• Journal of Chest Surgery
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• v.35 no.5
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• pp.343-349
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• 2002

background: In an attempt to investigate the role of oxidants in the activation of phospholipase $A_2$(PLA$_2$) and endogenous oxidative stress in the lung. acute inflammatory lung injury was induced by the instillation of hydrogen peroxide into the trachea of Sprague-Dawley rats. Material and Method: To prove the hypothesis thats released oxidants from neutrophils activate the PLA$_2$ retrogradely, activities of PLA$_2$ and lysoplatelet activating factor acetyltransferase(lysoPAF AT) were assayed i hours after instillation of hydrogen peroxide. In addition, to confirm the impairing effects of the activation of PLA$_2$ associated with endogenous oxidative stress, lung weight/body weight ratio(L$\times$10$^{-3}$ B), protein contents(mg/two lungs) in bronchoalveolar lavage(BAL) were measured. As neutrophilic respiratory burst has been known to play a pivotal role in the genesis of endogenous oxidative stress associated with acute inflammatory lung injury, BAL neutrophils counts and level of lung myelperoxidase(MPO) were measured after hydorgen peroxide insult. Morphological and histochemical studies were also performed to identify the effect of the endogenous oxidative stress. Result: Five hours after hydrogen peroxide instillation, lungs showed marked infiltration of neutrophils and increased weight. Protein contents in BAL increased significantly compared to those of normal rats. PLA$_2$ activity was enhanced in the hydrogen peroxide instilled group. Interestingly, the accelerated production of platelet activating factor(PAF) was confirmed by the increased activity of lysoPAF AT in the $H_2O$$_2$ employed lung. Morphologically, light microscopic findings of lungs after instillation of hydrogen peroxide showed atelectasis and infiltration of inflammatory cells, which was thought to be caused by lipid mediators produced by PLA$_2$ activation. In cerium chloride cytochemical electron microscopy, dense deposits of cerrous perhydroxide were identified. In contrast, no deposit of cerrous perhydroxide was found in the normal lung.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.501-510
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• 2002

Background: The various pathogeneses of acute respiratory distress syndrome have been suggested but not established yet. In the present study, the role of group II phospholipase $A_2$($PLA_2$) in the pathogenesis of gut ischemia-reperfusion(I/R) induced acute lung injury (ALI), especially in the pulmonary oxidative stress with infiltration of neutrophils was investigated. Material and Method: To induce ALI, reperfusion of mesentery was done for 120 min after clamping of superior mesenteric artery for 60 min in Sprague-Dawley rats that weighed about 300g. To exmaine the role of group II $PLA_2$ in ALI, especially endothelial injury associated with the action of neutrophils, lung myeloperoxidase activity, lung leak index, bronchoalveolar lavage fluid protein were measured, and pulmonary $PLA_2$ activity changes in gut I/R were also measured. The role of group II $PLA_2$in the neutrophilic generation of free radicals was assessed by inhibiting group II $PLA_2$ with rutin, manoalide and scalaradial. Furthermore, to verify the oxidative stress in the lung, histologic and free radical detecting cytochemical electron microscopy were done. Result: After reperfusion, ALI was developed with accumulation of neutrophils in the lung, which was confirmed by the increase of myeloperoxidase activity, lung leak index and bronchoalveolar lavage protein (p<0.001). The pulmonary and intestinal group II $PLA_2$ activities significantly increased after gut I/R which were reversed by rutin(p<0.001). In vitro, cytochrome-c reduction assay denoted the inhibitory effects of rutin, scalaradial and manoalide on the production of free radicals from isolated human neutrophils. Histologically, neutrophilic accumulation and pericapillary edema in the lung after gut I/R was detected by light microscopy which was suppressed by rutin. In $CeCl_3$ cytochemical electron microscopy, the increased production of hydrogen peroxide in the lung after gut I/R was confirmed and also the production of hydrogen peroxide was decreased by rutin. Conclusion: On the basis of these experimental results, the inhibition of group II $PLA_2$ seemed to mitigate gut I/R-induced ALI by suppressing the production of free radicals from the infiltrated neutrophils. Collectively, group II $PLA_2$ seems to play a crucial role in gut I/R-induced ALI by neutrophilic oxidative stress.

• Tuberculosis and Respiratory Diseases
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• v.63 no.5
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• pp.423-429
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• 2007

Background: Alveolar recruitment (RM) is one of the primary goals of respiratory care for an acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The purposes of alveolar recruitment are an improvement in pulmonary gas exchange and the protection of atelectrauma. This study examined the effect and safety of the alveolar RM using pressure control ventilation (PCV) in early ALI and ARDS patients. Methods: Sixteen patients with early ALI and ARDS who underwent alveolar RM using PCV were enrolled in this study. The patients data were recorded at the baseline, and 20 minutes, and 60 minutes after alveolar RM, and on the next day after the maneuver. Alveolar RM was performed with an inspiratory pressure of $30cmH_2O$ and a PEEP of $20cmH_2O$ in a 2-minute PCV mode. The venous $O_2$ saturation, central venous pressure, blood pressure, pulse rate, $PaO_2/FiO_2$ ratio, PEEP, and chest X-ray findings were obtained before and after alveolar RM. Results: Of the 16 patients, 3 had extra-pulmonary ALI/ARDS and the remaining 13 had pulmonary ALI/ARDS. The mean PEEP was 11.3 mmHg, and the mean $PaO_2/FiO_2$ ratio was 130.3 before RM. The $PaO_2/FiO_2$ ratio increased by 45% after alveolar RM. The $PaO_2/FiO_2$ ratio reached a peak 60 minutes after alveolar RM. The Pa$CO_2$ increased by 51.9 mmHg after alveolar RM. The mean blood pressure was not affected by alveolar RM. There were no complications due to pressure injuries such as a pneumothorax, pneumomediastinum, and subcutaneous emphysema. Conclusion: In this study, alveolar RM using PCV improved the level of oxygenation in patients with an acute lung injury and acute respiratory distress syndrome. Moreover, there were no significant complications due to hemodynamic changes and pressure injuries. Therefore, alveolar RM using PCV can be applied easily and safely in clinical practice with lung protective strategy in early ALI and ARDS patients.

• Journal of Trauma and Injury
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• v.37 no.2
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• pp.147-150
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• 2024

This case report describes the management of a 51-year-old female patient who arrived at the emergency room with a stab wound to the upper right chest. Immediate medical interventions were undertaken, including blood transfusions and endotracheal intubation. To prevent tension and control bleeding, gauze packing was applied directly through the large open wound. Further surgical exploration identified a laceration in the lung, necessitating a right upper lobe resection. Postoperatively, the patient's vital signs stabilized, and she was subsequently discharged without complications. This case highlights the decision-making process in selecting between an emergency department thoracotomy and an operating room thoracotomy for patients with penetrating chest trauma. It also illustrates the role of gauze packing in managing tension and hemorrhage. In summary, gauze packing can be an effective interim measure for stabilizing patients with traumatic injuries, unstable vital signs, and large open chest wounds, particularly when a chest tube is already in place, to prevent tension and facilitate bleeding control prior to surgical intervention.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.379-390
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• 1997

Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

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

• Korean Journal of Veterinary Service
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• v.47 no.2
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• pp.95-100
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• 2024

An 11-year-old neutered male Dachshund dog weighing 7 kg presented with acute onset of respiratory distress after subcutaneous administration of cytosine arabinoside (CA). The patient previously diagnosed with meningoencephalitis of unknown origin and was being treated with oral prednisolone, levetiracetam, potassium bromide, gabapentin, and periodic subcutaneous CA administration (50 mg/m², q 12 h, subcutaneous, 4 times, every 3 weeks). The patient developed tachypnea with labored respiratory effort after 9th CA administration. Thoracic radiograph revealed bilateral diffuse interstitial to alveolar pulmonary opacities, and echocardiogram indicated no evidence of left-sided heart failure. Based on the onset coinciding with the administration of CA, low possibility of other pulmonary disease, remission of symptom showed after discontinuation of CA, we suspected CA-induced interstitial lung disease. The patient's pulmonary opacities on the radiograph improved to a similar degree as before the adverse event over time, but respiratory symptoms were not fully resolved. Sildenafil (2 mg/kg, per oral, q 12 h) was given as therapeutic trial to manage possible pulmonary hypertension, suspected a sequela of the lung disease, based on an echocardiographic evidence and clinical signs. The patient's respiratory symptom was well managed since, and achieved discontinuation of sildenafil.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.546-555
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• 2024

Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid and inducible nitric oxide synthase/cyclooxygenase-2/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of ALI mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1/ NAD(P)H quinone dehydrogenase 1 in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.547-557
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• 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
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• v.42 no.4
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• pp.476-484
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• 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.