개의 관상동맥에서 Mg++ 결핍에 의한 혈관 확장반응의 기전

안형수(Hyung Soo Ann) 대한약학회 1989 약학회지 Vol.33 No.1

We have recently reported that Mg++-deficiency showed endothelium dependent relaxation in isolated canine coronary arteries precontracted with PGF2alpha. To differentiate the release of EDRF or PGI2 from the endothelium cells as the cause of vasorelaxation by Mg++-deficiency, effects of several inhibitors of arachidonic acid metabolism on the relaxation by Mg++-deficiency were evaluated and also compared with that of acetylcholine. Ibuprofen and tranylcypromine (10mcM), an inhibitor of cyclo-oxygenase and PGI2 synthetase, respectively, did not effect on Mg++-free induced vasorelaxation. Pretreatment of quinacrine (10mcM), an inhibitor of phospholipase A2 and also Ca++ uptake, blocked vasorelaxation by Mg++-free. But trifluoperazine (10mcM), which is about as potent as quinacrine in the inhibition of Ca++ uptake, did not effect on Mg++-deficiency induced vasorelaxation. NDGA (10mcM), an inhibitor of lipoxygenase, completely restored Mg++-free induced vasorelaxation, even though pretreatment of that was not blocked which might be due to the characteristics of vasorelaxation of NDGA itself. Pretreatment of methylene blue (10mcM), which is known as a inhibitor of EDRF through the blocking effect of guanylate cyclase, completely blocked vasorelaxation by Mg++-free as well as acetylcholine (0.1mcM). Acetylcholine-induced dose response curve was also antagonized by pretreatment of quinacrine (10mcM), but not by ibuprofen, tranylcypromine and NDGA. These results appear to suggest that Mg++-free induced vasorelaxation was mediated by the release of EDRF through the activation of phospholipase A2 and noncyclo-oxygenase on arachidonate metabolism.

Anemia-inducing Murine Friend Virus 감염에 대한 2 ,3 -dideoxycytidine 및 Interferon-α-A의 항retrovirus효과

안형수(Hyung Soo Ann),안령미(Ryoung Me Ahn),김동섭(Dong Seop Kim) 대한약리학회 1995 대한약리학잡지 Vol.31 No.3

Anemia-inducing strain of Friend virus (FVA)는 적혈구 progenitor cell의 증식을 촉진하는 생쥐 retrovirus의 일종이다. FVA에 감염된 생쥐는 생성이 촉진된 progenitor cell이 분화되지 못하고 비장내에 축적되므로서 비장비대를 초래한다. 이에 본 실험에서는 FVA에 감염된 생쥐의 비장비대를 지표로 사용하여 2 ,3 -dideoxycytidine (ddC) 및 interferon-α-A (rIFN-α-A)의 항retrovirus효과를 측정하였다. 매일 ddC (100 mg/kg) 및 rIFN-α-A (10 KU/mouse)를 각각 단독 또는 병용하여 18일간 복강내 투여시 비장의 비대가 각각 15.1%, 52.7%, 61.6% 억제되었다. 또 다른 실험군으로 ddC를 식수중에 용해하여 (0.1 mg/ml) 경구로 18일간 투여시, 그리고 ddC의 경구투여와 병용하여 rIFN-α-A을 위와 마찬가지 용량으로 복강내 투여시, 비장비대를 각각 38.4% 및 83.2% 억제하였다. 이 결과는 ddC의 투여시 복강내 주사보다는 경구투여가 더 유효하며, ddC와 rIFN-α-A는 병용투여시 상가적인 효과가 있음을 제시한다. ddC 투여시 progenitor cell의 특성상 변화를 검토하기 위해, Ca⁺⁺ uptake [³H]cyclohexyladenosine (CHA) binding 실험을 실시하였다. CHA bindng 실험결과 성숙된 적혈구에서는 저친화성의 결합부위 하나뿐인데 반해, progenitor cell에서는 고친화성과 저친화성의 두가지 결합부위를 나타내었다. Ca⁺⁺ uptake 측정결과 성숙된 적혈구에 비해 대조군의 정상적인progenitor cell은 약 20배 증가를 나타내었으며, ddC를 연속투여한 군에서도 유사한 결과를나타내었다. 이때 CHA에 의한 Ca⁺⁺ uptake의 억제효과를 측정한 바, ddC 100 mg/kg 투여군의 경우 76%로 대조군의 86% 보다 억제효과가 크게 나타났으며, 이들 모두는 adenosine 길항약인 theophylline의 전처치시 대조군과 유사하게 회복되었다. The anemia-inducing strain of Friend virus (FVA) is a murine retrovirus which stimulates the proliferation of erythroid progenitor cells. The progenitor cells synthesized by FVA-stimulation are unable to proceed with differentiation and accumulate in the spleen resulting in splenomegaly in infected mice. Using FVA-inoculated mice as a model, we have investigated the antiretroviral effects of 2 ,3 -dideoxycytidine (ddC) and recombinant interferon-α-A (rIFN-α-A) on FVA infection. The extent of the infection was determined by measuring the weights of the spleens. Daily intraperitoneal injection of ddC (100 mg/kg body weight), rIFN-α-A (10 KU/mose) and the combination of both drugs to FVA inoculated mice for 18 days resulted in suppression of the growth of spleens by 15.1%, 52.7% and 61.6%, respectively. When ddC was dissolved in drinking water (0.1 mg/ml) and administered to a group of FVA inoculated mice ad libitum, and rIFN-α-A (10 KU/mouse) was intraperitoneally injected daily to another group of ddC (0.1 mg/ml) drinking mice for 18days, the growth of spleens was suppressed by 38.4% and 83.2%, respectively. These results indicate that administration of ddC via drinking water is more effective in suppressing FVA infection than the daily injection of ddC, and that the combined effects ddC and rIFN-α-A are not synergistic but additive. In order to determine whether ddC treatment alters the characteristic of the progenitor cells with respect to Ca⁺⁺ uptake, Ca⁺⁺ uptake in erythroid cells and the effect of cyclohexyladenosine (CHA) on the Ca⁺⁺ uptake were studied. Ca⁺⁺ uptake in the erythroid progenitor cells was about 20-fold greater than in mouse erythrocytes and the inhibition of Ca⁺⁺ uptake by CHA was the greatest in the progenitor cells from FVA infected mice which were treated with ddC. The inhibition was obviated by theophylline. Results of CHA binding studies showed that the erythroid progenitor cells contain both high and low affinity CHA binding sites, whereas mose erythrocytes contain only the low affinity CHA binding sites.

Captopril에 의한 폐동맥 내피세포중 활성형 Angiotensin 전환효소의 변화

안형수(Hyung Soo Ann) 대한약학회 1993 약학회지 Vol.37 No.1

The effect of captopril on the lung angiotensin converting enzyme (ACE) was investigated after 3 weeks oral administration (120-160 mg/kg/day) through drinking water in Sprague-Dawley rats. On the 125I-351A, an ACE inhibitor, binding assay in the isolated perpused lungs, the number of ACE molecules at the intrapulmonary endothelial cell surface was significantly decreased (p<0.001), and recovered to the normal level 7 days after discontinuation of captopril treatment. Intrapulmonary conversion ratio of AI to AII was also significantly decreased (p<0.05) in the isolated perpused lungs. Bolus intravenous injection of angiotensin I did not showed pressor response in the both of systemic and pulmonary blood pressure of the anesthetized rats. ACE activity of the lung homogenates was also significantly reduced. These data consistently indicate the decrease of functionally active ACE molecule at the pulmonary artery after chronic captopril treatment. However, serum ACE activity was increased three fold in captopril treated rats compared to the normal rats. So, these results suggest that the functionally active ACE molecule at the pulmonary artery was still inhibited, which is directly associated with the antihypertensive effects, even if the total angiotensin converting enzyme induction was resulted after chronic captopril treatment.

Friend Anemia Virus에 감염된 BALB/c 생쥐를 이용한 항AIDS약물의 생체내 약효검색

안형수(Hyung Soo Ann),염윤기(Yoon Ki Yom),장영수(Young Soo Chang) 대한약학회 1995 약학회지 Vol.39 No.6

Inoculation of Friend anemia virus, which was a kind of retro virus such as HIV, results splenomegaly, anemia, the increase of WBC counts and reverse transcriptase activity in serum. These results were due to the inhibition of the differentiation of erythroid progenitor cell by the FVA at the spleen. Using these as index of antiviral effects, we pursued the establishment of in vivo screening method for the new anti-AIDS drugs. Among zidovudine, didanosine and zalcitabine, which were already approved as anti-AIDS drugs, treatment of zidovudine for 18 days in BALB/c mice inoculated with Friend anemia virus resulted the most potent inhibitory effects on the splenomegaly, the increase of WBC counts and reverse transcriptase activity, but did not recover the anemia due to the toxicity of zidovudine itself on the bone marrow. The antiviral effects of zidovudine was reduced in case of zidovudine treatment 7 days after Friend anemia virus inoculation. These results suggested that the sooner treatment of zidovudine would be better improved when the virus was inoculated. Human recombinant interferon alpha itself did not show the antiviral activity against Friend anemia virus and also did not affect the antiviral activity of zidovudine. These results suggested that Friend anemia virus would be used as a tool in vivo screening method for the inhibitor of reverse transcriptase.

Antiretroviral Effects of 2',3'-Dideoxycytidine and Recombinant $Interferon-{\alpha}-A$ on the Infection of Anemia-inducing Murine Friend Virus

안형수,안령미,김동섭,Ann, Hyung-Soo,Ahn, Ryoung-Me,Kim, Dong-Seop The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.3

Anemia-inducing strain of Friend virus (FVA)는 적혈구 progenitor cell의 증식을 촉진하는 생쥐 retrovirus의 일종이다. FVA에 감염된 생쥐는 생성이 촉진된 progenitor cell이 분화되지 못하고 비장내에 축적되므로서 비장비대를 초래한다. 이에 본 실험에서는 FVA에 감염된 생쥐의 비장비대를 지표로 사용하여 2',3'-dideoxycytidine (ddC) 및 $interferon-{\alpha}-A\;(rIFN-{\alpha}-A)$의 항retrovirus효과를 측정하였다. 매일 ddC (100 mg/kg) 및 $rIFN-{\alpha}-A$ (10 KU/mouse)를 각각 단독 또는 병용하여 18일간 복강내 투여시 비장의 비대가 각각 15.1%, 52.7%, 61.6% 억제되었다. 또 다른 실험군으로 ddC를 식수중에 용해하여 (0.1 mg/ml) 경구로 18일간 투여시, 그리고 ddC의 경구투여와 병용하여 $rIFN-{\alpha}-A$을 위와 마찬가지 용량으로 복강내 투여시, 비장비대를 각각 38.4% 및 83.2% 억제하였다. 이 결과는 ddC의 투여시 복강내 주사보다는 경구투여가 더 유효하며, ddC와 $rIFN-{\alpha}-A$는 병용투여시 상가적인 효과가 있음을 제시한다. ddC 투여시 progenitor cell의 특성상 변화를 검토하기 위해, $Ca^{++}$ uptake $[^3H]cyclohexyladenosine$ (CHA) binding 실험을 실시하였다. CHA bindng 실험결과 성숙된 적혈구에서는 저친화성의 결합부위 하나뿐인데 반해, progenitor cell에서는 고친화성과 저친화성의 두가지 결합부위를 나타내었다. $Ca^{++}$ uptake 측정결과 성숙된 적혈구에 비해 대조군의 정상적인progenitor cell은 약 20배 증가를 나타내었으며, ddC를 연속투여한 군에서도 유사한 결과를나타내었다. 이때 CHA에 의한 $Ca^{++}$ uptake의 억제효과를 측정한 바, ddC 100 mg/kg 투여군의 경우 76%로 대조군의 86% 보다 억제효과가 크게 나타났으며, 이들 모두는 adenosine 길항약인 theophylline의 전처치시 대조군과 유사하게 회복되었다. The anemia-inducing strain of Friend virus (FVA) is a murine retrovirus which stimulates the proliferation of erythroid progenitor cells. The progenitor cells synthesized by FVA-stimulation are unable to proceed with differentiation and accumulate in the spleen resulting in splenomegaly in infected mice. Using FVA-inoculated mice as a model, we have investigated the antiretroviral effects of 2',3'-dideoxycytidine (ddC) and recombinant $interferon-{\alpha}-A\;(rIFN-{\alpha}-A)$ on FVA infection. The extent of the infection was determined by measuring the weights of the spleens. Daily intraperitoneal injection of ddC (100 mg/kg body weight), $rIFN-{\alpha}-A$ (10 KU/mose) and the combination of both drugs to FVA inoculated mice for 18 days resulted in suppression of the growth of spleens by 15.1%, 52.7% and 61.6%, respectively. When ddC was dissolved in drinking water (0.1 mg/ml) and administered to a group of FVA inoculated mice ad libitum, and $rIFN-{\alpha}-A$ (10 KU/mouse) was intraperitoneally injected daily to another group of ddC (0.1 mg/ml) drinking mice for 18days, the growth of spleens was suppressed by 38.4% and 83.2%, respectively. These results indicate that administration of ddC via drinking water is more effective in suppressing FVA infection than the daily injection of ddC, and that the combined effects ddC and $rIFN-{\alpha}-A$ are not synergistic but additive. In order to determine whether ddC treatment alters the characteristic of the progenitor cells with respect to $Ca^{++}$ uptake, $Ca^{++}$ uptake in erythroid cells and the effect of cyclohexyladenosine (CHA) on the $Ca^{++}$ uptake were studied. $Ca^{++}$ uptake in the erythroid progenitor cells was about 20-fold greater than in mouse erythrocytes and the inhibition of $Ca^{++}$ uptake by CHA was the greatest in the progenitor cells from FVA infected mice which were treated with ddC. The inhibition was obviated by theophylline. Results of CHA binding studies showed that the erythroid progenitor cells contain both high and low affinity CHA binding sites, whereas mose erythrocytes contain only the low affinity CHA binding sites.

지유로부터 분리한 다당류의 분석과 항응고작용

김영식,노지은,안형수,Kim, Yeong-Shik,Roh, Ji-Eun,Ann, Hyung-Soo 한국생약학회 1993 생약학회지 Vol.24 No.2

Polysaccharide from Sanguisorba officinalis was separated and fractionated using DEAE-Sephadex ion-exchange chromatography and Sephacry HR-200 gel filtration chromatography. One of the fraction(Fr. II) was sulfated and its anticoagulant activity was tested in vitro. Sulfation could increase the clotting time 50 times compared to unsulfated one. Fr. II was hydrolyzed and its composition was analyzed by conjugation with 7-amino-1, 3-naphthalene disulfonic acid using HPLC and electrophoresis. Arabinose and galactose were mainly composed at the ratio of 4 : 1. In addition, xylose and rhamnose were also found.

생쥐에 있어 Enalapril 및 Ginkgo biloba Extract(EGb 761) 복합체의 경구 아급성 독성실험

김은진,김진이,이영미,안형수,신완균,Kim, Eun-Jin,Kim, Lin-Lee,Lee, Young-Mi,Ann, Hyung-Soo,Shin, Wan-Kyun 한국독성학회 1998 Toxicological Research Vol.14 No.3

Group of 40 male and 40 female ICR mice was given daily per oral treatment with the combination of enalapril plus Ginkgo biloba extract (EGb 761), 3+9mg/kg/day(low dosage group), 10+30mg/kg/day (middle dosage group), 30+90mg/kg/day (high dosage group) for 3 months in drinking water according to Established Regulation of Korean National Institute of Safety Research (1994. 4.14). Appearance, behavior, mortality, and food consumption of mouse of treated groups were not affected during the experimental periods. No significant the combination of enalapril plus Ginkgo biloba extract (EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight, Lung edema were observed and the weight of lung were increased in low dosage treated group of the male mice, which be associated with enalapril treatment, but these changes were not found in middle and high dosage group. Our results suggest that to toxic changes were found in rat treated orally with the combination of enalapril plus Ginko biloba extract (EGb 761) for 3 months.

Cinnarizine을 Propranolol이나 Metoprolol과 병용할 때의 혈압 강하 효과에 관한 약리학적 연구(I) 혈압 변화에 대한 효과

허인회(In Hoi Huh),안형수(Hyung Soo Ann) 대한약학회 1984 약학회지 Vol.28 No.5

The effects of Ca2+-antagonist, cinnarizine, on the antihypertensive effects of propranolol and metoprolol were investigated in normal cat (i.v.) and SHR (p.o.). Cinnarizine increased the antihypertensive effect of propranolol, but not of metoprolol. It inhibited the heart rate decreasing effects of propranolol and metoprolol slightly. It decreased the norepinephrine-induced blood pressure increasing effect and isoproterenol-induced blood pressure decreasing effect when coadministered with metoprolol orally for 4 weeks in SHRs.

Amlodipine 과다 복용에 의한 고혈당증 2예

나현식 ( Hyun Sik Na ),안형수 ( Hyung Soo Ann ),하태훈 ( Tae Hoon Ha ),길효욱 ( Hyo Wook Gil ),양종오 ( Jong Oh Yang ),이은영 ( Eun Young Lee ),홍세용 ( Sae Yong Hong ) 대한신장학회 2005 Kidney Research and Clinical Practice Vol.24 No.5

Rat에서 Cromakalim에 의해 유발된 혈관이완 및 혈압강하작용에 대한 Glipizide의 억제작용

허인회(In Hoi Huh),안형수(Hyung Soo Ann),윤성훈(Seong Hun Yoon) 大韓藥學會 1991 약학회지 Vol.35 No.3

The inhibitory effects of glipizide on cromakalim-induced relaxation of aortae and hypotension in the anesthetized rats was examined. In rat thoracic aortic rings pre-contracted with norepinephrine, cromakalim produced a relaxation sustainedly. This relaxation was completely inhibited by pre- or post-treatment of glipizide. In the anesthetized rat, cromakalim produced a rapid and sustained fall in the arterial blood pressure. This hypotensive action of cromakalim was abolished by pre- or post-treatment of glipizide. It is suggested that glipizide is the potent inhibitor of cromakalim, K+ channel opener, in the rats.