• The Korean Journal of Pesticide Science
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• v.8 no.4
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• pp.239-254
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• 2004

It has been debating about conducting and interpretating of 2-year rodent carcinogenicity bioassay. Although some criticisms arising in usefulness, it has been still known that long-term carcinogenicity studies using rodents would be the only assay system to predict any possible human risks, which would not be replaced. Both regulatory agencies and academies have developed some assay models, however, there have been controversy whether those study designs and interpretations are based on sound scientific rationale and validated data. Such kinds of issues including choice of species/strain, dose level selection, duration of study, number of animals per group, historical control data, monitoring parameters, terminal investigations, peer review, statistics, alternative assay models, interpretation of neoplastic lesions, and risk assessments, were reviewed.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.316-326
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• 2006

Backgrounds & Objects: The aim of this study was to investigate the radioprotective effect of Shengmai-san(SMS), a herbal medicine, on mice jejunal crypt cell survival and Apoptosis. Methods: Mice were devided into 4 groups according to radiation dose and SMS treatment: Normal was the group without irradiation. Control was the group treated with D.W before 10 Gy irradiation. SMS 2.9 was sample group treated with 2.9 mg/10 g of SMS extract before 10 Gy irradiation and SMS 29 was sample group treated with 29 mg/10 g of SMS extract before 10 Gy irradiation. And Each group were sacrificedat 24 hours and 72 hours after irradiation. To analyze the crypt survival, hematoxylin-eosin staining was used and to analyze the apoptosis, the TUNEL assay was done. Results: 1. From the microcolony survival assay, the SMS 2.9 and SMS 29 showed the radioprotective effect with a statistical significance compared to the control group at 24 hr (P < 0.01) and 72 hr (p < 0.001) after 10 Gy irradiatien. And the differences of radioprotective effect between SMS 2.9 and SMS 29 were net significant. 2. The results of the TUNEL assay showed that the apoptotic index in SMS 2.9 and SMS 29 was significantly decreased, as compared to the control group at both 24 hr ( p < 0.01) and 72 hr (SMS 2.9 : p < 0.001. SMS 29 : P < 0.01) after 10Gy irradiation And the differences of between SMS 2.9 and SMS 29 were not significant. Conclusions: It could be suggested that the Shengmai-san has a prominent Protective effect in mice intestines against the radiation damage. And the radieprotective effect seems to be related to inhibition of the apoptosis.

• Proceedings of the Korean Vacuum Society Conference
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• 1998.02a
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• pp.133-133
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• 1998

In the thin film alloy formation of the transition metals ion-beam-mixing technique forms a metastable structure which cannot be found in the arc-melted metal alloys. Sppecifically it is well known that the studies about the electronic structure of ion-beam-mixed alloys pprovide the useful information in understanding the metastable structures in the metal alloy. We studied the electronic change in the ion-beam-mixed ppt-Ct alloys by XppS and XANES. These analysis tools pprovide us information about the charge transfer in the valence band of intermetallic bonding. The multi-layered films were depposited on the SiO2 substrate by the sequential electron beam evapporation at a ppressure of less than 5$\times$10-7 Torr. These compprise of 4 ppairs of ppt and Cu layers where thicknesses of each layer were varied in order to change the alloy compposition. Ion-beam-mixing pprocess was carried out with 80 keV Ae+ ions with a dose of $1.5\times$ 1016 Ar+/cm2 at room tempperature. The core and valence level energy shift in these system were investigated by x-ray pphotoelectron sppectroscoppy(XppS) pphotoelectrons were excited by monochromatized Al K ａ(1486.6 eV) The ppass energy of the hemisppherical analyzer was 23.5 eV. Core-level binding energies were calibrated with the Fermi level edge. ppt L3-edge and Cu K-edge XANES sppectra were measured with the flourescence mode detector at the 3C1 beam line of the ppLS (ppohang light source). By using the change of White line(WL) area of the each metal sites and the core level shift we can obtain the information about the electrons pparticippating in the intermetallic bonding of the ion-beam-mixed alloys.

• Molecules and Cells
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• v.25 no.4
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• pp.479-486
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• 2008

Mitogen-activated protein kinases (MAPKs) play an indispensable role in activation of the myogenic program, which is responsive to mechanical stimulation. Although there is accumulating evidence of mechanical force-mediated cellular responses, the role of MAPK in regulating the myogenic process in myoblasts exposed to cyclic stretch is unclear. Cyclic stretch induced the proliferation of C2C12 myoblasts and inhibited their differentiation into myotubes. In particular, it induced persistent phosphorylation of p38 kinase, and decreased the level of phosphorylation of extracellular-signal regulated kinase (ERK). Partial inhibition of p38 phosphorylation increased cellular levels of MyoD and p-ERK in stretched C2C12 cells, along with increased myotube formation. Treatment with $10{\mu}M$ PD98059 prevented myogenin expression in response to a low dose of SB203580 ($3{\mu}M$) in the stretched cells, suggesting that adequate ERK activation is also needed to allow the cells to differentiate into myotubes. These results suggest that cyclic stretch inhibits the myogenic differentiation of C2C12 cells by activating p38-mediated signaling and inhibiting ERK phosphorylation. We conclude that p38 kinase, not ERK, is the upstream signal transducer regulating cellular responses to mechanical stretch in skeletal muscle cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.101-109
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• 2004

Spatholobus suberectus belonging the family Leguminosae has been used for promoting blood circulation, removing blood stasis, tonifying the blood, relaxing tendons, stopping internal bleeding and eliminating dampness in oriental traditional medicine. This study investigates whether the water extracts of S. suberectus induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by S. suberectus, as measured by cell morphology. The capability of S. suberectus to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly (ADP­ribose)polymerase protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of S. suberectus on cell cycle progression. G1 checkpoin related gene products tested (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2Fl) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by S. suberectus may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.325-331
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• 2000

The present study was designed to assess the role of spinal adenosine $A_2$ receptor in the regulation of cardiovascular functions such as mean arterial pressure (MAP) and heart rate (HR) in male Sprague-Dawley rats. Rats (250~300 g) were anesthetized with urethane and paralyzed with d-tubocurarine and artificially ventilated. blood pressure and HR were continuously monitored via a femoral catheter connected to a pressure transducer and a polygraph. Drugs were administered intrathecally using injection cannula through guide cannula which was inserted inthrathecally at lower thoracic level through a puncture of an atlantooccipital mombrane. Intrathecal injection of an adenosine $A_2$ receptor agonist, 5'-(N-cyclopropyl)-carboxamaidoadenosine (CPCA; 1, 2 and 3 nmol, respectively), produced a dose-dependent decrease in MAP and HR. Pretreatment with $N^{G}$-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or 10 nmol of MDL-12,330, an adenylate cyclase inhibitor blocked significantly the depressor and bradycardic effect of 2 nmol of CPCA. But, Pretreatment with 3 nmol of bicuculline, gamma-aminobutyric acid A (GAB $A_{A}$) receptor antagonist, or 50 nmol of 5-aminovaleric acid, GAB $A_{B}$ receptor antagonist did not inhibit the depressor and bradycardic effect of 2 nmol of CPCA. These results indicate that adenosine $A_2$ receptor in the spinal cord plays an inhibitory role in the regulation of cardiovascular function and that the depressor and bradycardic action of adonosine $A_2$ receptor are mediated via the synthesis of nitric oxide and the activation of adenylate cyclase in the spinal cord of rats.s.s.s.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.449-457
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• 2015

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

• Korean Journal of Weed Science
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• v.9 no.2
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• pp.103-107
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• 1989

Five rice cultivars were treated by four dose of butachlor at transplanting seedling stage. Visual injury rate by butachlor was lowest in Zhy-Lian-Ai-dun-Nam and highest in Samseungbyeo, but reduction of yield was higher in Zhy-Lian-Ai-Yun-Nam and Hangangchalbyeo than in Samseungbyeo and Cheungcheungbyeo. Reduction of panicle number by butachlor was most effective factor to yield reduction.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Animal cells and systems
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• v.13 no.4
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• pp.391-397
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• 2009

The house dust mite (Dermatophagoides pteronissinus) is an important factor in triggering allergic diseases. The function of eosinophils, particularly in the production of cytokine or chemokine, is critical in understanding the pathogenesis of inflammatory diseases. In this study, we examined whether D. pteronissinus extract (DpE) induces the expression of monocyte chemotactic protein 1 (MCP-1)/CCL2, IL-8/CXCL8, and IL-6 that mediate in the infiltration and activation of immune cells and in its signaling mechanism in the human eosinophilic cell line, EoL-1. DpE increased the mRNA and protein expression of MCP-1, IL-8, and IL-6 in a time- and dose-dependent course in EoL-1 cells. In our experiments using signal-specific inhibitors, we found that the increased expression of MCP-1, IL-8, and IL-6 due to DpE is associated with Src family tyrosine kinase and protein kinase C $\delta$ (PKC $\delta$). In addition, the activation of extracellular signal-regulated kinase (ERK) is required for MCP-1 and IL-8 expression while p38 mitogen-activated protein kinase (MAPK) is involved in IL-6 expression. DpE induced the phosphorylation of ERK and p38 MAPK. PP2, an inhibitor of Src family tyrosine kinase, and rottlerin, an inhibitor of PKC $\delta$, blocked the activation of ERK and p38 MAPK. DpE induces the activation of ERK and p38 MAPK via Src family tyrosine kinase and PKC $\delta$ for MCP-1, IL-8, or IL-6 production. Increased cytokine release due to the house dust mite and the characterization of its signal transduction may be valuable in understanding the eosinophil-related pathogenic mechanism of inflammatory diseases.