N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

( Daewoo Lee ),( Sung Ho Kook ),( Hyeok Ji ),( Seung Ah Lee ),( Ki Choon Choi ),( Kyung Yeol Lee ),( Jeong Chae Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.11

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC. [BMB Reports 2015; 48(11): 636-641]

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Kim, Seung Tae,Lee, Su Jin,Lee, Jeeyun,Park, Joon Oh,Park, Young Suk,Lim, Ho Yeong,Kang, Won Ki Grune & Stratton 2017 Journal of clinical oncology Vol.35 No._suppl15

<P> e15686 </P><P> Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs. </P>

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

Glucose deprivation으로 유발된 Neuro 2A 세포의 산화적 손상에 대한 七氣湯의 보호효과

성기호(Ki-Ho Seong),이정섭(Jung-Sup Lee),신선호(Sun-Ho Shin) 대한한의학회 2010 대한한의학회지 Vol.31 No.2

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

소켓 용접부 내부 결함 검사용 초음파 자동 검사 장비 개발

이정기,박문호,박기성,이재호,임성진 한국비파괴검사학회 2003 학술대회 논문집 Vol.- No.1

대구경 배관에서 소구경 배관으로 연결하는 부위 및 배관의 방향 전환을 위해 연결하는 소켓용 접부의 용입 불량 및 사용시간이 경과되면서 내부로부터 진전될 수 있는 균열 검출을 위한 초음파 검사 기법을 확립하였고, 검사를 수행할 수 있는 초음파 탐촉의 개발과 더불어 자동으로 검사할 수 있는 검사 장비와 제어용 운영 프로그램을 개발하였다. 개발된 장비는 컴퓨터를 기반으로 하고 있으며, pulser/receiver를 내장하고 고속 A/D board를 사용하여 초음파 탐상기 역할을 프로그램으로 구현하였으며, ISA interface type으로 4축 제어용 motion controller를 개발하여 자동 검사를 수행하는 scanner를 제어하도록 하였으며, 검사 결과는 소켓용접부 단면을 실시간 영상으로 나타내도록 되어 있다. 개발된 장비는 원자력 발전소나 화학플랜트에 많이 널려 있는 소켓용접부 내의 용입불량, 피로 균열 등을 검출하여 객관적인 검사 결과를 제시할 수 있으므로 설비 안전 관리 및 보수 부위 결정에 기여가 있을 것으로 기대된다.

Adult Patients with Congenital Muscular Torticollis Treated with Bipolar Release : Report of 31 Cases

Lee, Gun Sang,Lee, Myung Ki,Kim, Woo Jae,Kim, Ho Sang,Kim, Jeong Ho,Kim, Yun-Suk The Korean Neurosurgical Society 2017 Journal of Korean neurosurgical society Vol.60 No.1

Objective : We assessed the surgical results of bipolar release in 31 adult patients with uncorrected congenital muscular torticollis (CMT) and more than 12 months of follow-up. Methods : Thirty-one patients underwent a bipolar release of the sternocleidomastoid muscle (SCM) and were retrospectively analyzed. The mean follow-up period was 14.9 months (range, 12-30). The mean age at time of surgery was 30.3 years (range, 20-54). Patients were evaluated with a modified Lee's scoring system, cervicomandibular angle (CMA) measurement, and a global satisfaction rating scale using patient self-reporting. Results : The modified Lee's scoring system indicated excellent results in 4 (12.9%) patients, good in 18 (58.1%), and fair in 9 (29.0%) at the last follow-up after surgery. The improvements in neck movement and head tilt were statistically significant (p<0.05). The preoperative mean CMA was $15.4^{\circ}$ (range, 5.4-29.0), which was reduced to a mean of CMA of $6.3^{\circ}$ (range, 0-25) after surgery (p<0.05). The global satisfaction rating scale was 93.7% (range, 90-100). A transient sensory deficit on the ipsilateral lower ear lobe was noted in three cases. No significant permanent complications occurred. Conclusion : Bipolar release of the SCM is a safe and reliable technique for the treatment of CMT in adults.

소켓 용접부 결함 검사용 초음파 자동 검사 장비 개발

이정기,박문호,박기성,이재호,임성진 한국비파괴검사학회 2004 한국비파괴검사학회지 Vol.24 No.3

대구경 배관에서 소구경 배관으로 연결하는 부위 및 배관의 방향 전환을 위해 사용하는 소켓용접부는 용입불량 및 사용기간이 경과되면서 내부로부터 진전될 수 있는 균열 등의 결함을 가질 수 있다. 그러나 지금까지 적용하고 있는 비파괴검사법인 액체침투탐상과 방사선투과검사로는 내부에 존재하는 균열성 결함의 검출이 어렵다. 본 연구에서는 소켓용접부 내부의 균열성 결함 검출을 위한 초음파 검사 기법을 확립하였고, 검사를 수행할 수 있는 초음파 탐촉자를 설계 제작하였으며, 자동으로 검사할 수 있는 검사 장비와 제어용 운영 프로그램을 개발하였다. 개발된 장비는 컴퓨터를 기반으로 하고 있으며, pulser/receiver를 내장하고 100㎒ 고속 A/D board를 사용하여 초음파 탐상기 역할을 프로그램으로 구현하였으며, ISA interface type으로 4축 제어용 motion controller를 개발하여 자동 검사를 수행하는 scanner를 제어하도록 하였으며, 검사 결과는 소켓용접부 단면을 실시간 영상으로 나타내도록 되어 있다. 인공결함 ㅅ험편의 결함을 평가한 결과 결함의 깊이가 1㎜인 결함의 평가 길이는 실제 크기보다 작게 나타내고 있으며, 결함의 깊이가 증가할수록 결함의 길이가 더 크게 평가되었다. 본 연구로 개발한 장비는 원자력 발전소나 화학플랜트에 많이 널려 있는 소켓용접부 내의 용입불량, 피로 균열 등을 검출하여 객관적인 검사 결과를 제시할 수 있으므로 설비 안전 관리 및 보수 부위 결정에 기여할 수 있을 것으로 기대된다. Socket weldment used to change the flow direction of fluid may have flaws such as lack of fusion and cracks. Liquid penetrant testing or Radiography testing have been applied as NDT methods for flaw detection of the socket weldment. But it is difficult to detect the flaw inside of the socket weldment with these methods. In order to inspect the flaws inside the socket weldment, a ultrasonic testing method is established and a ultrasonic transducer and automated ultrasonic testing system are developed for the inspection. The automated ultrasonic testing system is based on the portable personal computer and operated by the program based Windows 98 or 2000. The system has a pulser/receiver, 100 ㎒ high speed A/D board, and basic functions of ultrasonic flaw detector using the program. For the automated testing, motion controller board of ISA interface type is developed to control the 4-axis scanner and a real time iC-scan image of the automated testing is displayed on the monitor. A flaws with the size of less than 1 ㎜ in depth are evaluated smaller than its actual size in the testing, but the flaws larger than 1 ㎜ appear larger than its actual size on the contrary. This tendency is shown to be increasing as the flaw size increases. A reliable and objective testing results are obtained with the developed system, so that it is expected that it can contribute to safety management and detection of repair position of pipe lines of nuclear power plants and chemical plants.