인면역결핍바이러스감염에서 Ribavirin의 Lamivudine에 대한 길항효과

허애정,남정구,장경희,염준섭,최준용,송영구,김성순,이주실,이꽃실,김영근,김명수,박우일,김준명 대한화학요법학회 2002 대한화학요법학회지 Vol.20 No.1

배경 : HIV 감염자 수의 증가와 다양한 치료제 개발로 인해 HIV 감염자의 수명이 연장되면서 HCV 감염이 HIV 감염의 자연경과 및 사망률에 악영향을 미치는 중요한 병원균으로 대두되고 있다. 또한 HIV가 HCV의 질병경화를 악화시킬 수 있음이 밝혀지면서 동시감염의 치료에 대한 관심이 높아지고 있으며, 약물 상호작용도 그 주요 관심사 중 하나이다 RBV과 다양한 항레트로바이러스제제들간의 약물 상호작용에 대한 연구가 진행된 결과 ZDV과 d4T에 대하서 길항작용을, ddI에 대해서는 상승작용을 보임이 밝혀져 있다. 본 연구에서는 이러한 뉴클레오시드 유사체들과 세포내 대사과정을 달리하는 3TC에 대한 영향을 알아보고자 하였다. 방법 : 분주하여 부관되어 있던 세포주 MT-4를 48-72시간마다 계대배양하여 1.96×10^(6)cell/㎖의 수준으로 유지하였고, 96 well plate에 각 well 당 1.0×10⁴cells/㎖씩 분주하였다. ZDV(0.0001-1000μM/L)과 3TC(0.00001-100mM/L)의 농도를 각각 10배씩 희석하여 투여한 후 세포를 5일간 배양하여 각농도에서의 세포독성을 MTT assay로 평가하였으며, RBV(2μM/L) 투여전후의 변화를 비교하였다. 항바이러스 효과를 평가하기 위하여 MT-4세포에 각 well 당 100 TCID_(50)의 HIV-1 strain HTLV-Ⅲ을 첨가하여 감염시킨 상태에서 유사한 방법으로 ZDV과 3TC의 농도를 10배씩 희석하여 투여한 후 37℃, 5% CO₂ incubator에서 배양하였다. 배양 1주일후 상층액을 얻어 HIV-1 p24 core profile ELISA를 사용하여 p24 Ag을 정량적으로 측정하였고, IC_(50)를 평가하였다. 약물들과 함께 RBV을 투여한 후 같은 방법으로 세포독성 및 항바이러스 효과를 평가하였다. ZDV, 3TC를 단독투여한 결과와 RBV을 함께 투여한 결과를 비교분석 하기 위하여 Wilcoxon rank sum test로 분석하였다. 결과 : ZDV 단독투여시 CD_(50)는 36.8μM이었고 RBV을 함께 투여시 CD_(50)가 39.9μM로 증가하였으며, 3TC의 경우 RBV 투여전후의 CD_(50)는 각각 2357.2μM, 2248.8μM이었다. MTT assay상 ZDV 0.01 및 0.1μM/L 농도에서 (p=0.003, 0.039), 3TC 100μM/L 농도에서(p=0.027) RBV 투여 전후 세포생존율의 차이를 보였다. 3TC 단독 투여시에 비해 RBV과 병용투여한 경우 통계적으로 유의하게 p24 Ag 생성이 증가하였고 (p=0.007) 이러한 결과는 ZDV에서와 유사하였다(p=0.026). ZDV 단독투여시 IC_(50)는 0.03μM였고, ribavirin을 함께 투여후 0.067μM에서 0.152μM로 2.3배 증가된 소견을 보였다. 결론 : 이상의 실험결과로부터 RBV 투여가 3TC의 세포독성 및 항바이러스효과를 감소시키며 이러한 길항작용은 농도의존적임을 알 수 있었다. 본연구는 이전에 제시된 연구들과 함께 RBV이 항레트로바이러스제제와 병합투여 되었을 때 약물대사에 미치는 영향을 보여준 중요한 자료중 하나가 될 것이다. HIV/HCV 동시감염자에서 상용량의 RBV을 병용투여할 경우 3TC의 농도가 낮게 유지되어 HIV의 내성을 유도할 가능성을 내포한다고 볼 수 있겠으나, 실제로 직접 임상에 적용하기는 어려우며 생체내에서의 이들 약물의 상호작용 및 대사변화를 평가하기 위해서는 생체내에서의 약동학 및 약력학적 평가를 포함한 광범위한 임상연구가 필요할 것으로 생각된다. Background : One of the main concerns of interferon/ribavirin(RBV) treatment in Human immunodeficiency virus(HIV)/Hepatitis C virus(HCV) coinfected patients is that of drug-drug interactions. Recent studies reveal that RBV is antagonistic with zidovudine(ZDV), stavudine(d4T) and synergistic with didanosine(ddl). The phosphorylation of lamivudine(3TC) utilizes the enzyme deoxycytidine kinase. Manipulation of 3TC phosphorylation is a possible therapeutic strategy for modulating antiretroviral efficacy and cytotoxicity of 3TC. Methods : MT-4 cell lines were maintained in RPMI 1640 growth medium as a cell suspension 1.96 × 106cells/㎖), doubling approximately every 48-72 hr. Cells were incubated with ZDV(0.0001-1000mM) and 3TC(0.00001-100mM) in the presence and absence of RBV(2uM) in 96-well microtiter plates and cytotoxicity was determined using modified MTT assay. At the end of the 7 days, the cell-free supernatant was serially diluted and samples(100uL) were then assayed for p24 antigen with ELISA to evaluate the inhibitory effect on HIV-1 replication. The results were expressed in terms of the 50% inhibitory concentration(IC50). Analysis was done by Wilcoxon rank sum test. Results : 3TC alone significantly reduced p24 antigen production, with an IC50 0.067mM and addition of RBV increased the IC50 approximately 8.4 fold (0.563mM). However, at higher concentration of 3TC, the antagonistc effect of RBV was lost The decrease in the cytotoxic and antiviral efficacy of ZDV in the presence of RBV is consistent with previous studies that have demonstrated reduced ZDV activation. Conclusion : The addition of RBV siginificantly reduced cytotoxicity and antiretroviral efficacy of 3TC in MT-4 cell lines and the antagonistic effect of RBV is concentration dependent. This study provides further insight into the complex interaction between RBV and 3TC in vitro.

Endoscope‐assisted intraoral resection of external dermoid cyst

Kim, Jin Pyeong,Park, Jung Je,Jeon, Sea‐,Yuong,Ahn, Seong‐,Ki,Hur, Dong Gu,Kim, Dae‐,Woo,Park, Hyun Woo,Woo, Seung Hoon,Rosenthal, Eben L. Wiley Subscription Services, Inc., A Wiley Company 2012 Head & neck Vol.34 No.6

<P><B>Abstract</B></P><P><B>Background</B></P><P>Surgical removal of a dermoid cyst is usually accomplished through an external neck incision. However, this procedure inevitably results in a neck scar.</P><P><B>Methods</B></P><P>We report the case of a 17‐year‐old woman with a submental mass. We implemented a modified approach to dermoid cyst removal through the floor of the mouth using an endoscope system.</P><P><B>Results</B></P><P>The patient received a modified approach to dermoid cyst removal and remains free of disease 6 months after excision.</P><P><B>Conclusion</B></P><P>Resection of the submental type dermoid cyst can be performed by an intraoral endoscope‐assisted approach through the floor of the mouth. We describe the procedure of the endoscope‐assisted intraoral resection. © 2011 Wiley Periodicals, Inc. Head Neck, 2011</P>

Wound healing of nasal mucosa in a rat

Khalmuratova, Roza,Jeon, Sea-Yuong,Kim, Dae Woo,Kim, Jin-Pyeong,Ahn, Seong-Ki,Park, Jung-Je,Hur, Dong-Gu SAGE Publications 2009 American journal of rhinology & allergy Vol.23 No.6

<P>BACKGROUND: Postoperative wound healing of the nasal mucosa is a highly organized process. However, this process still has not been fully understood. The present study aimed to establish a wound healing model in a rat and describe histomorphological changes of the nasal mucosa after mechanical injury. METHODS: Unilateral wound in the nasal cavity was induced using the brushing technique in 4-week-old, Sprague-Dawley rats. Experimental rats were divided into five groups (n = 7 for each group). Animals were killed 1 hour and 2, 5, 14, and 28 days after injury. The histological sections were examined for inflammatory cell infiltration, goblet, and ciliated cell formation in hematoxylin and eosin staining. The subepithelial and epithelial thicknesses were measured and expressed as the subepithelial thickness index (STI) and epithelial thickness index (ETI). Fibrosis was evaluated by subepithelial fibrosis index (SFI) in Masson's trichrome-stained sections. RESULTS: Respiratory epithelial discontinuity and hemorrhage were observed 1 hour after injury. On day 2, edematous subepithelium and infiltration of neutrophils could be found on the injured site. Day 5 was characterized by the infiltration of monocytes and granulation tissue. SFI and ETI values increased significantly at day 14. Goblet cells and ciliated cells began to regenerate from day 14 and restored to near normal at day 28. CONCLUSION: Using mechanical injury, the wound healing model of the nasal mucosa was established in a rat. The regeneration of respiratory mucosa was completed on day 28 after injury.</P>

Clinical characteristics and natural course of recurrent vestibulopathy: a long-term follow-up study.

Lee, Hong-Kyoung,Ahn, Seong-Ki,Jeon, Sea-Yuong,Kim, Jin-Pyeong,Park, Jung Je,Hur, Dong Gu,Kim, Dae Woo,Woo, Seung Hoon,Kang, Hung-Soo Triological Foundation [etc.] 2012 The Laryngoscope Vol.122 No.4

<P>To investigate the clinical characteristics and the natural course of recurrent vestibulopathy (RV).</P>

Sensation recovery of auricle following chronic ear surgery by retroauricular incision.

Kang, Hung-Soo,Ahn, Seong-Ki,Jeon, Sea-Yuong,Hur, Dong Gu,Kim, Jin-Pyeong,Park, Jung Je,Kim, Dae Woo,Woo, Seung Hoon Springer International 2012 European archives of oto-rhino-laryngology Vol.269 No.1

<P>The aim of this prospective analysis was to objectify and quantify the sensory loss in the auricular area that occurs following surgery for chronic otitis media or cholesteatoma, and to assess the exact recovery time of the auricular sensation. Till now, no study has yet been conducted on the sensory loss that is developed after retroauricular incision is performed for chronic ear surgery. Forty-eight patients underwent surgery via retroauricular incision for chronic otitis media or for chronic otitis media or cholesteatoma between March 2009 and January 2010. The skin around the auricle was divided into six areas. The sensation of each area was assessed before the surgery and 3 days, 7 days, 1 month, 3 months, and 6 months after the surgery, using the Semmes-Weinstein monofilaments. The patients were also asked to record the sensation that they felt using the visual analog scale (VAS). In the objective sensory assessment, only area 5, which corresponds to the retroauricular area, showed significant sensory loss. Three months after the surgery, the sensation was recovered to a level comparable to that before the surgery in most of the patients. The mean subjective VAS score was 10 prior to the surgery, 8.56 ( 1.08) 3 months after the surgery, and 9.32 ( 0.74) 6 months after the surgery, respectively. In conclusion, following chronic ear surgery, the sensation of the auricle was recovered to the previous level within 3 months. Therefore, patients who are to undergo retroauricular incision should be informed that they will experience temporary sensory loss for approximately 3 months after the surgery.</P>

Surgical Correction of Chronic Hypertropic Pyloric Gastropathy in a Dog

김준영,Soon-wuk Jeong,Sang-heuk Park,윤헌영,Hyun-jung Han,Ha-young Jang,Bo-ra Lee,Gu-yuong Kim 한국임상수의학회 2004 한국임상수의학회지 Vol.21 No.4

A ten-year-old, female Yorkshire terrier dog with intermittent vomiting, weight loss, polydipsia and depression was referred to the Veterinary Medical Teaching Hospital of Konkuk University. On the radiological survey, gas and fluid-filled gastric distention was detected. No contrast medium entranced to the small bowel, in 60 minutes after contrast medium administration. And marked fluid accumulation in gastric body and thickening of the pyloric mucosa were found with ultrasonograph. So gastric obstruction by reason of pyloric stenosis was strongly suspected. At the surgery, hypertrophied mucosa was resected adequately, and Heineke-Mikulicz pyloroplasty was applied. Microscopically the symptom was characterized by gastric mucosa hyperplasia and mild diffuse lymphoplasmocytic gastritis. So this condition was diagnosed as chronic hypertrophic pyloric gastropathy. Intermittent vomiting and mild depression were shown for 9 days after the operation. After that, the patient was recovered gradually. One month later, the patient had normal appetite and activity without complications. 10년령의 암컷 요크셔테리어 개가 간헐적인 구토와 만성 체중감소, 다갈증 그리고 쇠약증으로 건국대학교 수의과대학 부속 동물병원에 내원하였다. 방사선 검사에서 가스와 액체가 찬 위 확장이 확인 되었고, 조영제 투여후 60분이 경과하여도 조영제가 위에서 소장으로 내려가지 않았다. 초음파 상에서는 위체 부위에 상당량의 액체가 저류 되어 있었고, 유문부 점막이 비후되어 있는 것이 확인되었다. 그래서 유문부 협착으로 의한 위 폐쇠가 강력하게 의심되었다. 수술에서 비대된 위점막은 충분히 제거하였고, Heineke-Mikulicz 유문성형술을 적용하였다. 조직학적 소견상 위점막의 비후와 미약한 미만성의 림포구성 형질세포성 위염을 나타내었다. 모든 소견을 종합하여 볼 때, 만성 비후성 유문 위장애로 진단하였다. 간혈적인 구토와 활력저하는 수술 후 9일간 보였다. 이후 환축은 점차적으로 회복되었다. 한달 뒤 환축은 정상적인 식욕과 활력을 나타내었다.