• Biomolecules & Therapeutics
• /
• v.26 no.6
• /
• pp.553-559
• /
• 2018

Investigations into the development of new therapeutic agents for lung inflammatory disorders have led to the discovery of plant-based alternatives. The rhizomes of Anemarrhena asphodeloides have a long history of use against lung inflammatory disorders in traditional herbal medicine. However, the therapeutic potential of this plant material in animal models of lung inflammation has yet to be evaluated. In the present study, we prepared the alcoholic extract and derived the saponin-enriched fraction from the rhizomes of A. asphodeloides and isolated timosaponin A-III, a major constituent. Lung inflammation was induced by intranasal administration of lipopolysaccharide (LPS) to mice, representing an animal model of acute lung injury (ALI). The alcoholic extract (50-200 mg/kg) inhibited the development of ALI. Especially, the oral administration of the saponin-enriched fraction (10-50 mg/kg) potently inhibited the lung inflammatory index. It reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Histological changes in alveolar wall thickness and the number of infiltrated cells of the lung tissue also indicated that the saponin-enriched fraction strongly inhibited lung inflammation. Most importantly, the oral administration of timosaponin A-III at 25-50 mg/kg significantly inhibited the inflammatory markers observed in LPS-induced ALI mice. All these findings, for the first time, provide evidence supporting the effectiveness of A. asphodeloides and its major constituent, timosaponin A-III, in alleviating lung inflammation.

• Journal of Trauma and Injury
• /
• v.22 no.2
• /
• pp.242-247
• /
• 2009

Purpose: Trauma is an important cause of death in children. In particular, the liver is the second most commonly organ injured by blunt abdominal trauma. Treatment of patients with liver injury is has changed, and non-operative treatment is the major treatment method at present. In this study, we reviewed traumatic liver injury in pediatric patients. Methods: Seventy-seven patients younger than 16 years of age with traumatic liver injury were assessed for 10 years from July 1999 to June 2009 at Wonju Christian hospital. Records of the patients were reviewed retrospectively. Demographic and clinical data were analyzed. Results: The median age was 6 years, and the male-to-female ratio was 1.2 : 1. The most common injury grade was grade I. The majority of injuries were caused by was traffic accidents, and the second most common cause of injuries was falls. Twenty-four patients had liver injuries alone, and the most common accopaning injury was a lung injury. The average hospital stay was 20.7 days, and the average ICU stay was 4.8 days. Four patients died (5.2%). There were 6 patients with under 10 points on the Glasgow coma scale (GCS). Among these patients, three died. All mortality cases had over 16 points on the Injury Severity Score (ISS). Two patients were treated surgically, one of whom died. Of the 75 patients with non-operative management, three died due to associated injuries. Conclusion: Most pediatric patients with liver injury have good results with non-operative management. Associated injuries and hemodynamic instability are predictive of patient outcome, and those with isolated liver injuries can be successfully managed non-operatively.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.4
• /
• pp.547-557
• /
• 1996

Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

• Journal of Ginseng Research
• /
• v.42 no.4
• /
• pp.476-484
• /
• 2018

Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.

• Journal of Chest Surgery
• /
• v.41 no.2
• /
• pp.177-188
• /
• 2008

Background: To evaluate the effects of inhaled nitric oxide (NO) and sphingosine 1-phosphate (S1P) as potential therapeutic agents of acute lung injury, we analyzed the morphology in vivo of the pulmonary microstructure using intravital videomicroscopy in a rat model of acute lung injury. Material and Method: Sprague Dawley rats were divided into five groups: a control group that underwent normal saline aspiration, an acute lung injury (ALI) group that underwent hydrochloric acid aspiration, and three treatment groups that underwent hydrochloric acid aspiration and were administered therapeutic agents- the S1P group, the NO group, and the S1P+NO group (n=7 per group). To quantify alveolar compliance and interstitial edema, the diameters of all measurable alveoli and interalveolar septa were averaged at one and two hours after aspiration. Alveolar compliance was determined according to diameter changes during the respiratory cycle and the change in tidal volume. Result: At two hours after aspiration, the mean alveolar compliance (% change) in the All group decreased significantly versus the control group of rats (respiratory cycle: 1.9% for the ALI group vs 6.5% for the control group, p=0.03; tidal volume: 3.2% for the ALI group vs 9.1% for the control group, p=0.003) and versus the NO group (tidal volume: 3.2% for the ALI group vs 16.9% for the NO group, p=0.001). At two hours after aspiration, the mean interalveolar septal thickness in the NO group tended to be smaller as compared to that in the All group ($15.2{\mu}m$ for the ALI group vs $12.3{\mu}m$ for the NO group, p=0.06). S1P did not exert a significant effect on the pulmonary microstructure of the injured rat lung. Conclusion: Improved alveolar compliance and reduced interstitial edema, observed by intravital videomicroscopy, suggest that inhaled NO ameliorates lung injury.

• Nuclear Medicine and Molecular Imaging
• /
• v.40 no.1
• /
• pp.28-32
• /
• 2006

Purpose: Conventional chest X-ray and pulmonary function test cannot sensitively detect inhalation injury. Bronchoscopy is known to be the gold standard but it is invasive method. We evaluated whether lung inhalation/perfusion scans can sensitively detect inhalation injury of fire victims. Materials and Methods: Nineteen patients (male 9, female 10, mean age 31.6 yr) of fire victims were enrolled in this study. Inhalation lung scan was performed 2 days later after inhalation injury with $^{99m}Tc$-technegas. Perfusion lung scan was performed 4 days later with $^{99m}Tc$- MAA (macroaggregated albumin). Follow up lung scans were performed 16 and 18 days later for each. Chest X-ray was performed in all patients and bronchoscopy was performed in 17 of 19 patients at the same period. Pulmonary function test was performed in 9 patients. Results: Four of 19 patients showed inhalation and perfusion defects and one showed inhalation defect but, normal perfusion scan findings. These five patients with abnormal scan findings showed abnormal bronchoscopic findings and severe respiratory symptoms. On chest X-ray, 2 of them had pulmonary tuberculosis and one of them showed pulmonary congestion. FEV1 /FVC was abnormal in 3 patients. On the follow up scan, all patients with abnormal initial scan findings showed improved findings and they had improved clinical state. Conclusion: Inhalation/perfusion lung scans can detect inhalation burn injury noninvasively in early stage and may be useful in therapeutic decision making and follow up of patients.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.26 no.1
• /
• pp.40-46
• /
• 2012

Cigarette smoking is known to be associated with various chronic pulmonary and cardiovascular diseases ranging from inflammation to cancer. Not only first-hand smoke but also second-hand smoke is suggested to be a factor of health risk. This study was to investigate whether Platycodi Radix extract administration would alter oxidative stress in lung leading to protection of cigarette smoke-induced lung damage. Sprague-Dawley rats were randomly divided into 3 groups; Intact, Smoke+PR and Smoke+Vehicle. In Smoke+PR and Smoke+Vehicle group, the exposure to cigarette smoke was performed for 15 min/day for 4 weeks in ventilated smoking chamber. The Platycodi Radix extract and saline were orally administrated to Smoke+PR and Smoke+Vehicle group each. The rats of Intact group were just kept in ventilated chamber without cigarette smoke. After the experiment for 4 weeks, the lung tissues were collected for histological observation and immunohistochemistry. In Results, airspace enlargement and goblet cell hyperplasia were observed after 4 weeks' exposure to cigarette smoke. Whereas, the oral administration of Platycodi Radix extract for 4 weeks reduced airspace enlargement and goblet cell hyperplasia. Moreover, the alterations of BAX/Bcl-2 proteins in lung tissues were observed. These results suggest that Platycodi Radix extract ameliorates lung damage in cigarette smoke-exposed rats and has protective effects on second-hand smoke injury.

• The Korean Journal of Physiology and Pharmacology
• /
• v.27 no.3
• /
• pp.209-220
• /
• 2023

This study is to determine the regulation of nitric oxide synthase 3 (NOS3) by edaravone in mice with hypoxic pulmonary hypertension (HPH). C57BL/6J mice were reared in a hypoxic chamber. HPH mice were treated with edaravone or edaravone + L-NMMA (a NOS inhibitor). Lung tissue was collected for histological assessment, apoptosis analysis, and detection of malondialdehyde, superoxide dismutase, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and NOS3. The levels of serum TNF-α and IL-6 were also measured. Immunohistochemistry was used to visualize the expression of α-smooth muscle actin (SMA) in pulmonary arterioles. Edaravone treatment improved hemodynamics, inhibited right ventricular hypertrophy, increased NOS3 expression, and reduced pathological changes, pulmonary artery wall thickness, apoptotic pulmonary cells, oxidative stress, and the expression of TNF-α, IL-6, and α-SMA in HPH mice. L-NMMA treatment counteracted the lung protective effects of edaravone. In conclusion, edaravone might reduce lung damage in HPH mice by increasing the expression of NOS3.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.478-486
• /
• 2000

Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group $171.6{\pm}24.1{\times}10^5$, 12 hour group $194.8{\pm}17.9{\times}10^5$, 24 hour group $207.6{\pm}27.1{\times}10^5$, p<0.05). oHoHH However the 48 hour group ($200.0{\pm}77.8{\times}10^5$) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group $0.7{\pm}0.2{\mu}m$, 12 hour group $1.5{\pm}0.4{\mu}m$, 24 hour group $2.3{\pm}0.4{\mu}m$, p<0.05). However the 48 hour group did not show further change ($2.5{\pm}0.4{\mu}m$). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge ($\beta=0.379$.$\beta=0.694$. p<0.05) ; however, fraction 3 was rather decreased following the hyperoxic challenge($\beta=0.815$. p<0.05), and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. Conclusion : In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in an acute hyperoxic lung injury model But further study, including biochemical and immunological function of these subpopulations, is needed.

• Journal of Trauma and Injury
• /
• v.23 no.1
• /
• pp.49-52
• /
• 2010

A hemothorax usually occur, due to injuries to the intercostal and great vessels, pulmonary damage, and sometimes fractured ribs. We report a case in which the hemothorax that occurred, neither intrathoracic injury nor injury to internal thoracic vessels and organs, via lacerated diaphragmatic and liver laceration due to a right upper part of anterior chest stab injury caused by a sharp object. The patient's general conditions gradually worsened, so chest and abdominal computed tomogram were taken. The abdominal computed tomogram revealed diaphragmatic injuries and bleeding from the lacerated liver. We performed an exploratory laparotomy to control the bleeding from the lacerated liver with simple primary sutures. In addition exploration was performed in the right pleural space through the lacerated diaphragm with a thoracoscopic instrument. There were no bleeding foci in the right pleural space, the vessels, or the lung on the thoracoscopic video. Closure of the lacerated diaphragm was achieved with simple, primary sutures. The postoperative course of the patient was uneventful, and the patient was discharged.