• Journal of Ginseng Research
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• v.31 no.1
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• pp.1-13
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• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

• Macromolecular Research
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• v.14 no.1
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• pp.66-72
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• 2006

The purpose of this study is to develop novel nanoparticles based on polyion complex formation between low molecular weight water-soluble chitosan (LMWSC) and all-trans retinoic acid (atRA). LMWSC nanoparticles encapsulating atRA based on polyion complex were prepared by mixing of atRA into LMWSC aqueous solution using ultrasonication. In FTIR spectra, the carbonyl group of atRA at 1690 $cm^{-1}$ disappeared or decreased when ion complexes were formed between LMWSC and atRA. In ${1}^H$ NMR spectra, specific peaks of atRA disappeared when atRA-encapsulated LMWSC (RAC) nanoparticles were reconstituted into $D_{2}O$ while specific peaks both of atRA and LMWSC appeared in $D_{2}O$/DMSO (1/3, v/v) mixture. XRD patterns also showed that the crystal peaks of atRA were disappeared by encapsulation into LMWSC nanoparticles. LMWSC nanoparticles encapsulating atRA have spherical shapes with particle size below 200 nm. The mechanism of encapsulation of atRA into LMWSC nanoparticles was thought to be an ion complex formation between LMWSC and atRA. LMWSC nanoparticles showed high atRA loading efficiency over 90$\%$ (w/w). AtRA was continuously released from nanoparticles over 10 days. In in vitro cell cytotoxicity test, free atRA showed higher cytotoxic effect against CT 26 colon carcinoma cell line on 1 day. However, RAC nanoparticles showed similar cytotoxicity against CT 26 cells on 2 day. These results suggest the potential for the introduction of LMWSC nanoparticles into various biomedical fields such as drug delivery.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.712-719
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• 2006

In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of PLGA. The synthesis of the DexLG copolymer was confirmed by $^1H$ nuclear magnetic resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles in water by self-aggregating process, and their particle size was around $50\;nm{\sim}300\;nm$ according to the graft ratio of PLGA. Morphological observations using a transmission electron microscope (TEM) showed that the nanoparticles of the DexLG copolymer have uniformly spherical shapes. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values determined from the fluorescence excitation spectra were increased as increase of DS of PLGA. $^1H-NMR$ spectroscopy using $D_2O$ and DMSO approved that DexLG nanoparticles have core-shell structure, i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano-particles became faster in the presence of dextranase in spite of the release rate not being significantly changed at high graft ratio of PLGA. Core-shell type nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In conclusion, size, morphology, and molecular structure of DexLG nanoparticles are available to consider as an oral drug targeting nanoparticles.

• Journal of Food Hygiene and Safety
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• v.28 no.1
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• pp.69-74
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• 2013

This study has been performed for 150 days from February 1 - June 31, 2012 aiming at analyzing biologically hazardous factors in order to develop HACCP system for the vinegared pickle radishes. A process chart was prepared as shown on Fig. 1 by referring to manufacturing process of manufacturer of general vinegared pickle radishes regarding process of raw agricultural products of vinegared pickle radishes, used water, warehousing of additives and packing material, storage, careful selection, washing, peeling off, cutting, sorting out, stuffing (filling), internal packing, metal detection, external packing, storage and consignment (delivery). As a result of measuring Coliform group, Staphylococcus aureus, Salmonella spp., Bacillus cereus, Listeria Monocytogenes, E. coli O157:H7, Clostridium perfringens, Yeast and Mold before and after washing raw radishes, Bacillus cereus was $5.00{\times}10$ CFU/g before washing but it was not detected after washing and Yeast and Mold was $3.80{\times}10^2$ CFU/g before washing but it was reduced to 10 CFU/g after washing and other pathogenic bacteria was not detected. As a result of testing microorganism variation depending on pH (2-5) of seasoning fluid (condiment), pH 3-4 was determined as pH of seasoning fluid as all the bacteria was not detected in pH3-4. As a result of testing air-borne bacteria (number of general bacteria, colon bacillus, fungus) depending on each workplace, number of microorganism of internal packing room, seasoning fluid processing room, washing room and storage room was detected to be 10 CFU/Plate, 2 CFU/Plate, 60 CFU/Plate and 20 CFU/Plate, respectively. As a result of testing palm condition of workers, as number of general bacteria and colon bacillus was represented to be high as 346 $CFU/Cm^2$ and 23 $CFU/Cm^2$, respectively, an education and training for individual sanitation control was considered to be required. As a result of inspecting surface pollution level of manufacturing facility and devices, colon bacillus was not detected in all the specimen but general bacteria was most dominantly detected in PP Packing machine and Siuping machine (PE Bulk) as $4.2{\times}10^3CFU/Cm^2$, $2.6{\times}10^3CFU/Cm^2$, respectively. As a result of analyzing above hazardous factors, processing process of seasoning fluid where pathogenic bacteria may be prevented, reduced or removed is required to be controlled by CCP-B (Biological) and threshold level (critical control point) was set at pH 3-4. Therefore, it is considered that thorough HACCP control plan including control criteria (point) of seasoning fluid processing process, countermeasures in case of its deviation, its verification method, education/training and record control would be required.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.301-314
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• 2005

Objective: Rebamipide is a propionic acid derivative that has an action of the inhibition of superoxide production and removal of hydroxyl radical with the sperm incubation and cryopreservation. In the present study, to investigate whether rebamipide is useful to treat male infertility and sterility, the author observed the antioxidative effects in patient with male infertility and also examined its absorption and distribution in rat genital organ. Methods: To measure the distribution of rebamipide in reproductive organ in the rat, carbon indicated rebamipide, $^{14}C-OPC-12759$, was orally administered to 10 Spraque-Dawley rats and its organ concentration in serum, liver, kidney, stomach, duodenum, colon, urinary bladder, seminal vesicle, epididymis and testicle were measured each time after 0.5, 1, 2, 4, 8 and 24 hours by using HPLC fluorescent method. The concentrations in semen were measured by HPLC fluorescent method in a sample of 50 infertile males who took 900 mg of rebamipide daily for 3 months. To measure the antioxidative effect and fertility rate for 3 months, each month before and after the treatment, sperm motility, vitality, the oxygen free radical formation, level of peroxidation, fetilizing capacity of semen sample which were obtained from infertile male patients by masturbation after at least 48 hours abstinence were analyzed by computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence, thiobarbituric acid method and hypo-osmotic swelling test. Simultaneously in a sample that wanted baby, both pregnancy and delivery were researched. Results: The $^{14}C-OPC-12759$ concentration in the body of white rats was highest in gastrointestinal organ like stomach, smal intestine and duodenum and followed by genital organ like seminal vesicle, testis and epididymis. The rebamipide concentration in semen of infertile males was $220.77{\pm}327.84ng/mL$ (SD) which showed a large deviation but it was higher than serum which was $126{\pm}76ng/mL$ (SD). In the infertile males, after the treatment with rebamipide, the level of seminal reactive oxygen species (ROS) and lipid peroxidation have significantly decreased in duration of the treatment (p<0.05) and sperm vitality and fertilizing capacity except sperm motility significantly improved on post treatment of 2~3 months (p<0.05). Out of the 41 cases who hoped for pregnancy, 15 cases (36.6%) became pregnant and 12 cases had childbrith, 2 cases had miscarriage and one case is ongoing. The side effect was observed in 1 case (2%) which experienced diarrhea but it was lost spontaneously. Conclusions: We conclude from this study that rebamipide showed relatively high tendancy of absorption and excretion in the genital organ. In infertile males who had elevated ROS in semen, by specifically inhibiting the cell damage from the antioxidation, a way to preserve sperm motility, vitality and fertilizing capacity was confirmed.

• Advances in pediatric surgery
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• v.5 no.1
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• pp.75-81
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• 1999

A survey on the intestinal atresias was made among 34 members of Korean Association of Pediatric Surgeons. The response rate was 82.4 %. Two hundred and fifteen patients from the January 1, 1994 to December 31, 1996 were analyzed. The lesions were 73 cases of duodenum(DA), 72 cases of jejunum(JA), 71 cases ileum(IA) and 2 cases cecum and sigmoid colon respectively. There were 2 cases of combined anomalies (DA + JA + IA and DA + JA). Male to female ratio was 1:1 in DA, and 1.8:1 in JA. Seventy four cases(34.3 %) were premature babies(DA 35.2 %, JA:48.6 %, IA:19.2 %), and 62 cases(28.7 %) had low birth weight (DA:39.4 %, JA 33.0 %, IA:13.7 %). Antenatal diagnosis was made in 92 cases(43.6 %). However 22 cases (23.9 %) of them were transferred to pediatric surgeon after delivery. Maternal polyhydramnios was observed in 63 cases(28.9 %). Seventy· five cases(34.4 %) were taken only simple abdominal film for diagnostic studies. The associated malformations were observed in 54 aresia and were observed more frequently in DA(35 cases, 47.9 %). Meconium peritonitis due to intrauterine bowel perforation was more frequently associated with IA compared to DA and JA. The overall mortality rate was 30 %. (Abbreuations: $P_{T}$;p-value in total, $P_{DJ,DI,JI}$;p value between two groups among duodenal, jejunal and ileal groups).