• Title/Summary/Keyword: drug development

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Development of Differential Diagnosis and Treatment Method of Reproductive Disorders Using Ultrasonography in Cows 1. Response of Ovarian Structures to CIDR Treatment at Day 16 of Estrous Cycle in Dairy Heifers (초음파검사에 의한 소의 번식장애 감별진단 및 치료법 개발 1. 처녀젖소에서 발정주기의 16일째에 CIDR의 치료에 대한 난소구조물의 반응)

  • 강현구;강병규;칠한선;중미역언;서국현;손창호
    • Journal of Veterinary Clinics
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    • v.15 no.1
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    • pp.131-139
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    • 1998
  • Progesterone을 함유하고 있는 CIDR(Controlled Internal Drug Release)의 질내삽 입은 황체기를 인위적으로 연장시킬 수 있다. CIDR의 삽입이,삽입시 존재했던 우세난포 (dominant follicle)의 반응과 난포의 발육반응 그리고 2회 또는 3회의 난포주기를 가지고 있는 처려우에서 CIDR의 삽입기간동안 난포의 성장 및 발육에 어떠한 영향을 미치는가를 비교검 토하기 위하여 배란후 16일째의 처녀우 4마리에 7일동안 CIDR를 삽입하였다. CIDR의 삽입 은 발정의 발현을 억제시켰으며 그리고 발정주기의 길이를 정상 발정주기보다 유의성있게 연 장시켰다($26.3{\pm} 0.5 vs 20.8{\pm}$ 1.5일, p<0.05). CIDR의 삽입시 혈장 progesterone 농도는 $3.6{\pm}$ 2.7 ng/ml 이었으며, 17일과 23일 사이에는 2.1-4.4 ng/ml($3.6{\pm}1.2 ng/ml$) 사이를 유지했다. 혈 장 estradiol-179의 농도는 난포의 발육 및 배란전 배란난포의 성숙을 나타내는 특징적인 변화 양상을 나타래었다. 4마리의 처녀우중 2마리는 CIDR 삽입전 발정주기당 2회의 난포주기를 가진 반면, 나머지 2마리는 주기당 3회의 난포주기를 가졌다. 그렇지만 CIDR의 삽입기간동안 모든 처녀우는 주기당 3회의 발정주기를 가졌다. CIDR의 삽입전 발정주기당 3회의 난포주기 를 갖는 처녀우에서 CRR의 삽입은 세 번째 난포주기에서 배란성 우세난포의 우세기 (dominant phase)를 연장시켰다. 3회의 난포주기를 갖는 2마리에서 CIDR의 삽입후 배란난포 는 존속시간과 우세기가 유의성있게 연장되었다. CIDR의 삽입전 발정주기당 2회의 난포주기 를 갖는 다른 2마리의 처녀우에서 CIDR의 삽입후 우세난포는 곧바로 퇴행되었고 새로운 난 포주기를 형성하였으며, 우세난포의 우세기와 배란난포의 존속기간을 연장시키지 않았다. CRR의 삽입은 CIDR의 삽입후 이어지는 발정주기동안 난포의 발육 및 성장에 영향을 미치 지 않았으며 발정주기의 길이, 난포주기, 혈장 progesterone 및 estradiol-179 농도에 영향을 미치지 않았다. 결과적으로 황체기 후반부에 CIDR의 삽입은 CIDR삽입전 발정주기동안 3회 의 난포주기를 갖는 처녀우에서 배란성 우세난포의 발육과 배란까지의 기간을 연장시켰고 2회 난포주기를 갖는 처녀우에서는 우세난포를 곧바로 퇴행시킨후, 새로운 난포주기를 형성 하였다.

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Cytotoxicity of natural killer cells on canine mammary carcinoma cells (개 유선종양세포에 대한 자연살해세포 독성)

  • Jeong, Da-Un;Byeon, Jeong Su;Gu, Na-Yeon;Jung, Moonhee;Kim, Eun Hee;Kim, Hyung-Seok;Cho, In-Soo;Song, Jae-Young;Hyun, Bang-Hun;Lee, Jienny
    • Korean Journal of Veterinary Research
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    • v.60 no.1
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    • pp.25-32
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    • 2020
  • Natural killer (NK) cells play have a crucial role in the early phase of immune responses against various pathogens. We compared characteristics of canine NK cells against two canine mammary carcinoma cell lines, REM134 and CF41.Mg. REM134 showed higher expression of progesterone receptor, proliferative cell nuclear antigen, Ki67, multiple drug resistance, Bmi-1, c-myc, E-cadherin, and human epidermal growth factor receptor type-2 than that of CF41.Mg. For specific expansion and activation of NK cells, we isolated CD5 negative cells from canine peripheral blood mononuclear cells and co-cultured K562 cells in the presence of interleukin (IL)-2, IL-15, and IL-21 for 21 days. As a result, we found that expression markers of activated NK cells such as NKp30, NKp44, NKp46, NKG2D, CD244, perforin, granzyme B, and tumor necrosis factor alpha were highly upregulated. In addition, we found there was upregulated production of interferon gamma of activated NK cells against target cells such as REM134 and CF41.Mg. Specifically, we observed that cytotoxicity of NK cells against target cells was more sensitively reacted to CF41.Mg than REM134. Based on the results of this study, we recommend the development of an experimental application of CF41Mg, which has not been reported in canine mammary carcinoma research.

Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana

  • Kim, Mi Seon;Lee, Yunmi;Sung, Gi-Ho;Kim, Ji Hye;Park, Jae Gwang;Kim, Han Gyung;Baek, Kwang Soo;Cho, Jae Han;Han, Jaegu;Lee, Kang-Hyo;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.367-373
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    • 2015
  • Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

  • Lu, Lin;Dong, Haixia;Liu, Guixiang;Yuan, Bin;Li, Yizhao;Liu, Huaxiang
    • Biomolecules & Therapeutics
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    • v.22 no.6
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    • pp.532-539
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    • 2014
  • Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway

  • Hwangbo, Hyun;Kim, So Young;Lee, Hyesook;Park, Shin-Hyung;Hong, Su Hyun;Park, Cheol;Kim, Gi-Young;Leem, Sun-Hee;Hyun, Jin Won;Cheong, Jaehun;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.443-455
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    • 2020
  • The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

Development of Hospice Oriented Medical Record (HOMR) for Cancer Patients (호스피스 암 환자를 위한 의무기록지의 개발)

  • Seng, Jeong-Won;Hong, Sung-Moon;Kim, Si-Wan;Kim, Jeong-A;Park, Joon-Chul;Kim, Su-Hyun;Seo, Min-Jeong;Her, Sin-Hoe;Kim, Hye-Won;Hong, Myung-Ho;Choi, Youn-Seon
    • Journal of Hospice and Palliative Care
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    • v.7 no.1
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    • pp.49-63
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    • 2004
  • Purpose: The Hospice Oriented Medical Record (HOMR) was developed for assessing the pain and symptoms of terminal cancer patients. Methods and Results: The HOMR consists of an instruction for users and 2 assessment pages which include the graph showing vital signs (temperature, blood pressure, pulse, respiration rate and pain score), current problem lists, performance status, laboratory data, pain characteristics and management, sedation score, associated symptoms and drug side effects, etc. Pilot study was performed in the inpatient Hospice Care Unit in Guro Hospital, Korea University Medical Center. Because an one-week progress data was recorded in HOMR as a flow sheet, the patient's condition and pain control status could be seen at a glance. Conclusion: The HOMR is useful for assessing the terminal cancer patients because it is simple and convenient to use. Further research is needed before it can be universally used in the clinical settings.

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Transition of Teachers' Perception and Improvement of Students' Perception on Food Additives through a Training Program (식품첨가물 바르게 알기 연수를 통한 교사들의 인식 전환과 학생들의 인식 개선 효과)

  • Kim, Jeong-Weon
    • Journal of Food Hygiene and Safety
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    • v.32 no.2
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    • pp.101-106
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    • 2017
  • Based on the previous reports that majority of teachers have negative perceptions on food additives, a teacher training program called 'Let's teach food additives correctly' was developed and applied to improve teachers' unbalanced perception on food additives and let them teach students with sound scientific background. The 15-hours training program consisted of understanding of food safety and food additives, education materials on food additives, development of teaching-learning plan, meeting with professionals from Ministry of Food and Drug Safety (MFDS), visiting MFDS labs, application to school class, and evaluation. A total of 63 teachers participated in the training through 2 sessions conducted in August 2016. As a result, teachers showed high satisfaction rates (4.2~4.5 in 5.0-Likert scale) and 91.5% answered the training helpful for the school class. Although their initial intention to participate the training was to know the details of negative intake effects of food additives, their such perception was totally changed in addition, they suggested a continuous training for teachers and immediate correction of incorrect information in school textbooks. Also, post-training education for 1,172 students by these teachers appeared to improve the understanding of and the native perceptions on food additives significantly (p < 0.001). Above results showed that the training program could solve the problem of transmitting unbalanced information on food additives to students by training teachers, and such channel could be used to facilitate food-related risk communication.

Effect of Extract from Glycyorrhiza uralensis and Curcula longa on Shelf-life and Quality of Bread (감초와 강황 추출물 첨가에 의한 식빵의 저장성 및 품질 증진 효과)

  • Lee, So-Young;Choi, Jung-Soo;Choi, Mee-Ok;Cho, Sun-Hee;Kim, Koth-Bong-Woo-Ri;Lee, Woo-Hun;Park, Sun-Mee;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.7
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    • pp.912-918
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    • 2006
  • This study examined the improvement of bread quality with Curcula longa and Glycyorrhiza uralensis extract (CGE). When counted, the viable cell number in bread with 5% of CGE dramatically was decreased by about 1 log cycle as compared to that of bread without CGE. With regard to oxidation, the content of malonaldehyde diminished in breads with increasing amounts of CGE. Breads with 1 and 5% of CGE were shown to have the highest antioxidative effect. The moisture contents of bread with CGE and bread without CGE were not much different during the early storage period. After six days of storage, however, the moisture contents of bread without CGE and bread with 0.5% of CGE decreased about 16%. On the other hand, the moisture contents of bread with 1% and 5% of CGE did not change dramatically. Their moisture content was decreased by only 4% during the same storage period. Although color, lightness and redness gradually diminished with increasing amounts of CGE in bread, conversely yellowness increased. In the sensory evaluation, bread with 0.5% and 1% of CGE scored the highest: 3.66 and 3.67 out of 5, respectively. Bread with 5% of CGE scored the lowest of the various bread tested. From these results, the addition of 1% CGE in bread had a good effect on improvement of preservation and development of quality.

Research and Development for Decontamination System of Spent Resin in Hanbit Nuclear Power Plant (한빛원전 폐수지 제염공정 개발연구)

  • Sung, Gi Hong
    • Journal of Radiation Industry
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    • v.9 no.4
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    • pp.217-221
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    • 2015
  • When reactor coolant leaks occur due to cracks of a steam generator's tube, radioactive materials contained in the primary cooling water in nuclear power plant are forced out toward the secondary systems. At this time the secondary water purification resin in the ion exchange resin tower of the steam generator blowdown system is contaminated by the radioactivity of the leaked radioactive materials, so we pack this in special containers and store temporarily because we could not dispose it by ourselves. If steam generator tube leakage occurs, it produces contaminated spent resins annually about 5,000~7,000 liters. This may increase the amount of nuclear waste productions, a disposal working cost and a unit price of generating electricity in the plant. For this reasons, it is required to develop a decontamination process technique for reducing the radioactive level of these resins enough to handle by the self-disposal method. In this research, First, Investigated the structure and properties of the ion exchange resin used in a steam generator blowdown system. Second, Checked for a occurrence status of contaminated spent resin and a disposal technology. Third, identified the chemical characteristics of the waste radionuclides of the spent resin, and examined ionic bonding and separation mechanism of radioactive nuclear species and a spent resin. Finally, we carried out the decontamination experiment using chemicals, ultrasound, microbubbles, supercritical carbon dioxide to process these spent resin. In the case of the spent resin decontamination method using chemicals, the higher the concentration of the drug decontamination efficiency was higher. In the ultrasound method, foreign matter of the spent resin was removed and was found that the level of radioactivity is below of the MDA. In the microbubbles method, we found that the concentration of the radioactivity decreased after the experiment, so it can be used to the decontamination process of the spent resin. In supercritical carbon dioxide method, we found that it also had a high decontamination efficiency. According to the results of these experiments, almost all decontamination method had a high efficiency, but considering the amounts of the secondary waste productions and work environment of the nuclear power plant, we judged the ultrasound and supercritical carbon dioxide method are suitable for application to the plant and we established the plant applicable decontamination process system on the basis of these two methods.

Investigation of Rhizome Enlargement Stage and Harvest Time in Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. (지황의 비대시기와 수확시기 구명 연구)

  • Lee, Sang Hoon;Hong, Chung Oui;Lee, So Hee;Koo, Sung Cheol;Hur, Mok;Lee, Woo Moon;Chang, Jae Ki;Han, Jong Won
    • Korean Journal of Medicinal Crop Science
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    • v.27 no.5
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    • pp.315-321
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    • 2019
  • Background: There have been no studies to date on rhizome development and optimal harvest timing for Rehmannia glutinosa. We therefore, undertook this investigation. Methods and Results: R. glutinosa 'Jihwang 1' was sown in early May and harvested in early November. Growth investigations were carried out at intervals of 10 days between 90 and 180 days after sowing (DAS). Leaf length, leaf width, and number of leaves increased until 150 DAS but decreased after 160 DAS. Rhizome length increased until 120 DAS subsequently, rhizome diameter increased rapidly between 130 and 150 DAS. Thus, the key period for rhizome enlargement in R. glutinosa is thought to be 130 to 150 DAS. Fresh root yield increased sharply from 916 kg/10a to 1,914 kg/10a between 4 and 5 months after sowing (MAS). Dry matter ratio increased gradually from 19.2% at 4 MAS to 24.4% at 6 MAS. Finally, the level of catalpol, a key active ingredient, increased sharply from 0.41% to 4.21% between 5 and 6 MAS. Given the dry matter ratio, catalpol content and yield measured, we suggest that optimal R. glutinosa harvest time is 6 MAS. Conclusions: Based on our results, the key period for rhizome enlargement is 130 to 150 DAS and optimal harvest timing is 6 MAS. We anticipate that these and other results of this study can be used to inform cultivation of R. glutinosa.