The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital cortex compared to controls. No change of total sodium concentration was observed in the amygdala, pre- and postcentral gyrus, frontal and temporal cortices or in the cerebellum. This is the first in vivo sodium MR imaging study carried out on a 4 T MR scanner in Huntington's disease gene carriers demonstrating a significant enhancement in sodium concentration in the bilateral striatum, a key region in Huntington's disease, and also in other disease-related atrophic areas. Sodium MR imaging may provide a deeper insight into the pathophysiological mechanisms of tissue degeneration in Huntington's disease, presenting potential to detect changes preceding neurodegeneration.

Our aim was to analyze the participation of inhibitory and stimulatory signals in the temporal dissociation between sodium depletion (SD) induced by peritoneal dialysis (PD) and the appearance of sodium appetite (SA), particularly 2h after PD, when the rats are hypovolemic/natremic but SA is not evident. We investigated the effects of bilateral injections of the serotonin (5-HT) receptor antagonist, methysergide, into the lateral parabrachial nucleus (LPBN) on hypertonic NaCl and water intake 2h vs. 24h after PD. We also studied plasma renin activity (PRA) and aldosterone (ALDO) concentration 2h vs. 24h after PD. Additionally, we combined the analysis of brain Fos immunoreactivity (Fos-ir) with the detection of double immunoreactivity in 5HT and oxytocinergic (OT) cells 2h after PD. Bilateral LPBN injections of methysergide (4μg/200nl at each site) increased NaCl intake when tested 2h after PD compared to controls. We found a significant increase in PRA and ALDO concentration after PD but no differences between 2 and 24h after PD. We also found for the first time a significant increase 2h after PD in the number of Fos-ir neurons in the brainstem nuclei that have been shown to be involved in the inhibition of SA. In summary, the results show that 5HT-mechanisms in the LPBN modulate sodium intake during the delay of SA when the renin angiotensin aldosterone system (RAAS) is increased. In addition, the activation of brainstem areas previously associated with the satiety phase of SA is in part responsible for the temporal dissociation between SD and behavioral arousal.

The objectives of this paper are to first present physiological and ecological aspects of the unique motivational state of sodium appetite, then to focus on systemic physiology and brain mechanisms. I describe how laboratory protocols have been developed to allow the study of sodium appetite under controlled conditions, and focus on two such conditions specifically. The first of these is the presentation a sodium-deficient diet (SDD) for at least one week, and the second is accelerated sodium loss using SDD for 1-2 days coupled with the diuretic furosemide. The modality of consumption is also considered, ranging from a free intake of high concentration of sodium solution, to sodium-rich food or gels, and to operant protocols. I describe the pivotal role of angiotensin and aldosterone in these appetites and discuss whether the intakes or appetite are matched to the physiological need state. Several brain systems have been identified, most recently and microscopically using molecular biological methods. These include clusters in both the hindbrain and the forebrain. Satiation of sodium appetite is often studied using concentrated sodium solutions, but these can be consumed in apparent excess, and I suggest that future studies of satiation might emulate natural conditions in which excess consumption does not occur, using either SDD only as a stimulus, offering a sodium-rich food for the assessment of appetite, or a simple operant task.

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Nav1.7 or the cardiac sodium channel Nav1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Nav1.7 and 0.43 mM for Nav1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Nav1.7 and Nav1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Nav1.7 and Nav1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Nav1.7 or show cardiotoxicity by blocking Nav1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

Single-ion selectivity with high precision has long been pursued for fundamental bioinspired engineering and applications such as in ion separation and energy conversion. However, it remains a challenge to develop artificial ion channels to achieve single-ion selectivity comparable to their biological analogs, especially for high Na+/K+ selectivity. Here, we report an artificial sodium channel by subnanoconfinement of 4'-aminobenzo-15-crown-5 ethers (15C5s) into ~6-Å-sized metal-organic framework subnanochannel (MOFSNC). The resulting 15C5-MOFSNC shows an unprecedented Na+/K+ selectivity of tens to 102 and Na+/Li+ selectivity of 103 under multicomponent permeation conditions, comparable to biological sodium channels. A co-ion-responsive single-file transport mechanism in 15C-MOFSNC is proposed for the preferential transport of Na+ over K+ due to the synergetic effects of size exclusion, charge selectivity, local hydrophobicity, and preferential binding with functional groups. This study provides an alternative strategy for developing potential single-ion selective channels and membranes for many applications.

Unsaturated oxidative formaldehyde is a noxious aldehyde in cigarette smoke that causes edematous acute lung injury. However, the mechanistic effects of formaldehyde on lung fluid transport are still poorly understood. We examined how formaldehyde regulates human epithelial sodium channels (ENaC) in H441 and expressed in Xenopus oocytes and exposed mice in vivo. Our results showed that formaldehyde reduced mouse transalveolar fluid clearance in vivo. Formaldehyde caused a dose-dependent inhibition of amiloride-sensitive short-circuit Na+ currents in H441 monolayers and of αβγ-ENaC channel activity in oocytes. α-ENaC protein was reduced, whereas phosphorylation of the extracellular regulated protein kinases 1 and 2 (ERK1/2) increased significantly post exposure. Moreover, both α- and γ-ENaC transcripts were down-regulated. Reactive oxygen species (ROS) was elevated significantly by formaldehyde in addition to markedly augmented membrane permeability of oocytes. These data suggest that formaldehyde contributes to edematous acute lung injury by reducing transalveolar Na+ transport, through decreased ENaC activity and enhanced membrane depolarization, and by elevating ROS production over long-term exposure.

This study aims to evaluate the ability of sodium thiosulfate (STS) to neutralize the adverse effect of sodium hypochlorite (NaOCl) on dentin micro-hardness.

Mineralocorticoid receptor (MR) has pathological roles in various cell types, including renal tubule cells, myocytes, and smooth muscle cells; however, the role of MR in intestinal epithelial cells (IECs) has not been sufficiently evaluated. The intestine is the sensing organ of ingested sodium; accordingly, intestinal MR is expected to have essential roles in blood pressure (BP) regulation.

Autolytic debridement can accelerate wound healing by removing necrotic tissue. A hydrogel was fabricated from an aqueous solution of gelatin, sodium alginate and carboxymethylcellulose sodium by radiation-induced cross-linking at room temperature, which was aiming at the application of debridement glue paste. The swelling ratio of the debridement glue paste is 30 times to its dry weight, when the weight ratio of gelatin/sodium alginate/carboxymethylcellulose sodium was 2:2:2 and the absorbed dose was 20 kGy, with dose rate of 20 Gy/min. The extrusion and compressive assay have confirmed that it possessed stable mechanical strength, and the weight ratio had little effect on the molecular structure by FTIR and TGA. Cell culture experiments demonstrated the debridement glue pastes with the cytotoxicity of grade 0 or 1 (biosafe). The debridement glue paste group could remove the necrotic tissue within 4 days and showed complete wound healing within 18 days; comparatively, the control group without treatment removed the necrotic tissue within 10 days and showed complete wound healing within 26 days in animal experiments using rabbit scald model. Histologic analysis exhibited that more granulation tissue was observed in debridement glue paste. The result of this study suggested that debridement glue pastes had excellent biocompatibility, could selectively remove necrotic tissue, induced granulation tissue formation and accelerated the wound healing.

Sodium butyrate (NaBu) and sodium 4-phenylbutyrate (4PBA) have promising futures in cancer treatment; however, their underlying molecular mechanisms are not clearly understood. Here, we show A549 cell death induced by NaBu and 4PBA are not the same. NaBu treatment induces a significantly higher level of A549 cell death than 4PBA. A gene expression microarray identified more than 5000 transcripts that were altered (>1.5-fold) in NaBu-treated A549 cells, but fewer than 2000 transcripts that were altered in 4PBA. Moreover, more than 100 cell cycle-associated genes were greatly repressed by NaBu, but slightly repressed by 4PBA; few genes were significantly upregulated only in 4PBA-treated cells. Gene expression was further validated by other experiments. Additionally, A549 cells that were treated with these showed changes in glucose consumption, caspase 3/7 activation and histone modifications, as well as enhanced mitochondrial superoxide production. TXNIP was strongly induced by NaBu (30- to 40-fold mRNA) but was only slightly induced by 4PBA (two to fivefold) in A549 cells. TXNIP knockdown by shRNA in A549 cells significantly attenuated caspase 3/7 activation and restored cell viability, while TXNIP overexpression significantly increased caspase 3/7 activation and cell death only in NaBu-treated cells. Moreover, TXNIP also regulated NaBu- but not 4PBA-induced H4K5 acetylation and H3K4 trimethylation, possibly by increasing WDR5 expression. Finally, we demonstrated that 4PBA induced a mitochondrial superoxide-associated cell death, while NaBu did so mainly through a TXNIP-mediated pathway. The above data might benefit the future clinic application.

The global burden of chronic kidney disease (CKD) has increased significantly over the past few decades. This reflects the rising prevalence of type 2 diabetes mellitus (T2DM) and hypertension, two leading causes of CKD. Hypertension, which can also be a complication of CKD, accelerates renal disease progression and augments cardiovascular risk, especially in individuals with diabetic kidney disease. Hence, blood pressure (BP) reduction is a vital component of CKD management. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a relatively novel class of medications developed to treat T2DM by inducing glycosuria and hence, lowering glycaemia. Additionally, SGLT2 inhibitors are antihypertensive, renoprotective and cardioprotective, even in individuals without T2DM, making them effective therapeutic agents for CKD. Another therapy that has proven to be antihypertensive, renoprotective and cardioprotective is dietary sodium restriction. This review evaluates the potential combined benefits of SGLT2 inhibition and dietary sodium restriction on the BP and renal parameters of individuals with CKD.

Sodium influx through voltage-gated sodium channels (VGSCs) coupled with balanced removal of sodium ions via Na+, K+-ATPase is a major determinant of cellular homeostasis and intracellular ionic concentration. Interestingly, many metastatic carcinomas express high levels of these channels. We hypothesized that if excess VGSCs are activated and Na+, K+-ATPase is simultaneously blocked, the intracellular Na+ concentration should increase, resulting in water movement into the cell, causing swelling and lytic cell death. MDA-MB-231 breast cancer cells over-express VGSCs by 7-fold. To test our hypothesis, we treated these cells in vitro with the Na+, K+-ATPase blocker, ouabain, and then stimulated with a sublethal electric current. For in vivo histologic and survival studies, MDA-MB-231 xenografts were established in Nu/J mice. Mice injected with saline or ouabain were electrically stimulated with trains of 10 msec 10V DC pulses. Within seconds to minutes, the cells swelled and lysed. MCF-10a cells, which express normal VGSCs levels, were unaffected by this treatment. Cells from the weakly-malignant cell line, MCF-7, which express 3-fold greater VGSCs than MCF-10a cells, displayed an intermediate time-to-lysis. The rate of lysis correlated directly with the degree of sodium channel expression and malignancy. We also demonstrated efficacy in cell lines from prostate, colon and lung carcinomas. Treated MDA-MB-231 xenografts showed 60-80% cell death. In survival studies, TOL-treated mice showed significantly slower tumor growth vs. controls. These results are evidence that this "targeted osmotic lysis" represents a novel method for selectively killing cancer cells and warrants further investigation as a potential treatment for advanced and end-stage breast cancer.

The increasing demand of tooth bleaching has also increased the need of researches focusing on the durability of the resultant color. The aim of this study was to evaluate the effect of a system based on calcium silicate, sodium phosphate and sodium monofluorophosphate (Regenerate™) on color maintenance of bleached enamel considering two waiting times for the contact with a cola drink.

Use of a catheter lock solution plays a decisive role in vascular access. The effects of different concentrations of heparin and different types of catheter lock solutions are controversial. Therefore, this study aimed to compare the efficacy and safety of sodium citrate and sodium heparin catheter lock solutions.

The objective of this study was to compare the effects of various salts on the physicochemical properties of pork emulsion sausages. Pork sausages were prepared using two different salts, sodium nitrite (SN) and sodium chloride (SC), and concentrated seawater (CSW). The CIE L*, CIE a*, and CIE b*, and chroma values of cooked and uncooked sausages with added CSW were significantly higher than those of the sausages with added SC (p<0.05). However, uncooked and cooked sausages with added SN and CSW had similar CIE a* values (p>0.05). The residual NO2 - content of sausages with added CSW was significantly lower than that of sausages with added SN. Addition of CSW to sausages resulted in a higher cooking yield compared to the other treatments (p<0.05). Addition of SC resulted in significantly higher volatile basic nitrogen (VBN) and thiobarbituric acid (TBA) values compared to the other treatments. Furthermore, addition of CSW enhanced important physicochemical properties, including CIE a*, CIE b*, residual nitrite content, cooking yield, VBN, TBA, textural properties, and cross-sectional area.

Diarrhea is a severe issue in calves that causes fertility problems and economic issues worldwide. Sodium acetate/sodium butyrate (SA/SB) alleviates diarrhea in mice; however, little information is available about the preventive effect of SA/SB on diarrheic yak calves living on the Tibet plateau. Yak calves (n = 19) of age ≥4 months and weight 37 ± 2 Kg were randomly divided into control (C, n = 10) and supplement groups (S, n = 9). Yaks belonging to the supplement group were given sodium butyrate (10 g/kg) and sodium acetate (5 g/kg) for 28 days, along with normal feed, seasonal grasses, pasture, and water. The blood and fecal samples from yak calves were collected for assessment of antioxidant capacity, inflammatory cytokines, microbiome, and short-chain fatty acids (SCFAs) concentration analysis. Results of this study revealed that a lower diarrhea rate, higher weight, and net weight gain were recorded in yaks belonging to group S supplemented with SA/SB. Similarly, increased antioxidant capacity with higher levels of T-AOC, SOD, and GSH-px and decreased inflammatory reactions by decreasing both TNF-α and IL-1β concentrations were recorded in yaks of group S. The concentration of SCFAs was significantly higher (p < 0.05) in yaks from group S than group C. Microbiome analysis revealed that 8 phyla and 54 genera were significantly different (p < 0.05) in both yak groups, with increased probiotics (Akkermansia, Oscillospira), SCFAs producing genera (Oscillospira, ASF356, Anaerosporobacter and Phascolarctobacterium), and decreased inflammatory related genus (Flavonifractor, Fournierella) and harmful bacteria (Oscillibacter, Achromobacter) in group S. In conclusion, the results demonstrated that SA and SB could decrease diarrhea rates in yak calves on the plateau via increasing antioxidant ability and SCFAs, while decreasing inflammatory responses in yaks by moderating gut microbiota. The current results provide new insights for the prevention and treatment of diarrhea in yaks.

Even modest reductions in blood pressure (BP) can have an important impact on population-level morbidity and mortality from cardiovascular disease. There are 2 promising approaches: the SaltSwitch smartphone app, which enables users to scan the bar code of a packaged food using their smartphone camera and receive an immediate, interpretive traffic light nutrition label on-screen alongside a list of healthier, lower-salt options in the same food category; and reduced-sodium salts (RSSs), which are an alternative to regular table salt that are lower in sodium and higher in potassium but have a similar mouthfeel, taste, and flavor.

The membrane-bound serine protease CAP2/Tmprss4 has been previously identified in vitro as a positive regulator of the epithelial sodium channel (ENaC). To study its in vivo implication in ENaC-mediated sodium absorption, we generated a knockout mouse model for CAP2/Tmprss4. Mice deficient in CAP2/Tmprss4 were viable, fertile, and did not show any obvious histological abnormalities. Unexpectedly, when challenged with sodium-deficient diet, these mice did not develop any impairment in renal sodium handling as evidenced by normal plasma and urinary sodium and potassium electrolytes, as well as normal aldosterone levels. Despite minor alterations in ENaC mRNA expression, we found no evidence for altered proteolytic cleavage of ENaC subunits. In consequence, ENaC activity, as monitored by the amiloride-sensitive rectal potential difference (ΔPD), was not altered even under dietary sodium restriction. In summary, ENaC-mediated sodium balance is not affected by lack of CAP2/Tmprss4 expression and thus, does not seem to directly control ENaC expression and activity in vivo.

Previous studies have reported an association between dietary sodium intake and overweight/central obesity. However, dietary survey methods were prone to underestimate sodium intake. Therefore, this study investigated the associations of calculated 24-h urinary sodium excretion, an index of dietary sodium intake, with various obesity parameters including body mass index (BMI) and waist circumference (WC) in a population with a relatively high sodium intake.

We recently reported that cerebral sodium-glucose transporter type 1 (SGLT-1) plays a role in exacerbation of cerebral ischemia. However, the mechanism by which cerebral SGLT-1 acts remains unclear. Here we demonstrated that sodium influx through cerebral SGLT-1 exacerbates cerebral ischemic neuronal damage. SGLT-specific sodium ion influx was induced using α-methyl-D-glucopyranoside (α-MG). Intracellular sodium concentrations in primary cortical neurons were estimated using sodium-binding benzofuran isophthalate fluorescence. SGLT-1 knockdown in primary cortical neurons and mice was achieved using SGLT-1 siRNA. The survival rates of primary cultured cortical neurons were assessed using biochemical assays 1 day after treatment. Middle cerebral artery occlusion (MCAO) was used to generate a focal cerebral ischemic model in SGLT-1 knockdown mice. The change in fasting blood glucose levels, infarction development, and behavioral abnormalities were assessed 1 day after MCAO. Treatment with 200mM α-MG induced a continuous increase in the intracellular sodium concentration, and this increase was normalized after α-MG removal. Neuronal SGLT-1 knockdown had no effect on 100µM H2O2-induced neuronal cell death; however, the knockdown prevented the neuronal cell death induced by 17.5mM glucose and the co-treatment of 100µM H2O2/8.75mM glucose. Neuronal SGLT-1 knockdown also suppressed the cell death induced by α-MG alone and the co-treatment of 100µM H2O2/0.01mM α-MG. Our in vivo results showed that the exacerbation of cerebral ischemic neuronal damage induced by the intracerebroventricular administration of 5.0µg α-MG/mouse was ameliorated in cerebral SGLT-1 knockdown mice. Thus, sodium influx through cerebral SGLT-1 may exacerbate cerebral ischemia-induced neuronal damage.