• Journal of Trauma and Injury
• /
• v.21 no.2
• /
• pp.91-99
• /
• 2008

Purpose: Multiple rib fracture (MRF) and a hemopneumothorax accompany with most blunt chest traumas. We aimed to analyze the factors increasing the probability of a hemopneumothorax. In addition, other injuries accompanying MRF were analyzed. Methods: We retrospectively reviewed the medical records of 154 mutiple rib fracture patients who visited our hospital between January 2005 and December 2007. The medical records were reviewed for sex, age, mechanism of injury, location, number of fractures, distance of dislocated rib fragments, and presence of complications. We measured the distance of bony dislocations by using the PACS (Picture Archiving and Communication System). Results: The average number of rib fractures was $3.7{\pm}2.1$, and the number of rib fractures significantly influenced the incidence of a hemothorax (p<0.001). The risk of a hemothorax was increased in a bilateral MRF compared to a unilateral MRF (p=0.027). The distance of dislocated rib fragments influenced the probability of a hemothorax significantly (p=0.018), and subcutaneous emphysema and lung contusion were significantly associated with a pneumothorax (p=0.021, p=0.036). Conclusion: The number of MRFs did not influence the risk for a pneumothorax, but did influence the risk for a hemothorax. The laterality, distance of dislocation, also had an influence on the risk for a hemothorax. Also, subcutaneous emphysema and lung contusion were increased in cases with a pneumothorax. We must consider the possibility of a hemothorax even when the initial chest X-ray shows no evidence of a hemothorax. If a lung contusion is present, then an occult pneumothorax must be considered.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1236-1251
• /
• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

• BMB Reports
• /
• v.36 no.1
• /
• pp.95-109
• /
• 2003

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.22 no.4
• /
• pp.301-308
• /
• 2012

Objectives: To evaluate the pulmonary toxicity of 2 Korea asbestos(chrysotile, anthophyllite), Sprague-Dawely rats were exposed to 2 mg domestic asbestos by intratracheal instillation(IT). Methods: Lung function of rats was analyzed by pressure transducer(MAX1320, Buxco Electronics, USA). The effects of 2 mg asbestos(chrysotile ; $8,814,244{\times}10^{6}$ fibers/mg, average diameter 0.08 ${\mu}m$, average length 4.39 ${\mu}m$, anthophyllite ; $5,182{\times}10^{6}$ fibers/mg, average diameter 0.95 ${\mu}m$, average length 7.29 ${\mu}m$) on pulmonary function and pathological changes were evaluated at after a single IT. Lung function and histopathological evaluation were assessed in 5 animals from each group at each time point. Results: Due to differences in fiber numbers, chrysotile induce marked lung pathology and lung function change than anthophyllite at the same mass dose. Chrysotile showed notable thickening of interstitial areas surrounding the alveolar ducts and terminal bronchioles. Conclusions: On a mass dose basis, chrysotile that have 1,700 times numbers of fibers per unit weight than anthophyllite produced a greater persistent lung injury than anthophllite for at least 4 weeks after exposure.

• Development and Reproduction
• /
• v.24 no.3
• /
• pp.197-205
• /
• 2020

Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.

• Journal of Chest Surgery
• /
• v.36 no.8
• /
• pp.545-558
• /
• 2003

Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
• /
• v.12 no.1
• /
• pp.11-16
• /
• 2001

Background and Objectives : A burn injury to the glottis differs from a burn injury to the trachea, bronchi, and lung parenchyma, in that thermal injury does not occur to any significant degree below the level of the larynx, due to the effective cooling of air by the upper airway and to reflex closure of the vocal cords from a blast of hot air. Therefore, the laryngeal inhalation injury give rise to airway problem and voice change. The objectives of this study is to assess management of laryngeal inhalation injury and voice change after management. Materials and Methods : Voice choses and laryngeal injuries of eight laryngeal inhalation patients were analyzed through questionnaire, voice dynamic laboratory, and laryngeal stroboscopy. Operative management was performed to five patients for airway patiency and vocal cord movement on laryngeal pathology ind voice therapy was performed to all patients. One-year after, voice changes and laryngeal injuries were reanalyzed with same methods. Results : Vocal breathiness, decreased voice intensity, reduced voice range, and easy fatigability were major complaints of laryngeal inhalation patients. Glottic stenosis were developed to five of eight patients, and vocal cord atrophy, bowing were developed to others. Vocal cord mucosal waves were significantly decreased in all patients. Jitter(%), Shimmer(dB) were increased and Maximal phonation time(MPT) was decreased. One-year after, subjective voice changes and objective voice parameters were improved. And vocal cord mucosal waves were recovered in all patients. Conclusions : Subjective voice quality and objective voice parameters were improved after operative management for laryngeal pathology and voice therapy. And we observed recovery of vocal fold mucosal waves by laryngeal stroboscopy. We think that early preventable tracheotomy is necessary to reduce the laryngeal contact injury in laryngeal inhalation patients.

• Tuberculosis and Respiratory Diseases
• /
• v.67 no.1
• /
• pp.14-20
• /
• 2009

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-$\alpha$, MIP-2, IL-1$\beta$ and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-$\alpha$ and IL-1$\beta$ was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-$\alpha$ and IL-1$\beta$. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

• Journal of Trauma and Injury
• /
• v.22 no.1
• /
• pp.77-86
• /
• 2009

Purpose: The appropriate management of traumatic truncal arterial injury is often difficult to determine, particularly if the injury is associated with severe additional truncal lesions. The timing of repair is controversial when patients arrive alive at the hospital. Also, there is an argument about surgery versus stent-graft repair. This study's objective was to evaluate the appropriate method and the timing for treatment in cases of truncal abdominal injury associated with other abdominal lesions. Methods: The medical records at Ajou University Medical Center were reviewed for an 8-year period from January 1, 2001, to December 31, 2008. Twelve consecutive patients, who were diagnosed as having had a traumatic truncal arterial injury, were enrolled in our study. Patients who were dead before arriving at the hospital or were not associated with abdominal organ injury, were excluded. All patients involved were managed by using the ATLS (Advanced Trauma Life Support) guideline. Data on injury site, the timing and treatment method of repair, the overall complications, and the survival rate were collected and analyzed. Results: Every case showed a severe injury of more than 15 point on the ISS (injury severity score) scale. The male-to-female ratio was 9:3, and patients were 41 years old on the average. Sites of associated organ injury were the lung, spleen, bowel, liver, pelvic bone, kidney, heart, vertebra, pancreas, and diaphragm ordered from high frequency to lower frequency. There were 11 cases of surgery, and one case of conservative treatment. Two of the patients died after surgery for truncal organ injury: one from excessive bleeding after surgery and the other from multiple organ failure. Arterial injuries were diagnosed by using computed tomography in every case and 9 patients were treated by using an angiographic stent-graft repair. There were 3 patients whose vessels were normal on admission. Several weeks later, they were diagnosed as having a truncal arterial injury. Conclusion: In stable rupture of the truncal artery, initial conservative management is safe and allows management of the major associated lesions. Stent grafting of the truncal artery is a valuable therapeutic alternative to surgical repair, especially in patients considered to be a high risk for a conventional thoracotomy.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.6
• /
• pp.1343-1352
• /
• 1997

Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.