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1.  Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms 
Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.
doi:10.4253/wjge.v4.i3.57
PMCID: PMC3309894  PMID: 22442742
Autofluorescence endoscopy; Confocal endomicroscopy; Endoscopy; Molecular imaging; Molecular probes, Near-infrared fluorescence imaging; Targeted endoscopic imaging
2.  Treatment Outcome of Combination Therapy Including Clarithromycin for Mycobacterium avium Complex Pulmonary Disease 
Background/Aims
The frequency of nontuberculous mycobacteria pulmonary disease in HIV-negative patients is increasing; the most common pathogen in Korea is the Mycobacterium avium complex (MAC). However, few studies have evaluated the treatment outcome of MAC pulmonary disease in Korea.
Methods
The efficacy of a clarithromycin-containing regimen for MAC pulmonary disease was studied in 42 patients treated for more than 6 months between January 2005 and December 2008. All patients were treated with a regimen consisting of clarithromycin, rifampin, and ethambutol. Streptomycin was added in 10 patients.
Results
Among the 42 patients, a negative culture conversion was achieved in 33 (78.6%), and the median duration of treatment in these patients was 19 months (interquartile range [IQR], 16 to 22). Of the 33 patients with a negative culture conversion, 14 completed treatment. During the follow-up period (median, 10 months; IQR, 4 to 20) for the 14 patients, one relapsed at 24 months after treatment completion. The culture conversion rate was significantly higher in patients who were treated with more than 500 mg/day clarithromycin (87.1% vs. 54.5%, p = 0.038).
Conclusions
The combined regimen including clarithromycin was effective against MAC pulmonary disease. High-dose clarithromycin of more than 500 mg/day may improve the outcome of patients with MAC pulmonary disease.
doi:10.3904/kjim.2011.26.1.54
PMCID: PMC3056256  PMID: 21437163
Mycobacterium avium complex; Treatment outcome; Clarithromycin
3.  Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl β-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells 
Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl β-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-1β and TNF-α. In addition, CG significantly suppressed LPS-induced degradation of IκB. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells.
doi:10.4196/kjpp.2014.18.1.79
PMCID: PMC3951828  PMID: 24634601
1-p-coumaroyl β-D-glucoside (CG); Akt; COX-2; iNOS; Lipopolysaccharide; NF-κB; RAW264.7 cells
4.  Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation in RAW264.7 Cells 
Biomolecules & Therapeutics  2014;22(1):10-16.
Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.
doi:10.4062/biomolther.2013.095
PMCID: PMC3936424  PMID: 24596616
Methyl p-hydroxycinnamate; RAW 264.7 cells; Lipopolysaccharide; iNOS; COX-2; NF-κB
5.  Was 2009 Pandemic Influenza A (H1N1) Mild Among Pregnant Korean Women? 
Chonnam Medical Journal  2013;49(2):96-99.
Clinical and laboratory data from Western countries suggest that pregnant women are at an increased risk for severe illness and complications associated with 2009 pandemic influenza A (H1N1). However, previous data among Korean women suggested a less severe outcome. In this study performed at a single referral center in Korea, rates of admission, pneumonia, intensive care unit admission, and death related to 2009 pandemic influenza A (H1N1) were significantly higher in 33 pregnant women than in 723 nonpregnant women of reproductive age (p<0.05 each). We report two cases of 2009 pandemic influenza A (H1N1) in pregnant Korean women who were admitted to the intensive care unit because of severe pneumonia that led to maternal and fetal death in one of the patients. This case series suggests that pregnant Korean women were also at increased risk of severe illness and complications during the 2009 pandemic influenza A (H1N1) outbreak.
doi:10.4068/cmj.2013.49.2.96
PMCID: PMC3759690  PMID: 24010074
Pandemics; Influenza; H1N1; Pregnancy
6.  Differences in classification of COPD group using COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores: a cross-sectional analyses 
Background
The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk. We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC.
Methods
Outpatients with COPD were enrolled from January to June in 2012. The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively. Additionally, correlations between mMRC scores and each item of CAT scores were analyzed.
Results
Classification of 257 patients using the CAT score vs mMRC scale was as follows. By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D. On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D. The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510. The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001).
Conclusions
The classification of COPD produced by the mMRC or CAT score was not identical. Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document.
doi:10.1186/1471-2466-13-35
PMCID: PMC3680333  PMID: 23731868
COPD; CAT; mMRC scores
7.  Aromadendrin Inhibits Lipopolysaccharide-Induced Nuclear Translocation of NF-κB and Phosphorylation of JNK in RAW 264.7 Macrophage Cells 
Biomolecules & Therapeutics  2013;21(3):216-221.
Aromadendrin, a flavonol, has been reported to possess a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-diabetic properties. However, the underlying mechanism by which aromadendrin exerts its biological activity has not been extensively demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of aromadedrin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Aromadendrin significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2. In accordance, aromadendrin attenuated LPSinduced overexpression iNOS and COX-2. In addition, aromadendrin significantly suppressed LPS-induced degradation of IκB, which sequesters NF-κB in cytoplasm, consequently inhibiting the nuclear translocation of pro-inflammatory transcription factor NF- κB. To elucidate the underlying signaling mechanism of anti-inflammatory activity of aromadendrin, MAPK signaling pathway was examined. Aromadendrin significantly attenuated LPS-induced activation of JNK, but not ERK and p38, in a concentration-dependent manner. Taken together, the present study clearly demonstrates that aromadendrin exhibits anti-inflammatory activity through the suppression of nuclear translocation of NF-κB and phosphorylation of JNK in LPS-stimulated RAW 264.7 macrophage cells.
doi:10.4062/biomolther.2013.023
PMCID: PMC3830120  PMID: 24265867
Aromadendrin; COX-2; iNOS; JNK; Lipopolysaccharide; NF-κB; RAW 264.7 cells
8.  Clinical characteristics and treatment outcomes of tuberculosis in the elderly: a case control study 
BMC Infectious Diseases  2013;13:121.
Background
The purpose of this study was to evaluate the differences in clinical characteristics and treatment outcomes between older and younger tuberculosis (TB) patients in Korea.
Methods
We retrospectively analyzed the medical records of 271 younger (20–64 years old at diagnosis) and 199 older (≥65 years) TB patients who had been newly diagnosed and treated at Chonnam National University Hospital from May 2008 to August 2010.
Results
Dyspnea and comorbid medical conditions were more frequent and positive TB culture rates were higher in older TB patients. In chest computed tomography (CT) scans of pulmonary TB patients, older patients were less likely to have micronodules (<7 mm in diameter), nodules (<30 mm in diameter), masses (>30 mm in diameter), and cavities compared with younger patients, but were more likely to have consolidations. Incidence of adverse drug reactions did not differ between the two groups, except for severe gastrointestinal disorders. There were no significant differences in favorable treatment outcomes between younger and older TB patients (97% vs. 94%, respectively; p = 0.251).
Conclusions
Older TB patients had more frequent dyspnea and less frequent active TB findings on chest CT. Treatment success and adverse drug reaction rates were similar in older and younger TB patients.
doi:10.1186/1471-2334-13-121
PMCID: PMC3599150  PMID: 23510403
Age; Clinical presentations; Diagnosis; Treatment outcome; Tuberculosis
9.  Repeated Favorable Responses to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in a Case of Advanced Lung Adenocarcinoma 
The presence of epidermal growth factor receptor (EGFR) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.
doi:10.4046/trd.2013.74.3.129
PMCID: PMC3617133  PMID: 23579627
Adenocarcinoma; Receptor, Epidermal Growth Factor; Gefitinib
10.  Mycobacterium avium lung disease combined with a bronchogenic cyst in an immunocompetent young adult 
We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin.
doi:10.3904/kjim.2013.28.1.94
PMCID: PMC3543967  PMID: 23346002
Nontuberculous mycobacteria; Bronchogenic cyst; Mycobacterium avium complex
11.  3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells 
Biomolecules & Therapeutics  2013;21(1):60-65.
3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-α, and IL-1β. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.
doi:10.4062/biomolther.2012.091
PMCID: PMC3762302  PMID: 24009860
Neuro-inflammation; 3; 4; 5-trihydroxycinnamic acid; Nrf2; Heme oxygenase-1
12.  Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection 
Infection and Immunity  2012;80(6):2100-2108.
Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious pathogens. However, little is known about the detailed information of NKT cells in patients with Mycobacterium tuberculosis infection. The aims of this study were to examine NKT cell levels and functions in patients with active M. tuberculosis infection, to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for the poor response to α-galactosylceramide (α-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the proliferative responses of NKT cells to α-GalCer were also lower in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls. Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, the poor response to α-GalCer in M. tuberculosis-infected patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in NKT cells. Notably, M. tuberculosis infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to α-GalCer. This study shows that NKT cell levels and functions are reduced in M. tuberculosis-infected patients and these deficiencies were found to reflect the presence of active tuberculosis.
doi:10.1128/IAI.06018-11
PMCID: PMC3370582  PMID: 22409933
13.  Avicularin Inhibits Lipopolysaccharide-Induced Inflammatory Response by Suppressing ERK Phosphorylation in RAW 264.7 Macrophages 
Biomolecules & Therapeutics  2012;20(6):532-537.
suppresAvicularin, quercetin-3-α-L-arabinofuranoside, has been reported to possess diverse pharmacological properties such as anti-inflammatory and anti-infectious effects. However, the underlying mechanism by which avicularin exerts its anti-inflammatory activity has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of avicularin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Avicularin significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein levels of iNOS and COX-2, which are responsible for the production of NO and PGE2, respectively. Avicularin also suppressed LPS-induced overproduction of pro-inflammatory cytokine IL-1β. Furthermore, avicularin significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. To understand the underlying signaling mechanism of anti-inflammatory activity of avicularin, involvement of multiple kinases was examined. Avicularin significantly attenuated LPS-induced activation of ERK signaling pathway in a concentration-dependent manner. Taken together, the present study clearly demonstrates that avicularin exhibits anti-inflammatory activity through the suppression of ERK signaling pathway in LPS-stimulated RAW 264.7 macrophage cells.
doi:10.4062/biomolther.2012.20.6.532
PMCID: PMC3762284  PMID: 24009846
Avicularin; RAW 264.7 cells; Lipopolysaccharide; iNOS; COX-2; NF-κB
14.  Endobronchial Schwannoma Treated by Rigid Bronchoscopy with Argon Plasma Coagulation 
Primary endobronchial schwannomas are extremely rare tumors that originate from Schwann cells. We report a case of primary endobronchial schwannoma. A 44-year-old woman, without respiratory symptoms, was presented with a nodule in the left main bronchus on her chest computed tomography scan. The nodule was removed by a rigid bronchoscopy with argon plasma coagulation. Biopsy confirmed the diagnosis of schwannoma. There was no recurrence during her 4-month follow-up.
doi:10.4046/trd.2012.73.3.174
PMCID: PMC3492403  PMID: 23166551
Neurilemmoma; Bronchi; Bronchoscopy
15.  Analysis of Patients with Hemoptysis in a Tertiary Referral Hospital 
Background
This study attempted to investigate the main causes of hemoptysis, the type of examinations used for diagnosis, the treatment modalities and outcomes.
Methods
A retrospective study was conducted on the medical records of 221 patients admitted to the Chonnam National University Hospital, between January 2005 and February 2010, with hemoptysis.
Results
Bronchiectasis (32.6%), active pulmonary tuberculosis (18.5%), fungus ball (10.8%), and lung cancer (5.9%) accounted for most causes of hemoptysis. Computed tomography scan was the most sensitive diagnostic test when employed alone, with positive yield of 93.2%. There were 161 cases of conservative treatment (72.9%), 42 cases of bronchial artery embolization (BAE) (19.0%), and 18 cases of surgery (8.1%). Regarding the amount of hemoptysis, 70 cases, out of 221 cases, were mild (31.5%), 36 cases moderate (16.2%), and 115 cases massive hemoptysis (52.0%). Most of the patients were treated conservatively, but if there was more bleeding present, BAE or surgery was more commonly performed than the conservative treatment (p≤0.0001). In the multivariate model, severe hemoptysis and lung cancer were independently associated with short-term recurrence. BAE was independently associated with long-term recurrence, and lung cancer was associated with in-hospital mortality. The overall in-hospital mortality rate was 11.3%.
Conclusion
Hemoptysis is a common symptom with a good prognosis in most cases. However, patients exhibiting massive bleeding or those with malignancy had a poorer prognosis. In-hospital mortality was strongly related to the cause, especially in lung cancer.
doi:10.4046/trd.2012.73.2.107
PMCID: PMC3492374  PMID: 23166543
Hemoptysis; Etiology; Diagnosis; Therapeutics; Treatment Outcome
16.  Bacterial Pathogens of Ventilator Associated Pneumonia in a Tertiary Referral Hospital 
Background
This study evaluates the bacterial pathogens of Ventilator-associated pneumonia (VAP) in a tertiary referral hospital.
Methods
A total of 109 bacterial pathogens from 91 adult patients with VAP, who were admitted to the medical intensive care unit from January 2008 to December 2009, were examined. Clinical characteristics, bacterial pathogens, and resistance profiles were analyzed.
Results
Staphylococcus aureus (44%) was the most frequently isolated. Acinetobacter baumanii (30%), Pseudomonas aeruginosa (12%), Stenotrophomonas maltophilia (7%), Klebsiella pneumoniae (6%), and Serratia marcescens (2%) were isolated from the transtracheal aspirates or bronchoalveolar lavage in patients with VAP. There was no significant difference of bacterial pathogens between early and late onset VAP. All isolated S. aureus were methicillin resistant S. aureus; the imipenem resistance rate of A. baumanii was 69%.
Conclusion
The two most frequent pathogens of VAP were S. aureus and A. baumanii. There were no pathogenic differences between early and late onset VAP.
doi:10.4046/trd.2012.73.1.32
PMCID: PMC3475477  PMID: 23101022
Pneumonia, Ventilator Associated; Staphylococcus aureus; Acinetobacter baumanii
17.  Comparison of docetaxel/cisplatin dosages of 75/60 and 60/60 mg/m2 for the treatment of non-small cell lung cancer 
A combination of docetaxel (D) and cisplatin (P) is one of the standard regimens for the initial treatment of advanced non-small cell lung cancer (NSCLC). Yet, the toxicity of D administered at 75 mg/m2 in three weekly doses to patients is a concern. The aim of this study was to assess the efficacy of a lower combination dose, 60 mg/m2 of D and 60 mg/m2 of cisplatin (P), as a treatment for NSCLC. In this randomized, phase III trial, we compared the response rates (RRs) and toxicity profiles of two combination regimens, D/P 75/60 vs. 60/60 mg/m2, to patients with stage IIIB or IV NSCLC. A total of 132 patients were randomized to the 75/60 (n=65) or 60/60 (n=67) dosage group. Non-inferiority of 60/60 group compared to the 75/60 group was confirmed by the RR (38.5% for the 75/60 group and 40.3% for the 60/60 group, 95% confidence interval −14.8 to 18.5, meeting the predefined non-inferiority criterion). The dose reduction rate and incidence of grade 3–4 neutropenia were significantly higher in the 75/60 group. The incidence of neutropenia was significantly higher in those with the non-expressing genotype (GG) compared to the AG or AA genotypes of CYP3A5. We determined that DP 60/60 was not inferior to DP 75/60 in RR, and that the reduced combination dosage provides a better safety profile for patients.
doi:10.3892/etm.2012.597
PMCID: PMC3460243  PMID: 23139720
non-small cell lung carcinoma; docetaxel; cisplatin; cytochrome P-450; CYP3A5
18.  Temozolomide-Associated Bronchiolitis Obliterans Organizing Pneumonia Successfully Treated with High-Dose Corticosteroid 
Journal of Korean Medical Science  2012;27(4):450-453.
Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patient's clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically.
doi:10.3346/jkms.2012.27.4.450
PMCID: PMC3314861  PMID: 22468112
Bronchiolitis Obliterans Organizing Pneumonia (BOOP); Temozolomide; Methylprednisolone
19.  3,4,5-Trihydroxycinnamic Acid Inhibits LPS-Induced iNOS Expression by Suppressing NF-κB Activation in BV2 Microglial Cells 
Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as neuronal protection against excitotoxicity and anti-inflammatory property, the biological activity of 3,4,5-trihydroxycinnamic acid (THC), a derivative of hydroxycinnamic acids, has not been clearly examined. The objective of the present study is to evaluate the anti-inflammatory effects of THC on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. THC significantly suppressed LPS-induced excessive production of nitric oxide (NO) and expression of iNOS, which is responsible for the production of iNOS. THC also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α in BV2 microgilal cells. Furthermore, THC significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm. Therefore, THC attenuated nuclear translocation of NF-κB, a major pro-inflammatory transcription factor. Taken together, the present study for the first time demonstrates that THC exhibits anti-inflammatory activity through the suppression of NF-κB transcriptional activation in LPS-stimulated BV2 microglial cells.
doi:10.4196/kjpp.2012.16.2.107
PMCID: PMC3339285  PMID: 22563255
3,4,5-Trihydroxycinnamic acid (THC); BV2 microglial cells; Lipopolysaccharide; iNOS; NF-κB
20.  Plasma N-terminal Pro-brain Natriuretic Peptide: A Prognostic Marker in Patients with Chronic Obstructive Pulmonary Disease 
Lung  2012;190(3):271-276.
Background
Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload. The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension.
Methods
Plasma NT-proBNP levels were measured in 61 patients with stable COPD. Plasma NT-proBNP levels, pulmonary function, PaO2, and PaCO2 levels and systolic pulmonary artery pressure were compared according to COPD severity. In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO2, PaCO2, and systolic pulmonary artery pressure.
Results
The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV1 < 50%) was 0.707 (95% confidence interval [CI] 0.566–0.847, P = 0.008). Plasma NT-proBNP levels significantly correlated with %FEV1 (r = −0.557; P < 0.001), arterial blood gas parameters such as PaCO2 (r = 0.476; P < 0.001) and PaO2 (r = −0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001).
Conclusions
Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.
doi:10.1007/s00408-011-9363-7
PMCID: PMC3339052  PMID: 22246552
Chronic obstructive pulmonary disease; NT-proBNP; Prognosis; Medicine & Public Health; Pneumology/Respiratory System
21.  A Case of Pulmonary Alveolar Microlithiasis 
Journal of Korean Medical Science  2011;26(10):1391-1393.
Pulmonary alveolar microlithiasis (PAM) is a rare disease with unknown etiology and pathogenesis. It is characterized by diffuse, innumerable, and minute calculi, called microlithiasis in the alveoli. More than half of reported cases are asymptomatic at the time of diagnosis. We describe the first case of PAM in Korea. A 19-yr-old man without respiratory symptoms presented with interstitial thickening on the chest radiograph. His chest high resolution CT scan showed diffusely scattered, ill defined tiny micronodules and interstitial thickening. Open lung biopsy confirmed the diagnosis of PAM. He was followed up for 6 months without treatment, and no progression was noticed.
doi:10.3346/jkms.2011.26.10.1391
PMCID: PMC3192355  PMID: 22022196
Calcinosis; Lung diseases; Computed Tomography
22.  Influence of Diaphragmatic Mobility on Hypercapnia in Patients with Chronic Obstructive Pulmonary Disease 
Journal of Korean Medical Science  2011;26(9):1209-1213.
A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters. However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients. Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. There were significant negative correlations between diaphragmatic mobility and PaCO2 (r = -0.373, P = 0.030). Diaphragmatic mobility correlated with airway obstruction (FEV1, r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003). Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation. No relationship was observed between diaphragm mobility and PaO2 (r = -0.028, P = 0.873). These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients.
doi:10.3346/jkms.2011.26.9.1209
PMCID: PMC3172660  PMID: 21935278
Pulmonary Disease, Chronic Obstructive; Diaphragm mobility; Hypercapnia; Ultrasonography
23.  First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea 
Chonnam Medical Journal  2011;47(2):127-129.
It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam National University Hospital because of a 7-day history of chest pain and dyspnea. The patient was at another clinic and had been medicated with oseltamivir (75 mg twice daily) beginning 7 days before admission. Empirical antibiotics were started on the first day of hospitalization. Reverse-transcriptase polymerase chain reaction for 2009 pandemic influenza A (H1N1) was reported to be positive, and a double dose of oseltamivir (150 mg twice per day) was started on day four of hospitalization. However, the pneumonia worsened and the patient died, despite 3 days of high-dose antiviral therapy and 6 days of antibacterial therapy. An H275Y mutation was detected in the neuraminidase gene sequence. This case shows that oseltamivir resistance after short-term drug exposure is possible and can be fatal, emphasizing that early use of zanamivir should be considered in suspicious cases.
doi:10.4068/cmj.2011.47.2.127
PMCID: PMC3214869  PMID: 22111074
Influenza A virus, H1N1 subtype; Pandemics; Oseltamivir; Drug resistance, viral
24.  Apoptosis of T Lymphocytes Isolated from Peripheral Blood of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease 
Yonsei Medical Journal  2011;52(4):581-587.
Purpose
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways and progressive destruction of lung parenchyma. Apoptosis is critical for the maintenance of normal tissue homeostasis and is in equilibrium with proliferation and differentiation. This study was undertaken to investigate relationship between apoptosis of peripheral blood lymphocytes during exacerbation of COPD and inflammatory response that characterizes this condition.
Materials and Methods
Seventeen patients with COPD exacerbation, 21 stable COPD, and 12 control subjects were included. T lymphocytes were isolated from peripheral blood using MACS. Apoptosis of T lymphocytes was assessed with FACS using annexin V and 7-aminoactinomycin. Serum levels of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α were determined by an immunoassay technique.
Results
There was significantly increased percentage of apoptotic lymphocytes, CD 4+, and CD 8+ T cells in the peripheral blood of patients with exacerbation of COPD compared with stable COPD. Serum levels of IL-6, IL-8, and TNF-α were significantly increased in patients with exacerbation of COPD compared with stable COPD. Only TNF-α presented a positive correlation with apoptotic lymphocytes in patients with exacerbation of COPD.
Conclusion
Increased apoptotic lymphocytes may be associated with upregulation of TNF-α in the peripheral blood of patients with acute exacerbation of COPD.
doi:10.3349/ymj.2011.52.4.581
PMCID: PMC3104462  PMID: 21623599
Chronic obstructive pulmonary disease; apoptosis; lymphocyte; tumor necrosis factor-α
25.  Anti-inflammatory Activity of 1-docosanoyl Cafferate Isolated from Rhus verniciflua in LPS-stimulated BV2 Microglial Cells 
Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as protection of neuronal cells against excitotoxicity, the biological activity of 1-docosanoyl cafferate (DC) has not been examined. The objective of the present study was to evaluate the anti-inflammatory effects of DC, isolated from the stem bark of Rhus verniciflua, on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of cells with DC significantly attenuated LPS-induced NO production, and mRNA and protein expression of iNOS in a concentration-dependent manner. DC also significantly suppressed LPS-induced release of cytokines such as TNF-α and IL-1β . Consistent with the decrease in cytokine release, DC dose-dependently and significantly attenuated LPS-induced mRNA expression of these cytokines. Furthermore, DC significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB induced by LPS stimulation was significantly suppressed with DC pretreatment. Taken together, the present study suggests that DC exerts its anti-inflammatory activity through the suppression of NF-kB translocation to the nucleus.
doi:10.4196/kjpp.2011.15.1.9
PMCID: PMC3062086  PMID: 21461235
1-Docosanoyl cafferate (DC); BV2 microglial cells; Lipopolysaccharide; Cytokines; iNOS; NF-kB

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