, hospitalization and costs, as well as the need to down titrate/discontinue renin-angiotensin-aldosterone system inhibitors (RAASIs), despite their well-known cardiovascular and nephroprotective benefits. Current potassium binders have limitations (slow onset of action, limited selectivity for potassium binding, risk of drug interactions or gastrointestinal intolerance). Sodium zirconium cyclosilicate (SZC) is a new potassium binder recently approved for the treatment of chronic hyperkalemia. It is a nonabsorbable, inorganic crystal which selectively binds potassium and ammonium in exchange of Na+ and H+ in the whole gastrointestinal tract, achieving a rapid correction of serum potassium levels (within 2 days) and maintaining normokalemia in the long term (up to 1 year), with a good safety profile (common adverse reactions include gastrointestinal events and a dose-dependent risk of edema), excellent tolerability and a low potential for drug interactions. Its potassium-lowering efficacy is maintained irrespective of the use of RAASIs. In summary, SZC is a new potassium binder recently approved for the treatment of hyperkalemia. Its differences with respect to currently available potassium binders make SZC an attractive therapeutic option.
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Gene Expression Profiling and Molecular Signaling of Various Cells in Response to Tricalcium Silicate Cements: A Systematic Review.
Rathinam, E, Rajasekharan, S, Chitturi, RT, Declercq, H, Martens, L, De Coster, P
Journal of endodontics. 2016;(12):1713-1725
Abstract
INTRODUCTION The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different variants of tricalcium silicate cements (TSCs). METHODS A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing any cell type except dental pulp stem cells and any variant of tricalcium silicate cement either as the experimental or as the control group were included. RESULTS A total of 41 relevant articles were included in this review. Among the included studies, ProRoot MTA (Dentsply, Tulsa, OK) was the most commonly studied (69.1%) TSC variant, and 11 cell types were identified, with 13 articles investigating gene expression in osteoblasts. A total of 39 different genes/molecules expressed were found in the selected studies. The experimental group (irrespective of the TSC variant) was identified to express significantly increased gene expression compared with the control group (untreated) in all included studies. Recent studies have provided useful insight into the gene expression and molecular signaling of various cells in response to TSCs, and new elements have been supplied on the pathways activated in this process. CONCLUSIONS TSCs are capable of eliciting a favorable cellular response in periapical regeneration.
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New potassium binders for the treatment of hyperkalemia: current data and opportunities for the future.
Pitt, B, Bakris, GL
Hypertension (Dallas, Tex. : 1979). 2015;(4):731-8
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Gene Expression Profiling and Molecular Signaling of Dental Pulp Cells in Response to Tricalcium Silicate Cements: A Systematic Review.
Rathinam, E, Rajasekharan, S, Chitturi, RT, Martens, L, De Coster, P
Journal of endodontics. 2015;(11):1805-17
Abstract
INTRODUCTION Signaling molecules and responding dental pulp stem cells are the 2 main control keys of dentin regeneration/dentinogenesis. The aim of this study was to present a systematic review investigating the gene expression of various dental pulp cells in response to different variants of tricalcium silicate cements. METHODS A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing all sorts of dental pulp cells (DPCs) and any variant of tricalcium silicate cement either as the experimental or as the control group were included. RESULTS A total of 39 articles were included in the review. Among the included studies, ProRoot MTA (Dentsply, Tulsa Dental, OK) was the most commonly used tricalcium silicate cement variant. The extracellular signal regulated kinase/mitogen-activated protein kinase pathway was the most commonly activated pathway to be identified, and similarly, dentin sialophosphoprotein osteocalcin dentin matrix acidic phosphoprotein 1, alkaline phosphatase, bone sialoprotein, osteopontin, type I collagen, and Runx2 were the most commonly expressed genes in that order of frequency. CONCLUSIONS Biodentine (Septodont Ltd, Saint Maur des Faussés, France), Bioaggregate (Innovative Bioceramix, Vancouver, BC, Canada), and mineral trioxide aggregate stimulate the osteogenic/odontogenic capacity of DPCs by proliferation, angiogenesis, and biomineralization through the activation of the extracellular signal regulated kinase ½, nuclear factor E2 related factor 2, p38, c-Jun N-terminal kinase mitogen-activated protein kinase, p42/p44 mitogen-activated protein kinase, nuclear factor kappa B, and fibroblast growth factor receptor pathways. When DPCs are placed into direct contact with tricalcium silicate cements, they show higher levels of gene activation, which in turn could translate into more effective pulpal repair and faster and more predictable formation of reparative dentin.
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A review of the bioactivity of hydraulic calcium silicate cements.
Niu, LN, Jiao, K, Wang, TD, Zhang, W, Camilleri, J, Bergeron, BE, Feng, HL, Mao, J, Chen, JH, Pashley, DH, et al
Journal of dentistry. 2014;(5):517-33
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Abstract
OBJECTIVES In tissue regeneration research, the term "bioactivity" was initially used to describe the resistance to removal of a biomaterial from host tissues after intraosseous implantation. Hydraulic calcium silicate cements (HCSCs) are putatively accepted as bioactive materials, as exemplified by the increasing number of publications reporting that these cements produce an apatite-rich surface layer after they contact simulated body fluids. METHODS In this review, the same definitions employed for establishing in vitro and in vivo bioactivity in glass-ceramics, and the proposed mechanisms involved in these phenomena are used as blueprints for investigating whether HCSCs are bioactive. RESULTS The literature abounds with evidence that HCSCs exhibit in vitro bioactivity; however, there is a general lack of stringent methodologies for characterizing the calcium phosphate phases precipitated on HCSCs. Although in vivo bioactivity has been demonstrated for some HCSCs, a fibrous connective tissue layer is frequently identified along the bone-cement interface that is reminiscent of the responses observed in bioinert materials, without accompanying clarifications to account for such observations. CONCLUSIONS As bone-bonding is not predictably achieved, there is insufficient scientific evidence to substantiate that HCSCs are indeed bioactive. Objective appraisal criteria should be developed for more accurately defining the bioactivity profiles of HCSCs designed for clinical use.
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Will mineral trioxide aggregate replace calcium hydroxide in treating pulpal and periodontal healing complications subsequent to dental trauma? A review.
Bakland, LK, Andreasen, JO
Dental traumatology : official publication of International Association for Dental Traumatology. 2012;(1):25-32
Abstract
Mineral trioxide aggregate (MTA) has over the last two decades begun to take the place of calcium hydroxide (CH) in the treatment of a variety of pulpal and periodontal healing complications following dental trauma. These conditions include teeth with: (i) exposed pulps, (ii) immature roots and pulp necrosis, (iii) root fractures and pulp necrosis located in the coronal part of the pulps, and (iv) external infection-related (inflammatory) root resorption. The main reasons for replacing CH with MTA in these situations have generally been the delayed effect when using CH to induce hard tissues, the quality of such induced hard tissues, and finally the dentin weakening effect of CH, which in some instances lead to cervical root fractures in immature teeth. MTA appears, from a relatively few clinical studies, to overcome these shortcomings of CH. The lack of long-term clinical studies, however, may warrant a certain reservation in an unrestricted replacement of CH with MTA. A definite need for randomized clinical studies comparing CH and MTA in trauma healing situations is urgently needed.