Hypertonic saline- and detergent-accelerated EDTA-based decalcification better preserves mRNA of bones.

Ethylenediaminetetraacetic acid (EDTA), a classically used chelating agent of decalcification, maintains good morphological details, but its slow decalcification limits its wider applications. Many procedures have been reported to accelerate EDTA-based decalcification, involving temperature, concentration, sonication, agitation, vacuum, microwave, or combination. However, these procedures, concentrating on purely tissue-outside physical factors to increase the chemical diffusion, do not enable EDTA to exert its full capacity due to tissue intrinsic chemical resistances around the diffusion passage. The resistances, such as tissue inner lipids and electric charges, impede the penetration of EDTA. We hypothesized that delipidation and shielding electric charges would accelerate EDTA-based penetration and the subsequent decalcification. The hypothesis was verified by the observation of speedy penetration of EDTA with additives of detergents and hypertonic saline, testing on tissue-mimicking gels of collagen and adult mouse bones. Using a 26% EDTA mixture with the additives at 45°C, a conventional 7-day decalcification of adult mouse ankle joints could be completed within 24 h while the tissue morphological structure, antigenicity, enzymes, and DNA were well preserved, and mRNA better retained compared to using 15% EDTA at room temperature. The addition of hypertonic saline and detergents to EDTA decalcification is a simple, rapid, and inexpensive method that doesn't disrupt the current histological workflow. This method is equally or even more effective than the currently most used decalcification methods in preserving the morphological details of tissues. It can be highly beneficial for the related community.

In situ pulmonary mucus hydration assay using rotational and translational diffusion of gold nanorods with polarization-sensitive optical coherence tomography.

Significance: Assessing the nanostructure of polymer solutions and biofluids is broadly useful for understanding drug delivery and disease progression and for monitoring therapy. Aim: Our objective is to quantify bronchial mucus solids concentration (wt. %) during hypertonic saline (HTS) treatment in vitro via nanostructurally constrained diffusion of gold nanorods (GNRs) monitored by polarization-sensitive optical coherence tomography (PS-OCT). Approach: Using PS-OCT, we quantified GNR translational (DT) and rotational (DR) diffusion coefficients within polyethylene oxide solutions (0 to 3 wt. %) and human bronchial epithelial cell (hBEC) mucus (0 to 6.4 wt. %). Interpolation of DT and DR data is used to develop an assay to quantify mucus concentration. The assay is demonstrated on the mucus layer of an air-liquid interface hBEC culture during HTS treatment. Results: In polymer solutions and mucus, DT and DR monotonically decrease with increasing concentration. DR is more sensitive than DT to changes above 1.5 wt. % of mucus and exhibits less intrasample variability. Mucus on HTS-treated hBEC cultures exhibits dynamic mixing from cilia. A region of hard-packed mucus is revealed by DR measurements. Conclusions: The extended dynamic range afforded by simultaneous measurement of DT and DR of GNRs using PS-OCT enables resolving concentration of the bronchial mucus layer over a range from healthy to disease in depth and time during HTS treatment in vitro.

Ultra-high-frequency radio-frequency acoustic molecular imaging with saline nanodroplets in living subjects.

Molecular imaging is a crucial technique in clinical diagnostics but it relies on radioactive tracers or strong magnetic fields that are unsuitable for many patients, particularly infants and pregnant women. Ultra-high-frequency radio-frequency acoustic (UHF-RF-acoustic) imaging using non-ionizing RF pulses allows deep-tissue imaging with sub-millimetre spatial resolution. However, lack of biocompatible and targetable contrast agents has prevented the successful in vivo application of UHF-RF-acoustic imaging. Here we report our development of targetable nanodroplets for UHF-RF-acoustic molecular imaging of cancers. We synthesize all-liquid nanodroplets containing hypertonic saline that are stable for at least 2 weeks and can produce high-intensity UHF-RF-acoustic signals. Compared with concentration-matched iron oxide nanoparticles, our nanodroplets produce at least 1,600 times higher UHF-RF-acoustic signals at the same imaging depth. We demonstrate in vivo imaging using the targeted nanodroplets in a prostate cancer xenograft mouse model expressing gastrin release protein receptor (GRPR), and show that targeting specificity is increased by more than 2-fold compared with untargeted nanodroplets or prostate cancer cells not expressing this receptor.

Comparison of porcine corneal decellularization methods and importance of preserving corneal limbus through decellularization.

BACKGROUND: The aim of this study is to compare the three previously applied, conventional porcine corneal decellularization methods and to demonstrate the importance of preserving the corneal limbus through decellularization. METHODS: Fresh, wild-type (with or without) limbus porcine corneas were decellularized using three different methods, including (i) sodium dodecyl sulfate (SDS), (ii) hypertonic saline (HS), and (iii) N2 gas (NG). Post-treatment evaluation was carried out using histological, residual nuclear material, and ultrastructural analyses. Glycerol was used to help reduce the adverse effects of decellularization. The corneas were preserved for two weeks in cornea storage medium. RESULTS: All three decellularization methods reduced the number of keratocytes at different rates in the stromal tissue. However, all methods, except SDS, resulted in the retention of large numbers of cells and cell fragments. The SDS method (0.1% SDS, 48h) resulted in almost 100% decellularization in corneas without limbus. Low decellularization capacity of the NG method (<50%) could make it unfavorable. Although HS method had a more balanced damage-decellularization ratio, its decellularization capacity was lower than SDS method. Preservation of the corneoscleral limbus could partially prevent structural damage and edema, but it would reduce the decellularization capacity. CONCLUSION: Our results suggest that SDS is a very powerful decellularization method, but it damages the cornea irreversibly. Preserving the corneoscleral limbus reduces the efficiency of decellularization, but also reduces the damage.

Hypertonic saline buffered with sodium acetate for intracranial pressure management.

BACKGROUND: 3 % hypertonic saline (HS) is a hyperosmolar agent often used to treat elevated intracranial pressure (ICP). However, the resultant hyperchloremia is associated with adverse outcomes in certain patient populations. In this study, HS solution buffered with sodium acetate (HSwSA) is used as an alternative to standard 3 % formulations to reduce overall chloride exposure. Our objectives are to establish whether this alternative agent - with reduced chloride content - is similar to standard 3 % HS in maintaining hyperosmolarity and investigate its effects on hyperchloremia. METHODS: A retrospective chart review was conducted from August 1, 2014 to August 1, 2017 on patients receiving hypertonic therapies for ICP management. Patients were categorized into three groups, those that received: (1) 3 % HS for at least 72 h, (2) HSwSA for at least 72 h, or (3) were switched from 3 % HS within 72 h of initiating therapy to HSwSA for at least 72 h. RESULTS: The average increase in serum osmolality after 72 h of therapy was 21.1 moSm/kg for those only on 3 % HS and 20.3 mOsm/kg for those only on HSwSA. Serum chloride levels after 24 h decreased on average by 2.5 mEq/L after switching from 3% HS to HSwSA and stayed below baseline, whereas matched patients only receiving 3% HS on average had serum chloride levels increase 4.3 mEq/L after 24 h and continued to rise. CONCLUSIONS: Hyperchloremia has been associated with decreased renal perfusion, increasing the risk of acute kidney injury and hyperchloremic metabolic acidosis. Compared to standard 3% HS, our findings suggest an alternative hyperosmolar therapy with less chloride maintains similar hyperosmolarity while reducing overall chloride exposure.

Factors determining self-assembly of hyaluronan.

The conditions determining network-forming and aggregation properties of hyaluronan on the mica surface were studied. The hyaluronan was deposited on the surface from aqueous and saline solutions and attached by a bivalent cation. The morphology of the immobilized assemblies was characterized by atomic force microscopy. The experimental results show that the morphology and size of the aggregates as well as the density of the interconnecting fibrillar network, both made of hyaluronan, at the liquid-solid phase interface are determined not only by its molecular weight or concentration in solution, but also by the dissolution conditions and storage time. These findings extend the current state of knowledge about the conformational variability of this biologically important polymer. Understanding the conformational variability is of great importance, as it governs the physiological functions of hyaluronan, as well as its processability and formulations. That in turn determines its usability in different pharmacological and biomaterial applications.

The implications of variations in nasal irrigation recipes in the United Kingdom.

OBJECTIVE: This study aims to investigate the variations in publicly available nasal irrigation recipes published in the United Kingdom (UK). DESIGN: Internet searches used to identify eligible nasal irrigation recipes. These were then examined for their physical and biochemical properties, through theoretical calculations and experimental measurement. SETTING: Recipes produced by healthcare providers or official national bodies in the UK. PARTICIPANTS: No human participants. MAIN OUTCOME MEASURES: Solution osmolality (classified into hypo-, iso- and hypertonic), acidity (pH) and specific gravity. RESULTS: Thirteen unique recipes were identified from 17 sources. Osmolality ranged from 166.2 to 1492.2 mosmol/kg in volumes ranging from 142 to 1136 mLs (isotonic range 275-295 mosmol/kg). Specific gravity ranged from 1.006 to 1.034. pH ranged from 7.74 to 8.11. No recipe produced a solution with isotonic properties. The majority produced hypertonic irrigations. CONCLUSIONS: Most publicly available nasal irrigation recipes produce hypertonic solutions but there is great variability in the osmolality and volume. UK organisations should take action to review published recipes to bring these into alignment with latest guidelines (recommending against hypertonic saline use) and reduce variability in patient interpretations.

The effect of osmotic dehydration on the polyphenols content in onion.

BACKGROUND: The onion is one of the most popular vegetables in the world, often used in the food industry. The purpose of this work was to determine the effect of osmotic dehydration of onions after storage in solutions containing various amounts of sucrose and sodium chloride on the course of osmoconcentration and the level of polyphenols in the dehydrated vegetables. The results could be useful to define the dehydration conditions under which a product retains the highest content of these health-promoting substances. METHODS: Onions var. Robusta were used. The vegetables were stored for six months at 0°C (air relative humidity 75–80%). They were cut into quarters just before dewatering. Samples of 20 ±1 g were dehydrated for five hours in a 40–60°Bx sucrose solution and a 5–15% NaCl solution (25°C); the weight ratio of the sample to the solution was 1:5. The contents of polyphenols and dry matter were determined. RESULTS: The use of a mixture of two osmotic agents (sucrose, sodium chloride) was more effective in the increase of dry matter content than using only sucrose. Nearly 49% dry matter content in onion was obtained by using a 60% solution (50% sucrose + 10% NaCl) for five hours. The greatest differences in the content of total polyphenols occurred during the first hour. After this time, retention amounted to 48–90%, depending on the concentration of sucrose (40–60%) and sodium chloride (5–15%). The retention of diglycosides of quercetin (mainly quercetin-3,4’-diglucoside) was lower than that of monoglycosides (mainly quercetin-4’- -glucoside). Following dehydration in a solution containing 60% sucrose and 10% NaCl, after three hours, there was about one third of the initial amount of the above-mentioned compounds in onion. CONCLUSIONS: The increase in the concentration of the hypertonic solution, being a mixture of sucrose and sodium chloride, causes a reduction in the retention of total polyphenols in osmotically dehydrated onions. The smallest losses occur after applying a 40% sucrose solution with NaCl up to 10%.

Stability and Compatibility of Ramosetron with Midazolam in 0.9% Sodium Chloride Injection for Postoperative Nausea and Vomiting Administration.

BACKGROUND: Combination antiemetic therapy has become a common practice for the prevention of postoperative nausea and vomiting (PONV). The aim of the present study was to evaluate the stability and compatibility of ramosetron hydrochloride and midazolam in 0.9% sodium chloride injection when stored at 4°C and 25°C for up to 14 days. METHODS: Admixtures were assessed initially and for 14 days after preparation in polyolefin bags and glass bottles using 0.9% sodium chloride injection as the diluent and stored at 4°C or 25°C. The initial concentrations were 0.3 mg/100 mL ramosetron hydrochloride and 0.5 mg/100 mL midazolam hydrochloride. For all samples, the compatibility parameters (including precipitation, cloudiness, discoloration and pH values) were evaluated. Chemical stability was also determined using high-performance liquid chromatography (HPLC) analysis. RESULTS: After a 14-day period of storage at 4°C or 25°C, the percent of the initial concentration of ramosetron hydrochloride and midazolam hydrochloride in the various solutions were maintained at a minimum of 97%. All of the mixtures remained clear and colourless throughout the observation period, and no colour change or precipitation was observed. CONCLUSION: The results indicate that admixtures of 0.3 mg/100 mL ramosetron hydrochloride and 0.5 mg/100 mL midazolam hydrochloride in normal saline were stable for 14 days at 4°C or 25°C when packaged in polyolefin bags or glass bottles and protected from light.

Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia.

Trauma/hemorrhagic shock is a complex physiological phenomenon that leads to dysregulation of many molecular pathways. For over a decade, hypertonic saline (HTS) has been used as an alternative resuscitation fluid in the setting of trauma/hemorrhagic shock. In addition to restoring circulating volume within the vascular space, studies have shown a positive immunomodulatory effect of HTS. Targeted studies have shown that HTS affects the transcription of several pro-inflammatory cytokines by inhibiting the NF-κB-IκB pathway in model cell lines and rats. However, few studies have been undertaken to assess the unbiased effects of HTS on the whole transcriptome. This study was designed to interrogate the global transcriptional responses induced by HTS and provides insight into the underlying molecular mechanisms and pathways affected by HTS. In this study, RNA sequencing was employed to explore early changes in transcriptional response, identify key mediators, signaling pathways, and transcriptional modules that are affected by HTS in the presence of a strong inflammatory stimulus. Our results suggest that primary human small airway lung epithelial cells (SAECS) exposed to HTS in the presence and absence of a strong pro-inflammatory stimulus exhibit very distinct effects on cellular response, where HTS is highly effective in attenuating cytokine-induced pro-inflammatory responses via mechanisms that involve transcriptional regulation of inflammation which is cell type and stimulus specific. HTS is a highly effective anti-inflammatory agent that inhibits the chemotaxis of leucocytes towards a pro-inflammatory gradient and may attenuate the progression of both the innate and adaptive immune response.

Homemade Hypertonic Saline: Essential Treatment Can Be Available and Affordable.

BACKGROUND: Nebulized hypertonic saline (HS) treatment is unavailable to large populations worldwide. OBJECTIVES: To determine the bacterial contamination and electrolyte concentrations in homemade (HM-HS) vs. pharmacy made (PM-HS). METHODS: We conducted three double-blind consecutive trials: 50 boiled-water homemade 3%-HS (B-HM-HS) bottles and 50 PM-HS. The bottles were cultured after 48 hours. Electrolyte concentrations were measured in 10 bottles (5 per group). Forty bottles (20 per group) were distributed to volunteers for simulation of realistic treatment by drawing 4 ml HS three times daily. From each bottle, 4 ml samples were cultured after 1, 5, and 7 days. Volunteers prepared 108 bottles containing 3%-HS, sterilizing them using a microwave oven (1100-1850W). These bottles were cultured 24 hours, 48 hours, and 1 month after preparation. RESULTS: Contamination rates of B-HM-HS and PM-HS after 48 hours were 56% and 14%, respectively (P = 0.008). Electrolyte concentrations were similar: 3.7% ± 0.4 and 3.5% ± 0.3, respectively (P = NS). Following a single day of simulation B-HM-HS bottles were significantly more contaminated than PM-HS bottles: 75% vs. 20%, respectively (P < 0.01). By day 7, 85% of PM-HS bottles and 100% of B-HM-HS bottles were contaminated (P = 0.23). All 108 microwave-oven prepared bottles (MICRO-HS) were sterile, which was significantly better than the contamination rate of B-HM-HS and PM-HS (P < 0.001). Calculated risk for a consecutive MICRO-HS to be infected was negligible. CONCLUSIONS: Microwave preparation provides sterile HS with adequate electrolyte concentrations, and is a cheap, fast, and widely available method to prepare HS.

[Effects of three different concentrations of hypertonic sodium salt resuscitation on liver injury of rats at the early stage of severe burned].

OBJECTIVE: To investigate the effects of three different concentrations of hypertonic sodium salt (HS) resuscitation on liver injury of rats at the early stage of severe burned. METHODS: 104 female Sprage-Dawley (SD) rats were randomly divided into five groups: sham group (n = 8), lactated Ringer solution (LR) group (n = 24), 600, 800, 1 000 mmol/L HS groups (HS600, HS800, and HS1000 groups, n = 24). Rats in LR group and HS groups were subjected to full-thickness scald with 30% total body surface area (TBSA), and then given liquid resuscitation treatment with LR and the corresponding HS. These rats were sacrificed at 2, 8 and 24 hours post injury to collect blood and liver tissue. Rats in sham group were given simulation of burns without resuscitation, which were immediately sacrificed and the specimens were harvested. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemical analyzer. The levels of liver tissue malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by ultraviolet spectrophotometry. The expression of liver tissue p38 mitogen-actirated protein kinase (p38MARK) was detected by Western Blot. RESULTS: Compared with sham group, the levels of ALT, AST, MDA and p38MAPK were increased, and the activities of SOD were decreased in LR group and different degrees in HS groups at each time point after injury. Compared with LR group, the levels of ALT, AST, MDA and p38MAPK were decreased and the activities of SOD were increased in different degrees with HS groups, among which HS600 group changed most significantly [ALT (U/L): 147±52 vs. 227±60 at 8 hours, 138±47 vs. 191±41 at 24 hours; AST (U/L): 288±79 vs. 548±237 at 2 hours, 567±167 vs. 841±338 at 8 hours, 515±180 vs. 712±159 at 24 hours; MDA (nmol/mg): 0.287±0.036 vs. 0.395±0.041 at 2 hours, 0.298±0.030 vs. 0.392±0.018 at 8 hours, 0.278±0.033 vs. 0.422±0.036 at 24 hours; SOD (U/mg): 230±16 vs. 159±30 at 2 hours, 251±14 vs. 194±15 at 8 hours, 296±8 vs. 243±11 at 24 hours; p-p38MAPK/p38MAPK (A value): 0.778±0.040 vs. 1.065±0.066 at 2 hours, 0.791±0.046 vs. 0.967±0.041 at 8 hours, 0.733±0.027 vs. 1.020±0.043 at 24 hours; all P < 0.05]. The levels of ALT and AST in HS600 group were significantly lower than those in HS1000 group at 2 hours and in HS800 group at 8 hours. The levels of MDA and p38MAPK in HS600 group were significantly lower than those of HS800 group and HS1000 group, and the level of SOD in HS600 group was significantly higher than that in HS800 group and HS1000 group at each time point after injury. There were no significant differences in all test indicators between HS800 group and HS1000 group at each time point after injury. CONCLUSIONS: High concentration of HS can reduce the early liver injury in severely scalded rats, of which the curative effect of HS 600 mmol/L is best.

Comparison of Melatonin, Hypertonic Saline, and Hydroxyethyl Starch for Resuscitation of Secondary Intra-Abdominal Hypertension in an Animal Model.

A variety of agents may have a beneficial effect in reducing injury-induced intestinal edema of fluid, but studies confirming the efficacy and mechanisms of these agents in secondary intra-abdominal hypertension (IAH) are lacking. This study was to compare the effectiveness of melatonin, 7.5% hypertonic saline (HS), and hydroxyethyl starch 130/0.4 (HES) on the resuscitation of secondary IAH in a rat model. Female SD rats were divided into: sham group, shock group, lactated Ringer solution (LR) group, melatonin group, HS group, and HES group. Except for the sham group, all rats underwent a combination of inducing portal hypertension, hemorrhaging to a MAP of 40 mmHg for 2 hr, and using an abdominal restraint device. The collected blood was reinfused and the rats were treated with LR (30ml/h), melatonin (50 mg/kg) + LR, HS (6 ml/kg) + LR, and HES (30 ml/kg) + LR, respectively. The shock group received no fluids. LR was continuously infused for 6hr. The intestinal permeability, immunofluorescence of tight junction proteins, transmission electron microscopy, level of inflammatory mediators (TNF-a, IL-1ß, IL-6) and of biochemical markers of oxidative stress (malondialdehyde, myeloperoxidase activity, and glutathione peroxidase) were assessed. Expressions of the protein kinase B (Akt) and of tight junction proteins were detected by Western blot. Compared with LR, HS, and HES, melatonin was associated with less inflammatory and oxidative injury, less intestinal permeability and injury, and lower incidence of secondary IAH in this model. The salutary effect of melatonin in this model was associated with the upregulation of intestinal Akt phosphorylation.

Nuclear versus cytosolic activity of the yeast Hog1 MAP kinase in response to osmotic and tunicamycin-induced ER stress.

We examined the physiological significance of the nuclear versus cytosolic localization of the MAPK Hog1p in the ability of yeast cells to cope with osmotic and ER (endoplasmic reticulum) stress. Our results indicate that nuclear import of Hog1p is not critical for osmoadaptation. Plasma membrane-anchored Hog1p is still able to induce increased expression of GPD1 and glycerol accumulation. This is a key osmoregulatory event, although a small production of the osmolyte coupled with the nuclear import of Hog1p is sufficient to provide osmoresistance. On the contrary, the nuclear activity of Hog1p is dispensable for ER stress adaptation.

Comparison of 3% and 7.5% Hypertonic Saline in Resuscitation After Traumatic Hypovolemic Shock.

Hypertonic saline solutions (HSSs) (7.5%) are useful in the resuscitation of patients with hypovolemic shock because they provide immediate intravascular volume expansion via the delivery of a small volume of fluid, improving cardiac function. However, the effects of using 3% HSS in hypovolemic shock resuscitation are not well known. This study was designed to compare the effects of and complications associated with 3% HSS, 7.5% HSS, and standard fluid in resuscitation. In total, 294 severe trauma patients were enrolled from December 2008 to February 2012 and subjected to a double-blind randomized clinical trial. Individual patients were treated with 3% HSS (250 mL), 7.5% HSS (250 mL), or lactated Ringer's solution (LRS) (250 mL). Mean arterial pressure, blood pressure, and heart rate were monitored and recorded before fluid infusion and at 10, 30, 45, and 60 min after infusion, and the incidence of complications and survival rate were analyzed. The results indicate that 3% and 7.5% HSSs rapidly restored mean arterial pressure and led to the requirement of an approximately 50% lower total fluid volume compared with the LRS group (P < 0.001). However, a single bolus of 7.5% HSS resulted in an increase in heart rate (mean of 127 beats/min) at 10 min after the start of resuscitation. Higher rates of arrhythmia and hypernatremia were noted in the 7.5% HSS group, whereas higher risks of renal failure (P< 0.001), coagulopathy (P < 0.001), and pulmonary edema (P < 0.001) were observed in the LRS group. Neither severe electrolyte disturbance nor anaphylaxis was observed in the HSS groups. It is notable that 3% HSS had similar effects on resuscitation because both the 7.5% HSS and LRS groups but resulted in a lower occurrence of complications. This study demonstrates the efficacy and safety of 3% HSS in the resuscitation of patients with hypovolemic shock.

Osmolarity of prevalent eye drops, side effects, and therapeutic approaches.

PURPOSE: Little is known about how the osmolarity of ophthalmic formulations affects the ocular surface. Because hyperosmolar eye drops could be therapeutic for treating corneal edema, this article presents an ex vivo model of corneal edema for testing ophthalmic drugs based on their osmolarity. The respective osmolarity of common eye drops found in the German market is also analyzed here. METHODS: For modeling corneal edema, an Ex Vivo Eye Irritation Test was used to simulate an ocular anterior chamber with a physiological corneal barrier. To induce corneal edema, the anterior chamber was supplied with a hypoosmolar medium (148 mOsm/L) for 24 hours. Preserved and preservative-free 5% sodium chloride (hyperosmolar Omnisorb and Ocusalin 5% UD) were used for 1 hour, on 5 corneas each, to test their efficiency to reduce corneal edema in this model. Corneal thickness was determined by optical coherence tomography. Osmolarity of 87 common eye drops was measured by freezing point osmometry. RESULTS: Ex vivo, the tested hypoosmolar condition induced corneal edema from 450 µm (±50 µm) at baseline to 851 µm (±94 µm, P < 0.0001). Omnisorb and Ocusalin 5% UD significantly reduced the corneal thickness by 279 µm (±28 µm, P < 0.001) for Omnisorb and 258 µm (±29 µm, P < 0.001) for Ocusalin 5% UD. Forty-three (49%) of the tested products had an osmolarity below and 44 (51%) above the physiological tear osmolarity of 289 mOsm/L. Osmolarity values of less than 200 mOsm/L were found in lubricant drops. The highest osmolarity was detected in Omnisorb (1955 mOsm/L). CONCLUSIONS: The Ex Vivo Eye Irritation Test has proven to be a reliable novel model of corneal edema for evaluating osmotic eye drops. Osmolarity measurements revealed a wide range from hypotonic to hypertonic formulations for commonly marketed ophthalmic drugs.

Treatment of hyponatremic encephalopathy with a 3% sodium chloride protocol: a case series.

BACKGROUND: 3% sodium chloride solution is the accepted treatment for hyponatremic encephalopathy, but evidence-based guidelines for its use are lacking. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Adult patients presenting to the emergency department of a university hospital with hyponatremic encephalopathy, defined as serum sodium level < 130 mEq/L with neurologic symptoms of increased intracranial pressure without other apparent cause, and treated with a continuous infusion of 500mL of 3% sodium chloride solution over 6 hours through a peripheral vein. PREDICTORS: Hyponatremic encephalopathy defined as serum sodium level < 130 mEq/L with neurologic symptoms of increased intracranial pressure without other apparent cause. OUTCOMES: Change in serum sodium level within 48 hours, improvement in neurologic symptoms, and clinical evidence of cerebral demyelination, permanent neurologic injury, or death within 6 months' posttreatment follow-up. RESULTS: There were 71 episodes of hyponatremic encephalopathy in 64 individuals. Comorbid conditions were present in 86% of individuals. Baseline mean serum sodium level was 114.1±0.8 (SEM) mEq/L and increased to 117.9±1.3, 121.2±1.2, 123.9±1.0, and 128.3±0.8 mEq/L at 3, 12, 24, and 48 hours following the initiation of 3% sodium chloride solution treatment, respectively. There was a marked improvement in central nervous system symptoms within hours of therapy in 69 of 71 (97%) episodes. There were 12 deaths, all of which occurred following the resolution of hyponatremic encephalopathy and were related to comorbid conditions, with 75% of deaths related to sepsis. No patient developed neurologic symptoms consistent with cerebral demyelination at any point during the 6-month follow-up period. LIMITATIONS: Lack of a comparison group and follow-up neuroimaging studies. Number of cases is too small to provide definitive assessment of the safety of this protocol. CONCLUSIONS: 3% sodium chloride solution was effective in reversing the symptoms of hyponatremic encephalopathy in the emergency department without producing neurologic injury related to cerebral demyelination on long-term follow-up in this case series.

Anomalous water diffusion in salt solutions.

The dynamics of water exhibits anomalous behavior in the presence of different electrolytes. Recent experiments [Kim JS, Wu Z, Morrow AR, Yethiraj A, Yethiraj A (2012) J Phys Chem B 116(39):12007-12013] have found that the self-diffusion of water (Dw) can either be enhanced or suppressed around CsI and NaCl, respectively, relative to that of neat water. Here we show that unlike classical empirical potentials, ab initio molecular dynamics simulations successfully reproduce the qualitative trends observed experimentally. These types of phenomena have often been rationalized in terms of the "structure-making" or "structure-breaking" effects of different ions on the solvent, although the microscopic origins of these features have remained elusive. Rather than disrupting the network in a significant manner, the electrolytes studied here cause rather subtle changes in both structural and dynamical properties of water. In particular, we show that water in the ab initio molecular dynamics simulations is characterized by dynamic heterogeneity, which turns out to be critical in reproducing the experimental trends.

Hemodynamic responses elicited by systemic injections of isotonic and hypertonic saline in hemorrhaged rats.

PURPOSE: The objectives of this study were (i) to characterize the hemodynamic responses caused by controlled hemorrhage (HEM) in pentobarbital-anesthetized rats, and (ii) to determine the responses elicited by systemic bolus injections of isotonic saline (0.15M) or hypertonic saline (3M) given 5min after completion of HEM. RESULTS: Controlled HEM (4.3±0.2ml/rat at 1.5ml/min) resulted in a pronounced and sustained fall in mean arterial blood pressure (MAP) to about 40mmHg. The fall in MAP was associated with a reduction in hindquarter vascular resistance (HQR) but no changes in renal (RR) or mesenteric (MR) vascular resistances. Systemic injections of isotonic saline (96-212µmol/kg i.v., in 250-550µl) did not produce immediate responses but promoted the recovery of MAP to levels below pre-HEM values. Systemic injections of hypertonic saline (750-3000µmol/kg, i.v., in 250-550µl) produced immediate and pronounced falls in MAP, RR, MR and especially HQR of 30-120s in duration. However, hypertonic saline prompted a full recovery of MAP, HQR and RR to pre-HEM levels and an increase in MR to levels above pre-HEM values. CONCLUSIONS: This study demonstrates that (i) HEM induced a pronounced fall in MAP which likely involved a fall in cardiac output and HQR, (ii) isotonic saline did not fully normalize MAP, and (iii) hypertonic saline produced dramatic initial responses, and promoted normalization of MAP probably by restoring blood volume and cardiac output through sequestration of fluid from intracellular compartments.