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Preparation of Solid Dispersions of a Poorly Water-soluble Drug Using Supercritical Fluid (초임계 유체를 이용한 난용성 약물의 고체분산체 제조)

  • Kim, Seok-Yun;Lee, Jung-Min;Jung, In-Il;Lim, Gio-Bin;Ryu, Jong-Hoon
    • KSBB Journal
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    • v.24 no.6
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    • pp.533-540
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    • 2009
  • In this work, 5'-nitroindirubinoxime (5'-NIO) has been prepared as solid dispersions using a supercritical aerosol solvent extraction system (ASES) process in order to enhance its water solubility and dissolution rate. Solid dispersions of 5'-NIO and poly(vinyl pyrrolidone) (PVP) were prepared in various weight percent ratios. Three-component solid dispersions consisting of 5'-NIO, PVP, and poloxamer 188 (P188) were also prepared to study the influence of P188 level on their morphology, crystallinity, and dissolution behavior. All samples were prepared at $35^{\circ}C$ and 180 bar using supercritical carbon dioxide. The particle morphology and size of the two-component solid dispersions were found to be nearly spherical and much smaller (100-200 nm) compared with the original 5'-NIO. The morphology of three-component solid dispersions became more agglomerated as the level of P188 increased. The crystallinity of the original 5'-NIO was not observed in the solid dispersions prepared by the ASES process. Faster dissolution rates were observed for the three-componet solid dispersions because the arrangement of ethylene oxide and propylene oxide blocks of the poloxamer 188 enabled the formation of micelles in an aqueous phase.

Enhancement of radiation effect using beta-lapachone and underlying mechanism

  • Ahn, Ki Jung;Lee, Hyung Sik;Bai, Se Kyung;Song, Chang Won
    • Radiation Oncology Journal
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    • v.31 no.2
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    • pp.57-65
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    • 2013
  • Beta-lapachone (${\beta}$-Lap; 3,4-dihydro-2, 2-dimethyl-2H-naphthol[1, 2-b]pyran-5,6-dione) is a novel anti-cancer drug under phase I/II clinical trials. ${\beta}$-Lap has been demonstrated to cause apoptotic and necrotic death in a variety of human cancer cells in vitro and in vivo. The mechanisms underlying the ${\beta}$-Lap toxicity against cancer cells has been controversial. The most recent view is that ${\beta}$-Lap, which is a quinone compound, undergoes two-electron reduction to hydroquinone form utilizing NAD(P)H or NADH as electron source. This two-electron reduction of ${\beta}$-Lap is mediated by NAD(P)H:quinone oxidoreductase (NQO1), which is known to mediate the reduction of many quinone compounds. The hydroquinone forms of ${\beta}$-Lap then spontaneously oxidizes back to the original oxidized ${\beta}$-Lap, creating futile cycling between the oxidized and reduced forms of ${\beta}$-Lap. It is proposed that the futile recycling between oxidized and reduced forms of ${\beta}$-Lap leads to two distinct cell death pathways. First one is that the two-electron reduced ${\beta}$-Lap is converted first to one-electron reduced ${\beta}$-Lap, i.e., semiquinone ${\beta}$-Lap $(SQ)^{{\cdot}-}$ causing production of reactive oxygen species (ROS), which then causes apoptotic cell death. The second mechanism is that severe depletion of NAD(P)H and NADH as a result of futile cycling between the quinone and hydroquinone forms of ${\beta}$-Lap causes severe disturbance in cellular metabolism leading to apoptosis and necrosis. The relative importance of the aforementioned two mechanisms, i.e., generation of ROS or depletion of NAD(P)H/NADH, may vary depending on cell type and environment. Importantly, the NQO1 level in cancer cells has been found to be higher than that in normal cells indicating that ${\beta}$-Lap may be preferentially toxic to cancer cells relative to non-cancer cells. The cellular level of NQO1 has been found to be significantly increased by divergent physical and chemical stresses including ionizing radiation. Recent reports clearly demonstrated that ${\beta}$-Lap and ionizing radiation kill cancer cells in a synergistic manner. Indications are that irradiation of cancer cells causes long-lasting elevation of NQO1, thereby sensitizing the cells to ${\beta}$-Lap. In addition, ${\beta}$-Lap has been shown to inhibit the repair of sublethal radiation damage. Treating experimental tumors growing in the legs of mice with irradiation and intraperitoneal injection of ${\beta}$-Lap suppressed the growth of the tumors in a manner more than additive. Collectively, ${\beta}$-Lap is a potentially useful anti-cancer drug, particularly in combination with radiotherapy.

The Effect of Cheonmagudeung-eum for Hypertension: A Systematic Review and Meta-analysis (고혈압에 대한 천마구등음의 효과 : 체계적 문헌고찰과 메타분석)

  • Kang, Ki-wan;Kang, Ja-yeon;Jeong, Min-jeong;Kim, Hong-jun;Sun, Seung-ho;Jang, In-soo
    • The Journal of Internal Korean Medicine
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    • v.39 no.1
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    • pp.22-43
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    • 2018
  • Objective: The purpose of this study is to investigate the effect of Cheonmagudeung-eum (CGE) for essential hypertension by systematic review and meta-analysis. Methods: The period of literature search was until October 30, 2016, and 14 electronic databases were utilized as search engines. The evaluation for the risk of bias (RoB) was conducted by using the Cochrane Risk of Bias Tool. The meta-analysis was performed by synthesizing outcome data, including total effective rate (TER), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of adverse events. Result: There were a total of 64 RCTs using CGE on adult essential hypertension. In the RoB evaluation, most of the items were unclear, and the qualities of studies were rated low. The concurrent treatment of CGE and antihypertensive drug (AHD) showed a significant hypotensive effect since the risk ratio (RR) of TER was 1.17 times (95% CI 1.14, 1.20, p<0.01) higher than that of AHD alone. In addition, the mean difference (MD) appeared low as 8.73 mm/Hg in SBP (95% CI -11.36, -6.09, p<0.01) and 5.81 mm/Hg in DBP (95% CI -7.50, -4.12, p<0.01). Conclusion: Through this study, it was identified that the combined treatment of CGE and AHD on hypertension would be more effective than that of AHD treatment alone. However, due to the low quality of the selected original articles, the significance of this conclusion is somewhat limited, and we hope that this would be complemented through more rigorous RCTs in the future.

Mutation Analysis of Synthetic DNA Barcodes in a Fission Yeast Gene Deletion Library by Sanger Sequencing

  • Lee, Minho;Choi, Shin-Jung;Han, Sangjo;Nam, Miyoung;Kim, Dongsup;Kim, Dong-Uk;Hoe, Kwang-Lae
    • Genomics & Informatics
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    • v.16 no.2
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    • pp.22-29
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    • 2018
  • Incorporation of unique barcodes into fission yeast gene deletion collections has enabled the identification of gene functions by growth fitness analysis. For fine tuning, it is important to examine barcode sequences, because mutations arise during strain construction. Out of 8,708 barcodes (4,354 strains) covering 88.5% of all 4,919 open reading frames, 7,734 barcodes (88.8%) were validated as high-fidelity to be inserted at the correct positions by Sanger sequencing. Sequence examination of the 7,734 high-fidelity barcodes revealed that 1,039 barcodes (13.4%) deviated from the original design. In total, 1,284 mutations (mutation rate of 16.6%) exist within the 1,039 mutated barcodes, which is comparable to budding yeast (18%). When the type of mutation was considered, substitutions accounted for 845 mutations (10.9%), deletions accounted for 319 mutations (4.1%), and insertions accounted for 121 mutations (1.6%). Peculiarly, the frequency of substitutions (67.6%) was unexpectedly higher than in budding yeast (~28%) and well above the predicted error of Sanger sequencing (~2%), which might have arisen during the solid-phase oligonucleotide synthesis and PCR amplification of the barcodes during strain construction. When the mutation rate was analyzed by position within 20-mer barcodes using the 1,284 mutations from the 7,734 sequenced barcodes, there was no significant difference between up-tags and down-tags at a given position. The mutation frequency at a given position was similar at most positions, ranging from 0.4% (32/7,734) to 1.1% (82/7,734), except at position 1, which was highest (3.1%), as in budding yeast. Together, well-defined barcode sequences, combined with the next-generation sequencing platform, promise to make the fission yeast gene deletion library a powerful tool for understanding gene function.

Efficacy Evaluation of Anti-wrinkle Products in Japan

  • Masaki Hitoshi
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.29 no.2 s.43
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    • pp.67-77
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    • 2003
  • Two categories of cosmetic products, cosmetics and quasi-drugs, have been established by the Ministry of Health, Labor and Welfare (MHLW) in Japan. Japanese pharmaceutical law has defined that products categorized as cosmetics do not exhibit any effects on human skin. In fact, cosmetic products are not permitted to claim any efficacy. On the other hand, products in the quasi-drug category can claim several efficacies such as anti-inflammatory effects, whitening/lightning effects, hair growth effects and so on. Unfortunately, the Japanese MHLW has not yet approved the efficacy of anti-aging/anti-wrinkle effects as a claim point. However, the population is aging, and the demand for anti-aging/anti-wrinkle products is increasing year by year. Japanese cosmetic companies have proposed to the MHLW that anti-aging/anti-wrinkle agents be approved as a claim concept of a quasi-drug. However, unified evaluation methods for anti-aging/anti-wrinkle effects have not been established. Currently, each company evaluates the efficacy of products/materials using their own original methods. Thus, to request approval of the MHLW, the establishment of a unified evaluation method is needed. Consequently, the Japan Cosmetic Industry Association (JCIA) has established a task force to develop guidelines for evaluating anti-wrinkle effects in 1998. In conclusion, the JCIA would like to adopt visual and image analysis scales to evaluate the anti-wrinkle effects objectively. Generally, wrinkles are roughly classified into three groups as fine wrinkles, linear deep wrinkles and crow's feet. However, academic societies of dermatology or cosmetics have not yet established a definition of wrinkles in Japan. Thus, in advance of setting up an evaluation method, the definition of wrinkles f3r evaluation must be decided. Wrinkles are defined by the task force of the JCIA as follows; furrows that people can recognize visually and that appear on the forehead, the corners of the eyes and the backs of the neck with aging. In addition, furrows are emphasized by exposure to solar light and by dry conditions. Visual evaluation is the most sensitive method and can be applied to most types of wrinkles. However, visual evaluation is hard to express digitally as results. Besides, in the case of image analysis, comparisons of data obtained from distinct examinations can not be done, because data from image analysis are relative values. Thus, to enhance the reliability of the evaluations, the adoption of an objective scale was required. The principle of the evaluation method is to analyze images taken from silicone replicas of wrinkle areas using several parameters, such as the proportion of the wrinkle $area({\%})$, the mean depth of the wrinkles (mm), the mean depth of the deepest wrinkle (m) and the deepest point on the deepest wrinkle. Lights are shown on the skin replica from an orthogonal direction of the main orientation of the wrinkle, and the resulting shadow images are quantified by the image analysis method. To increase the precision of the data or to allow comparisons of independent examinations, a scale with furrows of several depths, 200, 400, 600, 800, and $1000{\mu}m$, is adapted in the evaluation system. I will explain the guidelines established by the JCIA in the presentation.

Modulation of Hyaluronic Acid Properties by Electron Beam Irradiation (전자선 조사를 이용한 히알루론산의 특성 조절)

  • Shin, Young Min;Kim, Woo-Jin;Kim, Yong-Soo;Jo, Sun-Young;Park, Jong-Seok;Gwon, Hui-Jeong;Lim, Youn-Mook;Nho, Young-Chang
    • Journal of Radiation Industry
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    • v.5 no.2
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    • pp.159-164
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    • 2011
  • A variety of natural polymers have been used as tissue engineering scaffolds, drug delivery system, and cosmetic materials due to their higher biocompatibility and water uptake. As a major component of extracellular matrix, hyaluronic acid consisting of D-glucuronic acid and N-acetylglucosamine has been popularly used as a hydrogel material. Even though it has good properties to be used in the tissue engineering and cosmetic industry, its higher viscosity has limited a potential use in a variety of applications; only low content should be applied in preparing above products. In the present study, we investigated the effect of electron beam irradiation on the properties of hyaluronic acid. Hyaluronic acid paste containing low contents of water changed to solution after electron beam irradiation ranging from 1 to 10 kGy, which didn't exhibit any alteration of surface properties and morphological change after freeze-drying. However, its viscosity was significantly decreased as absorbed dose increased, which was approximately one by hundred in comparison with the viscosity of original hyaluronic acid solution with same concentration. In addition, it can still interact with positive charged chitosan generating polyelectrolyte complex. Therefore, only viscosity was decreased after electron beam irradiation, whereas other properties of hyaluronic acid maintained. Consequently, these hyaluronic acids with lower viscosities can be used in a variety of applications in tissue engineering, drug delivery, and cosmetic industry.

The Effect of Telemedicine Expansion on the Structural Change and the Competition Increase in the Health Care Industry and its Policy Implication- Focusing on the case of Amazon's foray on the health care industry (원격의료 확대가 의료산업 구조변화 및 경쟁 확대에 미치는 영향과 정책적 시사점 - 미국 아마존의 헬스케어 분야 진출 사례를 중심으로)

  • Lee, Jaehee
    • The Journal of the Convergence on Culture Technology
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    • v.8 no.3
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    • pp.405-413
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    • 2022
  • Since the COVID-19 outbreak, the active utilization of new health care service utilizing the ICT technology and data science such as telemedicine, smart hospital, AI dignosis has been increasingly found. In this study we examined the business model of Amazon healthcare which leads disruptive innovation in U.S. health care industry with the introduction of hybrid model of telemedicin, in-person care and customer-centric online drug delivery, home-use diagnostic kit, characterized by the integrated model combining medical care, drug delivery and the use of diagnostic kit. We showed using the multiproduct competition model that the synergy effect between the Amazon's original business areas and the healthcare business area causes the active market penetration and the increase in the customer value from utilization of the Amazon care. Using Hotelling's spatial competition model, we also showed that the competition in the health care market can be greater when consumer's choice of health care providers are available in telemedicine platform. In the long, run the issue of competition being weakened due to the exit of less competent healthcare providers may arise, to which the policymakers in the charge of fair competition in health care industry should pay attention.

Field Study For The Improvement of Medication System and Method for Inpatients at General Hospital (입원환자의 투약체계와 방법의 개선을 위한 현장연구)

  • Yoo, Hyung-Sook;Kuwan, Young-Mi;Song, Mi-Sook;Kim, Hyung-Ae;Park, Kyung-Sook
    • Journal of Korean Academy of Nursing Administration
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    • v.1 no.1
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    • pp.147-211
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    • 1995
  • Medication is a kind of medical service and a therapeutic nursing function which takes large portion of nursing service and requires complicated procedures. So many different medical personnel should be involved and cooporate each other in order to accomplish medication. Medication is also a vital nursing service, So nurse feels heavy responsibi lity in that she gives medication to the patient finally, so she has much responsibility if medication error is happened. Therefore it seems very important to clarify the problem of medication system and method, and find the subculture of medication situation because it may promote nursing productivity. The study was conducted to 1. Describe and interpret medication situation. 2. Find out the problem of medication system and method and on alternatives. 3. Compare the medication system and method of hospitals which are located in Seoul with object hospital Ethnographic methodology was used to study medication situation by doing participant observation and interview of health care personnel. Ten nurses and three nurse aids were interviewed. Two residents and internists, two phamacists and two accountants were also interviewed. Data was obtained and analized according to Developmental Research Sequence introduced by Spradly. On the basis of this data the results were as follows. 1. The overall flow of medication system was devided into six stage : first, checking doctor's order : second writing doctor's order, : third, transfering slip into the related departments such as account department, pharmacy : fourth, distribution of medication from pharmacy to unit : fifth, identifing medication by nurses : and finally, medicating to the patient. Behaviorors have been under a lot of stress in that they have to do much works, especially paperworks, So too much time were needed. They also have been suffered interpersonal conflicts among health care personnel and role conflicts in the process of doing medication service. 2. In the process of checking order, the problem was that too much time was required for checking order and paperwork. The more the order changes the more the paperwork is. Nurses have been suffering difficulties in calling internist in order to get bill. Even if writing down slip for medication order is doctor's job, Sometimes nurse has been expected to write slip by doctors or nurse would write slip beacuse of two much complexities and efforts for calling doctors. If the slip were incorrect, much time complicated procedures were more required for correcting it. So delay of administering drug would be resulted consequently. Drugs were delivered from pharmacy to units by delivery agent and phamacist. But because drugs were delivered without arranging room number of patient. Nurse should rearrange drugs in order of the room number So it had made waste time and effort, and Even when emergency drugs were needed, Prompt delivery of drug was not easy because of many reasons. For nurses, it took too long in the identification of the right drug. Actually nurses have heavy burden when medication error happens because nurse is the final actor who gives medication to the patient, So every three shift nurse ought to check drugs as soon as every shift begins. That's why it took too much time due to repeated confirming procedure. When nurses had to go patient room in order to give medications, there were difficulties in watching patient until the patient take medicine correctly. So it was impossible to check every patient wheather he took medicine or not especially in hectic situation. 3. There were many hospitals in Seoul which have similar medication system and method as object hospital according to the results of questionaire. This means that many hospitals have been suffering srimilar problems which were identified in object hospital. 4. Recommendations for promoting simplification of medication system and method were the following : Redesigning of slip from two pieces of paper into one : early discharge announcement system, and slip confirming through computer and controlling of period of prescreption from one day to two or three days : designing personal drug storage box for each patient and using it. If nurses follow the recommendations, they will make medication short & simple, and also have enough time of direct nursing care 5. Even though there were many difficulties in medicating patients. Medication itself has been considered as a caring among nurses because it makes rapport between nurse and patient. So nurses had better accept medication as a portion of nusing service not a original portion of phamacist. There are some limits in this research in terms of confining to only one unit of one hospital, and treating it especially in view of nurses' aspects, So further researchs should be continnued from various kmds of viewpoints of doctors, phamacists and so on. ${\cdot\cdot\cdot}$. Especially esthnographic study of computerized medication system and method seems to be followed.

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Current Status of Intervention Studies on Acupuncture for Parkinson's Disease

  • Kim, Deok Hyun;Sin, Dae Chul;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.34 no.3
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    • pp.13-21
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    • 2017
  • Objectives : The purpose of this study was to investigate the effect of acupuncture treatment (AT) in the tendency of increase of the need for AT for the treatment of Parkinson's disease (PD) worldwide and to investigate the advancements in AT research in Korea and the future directions of research on this topic. Methods : Until May 2017, the PubMed, Scopus, Medline, and four Korean databases were searched. The searched keywords were "Parkinson's disease", "Acupuncture", and "Intervention study". The intervention groups from all screened original studies were analyzed and the methods used to determine the effect of AT on PD were examined. Results : A total of 17 studies were grouped by country on the basis of the first author's position, of which 10 studies were conducted in China, four in the United States, two in Korea, and one in Brazil. The most common type of intervention was electroacupuncture (nine studies), followed by AT (six studies), and a combination of AT and bee venom AT (two studies). The most frequently used acupoints in AT were Baihui (GV20), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6), and Yanglingquan (GB34). The most commonly used tool for evaluation of PD was the Unified Parkinson's Disease Rating Scale III, which assesses motor functions. Conclusion : The screened studies reported that there were no adverse effects of AT on drug therapy, and AT reduced the dose of drugs used in PD treatment. Future studies on PD treatment with AT should use the acupoints GV20, LR3, ST36, SP6, and GB34, and the meridians Gallbladder meridian and Governor Vessel. Clinical studies on PD should use CONSORT or STRICTA to ensure the quality of national studies and allow the development of new tools for the assessment of the effect of AT on PD using the above criteria.

Antibiotics; Methicillin, Cefamandole and Oxytetracycline, Can Modulate the Activity of Human Neutrophil Elastases (Methicillin, Cefamandole, Oxytetracycline에 의한 사람 호중구 Elastase의 변화)

  • Ghim, Sa-Youl;Jeong, Hye-Young;Bae, Sung-Jun;Kang, Koo-Il
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.109-113
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    • 1989
  • Human neutrophil elastase (HNE, EC 3, 4 21, 11), a major causative factor in the induction of pulmonary emphysema, were purified by two steps of liquid chromatography. Purified elastases were cross-reacted with antibody to human neutrophil elastases. Methicillin and cefamandole, which are known as inhibitors of cell wall synthesis of microorganisms, could inhibit the activity of human neutrophil elastase up to 50% with 10mM of both agents and $IC_{50}$ of methicillin was 9.8 mM. Gentamicin, one of the aminoglycosides, also inhibits human neutrophil elastases up to 60% of original activity with 10 mM of this agent and $IC_{50}$ was 9.0 mM. We could demonstrate similar effects in oxytetracycline. 10 mM of oxytetracycline inhibited 95% of human neutrophil elastase and $IC_{50}$ was 0.3 mM. Overall, oxytetracycline, cefamandole and methicillin are strong inhibitors of human neutrophil elastase, and they could be a drug of cholice for the diseases which were known as pathogenesis related to elastase. We also suggest that the mechanism of action of these antibitics are different from the mechanism of antimicrobial effects like inhibition of both cell wall synthesis and protein synthesis.

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