항 히스타민제의 H₁ 수용체와 무스카린 수용체에 대한 상대적 역가

이신웅,박영주,이정수 영남대학교 약품개발연구소 1994 영남대학교 약품개발연구소 연구업적집 Vol.4 No.-

The muscarinic antagonist l-[benzilic-4, 4'-³H]quinuclidinyl benzilate([³H]QNB) bound to a single class of muscarinic receptor with high affinity in guinea pig ileal membranes. The K_(D) and B_(max) values for [³H]QNB calculated from analysis of saturation isotherms were 54 pM and 156 fmol/mg, respectively. H₁-blockers inhibited [³H]QNB binding to ileal membranes with K_(i) values ranged from 0.008 μM to 1.6 μM. The pseudo-Hill coefficients of H₁-blockers for inhibition of [³H]QNB binding to the ileal membranes were close to unit. The K_(i) values for H₁-blockers were similar to the K_(M) values calculated by Schild plot of functional data obtained from inhibition of the carbachol-induced contraction in guinea-pig ileum, suggesting that binding of H₁-blockers vs [³H]QNB in ileal membranes represents an interaction with a receptor of physiological relevance. The K_(H) values of H₁-blockers for H₁-receptor estimated from inhibition of the histamine-induced contraction were the range of 0.15 nM to 56.5 nM. The K_(M)/K_(H) ratio of H₁-blockers varied over a wide range of 3 to 2300. Thus, the antihistaminic potencies of H₁-blockers do not correlate with their antimuscarinic potencies, which suggest that antihistamines have different antimuscarinic potencies in therapeutic blood levels causing similar antiallergic effect. Among 13 traditional antihistaminics examined in this study, drug having the highest and the lowest K_(M)/K_(H) ratio is triprolidine and diphenidol, respectively. The present results demonstrate that the antimuscarinic property of antihistamines is not necessary for their antiallergic effect, and data on the affinity of antihistamines for muscarinic and H₁-receptors can be an important parameter in the selection and evaluation of these drugs.

쥐 심실에서 Digitalis Receptor Desensitization에 관한 연구

이신웅,이정수,장태수 영남대학교 약품개발연구소 1995 영남대학교 약품개발연구소 연구업적집 Vol.5 No.-

[³H]Ouabain binding parameters (K_(v) and B_(max)) to control rat ventricular strips and Langendorff preparations which were not previously exposed to ouabain were compared with those to both preparations that had been first exposed to a complete ouabain dose range of dose-response curve (10^(-5) M to 10^(-4) M). In rat ventricular strips and Langendorff perfused heart preparations, cumulative dose-response curves of ouabain revealed biphasic positive inotropic effects. a "low-dose" effect and a "high-dose" effect with ED_(50) values of 0.5 μM and 35 μM ouabain, respectively. The "low-dose" effect in ventricular strip disappeared or was diminished significantly when the ouabain dose-response curve was repeated after the washout of the effects of the first dose-response curve, whereas there were no significant differences in the maximal "high-dose" effect in both exposures to oubain. However, both of the control and ouabain-preexposed Langendorff perfused hearts revealed the same low-dose effects. The K_(D) value for [³H]ouabain binding and the ouabain binding site concentration (B_(max)) estimated by [³H]ouabain displacement assay in control preparations were 230 nM and 2 p㏖/㎎ protein, respectively. [³H]Ouabain binding parameters were not changed by repeated exposure to high concentrations of ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site (a₂ isoform).

人蔘根 製濟의 製造 및 指肪酸 吸收에 미치는 影響에 關한 硏究

李相稷,金英熙,李神雄,陳甲德 嶺南大學校 環境問題硏究所 1984 環境硏究 Vol.4 No.2

Effect of perilla oil emulsion prepared by ginseng powder on absorption of free fatty acid of rat small intestine were investigated in this study. The results were as follow; 1. 4g of ginseng powder could enulsify 1g of perilla oil. 2. Total crude saponin could be separated and identified by method of Namba and Shibata et al, and be measured by weight and volumn. 3. The content of total crude saponin containing in fuor years old ginseng root caltivated in Gum San was 2.26 to 2.70% of total root weight. 4. Ginseng powder increased the absorption of free fatty acid and emulsion prepared by ginseng powder induced more effective increase in free fatty acid absorption than that of non-emulsion form in rat small intestine. 5. Emulsion prepared by ginseng powder was o/w type and more stable in lower water and higher mucosity than in high water and low mucosity. 6. Emulsion was stable for 36days at 5℃~8℃.

자궁 무스카린 수용체의 확인 및 분류

이신웅,이정수,박영주 영남대학교 약품개발연구소 1992 영남대학교 약품개발연구소 연구업적집 Vol.2 No.-

The muscarinic acetylcholine receptors of the dog unpregant uterus were characterized using [³H]quinuclidinyl benzilate(QNB) as a radioligand and the binding of muscarinic receptor agonists and antagonists in the uterus was compared to that in the urinary bladder which contains almost exclusively the M₂ receptors in order to determine the receptor subtypes in the uterus. [³H]QNB binding to uterus and bladder was rapid, saturable and reversible. Scatchard analysis of the saturation data gave linear plots and the Hill coefficients were close to unit, which indicated that each preparation contained a single population of specific binding sites for [³H]QNB. The K_(D) values(120 pM) for QNB were almost identical in both organs, whereas the B_(MAX) value of 256 fmol/mg protein in the uterus was significantly different from that of 563 fmol/mg protein in the bladder. Muscarinic agonists and antagonists inhibited in a competitive manner the [³H]QNB binding to the same extent in both organs. The competition binding studies using antagonists(atropine and pirenzepine) exhibited a single binding site and this site had a low affinity for pirenzepine with the Ki value of about 330 nM. However, high and low affinity binding sites were observed with carbachol, methacholine and oxotremorine. These binding studies with agonists and antagonists did not show any differences in drug affinities between uterus and bladder. These results indicate that the muscarinic receptors in the uterus are M₂ receptors which have a low affinity for pirenzepine.

인삼 사포닌이 개 심실 형질막의 K+-의존성 포스파타제 활성에 미치는 영향

이신웅,이정수 영남대학교 약품개발연구소 1992 영남대학교 약품개발연구소 연구업적집 Vol.2 No.-

The effects of ginseng saponins, gypsophila saponin, sodium dodecyl sulfate(SDS), and Triton X-100 on membrane K^(+)-dependent phosphatase activity which is lipid dependent and represents dephosphorylation step of the complete Na^(+), K^(+)-ATPase reaction were investigated in this study to elucidate whether the effects of ginseng saponins are due to the detergent action, using sarcolemma enriched preparation isolated from dog ventricle. Na^(+), K^(+)-ATPase and K^(+)-dependent phosphatase activities of cardiac sarcolemma were about 143 μmol Pi/mg protein/hr and 34 μmol p-nitrophenol/mg protein/hr, respectively. While ginseng saponins (triol>total>diol) inhibited K^(+)-dependent phosphatase activity, gypsophila saponin, and low dose of SDS(0.4 μg/μg protein), and Triton X-100 (0.6 μg/μg protein) increased the enzyme activity, indicating disruptive effect of detergents on membrane barriers. The activating effect of low doses of Triton X-100 on membrane K^(+)-dependent phosphatase appeared at concentration decreasing light scattering. However, the inhibitory effect of ginseng saponin appeared before a decrease in light scattering. These results suggest that low concentrations of ginseng saponins inhibit the membrane K^(+)-dependent phosphatase by interacting directly with enzyme before membrane disruption.

개 心室 形質膜의 Adenosine Triphosphate 依存性 Ca²+ 攝取에 미치는 Cd²+의 영향

李神雄,李正秀 嶺南大學校 環境問題硏究所 1988 環境硏究 Vol.7 No.1

Highly purified sarcolemmal vesicles were prepared from dog ventricles to investigate the effect of ?? on the ATP-dependent ?? uptake of sarcolemma. This sarcolemma showed high ??,??-ATP? activity and ??-pumping activity which was not affected by oxalate. Sarcolemmal vesicles rapidly accummulated ?? when ?? and ATP were added and ?? uptake reached at maximum 15 minutes after incubation. Apparent Km(??) and ?? of ?? transport were 11.9㎛ and 11.8nmol / ㎎ protein,respectively. ?? inhibited markly the ATP-dependent ?? uptake and in the presence of 50㎛ ?? the concentration ?? required for half maximal ingibition was ??. Apparent Km (Ca?) was not affected but ?? of ?? transport was decreased by ?? These results suggest that increased intracellular concentrations of ?? inhibit the ?? transport to extracellular fluid.

개 心室 形質膜의 Adenosinetriphosphate 依存性 Ca²+ 攝取에 미치는 Cd²+의 影響

李神雄,洪祥植,李正秀 嶺南大學校 環境問題硏究所 1988 環境硏究 Vol.8 No.1

Sarcolemmal fraction from canine ventricle was isolated to investigate the effect of cadmium on the ATP-dependent ?? uptake of sarcolemmal vesicles. About 29% and 26% of sarcolemma in sarcolemmal fraction, enriched in ouabain sensitive ??, ??-ATPase, were inside-out and rightside-out vesicles, respectively. Sarcolemmal vesicles rapidly accummulated ?? in the presence of ?? and ATP, and this ?? uptake reached at maximum 10minutes after incubation. Cadmium inhibited ATP-dependent ?? uptake of sarcolemmal vesicles, showing the half maximum inhibitory concentration (??) of ?? in the presence of ?? CaCl₂, Apparent Km (??) and Umax of active ?? transport across the plasma membrane were ?? and 11.7n mol/mg protein, respectively, and cadmium decreased the maximum capacity of ?? uptake (U max) without affecting Km of ?? . It is concluded that intracellular cadmium inhibits active transport of calcium from cytosol to extracellular fluid.

광주광역시 치매의 유병률과 위험인자의 도시-농촌 지역 비교

신일선,김재민,윤진상,김석재,양수진,김웅장,이승현,강순아,곽지영,이형영 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.6

연구목적 : 본 연구의 목적은 광주광역시의 도시 및 농촌 지역에 거주하는 노인에서 치매의 유병률과 위험인자를 조사하고자 하였다. 부가적으로 이 두 지역간에 치매의 유병률과 위험인자를 비교하고자 하였다. 방 법 : 광주광역시의 전형적인 도시와 농촌지역의 65세 이상의 노인(N=1,598)을 대상으로, 2단계의 역학연구를 수행하였다. 1차 선별 단계에서는 38명의 훈련된 연구보조원이 대상노인을 면담하여, 사회인구학적 특징을 조사하고 한국판 간이정신상태검사(Korean version of Mini-Mental State Examination ; MMSE-K)로 평가하였다. 2차 임상 진단 단계에서는 1차 단계에서 MMSE-K 점수가 24점 이하인 노인(N=431)을 대상으로, 전문연구팀의 임상적 평가를 통해 치매를 진단하고 원인질환별로 알쯔하이머병(Alzheimer's disease ; AD), 혈관성 치매(vascular dementia ; VaD) 및 기타 치매로 분류하였다. 대상노인에서 치매의 유병률을 측정한 후, 광주광역시 전체 노인의 연령보정 유병률을 산출하였다. 전체 대상에서 AD의 위험인자를 조사한 후, 도시와 농촌군으로 나누어 분석을 다시 시행하였다. 결 과 : 1차 및 2차 단계의 참가율은 각각 71.0%(N=1,134) 및 83.2%(N=410) 였다. 연구 참여 노인(N=1,134)에서 전체 치매, AD 및 VaD의 유병률은 최소 각각 9.7%, 5.2%, 1.8%였다. 광주광역시 전체 노인의 연령 보정 유병률은 각각 10.7%, 5.7%, 1.9%인 것으로 산출되었다. AD의 독립 위험인자는 고령, 여성, 무학이었다. 도시와 농촌에 따른 유병률의 차이는 파악되지 않았다. 그러나 AD의 위험인자는 지역에 따라 차이가 있었다. 도시 노인에게는 무학만이, 농촌 노인에게는 고령과 여성인 경우가 독립 위험인자였다. 결 론 : 광주광역시 노인에서 치매의 유병률은 높았고, 이는 국내 다른 지역에서 수행된 선행연구 결과와 유사하였다. 알쯔하이머형 치매의 위험인자는 도시와 농촌에 따라 다른 결과를 보였다. 본 연구 결과는 한국에서의 치매의 실태를 반영하며, 치매의 적절한 관리와 예방을 위해서는 지역성 특성이 고려되어야 함을 시사한다. Objectives : The purpose of this study was to investigate the prevalence rate and risk factors of dementia in an urban and a rural sample of older persons in the metropolitan Kwangju area, Republic of Korea. In addition, the prevalence rate and risk factors of dementia between the two samples were compared. Methods : A two-phase epidemiological study of residents aged 65 or over(N=1,598) was conducted in a highly developed, urban and a non-contiguous, poorly developed, rural area of metropolitan Kwangju. In the first(screening) phase, 38 trained research assistants collectively peformed in-home interviews for all participants. Detailed sociodemographic characteristics were gathered and the Korean version of Mini-Mental State Examination (MMSE-K) was administered. In the second (diagnosing) phase, diagnosis of dementia was established for those scoring 24 or less on the MMSE-K in the screening phase(N=431), and etiological types of dementia were classified to Alzheimer's disease(AD), vascular dementia(VaD) or miscellanous type by two teams of experts. Prevalence rate of dementia was determined in the participants, and age-standardized prevalence rate adjusted by age distribution in metropolitan Kwangju was estimated. For AD, the risk factors were investigated in all participants, and analyses were repeated for the urban and rural samples separately. Results : The participating rates in the first and second phases were 71.0%(N=1,134) and 83.2%(N=410), respectively. In the participants, the prevalence rates of dementia(all types), AD and VaD were 9.7%, 5.2% and 1.8%, respectively. The age-standardized prevalence rates were 10.7%, 5.7% and 1.9%, respectively. Aging, female gender and no education(complete lack of formal education) were identified as independent risk factors for AD. No difference between the urban and rural samples was observed in the prevalence rates of dementia(all types), AD and YaD. However, risk factors for AD differed between these areas. In the urban sample, no education was the only significant factor ; whereas, aging and female gender were identified as risk factors in the rural sample. Conclusion : A high prevalence rate of dementia was observed among old persons in metropolitan Kwangju, consistent with previous studies conducted in other Korean areas. The risk factor profi1es for AD differed between urban and rural settings. The results of this study reflect the current status of dementia in Korea and suggests that appropriate management and prevention strategies for dementia should be tailored toward the geographic settings.

니켈-크롬 합금에 폭로된 치과기공사들에서 자매염색분체 교환 빈도

신민정,성재혁,김웅철,이세훈 가톨릭대학산업의학센타 산업의학연구소 2002 韓國의 産業醫學 Vol.41 No.2

Nonprecious metal alloys were used in dental laboratories, may contain nickel, chromium, cobalt, molybdenum, beryllium, and small amounts gallium, ruthenium, or aluminum. Nonprecious metal alloys tend to rapid increase in use due to the economical merit. Despite the widespread use of Nickel-Chromium alloys, claims for safety of these alloys have not yet been accepted universally. This study was performed to investigate cytogenetic toxicity of Nickel-Chromium alloy in human cultured lymphocytes by sister chromatid exchange(SCE) which is a sensitive indicator of carcinogen and mutagen. Total subjects was divided into the two groups, including 34 Nickel-Chromium alloy exposed dental technicians and 24 control group members. 1. The frequencies of SCE were high in older than 40 years, but these was no statistical significance in two groups. 2. The effect of smoking on SCE values as higher than non-smokers in two groups, but there was no statistical significance. 3. The work duration also affected SCE frequencies, but these values didn't show any statistical difference between two groups. 4. The significant difference of SCE frequencies was found between Nickel-Chromium alloy exposed group and control group. 5. The SCE frequencies of current smoking exposed group was the highest and that of non-smoking control group was the lowest. The present study has shown that occupational exposure to Nickel-Chromium alloy is associated with an increase in SCE frequency.

수은(Hg2+) 및 니켈(Ni2+)이 [³H]Quinuclidinyl Benzilate의 Muscarinic Receptors 결합에 미치는 영향

이정수,임시덕,배기철,이신웅 嶺南大學校 環境問題硏究所 1991 環境硏究 Vol.11 No.1

[³H]Quinuclidinyl benzilate(QNB) binds specifically to muscarinic receptors which mediate a number of important physiological reponses of acetylcholine. In the present study, the effects of ?? and ?? on [³H]QNB binding to the cerebral microsome were investigated. Microsomes were treated with ?? or ?? for 15min at 37℃ and then binding experiments were carried out. ?? and ?? inhibited [³H]QNB binding in the presence of 100pM [³H]QNB to muscarinic receptors with ?? value of 2.1 μM and 350mM, respectively. The inhibition of [³H]QNB binding by these metals was irreversible. Both ?? and ?? decreased the binding site concentration for [³H]QNB binding without affecting ?? value of [³H]QNB. These results indicate that heavy metals inactivate the muscarinic receptors with different potency.