심전도의 디지털 기록화 모듈과 개인용컴퓨터 저장/분석시스템의 개발

조명찬,김기석,배장환,연태진,김동운,이태수,전은석,김유진 충북대학교 의학연구소 2001 忠北醫大學術誌 Vol.11 No.2

연구목적: 현재 우리나라의 의료분야에서는 정보기술의 발전으로 처방 전달 시스템과 전자차트의 활용이 상용화 되고 있으나 병원내에서 가장 많이 처방되고 검사되는 12-유도 심전도의 디지털화와 이에 연계된 심전도 결과의 개인용 컴퓨터로의 저장, 인터넷을 이용한 병원으로의 전송이나 타 기관에서의 심전도 결과의 동시 관찰 등에 관한 기술 등은 개발되지 못한 상태이다. 이에 본 연구에서는 심전도를 디지털화하며 저장이 가능한 PC 모듈을 개발하고 심전도 결과를 병원 전산 시스템에 포함시켜 병원내외에서 편리하게 조회, 검색할 수 있는 디지털 인터페이스를 개발하려 하였다. 재료 및 방법 : 낮은 전력에서 잡음특성이 우수한 대역여파기와 증폭기를 설계하였으며 각종기능이 내장된 고신뢰성 프로세서를 채택하였으며 전원 잡음이 고려된 필터와 전원 회로 설계로 하드웨어를 개발하였다. MSC 6.0과 Visual Basic 6.0을 바탕으로 하여 active X 모듈화를 유도하고 조회용 PC에서의 복원과 PACS로의 연동을 통해 순환기내과용 PACS 개발이 가능하도록 소프트웨어를 준비하였다. 결과: 심전도 검사자가 쉽게 장착, 검사가 가능한 소형화된 측정 모듈을 개발하였고 극저전류에서 동작이 가능하였으며 우수한 데이터의 압축 및 복원률을 구현하였다. 결론: 이번 심전도 디지털 모듈의 개발로 기존의 감광지에 의존하던 심전도 결과의 보존과 보관공간에 의한 경제적인 손실을 상당 부분 해결할 수 있으며 OCS에 연계된 결과로 인해 원내에서의 다면적 진료가 가능하다. 이번 연구에서 개발된 기술은 향후 디지털화된 심전도 기록장치와 같은 고부가 의료장치의 국산화와 광파일 의무기록 시스템이나 검사물의 무선 전송에 채용되어 의료 전달 체계나 응급체계의 발전에 기여하리라 사료된다. Purpose : The progressed communication technology commercialized the order communication system ( OCS) and the electric medical records( EMR) in the field of medicine in Korea. However, technologies of digitalization such as recording to personal computer, transfer to internet and simultaneous observation of electrocardiogram ( ECG) recorded at the different center were not realized yet. This study tried to invent personal computer module that can digitalize and record of the ECG and design the digital interface that can approach and search digitalized ECG in various part of hospital simultaneously. Materials and Methods : We had designed high-fidelity digital filter and amplifier which can work in very low voltage, had selected multifunctioned microprocessor. Activation X modulation was conducted by MSC 6.0 and Visual Basic 6.0. Softwares were prepared for the transfer of ECG informations from terminal PC to PACS and cardiologic PACS was designed for future application. Results : We have developed the small, portable, very low voltage managed ECG module and high quality digitalized information compression software in OCS and PACS. Conclusion : This invented ECG digital archive module can save hospital cost by substitution of ECG papers for digital storage or on-line storage, therefore ECG data can be handled in multisector of the hospital and through telemedicine. This technology can be applied to domestic ECG digitalizing device development and effective medical transfer system by adoption cordless medical information delivery.

Pharmaceutical Usefulness of Biopharmaceutics Classification System: Overview and New Trend

Youn, Yu-Seok,Lee, Ju-Ho,Jeong, Seong-Hoon,Shin, Beom-Soo,Park, Eun-Seok The Korean Society of Pharmaceutical Sciences and 2010 Journal of Pharmaceutical Investigation Vol.40 No.special

Since the introduction of the biopharmaceutics classification system (BCS) in 1995, it has viewed as an effective tool to categorize drugs in terms of prediction for bioavailability (BA) and bioequivalence (BE). The BCS consist of four drug categories: class I (highly soluble and highly permeable), class II (low soluble and highly permeable), class III (highly soluble and low permeable) and class IV (low soluble and low permeable), and almost all drugs belong to one of these categories. Likewise, classifying drugs into four categories according to their solubility and permeability is simple and relatively not controversial, and thus the FDA adopted the BCS as a science-based approach in establishing a series of regulatory guidance for the industry. Actually, many pharmaceutical companies have gained a lot of benefits, which directly connect to cost loss and failure decrease in the early stage of drug development. Recently, instead of solubility, using dissolution characteristics (e.g. intrinsic dissolution rate) have provided an improvement in the classification in correlating more closely with in vivo drug dissolution rather than solubility by itself. Furthermore, a newly modified-version of BCS, biopharmaceutics drug disposition classification system (BDDCS), which classify drugs into four categories according to solubility and metabolism, has been introduced and gained much attention as a new insight in respect with the drug classification. This report gives a brief overview of the BCS and its implication, and also introduces the recent new trend of drug classification.

Improved intestinal delivery of salmon calcitonin by Lys¹⁸-amine specific PEGylation: Stability, permeability, pharmacokinetic behavior and in vivo hypocalcemic efficacy

Youn, Yu Seok,Jung, Ju Young,Oh, Seung Hyun,Yoo, Sun Dong,Lee, Kang Choon Elsevier 2006 Journal of controlled release Vol.114 No.3

<P><B>Abstract</B></P><P>Peptides like salmon calcitonin (sCT) are subjected to aggressive proteolytic attack by various intestinal enzymes, and fractions that enter the systemic circulation via the intestinal route are rapidly inactivated by tissue accumulation and glomerular filtration. Here, we describe the beneficial effects of the Lys<SUP>18</SUP>-amine specific PEGylation of sCT on the intestinal delivery of sCT. Two key properties were enhanced by the PEGylation process: (i) the resistance of sCT to intestinal enzymes and (ii) the systemic clearance of sCT that had entered the circulation. Initially, we evaluated the cAMP-secreting activities of PEG<SUB>2K</SUB>-sCT isomers substituted at Cys<SUP>1</SUP>-, Lys<SUP>11</SUP>- or Lys<SUP>18</SUP>-amine position in T47D cells, and found that sCT PEGylated at Lys<SUP>18</SUP>-amine (Lys<SUP>18</SUP>-PEG<SUB>2K</SUB>-sCT) had the highest bioactivity. We then investigated the stability of Lys<SUP>18</SUP>-PEG<SUB>2K</SUB>-sCT in the presence of intestinal enzymes, its abilities to traverse the intestinal membrane, its pharmacokinetic behavior and in vivo hypocalcemic efficacy. Results show that Lys<SUP>18</SUP>-PEG<SUB>2K</SUB>-sCT has significantly increased resistance to pancreatic peptidases and brush-border peptidases. Despite the molecular size increase caused by PEGylation, Lys<SUP>18</SUP>-PEG<SUB>2K</SUB>-sCT was found to have an intestinal permeability similar to that of unmodified sCT (<I>p</I>>0.59) over an apical concentration range 12.5–100?μM in a Caco-2 cell monolayer transport system. In particular, tissue distribution results showed that <SUP>125</SUP>I-labeled Lys<SUP>18</SUP>-PEG<SUB>2K</SUB>-sCT markedly resists liver accumulation and glomerular filtration; levels were reduced by 75% and 50% vs. sCT. Finally, the hypocalcemic efficacy of intestinally administered Lys<SUP>18</SUP>-PEG<SUB>2K</SUB>-sCT, measured as total serum calcium in a rat model, was 5.8 and 3.0 times that of sCT at 100 and 200?IU/kg (<I>p</I><0.025). Our findings suggest that this site-specific conjugation of peptides with PEG of proper size enhances pharmacokinetic properties by increasing their abilities to resist both proteolysis and systemic clearance without significantly reducing their membrane permeabilities or bioactivities. We believe that this concept, namely, dual effects by PEGylation, has great potential value because it presents a practical means of enhancing the efficacies of the peroral/intestinal pharmacologic route.</P>

Carbohydrate-specifically polyethylene glycol-modified ricin A-chain with improved therapeutic potential

Youn, Yu Seok,Na, Dong Hee,Yoo, Sun Dong,Song, Soo-Chang,Lee, Kang Choon Pergamon 2005 The international journal of biochemistry & cell b Vol.37 No.7

<P><B>Abstract</B></P><P>Ricin A-chain, which exhibits excellent cytotoxicity to tumor cells, has been widely used as an immunotoxin source. However, it has the fatal shortcoming of poor pharmacokinetics due to the tremendous liver uptake via carbohydrate-mediated recognition. Modification of proteins with polyethylene glycol, PEGylation, has the advantages of shielding the specific sites and prolonging the biological half-life. In this study, the carbohydrate-specific PEGylation of ricin A-chain was considered to be a novel approach to overcome this limitation. The carbohydrate group of ricin A-chain was oxidized by sodium <I>m</I>-periodate and further specifically conjugated with hydrazide-derivatized PEG. For a comparative study, the PEGylated ricin A-chain at amino groups was prepared using the hydroxysuccinimide ester-derivatized PEG. The carbohydrate-specifically PEGylated ricin A-chain showed a markedly lower liver uptake and systemic clearance compared with the amine-directly PEGylated ricin A-chain as well as the unmodified ricin A-chain. Furthermore, carbohydrate-specifically PEGylated ricin A-chain showed a significantly higher in vitro ribosome-inactivating activity than the amine-directly PEGylated ricin A-chain. These findings clearly demonstrate that the carbohydrate-specificity as well as PEGylation plays an important role in improving the in vivo pharmacokinetic properties and in vitro bioactivity. Therefore, these results suggest that the therapeutic use of immunotoxins constructed using this carbohydrate-specifically PEGylated ricin A-chain has potential as a cancer therapy.</P>

Perspectives on the past, present, and future of cancer nanomedicine

Youn, Yu Seok,Bae, You Han Elsevier 2018 Advanced drug delivery reviews Vol.130 No.-

<P><B>Abstract</B></P> <P>The justification of cancer nanomedicine relies on enhanced permeation (EP) and retention (R) effect and the capability of intracellular targeting due primarily to size after internalization (endocytosis) into the individual target cells. The EPR effect implies improved efficacy. Affinity targeting for solid tumors only occur after delivery to individual cells, which help internalization and/or retention. The design principles have been supported by animal results in numerous publications, but hardly translated. The natures of EP and R, such as frequency of large openings in tumor vasculature and their dynamics, are not understood, in particular, in clinical settings. Although various attempts to address the issues related to EP and delivery, by modifying design factors and manipulating tumor microenvironment, are being reported, they are still verified in artificial rodent tumors which do not mimic the nature of human tumor physiology/pathology in terms of transport and delivery. The clinical trials of experimental nanomedicine have experienced unexpected adverse effects with modest improvement in efficacy when compared to current frontline therapy. Future nanomedicine may require new design principles without consideration of EP and affinity targeting. A possible direction is to set new approaches to intentionally minimize adverse effects, rather than aiming at better efficacy, which can widen the therapeutic window of an anticancer drug of interest. Broadening indications and administration routes of developed therapeutic nanotechnology would benefit patients.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Poly(benzyl-L-histidine)-b-Poly(ethylene glycol) Micelle Engineered for Tumor Acidic pH-Targeting, in vitro Evaluation

Yu Seok Youn,이은성 대한화학회 2008 Bulletin of the Korean Chemical Society Vol.29 No.8

diblock copolymer, was designed as a tumor-specific targeting carrier. The micelles (particle size: 67-80 nm, critical micelle concentration (CMC); 2-3 μg/mL) were formed from the diafilteration method at pH 7.4, as a result of self-assembly of the polyBz-His block at the core and PEG block on the shell. Removing benzyl (Bz) group from polyBz-His block provided pH-sensitivity of the micellar core; the micelles were physically destabilized in the pH range of pH 7.4-5.5, depending on the content of the His group free from Bz group. The ionization of His group at a slightly acidic pH promoted the deformation of the interior core. These pHdependent physical changes of the micelles provide the mechanism for pH-triggering anticancer drug (e.g., doxorubicin: DOX) release from the micelle in response to the tumor’s extracellular pH range (pH 7.2-6.5).

고강도 지구성 운동이 골격근내 p53, p-FoxO1 및 MuRF1 단백질의 발현에 미치는 영향

강윤석 ( Youn Seok Kang ),김정하 ( Jeong Ha Kim ),유성경 ( Seong Kyeong Yu ),박대령 ( Dae Ryoung Park ),김재철 ( Jae Cheol Kim ) 한국운동생리학회(구 한국운동과학회) 2011 운동과학 Vol.20 No.4

강윤석, 김정하, 유성경, 박대령, 김재철. 고강도 지구성 운동이 골격근내 p53, p-FoxO1 및 MuRF1 단백질의 발현에 미치는 영향. 운동과학. 제20권 제4호. 379-388. 2011. 고강도 지구력 운동(26 m/min, 10°, 15 min, 30 min, 45 min, 60 min, 90 min)을 하는 동안 쥐의 골격근내 p53, p-FoxO1 및 MuRF1 단백질의 발현을 규명하는데 연구의 목적이 있으며, 골격근내 단백질 발현은 western blotting 방법을 통해 분석하였다. p53 단백질의 발현의 경우 적색 및 백색 비복근 모두 운동 45분에 현저하게 증가하였다. p-FoxO1 단백질 발현의 경우적색 비복근에서는 운동 30분~45분의 증가한 반면에 백색 비복근에서는 운동 15분과 60분에서 높게 증가하는 것으로 나타났다. MuRF1 단백질 발현의 경우 운동 15분과 45분에서 증가한 반면에 백색 비복근에서는 운동 15분에서 높게 증가하는 것으로 나타났다. 이러한 결과는 고강도 지구력 운동을 하는 동안 p53, p-FoxO1 및 MuRF1 단백질이 근세포 손상에 대한 항상성을 유지하는데 중요하게 작용하고 있는 것으로 사료된다. Kang, Y. S., Kim, J. H., Yu, S. K., Park, D. R., Kim, J. C. The expression of p53, pFoxO-1 and MuRF1 protein in skeletal muscle during intensity endurance training. Exercise Science. 20(4): 379-388, 2011. The aim of this study was to investigate the expression of p53, p-FOXO-1, and MuRF-1 protein in the skeletal muscle of Sprague-Dawley rats during intensity endurance exercise (26 m/min, 10°, 15 min, 30 min, 45 min, 60 min, 90 min). The expression of p53, p-FoxO1, and MuRF1 protein in skeletal muscle by western blotting. The expression of p53, p-FoxO1, and MuRF1 protein significantly were increased at 15min to 30 min during intensity endurance exercise and then gradually returned to bofore exercise level. These finding suggest that p53, p-FoxO1, and MuRF1 protein plays a role in the maintennance of homeostasis in skeletal muscle during intensity endurance exercise.

북한강에서 출현한 Anabaena circinalis의 형태학적 특성 및 지오스민(geosmin) 발생 양상

윤석제 ( Youn Seok Jea ),김용진 ( Yong-jin Kim ),김헌년 ( Hun Nyun Kim ),김진용 ( Jin-yong Kim ),유미나 ( Mi-na Yu ),이은정 ( Eun Jeong Lee ),유순주 ( Soon Ju Yu ) 한국환경과학회 2018 한국환경과학회지 Vol.27 No.1

This study was carried out in the Bukhan River in the summer of 2014 and 2015, to identify the relationship between geosmin and the morphological changes in Anabaena. Identification of Anabaena was conducted using morphological and molecular analyses. Anabaena in this study was similar to Anabaena circinalis, A. crass, and A. spiroides with regard to regular coils, vegetative cell, akinete shape, and size, hoever, it was distinguishabl from A. crass and A. spiroides because of its larger trichome coil size. Additionally, the sequences of phycocyanin (PC) gene from Anabaena showed a 99% genetic similarity with A. circinalis NIES-1647 strain. The coil diameter of trichome ranged from 106 to 899 μm, and the diameter and abundance showed an insignificant positive correlation (r=0.544, p<0.05). The result of relationship between the coil diameter and the cell number per 360-degree rotation was kept at 33.8±5.2 cells per 100 μm diameter despite variable diameter. The average geosmin concentrations in 2014 and 2015 were investigated to be 99 ng/L and 35 ng/L, respectively. A. circinalis cell density contributed considerably to the change in geosmin and was positively correlated with geosmin concentration (2014; r=0.599, p<0.01, 2015; r=0.559, p<0.01). Our results suggest that geosmin and coil diameter could be estimated with the help of cell density.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

Yu, Jeong Il,Yoo, Gyu Sang,Cho, Sungkoo,Jung, Sang Hoon,Han, Youngyih,Park, Seyjoon,Lee, Boram,Kang, Wonseok,Sinn, Dong Hyun,Paik, Yong-Han,Gwak, Geum-Youn,Choi, Moon Seok,Lee, Joon Hyeok,Koh, Kwang C The Korean Society for Radiation Oncology 2018 Radiation Oncology Journal Vol.36 No.1

Purpose: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of $62-92GyE_{10}$. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Encapsulated Phase Change Material Embedded by Graphene Powders for Smart and Flexible Thermal Response

Yu, Chengbin,Youn, Jae Ryoun,Song, Young Seok 한국섬유공학회 2019 Fibers and polymers Vol.20 No.3