• Title/Summary/Keyword: in vitro/in vivo studies

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Addressing Early Life Sensitivity Using Physiologically Based Pharmacokinetic Modeling and In Vitro to In Vivo Extrapolation

  • Yoon, Miyoung;Clewell, Harvey J. III
    • Toxicological Research
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    • v.32 no.1
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    • pp.15-20
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    • 2016
  • Physiologically based pharmacokinetic (PBPK) modeling can provide an effective way to utilize in vitro and in silico based information in modern risk assessment for children and other potentially sensitive populations. In this review, we describe the process of in vitro to in vivo extrapolation (IVIVE) to develop PBPK models for a chemical in different ages in order to predict the target tissue exposure at the age of concern in humans. We present our on-going studies on pyrethroids as a proof of concept to guide the readers through the IVIVE steps using the metabolism data collected either from age-specific liver donors or expressed enzymes in conjunction with enzyme ontogeny information to provide age-appropriate metabolism parameters in the PBPK model in the rat and human, respectively. The approach we present here is readily applicable to not just to other pyrethroids, but also to other environmental chemicals and drugs. Establishment of an in vitro and in silico-based evaluation strategy in conjunction with relevant exposure information in humans is of great importance in risk assessment for potentially vulnerable populations like early ages where the necessary information for decision making is limited.

Dexamethasone Release from Glutaraldehyde Cross-Linked Chitosan Microspheres: In Vitro/In Vivo Studies and Non-Clinical Parameters Response in Rat Arthritic Model

  • Dhanaraju, Magharla Dasaratha;Elizabeth, Sheela;Poovi, Ganesan
    • Journal of Pharmaceutical Investigation
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    • v.41 no.5
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    • pp.279-288
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    • 2011
  • The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.

In Vitro and in Vivo Metabolism of Salsolinol, on Endogenous Isoquinoline Neurotoxin, in Rats

  • Rhee, Hee-Kyung;Kwon, Oh-Seung;Ryu, Jae-Chun
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.30-33
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    • 2001
  • Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL), a dopaminergic isoquinoline neurotoxin, has been implicated to contribute the etiology of Parkinson's disease and neuropathology of chronic alcoholism. In our previous results, SAL was reported to have the mutagenicity and clastogenicity not in bacteria but in mammalian cells, and its genotoxic potential was known to be potentiated in the presence of rat liver S-9 fraction. This may indicate that some metabolite(s) of SAL was involved in the mutagenic potentials. To investigate the SAL metabolites, the metabolism studies of SAL were conducted in vitro rat liver S-9 fraction and in vivo using rats by high performance liquid chromatography and gas chromatography/mass spectrometry. The methylated metabolite of SAL was found in urine of rats, while the same methylating form of metabolite was not produced from the in vitro metabolism system using rat liver S-9 fraction.

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Use of In Vivo and In Vitro Systems to Select Leishmania amazonensis Expressing Green Fluorescent Protein

  • Costa, Solange Dos Santos;Golim, Marjorie De Assis;Bergmann, Bartira Rossi;Costa, Fabio Trindade Maranhao;Giorgio, Selma
    • Parasites, Hosts and Diseases
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    • v.49 no.4
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    • pp.357-364
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    • 2011
  • Various Leishmania species were engineered with green fluorescent protein (GFP) using episomal vectors that encoded an antibiotic resistance gene, such as aminoglycoside geneticin sulphate (G418). Most reports of GFP-Leishmania have used the flagellated extracellular promastigote, the stage of parasite detected in the midgut of the sandfly vector; fewer studies have been performed with amastigotes, the stage of parasite detected in mammals. In this study, comparisons were made regarding the efficiency for in vitro G418 selection of GFP-Leishmania amazonensis promastigotes and amastigotes and the use of in vivo G418 selection. The GFP-promastigotes retained episomal plasmid for a prolonged period and G418 treatment was necessary and efficient for in vitro selection. In contrast, GFP-amastigotes showed low retention of the episomal plasmid in the absence of G418 selection and low sensitivity to antibiotics in vitro. The use of protocols for G418 selection using infected BALB/c mice also indicated low sensitivity to antibiotics against amastigotes in cutaneous lesions.

Recent Studies of Breast Cancer in Traditional Chinese Medicine Journals (중의학 논문에 나타난 유방암의 연구 동향에 대한 고찰 - 중의학 논문을 중심으로 -)

  • Jerng, Ui-Min;Jeong, Jong-Soo;Park, Jae-Woo;Jung, Hyun-Sik;Yoon, Seong-Woo
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.1
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    • pp.263-278
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    • 2009
  • Purpose: The purpose of this study is to research trends in the study of breast cancer in Traditional Chinese Medicine (TCM) and to establish the further direction for its study. Methods: We reviewed TCM papers published in the last 29 years (1979-2008). Results: 1. We researched 49 papers and the patterns of study were as follows: in vitro studies were 27 papers (55.1%), in vivo studies were 9 papers (18.4%) and clinical studies were 19 papers (38.8%). 2. In vitro studies on breast cancer research in TCM were focused on cytotoxicity (17 papers) and apoptosis (8 papers). Most of in vivo studies (6 papers) were done for the purpose of inducing growth suppression of tumor cell after administration of the test drug. Each drug acted on this effect through various types of mechanism. 3. Unlike in vitro and in vivo studies, clinical studies on growth suppression of tumor cell were rare (4 papers). Most of the studies were focused on reduction of side effect of chemotherapy or synergistic effect with chemotherapy (7 papers), immune regulation (7 papers), and improvement of quality of life (6 papers). 4. Among the treatment method we reviewed, 'Runing Ⅱ(Ⅱ號方)' was the only medication that further studied as clinical trial after experimental study. 5. Since almost all studies have defects like poorly designed model or insufficient data description, it was difficult to make any definite conclusion about these studies. Conclusion: More subsequent clinical studies based on experimental study will be needed afterwards. Strict and high-level study design with detailed description will be needed in further study.

Screening and Characterization of Lactic Acid Bacteria Strains with Anti-inflammatory Activities through in vitro and Caenorhabditis elegans Model Testing

  • Lee, Hye Kyoung;Choi, Sun-Hae;Lee, Cho Rong;Lee, Sun Hee;Park, Mi Ri;Kim, Younghoon;Lee, Myung-Ki;Kim, Geun-Bae
    • Food Science of Animal Resources
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    • v.35 no.1
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    • pp.91-100
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    • 2015
  • The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities.

Experimental Studies on the Effect of Gamibaegi-eum

  • Kim Won-Ill
    • The Journal of Korean Medicine
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    • v.25 no.4
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    • pp.61-78
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    • 2004
  • Objective : This study was undertaken to determine whether Gamibaegi-eum (BGU) in vitro and in vivo exerts a beneficial effect against cell injury induced by reactive oxygen species (ROS) in the human intestine. Methods : Effects of BGU in vitro on cell injury were examined using Caco-2 cells, cultured human intestinal cell line. Exposure of cells to H₂O₂ induced increases in the loss of cell viability in a time and dose-dependent fashion. Results : BGU prevented H₂O₂-induced cell death and its effect was dose-dependent over a concentration range of 0.05­1%. H₂O₂-induced cell death was prevented by catalase, the hydrogen peroxide scavenger enzyme, and deferoxamine, the iron chelator. However, the potent antioxidant DPPD did not affect H₂O₂-induced cell death. H₂O₂ increased lipid peroxidation, which was inhibited by BGU and DPPD. H₂O₂ caused DNA damage in a dose-dependent manner, which was prevented by BGU, catalase, and deferoxamine, but not DPPD. BGU restored ATP depletion induced by H₂O₂. BGU inhibited generation of superoxide and H₂O₂ and scavenged directly H₂O₂. Oral administration of mepirizole in vivo at a dose of 200mg/kg resulted in ulcer lesions in the stomach and the proximal duodenum. Pretreatment of BGU(0.1%/kg, orally) and catalase (800Units/kg, i.v.) significantly decreased the size of ulcers. Mepirizole increased lipid peroxidation in the mucosa of the duodenum, suggesting an involvement of ROS. Pretreatment of BGU and catalase significantly inhibited lipid peroxidation induced by mepirizole. Morphological studies showed that mepirizole treatment causes duodenal injury and its effect is prevented by BGU. Conclusion : These results indicate that BGU exerts a protective effect against cell injury in vitro and in vivo through antioxidant action. The present study suggests that BGU may playa therapeutic role in the treatment of human gastrointestinal diseases mediated by ROS.

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The Evaluation of the Effect of Herbal Extract on Osteoarthritis: In Vitro and In Vivo Study

  • Kim, Jaeyong;Yang, Siyoung;Choi, Chul-yung
    • Preventive Nutrition and Food Science
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    • v.21 no.4
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    • pp.310-316
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    • 2016
  • In this study, the anti-osteoarthritis effects of Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas extract (CPAE), observed and confirmed in previously clinical studies were further investigated by in vitro and in vivo studies. Anabolic biomarkers related to healthy cartilage maintenance, such as aggrecan, type II collagen ${\alpha}$-1 (Col2a1), sex determining region Y-box-9 (Sox-9), and catabolic biomarkers related to osteoarthritis, such as cyclooxygenase-2 (Cox-2), matrix metalloproteinase-13 (Mmp13), and nuclear factor kappa-light-chain-enhancer of activated B cells ($Nf{\kappa}b$), were evaluated by quantitative reverse transcriptase polymerase chain reaction and reporter gene assay. In vitro study results showed significant changes in both anabolic and catabolic biomarkers. For anabolic factors, significant changes in the level of aggrecan (P<0.05), Col2a1 (P<0.05), and Sox-9 (P<0.01) activation were shown after treatment of cartilage cells with CPAE (50 ng/mL) with similar efficacy compared to insulin growth factor, the positive control (100 ng/mL). For catabolic factors, significant changes in the inhibition activity of Cox-2 (P<0.05), Mmp13 (P<0.01), and $Nf{\kappa}b$ (P<0.05) were shown for CPAE (50 ng/mL) with similar efficacy compared to Celecoxib, the positive control ($10{\mu}M$). In the in vivo carrageenan-induced paw edema model study results showed that CPAE-treated groups (100 mg/kg) and Celecoxib-treated groups (60 mg/kg) showed comparably significant efficacy of inhibition by 37.1% and 52.1%, respectively. Furthermore, CPAE (200 mg/kg) showed similar effect to Celecoxib (60 mg/kg) with an inhibition rate of 54.3%. This result confirms that CPAE effectively inhibited the inflammation-induced osteoarthritis symptoms.

Studies on the Anti - aging Action of Korean Ginseng (고려인삼(高麗人蔘)의 노화억제작용(老化抑制作用)에 관(關)한 연구(硏究))

  • Choi, Jin-Ho;Oh, Sung-Ki
    • Korean Journal of Food Science and Technology
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    • v.17 no.6
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    • pp.506-515
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    • 1985
  • The inhibitory effects of red-ginseng saponin hydrolyzates (prosapogenin, panaxadiol and panaxatriol) on lipoperoxide formation in vitro and in vivo were investigated and correlated with anti-aging. Saponin hydrolyzates showed the electron-donating ability (EDA) of 12.88 - 19.76% to DPPH in vitro, and the ability was distinctively decreased in order of prosapogenin, panaxatriol and panaxadiol. The induction period of saponin hydrolyzates, which was measured by the method of peroxide value (POV), was much longer than red-ginseng saponin and decreased in order of prosapogenin, panaxatriol and panaxadiol. The inhibitory effect of saponin, hydrolyzates in vivo was remarkably greater than control. In contrast to red-ginseng saponin, almost similar inhibitory effect in rat liver and kidney was observed, whereas they were much more effective than red-ginseng saponin in blood. The superoxide dismutase (SOD) activity of saponin hydrolyzates in vitro was also measured, and the inhibitory effect of saponin hydrolyzates was found to be 24.2-36.4% and 2-3 times greater than that of red-ginseng saponin (12.1%). Saponin hydrolyzates showed the inhibitory effects of 11.2-21.6% and 12.9-22.2% in oral and intraperitioneal administrations, respectively. It was also found from the measurement of peroxidase activity that the inhibitory effects of saponin hydrolyzates were 111.4-139.6% in oral administration and 129.0-188.6% in intraperitoneal administration.

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1, 5 - bis (4 - methoxyphenyls) - 6, 7 - Dioxa-bicyclo [3.2.2] nonane's Anti-toxoplasmosis Effect that was Separated in Artemisin annula (개똥쑥에서 분리 확인된 endoperoxide ring 구조를 갖는 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane의 항톡소포자충 효과)

  • Jiang, Jing-Hua;Kim, Hwa-Kyoung;Kim, Hye-Sook;Kamata, Masaki;Wataya, Yusuke;Park, Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.82-85
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    • 2007
  • The Chinese medicinal plant Artemisia annua is the source of the antimalarial compound artemisinin. By the way, Artemisin annula was known have endoperoxide ring structure is included and has anti-malarial effect. Malaria and Toxoplasma gondii (T. gondii) is belong to Apicomplexa genera. So, confirmed whether we go compound 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane that have endoperoxide ring structure and there is anti-toxoplasmosis effect. The efficacy of 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2] nonane alone was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were peformed with HeLa cell cultures, with quantification of Toxoplasma growth by a cell proliferation assay. Selectivity of 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane was 4.9 in vitro cell proliferation assay, this is higher than sulfadiazine (selectivity was 1.63). For in vivo studies, mice were acutely infected intraperitoneally with 10$^5$ tachyzoites of the virulent RH strain and then treated perorally for 4 days from 6 hours postinfection. Efficacy was assessed by sequential determination of parasite burdens in peritoneal cavity. in vitro, 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane inhibited Toxoplasma growth at a concentration of 150mg/kg of body weight per day, the inhibition ratio was estimated to be 85.72%.