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Four-Week Repeated-Dose Toxicity Studies of Hyrubicin ID6105, a Novel Anthracycline Anticancer Agent, in Rats (랫드에서 새로운 Anthracycline계 항암제 Hyrubicin ID6105에 대한 4주 반복투여 독성연구)

  • 장호송;서동석;인창훈;황재식;이수해;정미숙;신지순;이홍섭;유정수
    • Toxicological Research
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    • v.18 no.4
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    • pp.375-384
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    • 2002
  • Repeated-dose toxicity of hyrubicin ID6105, a novel anthrarycline anticancer agent, was investigated in Sprague-Dawley rats. ID6105 was injected intravenously to rats at dose levels of 0.04, 0.2 or 1.0 mg/kg/day for 4 week. As a result, there were no dose-related mortality and specific clinical signs of all animals treated with the drug. However body weight gain of both male and female rats treated with a high dose (l.0 mg/kg/day) of ID6105 significantly decreased compared to control. Interestingly, the numbers of RBC and platelets, and concentration of hemoglobin remarkably increased, while protein synthesis was suppressed, which may be related to the atrophy of spleen, thymus and liver. Moreover there were severe lymphocytic depletion in spleen and thymus as well as decrease in the number of hematopoietic cells in bone marrow. Also, degeneration of cardiac muscles and testicular germinal epithelia were observed. Taken together, it is suggested that Long-term administration of ID6105 at high doses over 0.2 mg/kg/day might cause hematopoietic and male reproductive system injuries, in addition to hepatic dysfunction.

The Impacts of the 40 Hour Work Week Standard on Actual Working Hours, Wages and Employment (주 40시간 근무제의 도입이 근로시간, 임금 및 고용에 미치는 영향)

  • Kim, Hyungrak;Lee, Jungmin
    • Journal of Labour Economics
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    • v.35 no.3
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    • pp.83-100
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    • 2012
  • This paper estimates the impacts of introducing the 40 hour work week standard in South Korea on actual working hours, wages and employment. We exploit variation in timing of implementing the 40 hour work week standard across industries and establishment size and estimate the causal effects by a triple difference model. Our results show that the 40 hour work week standard decreased actual working hours by about 43 minutes while it increased hourly wage rate by 6.6%. The probability of new hires decreased by about 2.3% points.

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The Effects of Dietary Iodine Intake on the Postpartum Thyroiditis(PPT) Manifestation (산모의 요오드섭취가 산후 갑상선염 발현에 미치는 영향)

  • 조여원
    • Journal of Nutrition and Health
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    • v.30 no.10
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    • pp.1195-1202
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    • 1997
  • Iodine-rich seaweed soup has been traditionally supplied to postpartum women in Korea. This dietary habit might introduce over-intake of iodine above the recommended requirements, and might provoke postpartum thyroid dysfunction. Although the response to excess iodine intake is highly variable, goiter, hyperthyroidism, hypothyroidism, and thyroiditis could follow the daily intake of 1,500$\mu\textrm{g}$ of iodine. A few studies are available concerning iodine toxicity in Korea. The purpose of this study was to investigate the relationships between the dietary intake of iodine and thyroid function change as well as the incidence of postpartum thyroiditis. One hundred and thirty-seven postpartum women who had experienced normal deliveries were studied. Dietary intake of iodine and excretion concentration of iodine in breast milk and maternal urine were measured . Serum T$_3$, T$_4$, TSH, anti-thyroglobulin antibody, and anti-microsomal antibody were anlayzed 1 week before delivery and 1, 6, 12, and24 weeks after delivery. Iodine intake was analyzed by one-to-one interviews using 24-hr recall and a food frequncy questionnaire. The result showed that the intake of dietary iodine before delivery and 1 and24 weeks after delivery were 483$\mu\textrm{g}$/day, 3367$\mu\textrm{g}$/day, and 1069$\mu\textrm{g}$/day, respectively. The concentration of iodine in urine at the first week after delivery was 63$\mu\textrm{g}$/dL, and 23.9$\mu\textrm{g}$/dL in breast milk . The levels of serum T$_3$ and T$_4$ before delivery were 2.01ng/mL and 11.49$\mu\textrm{g}$U/dL, respectively, showing that the levels were gradually dropping to normal values after delivery. Positive serum anti-thyroglobulin antibody and anti-microsomal antibody appeared in 3 cases. After a 24 week follow-up period , 6 women(10.3%) experienced cases of postpartum thyroiditis, 5 of which were cases of hyperthyroidism and one of which was a case of hypothyroidism. These figures of postpartum thyroiditis are similar to those of other countries.

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Study on the Effect of Ginseng on the cyclic AMP Content in the Rat Hearts (인삼(人蔘)이 백서심장(白鼠心臟)의 cyclic AMP함량(含量) 변화(變化)에 미치는 영향(影響)에 관(關)한 연구(硏究))

  • Kim, Nak-Doo;Cha, Soo-Man
    • Korean Journal of Pharmacognosy
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    • v.13 no.4
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    • pp.137-144
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    • 1982
  • It was previously reported from our laboratory that the rate of deterioration of the force of contraction was slower in heart from Panax ginseng extract treated rats. The study carried out to elucidate its mechanism of the action on hearts. The cyclic AMP content in the rat hearts was measured by the method of radioimmunoassay techniques. Panax ginseng extract (100mg/kg/day) was administered orally to male Sprague-Dawley rats weighing 150g to 250g for 1 week and after 24 hrs the hearts were isolated and the cyclic AMP content in the fresh heart was assayed. The difference in cyclic AMP content between the rats treated with Panax ginseng extracts and normal rats was not significant. Panax ginseng extract(l00mg/kg/day) was administered orally to the rats for I week and after 24 hrs the hearts were isolated and perfused with Krebs-Henseleit buffer (pH7.4) for 90min. The cyclic AMP content in the both treated and normal rats was not also significantly different. On the other hand, when total ginseng saponin (50mg/kg/day) was administered orally to rats for 1 week and after 24 hrs, the isolated hearts were perfused with Krebs Henseleit solution for 32min, the cyclic AMP content in total ginseng soponin treated hearts was decreased by 18.7% compared to normal rats. It was also observed that when isolated hearts were perfused with total ginseng saponin $(10^{-4}g/ml)$ for 12 min after 30 min equilibration period, the cyclic AMP content in total ginseng saponin treated hearts was decreased by 23.7% compared to normal rats. Isolated hearts were perfused with ginseng saponins $(10^{-4}g/ml)$ or with Krebs-Henseleit solution alone for 10min and subsequently with dl-isoproterenol $(1/2{\times}10^{-6}M)$ until the positive inotropic effect of isoproterenol was initiated. The cyclic AMP content in each rat hearts treated with total ginseng saponin, or with ginsenoside $Rb_1$, or with Krebs-Henseleit solution alone were increased by 35.5%, 42.4%, 47.5%, respectively, compared to normal rats.

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Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

  • Noh, Hye-Ji;Koh, Hong Bum;Kim, Hee-Kyoung;Cho, Hyang Hyun;Lee, Jeongmin
    • Nutrition Research and Practice
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    • v.11 no.1
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    • pp.11-16
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    • 2017
  • BACKGROUND/OBJECTIVES: Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS: The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), IL-$1{\beta}$, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS: G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-$1{\beta}$ and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION: G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention.

Efficacy of a DNA Vaccine Carrying Eimeria maxima Gam56 Antigen Gene against Coccidiosis in Chickens

  • Xu, Jinjun;Zhang, Yan;Tao, Jianping
    • Parasites, Hosts and Diseases
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    • v.51 no.2
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    • pp.147-154
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    • 2013
  • To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and $100{\mu}g/chick$). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with $5{\times}10^4$ sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control.

Effect of the Mixed Herbal Medicine for the Substitution of Antibiotics on the Performance of Laying Hens(II) - Part of Laying Period and Egg Quality - (산란계 사육에 있어서 한방 조성물의 항생제 대체 효과(II) - 산란과 계란품질 중심 -)

  • Park, Moon-Ki;Kim, Ki-Wook;Kwon, Ki-Chan
    • Journal of Environmental Science International
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    • v.17 no.5
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    • pp.537-546
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    • 2008
  • The experiment was conducted to determine the effect of the mixed herbal medicine for the substitution of antibiotics on the performance of laying hens. Day old hyline 1,500 layer chicks were randomly assigned to 4 treatments. Control were 600 and three each treatment was 300. Eggs were collected at every weeks for measuring egg production and week 26, 27, 28 for chemical analyses. Chemical analyses were done for fatty acid profile of egg yolks, amino acid, antibiotics residue in eggs(collect eggs after supplying OTC 21ppm/bird/day to control for four day at 26, 27, 28) during the laying period($19{\sim}77wk$). On $0{\sim}4$ week, T-3 showed higher feed intake than those fed the other diets and on $5{\sim}13$ week, T-2 showed highest feed intake among treatments. After birds were moved ($14{\sim}18$ wk) CT-3 showed highest, but for overall rearing period, there was not significantly different among treatments. In conclusion the mixed herbal medicine did not tended to influence palatability to rearing birds. Egg quality(egg yolk color, haugh unit, eggshell breaking strength) showed no difference among treatments. Ratio of unsaturated fatty acid (mg/100g)/saturated fatty acid (mg/100g) was not difference among treatments, but linolenic acid and docosahexaenoic acid(DHA) of the mixed herbal medicine treatments showed higher then control. The antibiotics residue of CT, T treatments egg was not detected and control was not detected or below allowance. In conclusion the mixed herbal medicine can be possible to feed laying hen without antibiotics.

The Effect of adding Hip Abductor Strengthening to Conventional Rehabilitation on Muscular Strength and Physical Function following Total Knee Replacement

  • Kim, San-Han;Park, Hye-Kang;Lee, Wan-Hee
    • Physical Therapy Rehabilitation Science
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    • v.11 no.1
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    • pp.16-23
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    • 2022
  • Objective: This study aimed to investigate the effect of adding hip abductor strengthening to conventional rehabilitation on muscle strength and physical function following total knee replacement (TKR) for knee osteoarthritis. Design: Randomized controlled trial Methods: Thirty-five participants were randomly allocated to exercise groups I (n=18) and II (n=17). Group I underwent hip abductor training and conventional rehabilitation for 30 min per day, 5 days per week for 4 weeks. Group II underwent conventional rehabilitation for 30 min per day, 5 days per week for 4 weeks. The participants in both groups also received continuous passive motion therapy for 15 min per day, 5 days per week for 4 weeks. To investigate the effect of the intervention, the Biodex dynamometer was used to measure the peak torque of both knee extensors and hip abductors. This study used the Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) to assess physical function, as well as the figure-of-8 walk test (F8W) and the stair climb test (SCT). Results: According to the interventions, exercise groups I and II showed significantly improved muscle strength and KOS-ADLS, F8W, and SCT scores (p<0.001). Compared with that of exercise group II, exercise group I showed significantly improved hip abductor strength (p<0.001) and KOS-ADLS, F8W, and SCT scores (p<0.05). Conclusions: The results of this study indicate that the combination of hip abductor strengthening and conventional rehabilitation is an effective exercise method to increase hip abductor muscle strength and physical function after TKR.

Two-Week Repeated Inhalation Toxicity Study of Dimethyl Disulfide in Rats (랫드에서 이황화메틸의 2주 반복투여 흡입독성연구)

  • Kim Jong-Choon;Shin Jin-Young;Shin Dong-Ho;Kim Sung-Ho;Lee Sung-Bae;Han Jung-Hee;Chung Yong-Hyun;Kim Hyeon-Yeung;Park Seung-Chun
    • Toxicological Research
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    • v.20 no.3
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    • pp.273-280
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    • 2004
  • The present study was carried out to investigate the potential toxicity of dimethyl disulfide by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the end of treatment period, all males and females were sacrificed. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher dose groups were significantly lower than those of the control group, respectively. The mean food consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared with the controls. Some treatment-related serum biochemical changes, including decreased alkaline phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300 ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent manner, but these findings were considered to be of no toxicological significance. There were no adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group. Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at the dose of male 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day for female rats.

Rule-based Normalization of Relative Temporal Information

  • Jeong, Young-Seob;Lim, Chaegyun;Lee, SeungDong;Mswahili, Medard Edmund;Ndomba, Goodwill Erasmo;Choi, Ho-Jin
    • Journal of the Korea Society of Computer and Information
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    • v.27 no.12
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    • pp.41-49
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    • 2022
  • Documents often contain relative time expressions, and it is important to define a schema of the relative time information and develop a system that extracts such information from corpus. In this study, to deal with the relative time expressions, we propose seven additional attributes of timex3: year, month, day, week, hour, minute, and second. We propose a way to represent normalized values of the relative time expressions such as before, after, and count, and also design a set of rules to extract the relative time information from texts. With a new corpus constructed using the new attributes that consists of dialog, news, and history documents, we observed that our rule-set generally achieved 70% accuracy on the 1,041 documents. Especially, with the most frequently appeared attributes such as year, day, and week, we got higher accuracies compared to other attributes. The results of this study, our proposed timex3 attributes and the rule-set, will be useful in the development of services such as question-answer systems and chatbots.