• Title/Summary/Keyword: model rat

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Pharmacokinetics of Anticancer Agent SB-31 in Rats & Rabbits and the Cardiovascular Effect on the Isolated Perfused Rat Heart & Blood Coagulation (SB-31의 Glycyrrhizin을 지표로 한 Rat과 Rabbit에서의 약물동태 및 심혈관계에 대한 효과 연구)

  • Kang, Won Ku;Park, Yong Soon;Lee, Dong Heum;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.2
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    • pp.122-132
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    • 1998
  • SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

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Differentiation of the Fetal Rat Pulmonary Epithelial Cells in Organotypic Culture (기관형 배양에서 흰쥐 태자 폐상피세포의 분화)

  • 홍혜남;조운복
    • The Korean Journal of Zoology
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    • v.35 no.3
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    • pp.295-307
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    • 1992
  • In order to study the differentiation of the epithelial cells during the development of fetal rat lung tissue, histological changeB in organotypic culture and in vivo were examined. Light microscopy and scanning electron microscopy were used to analvre the histological change in rat lung from the 15th nary of gestation to the 111th nary after birth. In organotypic culture system, the pulmonary epithelial cell differentiation was studied by scanning electron microscopy. The results obtained from this study were as follows. 1. During deveiopment of lung, the glandular stage lasted from the Isth day to the lsth naut of gestation; the canalicular stage from the 17th nay to the 19th naut of gestation; the saccuiar stage from 20th nary to the birth. Alveolar stage was observed at the 3rd nary of postnatal rat lung. 2. In organotvpic culture of fetal rat lung cells organized alveolar-like structures resembling those of in uiuo state were observed on the gelatin matrix. In contrast with in vivo state, fetal lung cells formed group of type ll pneumocytes predominently along the contours of the matrix. These cells have large apical surface, short microvilli and secreted materials which may be sunactant. These results suggested that an orsanotypic culture retaining epithelial- -mesenchvmal relationships is appropriate culture model to study the pulmonary epithelial cell (especially type ll pneumocvte) differentation.

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A Review of Rat Models of Avascular Necrosis of the Femoral Head Treated with Natural Extracts

  • Go-Woon, Kim;Hyoung-Yong, Park;Yeon-Cheol, Park
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.239-248
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    • 2022
  • To determine the effect of Korean medicine treatment of avascular necrosis of the femoral head (ANFH) this study reviewed both single ingredients and bioactive compounds in the treatment of ANFH in a rat model. Literature was retrieved from PubMed and Google Scholar using the keywords "femur head necrosis," "natural extract," and "rat." The data from studies analyzed included: rats' characteristics, development methods of ANFH, natural extracts administration, observation methods, and outcome indicators. Two independent researchers screened all articles retrieved and 26 studies were chosen. The most used rat species was the Sprague Dawley rat (76.9%). To induce ANFH, steroid injections (46.2%), and oral gavage (53.8%) were typically used. Studies focused mainly on factors affecting bone formation (65.3%), and apoptosis (53.8%). Research on ANFH focused on using traditional natural substances mentioned in classical literature to confirm its effectiveness against anti-inflammation, osteogenesis, and cell death. ANFH has a diverse etiology, therefore research models such as genetic analysis of human-derived samples from ANFH patients may shed more light on the condition. Moreover, research into herbal medicines and pharmacoacupuncture treatment of ANFH should precede.

Genetic Quality Control of the Rat Strains at the National Bio Resource Project-Rat

  • Kuramoto, Takashi;Nakanishi, Satoshi;Yamasaki, Ken-ichi;Kumafuji, Kenta;Sakakibara, Yuichi;Neoda, Yuki;Takizawa, Akiko;Kaneko, Takehito;Otsuki, Mito;Hashimoto, Ryoko;Voigt, Birger;Mashimo, Tomoji;Serikawa, Tadao
    • Interdisciplinary Bio Central
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    • v.2 no.4
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    • pp.12.1-12.7
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    • 2010
  • The National Bio Resource Project-Rat (NBRP-Rat) comprises the largest bank of laboratory rat (Rattus norvegicus) strains in the world. Its main focus is to develop infrastructure that will facilitate the systematic collection, preservation, and provision of rat strains. To breed effectively more than 180 rat strains in living stock, we establish the genetic control system in which a systematic set of genetic diagnoses and genetic monitoring are included. Genetic monitoring is performed by using 20 polymorphic markers. Monitoring is carried out when a living animal stock is re-established by using cryopreserved embryos or sperm or when a rat strain is first introduced to the NBRP-Rat by a depositor. Additional monitoring is then carried out on each strain every two years. Genetic diagnosis is performed largely by employing the Amp-FTA method. Protocols which detail how to perform a genetic diagnosis of 11 transgenes and 24 mutations have been made. Among the mutations, nine can be detected by simple gel electrophoresis of the PCR products, 11 by restriction enzyme treatment of the PCR products, and four by direct PCR product sequencing. Using this genetic control system, the NBRP-Rat can guarantee the genetic quality of its rat strains.

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.

Perfusion Techniques Using the Modified Isolated Working Rat Heart Model (흰쥐의 심장을 이용한 Modified Isolated Working Heart Perfusion Technique)

  • Lee, Chong-Kook;Choi, Hyeong-Ho
    • Journal of Chest Surgery
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    • v.13 no.4
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    • pp.338-345
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    • 1980
  • We have modified an isolated perfusion rat heart model of cardiopulmonary bypass, with which we are able to screen the effects of various cardioplegic solutions and hypothermia upon the ability of the heart to survivie during and recover from period of ischemic arrest. The modified experimental model was differed from the original as follow : a heat coil chamber of atrial and aortic reservoir provided temperature control, and the perfusate was gassed with each pure oxygen and pure carbon dioxide in 95:5 ratio. The Langendorff perfusion was initiated for a 10 minute period by introducing perfusate at $37^{\circ}C.$ into the aorta from the aortic reservoir located 100 cm above the heart. The isolated perfused working rat heart model was a left heart preparation in which oxygenated perfusion medium (at $37^{\circ}C.$) entered the cannulated left atrium at a pressure of 20 cm $H_{2}O$ and was passed to the ventricle, from which it was sponeously elected(no electrical pacing) via an aortic cannula, against a hydrostatic pressure of 100cm $H_{2}O$. during this working period various indices of cardiac functin were measured. The cardiac functions were stable for over 3 hour with perfusion of Krebs-Henseleit bicarbonate buffer solution containing only glucose (11.1 mM/L). The percentage of cardiac functins were maintained about 94% on heart rate, 80.6% on peak aortic pressure, 87.7% on coronary flow and 76.3% on aortic flow rate after 3 hour of working heart perfusion at a pressure of 20 cm $H_{2}O$. We believe this preparation to be a good biochemical model for the human heart which offers many advantages including economic, speed of preparation, reproducibility, and the ability to handle large numbers.

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Analgesic effect of Daeganghwal-Tang on a rat model of CFA-induced arthritis (CFA에 의해 유도된 백서(白鼠)모델 관절염(關節炎)에서 대강활탕(大羌活湯)의 진통효과(鎭痛效果))

  • Seo, Yoon-Jung;Koo, Sung-Tae;Yang, Yoon-Jung;Kim, San;Yoo, In-Sik;Lim, Kyu-Sang
    • Korean Journal of Acupuncture
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    • v.21 no.4
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    • pp.83-99
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    • 2004
  • Objectives : Daeganghwal-Tang(DGHT) is one of the prescriptions used for the treatment of rheumatoid arthritis(RA) in oriental medicine. The present study aimed to examine the analgesic effect of DGHT on a rat model of CFA-induced arthritis, and the relations between DGHT-induced analgesia and endogenous nitric oxide(NO) and inducible NO synthase(iNOS)/neuronal NOS. Methods : CFA-induced arthritis model used to test the effect of DGHT was chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least the next 18 days. the reduced stepping force of the limb was presumably due to a painful knee. DGHT dissolved in water was orally administrated. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 4 hours. Results : DGHT produced significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 2 hours. DGHT produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. Both NO production and nNOS/iNOS protein expression which is increased by arthritis were suppressed by DGHT administration. Conclusions : The data suggest 1) that DGHT produces a potent analgesic effect on the chronic knee arthritis pain model in the rat and 2) that DGHT-induced analgesia modulate endogenous NO through the suppression of nNOS/iNOS protein expression.

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Effects of a Proteasome Inhibitor on Cardiomyocytes in a Pressure-Overload Hypertrophy Rat Model: An Animal Study

  • Kim, In-Sub;Jo, Won-Min
    • Journal of Chest Surgery
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    • v.50 no.3
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    • pp.144-152
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    • 2017
  • Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of $NF-{\kappa}B$ and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and $NF-{\kappa}B$ was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not $NF-{\kappa}B$, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, $NF-{\kappa}B$ expression levels were not related to UPS function.

Expression of MCP-1 in Spinal Dorsal Horn in a Rat Model of Lumbar Disc Herniation (추간판 탈출증 흰 쥐 모델에서 척수후각에서의 MCP-1의 발현)

  • Cho, Yun-Woo;Park, Hea-Woon;Kim, Su-Jeong;Seo, Jeong-Min;Do, Sung-Jin;Ahn, Sang-Ho
    • The Journal of Korean Physical Therapy
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    • v.21 no.3
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    • pp.95-102
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    • 2009
  • Purpose: This study evaluates MCP-1 expression in the dorsal horn of a rat model of lumbar disc herniation by an autograft of the nucleus pulposus to the spinal nerve. Methods: After a coccygeal nucleus pulposus graft to the left $5^{th}$ lumbar spinal nerve, proximal to dorsal root ganglion, mechanical allodynia and thermal hyperalgesia were assessed 1 day before surgery, and 1, 10, 20, 30 days after surgery. The mRNA of MCP-1 in the dorsal horn was assessed by real time PCR to compare the temporal pattern of neuropathic pain of the lumbar disc herniation model. Results: In the ipsilateral side of the lumbar disc herniation models, mechanical allodynia and thermal hyperalgesia reached a maximum at 10 days after surgery with significant difference from the control group. Pain was also provoked in the contralateral side of the lumbar disc herniation models with less intensity than the ipsilateral side. The level of MCP-1 mRNA expression in the dorsal horn reached a peak at 20 days after surgery. Conclusion: Mechanical allodynia and thermal hyperalgesia was induced by nucleus pulposus in a rat lumbar disc herniation model, similar to a previously reported peripheral nerve injury model. The level of MCP-1 expression was higher in the dorsal horn of the ipsilateral and contralateral sides. These results suggest that MCP-1 might play a role in the maintenance of neuropathic pain.

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Application of Primary Rat Corneal Epithelial Cells to Evaluate Toxicity of Particulate Matter 2.5 to the Eyes (눈에 대한 미세먼지의 독성 평가를 위한 쥐 각막 상피 세포의 적용)

  • Kim, Da Hye;Hwangbo, Hyun;Lee, Hyesook;Cheong, Jaehun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.32 no.9
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    • pp.712-720
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    • 2022
  • The purpose of this study was to investigate the efficacy of rat corneal-derived epithelial cells as an in vitro model to evaluate the harmfulness of the cornea caused by particulate matter 2.5 (PM2.5). To establish an experimental model for the effect of PM2.5 on corneal epithelial cells, it was confirmed that primary cultured cells isolated from rat eyes were corneal epithelial cells through pan-cytokeratin staining. Our results showed that PM2.5 treatment reduced cell viability of primary rat corneal epithelial (RCE) cells, which was associated with the induction of apoptosis. PM2.5 treatment also increased the generation of reactive oxygen species due to mitochondrial dysfunction. In addition, the production of nitric oxide and inflammatory cytokines was increased in PM2.5-treated RCE cells. Furthermore, through heatmap analysis showing various expression profiling between PM2.5-exposed and unexposed RCE cells, we proposed five genes, including BLNK, IL-1RA, Itga2b, ABCb1a and Ptgs2, as potential targets for clinical treatment of PM-related ocular diseases. These findings indicate that the primary RCE cell line is a useful in vitro model system for the study of PM2.5-mediated pathological mechanisms and that PM2.5-induced oxidative and inflammatory responses are key factors in PM2.5-induced ocular surface disorders.