• Title/Summary/Keyword: Toxicity tests

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DA-7911, $^{188}Rhenium-tin$ Colloid, as a New Therapeutic Agent of Rheumatoid Arthritis

  • Shin, Chang-Yell;Son, Miwon;Ko, Jun-Il;Jung, Mi-Young;Lee, In-Ki;Kim, Soon-Hoe;Kim, Won-Bae;Jeong, Jae-Min;Song, Yeong-Wook
    • Archives of Pharmacal Research
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    • v.26 no.2
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    • pp.168-172
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    • 2003
  • Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

EVALUATION OF SODIUM DICHLOROISOCYANURATE AS A ROOT CANAL IRRIGATION SOLUTION;Cl- CONCENTRATION, pH, CYTOTOXICITY AND ANTIMICROBIAL EFFECT IN VITRO (이염화이소시아뉼산나트륨 제재의 근관세척액 사용 가능성 평가;염소이온농도, 세포독성, 항균성 및 pH)

  • Lee, Woo-Cheol;Kang, Bong-Sun;Kim, Cheol-Ho;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.28 no.5
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    • pp.425-430
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    • 2003
  • The purpose of this study was to evaluate the clinical applications of the Sodium Dichloroisocyanurate effervescent tablet as a routine root canal irrigant by performing several in vitro tests such as $Cl^{-}$ content. cytotoxicity. antimicrobial effect as well as its pH level compared to the equivalent concentration of sodium hypochlorite solution. 1. Sodium Dichloroisocyanurate demonstrated lower level of $Cl^{-}$ concentration than each dilution of sodium hypochlorite solution. Both solution has increased level of $Cl^{-}$ as the concentration of each solution increased. There was no significant change of $Cl^{-}$ concentration in sodium hypochlorite as time goes by. However. $Cl^{-}$ concentration in Sodium Dichloroisocyanurate was increased. 2. The antimicrobial effects of both solutions were increased when their concentrations were increased. One day after dilution. antimicrobial effect of Sodium Dichloroisocyanurate was slightly higher than sodium hypochlorite. however. there was no difference in 1 week dilution solution. One month dilution solution of sodium hypochlorite still retain its activity. but antimicrobial effect of Sodium Dichloroisocyanurate was drastically decreased 1 month after dilution. 3. The cytotoxicity of Sodium Dichloroisocyanurate was rather higher than same concentration of sodium hypochlorite solution until 1 week after dilution. Then in 1 month. cytotoxicity of Sodium Dichloroisocyanurate was decreased than that of 1 week dilution solution. especially 4% Sodium Dichloroisocyanurate solution has almost no toxicity. However. 1% and 2% sodium hypochlorite solution has unchanged moderate degree of cytotoxicity after the dilution. Furthermore. 4% sodium hypochlorite solution showed high level of toxicity. 4. The pH level of Sodium Dichloroisocyanurate showed that the solution was weak acid (pH5). On the other hand. sodium hypochlorite was revealed as a strong alkaline solution (pH12). There was no change in pH following the dilution of each solution. As results. Sodium Dichloroisocyanurate solution fully satisfy the basic requirements as a root canal irrigation solution. However. we strongly recommend to use this solution clinically in low concentration and try to apply into the root canal within 1 week after dilution.

Limits of Innovation in Korean Medicine Industry (한의학산업의 혁신 저해요인)

  • Ku, Nam-Pyong;Seol, Sung-Soo
    • Journal of Korea Technology Innovation Society
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    • v.18 no.4
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    • pp.667-692
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    • 2015
  • The study examined the Korean medicine industry from the perspective of the innovation system theory of each business, while it concentrated on the conflict between traditional Korean medicine and Western medicine, which have a major influence on the innovation system of Korean medicine industry, rather than the innovation system itself. The Korean healthcare system is a dual system of Western and Korean medicine, yet the definitions of Western medical practices and Korean medical practices are ambiguous. Thus the distinction of dual system depends on judicial precedents, and the innovation of Korean medicine has been inhibited due to the excessive emphasis placed on the Western medical practice in both healthcare system and pharmaceutical system. First of all, the usage of most medical devices derived from the development of modern medical engineering is not permitted in the Korean medicine industry, on the basis that most of the medical devices were originated from the Western medicine field. Secondly, new drugs using natural substances, once approved by the drug administration, cannot be prescribed by the Korean medicine industry although they are developed based on Korean medicine. Thirdly, the major safety issues on herbal medicine are about hazardous materials in medicinal herbs and liver toxicity of prescribed herbal medicine. The problem of hazardous materials can be solved by appropriate quality and safety tests in the cultivation and importation process. Whereas the Korean medicine circles points out that the liver toxicity issue is only a unilateral condemnation by the Western medicine circles.

Selection of Low Pathogenic Variety in Bacillus thuringiensis to Silworm, Bombyx mori (누에에 대한 저독성 Bacillus thuringiensis 균근의 선발)

  • Kim, Cheol-Yeong;Kim, Yeong-Hun;Gang, Seok-Gwan
    • Journal of Sericultural and Entomological Science
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    • v.28 no.1
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    • pp.43-53
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    • 1986
  • Among many microbial pesticides, Bacillus thuringiensis is one of the most hopeful pesticide and some commercial products have been appearing on the market. Because these commercial products contain living spores and toxins of the organism, there is a danger that living spores of B. thuringiensis may be scattered by wind and cause a great damage in the sericulture areas. In order to avoide these risks it is desirable to select the strain which has low pathogenicity to the silkworm, and at the sometime being highly pathogenic to the pest insects. Thus this study has been carried out to acquire some basic informations about the procedure of desicable strain selection. Three strains of B. thuringiensis var. kurstaki, var. dendrolimus and var. aizawai were used for the pathogenicity test on the silkworm, Bombux mori and the fall webwarm, Hyphantria cunea. Those strains were investigated by the agarose gel electrophoresis patterns of plasmid DNA determine whether mutation had occured. Pathogenicity tests were carried out of using isolated crystal proteins and spore-crystal protein to mixtures of each strain, seperatively. In case of using spore-crystal protein mixture, the order of pathogenicity in varities of B. thuringiensis against B.mopri and H.cunea were kurstaki, aizawai, dendrolimus and kurstaki, dendrolimus, aizawai, respectively. But using isolated crystal proteins, dendrolimus had the highest toxicity to H. cunea and the lowest toxicity to B. mori among tested three strains. From the above results, dendrolimus was presumed the most desirable straing for using microbial pesticide.

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The Protective Effect of Zizania latifolia Extract against t-BHP-induced Oxidative Stress in HepG2 Cells (고장초 추출물의 t-BHP로 산화적 손상이 유도된 HepG2 세포 보호 효과)

  • Park, Se-Ho;Lee, Jae-Yeul;Yang, Seun-Ah;Bang, Daesuk;Jhee, Kwang-Hwan
    • Journal of Life Science
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    • v.31 no.3
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    • pp.338-345
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    • 2021
  • Zizania latifolia has long been used as a tea for both edible and medicinal purposes. However, research into the use of Z. latifolia as a high value-added edible material is lacking. In a previous study, we confirmed that tricin is the major component in Z. latifolia. In this study, we investigated the protective effect of a Z. latifolia extract (ZLE). Toxicity tests of ZLE or tricin on HepG2 cells revealed no toxicity due to ZLE or tricin at all concentrations used. The reduction in cell viability by tert-butyl hydroperoxide (t-BHP) was suppressed by treatment with ZLE or tricin. In addition, ZLE or tricin effectively inhibited the production of reactive oxygen species (generation of hydrogen peroxide, alkoxy free radicals, and peroxyl free radicals by t-BHP) and oxidative damage. ZLE or tricin treatments also increased the protein expression of superoxide dismutase 1 (SOD1), catalase, heme oxygenase-1 (HO-1), and nuclear factor erythroid-related factor 2 (Nrf2), which are known as antioxidant enzymes, suggesting that the protective effect of ZLE is related to activation of tricin. Taken together, the results indicate that Z. latifolia can be developed as a functional food material for improving liver function.

Functional Characteristics of Soybean Oligosaccharide (콩 함유 올리고당의 기능적 특성)

  • 정명근;이재철
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.48
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    • pp.58-64
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    • 2003
  • To enjoy a healthy life, it is important to have a well-balanced diet. However, in today's society, there is an increase in the consumption of preprocessed foods and frequency of eating out. Also the western diet, which is becoming move popular worldwide, contains relatively high levels of protein and fat, and a low amount of fiber, Furthermore, the increased availability of favorite foods has created a condition were the individual diet is less variable. With these conditions, it is difficult to maintain a diet that is nutritionally balanced. With these unbalanced diets, which are difficult to change, there has been an increase in adult disease and health problems, such as colon and breast cancer, It is speculated that metabolites for carcinogens are produced from diet components and that intestinal bacteria contribute to the production of these metabolites. Therefore, it is necessary to evaluate the relationships between health, diet, and intestinal microflora. Soybean oligosaccharide is composed of water-soluble saccharides that have been extracted from soybean whey, a by-product from the production of soy protein. This is mainly a mixture of mono-, di-, tri-, and tetrasac-charides, with the principle components being the oligosaccharide raffinose and stachyose. When consumed by humans, the oligosaccharides cannot be digested in the human duodenal and small intestinal mucosa, and these are selectively utilized by beneficial bifidobacteria in intestines. The results of acute and subacute toxicity tests, soy-bean oligosaccharides were nonpoisonous. Soybean oligosaccharides promote the growth of indigenous bifido-bacteria in the colon which by their antagonistic effects, suppress the activity of putrefactive bacteria. Also, they reduce toxic metabolites, detrimental enzymes and plasma lipid, and increase in the frequency of bowel evacuation and fecal quantities. Consequently, soybean oligosaccharides as functional foods components have potential roles in the prevention and medical treatment of chronic adult diseases. The study of processing property and physiological function of soybean oligosacchavides and development of high oligosaccharide variety allow the creation of new and exciting foodstuffs that aye functional healthy.

Genotoxicity on Structural Derivatives of Sophoricoside, a Component of Sophora Japonica, in Bacterial and Mammalian Cells

  • Ryu, Jae-Chun;Kim, Youn-Jung;Kim, Mi-Soon;Kim, Min-Ji;Sarma, Sailendra Nath;Jung, Sang-Hun
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.179-188
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    • 2005
  • To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

Immortalization of Rabbit Corneal Fibroblasts by Overexpression of Simian Virus 40 Large T antigen

  • Cho, Seung-Ju;Park, Yuk-Pheel;Lim, Heon-Man;Kim, Jae-Chan;Yang, Eun-Kyung;Park, Jung-Keug;Yoon, Do-Young;Lee, Hee-Gu
    • Biomedical Science Letters
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    • v.10 no.2
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    • pp.85-92
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    • 2004
  • Immortalization of primary corneal cells has influence on pharmacy, medical and biological fields. Especially, investigation of immortalization mechanism using viral oncoproteins is useful for medical treatments, and these cell lines will be useful materials for toxic test of medical supplies and cell biological experiments. Rabbit corneal fibroblasts in culture undergo a finite number of divisions before they reach a terminally non-proliferating state known as replicative senescence. Therefore, we attempted to induce immortalization of rabbit corneal fibroblasts with SV 40 large T antigen. As a result of experiment, expression of SV 40 large T antigen was confirmed, and expression of proteins related to cell cycle repressor was decreased in the transfection group compared with non-transfection group. According to the results of cell cycle phase distribution test, SV 40 large T antigen-transfected cells had obtained higher proliferation rate than primary cells. It was confirmed that during induction of immortalization, SV 40 large T antigen was not able to increase telomerase activity. In conclusion, we made a rabbit corneal fibroblast cell line with SV40 large T antigen. This cell line will be useful for further studies of mammalian fibroblast biology, particularly with regard to angiogenesis and malignant transformation. In addition, this cell line offers opportunity for testing potential therapeutics and can be used for toxicity tests of materials or cosmetics. In the future, our cell line can potentially be utilized in a wide range of biology related fields.

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Partial Characterization of Bacillus thuringiensis var. kurstaki Temperature-sensitive Mutants (Bacillus thringiensis var. kurstaki 감온성 돌연변이주의 일부특성)

  • 김영권;유관희;이형환;이호원
    • Korean Journal of Microbiology
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    • v.23 no.3
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    • pp.203-208
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    • 1985
  • Partial characterization of B. thuringiensis var. kurstaki 3ab temperature-sensitive mutants was carried out through biochemical analyses, utilization tests of carbohydrate sources, antobiotic resistant test, hemolytic reaction test, growth measurement of Fructus gardenia sxtrant medium and toxicity test against mice. Six ts mutants, ts-U154, ts-U601, ts-U602, ts-U603, tsU-604, and ts-U788 could not produce urease, ts-U603 lost its motility, ts-U154 could not use salicin and cellobiose and ts-U603 not ribose. All ts mutants except ts-U154 and wild type strain were resistant to cephalothin, ampicillin, and penicillin. but ts-U154 was sensitive to the three. Four mutants, ts-U21, ts-U74, ts0U131 and ts-U154 did not form pigment colonies on the F. gardenia medium. All the mutants and wild type strain showed hemolysis reaction on the blood agar. The B. thuringiensis and mutants were not toxic to mice.

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Preparation and Characterization of Simvastatin Solid Dispersion using Aqueous Solvent

  • Kim, Kwang-Hyeon;Park, Jun-Bom;Choi, Won-Jae;Lee, Han-Seung;Kang, Chin-Yang
    • Journal of Pharmaceutical Investigation
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    • v.41 no.4
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    • pp.239-247
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    • 2011
  • Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.