• Title/Summary/Keyword: In vitro-in vivo prediction

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Determination of Water Content in Skin by using a FT Near Infrared Spectrometer

  • Suh Eun-Jung;Woo Young-Ah;Kim Hyo-Jin
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.458-462
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    • 2005
  • The water content of skin was determined using a FT near infrared (NIR) spectrometer. NIR diffuse reflectance spectra were collected from hairless mouse, in vitro, and from human inner arm, in vivo. It was found that the variation of NIR absorbance band 1450 nm from OH vibration of water and 1940 nm from the combination involving OH stretching and OH deformation, depending on the absolute water content of separated hairless mouse skin, in vitro, using the FT NIR spectrometer. Partial least squares regression (PLSR) was applied to develop a calibration model. The PLS model showed good correlation. For practical use of the evaluation of human skin moisture, the PLS model for human skin moisture was developed in vivo on the basis of the relative water content of stratum corneum from the conventional capacitance method. The PLS model predicted human skin moisture with a standard errors of prediction (SEP) of 3.98 at 1130-1830 nm range. These studies showed the possibility of a rapid and nondestructive skin moisture measurement using FT NIR spectrometer.

Hydraulic Design Optimization and Performance Analysis of a Centrifugal Blood Pump (원심형 혈액펌프의 최적화 수력설계 및 성능해석)

  • Park Moo Ryong;Yoo Seong Yeon;Oh Hyoung Woo;Yoon Eui Soo
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.30 no.1 s.244
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    • pp.87-94
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    • 2006
  • This paper presents the hydrodynamic design and performance analysis method for a miniaturized centrifugal blood pump using three-dimensional computational fluid dynamics (CFD) code. In order to obtain the hydraulically high efficient configuration of a miniaturized centrifugal blood pump for cardiopulmonary circulation, a well-established commercial CFD code was incorporated considering detailed flow dynamic phenomena in the blood pump system. A prototype of centrifugal blood pump developed by the present design and analysis method has been tested in the mock circulatory system. Predicted results by the CFD code agree very well with in vitro hydraulic performance data for a centrifugal blood pump over the entire operating conditions. Preliminary in vivo animal testing has also been conducted to demonstrate the hemodynamic feasibility for use of centrifugal blood pump as a mechanical circulatory support. A miniaturized centrifugal blood pump developed by the hydraulic design optimization and performance prediction method presented herein shows the possibility of a good candidate for intra and extracorporeal cardiopulmonary circulation pump in the near future.

Prediction of the Exposure to 1763MHz Radiofrequency Radiation Based on Gene Expression Patterns

  • Lee, Min-Su;Huang, Tai-Qin;Seo, Jeong-Sun;Park, Woong-Yang
    • Genomics & Informatics
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    • v.5 no.3
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    • pp.102-106
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    • 2007
  • Radiofrequency (RF) radiation at the frequency of mobile phones has been not reported to induce cellular responses in in vitro and in vivo models. We exposed HEI-OC1, conditionally-immortalized mouse auditory cells, to RF radiation to characterize cellular responses to 1763 MHz RF radiation. While we could not detect any differences upon RF exposure, whole-genome expression profiling might provide the most sensitive method to find the molecular responses to RF radiation. HEI-OC1 cells were exposed to 1763 MHz RF radiation at an average specific absorption rate (SAR) of 20 W/kg for 24 hr and harvested after 5 hr of recovery (R5), alongside sham-exposed samples (S5). From the whole-genome profiles of mouse neurons, we selected 9 differentially-expressed genes between the S5 and R5 groups using information gain-based recursive feature elimination procedure. Based on support vector machine (SVM), we designed a prediction model using the 9 genes to discriminate the two groups. Our prediction model could predict the target class without any error. From these results, we developed a prediction model using biomarkers to determine the RF radiation exposure in mouse auditory cells with perfect accuracy, which may need validation in in vivo RF-exposure models.

In vitro Biocompatibility Evaluation of Biomaterial-elution Using Inflammatory Cell Lines (염증세포주를 이용한 생체재료 용출물의 체외 생체적합성 평가)

  • Shin, Youn-Ho;Song, Kye-Yong;Seo, Min-Ji;Kim, Sung-Min;Park, Jung-Keug;Kim, Dong-Sup;Park, Ki-Jung;Hur, Chan-Hoi;Cha, Ji-Hun;Seo, Young-Kwon
    • KSBB Journal
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    • v.26 no.3
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    • pp.248-254
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    • 2011
  • Various biometerials have been researched and have been developed for treatment of some disease through transplantation to body. They have been evaluated by in vitro cytotoxicity test using some skin-derived cell lines for prediction of their biocompatibility in vivo. However, the results of experiments using mesenchymal or epithelial cells could not be considered in vivo immune reaction. In this study, we evaluated the biomaterial-elution (elute from high density polyethylene film) using some cell lines (L929, Jurkat, U937) in vitro, and then that results were compared with in vivo results from guinea pig sensitization test. In sensitization test, saline and elution of syringe could not induce erythema, but only DNCB (hypersensitive chemical) induce erythema at guinea pig sensitization test. In cell experiment, the cytotoxicity results of inflammatory cells (Jurkat; T lymphocyte, U937; monocyte) was no difference with L929 (fibroblast) in the overall trend. However, inflammatory cell lines were only secreted inflammatory cytokine (TNF-${\alpha}$, INF-${\gamma}$) in some materials (biomateriallution, FAC, DNCB). And the biomaterial-elution did not have toxicity to the cells, but it induced the inflammatory cytokines in inflammatory cell lines only. So, we were predicted inflammatory reaction through the cytokine resultes of inflammatory cell lines, and it was more correlated with in vivo results than cytotoxicity test. Therefore, we suggested that the inflammatory cytokine assay using inflammatory cell lines are more effective method in vitro for evaluation of biocompatibility of biomaterials or chemicals.

Evalution of Hemolysis in Axial Flow Blood Pump with Computational Fluid Dynamics Analysis (전산유체해석을 이용한 축류형 혈액펌프의 용혈평가)

  • 임상필;김동욱
    • Proceedings of the KAIS Fall Conference
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    • 2003.06a
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    • pp.256-259
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    • 2003
  • Artificial heart is divided pulsation style and nonpulsation style greatly according to flowing of blood. nonpulsation pump is advantage of miniaturization avaliable because it is simple and non-volumic-pump than pulsation pump. Non pulsation pump is derided axial flow style and centrifugal style accordig to rotating style. An axial flow blood pump can be made smaller than a centrifugal blood pump because of its higher specific speed. A hemolysis is an important factor for the development of an axial flow blood pump. It is difficult to identify the areas where hemolysis nun. Evaluation of hemolysis both in in vitro and in vivo require a long time and are costly. Computational fluid dynamics(CFD) analysis enables the engineer to predict hemolysis on a computer. The aims of this study is Computational fluid dynamics in the whole axial flow pump and to verify the accuracy of prediction results of CFD analysis compare with in vitro experimental results.

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Prediction of Exposure to 1763MHz Radiofrequency Radiation Using Support Vector Machine Algorithm in Jurkat Cell Model System

  • Huang Tai-Qin;Lee Min-Su;Bae Young-Joo;Park Hyun-Seok;Park Woong-Yang;Seo Jeong-Sun
    • Genomics & Informatics
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    • v.4 no.2
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    • pp.71-76
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    • 2006
  • We have investigated biological responses to radiofrequency (RF) radiation in in vitro and in vivo models. By measuring the levels of heat shock proteins as well as the activation of mitogen activated protein kinases (MAPKs), we could not detect any differences upon RF exposure. In this study, we used more sensitive method to find the molecular responses to RF radiation. Jurkat, human T-Iymphocyte cells were exposed to 1763 MHz RF radiation at an average specific absorption rate (SAR) of 10 W/kg for one hour and harvested immediately (R0) or after five hours (R5). From the profiles of 30,000 genes, we selected 68 differentially expressed genes among sham (S), R0 and R5 groups using a random-variance F-test. Especially 45 annotated genes were related to metabolism, apoptosis or transcription regulation. Based on support vector machine (SVM) algorithm, we designed prediction model using 68 genes to discriminate three groups. Our prediction model could predict the target class of 19 among 20 examples exactly (95% accuracy). From these data, we could select the 68 biomarkers to predict the RF radiation exposure with high accuracy, which might need to be validated in in vivo models.

Evaluation of the Anti-Tumor Effects of Paclitaxel-Encapsulated pH-Sensitive Micelles

  • Han, Jong-Kwon;Kim, Min-Sang;Lee, Doo-Sung;Kim, Yoo-Shin;Park, Rang-Woon;Kim, Kwang-Meyung;Kwon, Ick-Chan
    • Macromolecular Research
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    • v.17 no.2
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    • pp.99-103
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    • 2009
  • We evaluated the efficacy of pH-sensitive micelles, formed by methoxy poly(ethylene glycol)-b-poly($\beta$)-amino ester) (PEG-PAE), as carriers for paclitaxel (PIX), a drug currently used to treat various cancers. PTX was successful encapsulated by a film hydration method. Micelles encapsulated more than 70% of the PTX and the size of the PTX-encapsulated micelles (PTX-PM) was less than 150 nm. In vitro experiments indicated that the micelles were unstable below pH 6.5. After encapsulation of PTX within the micelles, dynamic light scattering (DLS) studies indicated that low pH had a similar demicellization effect. An in vitro release study indicated that PTX was slowly released at pH 7.4 (normal body conditions) but rapidly released under weakly acidic conditions (pH 6.0). We demonstrated the safety of micelles from in vitro cytotoxicity tests on HeLa cells and the in vivo anti-tumor activity of PTX-PM in B16F 10 tumor-bearing mice. We concluded that these pH-sensitive micelles have potential as carriers for anti-cancer drugs.

Alternatives to In Vivo Draize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

  • Lee, Miri;Hwang, Jee-Hyun;Lim, Kyung-Min
    • Toxicological Research
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    • v.33 no.3
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    • pp.191-203
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    • 2017
  • Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornealike epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.

Mathematical Optimization Techniques in Drug Product Design and Process Analysis. Optimization Techniques in Tablet Design (의약품 제조설계 및 조작분석의 최적화에 관한 연구 - 정제제조의 최적화)

  • 김용배
    • YAKHAK HOEJI
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    • v.18 no.1
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    • pp.49-58
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    • 1974
  • Tablet product design problem was structured as constrained optimization problem and subsequently solved by multiple regression analysis and Lagrangian method of optimization. Aluminum flufenamate was the drug chosen and microcrystalline cellulose nad starch were the binder and disintegrant, respectivley. The effect of the binder and disintegrant concentration on tablet hardness, friability, volume, in vitro release rate, and urinary excretion rate of drug in human subjects was recorded. Since a reasonably rapid release rate of drug is generally an important objective in the design of solid dosage form, optimization of this parameter was employed in studying the applicability of constrained optimization to a pharmaceutical product design problem. In addition to finding optimal sitivity analysis studies to such problems was also illustratd. It would appear that prediction of the in vivo t$_{50%}$ response from a knowledge of the incitro t$_{50%}$ response can be made fairly accurately for the tablet system used in this study.

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Gene Expression Analysis of Methotrexate-induced Hepatotoxicity between in vitro and in vivo

  • Jung, Jin-Wook;Kim, Seung-Jun;Kim, Jun-Sup;Park, Joon-Suk;Yeom, Hye-Jung;Kim, Ji-Hoon;Her, Young-Sun;Lee, Yong-Soon;Kang, Jong-Soo;Lee, Gyoung-Jae;Kim, Yang-Seok;Kang, Kyung-Sun;Hwang, Seung-Yong
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.256-261
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    • 2005
  • The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.