Low NaI Research Articles

Monte-Carlo simulations with mathematical phantoms to investigate the effectiveness of a whole-body counter for thyroid measurement

FASTSCAN (Canberra, Meriden, CT, USA), a standing-type whole-body counter with upper and lower NaI(Tl) detectors, has been mostly used to determine local residents’ level of internal contamination with 134/137Cs following the Fukushima Daiichi Nuclear Power Plant (FDNPP) disaster in 2011. In the present study, we performed Monte-Carlo simulations with age-specific mathematical human phantoms to investigate the counting efficiencies of the FASTSCAN counter for 131I thyroid measurements. As a result, although the lower detector had low sensitivity for 131I in the thyroids of the adult and 15 y phantoms as well as the 10 y phantom standing on a 30-cm-high stool, the response of this detector may be used as an indicator of surface contamination overlooked on a subject. The total counting efficiency investigated in this study was 0.017–0.018 (cps/Bq) among all age groups. Based on this sensitivity, the determination level for thyroid activity could be calculated to be ~300 Bq under the slightly elevated background radiation level observed after the FDNPP disaster.

Using the Influenza Patient-reported Outcome (FLU-PRO) diary to evaluate symptoms of influenza viral infection in a healthy human challenge model

BackgroundIn clinical studies involving a healthy volunteer human challenge model, a valid and reliable measure to assess the evolution of patient-reported symptom type and severity following viral exposure is necessary. This study examines the use of the InFLUenza Patient-Reported Outcome (FLU-PRO) diary as a standardized measure of symptom severity in a healthy volunteer human challenge model.MethodsHealthy adults admitted to the NIH Clinical Center (Day − 1) underwent a 9-day inpatient quarantine after intranasal challenge with a wild-type influenza A/H1N1pdm virus (Day 0). Participants completed the 32-item FLU-PRO diary twice daily for 14 days to assess presence, severity, and duration of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare scores on Day 3 post-challenge by presence of viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers.ResultsAll but one subject (99%), who was lost to follow-up, completed twice daily FLU-PRO diaries on all study assessment days. FLU-PRO demonstrated that 61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of whom 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (< 1:40) HAI and NAI titers, respectively. Nose, throat, body, and gastrointestinal (GI) symptoms reached peak intensity at Day 3, followed by chest/respiratory and eye symptoms at Day 4. Subjects with viral shedding had higher mean FLU-PRO scores compared to those without, except for Eye and GI domains (p <0.05). Mean FLU-PRO scores were significantly higher for subjects with low NAI titer (p <0.05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (p < 0.05) (high HAI-high NAI (n = 22), low HAI-high NAI (n = 29)).ConclusionsThe FLU-PRO had high adherence and low respondent burden. It can be used to track symptom onset, intensity, duration, and recovery from influenza infection in clinical research. In this human challenge study, scores were responsive to change and distinguished known clinical subgroups.Trial registrationNCT01971255 First Registered October 2, 2013.

Electrochemical Assessment of Molten NaI-AlCl3 Catholytes for Sodium Batteries

Large scale electrical energy storage is a key piece of the next generation electrical grid infrastructure. Sodium batteries offer great promise as safe, low cost and high energy density storage technologies that can be utilized to meet the growing demand for these types of grid scale storage systems. We are exploring a fully molten sodium battery system that operates at low to intermediate temperatures and provides inherent safety for a large scale battery application. Here we characterize the electrochemical properties of new molten salt catholyte chemistries that enable high performance cycling behavior at lower the operating temperature. We present electrochemical analysis of candidate NaI-AlCl3 molten salt catholytes at various temperatures and compositions. We find concentration dependencies on the iodide oxidation potentials as well as the observed current densities. Insight from these studies reveal catholyte compositions that can support high current densities and good cycle life that would be critical to reliable battery performance. Understanding the phase behavior of these salt compositions is key to optimizing the catholyte performance and a preliminary phase diagram is used help explain the promising electrochemical observations. For example, solids present in the catholyte at very high or very low NaI concentrations hinder mass and charge transport to electrode surfaces. Successful understanding and manipulation of this phase space will enable increases in catholyte performance, both in terms of lower operating temperatures and also increased current densities for improved molten sodium batteries for grid scale energy storage. Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Effect of polar aprotic solvents on hydroxyethyl cellulose-based gel polymer electrolyte

Quasi-solid bioelectrolytes based on hydroxyethyl cellulose (HEC) and sodium iodide (NaI) in three different polar aprotic solvent systems, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and dimethylacetamide (DMA), were fabricated and characterized. FTIR studies revealed active solvent-ion interactions in DMF-based electrolytes in comparison to DMA and DMSO. The effect of the solvent system on the crystallinity of HEC gel electrolytes was more significant at low NaI concentration. In each solvent system, the highest ionic conductivity was achieved at 70 wt% NaI and generally DMF-based electrolytes showed higher conductivity than the other solvents. The availability of multiple complexation sites present in DMF is ascribed to improvement in ion mobility and hence conductivity. Rheological analysis was carried out to elucidate the mechanical properties of the gels. Generally, the mechanical strength of the polymer gels was unaffected by the type of solvent.

Electrochemistry of the NaI-AlCl3 Molten Salt System for Use as Catholyte in Sodium Metal Batteries

Molten salt electrolytes show promise as safe, effective elements of emerging low to intermediate temperature molten sodium batteries. Here we investigate the NaI-AlCl3 molten salt system for its electrochemical and physical properties at 150 and 180°C, temperatures recently used to demonstrate a new NaI battery using this molten salt system. Molten salt compositions ranging from 20–75% NaI were prepared and electrochemically interrogated with carbon fiber ultramicroelectrodes utilizing cyclic voltammetry, chronoamperometry, and differential pulse voltammetry. Results indicate that at very high or very low NaI concentrations, secondary phases present hinder diffusion of the redox-active species, potentially impacting the current density of the system. Furthermore, a concentration-independent chronoamperometric analysis technique was leveraged to determine effective diffusion coefficients of active I− in the melt phase. Collectively, the physical characterization and electrochemical properties of the tested salts indicate that the catholyte composition can significantly affect the physical state, current density, ionic diffusion, and voltage window of these promising NaI-AlCl3 molten salt battery catholytes.

Evaluating Symptom Severity of Influenza Viral Infection Using the Influenza Patient-reported Outcomes Instrument (FLU-PRO) in a Healthy Human Challenge Model

BackgroundTo apply the validated FLU-PRO scoring method to assess influenza symptom severity in a healthy human challenge model.MethodsHealthy adults admitted to the NIH Clinical Center (Day -1) underwent a 9 day inpatient quarantine after intranasal challenge with H1N1pdm (Day 0). Participants completed the 32 item FLU-PRO diary twice daily for 14 days to assess presence and severity of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare severity scores on Day 3 post-challenge by viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers.Results61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of which 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (<40) HAI and NAI titers, respectively. Mean daily FLU-PRO symptom severity domain and total scores are shown in Figure 1. Symptoms were present across all FLU-PRO domains from Day 1 post-challenge. Nose, throat, body, and GI symptoms reached peak severity at Day 3, followed by chest and eye symptoms at Day 4. Subjects with viral shedding had significantly higher mean FLU-PRO scores compared with those without, except for Eye and GI domains (P < .05); mean FLU-PRO scores were significantly higher for subjects with low NAI titer (P < .05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (P < .05) ((high HAI-low NAI (n = 22), low HAI-high NAI (n = 29)).ConclusionThe FLU-PRO can be used to track symptom onset, severity, and recovery from influenza infection in clinical research. In this challenge study, scores were responsive to change even in mild disease and distinguished known clinical subgroups. The use of NAI as an independent predictor of influenza disease severity was also supported.Funded by NCI Contract No. HHSN261200800001E and in part by the Intramural Research Program of the NIH, NIAIDFigure 1.Trajectory of FLU-PRO scores from pre-challenge to Day 10 post-challengeDisclosures J. L. Poon, Evidera: Employee, Salary; R. Yu, Evidera: Employee, Salary; N. K. Leidy, Evidera: Employee, Salary

The initial mass functions of M31 and M32 through far red stellar absorption features

Using the Oxford Short Wavelength Integral Field specTrograph (SWIFT), we investigate radial variations of several initial mass function (IMF) dependent absorption features in M31 and M32. We obtain high signal-to-noise spectra at six pointings along the major axis of M31 out to ~ 700" (2.7 kpc) and a single pointing of the central 10 pc for M32. In M31 the sodium NaI {\lambda}8190 index shows a flat equivalent width profile at ~ 0.4 {\AA} through the majority of the bulge, with a strong gradient up to 0.8 {\AA} in the central 10" (38 pc); the Wing-Ford FeH {\lambda}9916 index is measured to be constant at 0.4 {\AA} for all radii; and calcium triplet CaT {\lambda}8498, 8542, 8662 shows a gradual increase through the bulge towards the centre. M32 displays flat profiles for all three indices, with FeH at ~ 0.5 {\AA}, very high CaT at ~ 0.8 {\AA} and low NaI at ~ 0.1 {\AA}. We analyse these data using stellar population models. We find that M31 is well described on all scales by a Chabrier IMF, with a gradient in sodium enhancement of [Na/Fe] ~ +0.3 dex in the outer bulge, rising within the central 10" to perhaps [Na/Fe] ~ +1.0 dex in the nuclear region. We find M32 is described by a Chabrier IMF and young stellar age in line with other studies. Models show that CaT is much more sensitive to metallicity and [{\alpha}/Fe] than to IMF. We note that the centres of M31 and M32 have very high stellar densities and yet we measure Chabrier IMFs in these regions.

Apoptosis of NOD.H2h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Enhanced iodide intake in NOD.H2(h4) mice accelerates the incidence and severity of spontaneous autoimmune thyroiditis (SAT) via an unknown mechanism. A plausible hypothesis is that iodide-induced apoptosis of thyrocytes can create imbalances in antigenic load and/or disruption of immunoregulatory mechanisms that facilitate activation of autoreactive T cells in cervical lymph nodes draining the thyroid. We examined whether NOD.H2(h4) thyrocytes, exposed to low NaI concentrations in vitro, are more susceptible to apoptosis compared to thyrocytes from CBA/J mice, which are resistant to iodide-accelerated SAT (ISAT). We also looked, at the transcriptional level, for differential activation of genes involved in apoptosis or oxidative stress pathways that may account for potential differences in iodide-mediated apoptosis between NOD.H2(h4) and CBA/J thyrocytes. We report that NOD.H2(h4) thyrocytes, cultured for 24 h at very low (4-8 μM) concentrations of NaI, exhibit high levels (40-55%) of apoptosis, as assessed microscopically following staining with fluorescent caspase inhibitors. Similar treatment of thyrocytes from CBA/J mice, which are resistant to ISAT, yielded significantly lower (10-20%) apoptotic rates. Expression analysis by real-time polymerase chain reaction using arrays of apoptosis- and oxidative stress-related genes showed that NaI intake upregulates the expression of 22 genes involved in ROS metabolism and/or antioxidant function in CBA/J thyrocytes, whereas only two of these genes were upregulated in NOD.H2(h4) thyrocytes. Among the set of overexpressed genes were those encoding thyroid peroxidase (Tpo; 5.77-fold), glutathione peroxidases (Gpx2, Gpx4, Gpx7; 2.03-3.14-fold), peroxiredoxins (Prdx1, Prdx2, Prdx5; 2.27-2.97-fold), superoxide dismutase 1 (Sod1; 3.57-fold), thioredoxin 1 (Txn1; 2.13-fold), and the uncoupling proteins 2 and 3 (Ucp2, Ucp3; 2.01-2.15-fold). The results demonstrate that an impaired control of oxidative stress mechanisms is associated with the observed high susceptibility of NOD.H2(h4) thyrocytes to NaI-mediated apoptosis, and suggest a contributing factor for the development of ISAT in this strain.

Time course of sodium-induced Na(+)-K(+)-ATPase recruitment in rabbit cortical collecting tubule.

In cortical collecting tubules (CCD) of aldosterone-repleted rabbit kidney, an increase in intracellular sodium concentration (Nai) induces the recruitment and/or activation of latent Na(+)-K(+)-ATPase pumps (Blot-Chabaud et al., J. Biol. Chem. 265: 11676-11681, 1990). The present study was addressed to determine the time course of this Nai-dependent pump recruitment and to examine some of the factors possibly involved in this phenomenon. CCD from adrenalectomized rabbits complemented with aldosterone and dexamethasone were incubated at 4 degrees C either in a K(+)-free saline solution (Na(+)-loaded CCD) or in a sucrose solution (control CCD) and then rewarmed for various time periods to allow pump recruitment to occur. The number of pumps in the membrane was determined by specific [3H]ouabain binding; Nai was measured using 22Na. A rise in Nai induced a threefold increase in the number of basolateral pumps, which was fully achieved within 1-2 min. This pump recruitment was reversible within 15 min after restoration of low Nai. It was unaffected by inhibitors of cytoskeleton and Ca2+ ionophore A 23187. The blocker of the Na(+)-H+ antiporter, amiloride, did not prevent it. The protein kinase C activator, phorbol 12-myristate 13-acetate, did not induce it in the absence of Na+. We conclude that Nai is a major determinant of pump recruitment and/or activation, which occurs over a very short period of time. It may constitute a rapid adaptative response to an increase in the cell Na+ load.

Interactions of external and internal H+ and Na+ with Na+/Na+ and Na+/H+ exchange of rabbit red cells: Evidence for a common pathway

We have studied the kinetic properties of rabbit red cell (RRBC) Na+/Na+ and Na+/H+ exchanges (EXC) in order to define whether or not both transport functions are conducted by the same molecule. The strategy has been to determine the interactions of Na+ and H+ at the internal (i) and external (o) sites for both exchanges modes. RRBC containing varying Nai and Hi were prepared by nystatin and DIDS treatment of acid-loaded cells. Na+/Na+ EXC was measured as Nao-stimulated Na+ efflux and Na+/H+ EXC as Nao-stimulated H+ efflux and delta pHo-stimulated Na+ influx into acid-loaded cells. The activation of Na+/Na+ EXC by Nao at pHi 7.4 did not follow simple hyperbolic kinetics. Testing of different kinetic models to obtain the best fit for the experimental data indicated the presence of high (Km 2.2 mM) and low affinity (Km 108 mM) sites for a single- or two-carrier system. The activation of Na+/H+ EXC by Nao (pHi 6.6, Nai less than 1 mM) also showed high (Km 11 mM) and low (Km 248 mM) affinity sites. External H+ competitively inhibited Na+/Na+ EXC at the low affinity Nao site (KH 52 nM) while internally H+ were competitive inhibitors (pK 6.7) at low Nai and allosteric activators (pK 7.0) at high Nai. Na+/H+ EXC was also inhibited by acid pHo and allosterically activated by Hi (pK 6.4). We also established the presence of a Nai regulatory site which activates Na+/H+ and Na+/Na+ EXC modifying the affinity for Nao of both pathways. At low Nai, Na+/Na+ EXC was inhibited by acid pHi and Na+/H+ stimulated but at high Nai, Na+/Na+ EXC was stimulated and Na+/H+ inhibited being the sum of both pathways kept constant. Both exchange modes were activated by two classes of Nao sites, cis-inhibited by external Ho, allosterically modified by the binding of H+ to a Hi regulatory site and regulated by Nai. These findings are consistent with Na+/Na+ EXC being a mode of operation of the Na+/H+ exchanger. Na+/H+ EXC was partially inhibited (80-100%) by dimethyl-amiloride (DMA) but basal or pHi-stimulated Na+/Na+ EXC (pHi 6.5, Nai 80 mM) was completely insensitive indicating that Na+/Na+ EXC is an amiloride-insensitive component of Na+/H+ EXC. However, Na+ and H+ efflux into Na-free media were stimulated by cell acidification and also partially (10 to 40%) inhibited by DMA; this also indicates that the Na+/H+ EXC might operate in reverse or uncoupled modes in the absence of Na+/Na+ EXC.(ABSTRACT TRUNCATED AT 400 WORDS)

Intermittent perfusion of ischemic myocardium. Possible mechanisms of protective effects on mechanical function in isolated rat heart.

Intermittent restoration of coronary flow during ischemia reduced myocardial damage and improved recovery of function. The mechanisms of the protective effects of intermittent perfusion were investigated in isolated rat hearts. Ventricular function was assessed as the product of developed pressure (left ventricular systolic pressure minus end-diastolic pressure) and heart rate. Recovery of function was calculated by division of the product at the end of reperfusion by that before ischemia. After 40 minutes of sustained global ischemia, intracellular Na+ (Nai) increased from 11 to 74 mumol/g dry wt. During 30 minutes of reperfusion, these hearts took up a large amount of 45Ca2+ (10 mumol/g dry wt), recovered only 24% of preischemic function, and had an increased left ventricular end-diastolic pressure (48 mm Hg). When the 40-minute period of ischemia was interrupted at 10-minute intervals by intermittent perfusion (three periods of 3 minutes) with either oxygenated or hypoxemic buffer, Nai increased to only 12 or 17 mumol/g dry wt, and reperfusion resulted in much lower 45Ca2+ uptake (0.5 and 0.5 mumol/g dry wt, respectively). Recovery of function was 100% of the preischemic value. When hypoxemic buffer without glucose was used for intermittent perfusion, Nai increased to 50 mumol/g dry wt, ATP was depleted, and reperfusion resulted in reduced recovery of function (76%) and moderately increased 45Ca2+ uptake (2.1 mumol/g dry wt). The role of Na(+)-K+ pump activity in maintaining low Nai was assessed by removing K+ from oxygenated or hypoxemic buffers used during intermittent perfusion. Under these conditions, Nai rose to 64 or 102 mumol/g dry wt, 45Ca2+ uptake increased to 4.4 or 9.4 mumol/g dry wt, and recovery of function was poor. There was a highly significant correlation between Nai during ischemia and reperfusion Ca2+ overload (r = 0.87) or impaired recovery of function (r = 0.96). These results indicate that prevention of an increase in Nai by maintenance of Na(+)-K+ pump activity is associated with a reduction of Ca2+ overload through Na+/Ca2+ exchange.

Cellular and Humoral Factors in Borderline Hypertension

In this article, we review the data about Na+ and K+ lymphocyte content in young subjects with borderline hypertension. These data indicate that many borderline subjects have an abnormally high lymphocyte Na+ content (Nai) and that their pressor response to stress and exercise is directly related to Nai. Lymphocyte K+ content (Ki) is increased in about 50% of borderline subjects. Subjects in whom Ki is high, in comparison with those having a normal Ki, have a lower Nai and lower diastolic blood pressure. This suggests that these subjects have an activation of some compensatory mechanism, possibly an increase in sodium pump function. A humoral factor causing an increase in Nai was detected not only in the plasma from essential hypertensives, but also in the plasma from borderline subjects and from normal subjects with familial hypertension having high Nai. This indirect evidence of a plasma factor impairing Na+ transport was confirmed by direct measurements of the plasma ability to inhibit Na+/K+ adenosine triphosphate. Moderate short-term dietary salt restriction reduces Nai and, proportionally, pressor response to stress. In the long-term, resting blood pressure is also reduced. Dietary K+ supplementation reduces pressor response to handgrip but not resting blood pressure. Intralymphocytic Na+ content is a good predictor of future sustained hypertension, since subjects with normal Nai do not develop hypertension within 5 years, whereas subjects with high Nai develop hypertension in 31% of cases. These subjects also have an altered pressor response to mental stress and do not respond to the low-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of ouabain binding and potassium pump fluxes by cellular sodium and potassium in human and sheep erythrocytes.

1. Erythrocytes were treated with nystatin to alter internal Na (Nai) and K (Ki) composition. Although the rates of K pumping and [3H]ouabain binding were altered dramatically, the relationship between glycoside binding and K pump inhibition was unaffected. 2. Human cells with high Nai and low Ki exhibited an increased rate of ouabain binding as compared to high Ki, low Nai cells; this paralleled the stimulated K pump activity of high Nai cells. 3. At constant Ki, increasing internal Na stimulated K pump and ouabain binding rates concomitantly. 4. At low Nai, increasing Ki inhibited both K pumping and ouabain binding. However, at high Nai, increasing Ki from 4 to 44 mM stimulated the rate of glycoside binding, parallel to its effect of increasing the rate of active K influx. 5. Anti-L, an isoantibody to low K (LK) sheep red cells, increased the rate of ouabain binding via its stimulation of K pump turnover. Since the latter effect is the result of affinity changes at the internal cation activation site(s) of the pump (Lauf, Rasmusen, Hoffman, Dunham, Cook, Parmelee & Tosteson, 1970), the antibody's effect on ouabain binding reflected the positive correlation between the rates of K pump turnover and glycoside binding. 6. These data provide the first evidence in intact cells for the occurrence of a Nai-induced conformational change in the Na/K pump during its normal operational cycle.

Calcium efflux from squid axons under constant sodium electrochemical gradient.

The effect of varying Nao and Nai on Ca efflux while maintaining the ratio Nao/Nai constant was explored in squid giant axons dialyzed with and without ATP. In the absence of ATP, the Ca efflux increased 3.4 +/- 0.2-fold when the Nao/Nai concentrations were reduced from 440/80 to 110/20 mM. In the presence of ATP a similar change did not have an appreciable effect. The inhibition of Ca efflux produced by Nai was studied in the presence and in the absence of ATP. In the absence of ATP, inhibition is very marked and is reminiscent of a unimolecular noncompetitive reaction (inactivation constant [KI] of 34 +/- 5 mM of Nai) whereas in the presence of ATP, the slight inhibition observed indicates that ATP probably increases the KI to 200mM. From the inhibition of the Ca efflux produced by Nai in the presence or absence of ATP a curve describing the dependence of Nai of the ATP-promoted fraction of Ca efflux was constructed. The effect of Nao on the Ca efflux was studied as a function of [Na]i: at low Nai, an activation constant (KA) of 41 mM for Nao was obtained either in the presence of in the absence of ATP. As the intracellular Na is increased in the presence of ATP, Nai seems to have no effect on the apparent half-activation constant. However, in the absence of ATP, the KA for activation increases along a sigmoid curve reaching a value of 112 mM at 100 mM Nai. It is concluded that the Ca efflux system uses the energy of the Na electrochemical gradient. The action of Nai appears to be such that the interaction of a single Na+ is sufficient to block Ca extrusion whereas several Naps externally are necessary to activate Ca extrusion.