Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway

Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.

[논문]Operational Characteristics of CO2 Laser Adopted by Superposing-Discharge

Hee-Je Kim,Hyun-Ju Chung,Byoung-Dae Min,Jong-Han Joung,Sung- lun Park 釜山大學校生産技術硏究所 2003 生産技術硏究所論文集 Vol.62 No.-

오늘날 현저한 CO2 레이저의 응용 추세에 발맞추어 보다 다양한 형태의 출력 제어 기술이 대두되고 있다. 본연구에서는multi-Pulse Superposing-Discharge 기술을 이용하여 다양한형태의 CO2 레이저의 펄스를 성형 하였다. 펄스 성형을 위한 방법으로 PIC one-chip microprocessor를 이용하여 삼중 PFN 모률의 SCR을 각각 고유의 지연시간을 가지도록 제어하였다. 실험에 사용된 삼중 PFN 모률의 전원 회로는 각각 캐패시터 인덕터,SCR,고압 펄스 트랜스 그리고 고압 트랜스 2차측에 브릿지 정류기로 구성 하였다. 고압 펼스 트랜스의 1차측을 제어하므로서 PFN 모률의 동작을 저 전압에서 수행 할 수 있다. 트랜스의 2차측에 연결된 전파 정류기는 펄스 에너지를 부하에 지속적으로 전달한다. 본 연구에서는 삼중 PFN 모률의 각각의 SCR을 다른 시간 가격을 두고 트리거 하므로서 다양한 Long pulse shaping을 실현하였다. 또한 약 250-1000μs 의 주기를 가지는 다양한 펄스형 레이저 빔을 얻었다.

기종성 방광염을 동반한 기종성 신우신염 1예

김선두,김순제,이길도,김정수,김지훈,윤호상,송종오,문언수 대한노인병학회 2000 Annals of geriatric medicine and research Vol.4 No.3

한국 정신장애의 역학 조사 연구[I] : 각 정신장애의 유병률

조맹제,함봉진,김장규,박강규,정은기,서동우,김선욱,조성진,이준영,홍진표,최용성,박종익,이동우,이기철,배재남,신정호,정인원,박종한,배안,이충경 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.4

Objectives : This study aims to estimate the prevalence of the DSM-IV psychiatric disorders in Korean population using the Korean version of Composite International Diagnostic Interview (K-CIDI). Methods : Subjects were selected by taking multi-stage, cluster samples of 7,867 adult household residents, 18 to 64 years of age, in ten catchment areas. Total 78 trained interviewers administered the K-CIDI to the selected respondents, from June 1 to November30,2001. Results : Total 6,275 respondents completed the interview. Some 33.5% of respondents reported at least one lifetime disorder, 20.6% reported at least one-year disorder, and 16.7% reported at least one-month disorder. The most common lifetime disorders were alcohol abuse/dependence (17.24%), nicotine dependence/withdrawal (11.19%), specific phobia (5.16%), and major de-pressive disorder (4.25%). The lifetime prevalence of substance abuse/dependence (0.25%) and schizophrenia (0.16%) was very low. Nicotine and alcohol use disorder showed very high male/female ratio. Mood disorder and anxiety disorder were more prevalent among female than male. Conclusion : The prevalence of psychiatric disorders was high. In comparison with other studies, remarkable differences in distributions of psychiatric disorders across the areas and times were observed.

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

사회적 음주자에서 날트렉손 투여가 급성 음주 반응에 미치는 영향

김종현,김성곤,신성현,박제민,김명정 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.6

Objectives : We investigated the effects of naltrexone on acute alcohol response, stimulant and sedative, in healthy social drinkers using two doses of alcohol intake. Methods : Twenty four healthy male medical students were voluntarily participated. The experimental method was Cross-over design, Subjects received 25 mg/day or 50 mg/day of naltrexone on the experimental days. Biphasic Alcohol Effects Scale (BAES), alcohol craving, and blood alcohol concentration (BAC) were measured before drinking and at 15, 30, 45, 60, 90,and 120 min after drinking. Results : 1) Group of 0.6 mg/kg of alcohol intake. When the scores of stimulative subscale of BAES were compared bet-ween the naltrexone and control group, the scores were significantly lower in the naltrexone group at 15 and 90 min after drinking. Alcohol induced sedative effect was significantly higher in the naltrexone group at 90 min after drinking. The alcohol induced alcohol craving at 45 and 60 min after drinking was significantly lower in the naltrexone group as compared to the control. 2) Group of 0.3 ing/kg of alcohol intake. The alcohol induced stimulative effect evident in the control group seen in the time span of 15 to 45 min after drinking was not seen in the naltrexone group. The increase of alcohol induced alcohol craving noticed at 30 min after drinking in the control group was not seen in the naltrexone group. BAC at 15 min after drinking was lower in the naltrexone group compared to the control. Conclusion : Naltrexone is suggested to attenuate stimulative effect, to intensify sedative effect, and to block alcohol induced alcohol craving. These triple actions might be utilized for treatment and prevention of relapse of alcohol dependence.

계약직공무원제도의 운영 실태에 대한 분석

김상묵,강제상,김종래 한국정책학회 2003 韓國政策學會報 Vol.12 No.2

우리 나라의 경우 계약직공무원제도는 공직사회의 전문성을 제고하고 공직 개방화에 따른 정부인적자원의 효율적 관리차원에서 1998년 도입되었다. 그 후 책임운영기관제도와 개방형 직위제도가 새로이 도입되었고, 행정서비스수요에 탄력적으로 대응하기 위하여 시간제공무원제도와 외국의 우수전문인력을 공직에 충원하기 위한 외국인공무원채용제도 등을 도입하는 등 계약직 공무원제도는 그 분야와 영역이 점차 확대되고 있는 실정이다. 이 연구의 목적은, 계약직공무원제도의 운영실태를 조사·분석하고, 이를 바탕으로 도입취지의 당위성을 확인하고 향후 인사관리정책의 방향성을 탐색하고, 계약직공무원제도의 개선을 위한 실현 가능한 정책대안을 모색하고자 한다. 특히 계약직공무원의 임용과 성과관리 방안 등 인력활용시스템의 개선에 대하여 중점적으로 고찰해보고자 한다. 먼저 면담조사를 통해 계약직공무원제도 운영실태를 파악한 후 이를 토대로 설문조사를 실시하였다. 전체 계약직 공무원 전원과, 비교집단으로 각 계약직 공무원과 유사한 위치에서 비슷한 업무를 수행하는 동일한 수의 일반직 등 비계약직 공무원을 선정하여 설문조사를 실시하였다. 이를 통해 계약직공무원제도의 운영실태를 파악한 후, 그 결과를 바탕으로 제도적·운영상 개선방안을 모색하였다. Given that the contingent employee is likely to be a familiar presence in the public service workplace of the future in Korea, this study explores the realities of contingent civil service system and discusses its institutional development. It reviews the characteristics and present situations of the contingent civil service system, analyzes its problems, and suggests the alternatives for improvement. Drawing upon survey evidence from two groups, 383 non-contingent public employees and 408 contingent public employees in the central government of Korea, our study shows that there is no difference between contingent and non-contingent public employees in the main reasons why they have entered to the government and in the factors which they have considered as more important, and that the major problems of current contingent civil service system are inappropriate performance evaluation and insufficient linkage between performance and reward, while most contingent and non-contingent public employees are agreed with the purposes of contingent civil service system. Such findings are discussed for the improvement of contingent civil service system in Korea.

ICP(Inductively Coupled Plasma) 처리에 따른 n-type SiGe/Metal contact의 SBH(Schottky Barrier Height) 연구

김이곤,장호원,전창민,송영주,강진영,심규환,제정호,이종람 대한금속재료학회 2005 대한금속·재료학회지 Vol.43 No.2

The effect of surface treatment of n-type SiGe using the inductively coupled plasma (ICP) was studied by current-voltage and x-ray photoemission spectroscopy measurements. The ICP treatment produced surface oxides and point defects at the surface of SiGe. The x-ray photoemission spectroscopy measurements showed that atomic ratio of Ge/Si was increased after the etching treatment. These results provide the evidence that Si vacancies were produced at the etched surface. Si vacancies acting as donor for electrons resulted in shift of Fermi level to near the conduction band. As a result, Fermi level could be pinned at such Si vacancies, leading to the remarkable reduction of Schottky barrier height and the reduced dependence of Schottky barrier height on metal work function. (Received September 7, 2004)