Inhibition of lactate dehydrogenase attenuated LPS-induced lung injury in mice

백애린,김미소,이준혁,장안수,김도진,박성우 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

Background: Increased lung lactate releases are found and are proportional to the severity in the patients with acute lung injury (ALI). So far, lactate has been regarded as just metabolite under tissue hypoxia. However, the role of lactate in the pathogenesis of ALI is unclear. Aims: In this study, we investigated whether inhibition of lactate production have beneficial effect in an animal model of ALI. Methods: In vitro studies including cell viability/proliferation, permeability and proinflammatory cytokine production were performed with LPS treatment in the presence of FX11, the lactate dehydrogenase A inhibitor. Murine model of LPS-induced lung injury was used to determine the therapeutic effect of FX11. Measurement and Results: FX11 significantly enhanced viability and proliferation of alveolar epithelial cells against LPS treatment. FX11 down-regulated LPS-induced increased pro-inflammatory cytokines in the alveolar macrophages. LPS-induced increased endothelial permeability was significantly attenuated by FX11. In LPS-induced ALI mice, increased lung inflammation, edema and hemorrhage were dramatically diminished by intranasal or intraperitoneal treatment of FX11. Conclusions: These findings implicate lactate could exaggerate ALI and inhibition of lactate may be a therapeutic target for ALI. GRANT : 2016R1E1A1A01943481.

Apolipoprotein A1 Inhibits TGF-β1–Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells

백애린,이지민,서현정,박종숙,이준혁,박성우,장안수,김도진,고은석,어수택,김용훈,박춘식 대한결핵및호흡기학회 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)–induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/ myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1–induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-β1–treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1–induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1–induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogenactivated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1–induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-β1–induced EMT in experimental lung fibrosis.

라미부딘 내성 만성 B형 간염 환자에서 아데포비어 병합치료의 지연 바이러스 반응 예측인자

백애린,김대용,김영석,김상균,김정현,김태진,이윤나,이세환,정승원,장재영,김홍수,김부성 순천향대학교 순천향의학연구소 2013 Journal of Soonchunhyang Medical Science Vol.19 No.1

Objective: Lamivudine (LAM) is the first nucleoside analog approved for chronic hepatitis B (CHB) patients, but acquired mutation of the reverse transcriptase of the virus during long-term therapy is limiting its use. Adeforvir dipivoxil (ADV) add-on therapy with ongoing LAM use has been a standard therapy for LAM resistance. The aim of this study was to explore the predictive factors associated with delayed virologic response at 12 months in patients who could not achieved initial virologic response (IVR) of add-on therapy. Methods: One hundred and ninety three LAM-resistant CHB patients who had been on ADV add-on therapy with LAM and were not achieved IVR at 6 months were enrolled. They were classified into delayed viral response (DVR) group and non-DVR group, according to delayed viral response (VR) at 12 months of add-on therapy. Clinical factors predicting delayed VR at 12 months of addon therapy were evaluated. Results: DVR rate was 20.7% (n=40) at 12 months after the add-on treatment. Female (adjusted odds ratio, 3.463; P=0.002), lower hepatitis B virus (HBV) DNA at baseline (<7.0 log copies/mL/≥7.0 log copies/mL; adjusted odds ratio, 0.369; P=0.012), and negative HBeAg at baseline (adjusted odds ratio, 0.332; P=0.034) were significant independent factors predicting DVR after 12 months of treatment. Conclusion: In LAM-resistant CHB patients with ADV add-on therapy, although there was no IVR after 6 months treatment, we could consider maintenance of treatment if patient is female, lower HBV DNA state, or HBeAg negative state at the time of starting add-on therapy.

Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice

백애린,Hong Jisu,송기성,장안수,김도진,진수지,박성우 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Spermidine is an endogenous biological polyamine that plays various longevity-extending roles and exerts antioxidative, antiaging, and cell growth-promoting effects. We previously reported that spermidine levels were significantly reduced in idiopathic pulmonary fibrosis (IPF) of the lung. The present study assessed the potential beneficial effects of spermidine on lung fibrosis and investigated the possible mechanism. Lung fibrosis was established in mice using bleomycin (BLM), and exogenous spermidine was administered daily by intraperitoneal injection (50 mg/kg in phosphate-buffered saline). BLM-induced alveolar epithelial cells showed significant increases in apoptosis and endoplasmic reticulum stress (ERS)-related mediators, and spermidine attenuated BLM-induced apoptosis and activation of the ERS-related pathway. Senescence-associated β-gal staining and decreased expression of p16 and p21 showed that spermidine ameliorated BLM-induced premature cellular senescence. In addition, spermidine enhanced beclin-1-dependent autophagy and autophagy modulators in IPF fibroblasts and BLM-induced mouse lungs, in which inflammation and collagen deposition were significantly decreased. This beneficial effect was related to the antiapoptotic downregulation of the ERS pathway, antisenescence effects, and autophagy activation. Our findings suggest that spermidine could be a therapeutic agent for IPF treatment.

일개 병원에서 조기대응팀 활동 중 조기 사망한 환자의 특성 분석

백애린,허진원,홍상범,임채만,고윤석 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.0

목적: 조기대응팀은 고위험 병동 환자를 조기에 발견 후 치료를 시작하여 중환자실 입실 및 사망을 줄이고 환자의 예후를 개선시키는 데에 목적이 있다. 조기대응팀 활동의 적절성을 알기 위해 조기대응팀 진료가 이루어졌음에도 불구하고 조기에 사망한 환자들의 특성을 분석하였다. 방법: 2010.1~ 2014.12까지 5년 동안 본원 조기대응팀 활동 총 11968건수 중 병동 환자 대상 활동 9446건수를 선별하고, 이 중 활동72시간 이내에 사망한 환자(951명, 10%)를 후향적으로 분석하였다. 심정지 코드에 의한 활동은 제외하였다. 결과: 조기사망 환자 나이의 중위값은 62세로, 남자가 62.4%로 많았다. 내과계 환자가 82.7%로 많았으며, 그 중 종양내과가(34.1%) 가장 많았다. 활동 시 재원일수의 중위값은 11일이었다. 조기대응팀 활동 중 사망은 3.9%, 활동 후 일반병동에서 사망은 66.4%, 중환자실 전실후 사망한 경우가 29.8% 이었다. 활동 당시 호흡곤란 47%, 중증 패혈증 및 패혈성 쇼크 19.1%, 저혈량성 쇼크 6.4%, 심폐정지 상태가 4.8% 였다. 병동 주치의와 심폐소생술 및 중환자실 전실 여부 등의 치료방향 상의만 이루어진 경우는 17.7%, 조기대응팀에 의한 검사 및 약물 처방 등의 처치는 82.4%, 관혈적 시술은 38.6%, 활동 중 심폐소생술은 9.4%에서 시행되었다. 치료 방향 상의는 스크리닝(61.3%)/주치의 콜(32.7%)/간호사콜(6.0%), 처치는 스크리닝(43.0%)/주치의콜(36.2%)/간호사콜(20.8%)에 의해 이루어졌다. 반면, 심폐소생술은 간호사콜에 의한 활동 시 가장 많았다(14.6%/41.6%/43.8%). 결론: 조기대응팀 활동 중 조기 사망한 환자들은 대부분 진행성 암질환이나 폐질환을 가지고 있었다. 적절한 조기대응팀의 활동을 위해서는 입원 초기에 환자와 의료진간의 치료 방향(중환자실 치료, Do not resuscitation)에 대한 상의가 필요하다.

Trichosporon asahii 에 의한 파종성 진균혈증 1례

임애린,윤석윤,최인호,정종탁,백예지,김태형,이은정 대한내과학회 2023 대한내과학회 추계학술대회 Vol.2023 No.2

Asymptomatic incidental co-existence double synchronous primary cancers; lung and breast

신형섭,백애린,이준혁,박성우,김도진,장안수 대한내과학회 2018 대한내과학회 추계학술대회 Vol.2018 No.1

Pulmonary Arteriovenous Malformations presenting as Lung Mass: A case report

이혜영,백애린,이준혁,박성우,김도진,장안수 대한내과학회 2018 대한내과학회 추계학술대회 Vol.2018 No.1

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 1. Introduction

박성우,백애린,이홍렬,정성환,양세훈,김용현,정만표,behalf of the Korean Interstitial Lung Diseases Study Group 대한결핵및호흡기학회 2019 Tuberculosis and Respiratory Diseases Vol.82 No.4

Idiopathic interstitial pneumonia (IIP) is a histologically identifiable pulmonary disease without a known cause that usually infiltrates the lung interstitium. IIP is largely classified into idiopathic pulmonary fibrosis, idiopathic non-specific interstitial pneumonia, respiratory bronchiolitis–interstitial lung disease (ILD), cryptogenic organizing pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Each of these diseases has a different prognosis and requires specific treatment, and a multidisciplinary approach that combines chest high-resolution computed tomography (HRCT), histological findings, and clinical findings is necessary for their diagnosis. Diagnosis of IIP is made based on clinical presentation, chest HRCT findings, results of pulmonary function tests, and histological findings. For histological diagnosis, video-assisted thoracoscopic biopsy and transbronchial lung biopsy are used. In order to identify ILD associated with connective tissue disease, autoimmune antibody tests may also be necessary. Many biomarkers associated with disease prognosis have been recently discovered, and future research on their clinical significance is necessary. The diagnosis of ILD is difficult because patterns of ILD are both complicated and variable. Therefore, as with other diseases, accurate history taking and meticulous physical examination are crucial.

Association between Cardiac Autonomic Neuropathy,Diabetic Retinopathy and Carotid Atherosclerosis in Patients with Type 2 Diabetes

정찬희,백애린,김규진,김보연,김철희,강성구,목지오 대한내분비학회 2013 Endocrinology and metabolism Vol.28 No.4

Background: It is not clear whether microangiopathies are associated with subclinical atherosclerosis in type 2 diabetes mellitus (T2DM). We investigated the relation of cardiac autonomic neuropathy (CAN) and other microangiopathies with carotid atherosclerosis in T2DM. Methods: A total of 131 patients with T2DM were stratified by mean carotid intima-media thickness (CIMT) ≥ or <1.0 mm and the number of carotid plaques. CAN was assessed by the five standard cardiovascular reflex tests according to the Ewing’s protocol. CAN was defined as the presence of at least two abnormal tests or an autonomic neuropathy points ≥2. Diabetic microangiopathies were assessed. Results: Patients with CAN comprised 77% of the group with mean CIMT ≥1.0 mm, while they were 29% of the group with CIMT <1.0 mm (P=0.016). Patients with diabetic retinopathy (DR) comprised 68% of the group with CIMT ≥1.0 mm, while they were 28% of the group without CIMT thickening (P=0.003). Patients with CAN comprised 51% of the group with ≥2 carotid plaques, while they were 23% of the group with ≤1 carotid plaque (P=0.014). In multivariable adjusted logistic regression analysis, the patients who presented with CAN showed an odds ratio [OR] of 8.6 (95% confidence interval [CI], 1.6 to 44.8) for CIMT thickening and an OR of 2.9 (95% CI, 1.1 to 7.5) for carotid plaques. Furthermore, patients with DR were 3.8 times (95%CI, 1.4 to 10.2) more likely to have CIMT thickening. Conclusion: These results suggest that CAN is associated with carotid atherosclerosis, represented as CIMT and plaques, independent of the traditional cardiovascular risk factors in T2DM. CAN or DR may be a determinant of subclinical atherosclerosis in T2DM.