• Title/Summary/Keyword: Pilocarpine

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Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

  • Cho, Kyung-Ok;Kim, Joo Youn;Jeong, Kyoung Hoon;Lee, Mun-Yong;Kim, Seong Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.4
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    • pp.281-289
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    • 2019
  • Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

Effect of Alcohol Extract of Rheum undulatum Linne on Isolated Rabbit Intestine Strip (대황의 알콜추출물이 토끼 적출장관에 미치는 영향)

  • Kim, Won-Ja;Paek, Un-Sang;Ha, Byoung-Kuk;Kim, Ki-Jin
    • The Korean Journal of Pharmacology
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    • v.8 no.1
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    • pp.77-87
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    • 1972
  • Korean rheum (Rheum undulatum Linne) as one of the botanical crude drugs which belong to polygonaceae family has been extensively applied in Chinese medicine during the last decades. It has been particularly used in cathartic and gastric tonic among the folk remedies. There are, however, a few reports with regard to the pharmacological effects on the motility of intestines of several animals. The authors hereby paid attention to this point of view and made experiment to examine the relationship between the alcohol extract of Korean rhei rhizoma and the motility of the isolated rabbit intestine, making the use of several drugs related to the motility of intestine such as acetylcholine, pilocarpine, atropine, papaverine, serotonin, and barium chloride. The movement of the isolated rabbit intestine in Tyrode's solution was recorded with the electric kymograph according to the Magnus method. The results of the experiment are as follows. 1. The motility of the isolated rabbit intestine represents the tendency of gradual dilatation in proportion to the concentration of R-A $10^{-4}$, $5{\times}10^{-4}$, and $10^{-3}$. 2. R-A $5{\times}10^{-4}$ does not seem to have the significant effect with acetylcholine, pilocarpine and atropine on motility of the isolated rabbit intestine strip. 3. R-A $5{\times}10^{-4}$ significantly blocks the contractile effect caused by serotonin $10^{-6}$ on motility of the isolated rabbit intestine strip. 4. R-A $5{\times}10^{-4}$ significantly blocks the contractile effect caused by barium chloride $10^{-4}$ on motility of the isolated rabbit intestine strip. 5. R-A $5{\times}10^{-4}$ significantly synergizes the dilatative effect caused by papaverine $10^{-6}$.

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The Inhibition of Epileptogenesis During Status Epilepticus by Ginsenosides of Korean Red Ginseng and Ginseng Cell Culture (Dan25)

  • N.E., Chepurnova;Park, Jin-Kyu;O.M., Redkozubova;A.A., Pravdukhina;K.R., Abbasova;E.V., Buzinova;A.A., Mirina;D.A., Chepurnova;A.A., Dubina;U.A., Pirogov;M., De Curtis;L., Uva;S.A., Chepurnov
    • Journal of Ginseng Research
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    • v.31 no.3
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    • pp.159-174
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    • 2007
  • Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one's biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides $(Rb_1$ Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models

  • Kim, Si-Hyung;Choi, In-Sun;Cho, Jin-Hwa;Park, Eun-Ju;Jang, Il-Sung;Choi, Byung-Ju;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • International Journal of Oral Biology
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    • v.31 no.2
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    • pp.33-43
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    • 2006
  • Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs)on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor amplitude and numbers of population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5 mg/kg; phenytoin 40, 60 mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320 mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.

IRRADIATION EFFECT ON SECRETING FUNCTION, AMYLASE ACTIVITY AND NUCLEIC ACID CONTENTS OF RAT PAROTID GLAND (방사선 조사가 이하선 기능에 미치는 영향에 관한 연구)

  • Cho Yong Jin;Park Tae-Won
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.20 no.1
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    • pp.53-62
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    • 1990
  • This experiment was performed to clarify the effects of /sup 60/Co gamma irradiation on secretory function, amylase activity and contents of nucleic acids of parotid gland in rat. Experimental animals were divided into 6th hours, 3rd, 7th, 14th and 28th days after irradiation and control. The experimental animals are singly irradiated with 20Gy (2,000rad) through protective lead block. Secretory function of parotid gland was evaluted by uptake and clearance of /sup 99m/TcO₄. /sup 99m/TcO₄. 0.2μ ci/gm, was injected into peritonium in uptake groups. Rats were sacrified with cervical dislocation after 30 minutes and gland was excised. In the clearance group. pilocarpine nitrate (8㎎/㎏) was intraperitoneally injected at 30 minutes after /sup 99m/TcO₄ injection and rats were sacrified 30 minutes after pilocarpine injection. Radioactivity of excised parotid gland was measured by using of gamma counter and stimulation-secretion coefficients, uptake radioactivity divided by clearance radioactivity, was calculated. Amylase activity and contents of DNA and RNA were determined by spectrophotometry. The results obtained were as follows: 1. In the uptake test, the radioactivity of /sup 99m/TcO₄ per unit weight increase in experimental group except 6th hours group, compared with control groups and showed a peak at 3rd days after irradiation. 2. In the clearance test, the radioactivity of /sup 99m/cO₄per unit weight rose to a peak at 3rd days after irradiation and gradually recovered thereafter. 3. Stimulation-secretion coefficient of parotid gland decreased at 6th hours, 3rd and 7th days after irradiation, and gradually increased. 4. Amylase activity of parotid gland decreased in 3rd and 7th days group, and especially lowest in 3rd days after irradiation. 5. The contents of DNA showed no definite difference in all the experimental groups, but RNA was seemed to decrease with time after irradiation.

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Pharmacological Study of Components of L. pseudo-laeve Nakai. (Lycoctonum 속식물성분의 약리학적연구 I)

  • 김재완
    • YAKHAK HOEJI
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    • v.7 no.4
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    • pp.86-91
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    • 1963
  • Crystal A and B were isolated from L. pseudo-leave Nakai and their pharmacological action was observed. Crystal A, in dose of 5 * $10^{-4}$ - 5 * $10^{-5}g/ml$, stimulated excised frog heat but at 2.5 * $10^{-6}$ - 0.5 * $10^{-5}g/ml$ of crystal B, depressant effect was observed. Mild stimulation of rhythmicity of exercised rabbit intestine was produced by 1 * $10^{-4}$ g/ml of crystal A and 2 * $10^{-4}g/ml$ of crystal B. Marked depression of tone was produced by 2 * $10^{-4}g/ml$ of crystal A, antagonizing by pilocarpine. Crystal B(4 * $10^{-4}gm/l)produced$ mild stimulation, followed by depression of tone. No curare-like action on excised frog abdominal muscle was elicited with both substances.

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Effect of Nifedipine on the Action of Drug Participating in Blood Pressure in Rabbits (가토에서 혈압에 관여하는 약물의 작용에 대한 니페디핀의 영향)

  • Ko, Suk-Tai;Jung, Chang-Ju;Kim, Hai-Suk
    • YAKHAK HOEJI
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    • v.36 no.4
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    • pp.379-389
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    • 1992
  • In order to investigate the effect of nifedipine, $Ca^{+2}$ channel antagoninst, on the action of some drugs participating in blood pressure, this experiment was peformed in rabbits. Nifedipine decreased the pressor actions of norepinephrine, angiotensin and carotid artery clamping, but did not affect the pressor actions of tyramine and depressor actions of acetylcholine and pilocarpine. Nifedipine inhibited the potentiated pressor action of norepinephrine and angiotensin, but did not influence the potentiated pressor action of tyramine in rabbits pretreated with chlorisondamine, ganglionic blocking agent. Nifedipine weakened the potentiated pressor action of norepinephrine, did not affect the pressor action of angiotensin and the potentiated pressor action of tyramine in rabbits pretreated with debrisoquine, sympathetic neuronal blocking agent.

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Function of the Neuronal $M_2$ Muscarinic Receptor in Asthmatic Patients (천식 환자에서 $M_2$ 무스카린성 수용체 기능에 관한 연구)

  • Kwon, Young-Hwan;Lee, Sang-Yeup;Bak, Sang-Myeon;Lee, Sin-Hyung;Shin, Chol;Cho, Jae-Youn;Shim, Jae-Jeong;Kang, Kyung-Ho;Yoo, Se-Hwa;In, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.4
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    • pp.486-494
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    • 2000
  • Background : The dominant innervation of airway smooth muscle is parasympathetic fibers which are carried in the vagus nerve. Activation of these cholinergic nerves releases acetylcholine which binds to $M_3$ muscarinic receptors on the smooth muscle causing bronchocontraction. Acetylcholine also feeds back onto neuronal $M_2$ muscarinic receptors located on the postganglionic cholinergic nerves. Stimulation of these receptors further inhibits acetylcholine release, so these $M_2$, muscarinic receptors act as autoreceptors. Loss of function of these $M_2$ receptors, as it occurs in animal models of hyperresponsiveness, leads to an increase in vagally mediated hyperresponsiveness. However, there are limited data pertaining to whether there are dysfunctions of these receptors in patients with asthma. The aim of this study is to determine whether there are dysfunction of $M_2$ muscarinic receptors in asthmatic patients and difference of function of these receptors according to severity of asthma. Method : We studied twenty-seven patients with asthma who were registered at Pulmonology Division of Korea University Hospital. They all met asthma criteria of ATS. Of these patients, eleven patients were categorized as having mild asthma, eight patients moderate asthma and eight patients severe asthma according to severity by NAEPP Expert Panel Report 2(1997). All subjects were free of recent upper respiratory tract infection within 2 weeks and showed positive methacholine challenge test ($PC_{20}$<16mg/ml). Methacholine provocation tests were performed twice on separate days allowing for an interval of one week. In the second test, pretreatment with the $M_2$ muscarinic receptor agonist pilocarpine($180{\mu}g$) through inhalation was performed be fore the routine procedures. Results : Eleven subjects with mild asthma and eight subjects with moderate asthma showed significant increase of $PC_{20}$ from 5.30$\pm$5.23mg/ml(mean$\pm$SD) to 20.82$\pm$22.56mg/ml(p=0.004) and from 2.79$\pm$1.51mg/ml to 4.67$\pm$3.53mg/ml(p=0.012) after pilocarpine inhalation, respectively. However, in the eight subjects with severe asthma significant increase of $PC_{20}$ from l.76$\pm$1.50mg/ml to 3.18$\pm$4.03mg/ml(p=0.161) after pilocarpine inhalation was not found. Conclusion : In subjects with mild and moderate asthma, function of $M_2$ muscarinic receptors was normal, but there was a dysfunction of these receptors in subjects with severe asthma. ηlese results suggest that function of $M_2$ muscarinic receptors is different according to severity of asthma.

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Experimental Studies on the Anti-cathartic Effects of Dolichoris Semen, Terminaliae Fructus and Bojanggunbi-tang (백편두(白扁豆), 가자(訶子) 및 보장건비탕(補腸健脾湯)의 항사하작용(抗瀉下作用)에 관(關)한 연구(硏究))

  • Ro, Woo-Seong;Kim, Jin-Sung;Yoon, Sang-Hyub;Ryu, Bong-Ha
    • The Journal of Internal Korean Medicine
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    • v.27 no.2
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    • pp.356-370
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    • 2006
  • Objectives: The aim of this experimental study is to investigate effects of Dolichoris Semen, Terminaliae Fructus and Bojanggunbi-tangon the anti-cathartic action of mice and guinea pigs to develop effective herbal medicine and prescription to cure diarrhea early and to prevent side effect of chronic diarrhea. Methods: To compare effects of Dolichoris Semen, Terminaliae Fructus and Bojanggunbi-tangon the anti-cathartic action of mice and guinea pigs, we evaluated the actions on isolated gastrointestinal smooth muscles. on the transportability of small and large intestines, onthe neostigmine-induced transportability of small intestine and on diarrhea induced by castor oil, pilocarpine, barium chloride. Results: (1) Dolichoris Semen, Terminaliae Fructus and Bojanggunbi-tang showed the strong alleviation on the contraction of mice's isolated gastrointestinal smooth muscles induced by acetylcholine chloride and barium chloride. while Terminaliae Fructus, strong, Bojanggunbi-tang, intermediate and Dolichoris Semenshowed the minor alleviation on the contraction of guinea pigs' isolated gastrointestinal smooth muscles induced by acetylcholine chloride and histamine. All effects depended on the density in each medicine. (2) The tranbportability of small intestine was contrained in the groups controlled by 600 mg/kg of Dolichoris Semen, Terminaliae Fructus and Bojanggunbi-tang, and 200 mg/kg of D olichoris Semen and Terminaliae Fructus. However, the enhancement of neostigmine-induced transportability of small intestine was constrained only in the groups controlled by 600 mg/kg of Dolichoris Semen, Terminaliae Fructus and Boianggunbi-tang. (3) The transportability of large intestine was constrained by Dolichoris Semen and Bojanggunbi-tang. They showed substantial results. which depended on the amount of each medicine. (4) Terminaliae Fructus showed substantial anti-cathartic effects on diarrhea induced by caster oil in both groups controlled by 200 and 600 mg/kg of it. However, Bojanggunbi-tangshowed the effects only in the group controlled by 600 mg/kg. in diarrhea induced by pilocarpine, the groups controlled by 600 mg/kg or Terminaliae Fructus and 200 and 600 mg/kg of Boianggnbi-tangshowed substantial results. In diarrhea induced by barium chloride. the groups controlled by 200 and 600 mg/kg of Terminaliae Fructus and 600 mg/kg of Boianggunbi-tangshowed substantial results in anti-cathartic effects. Conclusions: These results show that Terminaliae Fructus is more effective on the contraction of mice and guinea pigs' isolated gastrointestinal smooth muscles, Dolichoris Semen is more effective on the transportability of small intestine, Dolichoris Semen and Bojanggunbi-tang are more effective on the transportability of large intestine. Terminaliae Fructus and Bojanggunbi-tang show substantial results in anti-cathartic actions.

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