Role of Central opiate System in Control of Cardiovascular Function of Experimental Hypertensive Rats

김기원,곽용근,채준석,조규박,Kim, Kee-Won,Kwak, Yong-Geun,Chae, Joon-Seak,Cho, Kyu-Park The Korean Society of Pharmacology 1987 대한약리학잡지 Vol.23 No.2

Morphine을 비롯한 opioid peptide가 말초 또는 중추에 투여시 혈압하강과 심박동수감소를 보이며 opiate 수용체 길항제인 naloxone에 의해 길항됨이 관찰되었던바 근래 몇몇 보고들은 중추신경내에서 adrenergic및 opioidergic system이 서로 관련되어 있음을 시사하고 있다. 이에 본 실험에서 고혈압 연구에 널리 사용되고 있는 2-kidney, 1-clip (2K1C) 방법으로 실험적 고혈압을 유발시킨 백서의 측뇌실내 clonidine또는 morphine의 심맥관계에 대한 효과와 각각의 차단제에 의한 영향 그리고 정상 및 고혈압상태 백서의 뇌내 ${\beta}-endorphin$의 함량과 specific opiate receptor binding을 정량하여 고혈압 유발에 따른 뇌내 opiate system의 변동을 관찰하였다. 2K1C 고혈압 또는 sham-operated대조백서에서 측뇌실내 clonidine $(3-30\;{\mu}g/kg)$은 용량에 비례하여 혈압하강과 심박동수감소를 일으켰으며 clonidine의 혈압강하 효과는 2K1C고혈압 백서에서 더욱 현저하였다. clonidine의 혈압강하효과는 고혈압 백서에서 측뇌실내 yohimbine 또는 naloxone 전처리에 의해 약화되었고 대조군에서는 yohimbine ($30\;{\mu}g/kg$, i.v.t.)에 의해 억제되었으나 naloxone ($50\;{\mu}g/kg$, i.v.t.)에 의해서는 영향 받지 않았다. clonidine과 마찬가지로 측뇌실내 morphine $(10-100\;{\mu}g/kg)$은 2K1C 고혈압 또는 sham-operated 대조백서에서 용량에 비례하여 혈압하강과 심박동수감소를 일으켰으며, morphine의 혈압강하효과는 2K1C 고혈압백서에서 더욱 현저하였다. 대조군과 고혈압군에서 morphine의 혈압강하효과는 naloxone 전처리에 의해 현저히 약화되었으나 yohimbine에 의해서는 영향 받지 않았다. 2K1C 시술익일부터 투여한 clonidine은 2K1C 시술에 의한 혈압 상승을 억제하였으며 naloxone (2 mg/kg, i.p.)에 의해 반전되었다. 2K1C 시술에 의해 고혈압이 유발된 백서의 뇌내 ${\beta}-endorphin$ 함량은 sham-operated 군에 비하여 유의하게 감소되어 있었고 (3H)-naloxone의 specific binding의 Bmax는 증가되었으나 Kd치는 변동되지 않았다. 이상의 실험 성적은 뇌내 opiate계가 혈압조절에 중요한 역할을 담당하고 있으며 2K1C 고혈압백서의 고혈압상태 유지에 뇌내 opiate계의 기능저하가 일부관여하고 있음을 강력히 시사한다. The possible inolvement of central opiate system in the control of cardiovascular function and in the antihypertensive action of clonidine has been examined in unanesthetized rats with shamoperated or 2-kidney, 1-clip (2K1C) renal hypertension. In both groups of rats, intraventricular clonidine $(3-30\;{\mu}g/kg)$ produced hypotension and bradycardia. Hypotensive action of clonidine was more potent in the hypertensive rats than in the normotensive sham-operated rats. Yohimbine $(30\;{\mu}g/kg,\;i.v.t.)$ inhibited the hypotension and bradycardia produced by clonidine. Naloxone ($50\;{\mu}g/kg$, i.v.t.) inhibited the action of clonidine in 2K1C hypertensive rats but not influenced in the sham-operated rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced blood pressure and heart rate in both groups of rats. But these effects were not affected by yohimbine, but antagonized by naloxone ($50\;{\mu}g/kg$, i.v.t.). Chronic treatment of 2K1C rats with clonidine ($3{\times}20\;{\mu}g/kg$, p.o.,) for 14 days from 1 day after 2K1C operation) suppressed the development of hypertension and maintained the blood pressure in normal level and this errect of clonidine was abolished by naloxone (2 mg/kg, i. p.). In the 2K1C hypertensive rats, immunoreactive ${\beta}-endorphin$ content was significantly decreased, but maximum binding (Bmax) of $(^3H)-naloxone$ was significantly increased in brain of 2K1C hypertensive rats. However, Kd value was not changed. These results suggest that the opioidergic component might be involved in the antihypertensive action of clonidine only in hypertensive and that central opiate system might play important roles in pathophysiology of development and maintenance of hypertension.

백서와 기니픽의 대뇌피질에서 Opioid Kappa 수용체의 특성에 관한 연구

김기원(Kee-Won Kim),노혜원(Hye-Won Rho),김형일(Hyoung-Il Kim),은재순(Jae-Soon Eun),소수미(Soo-Mi Soh),조규박(Kyu-Park Cho) 대한약리학회 1994 대한약리학잡지 Vol.30 No.2

In this study, we tested the influences of several κ opioid ligands on the [³H]diprenorphine binding in rat and guinea pig cortex membrane preparations. Using paradigm to block μ and δ opioid receptors with DAMGO(1μM) and DPDPE(1μM), [³H]diprenorphine labeled κ sites. Competition analysis in both rat and guinea pig cortex has shown a single population of [³H]diprenorphine binding site with different Kd values, respectively. There is a significant difference in Ki values of (-) WIN44441 and (+)WIN44441 in both rat and guinea pig cortex. Bremazocine, (-)ethylketocyclazocine, (-)cyclazocine, nor-binaltorphimine effectively inhibited the [³H]diprenorphine binding with different Ki values in rat and guinea pig cortex. U-69,593, U-50,488H and dynorphine-A (1-8) did not inhibit the [³H]diprenorphine binding in rat but in guinea pig cortex. Nor-binaltorphimine was a ligand discriminate the κ₁, and κ₂ receptor most effectively. We, also, examined the influence of Na ion and GTPγS, a nonhydrolyzable guanine nucleotide analog, on the inhibition of [³H]diprenorphine binding by diprenorphine, (-)ethyl-ketocyclazocine, U-69,593 and bremazocine. By the replacement of NaCl with N-methy-D-glucamine or addition of GTPγS, Ki values of diprenorpnine were not changed and that of ethylketocyclazocine were changed significantly in both rat and guinea pig cortex. The Ki value of bremazocine was decreased by removal of Na ion, and increased by GTPγS, however, was not changed by any one of either. These results suggest that there are 2 kinds of subtypes of κ opioid receptor, κ₁, and κ₂, showing different Ki values for various κ opioid ligands, also, bremazocine possess the antagonistic property at κ₂ site which is dominant subtype of K receptor in rat cortex.

Al-Li계 합금의 가공열처리에 따른 조직과 기계적성질의 변화

김기원,우기도,이광로,이민상,이민호,황호을 ( Ki Won Kim,Kee Do Woo,Kwang Ro Lee,Min Sang Lee,Min Ho Lee,Ho Eul Hwang ) 한국열처리공학회 1991 熱處理工學會誌 Vol.4 No.3

The present work was aimed to examine the variation of precipitations and mechanical properties by thermomechanical treatments(TMT) in Al-2.19wt%Li and Al-2.0wt%Li-0.11wt%Zr alloys. This study was perfomed by TEM, SEM observation, DSC, electrical resistance measurement, hardness and tensile strength measurment. First peak of resistivity aged at 90℃ was caused by precipitation of δ` -precursor phase, and second peak was caused by precipitation of δ` phase. According to this result, the precipitation process of Al-2.19wt%Li alloy was as follow : SSSS→δ` -precursor phase→δ`(Coherent→Semi-coherent)→δ In a Al-2.0wt%Li-0.11wt%Zr ternary alloy, the first peak of resistivity was appeared at initial aging heat-treatment. It is result from exsistant of δ` -precursor phase. The effect acceleration in a binary alloy was not appeared and the over-aging ternary alloy was accelerated with increase of the reduction rate. 1t is caused by combination effect of δ` and composite phase.

유한체 GF(2^m)상의 낮은 지연시간의 AB² 곱셈 구조 설계

김기원,이원진,김현성,Kim, Kee-Won,Lee, Won-Jin,Kim, HyunSung 대한임베디드공학회 2012 대한임베디드공학회논문지 Vol.7 No.2

Efficient arithmetic design is essential to implement error correcting codes and cryptographic applications over finite fields. This article presents an efficient $AB^2$ multiplier in GF($2^m$) using a polynomial representation. The proposed multiplier produces the result in m clock cycles with a propagation delay of two AND gates and two XOR gates using O($2^m$) area-time complexity. The proposed multiplier is highly modular, and consists of regular blocks of AND and XOR logic gates. Especially, exponentiation, inversion, and division are more efficiently implemented by applying $AB^2$ multiplication repeatedly rather than AB multiplication. As compared to related works, the proposed multiplier has lower area-time complexity, computational delay, and execution time and is well suited to VLSI implementation.

Regulation of Histamine Release by Kappa Opioid Receptor in Rat Cortical Slices

김기원,조규박,Kim, Kee-Won,Cho, Kyu-Park The Korean Society of Pharmacology 1994 대한약리학잡지 Vol.30 No.1

Opioid 수용체에는 ${\mu},\;{\delta}$ 그리고 ${\kappa}$의 세가지 주된 형이 존재함이 알려져 있는 바, 최근 수용체 동정 기법과 선택적인 약물의 개발로 인해 그 아류들이 존재함이 보고되고 있다. 그러나 Opioid ${\kappa}_{2-}$ 수용체의 기능에 대해서는 이 수용체에 있어서의 선택적인 효현제 또는 길항제가 밝혀져 있지 않으므로써 현재까지 잘 알려져 있지 않다. 본 연구에서는 백서 대뇌피질 세표막표본에 opioid ${\mu}$와 ${\delta}$ 수용체를 과량의 DAMGO와 DPDPE로 봉쇄한 후 수종 ${\kappa}$수용체 결합자의 $[^3H]\;idprenorpnine(DIP)$ 결합억제효과와 이에 대한 sodium과 $GTY{\gamma}S$의 영향을 관찰하여 이를 지표로 각 ligand의 수용체에서의 작용양상을 검토하여 이를 토대로 동일 표본에서 $[^3H]diprenorpnine[^3H]DIP$ 결합은 DIP, ethylketocyclazocine 그리고 bremazocine에 의해 효과적으로 억제되었으나, ${\kappa}_1$, 수용체 효현제인 U69593에 의해서는 억제되지 않았다. Opioid ${\kappa}_1$, 및 ${\kappa}_2$-수용체 효현제인 EKC의 Ki치는 배양액내 NaCl을 NMDG로 알려진 $GTP{\gamma}S\;100{mu}M$ 첨가에 의해 증가되었다. 그러나 Bremazocine과 DIP의 Ki치는 sodium 제거 또는 $GTP{\gamma}S\;100{mu}M$ 첨가에 의해 증가되었다. 그러나 Bremazocine과 DIP의 Ki치는 sodium 제거 또는 $GTP{\gamma}S$ 첨가에 의해 영향받지 않았다. $1-[^3H]\;histidine$을 미리 부하한 대뇌피질 절편에서 $30mM\;K^+$ 에 의한 $[^3H]\;histamine$의 유리는 (-)EKC에 의하여 영향받지 않았다. (-)EKC의 histamine유리 억제효과는 naloxone, norbinaltorpmine 또는 bremazocine에 의하여 각각 억제되었다. 본 실험 성적은 백서 대뇌피질에서 histamine의 유리는 이 부위에 존재하는 opioid ${\kappa}_2$-수용체에 의하여 조절됨을 시사한다. It has been shown that there are several subtypes of ${\kappa}$ opioid receptor. We examined ligand binding profiles and the effects of various opioid agonists on high potassium-stimulated release of $[^3H]$ histamine. We have evaluated the properties of $non-{\mu},\;non-{\delta},$ binding of $[^3H]\;DIP\;([^3H]\;diprenorphine),$ anonselective opioid antagonist, in rat cortex membranes. Binding $to\;{\mu}\;and\;{\delta}$ sites was inhibited by the use of an excess of competing selective agonists (DAMGO, DPDPE) for these sites. (-) Ethylketocyclazocine (EKC), DIP and bremazocine inhibited $[^3H]$ DIP binding. However, arylacetamides (U69593 and U50488H) gave little inhibition Replacement of sodium by NMDG and the addition of guanine nucleotide influenced the inhibitory potency of (-) EKC, an agonist for {\kappa}_1-and-{\kappa}_2-binding site, but not of bremazocine. This result suggests that bremazocine can be an antagonist at this binding site. Also, we have examined the opioid modulation of $K^+(30mM)-induced\;[^3H]\;histamine$ release in rat frontal cortex slices labeled with $1-[^3H]\;histidine$. The $[^3H]\; histamine$ release from cortex slices was inhibited by EKC in a concentration-dependent manner. However, the ${\delta}$ receptor selective agonists, DPDPE and deltorphine II, ${\mu}$ receptor agonists, DAMGO and TAPS, ${\kappa}_1-agonists$, U69593 and U50488H, and ${\varepsilon}-agonist,\;{\beta}-endorphin,$ did not. The concentration-response curve of EKC was shifted to right in the presence of naloxone, nor-binaltorphimine and bremazocine, respectively. These results suggest that ${\kappa}_2$ opioid receptor regulates histamine release in the fromtal cortex of the rat.

기약 AOP를 이용한 GF(2^m)상의 낮은 지연시간의 시스톨릭 곱셈기

김기원,한승철,Kim, Kee-Won,Han, Seung-Chul 대한임베디드공학회 2016 대한임베디드공학회논문지 Vol.11 No.4

Efficient finite field arithmetic is essential for fast implementation of error correcting codes and cryptographic applications. Among the arithmetic operations over finite fields, the multiplication is one of the basic arithmetic operations. Therefore an efficient design of a finite field multiplier is required. In this paper, two new bit-parallel systolic multipliers for $GF(2^m)$ fields defined by AOP(all-one polynomial) have proposed. The proposed multipliers have a little bit greater space complexity but save at least 22% area complexity and 13% area-time (AT) complexity as compared to the existing multipliers using AOP. As compared to related works, we have shown that our multipliers have lower area-time complexity, cell delay, and latency. So, we expect that our multipliers are well suited to VLSI implementation.

전자 환자 기록 정보 시스템을 위한 패스워드 기반 인증 그룹 키 합의 프로토콜에 대한 취약점 분석

김기원(Kee-Won Kim) 한국정보기술학회 2015 한국정보기술학회논문지 Vol.13 No.11

Many authentication and key agreement protocols have been proposed for e-medicine systems, such as telecare medicine information systems and integrated EPR information systems, to ensure the security, integrity, and privacy of patient records. As e-medicine system become more sophisticated, many applications involving multiple participants, such as the healthcare teams collaboration, become necessary. Recently, Lee et al. proposed a simple password-based authenticated group key agreement protocol for the integrated EPR information system. They claimed that their protocol is secure and robust. However, we point out that Lee et al.s protocol is vulnerable to off-line password guessing attacks and impersonation attacks.

GF(2^m)상에서 2 - 디지트 시리얼 시스톨릭 곱셈기 설계 및 분석

김기원(Kee-Won Kim),이건직(Keon-Jik Lee),유기영(Kee-Young Yoo) 한국정보과학회 2000 한국정보과학회 학술발표논문집 Vol.27 No.2Ⅰ

본 논문에서는 유한 필드 GF(2^m)상에서 모듈러 곱셈 A(x)B(x) mod P(x)를 수행하는 2-디지트 시리얼(2-digit-serial) 시스톨릭 어레이 구조인 곱셈기를 제안하였다. LSB-first 곱셈 알고리즘을 분석한 후 2-디지트 시리얼 형태의 자료의존 그래프(data dependency graph, 이하 DG)를 생성하여 시스톨릭 어레이를 설계하였다. 제안한 구조는 정규적이고 서로 반대 방향으로 진행하는 에지들이 없다. 그래서 VLSI 구현에 적합하다. 제안한 2-디지트 시리얼 곱셈기는 비트-패러럴(bit-parallel) 곱셈기 보다는 적은 하드웨어를 사용하며 비트-시리얼(bit-serial) 곱셈기 보다는 빠르다. 본 논문에서 제안한 2-디지트 시리얼 시스톨릭 곱셈기는 기존의 같은 종류의 곱셈기 보다 처리기의 최대 지연 시간이 적다. 그러므로 전체 시스톨릭 곱셈기의 처리시간을 향상시킬 수 있다.

유한 체상의 몽고메리 알고리즘 및 하드웨어 구조 설계

김기원(Kee-Won Kim),전준철(Jun-Cheol Jeon) 한국산업정보학회 2013 한국산업정보학회논문지 Vol.18 No.2

유한체상의 곱셈기는 오류 제어 코드, 암호시스템 및 디지털 신호처리와 같은 여러 분야의 기본적인 구성 요소이다. 최근 다양한 유한체상의 곱셈기가 세미-시스톨릭 구조를 기반으로 제안되었다. 또한, 몽고메리 알고리즘은 효율적인 곱셈 연산 알고리즘으로 잘 알려져 있다. 본 논문은 유한체 상에서 다항식 표현을 사용하여 효율적인 몽고메리 곱셈 알고리즘을 유도하고 이를 기반으로 세미-시스톨릭 몽고메리 곱셈기를 제안한다. 제안한 곱셈기는 병렬 구조에 적합한 몽고메리 인자를 선택하였으며 전체 계산 구조를 두 부분으로 나누어 동시에 계산할 수 있다. 제안한 곱셈기는 기존의 곱셈기에 비해 시간 복잡도를 30%~50% 정도 줄임으로써 전체 시간 복잡도의 30% 정도를 줄였다. Finite field multipliers are the basic building blocks in many applications such as error-control coding, cryptography and digital signal processing. Recently, many semi-systolic architectures have been proposed for multiplications over finite fields. Also, Montgomery multiplication algorithm is well known as an efficient arithmetic algorithm. In this paper, we induce an efficient multiplication algorithm and propose an efficient semi-systolic Montgomery multiplier based on polynomial basis. We select an ideal Montgomery factor which is suitable for parallel computation, so our architecture is divided into two parts which can be computed simultaneously. In analysis, our architecture reduces 30%~50% of time complexity compared to typical architectures.

원저 : 실험적 고혈압 백서의 심맥관계 기능조절에 있어서 중추 (中樞) Opiate System 의 역할

김기원(Kee Won Kim),조규박(Kyu Park Cho),송태효(Tae Hyo Song) 전북대학교 의과학연구소 1989 全北醫大論文集 Vol.13 No.2