• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.93-98
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• 2001

The precise mechanism of set-point regulation in hypothalamus was not elucidated. Nitric oxide synthases(NOS) were detected in hypothalamus, however, the roles of NO in hypothalamus was not fully studied. So, we tested the effects of NO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. NO donor sodium nitroprusside (SNP, 4 nmol, i.c.v.) elicited marked febrile response, and this febrile response was completely blocked by indomethacin (a cyclooxygenase inhibitor). But, ODQ (selective guanylate cyclase inhibitor, $50\;{\mu}g,$ i.c.v.) did not inhibit fever induced by SNP. The cyclic GMP analogue dibutyryl-cGMP $(100\;{\mu}g,\;i.c.v.)$ induced significant pyreses, which is blocked by indomethacin. $N^G-nitro-L-arginine$ methyl ester (L-NAME, non selective NOS inhibitor) inhibited fever induced by $interleukin-1{\beta}\;(IL-1{\bata},\;10\;ng,\;i.c.v.),$ one of endogenous pyrogens. These results indicate that NO may have an important role, not related to stimulation of soluble guanylate cyclase, in the signal pathway of thermoregulation in hypothalamus.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1013-1018
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• 2003

Cheonghunhwadam-tang(CHT) have been used in oriental medicine for many centuries as a therapeutic agent of vertigo by wind, fire and phlegm. CTG was CHT adding Aurantii FructusㆍGastrodae Rhizoma. CTG was significantly increased regional cerebral blood f1ow(rCBF) in a dose-dependent, and CTG was decreased mean arterial blood pressure(MABP) compared with normal MABP(100%) in a low dosage, but was increased MABP in a dose-dependent, was aliked with normal MABP in a high-dosage. Therefore, purpose of this Study was to investigate experimental mechanism of CHTAG on the cerebral hemodynamics(rCBF, MABP) in rats. The changes of rCBF and MABP were determinated by Laser-Doppler Flowmetry(LDF). The results were as follows ; Pretreatment with indomethacin(3㎎/㎏, i.v.) was significantly inhibited CTG induced increase of rCBF and pretreated with propranolol(3㎎/㎏, i.v.) was inhibited CTG induced increase of rCBF, but pretreatment with methylene blue(10㎍/㎏, i.v) was increased CTG induced increase of rCBF. Pretreatment with indomethacin was decreased CTG induced increase of MABP, but pretreatment with propranolol and methylene blue were increased CTG induced increase of MABP. This results suggest that the mechanism of CTG is mediated by cyclooxygenase.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.124-132
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• 2002

Daebangpung-tang(DBPT) is one of the prescriptions used for the treatment of rheumatoid arthritis(RA) in oriental medicine. The present study aimed to examine the analgesic effect of DBPT on a rat model of CFA-induced arthritis, which is not identical to human auto-immune arthritis although it does have many features in common with RA, and the relation between DBPT-induced analgesia and steroid hormones. CFA-induced arthritis rat model used to test the effect of DBPT was chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least the next 18 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral injection of indomethacin produced temporary improvement of weight bearing. DBPT dissolved in water was orally administrated. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 4 hours. DBPT produce significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 3 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. The reduced stepping force was divided into three stages(10-30g, 30-50g, and 50-70g). All experiments was performed at 50-70g of stepping force, since both DBPT and indomethacin showed the most excellent analgesic effect at 50-70g of stepping force. DBPT produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner and showed analgesic effect on neuropathic pain as well. DBPT-induced analgesic effect could not be blocked by systemic injection of steroid antagonist mifepristone. The present study suggest 1) that DBPT produces a potent analgesic effect on the chronic knee arthritis pain model in the rat and 2) that steroids system does not mediate DBPT-induced analgesia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1714-1721
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• 2004

This experimental study was designed to investigate the mechanism of Palmul-Tang(PMT) on the changes of cerebral hemodynamics in rats. The changes of cerebral hemodynamics in normal rats were as follows ; The PMT-induced increase in regional cerebral blood flow was significantly inhibited by pretreatment with indomethacin(1㎎/㎏, i.p.), an inhibitor of cyclooxygenase, and was inhibited by methylene blue(10㎍/㎏, i.p.), an inhibitor of guanylate cyclase. The PMT-induced dilation in pial arterial diameter was significantly inhibited by pretreatment with indomethacin and methylene blue. The PMT-induced increase in mean arterial blood pressure was significantly inhibited by pretreatment with indomethacin but was increased by methylene blue. This results were suggested that the mechanism of PMT was mediated by cyclooxygenase. The changes of cytokine production in cerebral ischemic rats were as follows ; In cytokine production of serum by drawing from femoral arterial blood after middle cerebral arterial occlusion 1hr, sample group was decreased IL-1β and TNF-α production compared with control group, IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 1hr, sample group was significantly decreased IL-1β production compared with control group and decreased TNF-α production compared with control group. IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 4 hrs, sample group was significantly decreased IL-1β production compared with control group, but IL-10 production of sample group was similar to that of control group. sample group was increased TNF-α and TGF-β production compared with control group. These results suggested that PMT had inhibitive effect on the brain damage by inhibiting IL-1β and TNF-α production, but by accelerating TGF-β production. The present author thought that PMT had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of Chest Surgery
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• v.23 no.2
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• pp.222-230
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• 1990

Protamine, a polycationic peptide extracted from fish, has been widely used for the reversal of anticoagulant action of heparin. However it may cause untoward circulatory side effects including hypotension and bradyarrhythmia. Nowadays, histamine and prostacyclin are regarded as one of the causative agents in the underlying mechanism of hemodynamic changes. To certify the possible role of histamine and prostacyclin, we observed simultaneous changes of the hemodynamic status, plasma concentration of thromboxane B, and circulating platelet count before and after intravenous injection of protamine. Experimental dogs, weighing 12-14kg, were divided into 2 groups; group A animals [n=10], were pretreated with indomethacin[2.5mg/kg] and group B animals[n=10] were pretreated with chlorpheniramine[0.5mg/kg] Heparin[3mg/kg] and protamine [3mg/kg] were administered sequentially in both groups. The results were as follows ; 1. The mean systemic arterial pressure was maintained well in groups A, whereas in group B it decreased from 165\ulcorner18mmHg to 138\ulcorner30mmHg[p<0.01] and 151\ulcorner21 mmHg[p<0.05] at 1 minute and 2 minutes after protamine injection. The mean pulmonary arterial pressure was not changed significantly in group A, whereas in group B it increased from 852 mmHg to 11\ulcorner3 mmHg[p<0.05], 11\ulcorner3 mmHg[p<0.05] and 10\ulcorner3 mmHg[p<0.05] at 1 minute, 3 minutes and 5 minutes after protamine injection. 2 The thromboxane B2 was not changed significantly in group A, whereas in group B it increased from 399\ulcorner401 \ulcornerg/ml to 744\ulcorner615 \ulcornerg/ml[p<0.05] and 814\ulcorner1070 \ulcornerg/ml [p<0.0 5] at 1 minute and 3 minutes after protamine injection without concomitant changes of pulmonary vascular resistance and pulmonary capillary wedge pressure. 3. The number of circulating platelet was not changed in group A, whereas in group B it decreased from 207100\ulcorner103600/\ulcornerl to 159700\ulcorner90900/\ulcornerl [p<0.05] at 1 minute after protamine injection, Although thromboxane B2 and platelet count were changed significantly after protamine injection, they did not cause the remarkable hemodynamic changes. Considering the above results, hemodynamic changes may be caused mainly by prostacyclin rather than thromboxane or platelet. Therefore, the pretreatment with cyclooxygenase inhibitor would be beneficial to prevent circulatory adverse effects of protamine for the patients undergoing cardiac surgery.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.188-203
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• 2005

Objectives : This study was designed to investigate the effects of Jayun-tang extract (JYT) on the change of cerebral hemodynamics [regional cerebral blood flow (rCBF), pial arterial diameter (PAD) and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats, na to determine the mechanisms of action of JYT. Methods : We investigated whether JYT inhibits lactate dehydrogenase activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. Results : 1. JYT significantly increased rCBF and PAD in a dose-dependent manner, but MABP was not changed by injecting JYT. These results suggested JYT significantly increased rCBF by dilating PAD. 2. The JYT-induced increase in rCBF was significantly inhibited from pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue $(10{\mu}g/kg, i.p.)$, an inhibitor of guanylate cyclase. 3. The JYT-induced dilation in PAD was significantly inhibited from pretreatment with indomethacin, but was increased by pretreatment with methylene blue. 4 The JYT-induced increase in MABP was reduced by pretreatment with indomethacin and methylene blue. 5. JYT significantly inhibited lactate dehydrogenase activity in neuronal cells. These results suggest that JYT prevented the neuronal death. 6. Both rCBF and PAD were significantly and stably increased by JYT $(10{\mu}g/kg,\;i.p.)$ during the Period or cerebral reperfusion, which contrasted with the findings of rapid and marked increase in the control group. 7. In cytokine production in the serum drawn from femoral artery 1hr after middle cerebral artery occlusion, the sample group showed significantly decreased production of $IL-1\beta$ and $TNF-\alpha$ as well as increased production of IL-10 and $TGF-\beta$ compared with rho control group. 8. In cytokine production in the serum drawn from femoral artery 1hr after reperfusion, the sample group showed significantly decreased production of $IL-1\beta$ and $TNF-\alpha$ as well as significantly increased production of IL-10 and $TGF-\beta$ compared with the control group. Conclusions : JYT mediated by cyclooxygenase had an inhibitive effect on brain damage by inhibiting lactate dehydrogenase activity, $IL-1\beta$ and $TNF-\alpha$ production, and by accelerating IL-10 and $TGF-\beta$ production. The author feels that JYT had anti-ischemic effects through the improvement of cerebral hemodynamics and inhibitive effects on brain damage.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.143-149
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• 1987

We determined the maternal peripheral lymphocyte response to mitogen during the period of implantation and evaluated the effects of hormones, which are known to be involved in the process of implantation, on the lymphocyte activity in rabbits. As compared with peripheral lymphocyte activity in non-pregnant rabbits, lymphocyte activity was significantly depressed on days 6, 7 and 9 of pregnancy. Although concentrations of serum progesterone were gradually increased during the implantation period, progesterone did not inhibit lymphocyte activity at physiological concentration. Serum $PGF_{2{\alpha}}$ was significantly increased on day 7 while PGE was slightly increased. $PGF_{2{\alpha}}$ did not modify lymphocyte activity even with greater concentrations than physiological level. However, lymphocyte activity was significantly inhibited by PGE even with physiological doses. The treatment of indomethacin at doses of 0.1 or $1.0\;{\mu}g/ml$ tended to enhance lymphocyte response, which was depressed on day 8 of pregnancy, 28% or 23% respectively. Although in non-pregnant rabbit, enhancement of lymphocyte response was also shown after the treatment of indomethacin, this enhancement was much less than that in pregnant rabbits. These results strongly suggest that maternal immune response was depressed during the process of implantation and PGE might be one of factors for immunomodulation during this period.

• Journal of Periodontal and Implant Science
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• v.24 no.1
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• pp.155-164
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• 1994

치조골흡수는 만성치주질환의 전형적인 증상이다. 골흡수에 작용하는 여러 요인들 중에서도, 특히 최근에 들어서 몇몇 cytokine들에 대한 관심이 높아지고 있는데, interleukin-1(IL-1), tumor necrosis factor(TNF) 및 interleukin-6(IL-6) 등이 치주질환의 진행과정에서 중요한 치조골흡수요인으로 제안되고 있다. 본 연구의 목적은 신생쥐의 골조직 배양실험을 통해서 recombinant human $interleukin-1{\beta}$ ($rHuIL-1{\beta}$), recombinant human tumor necrosis $factor-{\alpha}$($rHuTNF-{\alpha}$) 및 recombinant human interleukin-6(rHuIL-6) 의 골흡수 유도효과를 알아보고, cyclooxygenase 억제제인 indomethacin과 recombinant murine $interferon-{\gamma}$($rMurIFN-{\gamma}$)가 이들 cytokine의 골흡수 유도능력에 미치는 영향을 알아봄으로써 이들 cytokine의 작용기구에 대해서 알아보고자 하는데 있다. 생후 1-2일된 쥐에게 $1{\mu}Ci^{45}CaCl_2$를 피하주사하고 4일 후에 쥐를 희생시켜 $^{45}Ca$ 로 표지된 두개골을 얻어 24시간 전배양 후, 각 cytokine ($rHuIL-1{\beta}$, $rHuTNF-{\alpha}$ 및 rHuIL-6)과 cytokine 및 첨가약제 (indomethacin 및 $rMurIFN-{\gamma}$)가 함유된 배지로 교환하여 48시간 배양한다. 골흡수 유도효과는 두개골에서 48시간의 배양 중 유리되는 $^{45}Ca$의 방사능 정도로 평가하였다. 본 연구를 통해 다음과 같은 결과를 얻었다. 1. $rHuIL-1{\beta}$ ($10^{-12}-10^{-9}M$) 및 $rHuTNF-{\alpha}$ ($10^{-10}-10^{-8}M$)는 농도변화에 따르는 골흡수 유도효과를 보였으나 , rHuIL-6 ($10^{-10}-10^{-8}M$)는 유의할 만한 효과를 보이지 않았다. 2. Indomethacin ($10^{-6}M$)은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의할 만한 억제효과를 나타내지 않았다. 3. $rMurIFN-{\gamma}$ (1000 U/ml) 은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의한 억제효과를 나타내었다. 본연구를 통해 치주질환 환자의 치주조직에서 검출되는 $IL-1{\beta}$ 및 $TNF-{\alpha}$가 치조골 흡수에 중요한 역할을 할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.8-15
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• 1991

It has been well known that the integrity of airway epithelium is important in development of bronchial hyperreactivity and bronchial asthma. But the mechanisms involved are still unclear. To evaluate that airway epithelium is able to modulate the contraction of guinea pig tracheal smooth muscle, we investigated the responsiveness of intact and epithelium-denuded tracheal strips to histamine and acetylcholine. And to evaluate whether cyclooxgenase products play a role in this modulatory mechanism, we also investigated the effect of indomethacin pretreatment on the tracheal responsiveness to histamine. Results were as follows: 1) In guinea pig tracheal smooth muscle the presence of airway epithelium significantly reduced the response to histamine. 2) In the presence of indomethacin dose-response curves and $EC_{50}$ values were similar between intact and epithelium-denuded tracheal strips, that is, indomethacin abolished the influence of epithelium on the contracion of tracheal smooth muscle. 3) The response of tracheal smooth muscle to acetylcholine was similar both in the presence and absence of epithelium. These results suggest that airway epithelium of guinea pig may generate an inhibitory signal to decrease the response of tracheal smooth muscle to histamine and cyclooxygenase products may contrbute to the modulation of airway epithelium on the contracion of tracheal smooth muscle.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.59-61
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• 2004

Several derivatives were synthesized from fructigenine A, which was isolated from Penicillium fructigenum. The anti-inflammatory properties of fructigenine A was evaluated in vivo with a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model and a carrageenan-induced rat paw edema model. Results showed that the anti-inflammatory activity was significantly higher with fructigenine derivatives than with indomethacin, which was used as a standard. We concluded that fructigenine derivatives could exert an anti-inflammatory effect.