• The Korean Journal of Pain
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• 제6권2호
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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.

• 대한약리학회지
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• 제29권1호
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• pp.43-55
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• 1993

흰쥐 관류부신에서 histamine의 catecholamine (CA) 분비작용의 특성과 기전을 규명코자 연구한 결과는 다음과 같다. Histamine $(37.5{\sim}150\;{\mu}g)$을 부신정맥내에 주사 하였을 때 현저한 용량 의존성의 CA 분비작용을 나타내었다. 그러나 histamine $(150\;{\mu}g)$을 120분 간격으로 반복 투여시 제 3차 투여시부터는 CA 분비효과가 뚜렷이 감소하였다. 즉, histamine의 반복투여로 인한 반응급강현상을 관찰할 수 있었다. Histamine의 CA 분비작용은 chlorisondamine, diphenhydrarmine, ranitidine, $Ca^{++}-free$ Krebs 용액의 관류, nicardipine 및 TMB-8 등의 전처치로 유의하게 억제 되었으나 pirenzepine의 전처치에 의해서는 별다른 영향을 받지 않았다. 더우기 histamine $(6.8{\times}10^{-5}M)$으로 30분간 관류시킨 후에 ACh $(50{\mu}g)$의 CA 분비작용이 상당히 억제됨을 나타내었다. 이상과 같은 연구 결과로 보아 histamine은 흰쥐 적출관류 부신에서 현저한 CA 분비작용을 나타내었으며 칼슘 의존성이었다. 이러한 CA 분비작용은 $H_1-$ 및 $H_2-$ 양수용체의 활성화를 통해서 일어나며 또한 부신의 nicotine 수용체와도 관련성이 있는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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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.

• 대한환경공학회지
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• 제28권7호
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• pp.697-703
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• 2006

물 재이용 목적으로 설계한 pilot scale의 하수 처리공정에서 배출되는 방류수 중 내분비계 장애물질을 GC/MS로 분석하였고, 처리 공정별로 제거율을 비교하였다. 각 처리 공정별 방류수에서 nonylphenol이 주로 검출되었고, 평균 $0.36{\sim}0.94$ ${\mu}g/L$으로 높게 검출되었으나, E2와 EE2는 처리수에서 정량 이하로 검출되었다. 내분비계 장애물질은 처리 공정별로 $50{\sim}100%$의 제거율을 보여주었다. E-screen assay에 의해 얻어진 양-반응 곡선에서 E2의 EC50값은 $9.0{\times}10^{-3}$ M로 bisphenol A와 p-octylphenol의 EC50값인 $2.736{\times}10^{-5}$ M, $9.760{\times}10^{-6}$ M에 비해 매우 높았다. 이는 알킬페놀류가 E2에 대한 상대적인 에스트로겐 활성도가 매우 낮음을 보여주었다. 환경 호르몬 농도와 이 물질의 상대적인 에스트로겐 활성도에 근거하여 계산된 에스트로겐 활성도(ng-EEQ/L)는 E-screen assay에 의해 실측한 총 에스트로겐 활성도(ng-EEQ/L)에 비해 평균 2배의 높은 활성도를 보여 주었다. 각 처리 공정별 방류수의 에스트로겐 활성도는 1 ng-EEQ/L 이하의 매우 낮은 활성도를 보여주었다.

• 한국식품과학회지
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• 제33권1호
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• pp.135-141
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• 2001

십전대보탕의 10가지 구성 천연물을 열수추출하여 장관면역 활성을 비교 검토한 결과, 창출(Atractylodes lancea DC., ALR)과 인삼(Panax ginseng C.A. Meyer, PG)에서는 높은 활성을 나타내었으나 약한 활성을 갖는 황기(Astragalus membranacues, ASR)와 당귀(Angelica aculiloba Kitagawa, AR)를 제외하고는 어떤 생약에서도 거의 활성을 갖지 않았다. 한편 이러한 활성을 가진 생약(ALR, PG와 ASR) 중에서도 특히 ALR만이 종류, 생산지 및 육종조건에 관계없이 항상 일정하게 높은 활성을 보여주어 창출의 열수추출물 획분(ALR-0)이 십전대보탕의 장관면역 활성에 중요하게 관여하는 시료로 선정되었다. ALR-0 획분은 다시 용매별로 분획되어 메탄올-가용성 획분(ALR-1), 메탄올-불용성/에탄올-가용성 획분(ALR-2) 및 조다당 획분(ALR-3)으로 조제되었으며 이들의 활성을 측정한 결과, 단지 ALR-3 획분만이 Peyer's patch를 통한 골수세포의 증식을 활성화시키는 장관면역 활성을 시료농도에 의존적으로 나타내었으며 그 외의 획분에는 활성이 거의 없었다. 한편 ALR-3 획분을 $NaIO_4,\;NaClO_2$ 및 pronase로 처리한 후 활성을 측정한 결과, 모든 처리군에서 활성이 감소되었으며 특히 periodate 산화에 의해 심한 활성감소를 보였다. 이러한 결과를 토대로 십전대보탕의 장관면역 활성은 10종의 생약 중에서도 특히 창출이 중요하게 활성에 관여하는 것으로 보이며 다양한 용매별 분획을 통해 저분자보다는 에탄올에 침전된 고분자가 주요 함유물질인 조다당 획분이 장관면역 활성에 관여하는 것으로 추정되었다. 또한 periodate 산화에 의해 활성이 크게 감소되는 것으로 보아 주로 다당류가 창출의 장관면역에 중요한 활성물질인 것으로 생각된다.

• 한국식품영양과학회지
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• 제44권11호
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• pp.1629-1636
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• 2015

본 연구에서는 신령버섯의 면역기능 개선 효과를 마우스를 이용한 동물 모델에서 면역기관의 무게와 세포증식, 자연살해세포 활성, 사이토카인 분비능을 측정하고 대식세포 증식과 활성을 측정하여 평가하였다. BALB/c 마우스에 저(4 mg/kg), 중(20 mg/kg), 고(100 mg/kg) 농도의 신령버섯을 21일간 경구로 투여하였다. 마우스를 희생하여 체중 및 면역장기 무게, 비장세포의 증식과 사이토카인 생성, 자연살해세포의 활성을 측정하였다. 그 결과 신령버섯은 마우스의 체중, 간, 비장, 흉선의 무게에 영향을 주지 않았으며, 비장세포의 증식에 유의한 효과가 없었다. 또한 비장세포의 IL-4과 IL-12 생성을 억제하였으며, 마우스 자연살해세포의 활성을 현저하게 증가시켰다. 정상 마우스에서 분리한 비장세포에 신령버섯을 처리한 in vitro 실험에서는 신령버섯 $5{\sim}100{\mu}g/mL$에서 농도 의존적으로 비장세포의 증식과 $IFN-{\gamma}$ 생성을 증가시켰다. 신령버섯은 대식세포인 RAW 264.7 세포의 증식을 $100{\mu}g/mL$ 농도까지 농도 의존적으로 증가시켰으며, 대식세포에 의한 NO의 생성을 농도 의존적으로 증가시켰다. 이상의 결과를 종합해 보면 신령버섯을 마우스에 3주간 투여하면 동물의 체중, 면역장기의 무게와 면역세포의 증식에는 영향을 미치지 않지만 자연살해세포의 활성을 70% 가량 증가시키며 IL-4와 IL-12의 생성을 억제한다. 정상 마우스에서 분리한 비장세포에 신령버섯을 처리하면 세포증식과 $IFN-{\gamma}$ 분비가 증가되고, 대식세포인 RAW 264.7 세포의 증식과 NO 생성이 증가된다. 따라서 신령버섯은 바이러스에 감염된 세포나 암세포를 죽이는 자연살해세포와 대식세포의 활성을 증가시켜 면역반응 조절에 중요한 역할을 할 것으로 기대된다.

• 한국식품영양과학회지
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• 제44권11호
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• pp.1607-1611
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• 2015

본 연구는 당뇨유발모델 쥐에서 아프리칸 망고(Irvingia gabonesis, IGOB $131^{TM}$) 추출물의 혈당 조절 효과를 알아보기 위해 SD계 수컷 흰쥐에 IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%(IGOB $131^{TM}$ 353 mg/kg body weight, IGOB $131^{TM}$ 706 mg/kg body weight)와 pinitol을 5주간 매일 강제 경구 투여하였다. 그리고 streptozotocin을 복강 주사하여 당뇨를 유발시킨 후 경구 당부하 검사(OGTT)를 실시하였다. 정상군에 비해 당뇨 유발군(DM, pinitol, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%)의 체중 증가는 유의적으로 감소하였고, 당뇨 유발군 간의 유의적인 차이는 나타나지 않았다. 경구 당부하 검사 결과에서 DM군이 정상군에 비해 유의적으로 높았고, pinitol군, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%군은 DM에 비해 각각 39.70%, 33.00%, 29.67% 유의적으로 감소하였다. 혈청 glucose 농도는 정상군에 비해 당뇨 유발군에서 유의적으로 높게 나타났고, pinitol, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%군은 DM에 비해 유의적으로 감소하였다. 또한 혈청 insulin 농도는 정상군에 비해 당뇨 유발군에서 유의적으로 낮게 나타났고, pinitol, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%군은 DM에 비해 유의적으로 증가한 것으로 나타났다. 따라서 아프리칸 망고 추출물이 STZ 유도 당뇨쥐의 혈청 insulin 함량을 개선시켜 혈청 glucose를 감소하는 효과가 있는 것으로 사료된다.

• Archives of Pharmacal Research
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• 제29권10호
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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.

• IMMUNE NETWORK
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• 제6권2호
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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.

• Journal of Acupuncture Research
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• 제23권2호
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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.