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Hypertension (Dallas, Tex. : 1979) Mar 2024Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives,... (Review)
Review
Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension-potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity.
Topics: Humans; Potassium; Hypertension; Diet; Potassium Chloride; Renal Insufficiency, Chronic; Sodium Chloride, Dietary; Blood Pressure
PubMed: 38284271
DOI: 10.1161/HYPERTENSIONAHA.123.21343 -
Environmental Toxicology and Chemistry May 2024The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival...
The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4-week and longer term (12-week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24-h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24-h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4-week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4-week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12-week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097-1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Animals; Nickel; Reproduction; Water Pollutants, Chemical; Potassium Chloride; Female; Bivalvia; Unionidae
PubMed: 38488680
DOI: 10.1002/etc.5843 -
Journal of Experimental & Clinical... Sep 2023Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis....
BACKGROUND
Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis. Due to its complex composition of cellular and acellular components malignant ascites creates a unique tumor microenvironment, which mediates immunosuppression and promotes progression of disease. However, the immunosuppressive mechanisms remain poorly understood.
METHODS
In the present study, we explored the antitumor activity of healthy donor NK and T cells directed against ovarian cancer cells in presence of malignant ascites derived from patients with advanced or recurrent peritoneal carcinomatosis. A wide range of methods was used to study the effect of ascites on NK and T cells (FACS, ELISA, EliSpot, qPCR, Live-cell and confocal microscopy, Western blot and electrolyte flux assays). The ascites components were assessed using quantitative analysis (nephelometry, potentiometry and clinical chemistry) and separation methods (dialysis, ultracentrifugal filtration and lipid depletion).
RESULTS
Ascites rapidly inhibited NK cell degranulation, tumor lysis, cytokine secretion and calcium signaling. Similarly, target independent NK and T cell activation was impaired in ascites environment. We identified imbalanced electrolytes in ascites as crucial factors causing extensive immunosuppression of NK and T cells. Specifically, high sodium, low chloride and low potassium content significantly suppressed NK-mediated cytotoxicity. Electrolyte imbalance led to changes in transcription and protein expression of electrolyte channels and impaired NK and T cell activation. Selected inhibitors of sodium electrolyte channels restored intracellular calcium flux, conjugation, degranulation and transcript expression of signaling molecules. The levels of ascites-mediated immunosuppression and sodium/chloride/potassium imbalance correlated with poor patient outcome and selected molecular alterations were confirmed in immune cells from ovarian cancer patients.
CONCLUSION
Our data suggest a novel electrolyte-based mechanism of immunosuppression in malignant ascites of patients with peritoneal carcinomatosis. We show for the first time that the immunosuppression of NK cytotoxicity in coculture assays is correlated to patient poor survival. Therapeutic application of sodium channel inhibitors may provide new means for restoring immune cell activity in ascites or similar electrolyte imbalanced environments.
Topics: Humans; Female; Peritoneal Neoplasms; Ascites; Chlorides; T-Lymphocytes; Ovarian Neoplasms; Potassium; Tumor Microenvironment
PubMed: 37684704
DOI: 10.1186/s13046-023-02798-8 -
The Journal of Nutrition Sep 2023Human milk is the preferred diet for very low birth weight (VLBW, <1500 g) infants. When mother's own milk is unable to meet the needs of VLBW infants, donor human milk...
BACKGROUND
Human milk is the preferred diet for very low birth weight (VLBW, <1500 g) infants. When mother's own milk is unable to meet the needs of VLBW infants, donor human milk (DHM) is the preferred alternative. Unfortunately, the composition of DHM remains elusive and no comparative studies between preterm human milk and DHM have been performed previously.
OBJECTIVES
We aimed to analyze the nutrient content of commercial pooled DHM and compare nutrient content in DHM with that of early and mature preterm human milk.
METHODS
We analyzed nutrient content in 15 DHM samples provided from 7 commercial milk banks including calories, carbohydrate, fat, protein, sodium, chloride, potassium, zinc, calcium, phosphorus, magnesium, and vitamin D and compared each nutrient to early (7 d of life) and mature (28 d of life) preterm human milk samples (n = 28-36 per nutrient, gestational age = 28 ± 3 wk). Protein-to-energy ratio and carbohydrate-to-nonprotein energy ratio were calculated for each sample and compared.
RESULTS
Mean values for all macro- and micronutrients in DHM are reported. In comparison to early or mature preterm human milk, DHM had significantly lower protein, sodium, chloride, potassium, and zinc content. Calorie, carbohydrate, calcium, phosphorus, magnesium, and vitamin D content did not differ statistically between DHM and early or mature preterm human milk. Fat content was modestly lower in early but not mature human milk when compared with DHM.
CONCLUSIONS
We provide mean values for several macro- and micronutrients for DHM and identify key differences between DHM and preterm human milk, which may be considered when designing human milk-based feeding plans. This study was registered at clinicaltrials.gov as NCT05742815.
Topics: Infant, Newborn; Infant; Humans; Adult; Milk, Human; Infant, Premature; Calcium; Magnesium; Potassium Chloride; Nutrients; Sodium; Phosphorus; Potassium; Carbohydrates; Micronutrients; Zinc
PubMed: 37517552
DOI: 10.1016/j.tjnut.2023.07.012 -
Molecules (Basel, Switzerland) Dec 2023The flotation agent is an important collector in the production of potassium chloride and is brought into the crystallization stage with the reflux of the mother liquor....
The flotation agent is an important collector in the production of potassium chloride and is brought into the crystallization stage with the reflux of the mother liquor. Octadecylamine Hydrochloride (ODA), 1-Dodecylamine Hydrochloride (DAH) and Sodium 1-dodecanesulfonate (SDS) were selected to study their effect on the nucleation of potassium chloride. Focused Beam Reflectance Measurement was used to collect the nucleation-induced periods of KCl in the presence of flotation agents at different supersaturations. Then, empirical equations, classical nucleation theory and growth mechanism equations were employed for data analysis. It was found that the presence of flotation agents increased the nucleation sequence , and (ODA) > (SDS) > (DAH) > (HO). In addition, the interfacial energy data obtained using classical nucleation theory suggest that the flotation agents used in our paper promoted the homogeneous nucleation of KCl (reduced from 5.3934 mJ·m to 5.1434 mJ·m) and inhibited the heterogeneous nucleation of KCl (increased from 2.8054 mJ·m to 3.6004 mJ·m). This investigation also revealed that the growth of potassium chloride was consistent with the 2D nucleation-mediated growth mechanism, and the addition of flotation agent did not change the growth mechanism of potassium chloride. Finally, the particle size distribution results were exactly consistent with the order of nucleation order . The study of nucleation kinetics and growth mechanisms of different flotation agents on potassium chloride can provide guidance for optimizing the production process of potassium chloride and developing new flotation agents.
PubMed: 38067652
DOI: 10.3390/molecules28237923 -
International Journal of Nephrology and... 2023Chloride anions are the most abundant in humans. For many years, it has been believed that chloride is simply a counterion of all other cations, ensuring the... (Review)
Review
Chloride anions are the most abundant in humans. For many years, it has been believed that chloride is simply a counterion of all other cations, ensuring the electroneutrality of the extracellular space. Recent data suggests that chloride anions possess a broad spectrum of important activities that regulate vital cellular functions. It is now evident that, apart from its contribution to the electroneutrality of the extracellular space, it acts as an osmole and contributes to extracellular and intracellular volume regulation. Its anionic charge also contributes to the generation of cell membrane potential. The most interesting action of chloride anions is their ability to regulate the activity of with-no-lysine kinases, which in turn regulate the activity of sodium chloride and potassium chloride cotransporters and govern the reabsorption of salt and excretion of potassium by nephron epithelia. Chloride anions seem to play a crucial role in cell functions, such as cell volume regulation, sodium reabsorption in the distal nephron, potassium balance, and sodium sensitivity, which lead to hypertension. All of these functions are accomplished on a molecular level via complicated metabolic pathways, many of which remain poorly defined. We attempted to elucidate some of these pathways in light of recent advances in our knowledge, obtained mainly from experimental studies.
PubMed: 37601040
DOI: 10.2147/IJNRD.S417766 -
The Journal of Headache and Pain Jul 2023Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking...
BACKGROUND
Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura.
METHODS
Wistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark-light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood-brain barrier integrity in cortex was examined with Evans blue assay.
RESULTS
LVC and NTG administration robustly reduced periorbital mechanical thresholds in rats and induced anxiety-like behaviors and photophobia within 30 and 120 min, respectively. LVC induced migraine-like phenotype recovered in 2 h while NTG group did not fully recover before 4 h. Both LVC and NTG did not provoke DC (direct current) shift, EEG alterations or cortical c-fos expression characteristic to CSD. LVC did not induce de novo CSD and affect KCl (potassium chloride)-induced CSD parameters except for an increase in propagation failure. However, NTG significantly increased both CSD susceptibility and propagation failure. Somatosensory evoked potential (SSEP) configurations were not altered in both LVC and NTG groups, but SSEP latencies were prolonged after CSD. Acute LVC or NTG injection did not increase cortical BBB permeability.
CONCLUSIONS
Single LVC administration induced the fastest manifestation and recovery of acute migraine-like phenotype which was not mediated by CSD waves in the cerebral cortex. We suppose LVC triggered rapid-onset migraine-like symptoms are probably related to functional alterations in the trigeminal nociceptive system and K channel opening properties of LVC. Understanding the neurobiological mechanisms of this nociceptive window, may provide a novel target in migraine treatment.
Topics: Animals; Rats; Rats, Wistar; Cromakalim; Migraine Disorders; Cerebral Cortex; Phenotype
PubMed: 37488480
DOI: 10.1186/s10194-023-01627-9 -
Bioelectrochemistry (Amsterdam,... Aug 2023Electromagnetic radiation (EMR) is omnipresent on earth and may interact with the biological systems in diverse manners. But the scope and nature of such interactions...
Electromagnetic radiation (EMR) is omnipresent on earth and may interact with the biological systems in diverse manners. But the scope and nature of such interactions remain poorly understood. In this study, we have measured the permittivity of cells and lipid membranes over the EMR frequency range of 20 Hz to 4.35 × 10 Hz. To identify EMR frequencies that display physically intuitive permittivity features, we have developed a model-free method that relies on a potassium chloride reference solution of direct-current (DC) conductivity equal to that of the target sample. The dielectric constant, which reflects the capacity to store energy, displays a characteristic peak at 10-10 Hz. The dielectric loss factor, which represents EMR absorption, is markedly enhanced at 10-10 Hz. The fine characteristic features are influenced by the size and composition of these membraned structures. Mechanical disruption results in abrogation of these characteristic features. Enhanced energy storage at 10-10 Hz and energy absorption at 10-10 Hz may affect certain membrane activity relevant to cellular function.
Topics: Electric Conductivity; Lipids
PubMed: 37146345
DOI: 10.1016/j.bioelechem.2023.108444 -
Hypertension (Dallas, Tex. : 1979) Dec 2023Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy.
METHODS
Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone.
RESULTS
The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all <0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups.
CONCLUSIONS
KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.
Topics: Aged; Humans; Middle Aged; Antihypertensive Agents; Blood Glucose; Blood Pressure; Chlorthalidone; Citrates; Hyperglycemia; Hypertension; Potassium; Potassium Chloride; Sodium Chloride Symporter Inhibitors
PubMed: 37846572
DOI: 10.1161/HYPERTENSIONAHA.123.21932 -
Current Opinion in Cardiology May 2024To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF). (Review)
Review
PURPOSE OF REVIEW
To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF).
RECENT FINDINGS
While loop diuretic therapy has remained the backbone of decongestive treatment in AHF, multiple randomized clinical trials suggest that early combination with other diuretic classes or molecules with diuretic properties should be considered. Mineralocorticoid receptor antagonists and sodium-glucose co-transporter-2 inhibitors are disease-modifying drugs in heart failure that favourably influence prognosis early on, advocating their start as soon as possible in the absence of any compelling contraindications. Short-term upfront use of acetazolamide in adjunction to intravenous loop diuretic therapy relieves congestion faster, avoids diuretic resistance, and may shorten hospitalization length. Thiazide-like diuretics remain a good option to break diuretic resistance. Currently, ultrafiltration in AHF remains mainly reserved for patient with an inadequate response to pharmacological treatment.
SUMMARY
In most patients with AHF, decongestion can be achieved effectively and safely through combination diuretic therapies. Appropriate diuretic therapy may shorten hospitalization length and improve quality of life, but has not yet proven to reduce death or heart failure readmissions. Ultrafiltration currently has a limited role in AHF, mainly as bail-out strategy, but evidence for a more upfront use remains inconclusive.
Topics: Humans; Sodium Potassium Chloride Symporter Inhibitors; Ultrafiltration; Quality of Life; Diuretics; Heart Failure; Acute Disease
PubMed: 38362936
DOI: 10.1097/HCO.0000000000001124