• Advances in Traditional Medicine
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• 제6권3호
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• pp.186-195
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• 2006

The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.

• Journal of Pharmaceutical Investigation
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• 제36권5호
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• pp.321-329
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• 2006

Albuterol, a selective ${\beta}_2$-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.

• Journal of Pharmaceutical Investigation
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• 제29권4호
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• pp.329-335
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• 1999

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic bronchitis and pulmonary emphysema. For the purpose of developing a transdermal preparation for clenbuterol, we attempted to select an optimal solvent system and permeation enhancer among fatty acids and fatty alcohols which are known to accelerate the penetration of various drugs in permeation experiments using hairless mouse skin and Franz diffusion cell. Apparent partition coefficient of clenbuterol was increased as pH of buffer solution was increased and solubility of clenbuterol was increased as the percent of propylene glycol(PG) in buffer solution(pH 10) was increased. Permeability of clenbuterol from different buffer(pH 10)/PG solvent mixtures was decreased as the percent of PG in pH 10 buffer solution was increased and among the various enhancers studied, lauryl alcohol was found to be the most effective enhancer, increasing the permeability of clenbuterol approximately 76-fold compared with control. Lauryl alcohol$(0{\sim}2%)$ enhanced the permeability of clenbuterol concentration-dependently. In this study, the optimal solvent system for the penetration of clenbuterol was found to be 50/50 buffer(pH 10)/PG solvent mixture containing 2% lauryl alcohol.

• Journal of Pharmaceutical Investigation
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• 제30권4호
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• pp.247-252
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• 2000

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease. For the development of transdermal systems containing clenbuterol, two limiting factors - long lag time and low flux - must be overcome. In this study, we attempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of clenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Furthermore, the clenbuterol patch composed of 15% clenbuterol, 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levels in in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

• Journal of Korean Neurosurgical Society
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• 제64권5호
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• pp.716-725
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• 2021

Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

• 한방재활의학과학회지
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• 제21권2호
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• pp.31-48
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• 2011

Objectives : In order to investigate the anti-obesity effects of Wolbi-tang(here in after referred to WBT) on the obese gene and obese inhibitory, C57BL/6 mice were induced by high-fat diet. Methods : C57BL/6 mice were divided into 5 groups(normal, only high-fat diet, high-fat diet with Reductil, high-fat diet with WBT 400, 200 mg/kg extract) and fed for 5 weeks. And observed body weight change, total cholesterol, low density lipoprotein cholesterol(LDL-cholesterol), high density lipoprotein cholesterol (HDL-cholesterol), triglyceride, glucose, leptin change, alanine transaminase(ALT), aspartate transaminase(AST), serum creatinine, the expression of ${\beta}3$-adrenergic receptor(${\beta}3AR$), leptin, uncoupling protein(UCP2) gene in 3T3-L1 adipocyte, 3T3-L1 adipocyte proliferation, histological analysis of adipose tissue and liver tissue. Results : 1. Refer to cell cytotoxicity, viability of human fibroblast cells(hFCs) showed not significant changes. 2. The amount of ALT, AST was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. The amount of creatinine showed not significant changes. 3. Body weight was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. 4. The amount of total cholesterol and triglyceride was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. LDL-cholesterol was decreased and HDL-cholesterol was increased significantly in WBT 400 mg/kg groups. 5. The amount of glucose was decreased significantly in WBT 400 mg/kg groups. 6. The amount of serum leptin was decreased significantly in WBT 400 mg/kg, 200 mg/kg groups. 7. The revelation of ${\beta}3AR$ in 3T3-L1 adipocyte was increased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The revelation of leptin was decreased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The revelation of UCP2 was decreased significantly in WBT $100{\mu}g/ml$ group. 8. 3T3-L1 adipocyte proliferation was decreased significantly in WBT $100{\mu}g/ml$, $50{\mu}g/ml$ groups. The size of adipocyte was decreased relative to the control group in WBT 400 mg/kg group. 9. The adipose vacuoles in liver tissue was decreased relative to the control group. Conclusions : These results suggested that WBT has inhibitory effects of obesity. WBT might be applicated on treatment of obesity and metabolic syndrome. Further studies analysing its effects were needed.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.815-821
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• 1997

연구배경 : ${\beta}_2$-수용체에 매우 선택성을 가지고 있는 salmeterol은 작용시간이 길고 부작용이 적어 최근 기관지 천식의 치료에 많이 사용되며 특히 야간성 발작이 있는 환자에서 좋은 효과가 있다고 보고되고 있다. 이에 저자는 경증 또는 중증도의 가역성이 있는 천식 환자에서 salmeterol과 salbutamol을 흡입 투여 하였을 때의 효과와 안정성을 비교 평가하고자 본 연구를 시행하였다. 방 법 : 대상환자 35명을 무작위추출 개방시험 방법으로 salmeterol 투여군과 salbutamol 투여군으로 나누어 시행하였다. 모든 대상환자들은 2주간의 치료 준비동안, 필요한 경우 salbutamol 100g씩 2회를 흡입하는 경우를 제외하고는 어떤 기관지 천식 약제를 금지시켰으며 그 후 6주간의 치료기간을 설정하여 salmeterol 군에서는 salmeterol 50g을 1일 2회, 기상직후와 취침직전에 흡입하도록 하였고, salbutamol군에서는 salbutamol 200g을 1일 4회, 기상직후 부터 4시간 간격으로 흡입하도록 하였다. 그후 2주동안은 규칙적인 흡입제를 중단하고 증상에 따라 salbutamol을 임식적으로 사용하였다. 결 과 : 주간 및 야간 천식 증상 평가에 있어서 salmeterol 치료군이 salbutamol 치료군에 비해 유의 있는 호전이 있었다(p<0.05). 추가 salbutamol 사용횟수나 사용날짜는 주간이나 야간에서 salmeterol 치료군에서 사용횟수 및 사용 날짜를 줄일 수 있었다(p<0.05). 폐기능검사에 있어서 $FEV_1$의 증가율은 2-4주간의 흡입 후에 salmeterol군에서 유의하게 높게 나타났다. Salmererol에 대한 부작용은 일부환자에서 경미한 손떨림이나 두근거림이 있었지만 salbutamol 군과는 차이가 없었으며 치료를 중단한 환자는 없었다. 결 론 : 이상의 실험 결과로 흡입용 salmeterol은 부작용이 비교적 적고 안전하며 효과적임을 알 수 있고, 특히 야간성 발작성 천식에 매우 효과적인 기관지 확장제로 생각된다.

• 사상체질의학회지
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• 제12권1호
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• pp.228-239
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• 2000

1. 연구목적 소음인(少陰人) 성향정기산(星香正氣散)은 "동의수세보원(東醫壽世保元)"의 곽향정기산(藿香正氣散)에 남성(南星)과 목향(木香)의 두 가지 약물이 가미되어 이루어진 처방이다. 이는 소음인이한병(少陰人裏寒病)을 치료하는 처방으로 근래에는 뇌졸중을 비롯한 중추신경계통 질환에 많이 사용되고 있다. 이러한 소음인(少陰人) 성향정기산(星香正氣散)의 용도를 과학기기를 이용하여 기전을 규명하고자 하였다. 2. 연구방법 백서를 urethane으로 마취시키고 소음인(少陰人) 성향정기산(星香正氣散)을 투여한 후 Pressure Transduer와 Laser-Doppler flowmetry를 이용하여 백서의 혈압과 국소뇌혈류량을 측정하였으며 이를 구성약물까지 진행하였다. 또한 소음인(少陰人) 성향정기산(星香正氣散)의 대뇌혈류에 관한 기전 규명을 위하여 propranolol과 methylene blue로 전처치한 후 소음인(少陰人) 성향정기산(星香正氣散)을 투여하여 이를 분석하였다. 3. 결과 및 결론 소음인(少陰人) 성향정기산(星香正氣散)의 투여로 혈압의 유의한 변화는 없었으며, 국소뇌혈류량은 유의하게 증가되었다. 구성약물 중 소엽(蘇葉), 창출(蒼朮), 대복피(大腹皮), 남성(南星)은 국소뇌혈류량을 유의하게 증가시켰으며 목향(木香)은 국소뇌혈류량을 유의하게 감소시켰다. 이 실험으로 소음인(少陰人) 성향정기산(星香正氣散)의 국소뇌혈류량 증가의 기전은 교감신경 ${\beta}$-수용체와 cyclic GMP의 생성효소인 guanylyl cyclase의 작용과 관련이 있는 것으로 생각된다.

• 사상체질의학회지
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• 제12권1호
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• pp.216-227
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• 2000

1. 연구목적 태음인(太陰人) 청심연자탕(淸心蓮子湯)은 "동의수세보원(東醫壽世保元)" 태음인병 24처방 중에 기재된 신정방으로 태음인 간조열증(肝燥熱證)에 응용되는 처방이다. 근래에는 뇌졸중을 비롯한 중추신경계통 질환에 많이 사용되고 있다. 이러한 태음인(太陰人) 청심연자탕(心蓮子湯)의 용도를 과학기기를 이용하여 기전을 규명하고자 하였다. 2. 연구방법 백서를 urethane으로 마취시키고 태음인(太陰人) 청심연자탕(淸心蓮子湯)을 투여한 후 Pressure Transducer와 Laser-Doppler flowmetry를 이용하여 백서의 혈압과 국소뇌혈류량을 측정하였으며 이를 구성약물까지 진행하였다. 또한 태음인(太陰人) 청심연자탕(淸心蓮子湯)의 대뇌혈류에 관한 기전 규명을 위하여 propranolol과 methylene blue로 전처치한 후 태음인(太陰人) 청심연자탕(淸心蓮子湯)을 투여하여 이를 분석하였다. 3. 결과 및 결론 태음인(太陰人) 청심연자탕(淸心蓮子湯)의 투여로 혈압의 유의한 변화는 없었으며, 국소뇌혈류량은 유의하게 증가되었다. 구성약물 중 연자육(蓮子肉), 맥문동(麥門冬), 천문동(天門冬), 원지(遠志), 산조인(酸棗仁), 룡안육(龍眼肉), 나복자, 감국(甘菊)은 국소뇌혈류량을 유의하게 증가시켰다. 이 실험으로 태음인(太陰人) 청심연자탕(淸心蓮子湯)의 국소뇌혈류량 증가의 기전은 교감신경 ${\beta}$-수용체와 cyclic GMP의 생성효소인 guanylyl cyclase의 작용과 관련이 있는 것으로 생각된다.

• 대한약리학회지
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• 제23권2호
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.