Study on Relaxing Effect of Oxybutynin on the Contractile Response of Arterial Smooth Muscle

고재기,백영홍,Ko, Jae-Ki,Baik, Yung-Hong The Korean Society of Pharmacology 1988 대한약리학잡지 Vol.24 No.1

돼지 우관상동백을 적출하여 항경련제인 oxybutynin의 약리작용을 조사하였다. 1. Acetylcholine (ACh)과 KCl은 관상동맥을 수축시켰고 이 수축효과는 용량의존적이었다. ACh의 수축효과는 내피손상표본 $(EC_{50}=0.52\;{\mu}M)$에서 내피표본 $(EC_{50}=0.52\;{\mu}M)$보다 약 2배 강화되있으나 KCl의 수축효과는 양군간에 차이가 없었다. 2. $ACh(1.0\;{\mu}M)$의 수축효과는 oxybutynin과 atropine에 의 하여 용량의존적으로 억제되었고 두 약물의 $(IC_{50}$는 각각 11.0 nM과 0.47 nM로 atropine이 약 23배나 더 예민하였다. 그러나 KCl (35 mM)의 수축효과는 atropine으로는 전혀 영향받지 않았고 oxybutynin으로는 용량의존적으로 억제 되었으며 $(IC_{50}=49.7\;{\mu}M)$이였다. 3. ACh의 용량반응곡선은 oxybutynin $(IC_{50}=11\;nM)$ 및 atropine $(IC_{50}=0.47\;nM)$ 전처 리 하에서 우측으로 평 행 이 동되 있고, KCI의 용량반응곡선은 oxybutynin $(IC_{50}=49.7\;nM)$ 전처리하에서 우측으로 비상경적 이동을 일으켰다. 4. Oxybutynin은 Bay K 8644 $(0.1\;{\mu}M)$의 수축효과를 용량의존적 으로 억제하였고 $(IC_{50}=63.0\;{\mu}M)$이었으며 , histamine $(35\;{\mu}M)$의 수축효과는 oxybutynin의 최대량 $(500\;{\mu}M)$으로 부분억제 (최대 50%)만을 일으켰다. 이상의 성적으로 적출돼지 관상동백에서 내피세포는 ACh에 의한 수축반응에 억제적 영향을 미치며, oxybutynin은 강력한 muscarine receptor 차단작용과 calcium influx 억제작용에 의하여 혈관근 이완을 일으킨다고 추론하였다. Pharmacological actions of an antispasmodic agent, oxybutynin were investigated in the isolated procine coronary arteries. The coronary rings were contracted by acetylcholine (ACh) and KCl in a dose-dependent fashion. The ACh-induced contractions were signifcantly potentiated by removal of endothelium and $EC_{50}=0.52\;{\mu}M$ of intact endothelial rings was about 2 times greater than $EC_{50}=0.28\;{\mu}M$ of rings without the endothelium. These results suggest that the endothelium plays an inhibitory role in ACh-induced contraction. Oxybutynin and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and the $IC_{50s}$ were 11.0 nM and 0.47 nM, respectively. Atropine did not affect 35 mM KCl-induced contraction but oxybutynin inhibited the contraction to the basal tension in a dose-dependent manner. The $IC_{50}$ of oxybutynin on the KCl-induced contraction was $49.7\;{\mu}M$. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with $IC_{50}$ of atropine (0.47 nM) or oxybutynin (11.0 nM) but the curve to KC1 was rightward shifted in a noncompetitive manner under pretreatment with $IC_{50}$ of oxybutynin $(49.7\;{\mu}M$). Oxybutynin inhibited $0.1\;{\mu}M$ Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but $35\;{\mu}M$ histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration $(5{\times}10^{-4}M)$ of oxybutynin. These results suggest that oxybutynin causes antispasmodic action through sensitive blocking action on muscarinic receptors and inhibitory action on calcium influx in the procine coronary artery.

경주 단석산 상수리나무 우점식분 군집구조의 19년간의 변화

고재기(Ko, Jae Ki) 한국습지학회 2018 한국습지학회지 Vol.20 No.3

본 연구는 경주 단석산 상부 남사면의 상수리나무 우점 식분의 군집구조 변화를 파악하기 위하여 고정 방형구 20개를 설치하고 1999년부터 2018년까지 5회의 매목조사를 실시하였다. 밀도는 1999년에 0.33에서 2012년에 0.20으로 감소하였으나 2018년에는 0.24로 다소 증가하였다. 전체 수목의 흉고직경계분포를 보면, 1999년에는 역J자 유사한 모양의 분포를 나타내었으나 그 후 분포가 변화되어 2018년에는 어린 개체들에서는 역J자 모양이, 성숙한 개체들에서는 종 모양이 나타나 전체적으로는 두 곡선이 연결된 형태의 분포를 나타내었다. 흉고직경 13cm이하에서는 수목들의 경쟁이 심하였으나 그 이상에서는 완화되는 것으로 나타났다. 최우점종인 상수리나무의 흉고직경계 분포는 종 모양의 분포를 보였고, 시간이 지남에 따라 흉고직경이 큰 쪽으로 분포가 이동하지만 개체수는 줄어들었고, 신갈나무는 낮은 종 모양의 분포가 점점 높아지는 변화를 보였다. 흉고직경계분포의 변화로 볼 때, 단석산의 상수리나무 식분은 이차천이의 초기 단계에서 중간 단계로 삼림천이가 진행 중인 것으로 판단이 되며, 현재 본 식분의 최우점종은 상수리나무이고 준우점종은 신갈나무이지만, 향후 신갈나무가 최우점종인 식분으로의 천이가 진행될 것으로 예상된다. This study was carried out to clarify changes in community structure of Quercus acutissima dominant stand on the south slope of Mt. Danseok-san with fixed twenty quadrates. Five field surveys were conducted from Aug. 1999 to May 2018. During the period, the density lessened to 0.20 in 2012 comparing with 0.33 in 1999. However recent field study in 2018 showed moderate rising to 0.24. In 1999, the DBH class distribution of all trees formed reverse J curve. However, the reverse J curve was torn down, forming bell curve. In 2018, the curve showed similar shape of reverse J shape on the group of young trees, forming bell shape on the group of mature trees. It reveals that DBH 13cm is on the threshold of trees competition trend where the downtrend in the trees are on uptrend. The most dominant Q. acutissima formed bell curve. The peak of the curve shows the shift to the right of the graph as it gets lower by year.In case of Q. mongolica, shows a change in the shape of a low bell as the distribution curve increases. The oak stand in this study is in the process of changing from the initial stage of the secondary forest succession to the intermediate stage. The most dominant tree is Q. acutissima, and the sub-dominant tree is Q. mongolica in present. Considering the age distribution of the two competing tree species, the succession of this stand is expected to transfer to the Q. mongolica-dominant community.

동맥근 수축에 대학 Oxybutynin의 이완효과에 관한 연구

고재기(Jae Ki Ko),백영홍(Yung Hong Baik) 대한약리학회 1988 대한약리학잡지 Vol.24 No.1

돼지 우관상동백을 적출하여 항경련제인 oxybutynin의 약리작용을 조사하였다. 1. Acetylcholine (ACh)과 KCl은 관상동맥을 수축시켰고 이 수축효과는 용량의존적이었다. ACh의 수축효과는 내피손상표본 (EC₅₀=0.52μM)에서 내피표본 (EC₅₀=0.52μM)보다 약 2배 강화되있으나 KCl의 수축효과는 양군간에 차이가 없었다. 2. ACh(1.0μM)의 수축효과는 oxybutynin과 atropine에 의 하여 용량의존적으로 억제되었고 두 약물의 (IC₅₀는 각각 11.0 nM과 0.47 nM로 atropine이 약 23배나 더 예민하였다. 그러나 KCl (35 mM)의 수축효과는 atropine으로는 전혀 영향받지 않았고 oxybutynin으로는 용량의존적으로 억제 되었으며 (IC₅₀=49.7μM)이였다. 3. ACh의 용량반응곡선은 oxybutynin (IC₅₀=11 nM) 및 atropine (IC₅₀=0.47 nM) 전처 리 하에서 우측으로 평 행 이 동되 있고, KCI의 용량반응곡선은 oxybutynin (IC₅₀=49.7 nM) 전처리하에서 우측으로 비상경적 이동을 일으켰다. 4. Oxybutynin은 Bay K 8644 (0.1μM)의 수축효과를 용량의존적 으로 억제하였고 (IC₅₀=63.0μM)이었으며 , histamine (35μM)의 수축효과는 oxybutynin의 최대량 (500μM)으로 부분억제 (최대 50%)만을 일으켰다. 이상의 성적으로 적출돼지 관상동백에서 내피세포는 ACh에 의한 수축반응에 억제적 영향을 미치며, oxybutynin은 강력한 muscarine receptor 차단작용과 calcium influx 억제작용에 의하여 혈관근 이완을 일으킨다고 추론하였다. Pharmacological actions of an antispasmodic agent, oxybutynin were investigated in the isolated procine coronary arteries. The coronary rings were contracted by acetylcholine (ACh) and KCl in a dose-dependent fashion. The ACh-induced contractions were signifcantly potentiated by removal of endothelium and EC₅₀=0.52μM of intact endothelial rings was about 2 times greater than EC₅₀=0.28μM of rings without the endothelium. These results suggest that the endothelium plays an inhibitory role in ACh-induced contraction. Oxybutynin and atropine inhibited dose-dependently 1.0μM ACh-induced contraction and atropine inhibited dose-dependently 1.0μM ACh-induced contraction and the IC_50s were 11.0 nM and 0.47 nM, respectively. Atropine did not affect 35 mM KCl-induced contraction but oxybutynin inhibited the contraction to the basal tension in a dose-dependent manner. The IC₅₀ of oxybutynin on the KCl-induced contraction was 49.7μM. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with IC₅₀ of atropine (0.47 nM) or oxybutynin (11.0 nM) but the curve to KC1 was rightward shifted in a noncompetitive manner under pretreatment with IC₅₀ of oxybutynin (49.7μM). Oxybutynin inhibited 0.1μM Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but 35μM histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration (5 × 10^-4M) of oxybutynin. These results suggest that oxybutynin causes antispasmodic action through sensitive blocking action on muscarinic receptors and inhibitory action on calcium influx in the procine coronary artery.

본태성 고혈압 환자의 치료경과에 따른 뇨중 N - Acetyl - β - D - Glucosaminidase 의 활성도

안중기(Joong Ki Ahn),이승호(Seung Ho Lee),하종영(Chong Young Ha),김원호(Won Ho Kim),고재기(Jae Ki Ko) 대한내과학회 1988 대한내과학회지 Vol.34 No.5

N/A The urinary excretion of N-acetyl-p-glucosamidase (NAG) is increased in patients whose renal function is impaired by a variety of kidney disease, and may provide an index of renal injury. To assess its role in essential hypertension, we measured urinary levels of NAG in 44 subjects with essential hypertension (and no evidence of renal disease), 14 subjects with well controlled hypertension and 41 normal control. NAG values were measured before therapy and after 2 months of antihypertensive therapy. The mean urinary NAG value (±S.E.) for the normo-tensive subjects was 31.6±2.42nmol hr-1mg creatinine-1. The mean value for the untreated hypertensive subjects was 121±9.09 (P<0.01). Systolic blood pressure was directly correlated with NAG levels. The urinary level of NAG in stage II hypertension (146±11, 16 nmol hr-1mg creatinine-1) was higher than that in the normal control (31.6±2.4nmol hr-1mg creatinine-1 , P<0.01), and stage I hypertension (81.8±8.49nmol hr-1mg creatinine-1, P<0.01). Fourteen patients followed for two months attained their ultimate blood pressure reduction within two months (from a mean of 176/110mmHg to one of 138/93mmHg), and therefore the urinary NAG level had changed significantly at two months (from 115,7±15.8 to 75.7±6.55, P<0. 05), These data suggest that NAG is frequently elevated in patients with high blood pressure even though there is no other evidence of renal damage, and that it can be reduced by successful antihypertensive therapy.

Comparison of Paclitaxel-Versus Sirolimus-Eluting Stents for the Treatment of Acute ST-Elevation Myocardial lnfarction

김현숙 ( Hyun Sook Kim ),이재환 ( Jae Hwan Lee ),성인환 ( In Whan Seong ),이승환 ( Seung Whan Lee ),이경석 ( Kyoung Suk Rhee ),김원호 ( Won Ho Kim ),고재기 ( Jae Ki Ko ) 전북대학교 의과학연구소 2007 全北醫大論文集 Vol.31 No.1

Objectives: Paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) are more effective than bare-metal stent for reducing restenosis. However, it is not known whether there are differences between PES and SES in terms of safety and efficacy in the setting of ST-elecation myocardial infarction (STEMI). Methods and Results: Acute STEMI patients (n=231) undergoing primary stenting were randomly assigned to PES (n=115) or SES (n=116) treatment. Primary end point was in-segment late loss at 6 months. Secondary end points were 6-month angiographic restenosis and major adverse cardiac events (MACE) at 9 months. At 6 months, in-segment late loss was higher in the PES than the SES group (0.33±0.70 vs. 0.05±0.40mm, respectively, p<0.001). During 9-month follow-up, 14 (6.1%) patients were died (9 in PES, 5 in SES group). Nine-month TLR (7.8% vs. 2.6%, p=0.09) and MACE (15.7% vs. 6.9%, p= NS) tended to be lower in SES group than PES group. Conclusions: Both PES and SES implantation was safe, and both showed favorable clinical outcomes in STEMI patients undergoing primary angioplasty. SES appeared to be superior to PES in preventing neointimal hyperplasia.

증례 : 순환기 ; 제세동기에서 발생한 트위들러 증후군

이경석 ( Kyoung Suk Rhee ),김원호 ( Won Ho Kim ),고재기 ( Jae Ki Ko ) 대한내과학회 2010 대한내과학회지 Vol.78 No.1

Here we describe a case of Twiddler`s syndrome in a patient with an implanted cardioverter-defibrillator who tinkered with the device, shifting it to a vertical position and causing her skin to protrude in various locations. Fluoroscopy was used to determine what direction the device was rotating in during specific body postures and physical activities. Inappropriate shocks were delivered whenever the patient pushed the device down toward her sternum. The syndrome did not recur following training of the patient in a lead-revision procedure that involved shifting the device down vertically toward her lateral side with her hands. (Korean J Med 78:113-116, 2010)

임상화보 : 우심방내 펄럭이는 벌레모양 혈전에 의한 치명적 폐색전증

이선화 ( Sun Hwa Lee ),채제건 ( Jei Keon Chae ),고재기 ( Jae Ki Ko ) 대한내과학회 2008 대한내과학회지 Vol.75 No.3

증예(症例) : 심장을 침범하고 염색체 이상을 동반한 원발성 과호산구 증후군 1예

권혁진 ( Hyeok Jin Kwon ),이호경 ( Ho Kyung Lee ),송은기 ( Eun Ki Song ),이승룡 ( Seung Ryong Lee ),김원호 ( Won Ho Kim ),채제건 ( Jei Keon Chae ),고재기 ( Jae Ki Ko ) 전북대학교 의과학연구소 2002 全北醫大論文集 Vol.26 No.2

The idiopathic hypereosinophilic syndrome(HES) is defined by the sustained eosinophilia without the apparent etiologies and with any organ involvement. Congestive heart failure resulting from cardiac involvement is a major cause of morbidity and mortality. A 21-year-old female patient had visited with hoarseness and exertional dyspnea. Fine crackles and holosystolic cardiac murmur were heard. Mild cardiomegaly in chest x-ray and hepato- and splenomegaly in computed tomography were observed. Severe mitral and tricuspid regurgitation accompanied with pulmonary hypertension was observed in echocardiographic examination. Limitation of mobility of the posterior mitral leaflet and tricuspid valve and thickening of endocardium may be caused by the eosinophilic infiltration. Cardiac involvement was confirmed by endomyocardial biopsy. The bone marrow biopsy was reported as a chromosomal abnormality of karyotype(46,XX,del(5)(p15)), which is exclusively seen in idiopathic HES. Therefore, we report a case of HES with chromosomal abnormality and cardiac involvement.

각종 간 , 담도질환에 있어서의 혈청 Variant Alkaline Phosphatase 변화에 대하여

안득수 ( Deuk Soo Ahn ),조병권 ( Byung Kwun Cho ),이양근 ( Yang Keun Lee ),고재기 ( Jae Ki Ko ),이중렬 ( Jung Yeol Rhee ) 대한내과학회 1980 대한내과학회지 Vol.23 No.8

약제 관련 서맥의 임상 경과

유경보 ( Kyung Bo Yoo ),이선화 ( Sun Hwa Lee ),이경석 ( Kyoung Suk Rhee ),이강휴 ( Kang Hyu Lee ),이상록 ( Sang Rok Lee ),채제건 ( Jei Keon Chae ),김원호 ( Won Ho Kim ),고재기 ( Jae Ki Ko ) 전북대학교 의과학연구소 2010 全北醫大論文集 Vol.34 No.2

배경 및 목적: 최근 약물과 관련되어 발생한 서맥성 부정맥의 예후에 대한 재평가가 이루어지고 있다. 본 연구는 약제 유발성 서맥으로 최초 진단받은 환자들의 임상 경과를 분석하여 그 예후를 평가하고자 하였다. 방법: 전북대학교 병원 심장내과에 2000년 1월 이후 약물 유발성 서맥으로 진단 받고 입원치료를 받았던 환자들을 대상으로 하여 의무기록 분석 및 전화상담을 통한 후향적 조사를 하였다 결과: 전체 환자 중 경과 관찰 기간 동안 영구적 심박동기 삽입술을 시행 받은 환자는 28명(26.9%)으로, 동기능 부전 증후군 군과 고도방실차단 군에서 각각 15명(/68, 22.1%)과 13명(/36, 36.1%)이었다 결론: 고전적으로 양호한 임상경과를 취하는 것으로 알려져 왔던 이차성 서맥성 부정맥 환자 상당수에서 유발인자가 없이도 서맥이 점차 진행하여 결국 영구형 인공심박동기 이식시술을 받게 된다. Background and Objectives: Recently, the prognosis of drug-induced bradyarrhythmias has been reported not as benign as previous considerations. We performed the investigations about the patients who had been diagnosed as drug-related bradyarrhythmias presenting it at first. Subjects and Methods: Medical records of those who had been admitted to Chonbuk National University Hospital due to drug-related bradyarrhythmias since January 2000 were investigated retrospectively and clinical follow-up was performed using phone call. Results: One hundred and four patients were enrolled. Mean age was 68±10(34-85) years. Underlying diseases that need relating drugs were hypertension (50, 48.1%), ischemic heart disease, atrial fibrillation, cardiomyopathy, etc. Most common single causative agent was β-blockers (53.0%) and the others were nondihydropyridine calcium channel blockers (18.9%), digoxin (10.6%), antiarrhythmics (9.1%) and herb-medications (3.8%). 68 patients showed sinus node dysfunction (SND, 65.4%) and 36 showed AVB (34.6%). Mean heart rate on admission was 37.0±7.1 beats/minute. Permanent pacemaker implantations were performed in 28 patients (26.9%). Fifteen among them were with SND (15/68, 22.1%), 13 were with AVB (13/36, 36.1%). Conclusion: Unlikely to the general considerations, it would be better to say that drug-related bradyarrhythmias are not drug-induced bradyrrhythmias itself, but unmasked underlying bradyarrythmias in substantial portion of the patients. Very close and cautious clinical monitoring should be performed, especially in patients with AVB.