Effect of Hypertonic Saline Solution on the Ventilatory Mechanics of Lungs Donated After Brain Death.

INTRODUCTION: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. METHODS: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. RESULTS: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). CONCLUSIONS: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.

Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N-terminal.

Pyroptosis is a type of programmed lytic cell death that could be activated by either the canonical or noncanonical inflammasome pathway. In this study, we aimed to examine the effect of hypertonic solution on noncanonical pyroptosis in macrophage. We found that although hypertonic solution had a general inhibitory effect on noncanonical pyroptosis, the underlying mechanism varied by the solute causing hypertonicity. Specifically, hypertonic NaCl or KCl solution inhibited the cleavage of gasdermin D, the pore-forming protein in pyroptosis, whereas hypertonic saccharide solution did not affect the cleavage or membrane binding of gasdermin D. In this case, nevertheless, pyroptosis was still inhibited as evidenced by the preserved mitochondria activity and cell membrane permeability.

Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND: Saline nasal irrigation is labelled as an add-on treatment in patients with allergic rhinitis (AR). The primary aim of this study was to compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus normal saline solution (NSS) on reducing nasal symptoms in children with seasonal AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of life, and sleep quality was the secondary aim. METHODS: In this 21-day, open-label, randomized controlled study, 36 SAR children (aged 6-13 years) with a Total 5 Symptom Score (T5SS) ≥5 received twice-daily BHS or NSS delivered through a nasal douche. Efficacy measures were least square mean changes (LSmc) in T5SS, NCC, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Pittsburgh Sleep Quality Index (PSQI) scores. RESULTS: BHS improved the T5SS total score to a greater extent than NSS (LSmc -6.45 vs. -5.45, p < 0.001). Concerning NCC, BHS significantly reduced the scores of neutrophils (LSmc -0.76, p = 0.004) and eosinophils (LSmc -0.46, p = 0.018), while NSS did not. Similarly, only BHS yielded a significant improvement in the PRQLQ score (LSmc -0.57, p = 0.009), whereas the improvement in PSQI score was comparable between the BHS (LSmc -0.77, p = 0.025) and NSS (LSmc -1.39, p < 0.001) groups. Overall, BHS was well tolerated. CONCLUSIONS: In children with SAR, BHS is effective in improving nasal symptoms and NCC, with an associated beneficial effect on quality of life.

Functional and structural characterization of axonal opioid receptors as targets for analgesia.

BACKGROUND: Opioids are the gold standard for the treatment of acute pain despite serious side effects in the central and enteric nervous system. µ-opioid receptors (MOPs) are expressed and functional at the terminals of sensory axons, when activated by exogenous or endogenous ligands. However, the presence and function of MOP along nociceptive axons remains controversial particularly in naïve animals. Here, we characterized axonal MOPs by immunofluorescence, ultrastructural, and functional analyses. Furthermore, we evaluated hypertonic saline as a possible enhancer of opioid receptor function. RESULTS: Comparative immunolabeling showed that, among several tested antibodies, which all provided specific MOP detection in the rat central nervous system (CNS), only one monoclonal MOP-antibody yielded specificity and reproducibility for MOP detection in the rat peripheral nervous system including the sciatic nerve. Double immunolabeling documented that MOP immunoreactivity was confined to calcitonin gene-related peptide (CGRP) positive fibers and fiber bundles. Almost identical labeling and double labeling patterns were found using mcherry-immunolabeling on sciatic nerves of mice producing a MOP-mcherry fusion protein (MOP-mcherry knock-in mice). Preembedding immunogold electron microscopy on MOP-mcherry knock-in sciatic nerves indicated presence of MOP in cytoplasm and at membranes of unmyelinated axons. Application of [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin (DAMGO) or fentanyl dose-dependently inhibited depolarization-induced CGRP release from rat sciatic nerve axons ex vivo, which was blocked by naloxone. When the lipophilic opioid fentanyl was applied perisciatically in naïve Wistar rats, mechanical nociceptive thresholds increased. Subthreshold doses of fentanyl or the hydrophilic opioid DAMGO were only effective if injected together with hypertonic saline. In vitro, using ß-arrestin-2/MOP double-transfected human embryonic kidney cells, DAMGO as well as fentanyl lead to a recruitment of ß-arrestin-2 to the membrane followed by a ß-arrestin-2 reappearance in the cytosol and MOP internalization. Pretreatment with hypertonic saline prevented MOP internalization. CONCLUSION: MOPs are present and functional in the axonal membrane from naïve animals. Hypertonic saline acutely decreases ligand-induced internalization of MOP and thereby might improve MOP function. Further studies should explore potential clinical applications of opioids together with enhancers for regional analgesia.

Angiotensin (1-7) re-establishes heart cell communication previously impaired by cell swelling: implications for myocardial ischemia.

UNLABELLED: The influence of hypertonic solution on dye coupling was investigated in cell pairs isolated from the left ventricle of adult Sprague Dawley rats.The hypertonic solution together with Lucifer Yellow CH, were dialyzed into one cell of the pair using the whole cell clamp tecnique, and the diffusion of dye in the dialyzed as well as in non-dialyzed cell, was followed by measuring the intensity of fluorescence in both cells as a function of time.The results indicated that: (1) Lucifer Yellow CH dialyzed into one cell of the pair diffuses easily into the nondialyzed cell through gap junctions; (2) the intracellular dialysis of an hypertonic solution into one cell of the pair, increases the area of the dialyzed cell and reduced the area of the non-dialyzed cell suggesting intercellular movement of water; (3) the hypertonic solution dialyzed into one cell of the pair abolished the dye coupling; (4) the gap junction permeability (Pj) estimated before and after administration of hypertonic solution showed an appreciably decrease of Pj; (5) angiotensin (1-7) (Ang (1-7) (10-9M) administered to the bath re-established the dye coupling abolished by hypertonic solution and reduced the cell area; (6) the effect of Ang (1-7) was related to the activation of Mas receptor and was dependent on the activation of PKA. CONCLUSIONS: the reestablishment of dye coupling elicited by Ang (1-7) seen in cell pairs dialyzed with hypertonic solution, might indicate that under similar conditions like that seen during myocardial ischemia, the peptide might be of benefit preventing the impairment of cell communication and impulse propagation associated with cardiac reentrant arrhytmias.

Wet table salt and its saturated hypertonic solution for treating retinoic acid resistant plane viral warts on face.

Plane viral warts on the face can be difficult to treat at times. Various treatment approaches for facial viral warts have had variable degrees of effectiveness. In contrast, the majority of existing treatments are more costly, painful, and difficult to manage. In approximately 15.6% of instances, retinoic acid (0.05%) is also ineffective. It is very difficult to cure warts on the face at a young age. In pyogenic granuloma, table salt (NaCl) is useful as a sclerosing agent, and its hypertonic solution (15%) is effective in prolabial mucoceles. The aim of treating viral warts is to necrose infected cells and sclerose or thrombose their feeding capillaries at the wart's base.

A Simple and Rapid Method of Probiotic Bacterial Ghost Cell Preparation to Deliver Mycobacterium tuberculosis Antigen.

A bacterial ghost cell is an empty cell envelope of bacteria lacking cytoplasmic content. Bacterial ghost cells (BGs) can be used for various applications such as vaccines, adjuvants, and drug delivery systems. Since BGs offer many advantages over classically prepared vaccines, developing novel methods for the preparation of high-quality BGs remains to be an interesting field of study by various research groups. Several novel methodologies have been reported that involve the biological (gene E mediated) and combination of various chemicals such as NaOH, SDS, H2O2, CaCO3, and ethanol, non-detergent method using Tween80, limulus antimicrobial peptide, and high hydrostatic pressure method, the porcine myeloid antimicrobial peptide (PMPA) 36-lysozyme fusion method, NaOH-Penicillin/Streptolysin combination method. In this study, we have reported a novel methodology that combines the action of chemical and physical factors to produce ghost cells from gram-negative bacteria, the probiotic E.coli Nissle 1917. The mild detergent Triton X-100 and NaCl alter the permeability of the cell membrane which is further amplified by heat shock induction. This enables the cell to expel its cytoplasmic components without affecting the external morphology. The efficiency of this method was analyzed based on viability assay, cell leakage assay, live-dead cell assay, and scanning electron microscopic analysis. Moreover, the protein loading capacity was optimized for Mycobacterium tuberculosis antigen namely, ESAT-6.

Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles.

Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of 111In-radiolabelled gold nanoparticles (AuNPs; 10-15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.

Effects of hypertonic solutions on two species of human intestinal parasites during fecal examination.

Aim: Ova and parasite examination by flotation requires hypertonic solutions, which can damage the egg and cyst membranes, leading to false negatives. The authors investigated the harmful effects of ZnSO4 and C12H22O11 solutions on the ova and parasite examination. Materials & methods: The authors processed samples using the Three Fecal Test technique. Aliquots were floated in different pH levels, temperatures and solution densities. Results: Densities above 1.12 g/ml led structures to collapse after 6-10 min. pH neutralization of the ZnSO4 solution did not prevent the parasites from changing. Conclusion: All structures were altered when standard methods were performed. To delay collapse, the parasite floating under 5 °C is highly desirable.

Fecal exams require solutions that can damage the intestinal parasite's shape. This is bad for diagnosis. The authors investigated the harmful effects of these solutions on fecal exams. The authors processed samples using a technique called the Three Fecal Test. Fecal samples were floated in different conditions, including neutral and acidic solutions, high and low temperatures and varying densities of chemical solutions. Densities above 1.12 g/ml altered the structures of parasites. Neutral solutions did not prevent the structures from changing. The structures of all parasites were altered when the usual techniques were performed. Thus, the techniques for diagnosing intestinal parasites in feces must be improved. Temperatures under 5 °C are the best for preventing the destruction of parasite membranes.

Budget Impact Analysis of Hypertonic Saline Inhalations for Infant Bronchiolitis: The Colombian National Health System Perspective.

OBJECTIVES: Nebulized 3% hypertonic solution (HS) is associated with lower total cost and higher quality-adjusted life-years. Nevertheless, the expected budget impact of this drug had not been explicitly estimated. The aim of this study was to evaluate the budget impact of 3% HS in the treatment of acute bronchiolitis in Colombia. METHODS: A budget impact analysis was performed to evaluate the potential financial impact of the use of 3% HS. The analysis considered a 4-year time horizon and a Colombian national health system perspective. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which 3 % HS (added to humidified oxygen) was reimbursed, from the cost of the conventional treatment without 3 % HS (only humidified oxygen or adrenaline nebulization). Univariate 1-way sensitivity analyses were performed. RESULTS: In the base-case analysis, the 4-year costs associated with HS and non-3% HS were estimated to be $47 792 230 and $53 312 832, respectively, indicating savings for Colombian national health system equal to $5 520 602 if HS is adopted for the routine management of patients with acute bronchiolitis. This result was robust in univariate 1-way sensitivity analysis. CONCLUSION: HS was cost saving in emergency settings for treating infants with acute bronchiolitis. This evidence can be used by decision makers in Colombia to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Budget impact analysis of high-flow nasal cannula for infant bronchiolitis: the Colombian National Health System perspective.

BACKGROUND: High-flow nasal cannula is a non-invasive ventilation system that was introduced as an alternative to continuous positive airway pressure), with a marked increase in its use in pediatric care settings. However, the expected budget impact of this intervention has not been explicitly estimated. This study aimed to evaluate the budget impact of the high-flow nasal cannula for acute bronchiolitis in Colombia. METHODS: A budget impact analysis was performed to evaluate the potential financial impact deriving from high-flow nasal cannula during 2020. The analysis considered a 5-year time horizon and Colombian National Health System perspective. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which a high-flow nasal cannula is reimbursed, from the cost of the conventional treatment without a high-flow nasal cannula (supplemental oxygen through a nasal cannula up to a maximum of 2 liters per minute). Univariate one-way sensitivity analyses were performed. RESULTS: In the base-case analysis the 5-year costs associated with high-flow nasal cannula and no- high-flow nasal cannula were estimated to be US$159,585,618 and US$172,751,689 respectively, indicating savings for Colombian National Health equal to US$13,166,071 if the high-flow nasal cannula is adopted for the routine management of patients with acute bronchiolitis. This result was robust in univariate sensitivity one-way analysis. CONCLUSION: High-flow nasal cannula was cost-saving in emergency settings for treating infants with acute bronchiolitis. This evidence can be used by decision-makers in our country to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

[Hypo- and hypernatremia in the intensive care unit : Pitfalls in volume management]. / Hypo- und Hypernatriämien auf der Intensivstation : Fallstricke des Volumenmanagements.

Hypo- and hypernatremias are very frequent in intensive care unit (ICU) patients and are closely related to volume disturbances and volume management in the ICU. They are associated with longer ICU stays and significant increases in mortality. Treating them is more complex than it may initially appear. Hyponatremias are differentiated based on tonicity and volume status. With hypertonic and isotonic hyponatremias, the primary focus of treatment is the underlying hyperglycemia. In case of hypotonic hypovolemic hyponatremia, the condition is treated with balanced crystalloid solutions. In eu-/hypervolemic hypotonic hyponatremias acute treatment with hypertonic saline is necessary. Hypervolemic hypernatremia occurs almost exclusively in ICU patients, often due to infusion of hypertonic solutions. There is little evidence to guide treatment, although hypotonic infusions in conjunction with diuretics may represent a legitimate approach. Great emphasis should be placed on prevention and the infusion of hypertonic solutions should be avoided. Disturbances in plasma sodium concentrations are common, requiring close attention. Exact diagnostic classification needs to be made and volume managed accordingly.

Does Bilevel Noninvasive Ventilation Have a Bronchodilating Effect and Alter Respiratory Mechanics in Asthmatic Individuals After Bronchoprovocation? Randomized, Crossover Study.

Background: Noninvasive ventilation (NIV) has an additional important effect that does not occur with medicinal therapy: a reduction in the work of breathing. Understanding the mechanical effects of these therapies is of considerable importance and can affect clinical decision making. Objective: Evaluate the effects of NIV compared to albuterol on lung function and respiratory mechanics in asthmatic adolescents and young adults after bronchoprovocation and determine the effects of a hypertonic saline solution on lung function respiratory mechanics. Methods: A randomized crossover study was conducted involving individuals with a diagnosis of asthma. Evaluations were performed with optoelectronic plethysmography (OEP) and spirometry at baseline, after the bronchial provocation test with 4.5% saline solution and after the intervention. The order of the procedures (bilevel NIV and albuterol) was randomized, with the participants crossing over to the other treatment after a 1-week washout period. Inspiratory positive airway pressure (IPAP) 12 and expiratory positive airway pressure (EPAP) 8 cmH2O were set for 10 minutes and the dose of albuterol was 400 µg. Results: Forty individuals were included in the study (mean age: 21.6 ± 4 years; 24 females). The recovery of FEV1% was 87.9% (80.8 ± 35 to 101.1 ± 46.1, p < 0.05) after NIV and 95.9% (84.4 ± 42.4 to 110.3 ± 44.3, p < 0.05) after albuterol. Inspiratory capacity (IC; L) reduced 12% to 15% after bronchoprovocation, with 100% recovery using NIV (2.1 ± 0.7 to 2.42.4 ± 0.6, p < 0.05) and 107.6% using albuterol (2.2 ± 0.8 to 2.8 ± 1.1, p < 0.05). Regarding OEP variables, tidal volume had greater participation in the thoracic compartment. NIV led to an increase in minute volume and a return to the baseline value, which did not occur with albuterol. Conclusion: NIV recovered FEV1 and improves signs of hyperinflation by improving IC. Bronchoprovocation with a hypertonic solution reduced FEV1 by 20% and reduced IC. NIV led to a faster recovery of minute volume and reduced the contraction velocity of the muscles of the rib cage compared to albuterol, although the effects on lung function were less intense.

Hypertonic solution-induced preconditioning reduces inflammation and mortality rate.

BACKGROUND: Dysregulated inflammatory response is common cause of organ damage in critical care patients. Preconditioning/tolerance is a strategy to prevent exacerbated inflammation. The aim of this study is to analyze hypertonic saline 7.5% as a potential inducer of preconditioning that protect from a lethal dose of LPS and modulates systemic inflammatory profile in mice. METHODS: Male Balb/C mice received intravenous (i.v.) injections of Hypertonic solution (NaCl 7.5%) (0.8 ml) for 3 days, on day 8th was challenged with LPS 15 mg/kg. Controls with Saline 0.9%, urea and sorbitol were performed. Microarray of mRNA expression was analyzed from HS versus saline from macrophages to identified the pathways activated by HS. RESULTS: HS preconditioning reduced mortality after LPS injection as well reduced the cytokines release in plasma of the animals challenged by LPS. In order to check how HS induces a preconditioning state we measured plasma cytokines after each HS infusion. Repeated HS injections induced a state of preconditioning that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production. A microarray of mRNA demonstrated that Hypertonic solution increased the expression of several genes in special Mapkbp1 and Atf3. CONCLUSION: hypertonic solution induces preconditioning/tolerance reducing mortality and inflammatory response after LPS challenge.

SIADH with Severe Hyponatremia in an Elderly Man with Herpes Zoster Infection: A Causal or Casual Association?

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion is the most common cause of hypotonic hyponatremia in hospitalized patients. An elderly man with severe symptomatic hyponatremia (109 mEq/L) was diagnosed with SIADH that was likely secondary to large cutaneous herpes zoster (HZ) infection. Hypertonic saline and tolvaptan improved the patient's sodium levels and clinical condition. A one month after discharge, tolvaptan was withdrawn, due to inadequate prescription criteria, after which hyponatremia relapsed several times and was properly treated; eventually fever and sopor occurred and the patient died. SIADH secondary to HZ may induce life-threatening and long-lasting hyponatremia, which requires a prompt diagnosis and treatment.

Saline nasal irrigations for chronic rhinosinusitis: From everyday practice to evidence-based medicine. An update.

Saline nasal irrigations (SNIs) are often recommended as an additional non-pharmacological treatment for adults with chronic rhinosinusitis (CRS), for which it could even be considered a first-line treatment. However, there is a wide range of different SNI protocols. The aim of this article is to review the published literature regarding all of the potential therapeutic effects of SNIs in adult CRS patients who had not undergone sinus surgery and clarify the role of the various saline nasal solutions and protocols (particularly the volume, frequency and duration of treatment), and describe the nasal devices used. A search was made of the PubMed, Google Scholar and Ovid databases using the key words 'saline nasal irrigation' and 'chronic rhinosinusitis', or medical subject headings. The search identified 11 studies involving 663 patients. There was no consensus about but substantial agreement concerning the frequency and duration of treatment, the type of device, and the amount of solution to be used when managing CRS. A hypertonic solution with the addition of the natural minerals and oligo-elements found in seawater and some thermal waters may be associated with greater clinical benefit in terms of endoscopic scores and mucociliary clearance than isotonic solutions. Further studies are required to compare the different forms of SNI and define SNI protocols and nasal devices, while considering patient compliance.

Clinical Improvement of Subacute and Chronic Otitis Media With Effusion Treated With Hyaluronic Acid Plus Hypertonic Solution via Nasal Lavage: A Randomized Controlled Trial.

Background. This study, a randomized controlled trial, aims to demonstrate a clinically significant improvement in subacute and chronic otitis media with effusion through the administration of hyaluronic acid associated with hypertonic solution compared with the administration of hypertonic solution alone. The setting was an outpatient clinic of 20 primary care pediatrician offices affiliated with the 3 Local Health Units (Azienda Sanitaria Locale) of Naples. Materials and Methods. The study was conducted for 6 months, from October 2014 to the end of March 2015. The study saw the participation of 20 pediatricians who were experts in pneumatic otoscopy, each of whom enrolled 15 children. Each investigator was randomized to carry out the treatment with 3% hypertonic solution or high-molecular-weight hyaluronic acid + 3% hypertonic solution. Results. A total of 275 children were enrolled, of whom 11(equal to 4% ) were lost to follow-up. A total of 264 children completed the trial according to the protocol, 120 in the hyaluronic acid + hypertonic solution group and 144 in the hypertonic solution group. Hyaluronic acid associated with hypertonic solution and hypertonic solution alone administered by nasal lavage have proven to be safe and effective in the treatment of prolonged otitis media with effusion (initial score of -0.5, final score of 0.9, P < 001, for the hypertonic + hyaluronic acid group; initial score of -0.3, final score of 0.2, P < .001, for the hypertonic solution group). Though starting from a less favorable initial clinical score (-0.5 vs -0.3, P < .016), hyaluronic acid associated with hypertonic solution resulted in a significant increase in clinical healing (0.9 vs 0.2, P < .001). One interesting outcome was the significant reduction in the consumption of drugs (cortisone and antibiotics) during the follow-up.

[Clinical pilot study to evaluate the efficacy of a preservative-free hypertonic ophthalmic solution for patients with symptomatic corneal edema]. / Étude clinique pilote évaluant l'efficacité d'une solution ophtalmique hyperosmolaire sans conservateur chez des patients présentant un œdème cornéen symptomatique.

This exploratory clinical trial aims to assess the effect on visual acuity and central corneal thickness of an unpreserved hypertonic ophthalmic solution containing sodium chloride (5%) and sodium hyaluronate, in patients with chronic corneal edema caused by endothelial disease reducing their visual acuity. Twenty patients were enrolled and treated with the hypertonic solution (1 to 2 drops per eye, 4 times a day over 28 days). Progression of visual acuity (ETDRS score) and corneal thickness (ultrasonic pachymetry) was measured from baseline (without treatment) through the treatment period (Day 7 and Day 28). The analyses were performed on 18 patients (Full Analysis Set [FAS] population). The causes of corneal edema were Fuchs endothelial dystrophy in 10 cases and post-cataract surgery endothelial decompensation in 8 patients. The mean visual acuity values for the FAS population compared between baseline (Day-7) and one week of treatment (Day+7) show a significant 5-point VA improvement (P<0.001 paired Wilcoxon test). For corneal thickness, there was also a significant decrease (P=0.033 paired Wilcoxon test). Functional improvement was observed at 28 days of instillation. No adverse events were recorded during the clinical study. In conclusion, the unpreserved hyperosmolar solution containing sodium chloride and sodium hyaluronate significantly improved ETDRS visual acuity after one week of use. In this clinical trial, the solution also showed excellent tolerability results.

Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury.

Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. At 24h after TBI, MSCs (1×10(6)cells/100µl) with glycerol or mannitol were administered via the right internal carotid artery. Rats were evaluated behaviorally and immunohistochemically, and hyperpermeability of the blood-brain barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. The mannitol-treated rats showed significant improvement in motor function. Intra-arterial transplantation of MSCs caused no thromboembolic ischemia. Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI.

Development and evaluation of a chloramphenicol hypertonic ophthalmic solution.

Hypertonic ophthalmic solutions are used to treat ocular diseases associated with edema. In this study, we developed a chloramphenicol hypertonic ophthalmic solution. These drops were developed based on the cosolvency and additional dielectric constant concepts. Two different solvents: PEG 300 and glycerol were used as cosolvents. Solubility curves were plotted. Based on the solubility curves, two different solutions were selected. These solutions were evaluated for physical parameters and accelerated stability. The results indicated that chloramphenicol was stable in these formulations. The selected blend of solutions was hypertonic. Thus, the solubility and stability of chloramphenicol was enhanced using a cosolvency technique so as to develop a chloramphenicol hypertonic ophthalmic solution.