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1.
Factors associated with heart failure hospitalization in patients with high sodium excretion: subanalysis of the ESPRIT, evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients, cohort study.
Sadanaga, T, Hirota, S, Mitamura, H
Heart and vessels. 2021;(1):85-91
Abstract
We have reported that high sodium excretion ≥ 4.0 g/day, assessed by repeated measurements of spot urine, is associated with composite cardiovascular (CV) events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and documented CV deaths in Japanese high-risk patients with either stable and compensated congestive HF, high brain natriuretic peptide, coronary artery disease, cerebrovascular disease, chronic kidney disease, or atrial fibrillation. A total of 520 patients were enrolled. During the median follow-up period of 5.2 years, 105 (20%) experienced composite CV events, which were predominantly driven by 60 (12%) HF hospitalizations. The aim of the present study was to elucidate which subgroups of patients with high sodium excretion were associated with HF hospitalization. We divided the enrolled patients into three groups according to the amount of sodium excretion (< 3.0 g/day, 3.0-3.99 g/day (reference), and ≥ 4.0 g/day) based on a median of 14 measurements during follow-up. We assessed the hazard ratio for HF hospitalization according to age, bodyweight, and gender, using the Cox hazard model. In the total population, high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization [hazard ratio (HR) 1.75, confidence interval (CI) 1.05-2.83] after adjustment for gender, age, and bodyweight, but was not associated with other CV events. In older patients (≥ 75 years old), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for gender and bodyweight (HR 3.25, CI 1.55-6.55), which was not observed in younger (< 75 years old) patients. In patients with lower bodyweight (< 60 kg), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for age and gender (HR 3.05, CI 1.34-6.61), which was not observed in heavier (≥ 60 kg) patients. High sodium excretion is associated with HF hospitalization in patients with older age and lower bodyweight in Japanese high-risk patients.
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2.
The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.
Raimann, JG, Chan, CT, Daugirdas, JT, Depner, T, Greene, T, Kaysen, GA, Kliger, AS, Kotanko, P, Larive, B, Beck, G, et al
Kidney & blood pressure research. 2021;(6):768-776
Abstract
INTRODUCTION The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity. METHODS Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis. RESULTS In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance. DISCUSSION/CONCLUSION In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.
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3.
Plasma sodium, extracellular fluid volume, and blood pressure in healthy men.
van den Bosch, JJJON, Hessels, NR, Visser, FW, Krikken, JA, Bakker, SJL, Riphagen, IJ, Navis, GJ
Physiological reports. 2021;(24):e15103
Abstract
In the general population we recently reported a consistent association between plasma sodium and volume markers, suggesting that individuals with higher plasma sodium have higher extracellular fluid volume (ECFV). To test this hypothesis, we analyzed the association between plasma sodium and directly measured ECFV (iothalamate distribution volume) in healthy men. Second, we studied whether plasma sodium is associated with blood pressure. We analyzed data from 70 men (age 24 ± 7 years) at the end of two 7-day periods on a low-sodium diet (LS, 50 mmol Na/24 h) and a high-sodium diet (HS, 200 mmol Na/24 h), respectively. The association of plasma sodium with blood pressure was assessed in the combined data of the different sodium intakes by linear mixed effects models. A positive univariable association between plasma sodium and ECFV was found during HS (β = 0.24, p = 0.042) and LS (β = 0.23, p = 0.058), respectively. Individual values of plasma sodium on LS and HS diet were strongly correlated (β = 0.68, p < 0.001), as were values for ECFV (β = 0.54, p < 0.001). In the combined data set plasma sodium level was significantly associated with ECFV (B [SE] = 0.10 [0.04], p = 0.02), and systolic blood pressure (SBP, B [SE] = 0.73 [0.26], p = 0.006), independent of ECFV. In conclusion, plasma sodium concentration is positively associated with ECFV on both LS and HS intake. Our data confirm and extend prior data on individual regulation of plasma sodium and suggest that this is associated with individuality of the regulation of ECFV. Finally, plasma sodium level is associated with SBP, independent of ECFV and diet.
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4.
Serum sodium on admission affects postoperative in-hospital mortality in acute aortic dissection patients.
Huang, P, Wang, H, Ma, D, Zhao, Y, Liu, X, Su, P, Zhang, J, Ma, S, Pan, Z, Shi, J, et al
PloS one. 2021;(12):e0261168
Abstract
BACKGROUND Acute aortic dissection (AAD) is very fatal without surgical treatment. Higher serum sodium can increase in-hospital mortality of many diseases; however, the effect of serum sodium on postoperative in-hospital mortality in AAD patients remains unknown. METHODS We collected a total of 415 AAD patients from January 2015 to December 2019. Patients were classified into four categories (Q1-Q4) according to the admission serum sodium quartile. The cox proportional hazards model evaluated the association between serum sodium and in-hospital mortality. All-cause in-hospital mortality was set as the endpoint. RESULTS By adjusting many covariates, cox proportional hazards model revealed the in-hospital mortality risk of both Q3 and Q4 groups was 3.086 (1.242-7.671, P = 0.015) and 3.370 (1.384-8.204, P = 0.007) respectively, whereas the risk of Q2 group was not significantly increased. Univariate and multiple Cox analysis revealed that Stanford type A, serum glucose, α-hydroxybutyrate dehydrogenase and serum sodium were risk factors correlated with in-hospital death in AAD patients. CONCLUSION The study indicates that the admission serum sodium of AAD patients has a vital impact on postoperative hospital mortality.
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5.
Sodium Abnormalities in Cardiac Surgery With Cardiopulmonary Bypass in Adults: A Narrative Review.
Leong, XF, Cheng, M, Jong, B, Hwang, NC, Roscoe, A
Journal of cardiothoracic and vascular anesthesia. 2021;(11):3374-3384
Abstract
Perioperative sodium abnormalities or dysnatremia is not uncommon in patients presenting for cardiac surgery and is associated with increased morbidity and mortality. Both the disease process of heart failure and its treatment may contribute to abnormalities in serum sodium concentration. Serum sodium is the main determinant of serum osmolality, which in turn affects cell volume. Brain cells are particularly vulnerable to changes in serum osmolality because of the nondistensible cranium. The potentially catastrophic neurologic sequelae of rapidly correcting chronic dysnatremia and the time-sensitive nature of cardiac surgery can make the management of these patients challenging. The use of cardiopulmonary bypass to facilitate surgery adds another layer of complexity in the intraoperative management of sodium and water balance. This narrative review examines the definition and classification of dysnatremia. It also covers the etiology and pathophysiology of dysnatremia, implications during cardiac surgery requiring cardiopulmonary bypass, and the perioperative management of dysnatremia.
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6.
Serum Sodium Concentration and Mental Status in Children With Diabetic Ketoacidosis.
Glaser, NS, Stoner, MJ, Garro, A, Baird, S, Myers, SR, Rewers, A, Brown, KM, Trainor, JL, Quayle, KS, McManemy, JK, et al
Pediatrics. 2021;(3)
Abstract
OBJECTIVES Diabetic ketoacidosis (DKA) is typically characterized by low or low-normal serum sodium concentrations, which rise as hyperglycemia resolves. In retrospective studies, researchers found associations between declines in sodium concentrations during DKA and cerebral injury. We prospectively investigated determinants of sodium concentration changes and associations with mental status alterations during DKA. METHODS Using data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis Trial, we compared children who had declines in glucose-corrected sodium concentrations with those who had rising or stable concentrations. Children were randomly assigned to 1 of 4 intravenous fluid protocols that differed in infusion rate and sodium content. Data from the first 4, 8, and 12 hours of treatment were analyzed for 1251, 1086, and 877 episodes, respectively. RESULTS In multivariable analyses, declines in glucose-corrected sodium concentrations were associated with higher sodium and chloride concentrations at presentation and with previously diagnosed diabetes. Treatment with 0.45% (vs 0.9%) sodium chloride fluids was also associated with declines in sodium concentration; however, higher rates of fluid infusion were associated with declines in sodium concentration only at 12 hours. Frequencies of abnormal Glasgow Coma Scale scores and clinical diagnoses of cerebral injury were similar in patients with and without declines in glucose-corrected sodium concentrations. CONCLUSIONS Changes in glucose-corrected sodium concentrations during DKA treatment are influenced by the balance of free-water loss versus sodium loss at presentation and the sodium content of intravenous fluids. Declines in glucose-corrected sodium concentrations are not associated with mental status changes during treatment.
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7.
Evolving Escherichia coli Host Strains for Efficient Deuterium Labeling of Recombinant Proteins Using Sodium Pyruvate-d3.
Kelpšas, V, Leung, A, von Wachenfeldt, C
International journal of molecular sciences. 2021;(18)
Abstract
Labeling of proteins with deuterium (2H) is often necessary for structural biology techniques, such as neutron crystallography, NMR spectroscopy, and small-angle neutron scattering. Perdeuteration in which all protium (1H) atoms are replaced by deuterium is a costly process. Typically, expression hosts are grown in a defined medium with heavy water as the solvent, which is supplemented with a deuterated carbon source. Escherichia coli, which is the most widely used host for recombinant protein production, can utilize several compounds as a carbon source. Glycerol-d8 is often used as a carbon source for deuterium labelling due to its lower cost compered to glucose-d7. In order to expand available options for recombinant protein deuteration, we investigated the possibility of producing a deuterated carbon source in-house. E. coli can utilize pyruvate as a carbon source and pyruvate-d3 can be made by a relatively simple procedure. To circumvent the very poor growth of E. coli in minimal media with pyruvate as sole carbon source, adaptive laboratory evolution for strain improvement was applied. E. coli strains with enhanced growth in minimal pyruvate medium was subjected to whole genome sequencing and the genetic changes were revealed. One of the evolved strains was adapted for the widely used T7 RNA polymerase overexpression systems. Using the improved strain E. coli DAP1(DE3) and in-house produced deuterated carbon source (pyruvic acid-d4 and sodium pyruvate-d3), we produce deuterated (>90%) triose-phosphate isomerase, at quantities sufficient enough for large volume crystal production and subsequent analysis by neutron crystallography.
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8.
Recent progress in understanding salinity tolerance in plants: Story of Na+/K+ balance and beyond.
Hussain, S, Hussain, S, Ali, B, Ren, X, Chen, X, Li, Q, Saqib, M, Ahmad, N
Plant physiology and biochemistry : PPB. 2021;:239-256
Abstract
High salt concentrations in the growing medium can severely affect the growth and development of plants. It is imperative to understand the different components of salt-tolerant network in plants in order to produce the salt-tolerant cultivars. High-affinity potassium transporter- and myelocytomatosis proteins have been shown to play a critical role for salinity tolerance through exclusion of sodium (Na+) ions from sensitive shoot tissues in plants. Numerous genes, that limit the uptake of salts from soil and their transport throughout the plant body, adjust the ionic and osmotic balance of cells in roots and shoots. In the present review, we have tried to provide a comprehensive report of major research advances on different mechanisms regulating plant tolerance to salinity stress at proteomics, metabolomics, genomics and transcriptomics levels. Along with the role of ionic homeostasis, a major focus was given on other salinity tolerance mechanisms in plants including osmoregulation and osmo-protection, cell wall remodeling and integrity, and plant antioxidative defense. Major proteins and genes expressed under salt-stressed conditions and their role in enhancing salinity tolerance in plants are discussed as well. Moreover, this manuscript identifies and highlights the key questions on plant salinity tolerance that remain to be discussed in the future.
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9.
Low sodium and tolvaptan have opposite effects in human small cell lung cancer cells.
Marroncini, G, Anceschi, C, Naldi, L, Fibbi, B, Baldanzi, F, Martinelli, S, Polvani, S, Maggi, M, Peri, A
Molecular and cellular endocrinology. 2021;:111419
Abstract
PURPOSE Hyponatraemia is frequently observed in cancer patients and can be due to the syndrome of inappropriate anti-diuresis (SIAD), related to ectopic vasopressin secretion, particularly in small cell lung cancer (SCLC). Hyponatraemia is associated with a worse outcome in cancer patients. The vasopressin receptor antagonist tolvaptan effectively corrects hyponatraemia secondary to SIAD and there is in vitro evidence that it has also an antiproliferative effect in cancer cells. The purpose of this study was i) to analyse the effect of low serum sodium concentrations ([Na+]) in SCLC cells and ii) to determine whether tolvaptan counteracts tumor progression. METHODS We evaluated cell proliferation, cell cycle, apoptosis, oxidative stress, invasivity in low [Na+] as well as after exposure to tolvaptan. We also analysed the intracellular signalling pathways involved. RESULTS In reduced [Na+] cell proliferation was significantly increased compared to normal [Na+] and cells were mostly distributed in the G2/M phase. Apoptosis appeared reduced. In addition, the ability to cross matrigel-coated membranes markedly increased. As observed in other cancer cell models, the expression of the heme-oxigenase-1 gene was increased. Finally, we found that in cells cultured in low [Na+] the RhoA/ROCK1/2 pathway, which is involved in the regulation of actin cytoskeleton, was activated. On the other hand, we found that tolvaptan effectively inhibited cell proliferation, anchorage-independent growth, invasivity and promoted apoptosis. Accordingly, the RhoA/ROCK-1/2 pathway was inhibited. CONCLUSIONS These findings demonstrate for the first time that low [Na+] favours tumor progression in SCLC cells, whereas tolvaptan effectively inhibits cell proliferation, survival and invasivity.
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10.
Plant HKT Channels: An Updated View on Structure, Function and Gene Regulation.
Riedelsberger, J, Miller, JK, Valdebenito-Maturana, B, Piñeros, MA, González, W, Dreyer, I
International journal of molecular sciences. 2021;(4)
Abstract
HKT channels are a plant protein family involved in sodium (Na+) and potassium (K+) uptake and Na+-K+ homeostasis. Some HKTs underlie salt tolerance responses in plants, while others provide a mechanism to cope with short-term K+ shortage by allowing increased Na+ uptake under K+ starvation conditions. HKT channels present a functionally versatile family divided into two classes, mainly based on a sequence polymorphism found in the sequences underlying the selectivity filter of the first pore loop. Physiologically, most class I members function as sodium uniporters, and class II members as Na+/K+ symporters. Nevertheless, even within these two classes, there is a high functional diversity that, to date, cannot be explained at the molecular level. The high complexity is also reflected at the regulatory level. HKT expression is modulated at the level of transcription, translation, and functionality of the protein. Here, we summarize and discuss the structure and conservation of the HKT channel family from algae to angiosperms. We also outline the latest findings on gene expression and the regulation of HKT channels.