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      Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

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          Abstract

          Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration.

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          Most cited references69

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          Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase).

          The small GTPase Rho is implicated in physiological functions associated with actin-myosin filaments such as cytokinesis, cell motility, and smooth muscle contraction. We have recently identified and molecularly cloned Rho-associated serine/threonine kinase (Rho-kinase), which is activated by GTP Rho (Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) EMBO J. 15, 2208-2216). Here we found that Rho-kinase stoichiometrically phosphorylated myosin light chain (MLC). Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase. Rho-kinase phosphorylated recombinant MLC, whereas it failed to phosphorylate recombinant MLC, which contained Ala substituted for both Thr-18 and Ser-19. We also found that the phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase. Thus, it is likely that once Rho is activated, then it can interact with Rho-kinase and activate it. The activated Rho-kinase subsequently phosphorylates MLC. This may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction.
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            Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.

            The amiloride-sensitive epithelial sodium channel constitutes the rate-limiting step for sodium reabsorption in epithelial cells that line the distal part of the renal tubule, the distal colon, the duct of several exocrine glands, and the lung. The activity of this channel is upregulated by vasopressin and aldosterone, hormones involved in the maintenance of sodium balance, blood volume and blood pressure. We have identified the primary structure of the alpha-subunit of the rat epithelial sodium channel by expression cloning in Xenopus laevis oocytes. An identical subunit has recently been reported. Here we identify two other subunits (beta and gamma) by functional complementation of the alpha-subunit of the rat epithelial Na+ channel. The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel.
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              Acute lung injury and the acute respiratory distress syndrome: a clinical review.

              Acute respiratory distress syndrome and acute lung injury are well defined and readily recognised clinical disorders caused by many clinical insults to the lung or because of predispositions to lung injury. That this process is common in intensive care is well established. The mainstay of treatment for this disorder is provision of excellent supportive care since these patients are critically ill and frequently have coexisting conditions including sepsis and multiple organ failure. Refinements in ventilator and fluid management supported by data from prospective randomised trials have increased the methods available to effectively manage this disorder.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                June 2017
                05 April 2017
                05 April 2017
                : 13
                : 6
                : 2591-2598
                Affiliations
                Department of Respiratory and Critical Care Medicine, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
                Author notes
                Correspondence to: Dr Faguang Jin, Department of Respiratory and Critical Care Medicine, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, Shaanxi 710038, P.R. China, E-mail: jinfag@ 123456fmmu.edu.cn
                Article
                ETM-0-0-4302
                10.3892/etm.2017.4302
                5450642
                28587319
                6b0a445c-09d4-41d3-a440-21fd27c918b0
                Copyright: © Jin et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 10 December 2015
                : 26 January 2017
                Categories
                Review

                Medicine
                acute respiratory distress syndrome,acute lung injury,near-drowning,seawater
                Medicine
                acute respiratory distress syndrome, acute lung injury, near-drowning, seawater

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