• Title/Summary/Keyword: In vivo rat model

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Development of physiological pharmacokinetic model

  • Kwon, Kwang-Il
    • Archives of Pharmacal Research
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    • v.10 no.4
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    • pp.250-257
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    • 1987
  • The development of physiologically based pharmacokinetic model for drug distribution and excretion is described. The physiological modeling procedure is useful in animal and clinical applications to obtain fundamental knowledge of the transport and metabolism of a substance in vivo. In this paper a review of physiologically based pharmacokinetics is presented in the hope of understanding and increasing the use of this modelling technique. The method of model development and the composition of equations based on the different models are explained. For the better understanding a physiological pharmacokinetic model of tenoxicam disposition in the rat is presented as an example of flow limited model.

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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.

Development of Local Drug Delivery System: Prolonged Sciatic Nerve Blockade From Biodegradable Microspheres

  • Lim, Jeong-Ok
    • Journal of Pharmaceutical Investigation
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    • v.25 no.3
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    • pp.33-35
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    • 1995
  • Microspheres containing tetracaine or bupivacaine with poly-lactic-glycolic acid were prepared with a range of compositions. Using the rat scicatic nerve model in vivo it was found that prolonged blockade for periods of 2-7 days. depending on composition variables. Polymer-local anesthetics microspheres are feasible delivery vehicle for prolonged regional nerve blockade.

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Effect of 4-hexylresorcinol on Blood Coagulation and Healing of Injured Vessel in a Rat Model

  • Park, Yong-Tae;Park, Si-Yeok;Kim, Min-Keun;Kim, Seong-Gon;Park, Young-Wook;Kwon, Kwang-Jun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.35 no.5
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    • pp.284-293
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    • 2013
  • Purpose: For reconstruction of craniomaxillofacial defects caused by tumor, trauma, infection etc, free flap transplantation with microvascular surgery is a very useful method. Thrombus formation at the anastomosis site is the major cause of graft failure. 4-Hexylresorcinol (4-HR) is generally known as an antiseptic and antiparasitic agent. This study was conducted in order to evaluate the effect of 4-HR on blood coagulation in vitro. In addition, we investigated thrombus formation and endothelial repair of an injured vessel in an animal model. Methods: In the in vitro experiment, we compared blood coagulation time between the 4-HR treated group and normal blood. Thirty rats were used for in vivo animal experiments. After exposure of the right femoral vein, a micro vessel clamp was placed and the femoral vein was intentionally cut. Microvascular anastomosis was performed on all rats using 10-0 nylon under microscopy. The animals were divided into two groups. In the experimental group (n=15), 4-HR (250 mg/kg) mixed with olive oil (10 mL/kg) was administered per os daily. Animals in the control group (n=15) were given olive oil only. The animals were sacrificed at three days, seven days, and fourteen days after surgery and rat femoral vein samples were taken. Vascular patency and thrombus formation were investigated just before sacrifice. Histologic analysis was performed under a microscope. Results: Results of an in vitro blood coagulation test showed that coagulation time was delayed in the 4-HR treated group. The results obtained from an in vivo 4-HR administered rat model showed that the patency of all experimental groups was better at thirty minutes, seven days, and fourteen days after microvascular anastomosis than that of the control group at seven and fourteen days after anastomosis, and the amount of thrombus in the experimental groups was much less than that of the control group. Endothelial repair was observed in the histologic analysis. Conclusion: Findings of this study demonstrated that blood coagulation was delayed in the vitro 4-HR treated group. In addition, good vascular patency, anti-thrombotic effect, and repair of venous endothelial cells were observed in the vivo 4-HR administered rat group.

Studies on the Air-Liquid Interface Culture as an Experimental Model for Physiology and Pharmacology of Tracheal Epithelial Cells (기관(氣管) 상피세포 생리 및 약리 실험모델로서의 공기-액체 접면 일차배양법 연구)

  • 이충재;이재흔;석정호;허강민
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.281-286
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    • 2002
  • In this study, we intended to get a preliminary data for establishing rat tracheal surface epithelial(RTSE) cell culture system as an experimental model for physiology and pharmacology of tracheal epithelial cells. Primary culture on the membrane support and application of the air-liquid interface system at the level of cell layer were performed. The cell growth rate and mucin production rate were measured according to the days in culture. The results were as follows: this culture system was found to manifest mucocilliary differentiation of rat tracheal epithelial cells, the cells were confluent and the quantity of produced and released mucin was highest on culture day 9, the mucin was mainly released to the apical side and tbe free $^3{H}$-glucosamine which was not incorporated to process of synthesis of mucin was left on the basolateral side. Taken together, we suggest that air-liquid interface culture system can be used as a substitute for immersion culture system and as an experimental model for in vivo mucus-hypersecretory diseases.

Synthesis and Anti-inflammatory Activity of Fructigenine A Derivatives

  • Chang, Jun-Hwan;Moon, Hong-sik
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.9 no.1
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    • pp.59-61
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    • 2004
  • Several derivatives were synthesized from fructigenine A, which was isolated from Penicillium fructigenum. The anti-inflammatory properties of fructigenine A was evaluated in vivo with a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model and a carrageenan-induced rat paw edema model. Results showed that the anti-inflammatory activity was significantly higher with fructigenine derivatives than with indomethacin, which was used as a standard. We concluded that fructigenine derivatives could exert an anti-inflammatory effect.

Metformin enhances the osteogenic activity of rat bone marrow mesenchymal stem cells by inhibiting oxidative stress induced by diabetes mellitus: an in vitro and in vivo study

  • Kai Dong;Wen-Juan Zhou;Zhong-Hao Liu
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.54-68
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    • 2023
  • Purpose: The purpose of this study was to determine whether metformin (MF) could alleviate the expresssion of reactive oxygen species (ROS) and improve the osteogenic ability of bone marrow mesenchymal stem cells derived from diabetic rats (drBMSCs) in vitro, and to evaluate the effect of MF on the ectopic osteogenesis of drBMSCs in a nude mouse model in vivo. Methods: BMSCs were extracted from normal and diabetic rats. In vitro, a cell viability assay (Cell Counting Kit-8), tests of alkaline phosphatase (ALP) activity, and western blot analysis were first used to determine the cell proliferation and osteogenic differentiation of drBMSCs that were subjected to treatment with different concentrations of MF (0, 50, 100, 200, 500 µM). The cells were then divided into 5 groups: (1) normal rat BMSCs (the BMSCs derived from normal rats group), (2) the drBMSCs group, (3) the drBMSCs + Mito-TEMPO (10 µM, ROS scavenger) group, (4) the drBMSCs + MF (200 µM) group, and (5) the drBMSCs + MF (200 µM) + H2O2 (50 µM, ROS activator) group. Intracellular ROS detection, a senescence-associated β-galactosidase assay, ALP staining, alizarin red staining, western blotting, and immunofluorescence assays were performed to determine the effects of MF on oxidative stress and osteogenic differentiation in drBMSCs. In vivo, the effect of MF on the ectopic osteogenesis of drBMSCs was evaluated in a nude mouse model. Results: MF effectively reduced ROS levels in drBMSCs. The cell proliferation, ALP activity, mineral deposition, and osteogenic-related protein expression of drBMSCs were demonstrably higher in the MF-treated group than in the non-MF-treated group. H2O2 inhibited the effects of MF. In addition, ectopic osteogenesis was significantly increased in drBMSCs treated with MF. Conclusions: MF promoted the proliferation and osteogenic differentiation of drBMSCs by inhibiting the oxidative stress induced by diabetes and enhenced the ectopic bone formation of drBMSCs in nude mice.

Improvement of antithrombotic activity of red ginseng extract by nanoencapsulation using chitosan and antithrombotic cross-linkers: polyglutamic acid and fucoidan

  • Kim, Eun Suh;Lee, Ji-Soo;Lee, Hyeon Gyu
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.236-245
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    • 2021
  • Background: Red ginseng (RG) extract, especially ginsenoside Rg1 and Rb1 fractions has been reported to have antithrombotic activities. However, gastric instability and low intestinal permeability are considered to be obstacles to its oral administration. We hypothesized that stability, permeability, and activities of RG might be improved by encapsulation within nanoparticles (NPs) prepared with antithrombotic coating materials. Methods: RG-loaded chitosan (CS) NPs (PF-NPs) were prepared by complex ionic gelation with the antithrombotic wall materials, polyglutamic acid (PGA), and fucoidan (Fu). The concentrations of PGA (mg/mL, X1) and Fu (mg/mL, X2) were optimized for the smallest particle size by response surface methodology. Antithrombotic activities of RG and PF-NPs were analyzed using ex vivo and in vivo antiplatelet activities, in vivo carrageenan-induced mouse tail, and arteriovenous shunt rat thrombosis models. Results: In accordance with a quadratic regression model, the smallest PF-NPs (286 ± 36.6 nm) were fabricated at 0.628 mg/mL PGA and 0.081 mg/mL Fu. The inhibitory activities of RG on ex vivo and in vivo platelet aggregation and thrombosis in in vivo arteriovenous shunt significantly (p < 0.05) increased to approximately 66.82%, 35.42%, and 38.95%, respectively, by encapsulation within PF-NPs. For an in vivo carrageenan-induced mouse tail thrombosis model, though RG had a weaker inhibitory effect, PF-NPs reduced thrombus significantly due to the presence of PGA and Fu. Conclusion: PF-NPs contributed to improve the activities of RG not only by nanoencapsulation but also by antithrombotic coating materials. Therefore, PG-NPs can be suggested as an efficient delivery system for oral administration of RG.

Anti-inflammatory Effects of Co-treatment of Jingyoganghwaltang and Cheongsimhwan on Croton Oil Induced Hemorrhoid Model in Rats

  • Jo, Nayoung;Mou, Jong-Cheng;Leem, Kanghyun;Kim, Taeyeon
    • The Korea Journal of Herbology
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    • v.33 no.6
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    • pp.79-86
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    • 2018
  • Objectives : Hemorrhoids are one of the most common diseases in humans. Jingyoganghwaltang (JG) and Cheongsimhwan (CS) have been used for treating hemorrhoids in Korean traditional clinical practice. The present study was designed to evaluate the traditional effects of JG and CS on the experimental hemorrhoid model in rats. Methods : Hemorrhoids are closely related to inflammation. Accordingly, we examined the nitric oxide (NO) production in macrophage cell line in order to evaluate the anti-inflammatory effect. The expression levels of inflammation related genes including IL-1 beta, IL-6, INOS, and TNF-alpha were examined via a real-time quantitative PCR. Croton oil-induced hemorrhagic animal model was used to test the in vivo efficacy against hemorrhoids. The rectal tissues were weighed and the inflammatory proteins were measured to confirm the anti-inflammatory effects. Results : JG and CS have a statistically significant effect on inhibition of NO production and on the reduction of inflammatory gene expression such as IL-1 beta, IL-6, INOS, and TNF-alpha. The synergistic effects of co-treatment of JG and CS were found out in the IL-6 gene expression. The in vivo study using croton oil-induced hemorrhoid model in rat was performed to check the co-treatment effects. As a result, the co-treatment reduced the inflammation of the rectal tissue and decrease the inflammation related protein productions including ICAM1, MMP2 and MMP9. Conclusions : These results suggest that JG and CS co-treatment demonstrated anti-inflammatory effects in croton oil-induced hemorrhoid model in rat.