• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.421-426
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• 1997

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[$^{18}F$]fluoromethylbenzyl)spiperone ([$^{18}F$]FMBS), a newly developed derivative of spiperone, as a potentially more selective radiotracer for the dopamine (DA) $D_2$ receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [$^{18}F$]FMBS by tail vein injection. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA $D_2$ receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA $D_1$ (SCH 23390), DA transporter (GBR 12909), and serotonin $S_2$ ($5-HT_2$) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabeled FMBS (1 mg/kg) and spiperone (1 mg/kg) reduced [$^{18}F$]FMBS striatal-to-cerebellar ratio by 41% and 80%, respectively. (+)-Butaclamol (1 mg/kg) blocked 80% of the striatal [$^{18}F$]FMBS binding, while (-)-butaclamol (1 mg/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect on [$^{18}F$]FMBS binding. Ketanserin (1 mg/kg), a ligand for the $5-HT_2$ receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [$^{18}F$]FMBS labels DA $D_2$ receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA $D_2$ receptors in vivo by PET.

• Korean Journal of Food Science and Technology
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• v.48 no.6
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• pp.610-617
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• 2016

Melatonin, known as a powerful wide-spectrum antioxidant, is consumed as a food supplement in some countries, but its applicability as an antioxidant additive was not yet studied. Therefore, we evaluated the antioxidant activity of melatonin by DPPH, ABTS, FRAP and ORAC assays as well as its ability to inhibit perilla oil oxidation. The activities of four other related indoles were also compared. Melatonin showed the highest antioxidant activity (mmol trolox equivalent per mol indole, mmol TE) in ORAC (2,159) assay, but a low antioxidant activity in DPPH (0.63), ABTS (91), and FRAP (764) assays, whereas serotonin showed an opposite result. Addition of 1% (w/w) melatonin to perilla oil extended the induction period of oxidation up to about 2 times ($2.93{\pm}0.47h$) compared to that of control ($1.43{\pm}0.26h$) in the Rancimat assay, corresponding to almost 50% of the ability of butylated hydroxyl toluene (BHT). Tryptamine was the most effective indole that inhibited perilla oil oxidation ($9.53{\pm}1.43h$).

• Journal of Food Hygiene and Safety
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• v.24 no.1
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• pp.102-109
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• 2009

This study was carried out to analyse the microbio\logical contamination and biogenic amines(BA) content in Korea traditional soybean paste and commercial soybean paste. The results of microbio\logical analysis through Korean traditional soybean pastes($L1{\sim}L4$) were $7.8{\pm}0.1\;\log\;CFU/g{\sim}7.9{\pm}0.1\;\log\;CFU/g$, commercial soybean pastes($H1{\sim}H6$) were $6.2{\pm}0.1\;\log\;CFU/g{\sim}7.4{\pm}0.1\;\log\;CFU/g$ for APC (Aerobic Plate Count), and $L1{\sim}L4$, H5, H6 soybean pastes were $2.3{\pm}0.4\;\log\;CFU/g{\sim}2.6{\pm}0.1\;\log\;CFU/g$ for Bacillus cereus. But other microorganism was not dectected. Among biogenic amines, PUT(putrescine), TYR(tyramine), HIS(histamine), PHE(2-Phenylethylamine) were dectected high level and CAD(cadaverine), TRY(trypramine), AGM(agmatine) were dectected medium level and SPD(spermidine), SPM(spermine), NOR(noradrenaline), SER(serotonin) were dectected low level. Dectected contents of biogenic amines were higher in commercial soybean paste compared to the traditional soybean paste.

• Toxicological Research
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• v.6 no.2
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• pp.205-213
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• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.106-106
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• 1995

A polysaccharide, G009, isolated from Ganoderma lucidum IY009 subjected to investigating on general pharmacology. This material at the large oral doses of 1000 and 2000mg/kg in mice did neither exhibit any abnormal behaviors nor effects on central nervous system. It also had no influences on hexobarbital-induced sleeping time, rotarod test and spontaneous activity test at each oral dose of 1000mg/kg in mice. No effects on the body temperature and on acetic acid induced writhing syndrome in mice were observed with its oral administration at 1000mg/kg, and the convulsions induced by strychnine and pentetrazole were not inhibited at its oral doses of 1000mg/kg in mice. The solution of G009 as given intravenously at the doses of 30 and 60mg/kg in rabbit had no influences on blood pressure and respiration rates and depth. In isolated organs of rat uterus and fundus muscles and guinea-pig ileum and trachea, it did not show any contraction or relaxation at the concentration of 2$\times$10$^{-3}$g/ml, and the contractive actions produced by oxytocin, acetylcholine, serotonin and histamine did not inhibited by the same doses. This material showed no effect on intestinal propulsion test in mice and gastric secretion in rats at the oral doses of 1000mg/kg. However, it is interesting that the material exhibited potent inhibition of acidified aspirin induced gastric damage at the doses of 500 and 1000mg/kg in rats.

• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.37-43
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• 1984

노화는 모든 다세포 유기물의 특징이다. 노화가 됨에 따라서 효소활성 및 면역반응의 감소와 과산화지질과 지방갈색물질의 축적, 효소와 염색질을 포함하는 단백질 구조의 변화, 호르몬계의 불균형 등이 일어난다. 그렇지만, 노화가 어떻게 일어나는지에 관하여는 현재까지 확실하지 않다. 본 연구진은 노화와 관련된 효소들에 관하여 연구를 하여 왔으며, 노화가 진행되는 동안의 효소의 활성을 유지시켜주거나, 또는 효소의 활성이 감소되는 것을 지연시켜 주는 물질을 찾고자 노력하였다. 그 가운데 하나로서, 고려인삼 추출물을 흰쥐에 기간별로 투여하여 효소활성의 차이, 열에 대한 안정성, 기질에 대한 친화력, 전기 영동 상의 이동성과 면역적인 반응을 대조군과 비교하였다. Glucose-6-phosphate dehydrogenase, 6-phosphog-luconate dehydrogenase, glutathione redutease, glutathion peroxidase와 같은 노화와 관련된 효소들의 활성을 고려인삼 추출물을 1개월간 흰쥐에 ($60{\~}80$g)투여하여 대조군과 비교 조사하였으나, 별 차이가 없었다. 그러나 고려인삼 추출물을 15개월간 투여하였을 때에는 이러한 노화관련 효소들의 활성이 급격히 증가함이 ($70{\~}200\%$) 관찰되었다. 예견된 바와 같이, 효소의 열에 대한 안정성과 기질에 대한 친화력도 증가함이 관찰되었다. 그러나 glucose-6-phosphate dehydrogenase의 경우에서 전기영동상의 차이 및 면역적인 반응은 대조군과 유사하였다. 이상의 결과는 고려인삼 추출물이 노화와 관련된 효소들의 활성이 감소되는 것을 지연시켜줄 수 있으며, 노화를 어느정도 지연시켜 줄 수 있음을 의미한다. 이와 같은 결과를 포함한 실험자료를 국제 인삼심포지움에서 발표할 것이다.$-tocopherol의 항 산화작용을 더욱 효과적으로 촉진 시킬 것으로 생각된다.-L(독성 호르몬-L)의 작용을 억제함으로서 암환자의 체중 감소를 방지하고, 식욕감퇴를 개선할것으로 생각된다.해되었으며, $Rb_{1}$은 장내의 효소와 tetracycline-resistantant bacteria에 의해 Rd와 2 종류의 미확인 물질로 분해되었다.xA_{2}$ synthetase 억제제인 imidazole의 효과와 유사하였다. 4. G-Re는 $1{\times}10^{-5}g/ml$ 이하의 농도에서는 효과가 없으나 $1{\times}10^{-4}g/ml$ 이상의 농도에서 농도의존적으로 유의성 있는 $PGE_{2},\;PGF_{2}{\alpha},\;TXB_{2}$의 생성억제와 함께 6-keto-$PGF_{1}{\alpha}$ 증가를 보였다. 이는 prostacyclin synthetase를 자극하는 serotonin의 효과와 같은 작용으로서 prostacyclin synthetase 억제제인 tranylcypromine에 대하여 길항효과를 보였다. 5. $TxB_{2}$생성억제 작용을 나타내는 ginsenoside들의 효과를 뒷받침하기 위하여 인삼 saponin 성분을 전처치한 patelet rich plasma에서 혈소판 응집시험 결과, ADP로 유도된 혈소판 응집반응에는 모든 인삼 saponin 성분들이 효과가 없었으나 arachidonic acid로 유도된 혈소판 응집반응에는 $G-Rb_{2}$, G-Rc, G-Re의 순으로 농도 의존적인 억제현상을 보였다. 이상의 결과와 같이 인삼 saponin 성분들은 arachidonic acid로부터 cyclooxygenase를

• Journal of Ginseng Research
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• v.34 no.4
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• pp.314-320
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• 2010

The previous reports have showed that ginseng saponins, which are the active ingredients of Panax ginseng, cause the relaxation of artery that are contracted due to a various of hormones or potassium ($K^+$). Recently, we also showed that ginsenosides differentially regulate channel activity. The purpose of this study was to examine whether ginseng saponins affect contraction induced by $K^+$, serotonin (5-HT), or acetylcholine (Ach) in porcine coronary vessel. Treatment with concentrations of ginseng saponins caused a relaxation of 25 mM KCl-induced porcine coronary artery contraction. Also, ginseng saponin induced a significant dose-dependent relaxation of $3\;{\mu}M$ 5-HT-induced porcine coronary artery with the endothelium. In the porcine artery with the endothelium, ginseng saponins induced a relaxation by $3\;{\mu}M$ 5-HT in a concentration-dependent pattern. Ginseng saponins induced relaxation of both 25 mM KCl- and $3\;{\mu}M$ 5-HT-induced coronary artery contraction in the absence and presence of the endothelium. In contrast, treatment with $100\;{\mu}g/mL$ ginseng saponin did not induce relaxation in coronary artery contraction induced by Ach ($0.01\;{\mu}M$ to $30\;{\mu}M$) in the presence of the endothelium, but did cause significant relaxation of coronary artery contractions by Ach ($0.01\;{\mu}M$ to $30\;{\mu}M$) in the absence of the endothelium. These findings indicate that ginseng saponin (> $100\;{\mu}g/mL$) significantly inhibits porcine coronary artery contractions caused by $K^+$, 5-HT, and Ach. Therefore, in this study, we demonstrated that ginseng saponin may show beneficial roles on abnormal coronary contraction.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.207-213
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• 2007

This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.898-903
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• 2006

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.5 no.1
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• pp.93-101
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• 1994

This study was performed to assess the amount of altered serotonergic responsivity in individuals with repeated aggressive behaviors compared with normal controls. Sixteen aggressive(delinquent criminals with repeated aggressive behaviors) and seventeen controls(medical college students) were selected and assessed their severity of aggression by several psychological instruments. The platelet $^3H$-imipramine binding sites which is known to correlate the serotonergic function of the central nervous system were measured. The results are as follows. 1) Mean scores of physical aggression in the aggressive subjects were found to be significantly higher than normal controls(p<.01). And impulsivity, hostility, psychoticism in the aggressives were found higher than controls, also. 2) In the paltelet $^3H$-imipramine binding, the aggressives had a tendency of reduced maximal binding sites(Bmax) comparing with controls(p=.0841). 3) There was no statistically significant differences between two groups in the binding coefficients(Kd) of platelet $^3H$ Imipramine binding. 4) The value of maximal binding sites(Bmax) showed significant inverse correlations with aggressive scale scores of PFAV(r=-.6311), and physical aggression scale scores of CTS(r=-.5377).