Institute of Aerospace and Undersea Medicine

Taipei, Taiwan

Institute of Aerospace and Undersea Medicine

Taipei, Taiwan

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Wu S.-Y.,Institute of Aerospace and Undersea Medicine | Li M.-H.,Institute of Aerospace and Undersea Medicine | Ko F.-C.,Taoyuan Armed Forces General Hospital | Wu G.-C.,Taoyuan Armed Forces General Hospital | And 3 more authors.
PLoS ONE | Year: 2013

Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in part by the anti-inflammatory and anti-apoptotic action of HO-1. © 2013 Wu et al.


Wu S.-Y.,Graduate Institute of Medical science | Wu C.-P.,Landseed Hospital | Kang B.-H.,Institute of Aerospace and Undersea Medicine | Li M.-H.,Institute of Aerospace and Undersea Medicine | And 4 more authors.
Critical Care Medicine | Year: 2012

Objective: Although ischemia-reperfusion injury is a major determinant of primary graft dysfunction after lung transplantation, an approach to extend preoperative lung preservation to postoperative protection has not yet been defined. The purpose of this study was to determine the protective effects of and the signal pathway regulated by hypercapnic acidosis in ischemia- reperfusion-induced lung injury. Design: Animal study. Setting: Animal care facility procedure room in a medical center. Subjects: Adult male Sprague-Dawley rats. Interventions: Lung injury was induced in a clinically relevant ex vivo animal model. Animals were divided into a control group (FICO2, 5%; n = 6), ischemia-reperfusion group (FICO2, 5%; n = 6), and hypercapnic acidosis (ischemia-reperfusion + hypercapnic acidosis) group (FICO2, 10%; n = 6). Measurements and Main Results; Ischemia-reperfusion caused significant increases in alveolar lavage and perfusate tumor necrosis factor-α, inflammatory cell infiltration, lung tissue malondialdehyde, bronchoalveolar lavage fluid protein concentration and lactate dehydrogenase activity, lung weight gain, and infiltration coefficient. Ventilation with 10% CO2 significantly suppressed the inflammatory response and attenuated lung ischemia-reperfusion injury. Our results also showed that hypercapnic acidosis significantly inhibited the ischemia-reperfusion-induced phosphorylation and nuclear translocation of nuclear factor-κB. This was associated with elevation of inhibitor of nuclear factor-κB-α level and reduced IκB kinase-β phosphorylation, suggesting a suppression of IκB kinase and thus IκB-α activation. Conclusions: Hypercapnic acidosis may attenuate lung ischemia-reperfusion injury by suppressing the activation of the IκB kinase-nuclear factor-κB pathway. Copyright © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Wu S.-Y.,Institute of Aerospace and Undersea Medicine | Tang S.-E.,Tri Service General Hospital | Ko F.-C.,Taoyuan Armed Forces General Hospital | Wu G.-C.,Taoyuan Armed Forces General Hospital | And 3 more authors.
Anesthesiology | Year: 2015

Background: Evidence reveals that histone deacetylase (HDAC) inhibition has potential for the treatment of inflammatory diseases. The protective effect of HDAC inhibition involves multiple mechanisms. Heme oxygenase-1 (HO-1) is protective in lung injury as a key regulator of antioxidant response. The authors examined whether HDAC inhibition provided protection against ischemia-reperfusion (I/R) lung injury in rats by up-regulating HO-1 activity. Methods: Acute lung injury was induced by producing 40 min of ischemia followed by 60 min of reperfusion in isolated perfused rat lungs. The rats were randomly allotted to control group, I/R group, or I/R + valproic acid (VPA) group with or without an HO-1 activity inhibitor (zinc protoporphyrin IX) (n = 6 per group). Results: I/R caused significant increases in the lung edema, pulmonary arterial pressure, lung injury scores, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 concentrations in bronchoalveolar lavage fluid. Malondialdehyde levels, carbonyl contents, and myeloperoxidase-positive cells in lung tissue were also significantly increased. I/R stimulated the degradation of inhibitor of nuclear factor-κB-α, nuclear translocation of nuclear factor-κB, and up-regulation of HO-1 activity. Furthermore, I/R decreased B-cell lymphoma-2, heat shock protein 70, acetylated histone H3 protein expression, and increased the caspase-3 activity in the rat lungs. In contrast, VPA treatment significantly attenuated all the parameters of lung injury, oxidative stress, apoptosis, and inflammation. In addition, VPA treatment also enhanced HO-1 activity. Treatment with zinc protoporphyrin IX blocked the protective effect of VPA. Conclusions: VPA protected against I/R-induced lung injury. The protective mechanism may be partly due to enhanced HO-1 activity following HDAC inhibition. © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.


PubMed | Tri Service General Hospital, Taoyuan Armed Forces General Hospital and Institute of Aerospace and Undersea Medicine
Type: Journal Article | Journal: International immunopharmacology | Year: 2015

Trichostatin A (TSA) is a histone deacetylase inhibitor with anti-inflammatory effects. Nonetheless, little information is available about the effect of TSA in ischemia-reperfusion (IR)-induced lung injury. In a perfused rat lung model, IR was induced by 40min of ischemia followed by 60min of reperfusion. The rat lungs were randomly divided into several groups including control, control+TSA (0.1mg/kg), IR, and IR+various dosages of TSA (0.05, 0.075, 0.1mg/kg). Bronchoalveolar lavage fluids and lung tissues were obtained and examined at the end of the experiment. TSA dose-dependently diminished IR-induced increased vascular permeability and edema, pulmonary artery pressure, and histological changes in the lungs. Additionally, TSA suppressed lavage tumor necrosis factor- and cytokine-induced neutrophil chemoattractant concentrations, cell infiltration, and myeloperoxidase-positive cells in the lung tissue. Furthermore, TSA attenuated the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase, degradation of the inhibitor of nuclear factor (NF)-B, and nuclear NF-B levels. TSA also decreased poly (ADP-ribose) polymerase but enhanced acetylated histone H3 acetylation, Bcl-2, and mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in IR lung tissue. Therefore, TSA exerted a protective effect on IR-induced lung injury via increasing histone acetylation and MKP-1 protein expression, repressing NF-B, mitogen-activated protein kinase, and apoptosis signaling pathways.


PubMed | Fu Jen Catholic University and Institute of Aerospace and Undersea Medicine
Type: Journal Article | Journal: PloS one | Year: 2015

Ventilator-induced lung injury is associated with inflammatory mechanism and causes high mortality. The objective of this study was to discover the role of IL-33 and its ST2 receptor in acute lung injury induced by mechanical ventilator (ventilator-induced lung injury; VILI). Male Wistar rats were intubated after tracheostomy and received ventilation at 10 cm H2O of inspiratory pressure (PC10) by a G5 ventilator for 4 hours. The hemodynamic and respiratory parameters were collected and analyzed. The morphological changes of lung injury were also assessed by histological H&E stain. The dynamic changes of lung injury markers such as TNF- and IL-1 were measured in serum, bronchoalveolar lavage fluid (BALF), and lung tissue homogenization by ELISA assay. During VILI, the IL-33 profile change was detected in BALF, peripheral serum, and lung tissue by ELISA analysis. The Il-33 and ST2 expression were analyzed by immunohistochemistry staining and western blot analysis. The consequence of VILI by H&E stain showed inducing lung congestion and increasing the expression of pro-inflammatory cytokines such as TNF- and IL-1 in the lung tissue homogenization, serum, and BALF, respectively. In addition, rats with VILI also exhibited high expression of IL-33 in lung tissues. Interestingly, the data showed that ST2L (membrane form) was highly accumulated in the membrane fraction of lung tissue in the PC10 group, but the ST2L in cytosol was dramatically decreased in the PC10 group. Conversely, the sST2 (soluble form) was slightly decreased both in the membrane and cytosol fractions in the PC10 group compared to the control group. In conclusion, these results demonstrated that ST2L translocation from the cytosol to the cell membranes of lung tissue and the down-expression of sST2 in both fractions can function as new biomarkers of VILI. Moreover, IL-33/ST2 signaling activated by mechanically responsive lung injury may potentially serve as a new therapy target.


Chu H.,Institute of Aerospace and Undersea Medicine | Chu H.,Tri Service General Hospital | Li M.-H.,Institute of Aerospace and Undersea Medicine | Juan S.-H.,Institute of Aerospace and Undersea Medicine | Chiou W.-Y.,Gangshan Armed Forces Hospital
Journal of Alternative and Complementary Medicine | Year: 2012

Objectives: Motion sickness (MS) is evoked by the conflict among somatosensory, visual, and vestibular input. Some of the MS symptoms and signs are mediated by activation of the autonomic nervous system (ANS). Transcutaneous electrical nerve stimulation (TENS), a maneuver used for pain control, was found to influence cardiovascular responses through ANS reflex, and to enhance motor function, visuospatial abilities, postural control, and cognitive function. The purpose of the present study is to investigate the effects of TENS on MS. Subjects and design: Fifteen (15) healthy young men participated in a within-subjects crossover study. Each completed four test sessions (control, rotation, TENS, TENS+rotation) in randomized order. Rotary chair (120°/s) combined with pitch movement of the subject's head was used as a model to provoke MS. Whole rotation protocol consisted of 5 1-minute rotations, each separated by a 1-minute rest period. TENS protocol involved simultaneous electrical stimulation of posterior neck and Zusanli acupoint. Outcome measures: Motion sickness susceptibility was rated on a standardized questionnaire (Motion Sickness Susceptibility Questionnaire). Motion sickness symptoms, blood pressure (BP), skin temperature, heart rate (HR), and heart rate variability (HRV) were measured. Saliva samples were collected to analyze the level of stress markers. Cognitive function was evaluated with d2 test prior to and after MS provocation. Results: Spinning by itself significantly decreased task response speed and contraction. MS symptom scores, BP, as well as the sympathetic parameter of HRV increased progressively with MS provocation (p<0.05), but skin temperature decreased (p=0.023). Severity of MS symptoms significantly decreased with TENS intervention (p<0.05). After TENS treatment, subjects were able to concentrate better and showed fewer errors in a cognitive test. Salivary cortisol concentration significant decreased after TENS treatment. Conclusions: Sympathetic activity increased but parasympathetic activity decreased during MS. TENS was effective in reducing MS symptoms as well as alleviating cognitive impairment. © Copyright 2012, Mary Ann Liebert, Inc. 2012.


Chu H.,Institute of Aerospace and Undersea Medicine | Chu H.,Tri Service General Hospital | Li M.-H.,Institute of Aerospace and Undersea Medicine | Huang Y.-C.,Institute of Aerospace and Undersea Medicine | Lee S.-Y.,Institute of Aerospace and Undersea Medicine
BMC Complementary and Alternative Medicine | Year: 2013

Background: Flight simulators have been used to train pilots to experience and recognize spatial disorientation, a condition in which pilots incorrectly perceive the position, location, and movement of their aircrafts. However, during or after simulator training, simulator sickness (SS) may develop. Spatial disorientation and SS share common symptoms and signs and may involve a similar mechanism of dys-synchronization of neural inputs from the vestibular, visual, and proprioceptive systems. Transcutaneous electrical nerve stimulation (TENS), a maneuver used for pain control, was found to influence autonomic cardiovascular responses and enhance visuospatial abilities, postural control, and cognitive function. The purpose of present study was to investigate the protective effects of TENS on SS.Methods: Fifteen healthy young men (age: 28.6 ± 0.9 years, height: 172.5 ± 1.4 cm, body weight: 69.3 ± 1.3 kg, body mass index: 23.4 ± 1.8 kg/m2) participated in this within-subject crossover study. SS was induced by a flight simulator. TENS treatment involved 30 minutes simultaneous electrical stimulation of the posterior neck and the right Zusanli acupoint. Each subject completed 4 sessions (control, SS, TENS, and TENS + SS) in a randomized order. Outcome indicators included SS symptom severity and cognitive function, evaluated with the Simulator Sickness Questionnaire (SSQ) and d2 test of attention, respectively. Sleepiness was rated using the Visual Analogue Scales for Sleepiness Symptoms (VAS-SS). Autonomic and stress responses were evaluated by heart rate, heart rate variability (HRV) and salivary stress biomarkers (salivary alpha-amylase activity and salivary cortisol concentration).Results: Simulator exposure increased SS symptoms (SSQ and VAS-SS scores) and decreased the task response speed and concentration. The heart rate, salivary stress biomarker levels, and the sympathetic parameter of HRV increased with simulator exposure, but parasympathetic parameters decreased (p < 0.05). After TENS treatment, SS symptom severity significantly decreased and the subjects were more able to concentrate and made fewer cognitive test errors (p < 0.05).Conclusions: Sympathetic activity increased and parasympathetic activity decreased after simulator exposure. TENS was effective in reducing SS symptoms and alleviating cognitive impairment.Trial registration number: Australia and New Zealand Clinical Trials Register: http://ACTRN12612001172897. © 2013 Chu et al.; licensee BioMed Central Ltd.


Tang S.-E.,Graduate Institute of Medical science | Tang S.-E.,Tri Service General Hospital | Wu C.-P.,Landseed Hospital | Wu S.-Y.,Institute of Aerospace and Undersea Medicine | And 6 more authors.
Free Radical Biology and Medicine | Year: 2014

Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory effects occur through induction of uncoupling proteins to reduce oxidative stress. In this study, we tested the hypothesis that exogenous recombinant human STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20 μg/10 g body wt), and lung injury was assessed 24 h later by analyzing pulmonary edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation, oxidative stress, and expression of STC1 and its downstream uncoupling protein 2 (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed initially but was subsequently upregulated after STC1 elevation in response to intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1 h before or after LPS spraying significantly attenuated pulmonary inflammation, oxidative stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and UCP2 and significantly increased the extent of lung injury. These findings suggest that STC1 is an endogenous stress protein that may counteract LPS-induced lung injury by inhibiting the inflammatory cascade and inducing antioxidant and antiapoptotic mechanisms. However, the potential clinical application of STC1 and the direct linkage between UCP2 and LPS-induced lung injury remain to be further investigated. © 2014 Elsevier Inc.


PubMed | China Medical University at Taichung, National formosa University, Institute of Aerospace and Undersea Medicine and National Defense Medical Center
Type: Journal Article | Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology | Year: 2015

Rhodiola, a popular herb, has been used for treating high altitude sicknesses, depression, fatigue, and diabetes. However, the detailed mechanisms by which Rhodiola crenulata functions in the liver need further clarification.The current study was designed to examine the effects of Rhodiola crenulata root extract (RCE) on hepatic glucose production.Human hepatoma HepG2 cells were treated with RCE for 6 h. Glucose production, the expression level of p-AMPK, and the expression of key gluconeogenic genes were measured. The effects of RCE were also studied in Sprague-Dawley (SD) rats. The efficacy and underlying mechanism of RCE in the liver were examined.RCE significantly suppressed glucose production and gluconeogenic gene expression in HepG2 cells while activating the AMPK signaling pathway. Interestingly, RCE-suppressed hepatic gluconeogenesis was eliminated by an AMPK-specific inhibitor, but not by the PI3K/AKT-specific inhibitor. In addition, oral administration of RCE significantly increased phosphorylated AMPK levels and inhibited gluconeogenic gene expression in the rat liver. Furthermore, RCE treatment also decreased plasma glucose concentration in rats.We present in vitro and in vivo evidence that RCE might exert the glucose-lowering effect partly by inhibiting hepatic gluconeogenesis through activating the AMPK signaling pathway. These findings provide evidence that Rhodiola crenulata may be helpful for the management of type II diabetes.


PubMed | Gangshan Branch of Armed Forces Kaohsiung General Hospital, Institute of Aerospace and Undersea Medicine and Chinese Institute of Aviation Medicine
Type: Journal Article | Journal: Case reports in plastic surgery & hand surgery | Year: 2016

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, locally infiltrative tumor of intermediate malignancy. It is mostly found on the trunk and head, rarely on hands. The course of evaluation and treatment of a young pilot with DFSP on left middle finger is reported. The clinical issues and aeromedical considerations of this rare tumor is discussed.

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