폐쇄성 수면 무호흡증의 역학과 병인

윤대위 ( Dae Wui Yoon ),김진관 ( Jin Kwan Kim ),신철 ( Chol Shin ) 대한내과학회 2015 대한내과학회지 Vol.89 No.1

Obstructive sleep apnea (OSA) is one of common sleep disorders in western countries, affecting 4% of males and 2% of females. It is characterized by repeated obstruction of the upper airway during sleep, leading to intermittent hypoxemia, sympathetic activation, and sleep fragmentation. OSA is an independent risk factor for a range of medical problems, including cardiovascular disease, diabetes, depression, and cognitive dysfunctions. The etiology of OSA is complex and incompletely understood, but recent studies have shown that the development of OSA depends on the structure of the airway anatomy, the responsiveness of the upper airway dilator muscle to stimulation, and the stability of the respiratory control system. This review details the epidemiological and experimental evidence surrounding the associations between OSA and chronic diseases. Recent findings on the etiology of OSA will also be discussed. (Korean J Med 2015;89:6-12)

Association of Sasang Constitutional Type with Bone Mineral Density, Osteopenia, and Osteoporosis

이승구,윤대위,김종렬,김진관,이혜련,이성희,애보트 로버트,신철,Lee, Seung Ku,Yoon, Dae Wui,Kim, Jong Yeol,Kim, Jin Kwan,Yi, Hyeryeon,Lee, Sunghee,Abbott, Robert D.,Shin, Chol The Society Of Sasang Constitutional Medicine 2020 사상체질의학회지 Vol.32 No.3

Object Although Taeeum and Soyang constitutional types have bigger body shapes and higher body mass index values than those with the Soeum, the relationship between the Sasang constitutional type and bone mass density is controversial and the association of osteopenia and osteoporosis remains unknown. Therefore, we investigated the relationship between bone mineral density, osteopenia, and osteoporosis according to Sasang constitutional type. Methods A total of 2,508 participants were included in this study. Among the study participants, 1,396 had Taeeum type, 276 had Soeum type, and 836 had Soyang type, respectively. The relationships to bone mass density, osteopenia, and osteoporosis in those with Sasang constitutional type were estimated using logistic and linear regression models. Results Bone mass density was significantly higher in the order of Taeeum, Soyang, and Soeum group (p < 0.01). Soeum group in comparison with Taeeum or Soyang group was significantly associated with a high odds ratio for osteopenia and osteoporosis except in the hip and femoral neck in the comparison of Taeeum and Soeum group (p < 0.01). Moreover, the bone mass density of Soeum group decreased more rapidly as the age increased when compared with Taeeum and Soyang group. Conclusions Our findings may contribute to the early prevention and management of high-risk individuals with poor bone mass density, osteopenia, and osteoporosis using Sasang constitution medicine.

기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할

김제형 ( Je Hyeong Kim ),윤대위 ( Dae Wui Yoon ),허규영 ( Gyu Young Hur ),정기환 ( Ki Hwan Jung ),이승룡 ( Sung Yong Lee ),이상엽 ( Sang Yeub Lee ),신철 ( Chol Shin ),심재정 ( Jae Jeong Shim ),인광호 ( Kwang Ho In ),유세화 ( Se H 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.4

연구배경: 활성산소종은 기계환기로 인한 폐손상 (ventilator-induced lung injury, VILI)에서 주요한 역할을 한다. Poly (ADP-ribose) polymerase-1 (PARP1)은 DNA 손상 감시 기능을 하는 단백질로서, DNA 파열을 신호하고 복구에 관여한다. 그러나 활성 산소종에 의한 것과 같은 심한 유전자 손상을 받게 되면, 과활성화되어-nicotinamide adenine dinucleotide (NAD(+))의 결핍을 통한 세포의 사멸을 초래하여, 염증 반응을 일으킨다. 본 연구에서는 VILI의 기전에 있어서 PARP1의 역할 및 그 억제제의 효과를 고찰하고자 하였다. 방법: 48마리의 수컷 C57BL/6 생쥐를 겉보기 수술군 (Sham군), 폐보호적 환기군(lung protective ventilation group, LPV군), 기계환기기로 인한 폐손상군 (ventilator-induced lung injury group, VILI군) 및 PARP1 억제제인 PJ34 전처치 후 기계환기로 인한 폐손상군 (PJ34+VILI군)으로 나누어 실험하였다. LPV군에 대한 기계환기는 PIP 15 cmH2O+PEEP 3 cmH2O+RR 90/min. 조건으로, VILI 및 PJ34+VILI군에 대해서는 PIP 40 cmH2O+PEEP 0 cmH2O+RR 90/min.의 조건으로 2시간 동안 시행하였다. PJ34+VILI군에서 PARP1 억제제로는, PJ34 20 mg/Kg을 기계환기 2시간 전에 복강 내로 주사하였다. VILI의 정도는 습건중량비 및 급성폐손상 지수로 측정하였고, PARP1의 활성은 biotinylated NAD를 이용한 면역조직화학적 방법을 이용하였다. 또한 기관지폐포세척액 (bronchoalveolar lavage fluid, BALF) 내에서 myeloperoxidase (MPO) 활성 및 tumor necrosis factor- (TNF- ), interleukin-1 (IL-1), IL-6 등의 염증성 시토카인의 농도를 측정하였다. 결과: PJ34+VILI군에서 VILI군과 비교하여, PJ34 전처치로 인하여 폐손상의 정도가 현저히 감소 하였다(p<0.05). 5개의 고배율 시야에서 관찰한 PARP1의 활성을 보이는 세포의 수는 VILI군에서 유의하게 증가하였고, PJ34+VILI군에서 현저히 감소하였다(p=0.001). BALF 내에서 측정한 MPO 활성 및 TNF-, IL-1, IL-6의 농도 역시 PJ34+VILI군에서 의미 있게 감소하였다(p<0.05). 결론: VILI의 기전에 있어서 PARP1의 과활성이 주요한 역할을 하고, PARP1 억제제가 MPO 활성 및 염증성 시토카인의 감소와 함께 VILI의 발생을 억제한다. Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through-nicotinamide adenine dinucleotide (NAD(+)) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was PIP 15 cmH2O+PEEP 3 cmH2O+RR 90/min+2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of PIP 40 cmH2O+PEEP 0 cmH2O+RR 90/min+2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor (TNF)-, interleukin (IL)-1, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, TNF-, IL-1, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines. (Tuberc Respir Dis 2006; 60: 451-463)

리포다당질로 인한 직접성 급성폐손상에서 Nuclear Factor-κB Decoy Oligodeoxynucleotide의 효과

김제형 ( Je Hyeong Kim ),윤대위 ( Dae Wui Yoon ),정기환 ( Ki Hwan Jung ),김혜옥 ( Hye Ok Kim ),하은실 ( Eun Sil Ha ),이경주 ( Kyoung Ju Lee ),허규영 ( Gyu Young Hur ),이승룡 ( Sung Yong Lee ),이상엽 ( Sang Yeub Lee ),신철 ( Chol 대한결핵 및 호흡기학회 2009 Tuberculosis and Respiratory Diseases Vol.67 No.2

Background: The pathophysiologic mechanisms of early acute lung injury (ALI) differ according to the type of primary insult. It is important to differentiate between direct and indirect pathophysiologic pathways, and this may influence the approach to treatment strategies. NF-κB decoy oligodeoxynucleotide (ODN) is a useful tool for the blockade of the expression of NF-κB-dependent proinflammatory mediators and has been reported to be effective in indirect ALI. The purpose of this study was to investigate the effect of NF-κB decoy ODN in the lipopolysaccharide (LPS)-induced direct ALI model. Methods: Five-week-old specific pathogen-free male BALB/c mice were used for the experiment. In the preliminary studies, tumor necrosis factor (TNF)-α, interleukine (IL)-6 and NF-κB activity peaked at 6 hours after LPS administration. Myeloperoxidase (MPO) activity and ALI score were highest at 36 and 48 hours, respectively. Therefore, it was decided to measure each parameter at the time of its highest level. The study mice were randomly divided into three experimental groups: (1) control group which was administered 50 μL of saline and treated with intratracheal administration of 200 μL DW containing only hemagglutinating virus of Japan (HVJ) vector (n=24); (2) LPS group in which LPS-induced ALI mice were treated with intratracheal administration of 200 μL DW containing only HVJ vector (n=24); (3) LPS+ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 μL DW containing 160 μg of NF-κB decoy ODN and HVJ vector (n=24). Each group was subdivided into four experimental subgroups: (1) tissue subgroup for histopathological examination for ALI at 48 hours (n=6); (2) 6-hour bronchoalveolar lavage (BAL) subgroup for measurement of TNF-α and IL-6 in BAL fluid (BALF) (n=6); (3) 36-hour BAL subgroup for MPO activity assays in BALF (n=6); and (4) tissue homogenate subgroup for measurement of NF-κB activity in lung tissue homogenates at 6 hours (n=6). Results: NF-κB decoy ODN treatment significantly decreased NF-κB activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-α and interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score. Conclusion: NF-κB decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.

리포다당질에 의한 급성폐손상에서 Ethyl Pyruvate의 효과

이승현 ( Seung Hyeun Lee ),윤대위 ( Dae Wui Yoon ),정진용 ( Jin Yong Jung ),이경주 ( Kyung Joo Lee ),김세중 ( Se Joong Kim ),이은주 ( Eun Joo Lee ),강은해 ( Eun Hae Kang ),정기환 ( Ki Hwan Jung ),이승룡 ( Sung Yong Lee ),이상엽 ( 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.61 No.4

연구배경: 급성폐손상에서 활성산소종에 의한 산화 손상은 주요한 역할을 한다. Ethyl pyruvate (EP)는 체내에서 생성되는 pyruvate의 유도체로 항산화 및 항염증 효과가 있음이 알려졌다. 저자들은 리포다당질에 의한 급성폐손상 모델에서 EP가 염증반응에 미치는 영향을 연구하고자 하였다. 방법: 5주 령의 BALB/c 생쥐를 이용하여 리포다당질을 기관 내로 투여하여 급성폐손상을 유도하였다. 대조군, LPS군, EP+LPS군, LPS+EP군으로 나누어 기관지폐포세척액에서 TNF-α, IL-6 및 myelo-peroxidase (MPO)의 활성을, 폐조직에서 급성폐손상지수와 NF-κB의 농도를 측정하였다. 결과: EP+LPS군에서 TNF-α및 IL-6의 농도는 LPS군과 비교하여 감소하였고 (p<0.05) 이들 염증성 시토카인의 농도의 변화는 NF-κB의 농도의 변화와 상관 관계를 보였다 (p<0.01). 급성폐손상 지수는 EP+LPS군 및 LPS+EP군에서 LPS군과 비교하여 낮았고 (p<0.05) MPO활성은 EP+LPS군에서 LPS군에 비해 낮았다 (p<0.05). 결론: EP는 LPS로 인한 급성폐손상에 있어서 예방 및 치료 효과가 있는 것으로 판단된다. Background: Ethyl pyruvate (EP) is a derivative of pyruvate that has recently been identified by both various in vitro and in vivo studies to have antioxidant and anti-inflammatory effects. The aim of this study was to determine the effect of EP on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: 5 weeks old, male BALB/c mice were used. ALI was induced by an intratracheal instillation of LPS 0.5㎎/㎏/50μL of saline. The mice were divided into the control, LPS, EP+LPS, and LPS+EP groups. In the control group, balanced salt solution was injected intraperitoneally 30 minutes before or 9 hours after the intratracheal instillation of saline. In the LPS group, a balanced salt solution was also injected intraperitoneally 30 minutes before or 9 hours after instillation the LPS. In the EP+LPS group, 40㎎/㎏ of EP was injected 30 minutes before LPS instillation. In the LPS+EP group, 40㎎/㎏ of EP was injected 9 hours after LPS instillation. The TNF-α and IL-6 concentrations in the bronchoalveolar lavage fluid (BALF), and that of NF-kB in the lung tissue were measured in the control, LPS and EP+LPS groups at 6 hours after instillation of saline or LPS, and the ALI score and myeloperoxidase (MPO) activity were measured in all four groups 24 and 48 hours after LPS instillation, respectively. Results: The TNF-α and IL-6 concentrations were significantly lower in the EP+LPS group than in the LPS group (p<0.05). The changes in the concentration of these inflammatory cytokines were strongly correlated with that of NF-κB (p<0.01). The ALI scores were significantly lower in the EP+LPS and LPS+EP groups compared with the LPS group (p<0.05). In the EP+LPS group, the MPO activity was significantly lower than the LPS group (p=0.019). Conclusion: EP, either administered before or after LPS instillation, has protective effects against the pathogenesis of LPS-induced ALI. EP has potential theurapeutic effects on LPS-induced ALI. (Tuberc Respir Dis 2006; 61: 374-383)

비만, 폐쇄성 수면무호흡증과 대사장애

김진관 ( Jinkwan Kim ),표상신 ( Sang Shin Pyo ),윤대위 ( Dae Wui Yoon ) 대한임상검사과학회 2021 대한임상검사과학회지(KJCLS) Vol.53 No.4

수면은 필수적인 생리적 기능일 뿐만 아니라 인간의 성장, 성숙 및 전반적인 건강을 증진시키는 데 중요한 역할을 한다. 수면과 수면 장애가 대사성 질환에 미치는 영향에 대한 관심이 높아지고 있다. 폐쇄성 수면무호흡증은 일반적인 건강 문제이며, 지난 10년 동안 비만율의 증가로 인해 더 두드러진 대사 질환과 함께 폐쇄성 수면무호흡증의 유병률이 현저하게 증가했다. 폐쇄성 수면무호흡증에 의한 대사성 질환을 유발하는 근본적인 메커니즘은 다인성일 가능성이 높으며, 완전히 밝혀지지 않고 있지만, 염증과 산화 스트레스의 활성화와 식욕 조절 호르몬의 조절장애는 폐쇄성 수면무호흡증 환자에게 나타나는 대사 기능 장애와 비만의 중요한 병리 생리학적 성분으로 나타났다. 본 연구에서는 폐쇄성 수면무호흡증과 대사질환의 연관성에 대한 연구 현황과 폐쇄성 수면무호흡증이 이러한 질병을 유발하는 병리생리학적 메커니즘에 대해 검토하고자 한다. 이를 통해 폐쇄성 수면 무호흡증과 비만, 그리고 폐쇄성 수면무호흡증과 대사 기능 장애 사이의 잠재적인 상호작용을 이해할 수 있다. Sleep plays an important role in maintaining overall human health. There is increasing interest regarding the impact of sleep related disorders on metabolic diseases. Obstructive sleep apnea (OSA) is a common health problem, and in the last decade, the emergence of increasing obesity rates has further led to a remarkable increase in the prevalence of OSA, along with more prominent metabolic diseases. Obesity is the strongest risk factor for OSA. However, OSA is also known to cause obesity, suggesting an interaction between OSA and obesity. Although the underlying mechanisms leading to OSA-induced metabolic diseases are probably multi-factorial and are yet to be fully elucidated, the activation of inflammation and oxidative stress and the dysregulation of appetite-regulating hormones have emerged as important pathophysiological components of metabolic dysfunction and obesity observed in patients with OSA. Here, we will review the current state of research regarding the association of OSA with metabolic diseases and the possible pathophysiological mechanisms by which OSA could lead to such diseases. This will enhance our understanding of the potential interactions between OSA and obesity and between OSA and metabolic dysfunction.