• BMB Reports
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• v.47 no.8
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• pp.451-456
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• 2014

Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of $NF-{\kappa}B$ ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and $I{\kappa}B$, as well as $I{\kappa}B$ degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.

• Journal of The Korean Society of Emergency Medicine
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• v.29 no.5
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• pp.474-484
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• 2018

Objective: The time to positivity (TTP) of blood culture reflects bacterial load and has been reported to be associated with outcome in bloodstream infections. This study was performed to evaluate the relationship between the TTP of blood culture and the mortality rates associated with sepsis and septic shock according to the site of infection. Methods: We performed a retrospective cohort study on patients with sepsis and septic shock. The rates of blood culture positivity and mortality as well as the relationship between the TTP and 28-day mortality rate were compared among patients with different sites of infection, such as the lungs, abdomen, urogenital tract, and other sites. Results: A total of 2,668 patients were included, and the overall mortality rate was 21.6%. The rates of blood culture positivity and mortality were different among the different infection sites. There was no relationship between the TTP and mortality rates of total, lung, and urogenital infections. Patients with abdominal infections showed a negative correlation between the TTP and 28-day mortality rate. In patients with abdominal infections, a TTP<20 hours was independently associated with 28-day mortality compared with patients with negative blood culture (hazard ratio, 1.73; 95% confidence interval, 1.16-2.58). However, there was no difference in mortality rates of patients with a $TTP{\geq}20$ hours and a negative blood culture. Conclusion: The shorter TTP in patients with abdominal infections in sepsis and septic shock was associated with a higher 28-day mortality rate.

• BMB Reports
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• v.48 no.6
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• pp.336-341
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• 2015

Sepsis is a life-threatening, infectious, systemic inflammatory disease. In this study, we investigated the therapeutic effect of α-cubebenoate, a novel compound isolated from Schisandra chinensis against polymicrobial sepsis in a cecal ligation and puncture (CLP) experimental model. Administration of α-cubebenoate strongly enhanced survival in the CLP model. α-cubebenoate administration also markedly blocked CLP-induced lung inflammation and increased bactericidal activity by enhancing phagocytic activity and hydrogen peroxide generation in mouse bone marrow-derived macrophages and neutrophils. Expression of two important inflammatory cytokines, IL-1 and IL-6, was strongly increased in the CLP model, and this was dramatically blocked by α-cubebenoate. Lymphocyte apoptosis and caspase-3 activation, which are associated with immune paralysis during sepsis, were markedly attenuated by α-cubebenoate. Taken together, our findings indicate that α-cubebenoate, a natural compound isolated from Schisandra chinensis, is a powerful potential anti-septic agent. [BMB Reports 2015; 48(6): 336-341]

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.62-69
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• 2002

Acute interstitial pneumonia (AIP) is a rare fulminant form of lung injury that presents acutely; usually in a previously healthy individual. It corresponds to a subset of cases of idiopathic adult respiratory distress syndrome (ARDS). Invasive pulmonary aspergillosis is a disease occuring predominantly with defects in immunity such as hematologic malignancy, influenza infection, postchemotherapy, long-term corticosteroid treatment. Invasive aspergillosis has worse prognosis and most cases are diagnosed at postmortem autopsies. We experienced a case of acute interstitial pneumonia with an invasive aspergillosis during corticosteroid treatment. Acute interstitial pneumonia with invasive aspergillosis was diagnosed by an open lung biopsy using thoracoscopy, showing fungal hyphae with sepsis and an acute angle branching invasion of the lung tissue and blood vessels. The patient was treated with IV amphotericin-B, but died due to septic shock.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.443-449
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• 2001

Previously we reported that THI 52 inhibits tumor necrosis factor $(TNF)-{\alpha}$ mRNA expression in mouse peritoneal macrophages exposed to LPS plus $IFN-{\gamma}.$ In the present study, the effects of THI 52 on vascular reactivity ex vivo, and iNOS protein expression (rat lung) were investigated in LPS-treated rats. Treatment of THI 52 concentration-dependently reduced not only serum nitrite production but also the expression of iNOS protein in rat lung tissues. Thoracic aorta taken from LPS injected rat for 8 h ex vivo resulted in suppression of vasoconstrictor effects to phenylephrine (PE), which was restored by THI 52 (20 mg/kg) 30 min prior to LPS. When measured iNOS activity, treatment of THI 52 concentration-dependently reduced the enzyme activity in RAW 264.7 cells activated with LPS plus $IFN-{\gamma}.$ Likewise, iNOS activity was significantly reduced in lung tissues taken those rats that were injected THI 52 prior to LPS injection compared with LPS injection alone. These results strongly suggest that THI 52 can suppress iNOS gene expression induced by LPS, and restore the vascular contractility to PE. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where production of NO is excessed by iNOS expression.

• Journal of Trauma and Injury
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• v.19 no.1
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• pp.14-20
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• 2006

Purpose: Although hypothermia has been used in many clinical situations, such as post cardiopulmonary resuscitation, stroke, traumatic brain injury, septic shock, and hemorrhagic shock, the mechanism by which it works has not been clearly elucidated. We aimed to evaluate the effect of hypothermia on the plasma nitric oxide (NO) concentration, lung iNOS expression, and histologic changes in intestinal ischemia-reperfusion (IR). Method: Male Sprague-Dawley rats were randomly divided into the hypothermia group (HT, n=8, $27{\sim}30^{\circ}C$) and the normothermia group (NT, n=8, $36{\sim}37^{\circ}C$). They underwent 30 min of intestinal ischemia by clamping the superior mesenteric artery, which was followed by 1.5 h of reperfusion. They were then sacrificed. The acute lung injury (ALI) score, the plasma NO concentration, and lung iNOS gene expression were measured. Results: Compared with the HT group, the NT group showed severe infiltrations of inflammatrory cells, alveolar hemorrhages, and interstitial hypertrophies in lung tissues. There were significant differences in the ALI scores between the NT and the HT groups ($8.7{\pm}1.5/HPF$ in NT vs $5.8{\pm}1.2/HPF$ in HT, p=0.008). Although the plasma NO concentration was slightly lower in the HT group, there was no significant difference between the two groups ($0.80{\pm}0.24{\mu}mol/L$ in NT vs $0.75{\pm}0.30{\mu}mol/L$ in HT, p=0.917). Lung iNOS gene expression was stronger in the NT group than in the HT group. The band density of the expression of iNOS in lung tissues was significantly increased in the NT group compared to the HT group ($5.54{\pm}2.75$ in NT vs$0.08{\pm}0.52$ in HT, p=0.002). Conclusions: This study showed that hypothermia in intestinal IR reduces inflammatory responses, ALI scores, and iNOS gene expression in lung tissues. There was no significant effect of hypothermia on the plasma NO concentration.

• Journal of Chest Surgery
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• v.20 no.1
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• pp.139-147
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• 1987

in general rapid and complete resolution of pulmonary emboli, even massive, is the natural history. However, rarely, the emboli do not resolve but rather became fibrotic organization and densely adherent to the arterial wall, therefore, may lead to significant clinical disability. In patients with chronic pulmonary embolism, medical management usually has little effect and only surgical treatment can offer improvement. The case was 30-year-old man who had admission to the Hanyang University Hospital due to fall-down from 11th floor 407 days before operation and then transferred to our department for surgical management under the diagnosis of chronic pulmonary embolism, Pulmonary angiogram demonstrated multifocal thromboembolism with infarction and lung scans showed no improvement in spite of anticoagulant and thrombolytic therapy. At median sternotomy for pulmonary artery thromboembolectomy, the well organized and multiple septic emboli could be removed by gallstone forceps. But reoperation of left upper lobectomy was performed because of the repeated hemoptysis and suspicious pulmonary arterio-bronchial fistula 19 days postoperatively. Despite of ventilatory support and drug treatment, the patient died due to right heart failure associated with cor pulmonale 27 days after first operation. Discussion of the operative and perioperative problems are offered.

• Tuberculosis and Respiratory Diseases
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• v.77 no.1
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• pp.6-12
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• 2014

Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units. In 2002, the guideline titled "Surviving Sepsis Campaign" was published by American and European Critical Care Medicine to decrease the mortality of severe sepsis and septic shock patients, which has been the basis of the treatment for those patients. After the first revised guidelines were published on 2008, the most current version was published in 2013 based on the updated literature of until fall 2012. Other important revised guidelines in critical care field such as 'Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit' were revised in 2013. This article will review the revised guidelines and several additional interesting published papers of until March 2014, including the part of ventilator-induced lung injury and the preventive strategies.

• Molecules and Cells
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• v.44 no.12
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• pp.893-899
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• 2021

BLT2 is a low-affinity receptor for leukotriene B₄, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB₄ [leukotriene B₄] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB₄ and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

• Korean Journal of Veterinary Research
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• v.22 no.2
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• pp.211-219
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• 1982

Chickens from 10 to 32 weeks of age were inoculated with P. multocida via seven routs(intravenous, intramuscular, intraperitoneal, subcutaneous, into ear, intranasal, per oral). The development or distribution of disseminated intravascular coagulation (DIC) in multiple organs and the role of P. multocida endotoxins in disease process of fowl cholera were studied. The histological diagnosis of DIC was made by demonstration of fibrinous in arterioles, capillaries, venules and medium-sized blood vessels. The presence of fibrinous thrombi in blood vessels of multiple organs was observed in chickens which died within approximately 3 days post inoculation. Fibrinous thrombi were observed most frequently in the lung(90% of all cases with DIC) followed by liver (70%), kidney (60%), heart(20%), spleen, brain, pancreas, thymus and thyroid gland. The density of fibrinous thrombi (i.e. the number of thrombi per section) was greatest in the lung, followed by spleen, kidney, liver and heart. It is thought that the widespread hemorrhage of acute fowl cholera is also caused by P. multocida endotoxin which initiates DIC in variety of organs. The cause of death for the chickens after infection with acute fowl cholera is probably due to an endotoxin (septic) shock accompanied with DIC in multiple organs.