• Title/Summary/Keyword: Dose-response

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Clinical Efficacy of Transdermal Clonidine (St 155 BS) for Anesthetic Management in Hypertensive Patients (고혈압 환자 마취시 Transdermal Clonidine (St 155 BS)의 임상적 유용성)

  • Lee, Hyun-Hwa;Kim, Dong-Ok;Kim, Keon-Sik;Choi, Young-Kyoo;Shin, Ok-Young;Kwon, Moo-Il;Lee, Doo-Ik
    • The Korean Journal of Pain
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    • v.6 no.2
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    • pp.231-236
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    • 1993
  • Clonidine, a centrally-acting antihypertensive agent known to reduce central sympathetic outflow and modulate presynaptic transmitter's release, has shown to suppress central noradrenergic hyperactivity induced by immobilization stress in animals, by decreasing the MAC of halothane and the dose of narcotics required to prevent reflex cardiovascular response to noxious stimuli, and to have potent analgesic properties in humans. These characteristics suggest that clonidine might be a useful adjunct to the anesthetic management of patients with preexisting hypertension. Accordingly, we determined the clinical efficacy and safety on analgesia, sedation and hemodynamic stability in the perioperative period. Thirty patients(ASA physical status II-III) with a history of arterial hypertension, scheduled for elective orthopedic surgery were randomly assigned to two groups. We applied CPA-clonidine patch($6.9\;mg/cm^2$, 0.2 mg delivered daily) or placebo patch to each groups, 48 hours prior to induction of anesthesia. Antihypertensive medication was continued until the morning of the scheduled surgery. All patients received premedication of atropine and lorazepam, and induced anesthesia with thiopental and succinylcholine, and maintained with enflurane and 50% nitrous oxide, while sustaining the BP and pulse rate at acceptable range. For the relief of pain postoperatively, diclofenac and fentanyl were administered intramuscularly on demand. The results were as follows: 1) The change of hemodynamic responses in clonidine group was less compared to the placebo group. 2) Intraoperative anesthetic requirement for enflurane in clonidine group were significantly lower than placebo group. 3) Postoperative analgetic requirement in clonidine group were significantly lower than placebo group. In clonidine group, 5 cases out of 15 cases were required no analgetics, and the incidence of administration of additional fentanyl was decreased to 5 cases, comparing with 10 cases in placebo group.

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Influence of Histaminergic Receptor Activation on Catecholamine Secretion in The Perfused Rat Adrenal Gland (흰쥐 관류부신에서 Histamine 수용체 활성화가 Catecholamine 분비작용에 미치는 영향)

  • Lim, Dong-Yoon;Rho, Sang-Hyun
    • The Korean Journal of Pharmacology
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    • v.29 no.1
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    • pp.43-55
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    • 1993
  • The present study was conducted to examine the characteristics of histamine on catecholamine secretion in the isolated perfused rat adrenal gland and to clarify the mechanism of its secretory action. Histamine (37.5 to 150 ug) injected into an adrenal vein evoked a dose-dependent significant secretory response of catecholamines (CA) from the rat adrenal gland. However, upon the repeated injection of histamine (150 ug) at 120 min intervals, CA secretion was rapidly decreased after third injection of histamine. Tachyphylaxis to releasing effects of CA evoked by histamine was observed by the repeated administration. The histamine-induced CA secretion was markedly inhibited by the pretreatment with chlorisondamine, diphenhydramine, ranitidine, $Ca^{++}-free$ Krebs solution, nicardipine and TMB-8 while was not affected by pirenzepine. Moreover, the CA secretion evoked by ACh was considerably reduced by the prior perfusion of histamine $(6.8{\times}10^{-5} M)$ for 30 min. These experimental data suggest that histamine causes secretion of CA in a calcium dependent manner from the perfused rat adrenal gland and that its secretory effect is mediated through activation of both $H_1-$ and $H_2-histaminergic$ receptors located in adrenal medulla, which may be associated with stimulation of cholinergic nicotinic receptors.

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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.

Estimation of Estrogenic Activity by E-screen Assay and Stepwise Analysis of Endocrine Disruptors in Pilot Sewage Treatment Plant (파일럿 규모의 하수 처리 공정별 E-screen Assay에 의한 에스트로겐 활성과 내분비계 장애물질의 농도 평가)

  • Lee, Ji-Ho;Park, Jong-Yol;Ra, Jin-Sung;Duong, Cuong N.;Lee, Byoung-Cheun;Kim, Sang-Don
    • Journal of Korean Society of Environmental Engineers
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    • v.28 no.7
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    • pp.697-703
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    • 2006
  • Endocrine disruptors were measured with GC/MS in effluents discharged from sewage treatment processes in pilot scale for the purpose of water reuse. From that analysis, we compared the removal rate of them by treatment processes. Nonylphenol was mainly detected in effluents and high concentration from 0.36 to 0.94 ${\mu}g/L$. $17{\beta}$-estradiol(E2) and $17{\alpha}$-ethynylestradiol(EE2) were detected as below the limit of detection in effluent. Endocrine disruptors were removed effectively in the range from 50 to 100% by treatment process. EC50 value($9.0{\times}10^{-3}$ M) of $17{\beta}$-estradiol(E2) by dose response curve of E-screen assay has higher than that of bisphenol A($2.736{\times}10^{-5}M$) and p-octylphenol($9.760{\times}10^{-6}$ M). These results showed that alkylphenols have lower relative estrogen potency than other estrogens such as $17{\beta}$-estradiol(E2). Calculated estrogenic activity(ng-EEQ/L) was 2 times higher than measured total estrogenic activity which estimated by E-screen assay. Moreover estrogenic activity of effluent by treatment process showed very low as below 1 ng-EEQ/L.

Bone Marrow Cell Proliferation Activity through Intestinal Immune System by the Components of Atractylodes lancea DC. (창출 성분의 장관면역 자극을 통한 골수세포 증식활성)

  • Yu, Kwang-Won;Shin, Kwang-Soon
    • Korean Journal of Food Science and Technology
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    • v.33 no.1
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    • pp.135-141
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    • 2001
  • Of hot-water extracts prepared from 10 herbal components of Sip-Jeon-Dae-Bo-Tang, Atractylodes lancea DC. (ALR) and Panax ginseng C.A. Meyer (PG) showed the most potent bone marrow cell proliferation activity through intestinal immune system whereas other extracts did not have the activity except for Astragalus membranacues Bunge (ASR) and Angelica acutiloba Kitagawa (AR) having low activity. Especially, ALR had the potent activity irrespective of classes of ALR, a place of production and the condition of breeding. In addition, we found that hot-water extract from Atractylodes lancea DC rhizomes (ALR-0) contributed mainly to Peyer's patch cells mediated-hematopoietic response of Sip-Jeon-Dae-Bo-Tang. ALR-0 was further fractionated into MeOH-soluble fraction (ALR-1), MeOH-insoluble and EtOH-soluble fraction (ALR-2), and the crude polysaccharide fraction (ALR-3). Among these fractions, only ALR-3 showed potent stimulating activity for proliferation of bone marrow cells mediated by Peyer's patch cells, dose-dependently. In treatments of ALR-3 with $NaIO_4,\;NaClO_2$ and pronase, all significantly reduced the intestinal immune system modulating activity of ALR-3, and the activity of ALR-3 was much affected by $NaIO_4$ oxidation particularly. These results reveal that macromolecules, such as polysaccharide, rather than low-molecular-weight substances, are the potent intestinal immune system modulating compound of ALR.

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Effects of Agaricus blazei Murill Water Extract on Immune Response in BALB/c Mice (신령버섯(Agaricus blazei Murill) 열수 추출물의 면역 활성에 미치는 영향)

  • Kang, In Soon;Kim, Rang Ie;Kim, Gwang Sub;Kim, Na Ri;Shin, Joong Yup;Kim, Chaekyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1629-1636
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    • 2015
  • The edible mushroom Agaricus blazei Murill is known to have many physiological functions, including antitumor, antiviral, and anti-inflammatory effects. Aqueous extracts were obtained by extracting A. blazei in water at $90^{\circ}C$ for 15 h, followed by spray-drying with dextran at a 70:30 ratio. In this study, we examined the immunomodulatory effect of A. blazei Murill water extract (ABM) in BALB/c mice. Mice were administered orally with 4, 20, and 100 mg/kg of ABM for 21 days. ABM-treated mice did not show significant differences in body and organ weights compare to saline-treated control mice. Splenocytes isolated from ABM-administered mice revealed similar levels of cellularity and proliferation compared to control mice, whereas they showed increased natural killer (NK) cell activity and decreased IL-4 and IL-12 production. Different from in vivo results, splenocytes isolated from normal mice showed increased proliferation and $INF-{\gamma}$ production following ABM treatment in vitro. In addition, ABM treatment enhanced macrophage proliferation and nitric oxide (NO) production in a dose-dependent manner. However, ABM had no effect on LPS-induced NO production. These results suggest that A. blazei modulates immune function by increasing NK cell activity and macrophage function.

Effect of African Mango (Irvingia gabonesis, IGOB 131TM) Extract on Glucose Regulation in STZ-Induced Diabetes (Streptozotocin으로 유발한 당뇨동물 모델에서 아프리칸 망고 추출물의 혈당 조절 효과)

  • Ha, Yejin;Lee, Minhee;Kwon, Han Ol;Lee, Yoo-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1607-1611
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    • 2015
  • This study investigated the regulatory effects of African mango (Irvingia gabonesis, IGOB $131^{TM}$) extract on blood glucose level in streptozotocin (STZ)-induced diabetic rats. Experimental groups were treated with two different doses of IGOB $131^{TM}$ (1% and 2% in each AIN93G supplement) for 5 weeks [4 weeks pre-treatment and 1 week post-STZ treatment (60 mg/kg body weight)]. STZ-induced diabetic rats showed significantly reduced body weight gain compared to normal control (NC). Oral glucose tolerance test (OGTT) was measured using glucose oxidase-peroxidase reactive strips. The area of under the curve for the glucose response from OGTT in STZ-induced diabetic rats was higher than that of NC rats, and there was a significant difference between the DM and the IGOB $131^{TM}$-treated groups. Serum glucose levels after sacrifice were significantly lower in the IGOB $131^{TM}$ group than the DM group. However, there was no statistical difference between low- and high-dose treatments. Serum insulin levels increased by 234.4% and 175.9%, respectively, upon treatment with IGOB $131^{TM}$. Serum lipid profiles were not significantly different among the experimental groups. The tested samples had no effects on serum levels of lipid profiles (triglyceride, total cholesterol, low density lipoprotein/very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol). These results suggest that IGOB $131^{TM}$ is able to ameliorate diabetes by reducing serum glucose levels that may result from increased insulin levels.

Anti-inflammatory Action of Phenolic Compounds from Gastrodia elata Root

  • Lee, Ji-Yun;Jang, Young-Woon;Kang, Hyo-Sook;Moon, Hee;Sim, Sang-Soo;Kim, Chang-Jong
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.849-858
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    • 2006
  • Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The antiinflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl-methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.

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.

Anti-hyperglycemic and Anti-hyperlipidemic Activities of Acanthopanax Senticosus Herbal Acupuncture in C57BL/6J ob/ob Mice

  • Lee, Sang-Keel;Kim, Yong-Suk;Kang, Sung-Keel
    • Journal of Acupuncture Research
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    • v.23 no.2
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    • pp.1-19
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    • 2006
  • Objectives : The aim of this study was to investigate the hypoglycemic and hypolipidemic activities and mechanisms of Acanthopanax senticosus (AS) herbal acupuncture. Methods : Anti-diabetic and anti-steatotic activity of the AS herbal acupuncture was investigated on C57BL/6J ob/ob mice. After random grouping at the age of 9 weeks, the herbal acupuncture groups were injected subcutaneously at the left and right Gansu (BL18) corresponding acupuncture points alternately on exactly the same time every day with 0.1ml of either 400 mg/kg or 800 mg/kg of AS (AS400 and AS800) for 8-week period. As a positive control, metformin was administrated at a dose of 300 mg/kg (MT300). Body weights were measured weekly, and on every other week blood was collected for blood glucose analysis. At the end of study, blood was also collected for determination of plasma insulin and lipid levels, after which they were killed and periepidydimal fat, liver, muscle, and pancreas were immediately removed. The removed tissues were instantly soaked in liquid nitrogen and stored at $-70^{\circ}C$ for morphological examination and mRNA analysis. Results : The AS herbal acupuncture significantly prevented weight gain on C57BL/6J ob/ob mice. The AS herbal acupuncture lowered blood glucose and improved glucose tolerance in C57BL/6J ob/ob mice. The increase of insulin response during the OGTT was inhibited by the AS herbal acupuncture. Insulin sensitivity of skeletal tissue was enhanced. Plasma lipid levels were significantly improved in the AS herbal acupuncture groups. The AS herbal acupuncture decreased hepatic lipogenesis and hepatic triglyceride production, and increased fatty acid (FA) transporter that involves in FA uptake. The AS herbal acupuncture inhibited the increase of liver mass by prevention of the accumulation of TG but did not inhibit weight gain of fat tissue on C57BL/6J ob/ob mice. Conclusion : In summary, we have demonstrated several unique properties of the AS herbal acupuncture in decreasing body weight, and reversing insulin resistance and hepatic steatosis in ob/ob mice. This AS herbal acupuncture acts as an insulin sensitizer and specifically decreases circulating glucose and lipids, and suppresses hepatic lipogenesis.

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