• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.327-332
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• 2001

In recent years, experimental evidence have been suggested that melatonin has either contractive or relaxing effects on the vascular smooth muscle in vitro. But the effect of melatonin on the cardiovascular system in vivo had been emphasized about the hypotensive effect. In this work, we found not only hypotensive effect but also hypertensive effect of melatonin in rats and attempted to determine the mechanism of these effects elicited by melatonin. Regadless of concentration, melatonin(0.002~5 mg/kg) produced increase in mean blood pressure (MBP) in 36% (54/150 cases) and decrease in mean blood pressure in 64%(96/150 cases). As a whole melatonin caused an increase or a decrease in MBP without compensatory decrease or increase in heart rate. The melatonin-induced hypertension was abolished by the pretreatment of phenoxybenzamine, a ${\alpha}$-adrenoceptor antagoninst. The melatonin-induced hypotension was abolished by the pretreatment of propranolol, a ${\beta}$-adrenoceptor antagonist, ODQ, a NO-sensitive guanylate cyclase inhibitor, or nifedipine, a L-type $Ca^{2+}$ channel blocker, but not by bilateral cervical vagotomy. The results indicate that melatonin-induced hypertension may be related to ${\alpha}$-adrenoceptor stimulation and melatonin-indued hypotension may be related to ${\beta}$-adrenoceptor stimulation, inhibition of $Ca^{2+}$ channel and/or activation of guanylate cyclase.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.4
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• pp.225-233
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• 2002

Kanagawa hemolysin (KH), an exotoxin produced from Kanagawa phenomenon-positive Vibrio parahemolyticus, has been shown to possess various biological activities including hemolysis, enterotoxicity, cytotoxicity, and cardiotoxicity. The aim of this study was to investigate the effect of KH on the cardiovascular system and its mechanism, employing in vivo and in vitro experiments of the rat. Intracerebroventricular (icv) administration of 100 mHU KH produced a marked and continuous pressor effect (icv KH-pressor effect), and the icv pressor effect was not repeatable. However, intravenous (iv) injection of the same dose of KH induced a prominent depressor effect (iv KH-depressor effect). The icv KH-pressor effect was inhibited by acid-denaturation, while the iv KH-depressor effect was not. Simultaneous icv administration of the three agents (ouabain, diltiazem, or bumetanide: $10{\mu}g/kg$ each) significantly reduced the pressor effect. The icv KH-pressor effect was inhibited by treatment with iv phentolamine or chlorisondamine, but was not affected by iv candesartan. The iv KH-depressor effect was repeatable and was attenuated by treatment with iv NAME or methylene blue. In vitro experiments using isolated thoracic aorta, $10^{-6}$ M phenylephrine (PE) and 50 mM KCl produced a sustained contraction. In rings contracted with either agents, KH showed relaxant responses in a concentration- dependent fashion and the relaxation (KH-vasorelaxation) was not dependent on the existence of the endothelium. The KH-vasorelaxation in the endothelium-intact rings contracted by PE was abolished by methylene blue treatment. In summary, the present findings suggest that in the icv KH-pressor effect the cation leak-inducing action of KH is implicated, which leads to the increased central sympathetic tone, that the iv KH-depressor effect results from the vasorelaxation via NO-guanylate cyclase system, and that the KH-vasorelaxation is independent of the endothelium and the guanylate cyclase system is involved in it. In conclusion, the mechanism of KH producing the icv pressor effect may not be identical to that of KH producing the iv depressor effect.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1194-1201
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centries as a therapeutic agent of vertigo caused by deficiency of qi(氣) and blood(血). Effect of Aurantii Fructus(AF) take off the phlegm by promoting the circulation of qi, Gastrodae Rhizoma(GR) has effects treating for headarch, vertigo by calming the liver and suppressing hyperactivity of the liver-yang (陽). I investigated whether injection of JGT adding AFㆍGR extract(JTG) affects cerebral hemodynamics [regional cerebral blood f1ow(rCBF), pial arterial diameter(PAD) in cerebral ischemia rats by MCA occlusion method, and I designed to make manifest whether JTG is mediated by adrenergic β-receptor, cyclooxygenase or guanylate cyclase. The changes of rCBF was determinated by laser-doppler flowmetry(LDF), and the changes of PAD was determinated by video microscope and width analyzer. The results were as follows in cerebral ischemic rats; The changes of rCBF and PAD were increased stabilizly by treatment with JTG(10 ㎎/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with propranolol and indomethacin were increased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. Pretreatment methylene blue was decreased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. In conclusion, JTG causes a diverse response of rCBF and PAD, and action of JTG is mediated by adrenergic β-receptor and cyclooxygenase. I suggest that JTG has an anti-ischemic effect through the improvement of crebral hemodynamics.

• Journal of Acupuncture Research
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• v.25 no.6
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• pp.1-12
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• 2008

Objectives : Joongjeo($TE_3$) Supplementation Aekmoon($TE_2$) Draining is a method belongs to Ohaeng-acupuncture, using directional supplementation and draining. Methods : This study was designed to investigate the effects of $TE_3$ supplementation $TE_2$ draining on changes in cerebral blood flow(rCBF) and mean arterial blood pressure(MABP) in normal rats. For these reasons, the present author investigated rCBF and MABP using laser doppler flowmeter in normal rats. In addtion, the present author also investigated action mechanisms of $TE_3$ supplementation $TE_3$ draining on changes in rCBF and MABP too. Results : In this results, $TE_3$ supplementation $TE_2$ draining elevated rCBF in time-dependent manner, but MABP levels decresed by $TE_3$ supplementation $TE_2$ draining. Pre-treatment with indomethacin (IDM), an inhibitor of cyclooxygenase, inhibited increase of rCBF effectively. But pre-treatment with methylene blue(MTB), an inhibitor of guanylate cyclase, decreased rCBF levels. In addition, pre-treatment with IDM also decreased MABP levels, but pre-treatement with MTB increased MABP levels. Conclusions : In conclusion, these results suggest that $TE_3$ supplementation $TE_2$ draining is effective to treat patient with disease related to cerebral ischemia, because $TE_3$ supplementation $TE_2$ draining can increase rCBF. In addition, the mechanisms are thought to be related to guanylate cyclase pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.416-422
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centuries as a therapeutic agent of vertigo caused by deficiency of qi(氣) and blood(血). Effect of Aurantii Fructus(AF) take off the phlegm by promoting the circulation of qi, Gastrodae Rhizoma(GR) has effects treating for headache, vertigo by calming the liver and suppressing hyperactivity of the liver-yang(陽). And, We reported that JGT adding AFㆍGR extract(JGTAG) was significantly increased regional cerebral blood f1ow(rCBF) by dilating pial arterial diameter(PAD). Therefor we designed to investigate whether JGTAG is mediated by adrenergic β-receptor, cyclooxygenase or guanylate cyclase in normal rats. The changes of rCBF and mean arterial blood pressure(MABP) were determinated by laser-doppler flowmetry(LDF), and the change of PAD was determinated by video microscope and width analyzer. The results were as follows in normal rats; Pretreatment with propranolol(1mg/kg, i.v.) was significantly inhibited JGTAG induced increase of rCBF, PAD and MABP, and pretreatment with indomethacin(1 mg/kg, i.v.) was significantly inhibited too. But pretreatment with methylene blue(10μg/kg, i.v.) were accelerated JGTAG induced increase of rCBF and MABP, but pretreatment with methylene blue was inhibited JGTAG induced increase of PAD. This results suggest that the mechanism of JGTAG is mediated by adrenergic β-receptor and cyclooxygenase.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.302-306
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• 2008

ChongMyeong-Tang(CMT) have been used clinically to treat patient with amnesia and dementia. In addition, CMT have been also used for examinee to improve learning ability in Korea. This experimental study was designed to investigate the effects of Gagam-ChongMeong-Tang(GCMT) to improve the retentive faculty and learning ability in terms of Cerebral blood flow(rCBF) and Mean Artery Blood Pressure(MABP) in rats. In our study, we investigated that increasing doses of GCMT (1 ug/ml, 10 ug/ml, 100 ug/ml, and 1000 ug/ml) affect the level of rCBF and MABP in rats. In our results, treatment with GCMT elevated level of rCBF in dose dependant manner. Cantraray, level of MABP was lowered by treatment with GCMT. The involved mechanisms in rCBF are guanylate cyclase pathway. During the period of cerebral re-perfusion, GCMT treated group showed stability of rCBF compared to control group. These results imply that GCMT increased rCBF through dilation of pial artery. And related mechanisms are involved in guanylate cyclase pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.1
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• pp.176-182
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• 2008

Scolopendra was known to cure erectile dysfunction. This study was aimed to investigate the effects of Scolopendra on the nitric oxide synthase activity, nitrite level, cyclic-GMP and erectile responses in rat's corpus cavernosum penis. The crushed Scolopendra was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 14.2 g. Scolopendra extract was oral-administered 50 mg per 1 kg of body weight for 30 days. First, samples were treated with Scolopendra, and then ethanol-treated rats and L-N-Nitroarginine methyl ester (L-NAME) treated rats were fed with the samples. The level of urethral nitrite and nitric oxide synthase activity in the ethanol-Scolopendra double administered rats were as high as in the normal group, while the one in the ethanol-treated group was decreased. The level of urethral cyclic-GMP and guanylate cyclase actiyity in the ethanol-Scolopendra double administered rats were as high as in the normal group, while the one in the ethanol-treated group was decreased. The level of urethral phosphodiesterase activity in the ethanol-Scolopendra double administered rats was as low as in the normal group, while the one in the ethanol-treated group was increased. The erectile response to a cavernous nerve stimulation in L-NAME $(10^{-4})-treated$ rats was restored by the Scolopendra to the similar level seen in the normal group. The electile response to cavernous nerve stimulation in the ethanol-Scolopendra double administered rats were increased as high as in the normal group while the one in the ethanol-treated group was decreased. Scolopendra was effective in restoring the ethanol-induced or L-NAME-induced erectile dysfunction in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.6
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• pp.601-606
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• 2014

The purpose of this study is to research the effects of acupuncturing BL40 and ST36 and to determine the mechanism of action of acupuncturing BL40 and ST36 by measuring the changes of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats. To determine the mechanism of action of acupuncturing BL40 and ST36, pretreatment with indomethacine and methylene blue was performed. Acupuncturing BL40 and ST36 significantly increased rCBF, and the increased rCBF by acupuncturing BL40 and ST36 was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase, and methylene blue($10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. Acupuncturing BL40 and ST36 decreased MABP, and decreased MABP by acupuncturing BL40 and ST36 was not changed by pretreatment with indomethacin and methylene blue. This result suggested that acupuncturing BL40 and ST36 might significantly increase rCBF by dilating arterial diameter and mechanism of acupuncturing BL40 and ST36 might be mediated by cyclooxygenase and guanylate cyclase.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.262-270
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• 2017

Yersinia enterocolitica is a well-known foodborne pathogen causing gastrointestinal infections worldwide. The strain Y. enterocolitica FORC_002 was isolated from the gill of flatfish (plaice) and its genome was sequenced. The genomic DNA consists of 4,837,317 bp with a GC content of 47.1%, and is predicted to contain 4,221 open reading frames, 81 tRNA genes, and 26 rRNA genes. Interestingly, genomic analysis revealed pathogenesis and host immune evasion-associated genes encoding guanylate cyclase (Yst), invasin (Ail and Inv), outer membrane protein (Yops), autotransporter adhesin A (YadA), RTX-like toxins, and a type III secretion system. In particular, guanylate cyclase is a heat-stable enterotoxin causing Yersinia-associated diarrhea, and RTX-like toxins are responsible for attachment to integrin on the target cell for cytotoxic action. This genome can be used to identify virulence factors that can be applied for the development of novel biomarkers for the rapid detection of this pathogen in foods.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1612-1619
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• 2006

This Study was designed to investigate the mechanism of Mixture of Bambusae Caulis in Liquamen and Bamboo Extract on the change of regional cerebral blood flow (rCBF) and blood pressure (BP) in normal rats, and further to investigate cytokines production in serum of cerebral ischemic rats. Mixture were as follows ; Bamboo Extract extracted with distilled water at 98 $^{\circ}C$ for 3 hrs, Mixture of Bambusae Caulis in Liquamen and bamboo Extracts (MLE) mixed at the ratio 1 to 100 (MLE100), 1 to 50 (MLE50), 1 to 20 (MLE20), 1 to 10 (MLE10), 1 to 5 (MLE5). The results were as follows ; The MLE-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin (1 mg/kg, I.p.), an inhibitor of cyclooxygenase as well as methylene blue (10 $^{\mu}g/kg$, I.p.), an inhibitor of guanylate cyclase. The MLE-induced increase in BP was significantly inhibited by pretreatment with methylene blue. In cytokines production in the serum drawn from femoral arterial 1 hr after middle cerebral artery occlusion, MLE5 significantly increased production of TGF-${\beta}$ and increased production of IL-10, but significantly decreased production of TGF-${\alpha}$ compared with control group. In cytokines production in the serum drawn from femoral arterial 1 hr after reperfusion, MLE5 significantly increased production of TGF-${\beta}$ and IL-10, but significantly decreased production of TGF-${\alpha}$ compared with control group. AS results above. And MLE5 had anti-ischemic effect by inhibiting TGF-${\alpha}$ production, and by accelerating IL-10 and TGF-${\beta}$ production.