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Influence of Nicorandil on Catecholamine Release in the Perfused Rat Adrenal Medulla

  • Koh, Young-Youp;Lee, Eun-Sook;No, Hae-Jeong;Woo, Seong-Chang;Chung, Joong-Wha;Seoh, Yoo-Seung;Lim, Dong-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.3
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    • pp.97-106
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    • 2007
  • The present study was attempted to investigate the effect of nicorandil, which is an ATP-sensitive potassium ($K_{ATP}$) channel opener, on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal glands. The perfusion of nicorandil ($0.3{\sim}3.0mM$) into an adrenal vein for 90 min produced relatively dose-and time-dependent inhibition in CA secretion evoked by ACh (5.32 mM), high $k^+$ (a direct membrane depolarizer, 56 mM), DMPP (a selective neuronal nicotinic receptor agonist, $100{\mu}M$ for 2 min), McN-A-343 (a selective muscarinic $M_1$ receptor agonist, $100{\mu}M$ for 4 min), Bay-K-8644 (an activator of L-type dihydropyridine $Ca^{2+}$ channels, $10{\mu}M$ for 4 min) and cyclopiazonic acid (an activator of cytoplasmic $Ca^{2+}$-ATPase, $10{\mu}M$ for 4 min). In adrenal glands simultaneously preloaded with nicorandil (1.0 mM) and glibenclamide (a nonspecific $K_{ATP}$-channel blocker, 1.0 mM), the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered to the considerable extent of the control release in comparison with that of nicorandil-treatment only. Taken together, the present study demonstrates that nicorandil inhibits the adrenal CA secretion in response to stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization from the isolated perfused rat adrenal glands. It seems that this inhibitory effect of nicorandil may be mediated by inhibiting both $Ca^{2+}$ influx and the $Ca^{2+}$ release from intracellular store through activation of $K_{ATP}$ channels in the rat adrenomedullary chromaffin cells. These results suggest that nicorandil-sensitive $K_{ATP}$ channels may play an inhibitory role in the regulation of the rat adrenomedullary CA secretion.

A Study on the Whitening Effect of the Oriental Medicinal Herb Forsythia suspensa Fruit as a Cosmetic Ingredient (천연한방소재인 연교 추출물의 미백 효과에 관한 연구)

  • Lee, Jung-Noh;Park, Jea-Hee;Kim, Sang-Woo;Yoo, Young-Kyoug;Lee, Ghang-Tai;Lee, Kun-Kook
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.2
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    • pp.79-86
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    • 2007
  • The aim of this study was to investigate the inhibitory effects of Forsythia suspensa fruit extracts (FSfE) ($0.1{\sim}1.0%$) and their active component on melanogenesis. FSfE dose-dependently inhibited melanin synthesis (up to $63.1{\pm}3.1%$ at the concentration of 1.0%) without cell cytotoxicity. We purifed one active compound from FSfE and identified its structure. It was identified as 4-[(3,4-Dimethoxyphenyl)methyl)]dihydro-3-[(4-hydroxy-3-methoxyphenyl)methyl]-2(3H)-furanone (arctigenin) by $^1H-NMR,\;^{13}C-NMR$, and Mass analysis. Arctigenin also inhibited melanin synthesis in a dose dependent manner (up to $52.7{\pm}3.1%$ at the concentration of $3.0{\mu}g/mL$). In order to verify the whitening activity of the cream containing 3% FSfE, we performed the clinical test with twenty five female volunteers for 8 weeks. Bioengineering analyses and visual assessment by doctors at the initial time point and 8 weeks after applications showed that cream containing FSfE have significant whiteining effect (paired t-test). From the results, we conclude that the FSfE can be used as a useful whitening agent.

Effect of Geranti Bio-Ge Yeast, a Dried Yeast Containing Biogermanium, on the Production of Antibodies by B Cells (B 세포의 항체 생산에 대한 게란티 바이오-게르마늄 효모의 영향)

  • Joo, Seong-Soo;Won, Tae-Joon;Lee, Yong-Jin;Kim, Min-Jung;Park, So-Young;Lee, Sung-Hee;Lee, Do-Ik;Hwang, Kwang-Woo
    • IMMUNE NETWORK
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    • v.6 no.2
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    • pp.86-92
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    • 2006
  • Background: Germanium compounds are increased to use in nutrient foods and medicines in terms of antibiotics to microbes, anticancer, modulation of immune system and neutralizing heavy metal toxins. Geranti Bio-Ge Yeast, containing stable organic germanium and bound to the yeast protein was developed by Geranti Pharm. LTD. and the modulation effect in the immune system was examined in vivo and in vitro. Methods: The compound, Geranti Bio-Ge Yeast, was fed to female Balb/c mice (each group has 10 mice) for 4 weeks and the yeast powder and steamed red ginseng powder were used as control during the same feeding time points. During 4 weeks there was no symptom to be considered, and after 4 weeks feeding all mice were sacrificed to check the changes of related immune cells and subsidiary responses (i.e. cell counting, FACS, MTT, LDH, PFC assay). Results: In pre-post comparison, B cell population was increased in the group of Geranti Bio-Ge Yeast in a dose dependent manner (100 to 800 mg/kg). However, the population of T cell, dendritic cell and macrophage was not comparably changed in all doses. The ability of cytokine production and proliferation was almost same level as shown in control group. In contrast, PFC assay informed that the compound increase the antibody production ability when fed over 200 mg/kg implying that the increase of PFC number might be due to the increase of B cells. Conclusion: Over the entire study, we concluded that the compound, Geranti Bio-Ge Yeast has better potential in immune response in terms of B cell proliferation than that of positive control, red ginseng, and the compound can be one of the future candidates for a new supplementary source improving immune system activity.

A Comparison Study of MMP Inhibitors' and Doxorubicin's Effects on the Apoptosis of U2OS Osteosarcoma Cell Line (U2OS 골육종 세포주의 세포자멸사에서 MMP억제제와 Doxorubicin 작용의 비교연구)

  • Moon, Jeong-Seok;Yeom, Bum-Woo
    • The Journal of the Korean bone and joint tumor society
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    • v.13 no.2
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    • pp.88-95
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    • 2007
  • Purpose: The purpose of this study was to compare the proapoptotic effects of matrix metal-loproteinase inhibitor (MMPI) and doxorubicin on wild-type p53 osteosarcoma cell line, socalled U2OS cell line. Materials and Methods: U2OS cells were treated with MMP inhibitor III (MMPI III) and doxorubicin, either respectively or simultaneously. In cells treated with doxorubicin, Fas-neutralizing antibody so called ZB4 was additionally treated to examine whether the doxorubicin played a role through the Fas/FasL pathway. Cells were analysed regarding to apoptosis and cell death by flow cytometry. Results: U2OS cells incubated with doxorubicin showed significant amount of cell death in dose-dependent manner. However, those incubated with MMPI III mostly remained viable state. In addition, there is no relationship between two drugs. Cells treated with doxorubicin and ZB4 at the same time did not show down regulation of apoptosis through inhibition of Fas/FasL pathway. Conclusion: It is important to re-examine MMP inhibitor's effect on other osteosarcoma cell line with wild-type p14 as well as wild-type p53 to evaluate its proapoptotic effect.

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A Study on the Effect of Physician Characteristics on the Cesarean Section Rate (의사의 일반적 특성이 재왕절개분만율에 미치는 영향에 관한 연구)

  • Cho, Eun-Hee
    • Research in Community and Public Health Nursing
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    • v.11 no.2
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    • pp.499-512
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    • 2000
  • The number of deliveries by cesarean section has increased internationally. However, The cesarean section rate is different by country to country. It is because each country has different social and cultural background and. practices its unique delivery policies. Hence, it is very important to understand the uniqueness that one country faces related with the cesarean section. In Korea, there have been many researches on the clinical. maternal. hospital and community factors and so on. However, few studies have attempted to reveal the physician factors in Korea because it is difficult to approach hospital records. So, in this study, the physician factors that influence the increase of cesarean section rate in Korea was investigated, and preliminary research agenda for policy establishment to keep the cesarean section rate from excessive increase was provided. In this study, all 2744 cesarean section deliveries performed by 36 physicians at the hospital was considered. and detailed delivery records of 12 months selected randomly from January 1996 to August 1998 was reviewed retrospectively. Chi-square analysis is used to examine the homogeneity of distribution of maternal, fetal, and clinical factors. In addition, multiple regression analysis is used to examine the effect of physician characteristics on the cesarean section rate. Physician characteristics as independent variable and the cesarean section rate as dependent variable was put in this analysis. Follows are the results of this study. 1) Total cesarean section rate is 34.8%. primary cesarean section rate is 12.5 % and repeated cesarean section rate is 22.3 %. Among the indications for the primary cesarean section, 15.6 % is for breech presentation. 40.2 % is for dystocia. 7.6 % is for fetal distress. and 36.6 % is for others. 2) There is positive correlation between physician's age and the cesarean section rate (p<0.001). And statistically significant correlation is found between the physician's educational attainment and the cesarean section rate (p<0.001). A physician with Ph.D degree has lower cesarean section rate than a physician with B.A only and M.A. degree (p<0.001). However. physician's gender, location of graduated university. position at the hospital, and the religious belief were not shown statistically significant relations with the cesarean section rate. 3) Among all cesarean sections in this study, only 15.4 % is performed during weekend. While 18.2 % is performed on monday only. This suggests that physicians may not prefer weekend operation of cesarean section. In addition, 86.1 % among all cesarean section operations is performed from 6 a.m. to 6 p.m. So the cesarean section rate could be related with a day of the week and a time of the day. From this results. there is a possibility that the physicians' personal comfort may influence the cesarean section rate.

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The Anticancer Effects and Drug Metabolic Enzyme Change by Oral Intake of Agrimonia Pilosa Ledeb (선학초(짚신나물) 경구투여시 항암효과 탐색 및 약물 대사효소의 변화)

  • Rhee, Si-Hyung;Jung, Hee;Lee, Ju-Ah;Go, Ho-Yeon;Choi, Yu-Kyung;Park, Jong-Hyung;Kim, Ji-Hye;Ko, Seong-Kyu;Jun, Chan-Yong
    • Journal of Society of Preventive Korean Medicine
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    • v.13 no.2
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    • pp.51-64
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    • 2009
  • Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.

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Induction of Spontaneous Neutrophil Apoptosis by 4-O-Methyl-Ascochlorin, A Prenyl Phenol Compound (프레닐 페놀계 항생제인 4-O-methyl-ascochlorin에 의한 호중구 세포사멸의 유도)

  • Son Dong-Aoon;Lee Sun-Young;Lee Min-Jung;Park Joo-In;Hong Young-Seob;Lee Yong-Hwan;Chang Young-Chae;Kwak Jong-Young
    • Journal of Life Science
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    • v.16 no.1
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    • pp.30-36
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    • 2006
  • Neutrophils are short-lived leukocytes that play a vital role in immune responses to bacteria, yeast, and fungi. This study was performed to investigate the effect of 4-O-methyl-ascochlorin (MAC), an anti-tumor, antibiotic, and anti-fungal prenyl-phenol compound on the spontaneous apoptosis of human neutrophils. MAC time- and dose-dependently accelerated the spontaneous apoptosis of human neutrophils. The effect of MAC on neutrophil apoptosis was blocked by pre-treatment of the neutrophils with specific inhibitors of pancaspase (zVAD-fmk), caspase-8 (zIETD-fmk), or caspase-3 (zDEVD-fmk). The cleavage of procaspase-8 and procaspase-3 was increased by MAC. Mitochondrial permeability, which was measured by the retention of $DiOC_6(3)$, was dose-de-pendently increased by MAC but the change of mitochondrial permeability was not blocked by pretreatment of neutrophils with zIETD-fmk. These results suggest that MAC induces neutrophil apoptosis by caspase-8-dependent but mitochondria-independent manner.

Anti-Obesity Activity of Euptelea Pleiosperma Ethanol Extract (Euptelea pleiosperma 에탄올 추출물의 항비만 활성)

  • Park, Jung Ae;Jin, Kyong-Suk;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.43 no.4
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    • pp.336-342
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    • 2015
  • Previously, Euptelea pleiosperma was identified as one of the useful sources containing anti-oxidative and anti-inflammatory activities for the first time in our research group. In this study, anti-obesity effect of E. pleiosperma ethanol extract (EPEE) was evaluated by using a pancreatic lipase enzyme inhibition assay and a cell culture model system. EPEE suppressed effectively pancreatic lipase enzyme activity dose dependently. Furthermore, EPEE significantly suppressed adipocyte differentiation, lipid accumulation, triglyceride contents, and triggered lipolysis activity on 3T3-L1 preadipocytes in a dose-dependent manner without cytotoxicity. Anti-adipogenic effect of EPEE was modulated by cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}(C/EBP{\alpha})$, $C/EBP{\beta}$ and peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ gene and protein expressions. Taken together, these results provide the important new insight that E. pleiosperma possesses anti-obesity activities such as pancreatic lipase inhibition, anti-adipogenic, and lipolysis effects. It might be utilized as promising sources in the fields of nutraceuticals. The identification of active compounds that confer anti-obesity activity of EPEE might be needed.

R-(-)-TNPA, a Dopaminergic $D_2$ Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla

  • Hong, Soon-Pyo;Seo, Hong-Joo;Lim, Dong-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.5
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    • pp.273-282
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    • 2006
  • The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$, an activator of L-type $Ca^2+$ channels and cyclopiazonic acid $(10\;{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were also inhibited. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

Statistical analyses in an occupational health study (산업보건연구에서의 통계학적 분석)

  • 백도명;최정근;손미아
    • The Korean Journal of Applied Statistics
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    • v.6 no.2
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    • pp.201-215
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    • 1993
  • The health status of workers in a foundry was analyzed in a study which consisted of evaluations of respiratory health together with environmental measurements. The results from environmental measurements showed values exceeding permissible exposure limits. A t-test was done with log transformed and untransformed data to examine the statistical significance for the noncompliance with exposure standards. For the analysis of categorical health outcomes, $\chi$-square test with 2 $\times$ 2 tables and logistic regression analysis were employed. For continuous variables, multiple linear regression was done against assessed risk factors. Pros and cons of different parameters in the compliance (or noncompliance) testing were presented. Respiratory function did not show any relation with occupational exposures, which may be due to the healthy worker effects. Strategies for controlling time dependent covariates were discussed in relation to the healthy worker effect. The scope of statistical analysis in occupational health studies is still limited in Korea without a suitable external comparison group such as credible vital statistics for the whole nation. Internal comparisons between different exposure status often result in unstable estimates of effect, and proportional morbidity study is discussed as an alternative potential research tool.

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