• Journal of Chest Surgery
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• v.34 no.11
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• pp.809-822
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• 2001

Background: Ischemic preconditioning(IP) is known to be effective in the protection of myocardial necrosis, arrhythmia, and the restoration of the myocardial function in the ischemia-reperfusion state of the heart. However the exact mechanism is not clearly understood. The purpose of this study was to elucidate the trigger mechanism 7f IP on the restoration of the myocardial function after ischemia-reperfusion. Material and Method: By connecting a Langendorff perfusion apparatus with an isolated heart of a rat, the normal temperature of the heart was maintained. The experiment was conducted in seven groups, which were divided according to the preconditioning stimuli and blockage methods Group I(n=10) was a group without IP, Group II(n=10) a group of three-minute IP, Group III(n=10) a group of PEIP, Group IV(n=10) a group of clonidine IP, Group V(n=10) a group of If after reserpine, Group Vl(n=10) a group of PE & prazosin IP, and Group Vll(n=10) a group of clonidine & yohimbine IP. Hemodynamic parameters of DP, LVEDP, $\pm$dP/dT and the changes of perfusion in the coronary artery were evaluated. Result: Developed pressure and +dP/dT changed per unit time. After 20 minutes of reperfusion, those of Group II and III were 63.1$\pm$3.7%, 64.8$\pm$4.6% and 64.5$\pm$4.6%, 63.8$\pm$4.4%, which improved more significantly than those of Group I(P<0.05), However, there were no significant differences between the Groups V and Vl, and Group I. Conclusion: The Brief ischemic preconditioning and pharmacological preconditioning using $\alpha$-receptor sympatho-mimetics have protecting effects on the restoration of myocardial function after reperfusion. And the protecting effect of preconditioning seems to be related to sympathetic neurotransmitters and to the selective action of the $\alpha$$_1$-adrenergic receptor.

• Journal of Life Science
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• v.28 no.1
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• pp.116-129
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• 2018

Living creatures possess long-conserved mechanisms to maintain homeostasis in response to various stresses. However, chronic and continuous exposure to stress can result in the excessive production of stress hormones, including catecholamines, which have harmful effects on health. Studies on the relationship between the sympathetic nervous system (SNS) and cancer have been conducted based on the traditional hypothesis that stress can promote cancer progression. Many preclinical and epidemiological studies have suggested that the regulation of ${\beta}$-adrenergic signaling, which mediates SNS activity, can suppress the progression of solid tumors. SNS activation has highly pleiotropic effects on tumor biology, as it stimulates oncogenes, survival pathways, the epithelial - mesenchymal transition, and invasion. Moreover, it inhibits DNA repair and programmed cell death and regulates the tumor microenvironment, including immune cells, endothelial cells, the extracellular matrix, mesenchymal cells, and adipocytes. Although targeted therapies on the molecular basis of tumor proliferation are currently receiving increased attention, they have clinical limitations, such as the compensatory activation of other signaling pathways, emergence of drug resistance, and various side effects, which raise the need for pleiotropic cancer regulation. This review summarizes the effects of the SNS on the development and progression of cancer and discusses the clinical perspectives of ${\beta}$-blockade as a novel therapeutic strategy for this disease.

• Journal of Haehwa Medicine
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• v.21 no.2
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• pp.95-104
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• 2013

스트레스로 인한 인체의 반응은 중추신경계, 시상하부, 변연계 및 기타 표적기관으로부터 시작되는데, 자율신경계 반응, 내분비계 반응, 면역계 반응 등을 통하여 복합적인 신체 증상으로 발현되며, 스트레스 상황에서는 시상하부-뇌하수체-부신 축 (HPA axis)과 교감신경계의 작용으로 여러 신경전달물질 방출에 변화가 생기며 이러한 변화는 면역기전에 중요한 역할을 하고 일부는 면역세포의 활성에 직접적으로 영향을 미쳐 신체 각종 질병의 원인이 될 것으로 추정된다. 한의학에서는 천인상응(天人相應)의 관점에서 육기(六氣)를 생체자극의 외적 요인으로 간주하고, 생체내적 현상인 정신이 외적 자극을 통하여 나타나는 생체반응을 칠정(七情)으로 보았으며, 이러한 관점에서 스트레스는 신체에 오장(五臟)의 허실(虛實), 혈허(血虛), 정손(精損), 기역(氣逆), 기(氣)의 순환장애, 담연(痰涎), 화(火) 등의 병적인 요인을 만들어 준다. 본 연구에서 재료로 사용된 호초 (Piper nigrum Linne)는 후추나무의 과실을 말린 것으로서 세계적으로 널리 사용되는 향신료이며, 한의학에서는 온중제한하기(溫中除寒下氣), 쾌격소담(快膈消痰), 해독(解毒)등의 효능으로 한담식적(寒痰食積) 완복냉통(脘腹冷通) 곽란(癨亂) 토사(吐瀉)등의 치료에 활용되어 왔다. 특히 쾌격소담(快膈消痰)하는 작용은 정신적 스트레스에 유효할 것으로 생각되므로 본 연구에 이용하게 되었다. 실험동물은 ICR계 생쥐를 이용하였으며, 심리적 스트레스는 옆쪽 cage에서 다른 마우스의 신체에 가해지는 전기 충격을 하루 1시간 동안 지켜보게 하는 것으로 유발하였으며, 이 상태에서 약물을 투여한 그룹을 실험군, 그렇지 않은 그룹을 대조군으로 하였다. 정상군은 아무런 자극 없이 하루 1시간 동안 일정 공간에 가두어 두는 것으로 하였다. 실험 결과, 호초(胡椒) 추출물을 100mg/kg/day 용량으로 5일간 투여한 실험군은 아무런 처치를 하지 않은 대조군에 비해 혈장 중 corticosterone 함량이 유의하게 감소되었고, 뇌에서의 noradrenalin 분비량이 유의하게 증가되었으며, plus maze test에서의 머무름 시간이 연장되는 것으로 나타나 호초(胡椒)가 심리적 스트레스를 효과적으로 억제하고 진정작용이 있는 것으로 사료되나 구체적인 작용기전 및 인체에서의 효과에 대해서는 향후의 보다 자세한 연구가 필요할 것으로 생각된다.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.21-31
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• 1991

When administered intracerebroventricularly (icv), cholinergic nicotinic agents, nicotine and DMPP, as well as cholinergic muscarinic agents, muscarine and bethanechol, produced pressor responses in urethane-anesthetized vagotomized rabbits. The response patterns to nicotine and to DMPP were similar, while the bethanechol response resembled the muscarine pattern. The pressor response to nicotine and DMPP was markedly inhibited by icv mecamylamine but not by icv pirenzepine, whereas the response to muscarine and bethanechol was inhibited by icv pirenzepine but not by icv mecamylamine, suggesting that both nicotinic and muscarinic receptors in the brain are involved in the action. Intravenous pretreatments of animals with regitine, reserpine, enalapril, saralasin, both regitine and enalapril, both regitine and saralasin, SK&F-100273 did not prevent the pressor response to nicotine and muscarine. Iv pretreatments with both regitine and SK&F-100273 inhibited the nicotine response without affecting the muscarine response, whereas pretreatments with three agents, regitine, enalapril and SK&F-100273, inhibited the muscarine response. The nicotine-induced elevated blood pressure as well as the muscarine-induced were lowered by regitine but not by enalapril or by SK&F-100273. Enalapril was without effect on the nicotine hypertension in rabbits treated with regitine or both regitine and SK&F-100273, whereas SK&F-100273 lowered the nicotine hypertension in regitine-treated animals. Enalapril did not enhance the lowering effect of SK&F-100273 in regitine-treated ones, nor did it cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and SK&F-100273. Likewise, SK&F-100273 did not cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and enalapril. These data suggest that the nicotine-induced hypertensive state is related to at least two systems in the periphery-sympathetic and vasopressin, whereas in the muscarine-induced hypertensive state three systems in the periphery are involved, i.e., the sympathetic, vasopressin and angiotensin system. The hypotensive effect of regitine on basal arterial blood pressure levels of rabbits was not influenced by pretreatment with either of enalapril or SK&F-100273, but significantly potentiated by treating with both enalapril and SK&F-100273, suggesting participation of the sympathetic and the renin-angiotensin system as well as the vasopressin system in maintenance of arterial blood pressure.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.479-486
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• 1994

Effects of catecholamines and the site of receptor of catecholamines were investigated in the longitudinal muscle of the rumen. In order to this experiment, specimens were obtained from 35 Korean Native Cattles, 2-3 years old, in the Kwang-ju area slaughterhouse. Longitudinal muscle strips of rumen were made from sample, and then measured the isometric contraction with physiograph in $37{^{\circ}C}$ organ bath. The results were summarized as follows. 1. 30% of all strips showed rhythmic contraction after short incubation time. 2. Relaxation produced by catecholamines in this preparations increased in a dose-dependant manner. 3. Isoproterenol(${\beta}$-agonist) caused relaxation, but phenylephrine(${\alpha}_1$-agonist) and xylazine(${\alpha}_2$-agonist) were unaffected. 4. The relaxation induced by epinephrine and norepinephrine were not affected by phentolamine(${\alpha}$-blocker) and prazosin(${\alpha}_1$-blocker), yohimbine(${\alpha}_2$-blocker). But propranolol(${\beta}$-antagonist) abolished the effect of catecholamines on relaxation. 5. It is concluded that catecholamines produced relaxation in the longitudinal muscle of rumen via the ${\beta}$-adrenoceptor.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.61-74
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• 1992

Influence of the blockade of the three major pressor systems-sympathetic nervous system (SNS), renin-angiotensin system (RAS) and vasopressin system-on the pressor responsiveness to norepinephrine (NE), angiotensin II (AII), and vasopressin (VP) as well as on basal blood pressure (BP) levels was investigated in urethane-anesthetized rabbits. To block the SNS and RAS, chlorisondamine (CS) and pirenzepine (PZ), sympathetic ganglionic blockers, and enalapril (ENAL), an inhibitor of angiotensin converting enzyme, respectively were used. And for suppressing the VP system bremazocine (BREM), a kappa opiate receptor agonist shown to suppress plasma levels of VP, was employed. Each of CS (0.4 mg/kg), ENAL (2 mg/kg), and BREM (0.25 mg/kg) produced almost same levels of steady hypotensive state. The hypotensive effect of BREM was significantly attenuated by desmopressin, a synthetic VP-like analogue, suggesting the hypotension being at least in part due to suppression of plasma levels of VP. CS, ENAL and BREM elicited further fall of the BP which had been lowered by ENAL or BREM, CS or BREM, and CS or ENAL, respectively. The hypotension produced by both CS and PZ together with either of ENAL or BREM was more marked than that produced by the three drugs other than CS. CS potentiated the pressor response not only to NE but to AII and VP. The pressor effect of AII was increased by ENAL and BREM, too. The pressor response to VP was also enhanced by BREM. Blockade of ${\alpha}-adrenergic$ receptors with phentolamine or phenoxybenzamine potentiated the pressor response to AII and that to VP. The results on basal BP levels indicate that the three major pressor systems are all participating in control of BP, but SNS has the greatest potential for supporting BP. The finding that blockade of one of the pressor systems induced enhanced pressor responsiveness to the pressor hormone of that particular system as well as to the pressor hormone(s) of the other systems(s) provides evidence for important interactions among the three major pressor systems.

• Journal of Chest Surgery
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• v.34 no.6
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• pp.485-489
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• 2001

Background: The most important factor in preventing sternal complications is stable sternal approximation. We have tried to find the most effective sternal closure method by examining the incidence of sternal dehiscence with or without infection in patients with cardiac surgery through median sternotomy. Material and Method: This study was performed in 489 patients over 45 years of age with median sternotomy for open cardiac surgery. Simple closure with interrupted 6 wires was performed in 159 patients, figure-of-8 closure technique in 119, overlapping interrupted closure using 10 wires in 150, and combined closure technique of interrupted simple closure and figure-of-8 suture closure in 61. Two hundred thirty-four patients underwent valve and aortic operations and 213 patients coronary artery bypass surgery. Result: Sternal dehiscence with or without infection occurred in 12 (2.5 %) patients. The complication developed in 5 of 159 patients (3.1%) with six interrupted simple closure, in 4 of 119 patients (3.4%) with figure-of-8 closure, and in 3 of 150 patients (2.0%) with overlapping interrupted closure using 10 wires, but there was no complication in 61 patients with combined closure technique (relative risk for other closure techniques, p<0.05). There was no significant difference in the incidence of the sternal complication between valve and aortic operation group and coronary artery bypass group (3.0% vs 2.3%, not significant), but diabetes mellitus was a significant independent risk factor (odds ratio and multivariate analysis, p<0.05). Conclusion: The sternal closure technique that combines simple interrupted suture closure and figure-of-8 suture closure may be a more useful technique to enhance sternal stabilization compared to other closure techniques, such as simple interrupted closure, 8-figure closure, and overlapping interrupted closure.

• Journal of Chest Surgery
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• v.34 no.11
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• pp.823-830
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• 2001

Background: Paraplegia is a serious complication of thoracic or thoracoabdominal aortic operations, which is related to ischemic injury of the spinal cord induced by low perfusion pressure during cross clamping of the aorta. Ischemic preconditioning of heart or brain with reversible sublethal ischemic injury induces resistance to subsequent lethal ischemia. The aim of this study is to investigate whether ischemic tolerance could be induced by the preconditioning of the spinal cord using swine model. Material and Method: The animals were randomly assigned to three groups: sham group(n=3), control group(n=6) and pre-conditioning group(n=8). In the sham group, we performed the left thoracotomy only without any ischemic injury. In the preconditioning group, the swine received reversible spinal cord ischemic injury by aortic clamping for 20 minutes, whereas control group had no previous aortic cross- clamping. Forty-eight hours later, the aorta was clamped for 30 minutes in both groups. Neurological examination was done 24 hours later, then the animals were euthanized for histopathology and malonedialdehyde(MDA) spectrophotometry assay of the spinal cord. Result: Statistically significant difference in neurological outcome was observed between the control and preconditioning groups at 24 hours after ischemic injury. The incidence of paraplegia and severe paresis was 100% in the control group, and 62.5% in the preconditing group(p=0.028). There was no statistically significant difference in histopathology and MDA assay of the ischemic spinal cord between these two groups with borderline statistical difference in MDA assay(p=0.0745). Conclusion: In the present swine study, ischemic preconditioning could induce tolerance against 30 minute ischemic insult of the spinal cord, although the animals did not completely recover(stand-up or walk). We expect that combining this preconditioning with other currently existing protection methods might lead to a synergistic effect, which warrants further investigation.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.382-395
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• 1992

GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.

• Journal of Sasang Constitutional Medicine
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• v.10 no.2
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• pp.533-564
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• 1998

In order to know the effect of proliferation and differentiation on edipocyte 3T3-L1 by prescriptions and herbs, Taeyangin(太陽人)'s Okapijangcheok-tang(五加皮壯脊湯) Mihudeungsikjangtang Acanthopanacis Cortex(五加皮) Phragmitis Rhizoma(蘆根) and Taeumin(太陰人)'s Taeumjowi-tang(太陰調胃湯) Cheongsimyonja-tang(淸心蓮子湯) Cheongpaesagan-tang(淸肺瀉肝湯) Galkeunbupyong-tang(葛根浮萍湯) Coicis Semen(薏苡仁) Rhei Undulati Rhizoma(大黃) Mori Cortex(桑白皮) Ulmi Cortex(楡根白皮) Holotrichia Vermiculus Kalopanaxii Cortex(海桐皮) Ephedrae Herba(麻黃) Imperatae Rhizoma(白茅根), were used and had some effects. 1. The proliferation effect of edipocyte 1) At the Taeyangin(太陽人)'s prescriptions and herbs, Okapijangcheok-tang(五加皮壯脊湯) Mihudeungsikjang-tang Acanthopanacis Cortex(五加皮) have a control effect at the boiling water-extract and ethyl alcohol-extract. Phragmitis Rhizoma(蘆根) have a control effect at the ethyl alcohol-extract. 2) At the Taeyangin(太陽人)'s prescriptions and herbs, Taeumjowi-tang(太陰調胃湯) Cheongsimyonja-tang(淸心蓮子湯) Cheongpaesagan-tang(淸肺瀉肝湯) Galkeunbupyong-tang(葛根浮萍湯) have a control effect at the boiling water-extract and ethyl alcohol-extract. Coicis Semen(薏苡仁) Rhei Undulati Rhizoma(大黃) Morl Cortex(桑白皮) Ulmi Cortex(楡根白皮) Kalopanaxii Cortex(海桐皮) · Ephedrae Herba(麻黃) of the boiling water-extract, Holotrichia Vermiculus Kalopanaxii Cortex(海桐皮) of ethyl alcohol-extract have a control effect on edipocytes. Rhei Undulati Rhizoma(大黃) Ulmi Cortex(楡根白皮) Ephedrae Herba(麻黃) of high-density have a cyto-toxicity. 2. The differentiation effect of edipocyte 1) At the Taeyangin(太陽人)'s prescriptions and herbs during the natural differentiation, Phragmitis Rhizoma(蘆根) of the boiling water-extract, Okapijangchek-tang(五加皮壯脊湯) Acanthopanacis Cortex(五加皮) of the ethyl alcohol-extract have a cyto-toxicity on the first-differentiation. 2) At the Taeumin(太陰人)'s prescriptions and herbs during the natural differentiation, Ulmi Cortex (楡根白皮) Kalopanaxii Cortex(海桐皮) of the boiling water-extract have a cyto-toxicity on the first-differentiation. Cheongsimyonja-tang(淸心蓮子湯) Ephedrae Herba(麻黃) of ethyl alcohol-extract have a control effect on the redifferentiation. 3) At the Taeyangin(太陽人)'s prescriptions and herbs on the first-differentiation during the induced differentiation, Acanthopanacis Cortex(五加皮) of ethyl alcohol-extract has a control effect. Okapijangchek-tang(五加皮壯脊湯) Acanthopanacis Cortex(五加皮) Phragmitis Rhizoma(蘆根) of the boiling water-extract have a cyto-toxicity. 4) At the Taeumin(太陰人)'s prescriptions and herbs on the first-differentiation during the induced differentiation, Coicis Semen(薏苡仁) Ephedrae Herba(麻黃) Imperatae Rhizoma(白茅根) of the boiling water-extract and Ephedrae Herba(麻黃) of the ethyl alcohol-extract have a control effect. Kalopanaxii Cortex(海桐皮) of the boiling water-extract and the ethyl alcohol-extract has a cyto-toxicity. Considering this result, the Taeyangin(太陽人) Taeumin(太陰人)'s prescriptions and herbs have a control effect on edipocytes during the proliferation. Acanthopanacis Cortex(五加皮), Coicis Semen(薏苡仁) Ephedrae Herba(麻黃) Imperatae Rhizoma(白茅根) have a control effect on edipocytes during the induced differentiation. In the future, for treating a obesity need a vivo assay and hope this study to help to know the mechanisms of obesity.