• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.239-243
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• 1996

DW-116 {(1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride) is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after intraperitoneal and oral single administration. We prepared the bone marrow cells at 30hr after drug administration and they were used for measuring PCE with micronucleus. The results showed there was no statistically significant increase in the numbers of PCEs with micronucleus in all DW-116 administered groups compared with a negative control group. The results also showed that the ratio of normochromatic erythrocytes(NCEs) to PCEs of all DW-116 administered groups was not significantly different from that of a negative control group. These results suggested that DW-116 may not cause any chromosomal damage and it has no in vivo mutagenic potential under these experimental conditions.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.357-368
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• 1996

The in vitro antibacterial activity of a novel fluoroquinolone, DWP20373(1-Cyclopropyl-6-fluoro-8-methoxy-7-(2,7-diazabicyclo[3,3,0]oct-4-ene-7-yl)-1,4-dihydro-4 oxoquino line-3carboxylic acid) was compared with those of ciprofloxacin (CPFX), sparfloxacin (SPFX) and ofloxacin (OFLX). DWP20373 was more active than SPFX and OFLX but was less potent than CPFX against gram-negative bacteria. DWP20373 showed an excellent activity against L-MRSA and H-MRSA ($MlC_{90}=0.781{\sim}1.563{\mu}g/ml$).The activity of DWP20373 decreased moderately in the presence of 5mM $Mg^{2+}$. However, pH and serum had no effect on the activity of DWP20373. DWP20373 possessed a rapid bactericidal activity against gram-positive and gram-negative strains.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.284-291
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• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• Journal of the Korean Society of Tobacco Science
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• v.21 no.2
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• pp.119-127
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• 1999

This study was conducted to evaluate the effect of cigarette papers, flax and wood, on the delivery of mainstream smoke. The main components of cigarette papers were cellulose, hemicellulose, lignin, and pectin. Lignin contents, known as precursor of smoke's phenolic compounds, of the flax and wood cigarette papers were 5.8% and 10.6%, respectively. The pyrolysis products of cigarette papers were similar by the profile of total ion chromatogram. But, the area % of some components, such as 1,3-cyclopentanedione, 3,5- dimethyl cyclopentane-1,2-dione, 2-hydroxy-3-methyl-2-cyclopentenone, dihydro-2(3H)-furanone, 3-methyl-2(5H)-fruanone, and 5-methyl-2-furaldehyde delivered through pyrolysis of the flax cigarette paper were higher than that of wood cigarette paper. Otherwise, the area % of some components, such as 2-methyl-cyclopentene-l-one), 2,3-butanedione, 2-cyclopentene-l-one, and 5-hydroxy-2-methyl-furaldehyde, 2-furaldehyde delivered through pyrolvsis of the wood cigarette paper were higher than that of flax cigarette paper. To identify the difference between two cigarette papers, we used the cigarette column filled with the cut cigarette paper instead of the cut tobacco leaf. The amounts of semi-volatile fraction delivered from flax cigarette paper was more than that of wood cigarette paper. But, by using the cut tobacco, there was no big difference of delivery amount between flax and wood cigarette papers. Also, aroma of TPM by collecting from brening cut tobacco wrapped in flax and wood papers showed a different pattern by the electonic nose system. Although the difference between two cigarette papers by using the cut tobacco was smaller than that of cut cigarette paper, this result indicated that the fax and wood had the different effects on the delivery of smoke components as shown in the sensory test results.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.401-408
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• 2009

$K^+$-$Cl^-$-cotransport (KCC) has been reported to have various cellular functions, including proliferation and apoptosis of human cancer cells. However, the signal transduction pathways that control the activity of KCC are currently not well understood. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signal in the regulatory mechanism of KCC activity. Exogenous application of AA significantly induced $K^+$ efflux in a dose-dependent manner, which was completely blocked by R-(+)-[2-n-butyl-6,7 -dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1Hinden-5-yl]oxy]acetic acid (DIOA), a specific KCC inhibitor. N-Ethylmaleimide (NEM), a KCC activatorinduced $K^+$ efflux was significantly suppressed by bromoenol lactone (BEL), an inhibitor of the calciumindependent $PLA_2$ ($iPLA_2$), whereas it was not significantly altered by arachidonyl trifluoromethylketone ($AACOCF_3$) and p-bromophenacyl bromide (BPB), inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. NEM increased AA liberation in a doseand time-dependent manner, which was markedly prevented only by BEL. In addition, the NEM-induced ROS generation was significantly reduced by DPI and BEL, whereas $AACOCF_3$ and BPB did not have an influence. The NEM-induced KCC activation and ROS production was not significantly affected by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, markedly produced ROS and activated the KCC. Collectively, these results suggest that $iPLA_2$-AA signal may be essentially involved in the mechanism of ROS-mediated KCC activation in HepG2 cells.

• Korean Journal of Animal Reproduction
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• v.22 no.1
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• pp.29-34
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• 1998

Jugular plasma concentrations of luteinizing hormone, prolactin, estradiol-17\ulcorner and 13, 14-dihydro-15-keto-prostaglandin-F2봬(PGFM) were meausred prepartum during the last 12 days of pregnancy, at parturition, then 1 day after parturition in 16 goats. Plasma samples were analyzed for luteinizing hormone(LH), estradiol-17\ulcorner(E2), prolactin(PRL) and prostagladin F2봬(PGF2봬) concentrations by radioimmunoassay. 1. The concentrations of plasma luteinizing hormone in Korean native goats remained fairly constant(0.20 0.02\ulcorner0.38 0.04 mlu/ml) from 12 days prepartum to 1 postpartum but the concentrations of plasma prolactin rose slightly from 1 day prepartum. 2. The estradiol-17\ulcorner concentrations increased rapidly after day 1 before partum, reaching a peak at parturition(74.8 77.5 pg/ml), and falling to 63.8 2.8 pg/ml at day 1 postpartum. 3. Starting at 323.2 69.6 twelve days before parturition, the concentrations of plasma prostaglandin F2봬 rose during the 1 day preceeding parturition(650.7봬57.8 pg/ml) and peaked at 1081.4 164.9 on the day of parturition. At day 1 postpartum, the concentrations of PGF2봬 decreased to 425.3 60.4 pg/ml. Finally, these results show that changes in prostaglandin F2봬 concentrations before parturition were closely related to changes in estradiol-17\ulcorner concnetrations, but after parturition they remained elevated whereas estradiol-17\ulcorner concentrations fell abruptly.

• Applied Biological Chemistry
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• v.29 no.1
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• pp.90-95
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• 1986

A comparative study of chemical characteristics, efficacy and relative merits of extruded and coated granules, containing fungicide and insecticide, was conducted under laboratory and field conditions. Probenzole (3-allyloxy-1,2-benzisothiazole 1,1-dioxide) and carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methyl carbamate) were chosen as toxicants for rice blast(Pyricularia oryzae) and brown planthopper (Nilaparvata lugens) control, respectively. Stability of active ingredients in coated granule was superior to the extruded one under accelerated temperature. Active ingredient dissolution of coated one into distilled water showed slow release pattern. Pesticide residues in rice (Oryzae sativa, Chucheongbyeo) shoot applied with extruded one at the dosage of 3kg/10a retained higher levels than those with coated one on two days after application, while the residue levels were a reversed tendency on eight days after application. Efficacy on rice blast exhibited minute differences between the granules, on the other hand efficacy on brown planthopper by coated one was of higher rank than that by extruded one. Production cost of the combined pesticide granule by coating method could be cut down by 6% as compared to extrusion method.

• Korean Journal of Weed Science
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• v.17 no.1
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• pp.66-70
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• 1997

LGC-40863(proposed common name ; pyribenzoxim), (benzophenone O-[2,6-bis[(4,6-dimethoxy-2-pyrimidinyl)oxy]benzoyl]oxime) is a new rice herbicide being developed by LG Chemical Ltd. The herbicide is highly selective between rice(Oryza sativa L.) and weeds including barnyardgrass (Echinochloa crus-galli(L.) P. Beauv.), and assumed to inhibit acetolactate synthase(ALS ; EC 4.1.3.18) because other structurally related herbicides inhibit the enzyme. To know inhibitory activity and the mode of inhibition of LGC-40863, $I_{50}$(concentration inhibiting ALS activity by 50%) and inhibition kinetics were investigated using ALS extracted from rice and barnyardgrass. $I_{50}$ values of LGC-40863 were 14 and 16mM in rice and barnyardgrass, respectively. In contrast to imazapyr(2-[4,5-dihydro-4-mythyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridine-carboxylic acid) which showed an uncompetitive inhibition pattern, LGC-40863 was a noncompetitive inhibitor to ALS with respect to pyruvate similar to chlorsulfuron(2-chloro-N-((4-methoxy-6-methyl-l,3,5-triazin-2-yl) aminocarbonyl)benz-enesulfonamide) in both plants.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.395-399
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• 1998

DW2282, (S)- (+)-4-phenyl -1-[N-(4-am mob enzoyl) -indolin-5- sulfonyl]-4,5- dihydro-2-imidazolone hydrochloride, is a novel anticancer agent thought to have an unique mechanism of action on the inhibition of tumor growth. In this study, we estimated in vivo antitumor activities and pharmacokinetics of Dw2282 depending on various vehicles. The inhibition rate of tumor growth was increased by 50, 100 and 200 mg/kg of Dw2282 in a dose-dependent manner. When Dw2282 dissolved in 4 sorts of vehicles was orally single dosed to rats at 50 mg/kg, Cmax of Dw2282 in 0.5% CMC.Na was a half as high as those in PG, PG+CP and PG+CP+DW. When Dw2282 was orally administered to mice for 5 days, antitumor activity of 130 mg/kg suspended in 0.5% CMC.Na was as effective as that of 65 mg/kg dissolved in the rest of vehicles. Taken together, it is thought that antitumor activities of Dw2282 are resulted from the absorption extent of it and related to the vehicle used.

• YAKHAK HOEJI
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• v.30 no.5
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• pp.253-265
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• 1986

Among 230 species of herbal drugs screened, thirty one show the anthelmintic activities in vitro against Clonorchis sinensis, the chinese liver fluke. The active substances have been isolated and their structures identified. Some of the active substances and their derivatives have been synthesized, followed by anthelmintic activity tests. The extracts from the active drugs cause damages in organs of the adult worm in the hepatic duct of rabbit. Some fresh water fish, which function as bad hosts for the fluke, excrete defense substances against the cercaria of the fluke. The defense substances have been isolated from Cyprinus carpio and Cyprinus carpio nudus, followed by structural identification. The results are summarized as follows: l) The bark of Machilus thunbergii as well as the seed of Schizandra chinensis contain meso-dihydro-guaiaretic acid as the anthelmintic component. Among derivatives synthesized, 4-phenyl-1-((3, 4-dihydroxyphenyl)-, 4-phenyl-1-(3-hydroxy-4-methoxy phenyl)-and 4-phenyl-1-(4-hydroxy-3-methoxy phenyl)-2, 3-dimethyl butanes show considerable activities. Administration of the bark extract mainly damages the bladder of the adult worm. 2) The active substance from the roasted fruit of Prunus mume is 2-hydroxymethylfurfural. This substance is produced during the roasting process. Administration of the fruitextract causes a damage of the bladder of the adult worm. 3) The active substance from the root of Scutellaria baicalensis is 5.2'-dihydroxy-6, 7, 8, 6'-tetramethoxyflavone. 4) Beside alantolactone, a very strong anthelmintic component is contained in the root of Inula helenium. Administration of the root extract causes irreversible damage on the worm, affecting mainly the reproductive organs. 5) The cercaricidal substances from the epidermis of C. carpio and C. carpio nudus are ethyl linoleate and linoleic acid, respertively. 6) The cercaricidal substances from various kinds of fresh water fish have different $R_f$ values, implying that the defense substances are species-specific. Unexpectedly, the fish with good host function, for example Pseudorasbora parva, excrete the defense substances, too. The defense substances are possibly organ-specific in individual species; the organs essenstial for the existence of the species excrete the defense substances, allowing other parts to be invaded by the cercaria. 7) The cercaricidal fraction of Carassius carassius is detected only in the fish which have been collected during the summer time from May to September, Its secretion is not dependent on water temperature. Thus, it seems to be possible that the secretion of the defense substance would be stimulated through a contact between the fish and cercaria.