• Title/Summary/Keyword: In-vivo Test.

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The Hypoglycemic Effect of Saururus chinensis Baill in Animal Models of Diabetes Mellitus

  • Joo, Hee-Jeong;Kang, Ming-Jung;Seo, Tae-Jin;Kim, Hyun-A;Yoo, Sung-Ja;Lee, Soo-Kyung;Lim, Hwa-Jae;Byun, Boo-Hyeong;Kim, Jung-In
    • Food Science and Biotechnology
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    • v.15 no.3
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    • pp.413-417
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    • 2006
  • The purpose of this study was to investigate the hypoglycemic effect of Saururus chinensis Baill in vitro and in vivo. Methanol extract of S. chinensis Baill inhibited yeast ${\alpha}$-glucosidase activity by 49.8%, which was twice as strong as that of acarbose at a concentration of 0.5 mg/mL in vitro. The effect of S. chinensis Baill methanol extract on the postprandial increase in blood glucose levels was studied in streptozotocin-induced diabetic rats using a carbohydrate load test. Oral administration of S. chinensis Baill extract (500 mg/kg) significantly decreased incremental blood glucose levels at 60 and 90 min (p<0.05) after oral ingestion of starch (1 g/kg). The area under the glucose response curve of the S. chinensis Baill group was significantly decreased compared to that of the control group (p<0.05). The effect of prolonged feeding of S. chinensis Baill was studied in an animal model of type 2 diabetes. Three-week-old db/db mice were fed an AIN-93G diet or a diet containing 0.5% S. chinensis Baill extract for 7 weeks after 1 week of adaptation. Plasma glucose, insulin, and blood glycated hemoglobin levels of the mice fed S. chinensis Baill extract were significantly lower than those of the control group (p<0.05). Therefore, we conclude that S. chinensis Baill is effective in controlling hyperglycemia in animal models of diabetes mellitus.

Prediction of the human in vivo antiplatelet effect of S- and R-indobufen using population pharmacodynamic modeling and simulation based on in vitro platelet aggregation test

  • Noh, Yook-Hwan;Han, Sungpil;Choe, Sangmin;Jung, Jin-Ah;Jung, Jin-Ah;Hwang, Ae-Kyung;Lim, Hyeong-Seok
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.160-165
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    • 2018
  • Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

Analysis of genetic characteristics and development of substrate for cultivation in brown strains of Flammulina velutipes (갈색팽이버섯의 유전적 특성검정 및 배지재료 개발)

  • Choi, Jae-Sun;Noh, Jae-Goan;Jang, Who-Bong;Choi, Seong-Yeol;Min, Kyoung-Beom;Kong, Won-Sik
    • Journal of Mushroom
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    • v.5 no.1
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    • pp.13-20
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    • 2007
  • Analysis of genetic characteristics of Flammulina velutipes showed that strains have a range of 85% in genetic distribution diagram. According to this result, we divided these strains into five groups. In experiment of determinating the optimum media and condition in cultivating F. velutipes, we found the optimum temperature and pH range for hypha growth were $25^{\circ}C$ and 6.0 to 7.0, respectively. in addition, the best media for growth of that in plate was MCM (Mushroom Complete Media) which have a growth length from 68 to 83 mm. In vivo test, we observed that fast growth and good density of hyphae in mixture media of douglas fir sawdust, cotton seed meal and beet pulp (6:2:2 V/V). Also when we cultivated F. velutipes in this media, we harvested high yield of fruiting body.

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The effect of rhBMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization (골형성유도단백질의 첨가가 ${\Delta}^{12}-PGJ_2$가 유도하는 석회화에 미치는 영향)

  • Kim, Won-Kyung;Kim, Kyoung-Hwa;Kim, Jong-Jin;Lee, Young-Kyu;Ku, Young
    • Journal of Periodontal and Implant Science
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    • v.35 no.2
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    • pp.345-357
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    • 2005
  • Prostaglandin plays a significant role in the local control of bone metabolism associated with periodontal disease. ${\Delta}^{12}-PGJ_2$ is a natural $PGD_2$ metabolite that is formed in vivo in the presence of plasma. It is known for ${\Delta}^{12}-PGJ_2$ to stimulate calcification in osteoblastic cells. Bone morphogenetic protein(BMP) stimulated osteoblastic differentiation in various types of cells and greatly enhanced healing of bony defects. The purpose of this study was to evaluate the effect of rhEMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization in vitro. A human osteosarcoma cells line Saos-2 were cultured. In the test groups, 10-7M of ${\Delta}^{12}-PGJ_2$ or mixture of 10-8M of ${\Delta}^{12}-PGJ_2$ and 100ng/ml of rhBMP-2 or 100ng/ml of rhEMP-2 were added to culture media. After 1 day, 2 days and 4 days of culture period, the cell number was measured. Alkaline phosphatase activity was measure at 3 days. Reverse transcription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein at 8 hours, 1 day and 7 days. The ability to produce mineralized nodules in rat osteoblasts(MC3T3-E1) was evaluated at 21 days. The results were as follows : 1. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ inhibited cell proliferation of human osteosarcoma cells. 2. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated alkaline phosphatase activity significantly higher than ${\Delta}^{12}-PGJ_2$ alone. 3. rhBMP-2 or mixture of rhEMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated mineralization compared to ${\Delta}^{12}-PGJ_2$ alone. 4. mRNA of alkaline phosphatase, BMP-2, cbfa 1, Type I collagen were detected in the group treated with ${\Delta}^{12}-PGJ_2$/rhBMP-2, rhBMP-2 alone, ${\Delta}^{12}-PGJ_2$ alone. These results show that mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 causes more bone formation than ${\Delta}^{12}-PGJ_2$ alone while the bone formation effects of mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 are less than those of rhBMP-2 alone. Further researches would be necessary to clarify the interactions of these agents.

Application of Chitosan Preparations for Eco-friendly Control of Potato Late Blight (감자 역병의 친환경 방제를 위한 키토산 제형의 살포)

  • Chang, Taehyun;Kim, Byung Sup
    • Research in Plant Disease
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    • v.18 no.4
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    • pp.338-348
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    • 2012
  • Potato late blight caused by Phytophthora infestans Cooke is one of the major diseases in the cultivation of potatoes in Korea. Effect of chitosan preparations (SH-1 and SH-2) was evaluated on the inhibition of mycelial growth of P. infestans, and protective activity using detached potato leaf assay both in vivo and in the field test. SH-1 and SH-2 were showed protective activity of young plant with control values more than 95% potato late blight by inoculation with pathogens under growth chamber conditions. Mycelial growth was inhibited the radial growth over 74% at a concentration of $300{\mu}g/ml$ of both SH-1 and SH-2. Spraying with SH-1 and SH-2 on the leaves for detached leaf assay reduced disease development. The content of total polyphenol in stem was significantly increased by SH-1 and SH-2 application in the field. In field experiments, foliar application with both SH-1 and SH-2 were significantly reduced the development of late blight on potato plants. Control of late blight disease was obtained with control values of 72% and 53% by application of 1% SH-1 and SH-2, respectively, with 4 times at 7 days interval, and reduced with similar disease control values by application with 3 times at 14 days interval compared with untreated control. SH-1 and SH-2 applications increased the fresh weight of potato, and higher grade potatoes were also increased. The results showed that SH-1 and SH-2 applications can be used as eco-friendly natural fungicide for organic farming for the increase of yields and control of late blight.

Studies on Whitening and UV Damage Protection Effect of the Pterin Compounds (테린계 화합물의 미백 및 자외선 손상방어 효능에 관한 연구)

  • Kim, Nam-Kyoung;Kim, Mi-Hwa;Kang, Nae-Im;Choi, Shin-Wook
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.1 s.60
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    • pp.53-60
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    • 2007
  • (6R)-5,6,7,8-tetrahydrobiopterin ($6-BH_4$) cofactor is essential for various process, and is present in probably every cell or tissue of higher organism. $6-BH_4$ is required lot various enzyme activities, and for less defined functions at the cellular level. And it is well known about the antioxidant effects as a non-protein compound. Recently, scientists proposed another roles for $6-BH_4$ in melanogenesis. $6-BH_4$ is a well known tyrosinase inhibitor. In this study, we found that methyl-$BH_4$ and $6-BH_4$ have antioxidant activities and inhibitory activity for melanin synthesis. These pterin compounds were not toxic in HaCaT and B16F10 cells and showed scavenging activity against DPPH radicals. We also showed that pterin compounds decreased protein levels of tyrosinase and TRP-1. In a clinical test, pterin compounds showed the significant skin whiteining effect after treatment for 3 weeks. Furthermore pterin compounds significantly suppressed the UVB-induced expression of $PGE_2$ and IL-6 genes induced UVB In HaCaT and inhibited UVB-induced melanogenesis in B16F10 cells. These results showed the effect of pterin compounds as a cosmeceutical ingredient.

Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis

  • Seo, Jaesung;Kee, Hyun Jung;Choi, Hye Ji;Lee, Jae Eun;Park, Soo-Yeon;Lee, Seung-Hyun;Jeong, Mi-Hyeon;Guk, Garam;Lee, SooYeon;Choi, Kyung-Chul;Choi, Yoon Young;Kim, Hyunki;Noh, Sung Hoon;Yoon, Ho-Geun;Cheong, Jae-Ho
    • BMB Reports
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    • v.51 no.5
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    • pp.255-260
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    • 2018
  • Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

Establishment of ethanol-pretreating animal model to study Helicobacter pylori infection (Helicobacter pylori의 in vivo 연구를 위한 ethanol-pretreating animal model의 개발)

  • Lee, Jin-Uk;Kim, Seung-Hee;Park, Tan-Woo;Kim, Okjin
    • Korean Journal of Veterinary Research
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    • v.46 no.4
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    • pp.327-335
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    • 2006
  • A stable and reliable Helicobacter pylori (H. pylori) infection animal model would be necessary for evaluating vaccine efficacy and helpful for understanding the pathological mechanism of the organism. The aim of the present study is to investigate the effect of ethanol treatment prior to H. pylori inoculation on associated gastric mucosal injury and to establish ethanol-pretreating animal model to study H. pylori infection. Male Mongolian gerbils were used for the study. H. pylori was orally inoculated after 12 h fasting. 3 h prior to H. pylori inoculation, a group of gerbils was orally treated with absolute ethanol, 60% and 40% ethanol respectively. Another group of animals was treated either with H. pylori culture media alone or with different concentrations of ethanol plus culture media. Gerbils were killed 4 or 8 weeks after H. pylori inoculation. The colonization of H. pylori was confirmed by both histological examination and rapid urease test. Mucosal damage was evaluated grossly and histologically according to the criteria. The colonization of H. pylori and pathological changes in gastric mucosa of the animals were also observed. Although no significant change to the gastric mucose was observed in the animals treated either with H. pylori culture media alone or with different concentrations of ethanol plus culture media, persistent H. pylori infection was seen in the mucosa and mucosal leucocyte infiltration and severe epithelial damage was observed in the Helicobacter and ethanol + Helicobacter groups after 4 weeks. The gross and histological scores were higher in the ethanol + Helicobacter than in the Helicobacter alone group. As the results, ethanol-pretreatment with 60% concentration induced severe pathogenic changes by H. pylori infection in 5 weeks-old Mongolian gerbils. These results suggested that ethanol-pretreatment before H. pylori inoculation could increase the severity of gastric mucosal inflammation and enhance the colonization of H. pylori. The established ethanol-pretreating animal model would contribute to screen new drugs against H. pylori and be used as an useful tool for various animal experiments with H. pylori strains.

A Study of the Efficacy of Hair Analysis Relative to Serum and Organ Analysis for Assessing Heavy Metal Reduction in Living Animals Treated with an Herbal Medicine Remnant and Organic Selenium (한약박 및 유기셀레늄이 체내 중금속 축적도에 미치는 영향의 모발 분석과 혈액 및 장기 분석간의 상관도 연구)

  • Son, Young-Hee;Yoo, Ji-Eun;Heo, Ji-Youn;Jang, Sung-Pyo;Lee, Byung-Soo;Lee, Bo-Reum;Yun, Seon-Gi;Lee, Chi-Ho
    • Food Science of Animal Resources
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    • v.28 no.2
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    • pp.222-231
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    • 2008
  • This study was carried out to develop a method for decreasing the heavy metal composition of living stock. Sprague-Dawley (SD) male rats were pre-treated with heavy metals administered i.p. at the limits of regulation according to the feed CODEX in Korea. Herbal medicine remnant was administered p.o. (2, 4 ppm of average feeding amount) for the entire period of study with organic selenium (2 ppm of average feeding amount) before any other treatment. 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) was also administered i.p. in a single dose of 60 mg/kg body weight before animals were sacrificed. The TBARS test with the FOX assay demonstrates a decrease of heavy metals due to these functional materials in vitro. Moreover, this decrease in heavy metals was also demonstrated by in vivo tests based on SD rats hair analysis and organ analysis after 6 weeks. A good linear correlation between hair analysis and organ analysis represented by liver and blood was shown. The present findings suggest that measurement method of heavy metal composition using hair analysis for healthy livestock can be used in place of detection methods carried out by organ and blood analysis, and herbal medicines with organic selenium may be very effective at decreasing heavy metals of feed materials in feed manufacture industry.

Efficacy of Enrofloxacin and Silver Sulfadiaznine Topical Otic Suspension for the Treatment of Canine Otitis Externa (개 외이염에 대한 Enrofloxacin과 Silver Sulfadiazine 국소제제의 치료효과)

  • Bae, Seulgi;Kim, Byeongmok;Choi, Sungwon;Sin, Hui-Ju;Lee, Young-Ju;Oh, Tae-Ho
    • Journal of Veterinary Clinics
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    • v.30 no.3
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    • pp.172-177
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    • 2013
  • The aim of this study was to evaluate the in vivo and in vitro efficacy of enrofloxacin-silver sulfadiazine (Baytril$^{(R)}$ otic, Bayer, USA) for the treatment of otitis externa in dogs. Twenty-four dogs with otitis externa were included in this double-blinded, randomized study. The experimental group was treated with the Baytril$^{(R)}$ otic and the distilled water was applied to the control group. Both groups were administered each solution twice daily for 7 days and next 7 days off treatment. On days 0, 7 and 14, clinical signs, bacteriological and fungal counts were graded using semi-quantitative scales, respectively. For the evaluation of in vitro efficacy of Baytril$^{(R)}$ otic, we also performed Minimal Inhibitory Concentration (MIC) test by agar dilution method against Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Malassezia pachydermatis. In the experimental group, the sum of clinical scores was decreased 81.0% and microbial scores were significantly reduced 87.0% at days 14, compared with day 0. The results of MIC testing were showed the concentration of enrofloxacin and silver sulfadiazine in Baytril$^{(R)}$ otic is high enough to kill for 3 infectious agents. No adverse reactions were observed in any of the dogs during this study. These results suggest that Baytril$^{(R)}$ otic are efficient and safe treatment for canine otitis externa.