• Title/Summary/Keyword: drug combination

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PFG NMR Study of Intra-cellular Drug Uptake in Xenopus laevis Oocyte

  • Kwan, soo-Hong;Yeom Gyo-Seon;Kim, Eun-Hee;Lee, Chul-hyun;Lee, Sang-Do;Cheong, chae-joon
    • Journal of the Korean Magnetic Resonance Society
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    • v.9 no.1
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    • pp.29-37
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    • 2005
  • Intra-cellular drug uptake in Xenopus laevis oocyte has been elucidated using localized MR spectroscopy (MRS) and PFG NMR techniques at a 600 $MH_z$(Bruker, 14.1 T) NMR spectrometer. The localized MRS has been done with a homemade probe, and shows the intra-cellular uptake of nicotinamide. The self-diffusion of the molecule in Xenopus oocyte was obtained by PFG NMR technique. The measured data are well fitted with a linear combination of two exponential functions, which shows that there are two types of drug molecules, intra-and extra-cellular molecules. Diffusion coefficients of intra- and extra-cellular drug molecules are 3.7 $\times$ $10^{-11}$ $\m^{2}/s$and 6.4 $\times$ $10^{-10}$ $\m^{2}/s$, respectively. In the weighting factors there is shown that about 5% of drug molecule is inside the cells. These techniques can be used for drug screening in molecule-, cell-, and tissue-based preclinical test.

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A Case Report of Drug-Induced Parkinsonism Treated with Jodeung-san and Electro-acupuncture at GB34 (조등산(Diaoteng-san, Choto-san, 釣藤散)과 GB34(陽陵泉) 전침치료를 활용한 약인성파킨슨증후군 환자의 증례 1례)

  • Kim, Eun-ji;Song, Ho-joon;Kim, Hyun-ho;Han, Yang-hee;Leem, Jung-tae
    • The Journal of Internal Korean Medicine
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    • v.38 no.5
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    • pp.600-609
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    • 2017
  • Drug-induced Parkinsonism is the most frequently observed type among the cases of secondary Parkinsonism. Besides typical parkinsonian symptoms, such as tremor, rigidity and bradykinesia, drug-induced Parkinsonism manifests with additional simultaneous symptoms like orobuccolingual dyskinesia, mixed type of tremor (resting, action), and symmetry of expressions. We present a case of drug-induced Parkinsonism, affected by taking the antiulcer drug cimetidine. Jodeung-san extract (Choto-san, Tsumura Co. 10) was administered for 7 days and acupuncture (electronic, auricular, pharmacopuncture) was conducted 3 times. The clinical outcomes were then evaluated through the patient's global impression of change, visual analogue scale, and Hoehn and Yahr stage. After the treatment, the clinical features, such as tremor and orobuccolingual dyskinesia, disappeared. The combination of Jodeung-san and electro-acupuncture at GB34 could therefore be a remedy for the patients with drug-induced Parkinsonism.

Dual Drug-Loaded Liposomes for Synergistic Efficacy in MCF-7 Breast Cancer Cells and Cancer Stem Cells

  • Park, Hee-Bin;Kim, Yun-Ji;Lee, Seong-Min;Park, James S.;Kim, Keun-Sik
    • Biomedical Science Letters
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    • v.25 no.2
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    • pp.159-169
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    • 2019
  • Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

A Study on the Prediction of Drug Efficacy by Using Molecular Structure (분자구조 유사도를 활용한 약물 효능 예측 알고리즘 연구)

  • Jeong, Hwayoung;Song, Changhyeon;Cho, Hyeyoun;Key, Jaehong
    • Journal of Biomedical Engineering Research
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    • v.43 no.4
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    • pp.230-240
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    • 2022
  • Drug regeneration technology is an efficient strategy than the existing new drug development process, which requires large costs and time by using drugs that have already been proven safe. In this study, we recognize the importance of the new drug regeneration aspect of new drug development and research in predicting functional similarities through the basic molecular structure that forms drugs. We test four string-based algorithms by using SMILES data and searching for their similarities. And by using the ATC codes, pair them with functional similarities, which we compare and validate to select the optimal model. We confirmed that the higher the molecular structure similarity, the higher the ATC code matching rate. We suggest the possibility of additional potency of random drugs, which can be predicted through data that give information on drugs with high molecular similarities. This model has the advantage of being a great combination with additional data, so we look forward to using this model in future research.

Treatment of Drug Susceptible Pulmonary Tuberculosis

  • Shin, Hong-Joon;Kwon, Yong-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.78 no.3
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    • pp.161-167
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    • 2015
  • Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs.

Organizational Capabilities for Effective Knowledge Creation: An In-depth Case Analysis of Quinolone Antibacterial Drug Discovery Process (효과적 지식창출을 위한 조직능력 요건: 퀴놀론계 항생제 개발 사례를 중심으로)

  • Lee, Chun-Keun;Kim, Linsu
    • Knowledge Management Research
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    • v.2 no.1
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    • pp.109-132
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    • 2001
  • The purpose of this article is to develop a dynamic model of organizational capabilities and knowledge creation, and at the same time identify the organizational capability factors for effective knowledge creation, by empirically analyzing the history of new Quinolone antibacterial drug compound (LB20304a) discovery process at LG, as a case in point. Major findings of this study are as follows. First, in a science-based area such as drug development, the core of successful knowledge creation lies in creative combination of different bodies of scientific explicit knowledge. Second, the greater the difficulty of learning external knowledge, the more tacit knowledge is needed for the recipient firm to effectively exploit that knowledge. Third, in science-based sector such as pharmaceutical industry, the key for successful knowledge creation lies in the capability of recruiting and retaining star scientists. Finally, for effective knowledge creation, a firm must keep its balance among three dimensions of organizational capabilities: local, process, architectural capabilities.

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Practice Guideline of Use of Benzodiazepines in Psychiatric Field (정신과 영역에서 벤조다이아제핀계 약물의 사용과 문제점)

  • Oh Kang-Seob
    • Anxiety and mood
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    • v.1 no.1
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    • pp.37-42
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    • 2005
  • Benzodiazepines are widely used for a variety of conditions in psychiatric field. In this article, the author reviewed the indications, the effects on anxiety and sleep disorders, the side effects, the drug-drug interactions, and the tapering strategies. Benzodiazepines were relatively safe and useful for the treatment of anxiety and sleep disorders. However, used clinically, benzodiazepines can induce many adverse effects (e. g. over-sedation, cognitive impairments, paradoxical effects, dependence and withdrawal symptoms, and so on). Currently available informations about their effects on the developing fetus is controversial. For this reason, pregnant women and nursing mother should be cautioned against the use of benzodiazepines. Drug-drug interactions have to be considered in combination treatments. For the tapering issues, gradual tapering was important to prevent the withdrawal symptoms. Especially, the tapering schedules have to be individualized for the each long-term benzodiapzepine users.

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Drug-Induced Gastrointestinal Dysfunction in Parkinson's Disease: Treatment with Korean Medicine

  • Hwang, Ji Hye;Kim, Deok-Hyun;Kang, Mi Suk;Song, Ho-Seub
    • Journal of Acupuncture Research
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    • v.36 no.2
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    • pp.113-117
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    • 2019
  • Parkinson's disease (PD) is a neurodegenerative disease, where treatment with medication may lead to gastrointestinal (GI) symptoms. The objective of this case study was to investigate the effectiveness of Korean medicine (KM) in treating PD with drug-induced GI dysfunction. A 70-year-old female participant was diagnosed with PD in 2010 and drug-induced gastritis in 2016. Her major symptoms were related to GI, PD, and overall feeling of weakness. She was treated with KM including pharmacopuncture, acupuncture, moxibustion, and herbal medicines, in combination with Western medicines during 46 days of in-patient care. This study showed an improvement in symptoms and scores on the GI symptom scale, Unified Parkinson's disease rating scale, Hoehn and Yahr staging, Berg balance scale, PD quality of life, and stress index at discharge. This case demonstrated that the symptoms of drug-induced GI dysfunctions in PD was improved by treatment with KM.

Outpatient Prescription Pattern of Anti-inflammatory Drugs by Pediatricians and ENT Physicians in Ulsan City (울산 지역 소아청소년과 및 이비인후과에서의 항염증제 처방 형태 분석)

  • Kim, Sung-Chull;Kim, Young-Rok;Hwang, Jae-Yoon;Chang, Hyeun-Wook;Nam, Doo-Hyun
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.3
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    • pp.205-212
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    • 2010
  • The prescription sheets for outpatients from July 2008 to June 2009 from 7 community pharmacies in Ulsan City were surveyed for the anti-inflammatory drug (AID) prescription pattern. The AID prescription rate of pediatricians and ENT physicians were 30.0% and 34.8%, respectively. The oral steroidal anti-inflammatory drugs (SAIDs) were prescribed as much as 3.9% by pediatricians and 10.3% by ENT physicians. The chiefly prescribed oral SAID was prednisolone in pediatric clinics and methylprednisolone in ENT clinics. Meanwhile the prescription rate of oral non-steroidal anti-inflammatory drug (NSAID) was 22.5% by pediatricians and 21.4% in ENT physicians. The most favorable NSAIDs were propionate derivatives in both clinics. In case of externally-applied SAIDs, the prescription rate of pediatricians was 3.6% and that of ENT physicians was 2.8%. Among them, nasal spray, inhalant and gargle formulations for upper respiratory infection (URI) treatment occupied 35.8% of externally-applied SAIDs in pediatric clinics and 59.7% in ENT clinics. Further, it was observed that ENT physicians favored much stronger SAIDs in Group III of ATC classification (75.4% of externally-applied SAIDs) than pediatricians (49.2%). In the survey of AID combination rate, pediatric clinics showed much lower rate (1.4% of total AID prescriptions) than ENT clinics (7.5%). Among them, the combination rate of oral SAID and oral NSAID by ENT physicians (52.2% of total AID combinations) was much higher than pediatricians (36.6%), which might be over-prescription of AID agents. In conclusion, the AID prescription rate as well as AID combination rate, especially in SAID prescriptions, was much higher in ENT than pediatric clinics, which implies the higher confidency on AID drugs of ENT physicians even though the severity of patient's symptom could be considered.

Combination therapy with cilostazol, aripiprazole, and donepezil protects neuronal cells from β-amyloid neurotoxicity through synergistically enhanced SIRT1 expression

  • Heo, Hye Jin;Park, So Youn;Lee, Yi Sle;Shin, Hwa Kyoung;Hong, Ki Whan;Kim, Chi Dae
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.4
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    • pp.299-310
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    • 2020
  • Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and α7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.