• Title/Summary/Keyword: S1P agonist

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The Effect of Menstration on GnRH Agonist Treatment for the Uterine Myoma (자궁근종의 성선자극호르몬분비호르몬 효능제 치료에 있어 생리의 영향)

  • Han, Soo-Kyung;Lee, Myung-Koo;Han, Song-Yi;Park, Mi-Sook;Lim, Sung-Cil
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.402-408
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    • 2007
  • The aim of this study was to evaluate the effect of menstration among the influencing factors for the GnRH agonist (as G: depot goserelin 3.6 mg) therapy prior to the planned myomectomy for women who wanted to preserve their fertility. We reviewed total 48 patients. with the G therapy prior to the planned myomectomy from August 1st, 2005 to August 31st, 2006. The patients were classified by the G group (n=28) and the immediate surgery (as S) group (n=20). The G group (n=19) underwent the G therapy for 3 month courses, and then the efficacy was evaluated by menstruation and the myoma volumes. In the G group (n=19), therapy was effective, and the mean age was $32.4{\pm}6.5$ years. After the completion of G therapy, the mean volume of the myoma by ultrasonography was reduced to $85.2{\pm}71.2cm^3$ comparing of $430.6{\pm}248.8cm^3$ at first visit. The 11 patients had menstruation and the rest 8 patients with amenorrhea had less reduced volume of the myoma ($124.05{\pm}79.85cm^3\;v.s.\;329.41{\pm}234.0cm^3$ p<0.05). In the immediate S group, the myoma volumes by sonography was also checked for accuracy (${\alpha}=1.0$). As the result, the initial myoma volume had the positive correlations to the effectiveness with G therapy. However, the occurrence and frequency of the menstruation during the G therapy had a negative correlation. In conclusion, the use of G prior to the planned myomectomy was effective in reducing myoma volume and the menstruation.

Comparison of Pregnancy Rates by Intrauterine Insemination after Ovulation Trigger with Endogenous LH Surge, GnRH Agonist or hCG in Stimulated Cycles (인공수정시술주기에서 내인성 LH, GnRH Agonist 및 hCG를 이용한 배란유발후 임신율의 비교연구)

  • Lee, Jong-In;Hur, Young-Mun;Jeon, Eun-Suk;Yoon, Jeong-Im;Jung, Goo-Sung;Hong, Ki-Eon;You, Seung-Hwan;Lee, Hyeon-Sook;Hong, Jeong-Eui;Lee, Ji-Sam
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.3
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    • pp.389-398
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    • 1999
  • Objective: This study was designed to evaluate the effects of endogenous LH surge, GnRH agonist (GnRH-a) or human chorionic gonadotropin (hCG) as ovulation trigger on pregnancy rate by intrauterine insemination (IUI). Method: Patients received daily 100 mg of clomiphene citrate (CC) for 5 days starting on the third day of the menstrual cycle followed by human menopausal gonadotropin (hMG) for ovulation induction. Follicles larger than >16 mm in diameter were present in the ovary, frequent LH tests in urine were introduced to detect an endogenous LH surge. Final follicular maturation and ovulation were induced by GnRH-a 0.1 mg (s.c.) or hCG $5,000{\sim}10,000$ IU (i.m.) administration except natural ovulation. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. Results: There were no differences in age, duration of infertility and follicle size, but more ampules of hMG were used in GnRH-a group compared to hCG 10,000 IU treated group (p<0.05). Lower level of estradiol ($E_2$) on the day of hCG or GnRH-a injection was observed in hCG 10,000 IU group than other treatment groups (p<0.01). The overall clinical pregnancy rate was 19.8% per cycle (32/162) and 22.2% per patient (32/144). Pregnancy rate was higher in natural-endogenous LH surge group (37.5%, 9/24) than GnRH-a (18.8%) or hCG treated group (20.9% & 13.9%), but this difference was not statistically significant. No patient developed ovarian hyperstimulation. Abortion rate was 22.2% (2/9) in hCG 5,000 IU group. Delivery or ongoing pregnancy rate was 37.5% (9/24), 18.8% (3/16), 16.3% (7/43) and 13.9% (11/79) in endogenous LH surge, GnRH-a, hCG 5,000 IU and hCG 10,000 IU treatment groups, respectively. Conclusion: These results support the concept that use of natural-endogenous LH surge in stimulated cycles may be more effective to obtain pregnancies by IUI than GnRH-a or hCG administration.

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Cholinergic and Neurokinergic Agonist-induced $Ca^{2+}$ Responses in Rat von Ebner's Gland Acinar Cells

  • Chung, Ki-Myung;Kim, Sang-Hee;Cho, Young-Kyung;Roper, Stephen D.;Kim, Kyung-Nyun
    • International Journal of Oral Biology
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    • v.31 no.3
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    • pp.99-105
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    • 2006
  • Von Ebner's glands (vEG) are minor salivary glands associated with circumvallate and foliate papilla. The secretions of vEG consist of microenvironment of the taste buds in the circumvallate and foliate papillae, and thus saliva from vEG plays a role in the perception of taste. The $Ca^{2+}$ signaling system in rat vEG acinar cell was examined using the $Ca^{2+}$-sensitive fluorescent indicator Fura-2. Agonist-induced increase in intracellular $Ca^{2+}\;([Ca^{2+}]_i)$ was stimulated by carbachol (CCh) and substance P (SP), but not by norepinephrine (NE), and recovered to control levels by their receptor antagonists dose-dependently. The effects were also observed in $Ca^{2+}$-free medium, suggesting mobilization from intracellular $Ca^{2+}$ store. These results in the vEG acinar cell indicate that 1) $[Ca^{2+}]_i$ is at least regulated by muscarinic and neurokininergic (NK1) receptors; 2) the increases in $[Ca^{2+}])i$ activated by CCh and SP are mainly mediated by discharge of cytosolic calcium pool.

Ginsenoside Rg3 protects against iE-DAP-induced endothelial-to-mesenchymal transition by regulating the miR-139-5p-NF-κB axis

  • Lee, Aram;Yun, Eunsik;Chang, Woochul;Kim, Jongmin
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.300-307
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    • 2020
  • Background: Emerging evidence suggests that endothelial-to-mesenchymal transition (EndMT) in endothelial dysfunction due to persistent inflammation is a key component and emerging concept in the pathogenesis of vascular diseases. Ginsenoside Rg3 (Rg3), an active compound from red ginseng, has been known to be important for vascular homeostasis. However, the effect of Rg3 on inflammation-induced EndMT has never been reported. Here, we hypothesize that Rg3 might reverse the inflammation-induced EndMT and serve as a novel therapeutic strategy for vascular diseases. Methods: EndMT was examined under an inflammatory condition mediated by the NOD1 agonist, γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), treatment in human umbilical vein endothelial cells. The expression of EndMT markers was determined by Western blot analysis, real-time polymerase chain reaction, and immunocytochemistry. The underlying mechanisms of Rg3-mediated EndMT regulation were investigated by modulating the microRNA expression. Results: The NOD1 agonist, iE-DAP, led to a fibroblast-like morphology change with a decrease in the expression of endothelial markers and an increase in the expression of the mesenchymal marker, namely EndMT. On the other hand, Rg3 markedly attenuated the iE-DAP-induced EndMT and preserved the endothelial phenotype. Mechanically, miR-139 was downregulated in cells with iE-DAP-induced EndMT and partly reversed in response to Rg3 via the regulation of NF-κB signaling, suggesting that the Rg3-miR-139-5p-NF-κB axis is a key mediator in iE-DAP-induced EndMT. Conclusion: These results suggest, for the first time, that Rg3 can be used to inhibit inflammation-induced EndMT and may be a novel therapeutic option against EndMT-associated vascular diseases.

The Role of Central Postsynaptic ${\alpha}_2$-Adrenoceptor on the Immobility Duration in the Forced-swimming Test Mice (새앙쥐 강제수영시 부동자세 시간에 대한 Central postsynaptic ${\alpha}_2$-Adrenoceptor의 역할에 대한 연구)

  • Rhim, Byung-Yong;Kim, Sang-Kon;Lee, Won-Suk;Hong, Ki-Whan
    • The Korean Journal of Pharmacology
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    • v.21 no.2
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    • pp.90-98
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    • 1985
  • 1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.

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Regulation of Insulin-Sensitive Cyclic Nucleotide Phosphodiesterase in Adipocytes of Streptozotocin-Induced Diabetic Rats (Streptozotocin으로 당뇨병을 유발시킨 흰쥐의 지방세포에서 일어나는 Insulin-Sensitive Phosphodiesterase의 조절에 관한 연구)

  • Park, Kyung-Sun;Lee, Myung-Soon;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.253-261
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    • 1993
  • Possible changes in the role of insulin-sensitive cyclic nucleotide phosphodiesterase(PDE) in mediating the antilipolytic action of insulin were investigated in adipocytes from streptozotocin-induced diabetic rats. Isolated adipocytes prepared from epididymal adipose tissue were incubated, with or without insulin, at $37^{\circ}C$ for 15 min following pretreatment with various drugs or toxins, and three (plasma membranes, microsomal membranes, and cytosol) fractions prepared by differential centrifugation were then assayed for cAMP phosphodiesterase activity. The PDE activities only in the crude microsomal (P2) fractions were activated by insulin both in diabetic and control rats. The basal PDE activities in P2 fractions of adipocytes from diabetic rats were higher than those from control rats, although the maximal effects observed at 2 nM of insulin, $100\;{\mu}M$ of isoproterenol or the combination of both were not significantly different from each other. The insulin-stimulated PDE activities in P2 fractions of adipocytes from diabetic rats were not changed by PIA, a $A_{1}$ adenosine receptor agonist, whereas they were decreased to the basal PDE activities in those from control rats. In addition, the adipocytes from diabetic rats showed an increased sensitivity to pertussis toxin compared to those from controls. There were no differences between diabetic and control rats in the sensitivity of adipocytes to cholera toxin. These data indicate that the impaired signalling through inhibitory receptors such as adenosine receptors in adipocytes from streptozotocin-induced diabetes relates to the loss or the decreased function of $G_i$ proteins, and leads to the increased activity of the insulin-dependent PDE at the basal states.

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STUDY OF RESVERATROL AND ITS DERIVATIVES ON THE REGULATION OG GENE EXPRESSION IN MCF-7 CELLS TRANSFECTED WITH EITHER pERE-LUC OR phCYP1A1-LUC

  • Joung, Ki-Eun;Kim, Yeo-Woon;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.111-111
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    • 2001
  • Resveratrol (trans-3,4',5-trihydroxystilbene), which is a polyphenolic compound found in a variety of plants such as grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Recently resveratrol of was reported to serve as an estrogen agonist in MCF-7 cells Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol and its derivatives might be estrogenic using stable MCF-7-ERE cells. Resveratrol functioned as a superagonist at high concentrations (i.e., produced a greater maximal transcriptional response than estradiol) Among the resveratrol derivatives, 10 compounds showed significant estrogenic activity.

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Polysomnographic Characteristics and Prescription Status of Restless Legs Syndrome Patients in Naturalistic Setting (임상현장에서 하지불안증후군 환자의 수면다원검사결과의 특징과 약물처방현황)

  • Kang, Seung-Gul;Nam, Ji-Hye;Kim, Hana;Shin, Hong Beom
    • Sleep Medicine and Psychophysiology
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    • v.20 no.1
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    • pp.35-40
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    • 2013
  • Objectives: The aim of this study is to evaluate the polysomnographic characteristics and prescription status of restless legs syndrome (RLS) patients in naturalistic setting. Methods: We reviewed medical record of the patients over 18 years olds who (i) satisfied the clinical RLS diagnostic criteria and (ii) had the polysomnography and got treatment related thereto. As a baseline, we evaluated the four diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG) and the International Restless Legs Scale (IRLS) of the subjects. Then the polysomnography and the suggested immobilization test (SIT) were conducted and, after one month of pharmacotherapy using dopamine agonist, the IRLS was evaluated again. Results: A total of 211 subjects participated in this analysis and 94 (44.5%) of them were male and the other 117 (55.5%) were female and the average age of the 211 subjects was $46.9{\pm}14.2$. Out of such 211 subjects, 136 subjects (64.5%) also had the obstructive sleep apnea (OSA), and 53 subjects (25.1%) also had the periodic limb movement disorder (PLMD). 185 subjects (87.7%) out of the 211 subjects had some other sleep disorders except RLS. The results of the polysomnography were as follows : 78.0% of sleep efficiency, 86.8 min of wake after sleep onset, and 3.4% of N3. More specifically, 12.4/h of the average apnea hypopnea index, 14.8/h of the periodic limb movement during sleep (PLMS), 41.2/h of the periodic limb movement during wake during SIT and 21.6/h of total arousal index during sleep. Out of the total subjects, 149 (70.6%) of them took the ropinirole and 47 (22.3%) of them took the pramipexole, and the average dosage of ropinirole was 0.9mg(dosage range 0.125-5 mg) while the average dosage of pramipexole was 0.5 mg (dosage range 0.125-4 mg). The dosage of the ropinirole showed a significant positive correlation with the age (r=0.25, p=0.002) and also with the IRLS (r=0.23, p=0.038). The IRLS at the baseline was 24.9 while the same was decreased down to 13.4 after one month. Conclusions: Analyzing the result of this study, a majority of clinical RLS subjects demonstrated comorbidity with some other sleep disorder such as the OSA or PLMD. 25.1% of the subjects showed a PLMD, which was less than in previous researches and the average PLMS was not very high as 14.8/h. The dosage of dopamine agonist taken was often a bit more than the amount recommended in Korea. A prospective research using a large scale controlled subjects will be necessary with respect to this topic.

Time Courses of pCREB Expression after Dopaminergic Stimulation by Apomorphine in Mouse Brain

  • Jang, Choon-Gon;Lee, Seok-Yong;Lee, Han-Kyu;Suh, Hong-Won;Song, Dong-Keun
    • Archives of Pharmacal Research
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    • v.25 no.3
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    • pp.370-374
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    • 2002
  • Administration of dopamine agonist, apomorphine (2 mg/kg, s.c.), produces cage climbing behavior in mice that exhibit typical dopaminergic stimulation. The present study investigated the pCREB expression level in several brain regions following apomorphine treatment in order to determine whether the increased the dopaminergic activation produced by apomorphine accompanies the changes in pCREB immunoreactivity. A mouse brain was removed at 0min, 10 min, 30 min, 1 h, 2 h, 7 h, and 24 h after apomorphine treatment. The brain tissue was fixed by an intracardiac perfusion with ice-cold 4% paraformaldehyde in PBS. Immunohistochemical study was conducted using the ABC-DAB method. The data showed that the immunoreactivity of pCREB increased in the striatum, nucleus-accumbens, piriform cortex and the dentate gyrus of the hippocampus of a mouse brain 30 min after the apomorphine treatment. Increased immunoreactivity began to diminish 2 h after the apomorphine treatment in all the brain regions measured. The time course for the pCREB immunoreactivity was similar to the behavioral response induced by the apomorphine treatment. These results suggest that activation of the dopamine receptor is accompanied by an increase in pCREB expression in the mouse brain.