• Tuberculosis and Respiratory Diseases
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• v.69 no.5
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• pp.337-347
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• 2010

Background: Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. Methods: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which $50{\mu}L$ of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/$50{\mu}L$ of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor $(NF)-{\kappa}B$ were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-${\beta}1$ were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory's phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. Results: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-${\alpha}$ and IL-$1{\beta}$ concentrations and $NF-{\kappa}B$ activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-${\beta}1$ concentration, and Mallory's PTAH stain than the LPS group, but the differences were not significant (p>0.05). Conclusion: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.464-470
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• 2008

Background: This study examined the role of neutrophilc oxidative stress in an $O_2-induced$ acute lung injury (ALI). Methods: For 48 h, experimental rats were exposed to pure oxygen (normobaric hyperoxia) in a plastic cage. Forty-eight hours after $O_2$ breathing, the rats were sacrificed and the parameters for ALI associated with neutrophilic oxidative stress were assessed Results: Normobaric pure oxygen induced ALI, which was quite similar to ARDS. The $O_2-induced$ neutrophilic oxidative stress was identified by confirming of the increase in lung myeloperoxidase, BAL neutrophils, malondialdehyde (MDA), cytosolic phospholipase $A_2$ ($cPLA_2$) activity in the lung, histological changes and BAL cytospin morphology. Conclusion: In part, ALI-caused by oxygen is affected by neutrophils especially by the generation of free radicals.

• Journal of Life Science
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• v.22 no.10
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• pp.1352-1358
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• 2012

In acute lung injury (ALI) by lipopolysaccharide (LPS), the underlying cause of infiltration and migration of neutrophils into the alveoli is considered to be from increased production of platelet-activating factor (PAF) in the pulmonary surfactant lining the alveolar lumen. In this study I partially confirmed this concept. LPS increased lung leak and the infiltration of neutrophils in the lung of rats given LPS intratracheally. The migration of neutrophils into the lung, which had caused oxidative stress, was also morphologically identified. I verified that the metabolism of the pulmonary surfactant was affected and that there was increased production of PAF in the pulmonary surfactant, both of which are considered to contribute to ALI by LPS in rats.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.487-499
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• 2000

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.67 no.5
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• pp.402-408
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• 2009

Background: Pre-B-cell colony enhancing factor (PBEF) has been suggested as a novel biomarker in sepsis and acute lung injury. We measured the PBEF in bronchoalveolar lavage (BAL) fluid of acute critically ill patients with lung infiltrates in order to evaluate the clinical utility of measuring PBEF in BAL fluid. Methods: BAL fluid was collected by bronchoscope from 185 adult patients with lung infiltrates. An enzyme-linked immunosorbent assay was then performed on the collected fluids to measure the PBEF. Results: Mean patient age was 59.9 ${\pm}$14.5 years and 63.8% of patients were males. The mean concentration of PBEF in BAL fluid was 17.5 ${\pm}$88.3 ng/mL, and patients with more than 9 ng/mL of PBEF concentration (n=26, 14.1%) had higher Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores on the BAL exam day. However, there were no significant differences in clinical characteristics between survivors and non-survivors. In patients with leukocytosis (n=93) seen on the BAL exam day, the linear regression analysis revealed a significant, positive relationship between PBEF and APACHE II ($r^2$=0.06), SOFA score ($r^2$=0.08), Clinical Pulmonary Infection Score ($r^2$=0.05), and plateau pressure in patients on ventilators ($r^2$=0.07) (p<0.05, respectively). In addition, multivariate regression analysis with PBEF as a dependent variable showed that the plateau pressure ($r^2$=0.177, p<0.05) was correlated positively with PBEF. Conclusion: The PBEF level in the BAL fluid may be a useful, new biomarker for predicting the severity of illness and ventilator-induced lung injury in critically ill patients with lung infiltates and leukocytosis.

• Journal of Trauma and Injury
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• v.32 no.4
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• pp.238-242
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• 2019

Extreme acidosis is a life-threatening physiological state that causes disturbances in the cardiovascular, pulmonary, immune, and hematological systems. Trauma patients commonly present to the operating room (OR) in hypovolemic shock, leading to tissue hypoperfusion and the development of acute metabolic acidosis with or without a respiratory component. It is often believed that trauma patients presenting to the OR in severe metabolic acidosis (pH <7.0) will have a nearly universal mortality rate despite aggressive resuscitation and damage control. The current literature does not include reports of successful resuscitations from a lower pH, which may lead providers to assume that a good outcome is not possible. However, here we describe a case of successful resuscitation from an initial pH of 6.5 with survival to discharge home 95 days after admission with almost full recovery. We describe the effects of acute acidosis on the respiratory and cardiovascular systems and hemostasis. Finally, we discuss the pillars of management in patients with extreme acute acidosis due to hemorrhage: transfusion, treatment of hyperkalemia, and consideration of buffering acidosis with bicarbonate and hyperventilation.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.619-634
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• 2002

Background : Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods : Eighteen Sprague-Dawley rats were divided into three groups: low tidal Volume (LVT, 7mL/Kg tidal volume, 3 $cmH_2O$ PEEP, 40/min), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 $IgG_1$. Results : In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was $4.70{\pm}0.14$, $6.82{\pm}1.28$ and $4.92{\pm}0.98$, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was $3.25{\pm}1.17$, $12.83{\pm}1.17$ and $4.67{\pm}0.52$, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was $3.33{\pm}2.07$, $12.17{\pm}2.79$ and $3.60{\pm}1.95$, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion : VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.22-31
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• 2012

Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin $1{\beta}$ (IL-$1{\beta}$) were measured in BALF. Nuclear factor ${\kappa}B$ (NF-${\kappa}B$), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-${\alpha}$ and IL-$1{\beta}$ concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group ($5.5{\pm}2.8$ nmol/mL vs. $16.5{\pm}1.6$ nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group ($6.4{\pm}1.8$ unit/g vs. $11.2{\pm}6.3$ unit/g, tissue) (p<0.048). The concentration of NF-${\kappa}B$ in NAC treatment group was significantly lower than that of LPS group ($0.3{\pm}0.1\;ng/{\mu}L$ vs. $0.4{\pm}0.2\;ng/{\mu}L$) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-${\kappa}B$ activation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.2
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• pp.119-126
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• 2021

The aim of our paper was to present current knowledge, review literature and available practice guidelines of international hepatological associations regarding the effect of severe acute respiratory syndrome coronavirus 2 coronavirus on the liver, patients with underline liver disease, awaiting on liver transplantation (LTx) or being after LTx in the pandemic coronavirus disease 2019 area.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.157-166
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• 2018

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common clinical syndrome of diffuse lung inflammation with high mortality rates and limited therapeutic methods. Diosmetin, an active component from Chinese herbs, has long been noticed because of its antioxidant and anti-inflammatory activities. The aim of this study was to evaluate the effects of diosmetin on LPS-induced ALI model and unveil the possible mechanisms. Our results revealed that pretreatment with diosmetin effectively alleviated lung histopathological changes, which were further evaluated by lung injury scores. Diosmetin also decreased lung wet/dry ratios, as well as total protein levels, inflammatory cell infiltration and proinflammatory cytokine (eg. $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6) overproduction in bronchoalveolar lavage fluid (BALF). Additionally, increased MPO, MDA and ROS levels induced by LPS were also markly suppressed by diosmetin. Furthermore, diosmetin significantly increased the expression of Nrf2 along with its target gene HO-1 and blocked the activation of NLRP3 inflammasome in the lung tissues, which might be central to the protective effects of diosmetin. Further supporting these results, in vitro experiments also showed that diosmetin activated Nrf2 and HO-1, as well as inhibited the NLRP3 inflammasome in both RAW264.7 and A549 cells. The present study highlights the protective effects of diosmetin on LPS-induced ALI via activation of Nrf2 and inhibition of NLRP3 inflammasome, bringing up the hope of its application as a therapeutic drug towards LPS-induced ALI.