Sodium regulates clock time and output via an excitatory GABAergic pathway.

The suprachiasmatic nucleus (SCN) serves as the body's master circadian clock that adaptively coordinates changes in physiology and behaviour in anticipation of changing requirements throughout the 24-h day-night cycle1-4. For example, the SCN opposes overnight adipsia by driving water intake before sleep5,6, and by driving the secretion of anti-diuretic hormone7,8 and lowering body temperature9,10 to reduce water loss during sleep11. These responses can also be driven by central osmo-sodium sensors to oppose an unscheduled rise in osmolality during the active phase12-16. However, it is unknown whether osmo-sodium sensors require clock-output networks to drive homeostatic responses. Here we show that a systemic salt injection (hypertonic saline) given at Zeitgeber time 19-a time at which SCNVP (vasopressin) neurons are inactive-excited SCNVP neurons and decreased non-shivering thermogenesis (NST) and body temperature. The effects of hypertonic saline on NST and body temperature were prevented by chemogenetic inhibition of SCNVP neurons and mimicked by optogenetic stimulation of SCNVP neurons in vivo. Combined anatomical and electrophysiological experiments revealed that osmo-sodium-sensing organum vasculosum lamina terminalis (OVLT) neurons expressing glutamic acid decarboxylase (OVLTGAD) relay this information to SCNVP neurons via an excitatory effect of γ-aminobutyric acid (GABA). Optogenetic activation of OVLTGAD neuron axon terminals excited SCNVP neurons in vitro and mimicked the effects of hypertonic saline on NST and body temperature in vivo. Furthermore, chemogenetic inhibition of OVLTGAD neurons blunted the effects of systemic hypertonic saline on NST and body temperature. Finally, we show that hypertonic saline significantly phase-advanced the circadian locomotor activity onset of mice. This effect was mimicked by optogenetic activation of the OVLTGAD→ SCNVP pathway and was prevented by chemogenetic inhibition of OVLTGAD neurons. Collectively, our findings provide demonstration that clock time can be regulated by non-photic physiologically relevant cues, and that such cues can drive unscheduled homeostatic responses via clock-output networks.

Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation.

The bone-derived hormone fibroblast growth factor-23 (FGF23) has recently received much attention due to its association with chronic kidney disease and cardiovascular disease progression. Extracellular sodium concentration ([Na+]) plays a significant role in bone metabolism. Hyponatremia (lower serum [Na+]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na+] on FGF23 production. Here, we show that an elevated [Na+] (+20 mM) suppressed FGF23 formation, whereas low [Na+] (-20 mM) increased FGF23 synthesis in the osteoblast-like cell lines UMR-106 and MC3T3-E1. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. Furthermore, arginine vasopressin, which is often responsible for hyponatremia, did not affect FGF23 production. Next, we performed a comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low versus high [Na+], which revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9-mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na+]-mediated FGF23 regulation. In line with these in vitro observations, we found that hyponatremia patients have higher FGF23 levels. Our results suggest that [Na+] is a critical regulator of FGF23 synthesis.

Chemosensory modulation of neural circuits for sodium appetite.

Sodium is the main cation in the extracellular fluid and it regulates various physiological functions. Depletion of sodium in the body increases the hedonic value of sodium taste, which drives animals towards sodium consumption1,2. By contrast, oral sodium detection rapidly quenches sodium appetite3,4, suggesting that taste signals have a central role in sodium appetite and its satiation. Nevertheless, the neural mechanisms of chemosensory-based appetite regulation remain poorly understood. Here we identify genetically defined neural circuits in mice that control sodium intake by integrating chemosensory and internal depletion signals. We show that a subset of excitatory neurons in the pre-locus coeruleus express prodynorphin, and that these neurons are a critical neural substrate for sodium-intake behaviour. Acute stimulation of this population triggered robust ingestion of sodium even from rock salt, while evoking aversive signals. Inhibition of the same neurons reduced sodium consumption selectively. We further demonstrate that the oral detection of sodium rapidly suppresses these sodium-appetite neurons. Simultaneous in vivo optical recording and gastric infusion revealed that sodium taste-but not sodium ingestion per se-is required for the acute modulation of neurons in the pre-locus coeruleus that express prodynorphin, and for satiation of sodium appetite. Moreover, retrograde-virus tracing showed that sensory modulation is in part mediated by specific GABA (γ-aminobutyric acid)-producing neurons in the bed nucleus of the stria terminalis. This inhibitory neural population is activated by sodium ingestion, and sends rapid inhibitory signals to sodium-appetite neurons. Together, this study reveals a neural architecture that integrates chemosensory signals and the internal need to maintain sodium balance.

Effects of altered salt intake and diet on cytokines in humans: A 20-week randomized cross-over intervention study.

High sodium concentration alters leukocyte activation, and in particular T-helper (Th) lymphocyte polarization, and drives the development of autoimmune diseases in mouse studies. Similar results have been obtained with human leukocytes under in vitro settings and in few observational studies. Therefore, salt has been implicated as a risk factor for autoimmune diseases. Here, we examined whether physiologically relevant changes in salt intake or diet alter cytokine concentrations. In a 20-wk double-blinded, placebo-controlled study 106 participants were randomized to Habitual and Healthy Nordic diets, and further to Usual Sodium and Reduced Sodium intake groups using a cross-over setup. Plasma concentrations of 45 cytokines were measured at three different time-points using a multiplex assay. Repeated analyses of covariance revealed that high salt ingestion (or changes in the diet) did not induce significant changes in any of the signature cytokines controlling Th1, Th2 or Th17 polarization. Several other pro-inflammatory interleukins, chemokines and growth factors were also unaffected by the level of salt intake or changes in the diet. We conclude that in humans clinically relevant changes in salt intake or diet do not have reflections on the systemic concentrations of pro-inflammatory cytokines in vivo.

Unraveling the impact of pH, sodium concentration, and medium osmolality on Vibrio natriegens in batch processes.

BACKGROUND: Vibrio natriegens, a halophilic marine γ-proteobacterium, holds immense biotechnological potential due to its remarkably short generation time of under ten minutes. However, the highest growth rates have been primarily observed on complex media, which often suffer from batch-to-batch variability affecting process stability and performance. Consistent bioprocesses necessitate the use of chemically defined media, which are usually optimized for fermenters with pH and dissolved oxygen tension (DOT) regulation, both of which are not applied during early-stage cultivations in shake flasks or microtiter plates. Existing studies on V. natriegens' growth on mineral media report partially conflicting results, and a comprehensive study examining the combined effects of pH buffering, sodium concentration, and medium osmolality is lacking. RESULTS: This study evaluates the influence of sodium concentration, pH buffering, and medium osmolality on the growth of V. natriegens under unregulated small-scale conditions. The maximum growth rate, time of glucose depletion, as well as the onset of stationary phase were observed through online-monitoring the oxygen transfer rate. The results revealed optimal growth conditions at an initial pH of 8.0 with a minimum of 300 mM MOPS buffer for media containing 20 g/L glucose or 180 mM MOPS for media with 10 g/L glucose. Optimal sodium chloride supplementation was found to be between 7.5 and 15 g/L, lower than previously reported ranges. This is advantageous for reducing industrial corrosion issues. Additionally, an osmolality range of 1 to 1.6 Osmol/kg was determined to be optimal for growth. Under these optimized conditions, V. natriegens achieved a growth rate of 1.97 ± 0.13 1/h over a period of 1 h at 37 °C, the highest reported rate for this organism on a mineral medium. CONCLUSION: This study provides guidelines for cultivating V. natriegens in early-stage laboratory settings without pH and DOT regulation. The findings suggest a lower optimal sodium chloride range than previously reported and establish an osmolality window for optimal growth, thereby advancing the understanding of V. natriegens' physiology. In addition, this study offers a foundation for future research into the effects of different ions and carbon sources on V. natriegens.

Salt restriction for treatment of hypertension - current state and future directions.

PURPOSE OF REVIEW: Given the adverse effects of excess dietary sodium chloride (also known as table salt) on blood pressure (BP) and cardiovascular disease (CVD), restriction of dietary sodium is recommended by numerous guidelines. The strictest of these recommend no more than 1.5 g/day of dietary sodium among hypertensive persons. However, average dietary sodium intake in the population is closer to 5 g/day and there is debate about whether too much sodium restriction may be associated with increased CVD risk. Herein, we aim to provide a balanced update on this topic. RECENT FINDINGS: In 2021, the Salt Substitute and Stroke Study (SSaSS) demonstrated a significant reduction in BP, CVD, and death among Chinese adults randomized to a low sodium salt-substitute supplemented with potassium. This trial largely puts to rest any remaining debate about the benefits of dietary sodium restriction among persons with excess baseline intake (dietary sodium intake fell from approximately 5 down to 4 g/day in the active arm of SSaSS). However, whether achieving and maintaining a dietary sodium of less than1.5 g/day is feasible in real-world settings and whether this low an intake is harmful remain open questions. SUMMARY: Aiming for sodium intakes of 2--3 g/day in the general population and as low as 2 g/day in persons with hypertension or CVD seems most reasonable, but there is some uncertainty around lower targets.

Combining the Physical-Chemical Approach with Standard Base Excess to Understand the Compensation of Respiratory Acid-Base Derangements: An Individual Participant Meta-analysis Approach to Data from Multiple Canine and Human Experiments.

BACKGROUND: Several studies explored the interdependence between Paco2 and bicarbonate during respiratory acid-base derangements. The authors aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical-chemical approach, hypothesizing that (1) bicarbonate concentration during respiratory derangements is associated with strong ion difference; and (2) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess. METHODS: This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of Paco2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated. RESULTS: Eleven studies were included. Paco2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mM, and 32.6 and 60.0 mEq/l, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (ß-coefficient, 1.2; 95% CI, 1.2 to 1.3; P < 0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (ß-coefficient, -0.02; 95% CI, -0.11 to 0.07; P = 0.719), while a positive linear association was present in chronic studies (ß-coefficient, 1.04; 95% CI, 0.84 to 1.24; P < 0.001). CONCLUSIONS: The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.

Melatonin alters the excitability of mouse cerebellar granule neurons by inhibiting voltage-gated sodium, potassium, and calcium channels.

Besides its role in the circadian rhythm, the pineal gland hormone melatonin (MLT) also possesses antiepileptogenic, antineoplastic, and cardioprotective properties, among others. The dosages necessary to elicit beneficial effects in these diseases often far surpass physiological concentrations. Although even high doses of MLT are considered to be largely harmless to humans, the possible side effects of pharmacological concentrations are so far not well investigated. In the present study, we report that pharmacological doses of MLT (3 mM) strongly altered the electrophysiological characteristics of cultured primary mouse cerebellar granule cells (CGCs). Using whole-cell patch clamp and ratiometric Ca2+ imaging, we observed that pharmacological concentrations of MLT inhibited several types of voltage-gated Na+ , K+ , and Ca2+ channels in CGCs independently of known MLT-receptors, altering the character and pattern of elicited action potentials (APs) significantly, quickly and reversibly. Specifically, MLT reduced AP frequency, afterhyperpolarization, and rheobase, whereas AP amplitude and threshold potential remained unchanged. The altered biophysical profile of the cells could constitute a possible mechanism underlying the proposed beneficial effects of MLT in brain-related disorders, such as epilepsy. On the other hand, it suggests potential adverse effects of pharmacological MLT concentrations on neurons, which should be considered when using MLT as a pharmacological compound.

Diet supplementation with sodium pyruvate increases sleep time and lifespan in Drosophila model.

Sodium pyruvate is a natural metabolite commonly used in biological fields, including cell culture. This study investigated the effects of sodium pyruvate on the lifespan and other physiological characters of Drosophila melanogaster, by measuring feeding, fecundity, and spontaneous activity. The results indicated that 0.2 mol/L of sodium pyruvate increased the median lifespan of female flies by 8.33%. Moreover, the group sleep duration of female flies significantly increased by 53.98% when exposed to the sodium pyruvate concentration. However, the intake of sodium pyruvate did not significantly affect the fecundity or food intake of female flies. Our results also show that the effect of extending lifespan and increasing sleep time was dose-dependent and sex-specific. Our data provides the role of sodium pyruvate as an insect culture additive by enhancing survival.

Sodium dodecylbenzene sulphonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish.

1. Sodium dodecylbenzene sulphonate (SDBS) is one of the surfactants used worldwide in detergents which, due to high residual discharges, has great potential to cause ecotoxicological impacts. Therefore, the sublethal effects of SDBS on the gills and skin of male Danio rerio fish were investigated.2. The fish were distributed into three groups: GC (control), GT1 (0.25 mg/L of SDBS), and GT2 (0.5 mg/L of SDBS) and exposed for 21 days. After the experiment, histopathological analyses of the gills, histochemical analyses (counting of mucous cells), and biochemical analyses (antioxidant defense enzyme analysis, SOD, and CAT) were conducted.3. A significant increase (p < 0.05) in the incidence of circulatory disorders, progressive, and regressive alterations occurred in the GT1 and GT2 groups. Due to these changes, the total histopathological index of the gills was higher in these groups. Mucous cells in the gills and skin increased. There was an increase in SOD activity and a reduction in CAT activity in these groups. Haematology revealed neutrophilia and lymphocytosis in the blood of GT1 and GT2.4. The results clearly demonstrate that a 21-day exposure to SDBS causes severe morphophysiological damage to the gills, skin, and blood of D. rerio fish.

Effects of sodium dodecylbenzene sulfonate (SDBS) on zebrafish (Danio rerio) gills and blood.

Sodium dodecylbenzene sulfonate (SDBS) is an important surfactant used as a cleaning agent and industrial additive to remove unwanted chemicals which have been detected in the aquatic environment. The aim of this study was to examine the toxicological potential of SDBS on the gills of adult male zebrafish (Danio rerio) exposed to this chemical. For the 96 hr acute exposure, fish were divided into three groups: control, 0.25 mg/L, and 0.5 mg/L of SDBS. After the experiment, morphophysiological analyses (gill histopathology and histochemistry), oxidative stress (determination of gill activities of superoxide dismutase (SOD) and catalase (CAT)), and hematological analyses (leukocyte differentiation) were conducted. Data demonstrated that SDBS at both tested concentrations altered the histopathological index and initiated circulatory disturbances, as well as adverse, progressive, and immunological changes in the gills. In the 0.5 mg/L group, SOD activity decreased significantly, but CAT activity was not altered. Prominent blood changes observed in this group were neutrophilia and lymphocytosis. The number of mucous and chloride cells increased significantly in both groups. Taken together, our findings demonstrated that exposure of D. rerio to SDBS, even for 96 hr, produced adverse morphological and hematological effects associated with a reduction in SOD activity. Our findings indicate that exposure of aquatic species to the anionic surfactant SDBS may lead to adverse consequences associated with oxidative stress. Therefore, this study highlights the risks that this substance may pose to aquatic ecosystems and emphasizes the need for further investigations and strict regulations on its disposal.

Functional properties and skin care effects of sodium trehalose sulfate.

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.

Blood Pressure Stability and Plasma Aldosterone Reduction: The Effects of a Sodium and Bicarbonate-Rich Water - A Randomized Controlled Intervention Study.

Objective: Hypertension is a recognized risk factor for cardiovascular disease (CVD), and dietary sodium intake has been linked to its development. However, mineral water high in bicarbonate and sodium does not appear to have adverse effects on blood pressure.This study examines the effects of consuming a mineral water high in bicarbonate and sodium (HBS) compared to a low bicarbonate and sodium (LBS) mineral water on blood pressure and related factors.Methods: A randomized controlled intervention was conducted with 94 healthy participants, consuming 1,500 - 2,000 mL daily of either mineral water high in bicarbonate and sodium (HBS water, n = 49) or low in bicarbonate and sodium (LBS water, n = 45). Blood pressure, anthropometrics, and urinary calcium and sodium excretion were assessed at baseline and after 28 days. 3-day food protocols were assessed to evaluate possible dietary changes.Results: Blood pressure changes did not differ between the groups. Both normotensive and hypertensive subjects showed similar changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in response to the different test waters. Serum aldosterone decreased significantly in both groups, with a greater reduction in the HBS group. Urinary calcium excretion significantly decreased (p = 0.002) and sodium excretion increased in the HBS group. Multiple linear regression analyses indicated no association between urinary sodium excretion and systolic blood pressure increase in the HBS group (B = 0.046, p = 0.170). Changes in urinary sodium excretion did not correlate with changes in serum aldosterone in the same group (r=-0.146, p = 0.350).Conclusions: The study revealed no significant differences in blood pressure changes between individuals consuming HBS water and LBS water. Notably, the additional sodium intake from the test water was effectively excreted.Trial registration: This trial was registered in the German Clinical Trials Register (DRKS00025341, https://drks.de/search/en).

What is the context? High blood pressure is a risk factor for heart diseases, one of the leading causes of illness and death worldwide. Too much sodium in the diet has been linked to the development of high blood pressure. However, some high-sodium mineral waters appear to have a different effect on blood pressure. Researchers have demonstrated that mineral waters high in both sodium and bicarbonate may not have harmful effects on blood pressure.What is the study about? In this study, 94 healthy participants between the ages 30 to 65 were divided into two groups. One group drank high-bicarbonate, high-sodium mineral water, and the other group drank low-bicarbonate, low-sodium mineral water for four weeks. Blood pressure was measured before and at the end of the study. The participants were asked not to change their usual diet and physical activity during the study.What are the results? Blood pressure did not change differently between the two groups. Consumption of high-sodium, high-bicarbonate mineral water increased sodium intake, but sodium was effectively excreted in the urine. Moreover, aldosterone, a blood pressure regulating hormone, decreased with mineral water consumption. Its reduction is good for maintaining stable blood pressure.

Reactive oxygen species impair Na+ transport and renal components of the renin-angiotensin-aldosterone system after paraquat poisoning.

Paraquat (1,1'-dimethyl-4,4'-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur, leading to acute kidney injury (AKI) due to exacerbated reactive O2 species (ROS) production. However, the consequences of ROS exposure on ionic transport and the regulator local renin-angiotensin-aldosterone system (RAAS) still need to be elucidated at a molecular level. This study evaluated how ROS acutely influences Na+-transporting ATPases and the renal RAAS. Adult male Wistar rats received paraquat (20 mg/kg; ip). After 24 h, we observed body weight loss and elevation of urinary flow and serum creatinine. In the renal cortex, paraquat increased ROS levels, NADPH oxidase and (Na++K+)ATPase activities, angiotensin II-type 1 receptors, tumor necrosis factor-α (TNF-α), and interleukin-6. In the medulla, paraquat increased ROS levels and NADPH oxidase activity but inhibited (Na++K+)ATPase. Paraquat induced opposite effects on the ouabain-resistant Na+-ATPase in the cortex (decrease) and medulla (increase). These alterations, except for increased serum creatinine and renal levels of TNF-α and interleukin-6, were prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol; 1 mmol/L in drinking water), a stable antioxidant. In summary, after paraquat poisoning, ROS production culminated with impaired medullary function, urinary fluid loss, and disruption of Na+-transporting ATPases and angiotensin II signaling.

Synthesis and Insecticidal Evaluation of 3,5-Dicyanopyridines Against Cotton Aphids via Microwave-Assisted Multicomponent Reactions.

Certain 2-amino-6-alkoxy-4-arylpyridine-3,5-dicyanide 1a-e were prepared via a straightforward process using microwave technology rather than conventional methods. This involved reaction of arylidenemalononitrile thru propanedinitrile in the occurrence of sodium alkoxide under MW. While, their positional isomer 4-amino-6-alkoxy-2-arylpyridine-3,5-dicyanide 3a-j have been separated from the reaction of aryl aldehydes with 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 in the presence of sodium alkoxide using microwave technic. Furthermore, the insecticidal properties of all synthesized compounds were observed with respect to Cotton aphid nymphs and adults. Neonicotinoid pesticides are indicated as the most effective pesticides toward aphids and many other pests. Many insecticides are discovered as novelties. As a result, several pyridine compounds were chemical method synthesized to serve as equivalents of neonicotinoids, a broad class of insecticides. With LC50 value of 0.03 mg/L, components 3g exhibit the highest insecticidal bioactivity. This work discusses how to find new chemicals that could be used as insecticidal agents in the future.

The effect of nano silver fluoride, self-assembling peptide and sodium fluoride varnish on salivary cariogenic bacteria: a randomized controlled clinical trial.

OBJECTIVES: To compare the antibacterial effect of Nanosilver Fluoride varnish (NSF) varnish, P11-4 and Sodium Fluoride (NaF) varnish against salivary Streptococcus mutans (S. mutans) and Lactobacilli. METHODS: 66 patients aged 10-24 years old were randomly assigned to receive single application of NSF, P11-4 or NaF varnish. Baseline unstimulated saliva samples were collected before the agents were applied and S.mutans and Lactobacilli colony forming units (CFU) were counted. After one, three and six months, microbiological samples were re-assessed. Groups were compared at each time point and changes across time were assessed. Multivariable linear regression compared the effect of P11-4 and NSF to NaF on salivary S. mutans and Lactobacilli log count at various follow up periods. RESULTS: There was a significant difference in salivary S. mutans log count after 1 month between P11-4 (B= -1.29, p = 0.049) and NaF but not at other time points nor between NSF and NaF at any time point. The significant reduction in bacterial counts lasted up to one month in all groups, to three months after using P11-4 and NaF and returned to baseline values after six months. CONCLUSION: In general, the antimicrobial effect of P11-4 and NSF on salivary S. mutans and Lactobacilli was not significantly different from NaF varnish. P11-4 induced greater reduction more quickly than the two other agents and NSF antibacterial effect was lost after one month. CLINICAL RELEVANCE: NSF varnish and P11-4 have antimicrobial activity that does not significantly differ from NaF by 3 months. P11-4 has the greatest antibacterial effect after one month with sustained effect till 3 months. The antibacterial effect of NSF lasts for one month. NaF remains effective till 3 months. TRIAL REGISTRATION: This trial was prospectively registered on the clinicaltrials.gov registry with ID: NCT04929509 on 18/6/2021.

Sulfur-Oxidizing Bacteria Alleviate Salt and Cadmium Stress in Halophyte Tripolium pannonicum (Jacq.) Dobrocz.

The aim of this study was to investigate how introducing halophilic sulfur-oxidizing bacteria (SOB) Halothiobacillus halophilus to the growth substrate affects the physiological and biochemical responses of the halophyte Tripolium pannonicum (also known as sea aster or seashore aster) under salt and cadmium stress conditions. This study assessed the plant's response to these stressors and bacterial inoculation by analyzing various factors including the accumulation of elements such as sodium (Na), chloride (Cl), cadmium (Cd) and sulfur (S); growth parameters; levels of photosynthetic pigments, proline and phenolic compounds; the formation of malondialdehyde (MDA); and the plant's potential to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH). The results revealed that bacterial inoculation was effective in mitigating the deleterious effect of cadmium stress on some growth criteria. For instance, stem length was 2-hold higher, the growth tolerance index was 3-fold higher and there was a 20% increase in the content of photosynthetic pigments compared to non-inoculated plants. Furthermore, the SOB contributed to enhancing cadmium tolerance in Tripolium pannonicum by increasing the availability of sulfur in the plant's leaves, which led to the maintenance of an appropriate, about 2-fold-higher level of phenolic compounds (phenylpropanoids and flavonols), as well as chloride ions. The level of MDA decreased after bacterial application in all experimental variants except when both salt and cadmium stress were present. These findings provide novel insights into how halophytes respond to abiotic stress following inoculation of the growth medium with sulfur-oxidizing bacteria. The data suggest that inoculating the substrate with SOB has a beneficial effect on T. pannonicum's tolerance to cadmium stress.

Effect of Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs.

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2-5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS.

Color stability of bleached tooth enamel brushed with different stain-removing toothpastes.

OBJECTIVE: The effects of four toothpastes on the color stability of in-office bleached tooth specimens were determined. MATERIALS AND METHODS: We evaluated an experimental toothpaste (EXP) and three commercially available toothpastes: Colgate Optic White (OPW), Aquafresh White & Protect (AWP), and Crest 3D White (CDW). OPW, AWP, and CDW contained inorganic abrasives, whereas EXP and AWP contained sodium polyphosphate. Forty-eight randomly selected human-extracted maxillary central incisors were bleached and brushed twice daily over 30 days. We analyzed the final color difference (ΔE*ab, ΔE00 , ΔWID ), arithmetic average surface roughness (Ra) of the enamel measured on days 0 and 30, and scanning electron microscopy images of enamel surfaces and toothpastes. ΔE*ab, ΔE00 , ΔWID , and Ra were analyzed using one-way analysis of variance and Tukey's test (α = 0.05). RESULTS: ΔE*ab and ΔE00 values were significantly lower after toothbrushing with EXP, OPW, and CDW than with AWP. OPW induced the greatest positive ΔWID . Ra was significantly increased by OPW and CDW, but slightly increased by AWP, with cube-like particles, and EXP, with no particle-like structures. CONCLUSIONS: Only EXP stabilized the color of bleached teeth without increasing the enamel surface roughness. Sodium polyphosphate with approximately 10 phosphate groups was effective at removing stains. CLINICAL SIGNIFICANCE: The effect of toothpaste on the color stability of bleached teeth depends on the constituting abrasives and chemical components. Polyphosphoric acid has different stain-removal effects depending on its degree of polymerization. Additionally, although certain types of abrasives may be effective for color stability, they also increase the surface roughness of the enamel.

Salt-sensitive trait of normotensive individuals is associated with altered autonomous cardiac regulation: a randomized controlled intervention study.

Blood pressure (BP) responses to sodium intake show great variation, discriminating salt-sensitive (SS) from salt-resistant (SR) individuals. The pathophysiology behind salt sensitivity is still not fully elucidated. We aimed to investigate salt-induced effects on body fluid, vascular tone, and autonomic cardiac response with regard to BP change in healthy normotensive individuals. We performed a randomized crossover study in 51 normotensive individuals with normal body mass index and estimated glomerular filtration rate. Subjects followed both a low-Na+ diet (LSD, <50 mmol/day) and a high-Na+ diet (HSD, >200 mmol/day). Cardiac output, systemic vascular resistance (SVR), and cardiac autonomous activity, through heart rate variability and cross-correlation baroreflex sensitivity (xBRS), were assessed with noninvasive continuous finger BP measurements. In a subset, extracellular volume (ECV) was assessed by iohexol measurements. Subjects were characterized as SS if mean arterial pressure (MAP) increased ≥3 mmHg after HSD. After HSD, SS subjects (25%) showed a 6.1-mmHg (SD 1.9) increase in MAP. No differences between SS and SR in body weight, cardiac output, or ECV were found. SVR was positively correlated with Delta BP (r = 0.31, P = 0.03). xBRS and heart rate variability were significantly higher in SS participants compared to SR participants after both HSD and LSD. Sodium loading did not alter heart rate variability within groups. Salt sensitivity in normotensive individuals is associated with an inability to decrease SVR upon high salt intake that is accompanied by alterations in autonomous cardiac regulation, as reflected by decreased xBRS and heart rate variability. No discriminatory changes upon high salt were observed among salt-sensitive individuals in body weight and ECV.NEW & NOTEWORTHY Extracellular fluid expansion in normotensive individuals after salt loading is present in both salt-sensitive and salt-resistant individuals and is not discriminatory to the blood pressure response to sodium loading in a steady-state measurement. In normotensive subjects, the ability to sufficiently vasodilate seems to play a pivotal role in salt sensitivity. In a normotensive cohort, differences in sympathovagal balance are also present in low-salt conditions rather than being affected by salt loading. Whereas treatment and prevention of salt-sensitive blood pressure increase are mostly focused on renal sodium handling and extracellular volume regulation, our study suggests that an inability to adequately vasodilate and altered autonomous cardiac functioning are additional key players in the pathophysiology of salt-sensitive blood pressure increase.