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.

배치와 형태에 관한 분자궤도론적 연구 (제15보). 에틸렌 디아민의 Through-Space 및 Through-Bond 상호작용

이익춘,손창국,송창현,Ikchoon Lee,Chang Kook Sohn,Chang Hyun Song 대한화학회 1982 대한화학회지 Vol.26 No.2

여러 형태의(n${\pi}$/m) 및 (n-${\sigma}^*$) 구조가 에너지에 미치는 구조적인 기여를 살펴보기 위하여 n-프로필아민, n-프로필아민 라디칼, trans-및 cis-에틸렌 디아민에 대한 STO-3G 수준의 계산을 수행하였다. 그 결과 (5${\pi}$/5)구조가 (4${\pi}$/4)구조는 각각 인력 및 반발의 비결합 상호작용을 나타내었으며 서로 부가관계를 가짐을 알았다. anti(n-${\sigma}^*$) 구조는 syn(n-${\sigma}^*$)구조보다 강한 hyperconjugation효과를 보이지만 anti(n-${\sigma}^*$)구조에서 강한 핵간 반발력을 가지기 때문에 결과적으로 불안정한 겉보기 효과를 나타내었다. 더우기 안정화${\pi}$ -비결합 (5${\pi}$/5)구조는 anti(${\pi}$-${\sigma}^*$)구조를, 불안정화 ${\pi}$-비결합(4${\pi}$/4)구조는 syn(n-${\sigma}^*$)구조를 수반하며 상호 보강적으로 작용함을 알았다. 또한 이러한 상호 보강성이 일반적인 성질임을 알았다. 끝으로 말단의 고립 전자쌍에 의한 through-bond 상호작용을 논의하였으며 이러한 상호작용으로 에너지 준위가 $n_+ = \frac{1}{\sqrt{2}}(n_1\;+\;n_2)$와 $n_-\;=\;\frac{1}{\sqrt{2}}(n_1\;-\;n_2)$로 갈라지는데 이때 고립 전자쌍의 간단한 overlap pattern으로 n_준위가 안정한 준위임을 알았다. STO-3G level computations were performed on n-propylamine, n-propylamine radical and cis-and trans-ethylene diamines in order to investigate structural contributions of (n${\pi}$/m) and (n-${\sigma}^*$) structures to the energy variations accompanying the conformational changes. It was found that (5${\pi}$/5) and (4${\pi}$/4) structures had attractive and repulsive nonbonded interactions, respectively, which were approximately additive. anti(n-${\sigma}^*$) structures had more stabilzing hyperconjugative interactions than syn(n-${\sigma}^*$) structures, but due to the large internuclear repulsion the net effect was destabilizing inthe former in contrast with the net stabilizing contribution in the latter. Moreover it was found that the stabilizing ${\pi}$-nonbond structure, (5${\pi}$/5) was always cooperatively reinforced by the more stabilizing anti(n-${\sigma}^*$) interaction, whereas the destabilizing (4${\pi}$/4) structure was accompanied by the less stabilizing syn(n-${\sigma}^*$) interaction. This type of cooperativity was found general through-bond interaction of the terminal lone pair lobes split the energy levels into two, $n_+ = \frac{1}{\sqrt{2}}(n_1 + n_2)$ and $n_- = \frac{1}{\sqrt{2}}(n_1 - n_2)$, the latter being the lower level, which can be shown using simple overlap patterns of the two lobes with a common vicinal ${\sigma}^*$ orbital.

膀胱의 單臟器成 Shwartzman反應에 관한 超微形態學的 硏究

권민아,장세국,서인수,손태중 慶北大學校 醫科大學 1990 慶北醫大誌 Vol.31 No.4

본 연구는 감염성 방광염의 성립의 조건으로 Shwartzman반응의 기전이 참여할 것인가를 검토하고, 방광의 단장기성 Shwartzman반응에서 초기의 형태적 변화를 알아보기 위하여 시도하였다. 실험은 백색 암컷 가토를 실험동물로 하여 방광내에 내독소를 주입하고 24시간후에 정맥내로 같은 내독소를 주사하여 야기조작 15및 30분, 1, 2 및 4시간후에 방광을 적출하여 육안, 광학, 주사전자 및 투과 전자현미경으로 관찰하였던 바 그 성적을 요약하면 다음과 같다. 광학 현미경으로는 반응의 초기부터 표재세포가 호산성 덩어리로의 변성 및 괴사 탈락이 나타나고, 중간세포 및 기저세포는 야기조작 수시간 후부터 공포성 변성을 보이고, 같은 시기에 상피하 미소혈관은 울혈 및 주변 조직의 부종을 보이고, 호중구의 침윤도 관찰되었다. 주사 전자현미경으로는 표재세포 표면의 microridge의 blurring과 표면구조의 편평화 및 세포간 결합장치의 이완등을 초기에서 부터 볼 수 있었고, 수시간이 지난 후에는 군데군데에서 상피의 괴사 탈락이 관찰되었다. 투과 전자현미경으로는 포재세포의 apoptosis를 초기에서부터 볼 수 있었고, 수시간 후에는 상피층 전층의 괴사까지 관찰되었고, 기저세포에는 autophage가 증가된 것이 관찰되었다. 가장 특징적 변화는 상피직하 점막하층 미소혈관계의 변화로 반응의 초기에서부터 내피세포의 종창등의 상해성 변화를 보였고, 수시간후에는 혈소판의 응집과 호중구의 변연화 및 유주등을 관찰할 수 있었다. 이상의 성적으로 보아 방광염의 성립에 Shwartzman반응의 기전이 참여할 수 있는 것으로 생각되며, 방광의 단장기성 Shwartzman반응의 주된 반응을 하는 장소는 상피직하부의 미소혈관계인 것으로 사료된다. This study was carried out to investigate the possible role of Shwartzman reaction in the development of the cystitis and the morphologic changes in early stage of the reaction. Endotoxin extracted from E. coli was injecting same endotoxin via ear vein, 24 hours after first infection. Animals were sacrificed 15 and 30 minutes, and 1, 2 and 4 hours after the last injection. The Urinary bladders were extracted out and examined with the light, transmision electron, and scanning electron microscopes. The results obtained were summarized as follows: Ligth microscopy showed eosinophilic degradation, necrosis and detachment of the superficial cells within 1 hour after provocation treatment. Intermediate and basal cells also showed swelling after few hours. Subepithelial microvasculatures showed congestion with perivascular edema and neutrophilic infiltration from the early stages. Scanning electron microscopy dischlosed blurring of microridge structures on superficial cells with loosening of the intercellular junction from early stage. Necrosis and detachment of epithelial cells were noted in several areas after few hours, only remaining basement membranes. Transmission electron microscopy showed apoptosis of the superficial cells, with partial necrosis through total thickness of the epithelial layer after several hours. Many autophagic vacuoles were found in basal cells. Characteristic vascular change was noted in the microvasculatures on the submucosa, consisting of swelling and archade formation of the endothelial cells with platelet aggregation, and margination and emigration of neutrophils. The results suggest that Shwartzman reaction could be participated on the development of cystitis, and subepithelial small vessels were the main focus of the reaction.

Miltomycin C의 膀胱內注入에 依한 흰쥐 膀胱粘膜의 形態的 變化

韓大基,張世國,徐仁壽,孫泰重 慶北大學校 醫科大學 1988 慶北醫大誌 Vol.29 No.2

근래에 방광의 표재성 암이나 수술 혹은 방사선 치료의 보조화학요법제로 많이 이용되고 있는 mitomycin C의 방광내 주입요법에 대한 안정성은 임상적으로 별다른 주목을 받고 있지 못한 실정이다. 그러나 이 요법의 이용 빈도가 차츰 증가하는 추세에 비추어 안전성 검토는 매우 중요하다고 생각된다. 본 연구는 이런 견지에서 MMC의 방광주입후 방광점막에 미치는 영향을 형태학적으로 추구하고져 시도되었다. Sprague-Dowley종 흰쥐에 catheter를 이용하여 0.3mg의 MMC를 0.3㎎의 증류수에 녹여 방광내에 1회 및 하루 간격으로 연속 3회 주입하였다. 실험동물은 각기 마지막 주입 1주후 및 2주후에 방광을 적출하고 광학, 주사전자 및 투과전자현미경으로 관찰하였던 바 그 결과를 요약하면 다음과 같다. 광학현미경으로 MMC 1회 주입군보다 3회 주입군이 더 심한 변화를 나타내었으며 주입 1주일보다 2주일째 더 심한 변화를 보였다. 주사전자현미경으로 방광점막 상피는 1) microridge가 발달한 세포, 2) 미융모가 발달한 세포 및 3) 평활한 세포등의 3기본형과 4) microridge가 더 많고 미융모도 있는 세포, 5) 미융모가 더 많고 microridge가 형성되는 세포 등 5가지 종류로 나눌 수 있었다. 주사 및 투과전현상 표재세포에서 microridge의 변형과 괴사 및 탈락을 볼 수 있었고 표재세포의 괴사 및 탈락으로 하부의 중간 세포가 표면에 노출되어 주사전현상 미융모가 풍부한 세포로 대치된 것처럼 보인 것으로 생각된다. 이상화 같은 변화들은 방광점막 상피세포에 대한 MMC의 직접 독성작용으로 생각된다. Recently intraveisical instillation therapy of the bladder tumor is widely used, particulary for the superficial tumor and as supplementary chemotherapy after resection of the wide spread bladder tumor. It is widely accepted that this measure is relatively safe, but systemized evaluation of the therapy should be required. This study is carried out to investigate the effects of the mitomycin to the urothelium in the rat to clarify the direct morphologic effects of the mitomycin by the intravesical instillation of the drugs. Mitomycin, 0.3㎎ in 0.3㎖ of distilled water, is instillated to the urinary bladder of sprague-Dowley rats, 1 time and 3 times for 3 consequetive days respectively. Animals are sacrificed 1 week and 2 weeks after the instillation. Light, scanning electron and transmission electron microscopic examinations were done. The results obtained were summarized as follow : Light microscopic examination disclosed more severe changes in 3 times injected group than 1 time injected group ; the changes were more severe 2-weeks-later group than 1-week-later group. Scanning electron microscopic examination showed 5 types of epithelial cells according to their surface structures : 1) Those with full-brown development of microvilli; 2) those with covered by well developed microvilli; 3) those with smooth surface; which were thought to be basic types, corresponding to the superficial, intermediate and basal cells, respectively. Another two types were also distinguished, showing surface structure having both of microvilli and microridges. Mitomycin C induced distortion of the surface microridge structures and even necrosis of the superficial cells in both scanning and transmission microscopic examinations. Intermediate cells are exposed by the detachment of the overlying superficial cells, which showed well developed microvilli structures, but some of these structures were also distorted. These changes were thought to be induced by direct toxic effects of mitomycin to the urothelium.

질산기의 친핵성 치환반응. 아세토니트릴용매에서 질산치환벤질류와 아닐린류와의 반응속도론

김왕기,손창국,Wang Ki Kim,Chang Kook Sohn 대한화학회 1989 대한화학회지 Vol.33 No.1

순수한 아세토니트릴용매에서 질산파라-치환 벤질과 파라-치환 아닐린간의 친핵성 치환반응에 대한 2차반응속도상수를 전기전도도법으로 구하여 Hammett ${\rho}$x와 ${\rho}$y값 및 Bronsted ${\beta}$값을 계산하였다. 이때 아닐린의 치환기 변화에 따르는 ${\rho}$x는 음의 값으로 주어졌으며 기질의 치환기에 따라서는 U자 모양의 비직선성 Hammett 도시가 얻어졌다. 포텐셜에너지표면 및 양자역학적 모형을 적용하여 치환기 변화에 따른 천이상태 구조의 변화를 고찰하여 본 결과 본 반응은 기질의 치환기의 성질에 따라 결합형성의 정도가 크게 변화하는 $S_{N}2$ 반응 메카니즘으로 진행함을 알 수 있었다. The second-order rate constants for the nucleophilic substitution reactions of para-substituted benzyl nitrates with para-substituted anilines in acetonitrile were conductometrically determined. Hammett ${\rho}$x and ${\rho}$y values and Bronsted ${\beta}$ values were obtained from these kinetic data. The reactions of Benzyl nitrates with the series of anilines showed linear Hammett plots with negative slopes. For the change of substituents in the benzyl nitrates, nonlinear Hammett plots with a concave upwards curve were obtained. We applied the potential energy surface and the quantum mechanical models in order to examine the transition state variations caused by changes in substituents on the nucleophile and the substrate. The results showed that the reaction was proceeded via the $S_{N}2$-type reaction mechanism in which the extent of bond-formation was greatly changed depending on the property of the substituents in substrate.

Does hyaluronic acid stimulate tumor growth after endoscopic mucosal resection?

Sohn, Dae Kyung,Chang, Hee Jin,Choi, Hyo Seong,Jeong, Seung-Yong,Kook, Myeong-Cherl,Kim, Chan Gyoo,Choi, Il Ju Blackwell Publishing Asia 2008 Journal of gastroenterology and hepatology Vol.23 No.8

<P>Abstract</P><P>Background and Aim: </P><P>A submucosal injection of sodium hyaluronate is widely used for mucosal elevation in endoscopic mucosal resection (EMR) or endoscopic submucosal dissection procedures; however, the oncologic safety of sodium hyaluronate remains unknown. Hyaluronate is the main ligand for CD44 and this interaction was reported to promote tumor progression in <I>in vitro</I> or animal studies. This study aimed to evaluate the effects of sodium hyaluronate on tumor growth after EMR for gastrointestinal cancers.</P><P>Methods: </P><P>The study included 18 consecutive patients who underwent surgery for locally-recurrent or remnant gastrointestinal cancers after EMR from January 2001 to December 2006. The immunohistochemical expression levels of Ki-67, CD44, ErbB2, and epidermal growth factor receptor (EGFR) were evaluated in the primary tumor tissue and the recurrent tumor. The protein expression in recurrent or remnant lesions was also compared between the sodium hyaluronate group and non-sodium hyaluronate group.</P><P>Results: </P><P>Sodium hyaluronate was used in nine of 14 cases with EMR for gastric cancers and in one of four cases for colon cancers. The time to operation after EMR was 133 days (5–687 days). An analysis of the immunohistochemical expression levels between primary and recurrent or remnant tumors showed no significant differences in the expression levels of Ki-67, CD44, ErbB2, and EGFR with or without sodium hyaluronate.</P><P>Conclusions: </P><P>We found no evidence that sodium hyaluronate stimulates the growth of remnant tumors after EMR.</P>

Computational Study on Protolytic Dissociation of HCl and HF in Aqueous Solution

Kim, Chang Kon,Park, Byung Ho,Sohn, Chang Kook,Yu, Yu Hee,Kim, Chan Kyung Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.4

The protolytic dissociation process of hydrochloric acid (HCl) and hydrofluoric acid (HF) is studied using the B3LYP and MP2 methods with the 6-311+G(d,p) basis set in the gas phase and in aqueous solution. To study the phenomena in detail, discrete and discrete/continuum models were applied by placing water molecules in various positions around the acid. The dissociation process was studied using the thermodynamic cycle involving the structures optimized both in the gas phase and in aqueous solution and was analyzed with two key energy factors, relaxation free energy (${\Delta}G_{Rex(g)}$) and solvation free energy (${\Delta}G_s$). Based on the results, we could understand the dissociation mechanism and wish to propose the best way to study acid dissociation process using the CPCM methodology in aqueous solution.

Comparative Studies on the Reactions of Carbamyl and Thiocarbamyl Halides with NH₃ in the Gas Phase and in Aqueous Solution: A Theoretical Study

Kim, Chang-Kon,Han, In-Suk,Sohn, Chang-Kook,Yu, Yu-Hee,Su, Zhishan,Kim, Chan-Kyung Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.6

In this work, the reactions of carbamyl and thiocarbamyl halides with $NH_3$ were studied in the gas phase at the MP2(FC)/6-31+G(d) level of theory. Single point calculations were performed at the QCISD/6-311+G(3df,2p) to refine the energetics. The reaction mechanisms were also studied in aqueous solution. The structures were fully optimized at the CPCM-MP2(FC)/6-31+G(d) and refined by a single point CPCM-QCISD/6-311+G(3df,2p) calculations. The reaction mechanisms for the title compounds were compared with those for the acetyl and thioacetyl halides. The lower reactivity of carbamyl (and thiocarbamyl) groups was explained by comparing the C=O and C=S ${\pi}$-bond strengths as well as resonance contributions in the ground state.

당뇨유리체절제술 후 유리체 재출혈과 연관된 전신적 위험인자

김창국(Chang Kook Kim),윤준택(June Taek Yoon),손준홍(Jun Hong Sohn),윤영희(Young Hee Yoon) 대한안과학회 2001 대한안과학회지 Vol.42 No.3

LOW-DOSE RATE RADIATION CAUSES DAMAGE TO EARLY FOLLICLES IN YOUNG MOUSE OVARIES

Min Kook Kang,Se Yoon Seong,Hyunju Kang,Hae-June Lee,Yeong-Rok Kang,Chang Geun Lee,Dong Hyun Sohn,Eun Kyung Shin,Hye Min Kim,Jeong-Hwa Baek,Seung Jin Han 대한방사선방어학회 2023 대한방사선방어학회 학술발표회 논문요약집 Vol.2023 No.4