• Title/Summary/Keyword: Development of New Drug

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Impact of antimicrobial resistance in the $21^{st}$ century

  • Song, Jae-Hoon
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2000.04a
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    • pp.3-6
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    • 2000
  • Antimicrobial resistance has been a well-recognized problem ever since the introduction of penicillin into clinical use. History of antimicrobial development can be categorized based on the major antibiotics that had been developed against emerging resistant $pathogens^1$. In the first period from 1940 to 1960, penicillin was a dominating antibiotic called as a "magic bullet", although S.aureus armed with penicillinase led antimicrobial era to the second period in 1960s and 1970s. The second stage was characterized by broad-spectrum penicillins and early generation cephalosporins. During this period, nosocomial infections due to gram-negative bacilli became more prevalent, while those caused by S.aureus declined. A variety of new antimicrobial agents with distinct mechanism of action including new generation cephalosporins, monobactams, carbapenems, ${\beta}$-lactamase inhibitors, and quinolones characterized the third period from 1980s to 1990s. However, extensive use of wide variety of antibiotics in the community and hospitals has fueled the crisis in emerging antimicrobial resistance. Newly appeared drug-resistant Streptococcus pneumoniae (DRSP), vancomycin-resistant enterococci (VRE), extended-spectrum ${\beta}$-lactamase-producing Klebsiella, and VRSA have posed a serious threat in many parts of the world. Given the recent epidemiology of antimicrobial resistance and its clinical impact, there is no greater challenge related to emerging infections than the emergence of antibiotic resistance. Problems of antimicrobial resistance can be amplified by the fact that resistant clones or genes can spread within or between the species as well as to geographically distant areas which leads to a global concern$^2$. Antimicrobial resistance is primarily generated and promoted by increased use of antimicrobial agents. Unfortunately, as many as 50 % of prescriptions for antibiotics are reported to be inappropriate$^3$. Injudicious use of antibiotics even for viral upper respiratory infections is a universal phenomenon in every part of the world. The use of large quantities of antibiotics in the animal health industry and farming is another major factor contributing to selection of antibiotic resistance. In addition to these background factors, the tremendous increase in the immunocompromised hosts, popular use of invasive medical interventions, and increase in travel and mixing of human populations are contributing to the resurgence and spread of antimicrobial resistance$^4$. Antimicrobial resistance has critical impact on modem medicine both in clinical and economic aspect. Patients with previously treatable infections may have fatal outcome due to therapeutic failure that is unusual event no more. The potential economic impact of antimicrobial resistance is actually uncountable. With the increase in the problems of resistant organisms in the 21st century, however, additional health care costs for this problem must be enormously increasing.

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The history of ginseng cultivation in Orient (동양에 있어서의 인삼재배 역사)

  • Koh, Seungtae
    • Journal of Ginseng Culture
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    • v.1
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    • pp.57-66
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    • 2019
  • Ginseng has been recognized as a lifespan extending medicine which has been regarded as one of the medicines classified as top medicines, as the Boncho (medical herbs) study which is influenced by the idea of guidance's costume and food concept mainly in China is gaining its bona fide form. As the demand for ginseng has been expanded to other levels, the demand for ginseng has been increasing. Ginseng from the nature reached its supply chain limit due to its extinction and difficulty of picking, so it translated into ginseng cultivation of economy rather than harvesting in nature. After the start of ginseng cultivation, the ginseng cultivation was further enhanced by the rapid development of processing methods such as white-ginseng and red-ginseng, and the surge of consumption due to the traditional belief in ginseng drug efficacy and support of scientific research. In the Joseon Dynasty, the name Gasam (cultivated ginseng) had been created as ginseng was cultivated on farmland after the stage of SanYang (wild cultivated ginseng), the purpose of the new name Gasam is to differentiate from natural ginseng, and natural ginseng lost its firm position as the genuine ginseng as the Gasam replaced the genuine ginseng, and the natural ginseng got a new name of SanSam (wild ginseng). Because the real ginseng substance concept dissipated, and as Gasam is being called ginseng, the name Gasam was also disappeared. As a result, it was possible to grow large quantities according to the arrival of the Gasam era, and it was possible to supply the demand for ginseng, and it could become one agricultural industry. In this ginseng cultivation, in Japan where ginseng did not grow naturally, it was difficult to obtain ginseng from Joseon and faced with a shortage of ginseng at all times. Therefore, the shogun cultivated the Gasam systematically at the national level by the inside of the shogunate. However, since the natural ginseng is native to China and Korea, there is a concern about the deterioration of the quality of natural ginseng due to the incorporation of cultivated ginseng (Gasam). To protect the interests, the cultivation of ginseng was subject to control. For this reason, the lack of historical information on Gasam cultivation, which had to be started secretly, would be a natural result. In this paper, althouh not sufficient enough, the historical informations were used to summarize the history of ginseng cultivation in China, Japan and Korea.

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.

In vitro Antimicrobial Activity of a New Isolate Streptomyces sp. BCNU 1030 (신규 분리균주 Streptomyces sp. BCNU 1030의 in vitro 항균활성)

  • Bang, Ji-Hun;Choi, Hye-Jung;Ahn, Cheol-Soo;Kim, Dong-Wan;Jeong, Yong-Kee;Joo, Woo-Hong
    • Journal of Life Science
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    • v.21 no.4
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    • pp.589-595
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    • 2011
  • This work focused on screening and characterizing antibiotic-producing actinomycetes to develop new antibiotics that can overcome the growing resistance of disease-causing microbes. One-hundred actinomycetes strains were isolated from soil samples from Chungcheongbuk-do, Korea using various kinds of actinomycetes isolation media, including a starch casein agar medium and potato dextrose agar (PDA). Among them, strain BCNU 1030 was determined to show strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Biochemical, physiological, and 16S rRNA sequence analyses indicated that strain BCNU 1030 belonged to the genus Streptomyces. Strain BCNU 1030 exhibited antibiotic activity against a wide range of bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of BCNU 1030 dichloromethane extract was determined to be $0.78\;{\mu}g/ml$ for MRSA CCARM 3090. Therefore, Streptomyces sp. BCNU 1030 has potential for anti-MRSA drug development.

Development of Rapid Analytical Method for Heavy Metals (Cd, Pb) in Meju using fs LA-ICP-MS (fs LA-ICP-MS를 이용한 메주의 유해중금속(Cd, Pb) 신속 분석법 개발)

  • Shin, Hee-Chang;Choi, Ji-Hye;Kim, Yong-Kyoung;Kim, Dae-Jung;An, Jae-Min;Kim, Sung-Youn
    • Journal of Food Hygiene and Safety
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    • v.37 no.3
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    • pp.129-135
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    • 2022
  • The official analytical method for the analysis of harmful heavy metals in Meju, distributed in Korea, employs a strong acid to decompose the organic components. This analysis is time consuming and harmful to the users and/or the environment. This study aimed to develop a new pre-treatment technology using laser ablation, to rapidly analyze harmful heavy metals without using strong acids. The results obtained from this method were validated by the National Institute of Food and Drug Safety Evaluation guideline (NIFDS, 2016). Moreover, a comparison of the two methods showed that the analytical time for 55 Meju samples was shortened by 96% or more in the new method. The results showed no significant difference in the recovery ranging from 90-120%. The proposed method proved suitable for detecting harmful heavy metals in Meju.

COMPARISON OF TRAMADOL/ACETAMINOPHEN AND CODEINE/ACETAMINOPHEN/IBUPROFEN IN ONSET OF ANALGESIA AND ANALGESIC EFFICACY FOR POSTOPERATIVE ACUTE PAIN (수술후 급성 동통에 대한 Tramadol/Acetaminophen과 Codeine/Acetaminophen/Ibuprofen의 효과 발현시점과 진통효과의 비교)

  • Jung, Young-Soo;Kim, Dong-Kee;Kim, Moon-Key;Kim, Hyung-Jun;Cha, In-Ho;Han, Moo-Young;Lee, Eui-Wung
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.30 no.2
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    • pp.143-149
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    • 2004
  • Background: Some clinical trials have reported that a new analgesic combination of tramadol and acetaminophen provides good efficacy in various pain models. For the more clinical uses of this agent, comparisons about the onset of analgesia and analgesic efficacy in the acute state of pain with the other drugs known as strong analgesics were needed. Purpose: The goal of this study was to compare the times to onset of analgesia and the other analgesic efficacy of 75 mg tramadol/650 mg acetaminophen and 20 mg codeine/500 mg acetaminophen/400 mg ibuprofen in the treatment of acute pain after oral surgery. Patients and Methods: Using a randomized, single-dose, parallel-group, single-center, and active-controlled test design, this clinical study compared the times to onset of analgesia using a two-stopwatch technique and the other analgesic efficacy of the single-dose tramadol/acetaminophen and codeine/acetaminophen/ibuprofen. These were assessed in 128 healthy subjects with pain from oral surgical procedures involving extraction of one or more impacted third molars requiring bone removal. From the time of pain development, the times to onset of perceptible and meaningful pain relief, pain intensity, pain relief, an overall assessment, and adverse events of the study medications were recorded for 6 hours. Results: The demographic distribution and baseline pain data in the two groups were statistically similar. The median times to onset of perceptible pain relief were 21.0 and 24.4 minutes in the tramadol/acetaminophen and codeine/acetaminophen/ibuprofen groups respectively and those to onset of meaningful pain relief were 56.4 and 57.3 minutes, which were statistically similar. The other efficacy variables such as mean total pain relief (TOTPAR) and the sum of pain intensity differences (SPID) were also similar in the early period after pain development and drug dosing. The safety of tramadol/acetaminophen was well tolerated and very comparable to that of codeine/acetaminophen/ibuprofen. Conclusions: In this acute dental pain model, the onset of analgesia and analgesic efficacy of tramadol/acetaminophen was comparable to that of codeine/acetaminophen/ibuprofen. These results showed that tramadol/acetaminophen was recommendable for fast and effective treatment in the management of postoperative acute pain.

Potentiating Activity of (+)-Usnic Acid on EDTA and Sodium Azide Methicillin-resistant Staphylococcus aureus (메티실린-내성 포도상구균에 대하여 EDTA 및 Sodium Azide 병용에 의한 우스닌산 약효증대)

  • Lee, Young-Seob;Kim, Hye-Sung;Lee, Jae Won;Lee, Dae-Young;Kim, Geum-Soog;Kim, Hyoun-Wook;Noh, Geon-Min;Lee, Seung Eun;Lee, Sun Ae;Song, Ok Hee;Kwon, Dong-Yeul
    • Korean Journal of Pharmacognosy
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    • v.47 no.2
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    • pp.122-127
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    • 2016
  • Methicillin-Resistant Staphylococcus aureus(MRSA) is a multidrug-resistant(MDR) strain. (+)-Usnic acid(UA) is uniquely found in lichens, and is especially abundant in genera such as Usnea and Cladonia. UA has antimicrobial activity against human and plant pathogens. Therefore, UA may be a good antibacterial drug candidate for clinical development. In search of a natural products capable of inhibiting this multidrug-resistant bacteria, we have investigated the antimicrobial activity of UA against 17 different strains of the bacterium. In this study, the effects of a combination of UA and permeable agents against MRSA were investigated. For the measurement of cell wall permeability, UA with concentration of Ethylenediaminetetraacetic acid(EDTA) was used. In the other hand, Sodium azide($NaN_3$) was used as inhibitors of ATPase. Against the 17 strains, the minimum inhibitory concentrations(MICs) of UA were in the range of $7.81-31.25{\mu}g/ml$. EDTA or $NaN_3$ cooperation against MRSA showed synergistic activity on cell wall. UA and in combination with EDTA and $NaN_3$ could lead to the development of new combination antibiotics against MRSA infection.

The Structural and Functional Role of p53 as a Cancer Therapeutic Target (암 치료 표적으로서 p53의 구조적 및 기능적 역할)

  • Han, Chang Woo;Park, So Young;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.28 no.4
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    • pp.488-495
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    • 2018
  • The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

  • Lin, Ching-Ling;Tsai, Ming-Lin;Chen, Yu-hsin;Liu, Wei-Ni;Lin, Chun-Yu;Hsu, Kai-Wen;Huang, Chien-Yu;Chang, Yu-Jia;Wei, Po-Li;Chen, Shu-Huey;Huang, Li-Chi;Lee, Chia-Hwa
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.551-561
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    • 2021
  • Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Effect of Dietary Chlorella Complex on Anticancer Activity in Mice

  • Jung Jae-Hak;Jin Kyong-Suk;Kim Yong-Ho;Lee Yong-Woo
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.185-192
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    • 2005
  • Dietary chlarella has known as one of the best candidates for development of multifunctional probiotic foods owing to an excellent nutritional value such as high amount of proteins and various, valuable fatty acids. So many efforts were devoted to studying the chlorella as therapeutic agents or foods fighting against many diseases in the aged people such as cardiovascular diseases and cancers. In this study, we investigated sizes and weights of tumors derived from mice injected subcutaneously with tumorigenic cells to see if antitumor activity would be found in mice dieted with the chlarella complex. After BALB/c mice were dieted with $5\%$ organic cultured chlorella complex diet throughout for 19weeks, the fibrosarcoma was induced by subcutaneous injection of tumorigenic cells at the 3 weeks before sacrifice. The average weight of tumors in the diet group were significantly reduced to $60\%\;(P=0.012)$ of the one in control group, indicating that diet with the chlarella complex may have anticancer activity in mice. When the mice were dieted with $5\%$ organic cultured chlorella complex for 4 weeks before injecting the tumorigenic cells in order to see tumor-preventive effect of the diet, the potential preventive activity of the diet against cancer was implicated by the observation that the tumors were greatly reduced in the diet group to $37\%$ (P=0.l44) of the control group. Especially, when the $5\%$ diet were applied to mice after injecting with the tumorigenic cells, the tumors derived from the $5\%$ diet group were also decreased to $95\%$ (P=0.002) of those in the control group, suggesting that the diet with the organic cultured chlorella complex may also have therapeutic effect against tumor formation. As results, it was shown that the chlorella complex tested in this study had preventive and therapeutic effects on fighting against tumorigenesis. Therefore, the identification and further mechanistic study of the components which may be associated with antitumor activity from diet of the chlorella complex in the future will contribute to the development of anticancer probiotic foods, alternative therapeutic treatment against cancer, and a new anticancer drug.

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