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

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Utility of Structural Information to Predict Drug Clearance from in Vitro Data

  • Lee, So-Young;Kim, Dong-Sup
    • Interdisciplinary Bio Central
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    • v.2 no.2
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    • pp.3.1-3.4
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    • 2010
  • In the present research, we assessed the utility of the structural information of drugs for predicting human in vivo intrinsic clearance from in vitro intrinsic clearance data obtained by human hepatic microsome experiment. To compare with the observed intrinsic clearance, human intrinsic clearance values for 51 drugs were estimated by the classical methods using in vivo-in vitro scale-up and by the new methods using the in vitro experimental data and selected molecular descriptors of drugs by the forward selection technique together. The results showed that taking consideration of molecular descriptors into prediction from in vitro experimental data could improve the prediction accuracy. The in vitro experiment is very useful when the data can estimate in vivo data accurately since it can reduce the cost of drug development. Improvement of prediction accuracy in the present approach can enhance the utility of in vitro data.

Evaluation of the Apparent Ileal Digestibility (AID) of Protein and Amino Acids in Nursery Diets by In vitro and In vivo Methods

  • Cho, J.H.;Kim, I.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.7
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    • pp.1007-1010
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    • 2011
  • The objective was to evaluate in vitro prediction of ileal digestibility of protein and amino acids (AA) for current nursery pig diets (n = 10) by using pepsin and pancreatin incubations. To compare in vivo ileal digestibility, forty nursery pigs (4 pigs per diet) with an initial BW of $12.2{\pm}2.7$ kg were surgically equipped with T-cannula in the distal ileum. In all cases, the values of in vitro digestibility were higher than those of in vivo digestibility (p<0.05). With regard to the relationships of essential and non essential AA (CP), the $r^2$ value was 0.76. With regard to AA, high relationships were observed in Ile, Thr, and Gly (0.85, 0.83, and 0.89, respectively). Also, there was a lower relationship for Arg, Met, Ala, Asp, Glu, Pro, Ser, and Tyr with $R^2$ values of 0.56, 0.54, 0.40, 0.54, 0.45, 0.24, 0.49, and 0.35, respectively between in vitro and in vivo digestibility. The EAA relationship ($R^2$ = 0.71) was generally higher than that of NEAA ($R^2$ = 0.50) numerically. In conclusion, there were strong linear relationships between in vivo and in vitro ileal digestibility (CP, Ile, Thr, and Gly). In vitro prediction of ileal digestibility (CP, Ile, Thr, and Gly) seems to have significant potential for practical application.

Prediction of apparent total tract digestion of crude protein in adult dogs

  • Kangmin Seo;Hyun-Woo Cho;Min Young Lee;Chan Ho Kim;Ki Hyun Kim;Ju Lan Chun
    • Journal of Animal Science and Technology
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    • v.66 no.2
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    • pp.374-386
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    • 2024
  • To predict the apparent total tract digestibility (ATTD) of crude protein (CP) in dogs we developed an in vitro system using an in vitro digestion method and a statistical analysis. The experimental diets used chicken meat powder as the protein source, with CP levels of 20% (22.01%, analyzed CP value as dry-based), 30% (31.35%, analyzed CP value as dry-based), and 40% (41.34%, analyzed CP value as dry-based). To simulate in vivo digestive processes a static in vitro digestion was performed in two steps; stomach and small intestine. To analyze ATTD the total fecal samples were collected in eight neutered beagle dogs during the experimental period. CP digestibility was calculated by measuring CP levels in dog food, in vitro undigested fraction, and dog feces. In result, CP digestibility at both in vivo and in vitro was increased with increasing dietary CP levels. To estimate in vivo digestibility the co-relation of in vivo ATTD and in vitro digestibility was investigated statistically and a regression equation was developed to predict the CP ATTD (% = 2.5405 × in vitro CP digestibility (%) + + 151.8). The regression equation was evaluated its feasibility by using a commercial diet. The predicted CP digestibility which was calculated by the regression equation showed high index of similarity (100.16%) with that of in vivo in dogs. With that, it would be a feasible non-animal method to predict in vivo CP digestibility by using in vitro digestion method and the proposed linear regression equation in adult dogs.

Improvement of in vitro Sun Protection Factor Measurement (In vitro SPF 측정법 개선에 관한 연구)

  • 안성연;배지현;이해광;문성준;장이섭
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.1
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    • pp.129-133
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    • 2004
  • The major advantage of the in vitro test is that it is a rapid, objective and cost-effective screening methodology. In vitro tests can provide a formulation tool to identify new fillers that are optimized by combinations of old ones and they can be used to pre-screen protective formulas prior to in vivo testing in humans. Therefore, the accuracy of in vitro SPF measurement is very important. In this study, improvement of application method of samples was tried to improve the accuracy of in vitro SPF measurement. The outer part of Transpore$\^$(R)/ tape was used to apply samples as the substrates and the standard drying time was set at 15 min. The new method, topical applications at light scan areas, results in more accurate and reliable results. This result suggests that more accurate prediction system can be established for in vivo SPF with in vivo SPF measurement.

Comparing In Vitro and In Vivo Genomic Profiles Specific to Liver Toxicity Induced by Thioacetamide

  • Kang, Jin-Seok;Jeong, Youn-Kyoung;Shin, Ji-He;Suh, Soo-Kyung;Kim, Joo-Hwan;Lee, Eun-Mi;Kim, Seung-Hee;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.15 no.4
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    • pp.252-260
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    • 2007
  • As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

Assessment of Feasibility for Developing Toxicogenomics Biomarkers by comparing in vitro and in vivo Genomic Profiles Specific to Liver Toxicity Induced by Acetaminophen

  • Kang, Jin-Seok;Jeong, Youn-Kyoung;Suh, Soo-Kyung;Kim, Joo-Hwan;Lee, Woo-Sun;Lee, Eun-Mi;Shin, Ji-He;Jung, Hai-Kwan;Kim, Seung-Hee;Park, Sue-Nie
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.177-184
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    • 2007
  • As a possible feasibility of the extrapolation between in vivo and in vitro systems, we investigated the global gene expression from both mouse liver and mouse hepatic cell line treated with hepatotoxic chemical, acetaminophen (APAP), and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with APAP and sacrificed at 6 and 24 h. For in vitro study, APAP were administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose APAPtreated group, there was centrilobular necrosis (in vivo) and cellular toxicity with the elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified glutathione metabolism pathway as common pathways for hepatotoxicty caused by APAP. Our results suggest it may be feasible to develop toxicogenomics biomarkers or profiles by comparing in vivo and in vitro genomic profiles specific to this hepatotoxic chemical for application to prediction of liver toxicity.

Three-step in vitro digestion model for evaluating and predicting fecal odor emission from growing pigs with different dietary protein intakes

  • Lo, Shih-Hua;Chen, Ching-Yi;Wang, Han-Tsung
    • Animal Bioscience
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    • v.35 no.10
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    • pp.1592-1605
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    • 2022
  • Objective: The objective of this study was to select an effective in vitro digestion-fermentation model to estimate the effect of decreasing dietary crude protein (CP) on odor emission during pig production and to suggest potential prediction markers through in vitro and in vivo experiments. Methods: In the in vitro experiment, three diet formulations with different CP contents (170 g/kg, 150 g/kg, and 130 g/kg) but containing the same standardized ileal digestible essential amino acids (SID-EAA) were assessed. Each diet was evaluated by two different in vitro gastric-intestinal phase digestion methods (flask and dialysis), combined with fresh pig feces-ferment inoculation. Eighteen growing barrows (31.9±1.6 kg) were divided into three groups: control diet (180 g CP/kg, without SID-EAA adjustment), 170 g CP/kg diet, and 150 g CP/kg diet for 4 weeks. Results: The in vitro digestion results indicated that in vitro digestibility was affected by the gastric-intestinal phase digestion method and dietary CP level. According to the gas kinetic and digestibility results, the dialysis method showed greater distinguishability for dietary CP level adjustment. Nitrogen-related odor compounds (NH3-N, indole, p-cresol, and skatole) were highly correlated with urease and protease activity. The feeding study indicated that both EAA-adjusted diets resulted in a lower odor emission especially in p-cresol and skatole. Both protease and urease activity in feces were also closely related to odor emissions from nitrogen metabolism compounds. Conclusion: Dialysis digestion in the gastric-intestinal phase followed by fresh fecal inoculation fermentation is suitable for in vitro diet evaluation. The enzyme activity in the fermentation and the fecal samples might provide a simple and effective estimation tool for nitrogen-related odor emission prediction in both in vitro and in vivo experiments.

Foliar Micromorphological Response of In Vitro Regenerated and Field Transferred Plants of Oldenlandia umbellata L.: A Medicinal Forest Plant

  • Jayabal, Revathi;Rasangam, Latha;Mani, Manokari;Shekhawat, Mahipal Singh
    • Journal of Forest and Environmental Science
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    • v.35 no.1
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    • pp.54-60
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    • 2019
  • Plant tissue culture techniques offer quick methods of regeneration of plants of medicinal importance but the survival chances of such plants are always questionable when shifted to the in vivo conditions. The present study enumerates the micromorphological developments in the leaves of in vitro regenerated and field transferred plantlets of Oldenlandia umbellata. The leaves developed in vitro after $4^{th}$ subcultures of multiplication phase and after 6 weeks of field transferred plants were used. Statistically significant differences in the number of stomata, veins, raphides, crystals and trichome density per square mm were observed. The improvements in stomatal apparatus and density (decreased from 41.85 to 32.20), developments in leaf architectural parameters and emergence of defense mechanism through increased numbers of raphides (8 to 15), crystals and trichomes (13.5 to 18.2) proved acclimation of tissue culture raised plantlets from in vitro to the in vivo environments lead to 100 % success in field establishment of the plantlets. The in vitro induced foliar abnormalities (changes in stomata, venation pattern, vein density, trichomes, crystals etc.) were repaired while hardening of plantlets in the greenhouse and finally in the field. The observed micromorphological response of leaves under altered environmental conditions could help in determination of proper stage of field transfer and prediction of survival percentage of in vitro regenerated O. umbellata plantlets.

Prediction of Chemotherapeutic Response in Unresectable Non-small-cell Lung Cancer (NSCLC) Patients by 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) Assay

  • Chen, Juan;Cheng, Guo-Hua;Chen, Li-Pai;Pang, Ting-Yuan;Wang, Xiao-Le
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3057-3062
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    • 2013
  • Background: Selecting chemotherapy regimens guided by chemosensitivity tests can provide individualized therapies for cancer patients. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt (MTS) assay is one in vitro assay which has become widely used to evaluate the sensitivity to anticancer agents. The aim of this study was to evaluate the clinical applicability and accuracy of MTS assay for predicting chemotherapeutic response in unresectable NSCLC patients. Methods: Cancer cells were isolated from malignant pleural effusions of patients by density gradient centrifugation, and their sensitivity to eight chemotherapeutic agents was examined by MTS assay and compared with clinical response. Results: A total of 37 patients participated in this study, and MTS assay produced results successfully in 34 patients (91.9%). The sensitivity rates ranged from 8.8% to 88.2%. Twenty-four of 34 patients who received chemotherapy were evaluated for in vitro-in vivo response analysis. The correlation between in vitro chemosensitivity result and in vivo response was highly significant (P=0.003), and the total predictive accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for MTS assay were 87.5%, 94.1%, 71.4%, 88.9%, and 83.3%, respectively. The in vitro sensitivity for CDDP also showed a significant correlation with in vivo response (P=0.018, r=0.522). Conclusion: MTS assay is a preferable in vitro chemosensitivity assay that could be use to predict the response to chemotherapy and select the appropriate chemotherapy regimens for unresectable NSCLC patients, which could greatly improve therapeutic efficacy and reduce unnecessary adverse effects.