• Title/Summary/Keyword: in vitro data

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Benchmark Dose Modeling of In Vitro Genotoxicity Data: a Reanalysis

  • Guo, Xiaoqing;Mei, Nan
    • Toxicological Research
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    • v.34 no.4
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    • pp.303-310
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    • 2018
  • The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA's BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA's BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.

Correlation between in vitro release and in vivo bioavailability of Propranolol.HCI from Poly(vinyl alcohol) Hydrogel Suppositories (폴리비닐알코올 하이드로겔 좌제로부터 프로프라놀롤의 in vitro 방출과 in vivo 생체이용률간의 상관성)

  • Kim, Ho-Jeong;Ku, Young-Soon
    • Journal of Pharmaceutical Investigation
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    • v.28 no.4
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    • pp.275-282
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    • 1998
  • In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

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Establishment of a Release Test Reflecting in vitro Skin Permeation of Nicotine from Commercial Patches (니코틴 패취제로부터 니코틴의 피부투과를 반영하는 방출시험법의 설정)

  • Lee, Su-Jung;Kim, Jae-Keun;Yun, Mi-Ok;Kim, Ho-Jeong;Shim, Chang-Koo;Ze, Keum-Ryon
    • Journal of Pharmaceutical Investigation
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    • v.30 no.1
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    • pp.27-32
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    • 2000
  • Various release test methods have been applied for the evaluation of nicotine release in vitro from commercial patches. However, whether and how the release data reflect the permeation of nicotine across the skin, is not fully elucidated. To predict in vivo bioavailability from in vitro release tests, correlation between in vitro release and in vitro skin permeation was assessed in the present study. Release of nicotine from three commercial patches was measured for 24 hours under nine experimental conditions which were classified depending on the apparatus (i.e., paddle over disk, cylinder and reciprocating holder) and dissolution media (i.e., phosphate buffer pH 7.4, water and the 1 % phosphoric acid pH 1.5). In vitro permeation of nicotine from the patches across the human cadaver skin was also measured using a diffusion cell. The release of nicotine was better explained by the Higuchi's equation rather than by the first order rate equation. Correlation between the release rate and the in vitro skin permeation differed among the patches. However, in general, the cylinder method, in which water is used as a dissolution medium, showed the highest correlation among the nine release test conditions.

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In Vitro Sugar Accumulation in Juice Sacs of 'Shiranuhi' Mandarin

  • Moon, Doo-Gyung;Han, Sung-Gap;Joa, Jae-Ho;Kim, Chun-Hwan;Seong, Ki-Cheol
    • Horticultural Science & Technology
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    • v.31 no.3
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    • pp.269-274
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    • 2013
  • To further our understanding of sugar accumulation in 'Shiranuhi' mandarin [(C. unshiu ${\times}$ C. sinensis) ${\times}$ C. reticulate], we investigated the patterns of sugar uptake in juice sacs exposed to different concentrations of sucrose, fructose and glucose in vitro. Data was also collected on the change in weight and shape of the in vitro juice sacs over time. Soluble solids content, sugar content and acidity content were highest at 20% sucrose, fructose and glucose solution content; while fructose content was highest at 5% sucrose concentration. Furthermore, the juice sac's fresh weight was highest at 5% sucrose and lowest at 20% fructose content. The shape of the juice sacs also differed in different sugar concentration and type. Overall, sucrose, fructose and glucose content in juice sacs increased with the sugar concentration. These results suggest that sugar translocation into juice sacs is actively induced by high sugar concentration in the medium. Thus, it can be concluded that sugar and acid accumulation in juice sacs increased with sugar concentration in vitro culture.

Development of Multibody Dynamic Model of Cervical Spine for Virtual In Vitro Cadaveric Experiment (가상 생체외 사체 실험용 경추 다물체 동역학 모델 개발)

  • Lim, Dae Seop;Lee, Ki Seok;Kim, Yoon Hyuk
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.37 no.10
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    • pp.953-959
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    • 2013
  • In this study, a multibody dynamic model of the cervical spine was developed for a virtual in-vitro cadaveric experiment. The dynamic cervical spine model was reconstructed based on Korean CT images and the material properties of joints and soft tissue obtained from in-vitro experimental literature. The model was validated by comparing the inter-segmental rotation, multi-segmental rotations, load-displacement behavior, ligament force, and facet contact force with the published in-vitro experimental data. The results from the model were similar to published experimental data. The developed dynamic model of the cervical spine can be useful for injury analysis to predict the loads and deformations of the individual soft-tissue elements as well as for virtual in-vitro cadaveric experiments.

Replacement of the in vivo Bioassay for Erythropoietin with the in vitro Bioassay (Erythropoietin in vivo 시험법의 in vitro 대체 시험법 확립)

  • 백상훈;김진만;권기성;박송용;허재욱
    • KSBB Journal
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    • v.18 no.4
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    • pp.255-260
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    • 2003
  • In vivo bioassays for biological medicines have been considered final resort to unequivocally assess the biological activities for them because there are some cases in which the biological activities obtained from in vivo bioassay and in vitro bioassay quite differ each other. The in vivo biological activity of EPO depends on its sialic acid contents which confer microheterogeneity-isoforms to this protein. We have devise a method which consists of a in vitro bioassay using BaF3 cell line and a capillary zone electrophoresis (CZE) for the measurement of the EPO isoform distribution. The biological activity of EPO obtained using in vitro bioassay with BaF3 cell line showed good correlation (C.V.(%) 7.34, 5.85, 8,16, 8.08, 8.8) to EPO content measured either spectrophotometric assay (A280 0.1 % =0.743) or radio immunoassay. The assay validation results of in vitro bioassay with 3 lot of in house EPO showed good results to EPO content measured either in vivo assay or radio immunoassay. and also showed good results the robustness of our method in terms of precision, accuracy, repeatability. The isoform distribution for EPO-BRP (1 : 1 mixture of epoetin-${\alpha}$ and epoetin-${\beta}$, European Pharmacopoeia) by CZE method resulted in isoform 2 through isoform 8. The major peaks in electrophoregram were composed of isoform 3 through 7. Our recombinant EPO (epoetin-${\alpha}$) having equivalent in vivo biological activity showed the isoform distribution of isoform 3 through 9. The major peaks consisted of isoform 4 through 8. The peak area of isoform 4 was always smaller than that of isoform 5. The preparations of recombinant epoetin-${\alpha}$ with lower in vivo biological activity than EPO-BRP showed the isoform 2 through 8 in their electrophoregrams whose major peaks consisted of the isoform 3 through 7. The peak area of isoform 4 was larger than that of isoform 5.

Effects of Guided imagery on Stress and Anxiety of Women Receiving in Vitro Fertilization (지시적 심상요법이 체외 수정을 받는 여성의 스트레스와 불안에 미치는 효과)

  • Bae, Choon-Hee;Chang, Soon-Bok;Kim, Sue;Kang, Inn-Soo
    • Women's Health Nursing
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    • v.17 no.2
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    • pp.178-186
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    • 2011
  • Purpose: The purpose of this study was to identify effects of guided imagery on stress including cognitive, affective, marital and social, and anxiety among women receiving in vitro fertilization (IVF). Methods: Data were collected between April, 21 and June, 17, 2008. The participants in this study were 57 women (26 for the experimental group, 31 for the control group) receiving IVF for primary or secondary infertility in one of the outpatient infertility centers in Seoul. The guided imagery (Suk, 2001) was provided through audio CD to the experimental group by themselves 8 minutes per day for 2 weeks. Data were analyzed by SPSS 12.0 windows program. Results: After guided imagery, the experimental group showed significantly lower affective stress and total stress scores. Anxiety scores increased significantly in the control group, but not in the experimental group after treatment. Conclusion: The findings suggest that guided imagery is an effective nursing intervention for reducing stress especially affective stress and anxiety among infertile women receiving IVF in outpatient infertility center.

Comparison of In Vitro Cell Transformation Assay Using Murine Fibroblasts and Human Keratinocytes

  • Ahn, Jun-Ho;Park, Sue-Nie;Yum, Yung-Na;Kim, Ji-Young;Lee, Michael
    • Toxicological Research
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    • v.24 no.1
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    • pp.37-44
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    • 2008
  • The in vitro cell transformation assays (CTA) were performed using BALB/3T3 murine fibroblasts and HaCaT human keratinocytes in order to evaluate concordance between both in vitro CTAs and carcinogenicity with compounds differing in their genotoxic and carcinogenic potential. Six test articles were evaluated, two each from three classes of compounds: genotoxic carcinogens (2-amino-5-nitrophenol and 4-nitroquinoline-N-oxide), genotoxic noncarcinogens (8-hydroxyquinoline and benzyl alcohol), and nongenotoxic carcinogens (methyl carbamate and N-nitrosodiphenylamine). Any foci of size $\geq$2 mm regardless of invasiveness and piling was scored as positive in CTA with BALB/3T3. As expected, four carcinogens regardless of their genotoxicity had positive outcomes in two-stage CTA using BALB/3T3 cells. However, of the two genotoxic noncarcinogens, benzyl alcohol was positive CTA finding. We concluded that, of the 6 chemicals tested, the sensitivity for BALB/3T3 system was reasonably high, being 100%. The respective specificity for BALB/3T3 assay was 50%. We also investigated the correlation between results of BALB/3T3 assay and results from HaCaT assay in order to develop a reliable human cell transformation assay. However, evaluation of staining at later time points beyond the confluency stage did not yield further assessable data because most of HaCaT cells were detached after $2{\sim}3$ days of confluency. Thus, after test article treatment, HaCaT cells were split before massive cell death began. In this modified protocol for this HaCaT system, growing attached colonies were counted instead of transformed foci 3 weeks since last subculture. Compared to BALB/3T3 assay, HaCaT assay showed moderate low sensitivity and high specificity. Despite these differences in specificity and sensitivity, both cell systems did exhibit same good concordance between in vitro CTA and rodent carcinogenicity findings (overall 83% concordant results). At present the major weakness of these in vitro CTA is lack of validation for regulatory acceptance and use. Thus, more controlled studies will be needed in order to be better able to assess and quantitatively estimate in vitro CTA data.

Effects of a Yoga-focused Prenatal Program on Stress, Anxiety, Self Confidence and Labor Pain in Pregnant Women with In Vitro Fertilization Treatment (요가중심 산전프로그램이 체외수정 시술 임산부의 스트레스, 불안, 분만 자신감 및 분만통증에 미치는 효과)

  • Shim, Chung-Sin;Lee, Young-Sook
    • Journal of Korean Academy of Nursing
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    • v.42 no.3
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    • pp.369-376
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    • 2012
  • Purpose: The purpose of this study was to identify the effects of a Yoga-focused prenatal program on the stress, anxiety, self confidence and labor pain of pregnant women who had in vitro fertilization (IVF) treatment. Methods: A quasi experimental study with a non-equivalent control group pretest-posttest design was used. The data collection period and meditation program were between January 9 and August 31, 2009. Forty-six women who were pregnant following IVF, and were between 12-20 weeks gestation, participated in the study (23 experimental group, 23 control group). Data were analyzed using Chisquare test, Mann-Whitney U Test, ANCOVA, and Cronbach's alpha coefficients with the SPSS 12.0 for Windows Program. Results: Although the sample size was limited, women who participated in the program showed statistically significant improvements in stress, anxiety, labor pain, and labor confidence for women pregnant after IVF. Conclusion: The result indicate that this 12-week Yoga-focused educational program can be utilized for women pregnant following IVF to reduce their stress, anxiety, and labor pain, and to increase delivery confidence. It is suggested that the Yoga-focused educational program be offered to every pregnant woman.

Experiences of Infertile Women in Unsuccessful In Vitro Fertilization(IVF) (여성의 불임 경험 -체외수정 실패 경험자를 중심으로-)

  • Kang, Hee-Sun;Kim, Mi-Jong
    • Women's Health Nursing
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    • v.10 no.2
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    • pp.119-127
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    • 2004
  • Purpose: A Phenomenological study was conducted to investigate the experiences of infertile women who had an unsuccessful in vitro fertilization(IVF) attempt and the structure of these experiences was identified in a socio-cultural context. Method: In-depth interviews were done with five participants from Nov. 1997 to Feb. 1998. Data was recorded and analyzed by Colazzi's method. Result: Significant statements were extracted from the data resulting in 4 themes and 11 concepts. The concepts were: 'lack of information', 'unable to anticipate the outcome', 'reaffirmation of need', 'financial strain', 'emotional suppression', 'change of social relationships', 'physical fatigue', 'blaming oneself or God', 'trying different ways', 'famous place shopping', and 'praying to God'. The significant themes of the participants' experiences with IVF emerged as: "uncertainty", "burden", "blaming" and "vigorous desire". Conclusion: The results indicate that the care of infertile women with an unsuccessful IVF attempt should be based on a deep understanding of their personal experiences. Also, information on alternative choices should be offered and supported.

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