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.

췌장염에 의한 가성낭종내에 생긴 가성동맥류 : 1례 보고

오연희,이채경,김승현,이성우,양창현,이정호,이영현 동국대학교 경주대학 1996 東國論集 Vol.15 No.-

만성 췌장염의 합병증으로 생긴 가성동맥류는 드문질환으로, 반복적으로 다량의 출혈을 일으킬 수 있으며, 치료를 하지 않을 경우 사망율이 높기 때문에, 조기 진단과 치료가 필수적이다. 저자들은 38세 남자 환자에서 췌장염의 합병증으로 생긴 가성낭종내에서 발생한 가성동맥류 1예를 경험하였기에 보고하는 바이다. 가성 동맥류의 색혈류도플러상 낭종내에 양방향 흐름의 와류를 볼 수 있었다. Pancreatic Pseudoaneurysm within Pseudocyst from Pancreatitis: 1 Case Department of Diagnostic Radiology and Internal Medicine, College of Medicine,DongGuk University Yeon Hee OH M.D., Chae Kyeong Lee M.D., Seoung Hyeon Kim M.D., Sung Woo Lee M.D., Chang Heon Yang M.D., Jung Ho Lee M.D., Young Hyun Lee M.D. Pseudoaneurysm from pancreatitis is uncommon, but it can cause recurrent and massive hemorrhage. Because of high morbidity and mortality, early detection and treatment of the pseudoaneurysm is needed. We report a case of pseudoaneurysm within pseudocyst from pancreatitis. Color-flow Doppler sonography shows bidirectional flow and turbulent arterial flow, within anechoic mass.

에탄올을 장기간 섭취한 백서에서 Acamprosate 투여가 Nitric Oxide Synthase 발현에 미치는 영향

정홍경,이기철,이정호,이승휘,이희제,정주호 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

Fluoxetine이 Schedule-Induced Polydipsia가 유발된 백서 뇌에서 Tyrosine Hydroxylase 발현에 미치는 영향

이기철,이정호,최영민,정주호,정홍경,이용민,김도형,이대환 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.2

연구목적: Fluoxetine은 serotonin을 매개하여 간접적으로 dopamine 신경전달기능을 억제한다고 추정되고 있다. 또한 운동장애에서 운동기능의 악화를 유발한다고 알려져 있다. 그러나 신경세포체에서 fluoxetine이 dopamine에 어떠한 영향을 주는지는 아직까지 확실치 않다. 저자들은 schedule-induced polydipsia를 유발시킨 백서 뇌의 흑질, 복부피개영역, 미상핵에서 tyrosine hydroxylase(TH) 발현이 저하됨을 발견하였다. 이를 통해서 fluoxetine이 백서 뇌의 dopamine 기능에 긍정적인지 혹은 부정적인지를 규명하고자 하였다. 방법: 4주간의 schedule-induced polydipsia 과정을 거친 백서에서 면역죄치화학적인 방법으로 흑질, 복부피개영역, 미상핵의 tyrosine hydroxylase 발현이 저하됨을 확인한 후, 실험동물들에게 fluoxetine 10mg/kg를 3주간 복강내 주사하였다. 실험백서들을 희생시켜 뇌 조직을 적출하여, TH 면역조직화학 염색법을 이용하여 흑질, 복부피개영역, 그리고 미상핵의 TH 면역반응세포를 관찰하고 이를 정상백서와 비교하였다. 결과: 1) 다갈증이 유발된 백서의 흑질, 복부피개영역, 미상핵에서 tyrosine hydroxylase 발현이 정상백서 보다 저하됨을 관찰하였다. 2) 3주간에 걸친 fluoxetine 투여후 흑질, 복부피개영역, 미상핵의 tyrosin hydroxylase 발현이 다시 증가하는 소견을 보였다. 결론: Fluoxetine 만성투여가 흑질, 복부피개영역 그리고 미상핵의 tyrosin hydroxylase를 증가시키는 소견을 얻었다. 이러한 결과는 임상에서 dopamine 결핍과 연관된 질환들에서 fluoxetine을 만성투여하면 운동기능을 포함한 증상들의 개선을 가져올 수도 있다고 추정된다. Objective: It has been suggested that fluoxetine inhibits the dopaminergic neurotransmission by serotonergic mediation. And also, it has been shown to inhibit synthesis of DOPA in dopamine-rich areas of the rat forebrain. These dopamine-antagonistic capacity of fluoxetine is only supported by anecdotal report that the increased amount of motor disability in patients with idiopathic Parkinson's disease after exposure to fluoxetine. However, there is still no evidence of the direct effect of fluoxetine on dopaminergic neuronal cell body in the substantia nigra, VTA, caudate & putamen. This study was designed to evaluate the effects of fluoxetine in rat brain which showed decreased numbers of dopaminergic neuronal cell body induced by schedule-induced polydipsia(SIP). Method: We incidentally found that 4 weeks of schedule-induced polydipsic rats revealed the suppression of tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen with the immunohistochemistric measures. After 3 weeks of intraperitoneal injection of 10mg/kg of fluoxetine to the schedule induced polydipsic rats, the tyrosine hydroxylase expression was also measured with immunohistochemistry. We compared the tyrosine hydroxylase expression among the normal control, the polydipsic rats, and the rats with fluoxetine treatment. Results: 1) By contrast with the control, the polydipsic rats revealed the evidence of decreased tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen. 2)After daily injection of fluoxetine for 3 weeks, the polydipsic rats showed increment of tyrosine hydroxyase expression in those areas. Conclusions: In previous studies, a great deal of results suggest that fluoxetine negatively influence the dopaminergic systems indirectly via serotonergic activation such as inhibition of dopamine synthesis or transport system. Although our results are obtained from rodents, we suggest that fluoxetine directly and positively enhance the dopamine system in the substantia nigra, VTA, caudate & putamen. The chronic adminstration of fluoxetine may be helpful to dopamine-depleted condition in clinical situations. We anticipate the replication studies of our findings and well-controlled clinical trial.

에탄올이 백서의 해마에서 Neuropeptide Y 발현에 미치는 영향

정홍경,이기철,이정호,이희제,정주호,이주영 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

물-공기 계면에서 긴 사슬 양 말단 작용기 분자인 α,ω-13,16-Dimethyloctacosanedioate Dimethylester(C_30DME)의 거동에 관한 연구

이정근,손대원,이관수,송석호,김현명,정선호 한양대학교 자연과학연구소 2001 自然科學論文集 Vol.20 No.-

물-공기 계면에서 표면압력의 증가에 따른 C30DME 분자의 구조 변화를 살펴보았다. 표면압력(π)-표면적(A) 등온선을 통해 표면적이 줄어들 때 C30DME 분자가 선형으로부터 역 U 자형 구조로 변하는 것을 확인하였다. C30DME의 역 U 자형 구조의 형성을 확인하기 위하여 Surface Plasmon Resonance (SPR)와 ellipsometry를 이용하여 Langmuir-Blodgett (LB) film 의 두께를 측정하였고 이 두께는 C30DME 분자의 역 U 자형 구조의 높이와 일치함을 관찰하였다. 또한 Atomic Force Microscope (AFM)을 이용한 표면 거침도 측정의 결과는 선형으로부터 역 U자형 구조로의 구조적 변화가 불연속이라는 것을 보여주었다. We investigated the conformational change of C30DME molecule with an increase on surface pressure at the air-water interface. The surface pressure (π)-area (A) isotherm indicates that the structure of C30DME changed from linear to reverse U-shape as the surface area was compressed. In order to confirm the formation of reverse U-shape, we examined the thickness of Langmuir-Blodgett (LB) film by a surface plasmon resonance (SPR) and an ellipsometry. The result of surface roughness measurement using an atomic force microscope (AFM) showed that the conformational change from linear to reverse U-shape is discontinuous.

거동 가능한 정읍지역 노인층에서 영양 지표의 정상분포

이은주,심선진,김정호,이무송,이영수 대한노인병학회 2002 대한노인병학회지 Vol.6 No.1

Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

Lee, Young-Man,Auh, Q-Schick,Lee, Deok-Won,Kim, Jun-Yeol,Jung, Ha-Jin,Lee, Seung-Ho,Kim, Eun-Cheol Hindawi Publishing Corporation 2013 BioMed research international Vol.2013 No.-

<P>Although previous studies have shown that mollugin, a bioactive phytochemical isolated from <I>Rubia cordifolia</I> L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G<SUB>1</SUB> phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-<I><I>κ</I></I>B and NF-<I><I>κ</I></I>B-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2–related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-<I><I>κ</I></I>B.</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.

Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

Jung Kyung Hee,Kim Sang Eun,Go Han Gyeol,Lee Yun Ji,Park Min Seok,Ko Soyeon,Han Beom Seok,Yoon Young-Chan,Cho Ye Jin,Lee Pureunchowon,Lee Sang-Ho,Kim Kipyo,Hong Soon-Sun 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.6

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.