• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1992년도 제1회 신약개발 연구발표회 초록집
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• pp.40-40
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• 1992

opiate receptor들의 중추신경계에서의 분포 및 작용에 관한 실험물은 널리 알려져 있어 그 웅용 방법도 많이 있으나, 말초에 있는 opiate receptor의 존재 및 약물작용을 관찰하는 실험은 별로 알려진 것은 없다. 저자는 214mM의 sucrose 용역을 이용하여 전기적 자극에 따른 말초신경 및 말초조직(근육)에서의 opiate receptor애 대한 작용을 관찰하였다. 실험은 3분류의 약물을 이용하였다. 1) Pure agonists: morphine, meperidine, methadone, 2) Agonist-antagonist: buprenorphine 3) Pure antagonist: naloxone 위의 약물들을 이용하여 excitable cell membrane(좌골신경 및 근육)에서 일어나는 potential의 변화를 관찰하여 다음과 같은 결과를 얻었다. a. pure agonists들은 좌골신경 및 근육절편에서 action potentials을 의의있게 억제시켰으며 meperidine이 가장 강한 작용을 보였다. b. 이들의 작용은 naloxone 투여로 억제되었다. c. Agonist-antagonist인 buprenorphine은 투여용량 및 동시 투여한 pure agonist의 종류에 따라 biphasic pattern을 나타내었다. d. opiates 작용기전 및 약물작용장소를 알고자 두 종류, 즉 single 및 double technique을 사용하여 비교하였다.

• 대한약리학회지
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• 제30권2호
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• pp.181-190
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• 1994

In rat atrium the characteristics of purinergic receptors were investigated by observing the effects of some purinergic receptor agonists and antagonists on action potential and contractile force. The statistically significant effects of $ATP(10^{-6}{\sim}10^{-3}M)$ and adenosine $(10^{-6}{\sim}10^{-3}M)$ on normal action potential characteristics were a dose-dependent shortening of action potential duration $(APD_{90})$ by both agents and hyperpolarization by $ATP(10^{-4},10^{-3}M)$. $CAP(10^{-8}{\sim}10^{-4}M)$, an $A_1$ adenosine receptor agonist, shortened $(APD_{90})$ markedly in a dose-dependent manner and these effects were almost abolished by $DPCPX\;(10^{-6}\;M), an $A_1$, adenosine receptor antagonist, but not affected by $DMPX(2{\times}10^{-6}\;M)$, an $A_2$ adenosine receptor agonist. On the other hand, CGS $21680(10^{-7}{\sim}10^{-4}M)$, an $A_2$ adenosine receptor agonist, elicited a slight shortening of $(APD_{90})$ and these effects were inhibited by DPCPX but persisted in the presence of DPMX. Adenosine $(10^{-6}{\sim}10{\-4}\;M)$ decreased the basal contraction of atrial muscle in a dose-dependent manner and these effects were not inhibited by DMPX but by DPCPX. These results suggests that purinergic receptor agonists depress the cardiac activity by a short ening of action potential duration and this effect is mostly mediated by $A_1$ adenosine receptors in rat atrium.

• Archives of Pharmacal Research
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• 제14권3호
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• pp.271-278
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• 1991

To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific $[^3H]$QNB binding with $K_i$ values of 16.7\mu{M}$, 3.5\mu{M}$ and 15.5\mu{M}$ respectively. Saturation data of $[^3H]$QNB binding with $K_i$ VALUES OF 16.7\mu{M}$ 3.5\mu{M}$ and 15.5\mu{M}$ respectively. Saturation data of $[^3H]$QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of $[^3H]$nitrendipine to the high affinity DHP binding sites, but atropine did not, indicating that the muscarinic receptors and the DHP binding sites m but atropine did not, indicating that the muscarinic receptors and the DHP bindings sites on calcium channels are distinct. The $K_i$ value of Bay K 8644 for the DHP binding sites was 4nM. Nicardipine and nimodipine $(K_i:0.1-0.2\;nM)$ were at least 20 times more potent than Bay K 8644 in inhibiting $[^3H]$ nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than thes high afinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.

• Clinical and Experimental Reproductive Medicine
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• 제17권1호
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• pp.29-44
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• 1990

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation(COH) due to poor follicular growth or premature LH surge, the effectiveness of pituitary suppression with gonadotropin-releasing hormone agonist(GnRH agonist) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of Leuprolide acetate (Lupron TAP Pharmaceuticals, USA) and FSH/hMG or pure FSH from May to December, 1989 at SNUH. Starting on day 21 of the menstrual cycle(MCD #21, Day 1), Lupron (1.0mg/day, subcutaneous) was administered once a day till next MCD #3(suppression phase). After the confirmation of pituitary suppression, ovarian follicular growth was stimulated with FSH/hMG or pure FSH from MCD #3(Day + 1), and Lupron was continued with hMG or FSH until hCG administration (D 0) (stimulation phase). After suppression phase, serum E2 level decreased from 183.7${\pm}$95.1(Day 1) to 17.4${\pm}$12.3pg/ml (Day +1), and serum progesterone level from 19.17${\pm}$8.67 to 0.12${\pm}$0.05ng/ml. But there was no decresas in serum LH and FSH levels; LH from 12.74${\pm}$6.21 to 15.49${\pm}$4.93mIU/ml,FSH from 7.60${\pm}$3.84 to 8.58${\pm}$3.15 rnlU/ml. There was no occurrence of premature LH surge during COH. Eleven cycles(9.8%) were cancelled due to poor follicular growth during stimulation phase, and 3 cycles (3.0%) failed in the transvaginal oocytes fretrieval. Serum E2 level was 1366.8${\pm}$642.4 on D 0 and 1492.3${\pm}$906.9pg/ml on D+1. 7.00${\pm}$3.32 follicles(FD${\geq}$12mm) were observed on D 0, and 6.11${\pm}$4.15 oocytes were retrieved, with the oocyte retrieval rate per follicle of 95.0%. 3.59${\pm}$2.57 oocytes were fertilized and cleaved with the oocyte cleavage rate of 55.7%. In 83 IVF patients, 4.08${\pm}$2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET 2.39 mebryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83${\pm}$3.31 oocytes were retrieved and transferred with maximum number of 6, but no pregnancy was obtained. When compared with the previous 108 cycles of COH using FSH/hMG or pure FSH regimen, the cancellation rate during COH was significantly decreased, and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRH agonist therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.

• PNF and Movement
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• 제7권4호
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• pp.1-7
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• 2009

Purpose : This paper reviews on the method of PNF stretching. Methods : This is literature study with Pubmed, medline, SPORT Discus, EBSCO, ProQuest and books. Results : PNF stretching is effective for increasing range of motion than static and ballistic stretching. CR(contract-relax) technique is effective and CRAC(contract-relax with agonist contraction) technique including agonist contraction is more effective. A minimum of one repetition, twice or three times per week is required for range of motion gains, needs to be conducted continueously. A minimum of 20% contraction intensity and more than 3 seconds contraction duration are needed to increase range of motion. Inclusion of static stretching of antagonist and agonist contraction is more effective. Conclusions : PNF stretching is more effective for increasing range of motion than other stretching methods, but, clinicians need to select proper techniques according to subjects and muscles, and conduct carefully when applying technique.

• 대한약리학회지
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• 제25권1호
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• pp.23-30
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• 1989

함께 투여되는 마약성진통제에 따라 효능제 또는 길항제(mixed agonist-antagonist)로 작용하는 buprenorphine을 사용하여 개구리 좌골신경에 존재하는 아편수용체의 성질을 검토하였다. 실험은 sucrose-gap apparatus를 사용하여 활동전압에 대한 영향을 관찰하였으며 약물의 상호작용을 검토하고자 meperidine 또는 naloxone을 사용하여 다음과 같은 결과를 얻었다. 1) Buprenorphine은 현저하게 개구리 좌골신경의 활동전압을 저하시켰다. 2) 두 개의 최고작용농도를 보였는데 저농도에서는 $10^{-8}\;M$, 또 고농도에서는 $10^{-4}\;M$에서 현저하게 작용을 나타내었다. 3) Buprenorphine은 meperidine의 활동전압 저하작용을 의의있게 억제하였다. 4) Naloxone에 의하여 Buprenorphine의 저하 작용이 억제되었다. 위의 실험결과로 Buprenorphine은 순수 마약성진통제의 작용을 억제하여 차단제로 작용하는 한편 또한 효능제로 활동전압을 의의있게 억제하였다. 이로써 개구리 좌골신경에 있는 아편수용체는 세포막에 또는 세포막 주위에서 $Na^+-Channel$이 활성화되는 데 중요한 역할을 하는 것으로 간주되며 이 수용체는 또한 Naloxone에 매우 민감한 반응을 나타낸다.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.352-356
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• 2012

The present study was undertaken to determine whether ethanol influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Ethanol significantly inhibited thromboxane $A_2$ mimetic-induced contraction with intact endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction irrespective of endothelium suggesting that the pathway such as Rho-kinase activation, $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, ethanol didn't decrease thromboxane $A_2$ mimetic-induced increase of phospho-myosin phosphatase targeting subunit protein 1 (pMYPT1) or pERK1/2. Interestingly, ethanol didn't inhibit significantly phorbol ester-induced contraction in denuded muscles suggesting that thin filament regulation is less important on the ethanol-induced regulation in the muscle than endothelial NO synthesis. In conclusion, this study provides the evidence and possible related mechanism concerning the effect of ethanol on the agonist-dependent contraction in rat aortic rings with regard to endothelial function.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.249-254
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• 2008

The present study was undertaken to determine whether hypoxia influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Hypoxia significantly inhibited fluoride-induced contraction regardless of endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction suggesting that other pathway such as $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, hypoxia significantly decreased fluoride-induced increase of phospho-myosin-targeting subunit of myosin light chain phosphatase (pMYPT1). Interestingly, hypoxia didn't inhibit significantly phenylephrine-induced contraction suggesting that myosin light chain kinase (MLCK) activity or thin filament regulation is less important on the hypoxia-induced vasorelaxation in the denuded muscle than Rho-kinase activity. In conclusion, this study provides the evidence and possible related mechanism concerning the vasodilation effect of hypoxia on the agonist-specific contraction in rat aortic rings regardless of endothelial function.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.259-267
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• 2002

Objective: This study was performed to compare the clinical outcomes of GnRH antagonist (Cetrorelix) single dose and multiple dose protocols for controlled ovarian hyperstimulation with GnRH agonist long protocol. Materials and Method: From September 2001 to March 2002, 48 patients (55 cycles) were performed controlled ovarian hyperstimulation for ART using by either GnRH antagonist and GnRH agonist. Single dose of 3 mg GnRH antagonist was administered in 15 patients (17 cycles, single dose group) at MCD #8 and multiple dose of 0.25 mg of GnRH antagonist was administered in 15 patients (18 cycles, multiple dose group) from MCD #7 to hCG injection day. GnRH agonist was administered in 18 patients (20 cycles, control group) by conventional GnRH agonist long protocol. We compared the implantation rate, number of embryos, and clinical pregnancy rate among three groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: There were no significant differences in ampules of used gonadotropins, number of mature oocytes, obtained embryos between single and multiple dose group, but compared with control group, ampules of used gonadotropins, number of mature oocytes, obtained embryos were decreased significantly in both groups. Clinical pregnancy rate and implantation rate were not different in three groups. There were no premature LH surge and ovarian hyperstimulation syndrome in three groups. Multiple pregnancy were occurred 1 case in multiple dose group and 2 case in control group. Conclusions: GnRH antagonist is a safe, effective, and alternative method in the controlled ovarian hyperstimulation compared with GnRH agonist. Clinical outcomes and efficacy of both single and multiple dose protocol are similar between two groups.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.