• Title/Summary/Keyword: S-RAT model

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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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Human Embryonic Stem Cell Transplantation in Parkinson′s Disease (PD) Animal Model: II. In Vivo Transplantation in Normal or PD Rat Brain

  • Choe Gyeong-Hui;Ju Wan-Seok;Kim Yong-Sik;Kim Eun-Yeong;Park Se-Pil;Im Jin-Ho
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.19-19
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    • 2002
  • This study was to examine whether the in vitro differentiated neural cells derived from human embryonic stem (hES, MB03) cells can be survived and expressed tyrosin hydroxylase(TH) in grafted normal or PD rat brain. To differentiate in vitro into neural cells, embryoid bodies (EB: for 5 days, without mitogen) were formed from hES cells, neural progenitor cells(neurosphere, for 7-10 days, 20 ng/㎖ of bFGF added N2 medium) were produced from EB, and then finally neurospheres were differentiated into mature neuron cells in N2 medium(without bFGF) for 2 weeks. In normal rat brain, neural progenitor cells or mature neuron cells (1×10/sup 7/ cells/㎖) were grafted to the striatum of normal rats. After 2 weeks, when the survival of grafted hES cells was examined by immunohistochemical analysis, the neural progenitor cell group indicated higher BrdU, NeuN+, MAP2+ and GFAP+ than mature neuron cell group in grafted sites of normal rats. This result demonstrated that the in vivo differentiation of grafted hES cells be increased simultaneously in both of neuronal and glial cell type. Also, neural progenitor cell grafted normal rats expressed more TH pattern than mature neuron cells. Based on this data, as a preliminary test, when the neural progenitor cells were grafted into the striatum of 6-hydroxydopamine lesioned PD rats, we confirmed the cell survival (by double staining of Nissl and NeuN) and TH expression. This result suggested that in vitro differentiated neural progenitor cells derived from hES cells are more usable than mature neuron cells for the neural cell grafting in animal model and those grafted cells were survived and expressed TH in normal or PD rat brain.

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The Effect of Transcranial Direct Current Stimulation on Cognitive Function and Biochemical Change of Rats with Alzheimer's Desease

  • Kim, Jin-Young;Park, Seong-Doo;Song, Hyun-Seung;Yang, Kyung-Hee;Yu, Seong-Hun
    • The Journal of Korean Physical Therapy
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    • v.26 no.6
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    • pp.436-441
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    • 2014
  • Purpose: The objective of this study was to offer clinical primary data that it's aims to examine effects of transcranial direct current stimulation (tDCS) on cognitive function and biochemical change of rat with alzheimer's disease(AD) induced by injecting scopolamine. Methods: Subjects were instructed cognitive dysfunction model, rat of Sprague-Dawley system was injected with scopolamine and each experimental group was classified into three; group I (n=16) is non-treatment groups; group II (n=16) is applied with the tacrine; group III (n=16) is applied with the tDCS. The ziggurat task test was conducted to observe behavioral changes and cognitive function ability and 7, 14, 21, 28 days after the model. Acetylcholine Esterase (Ach E) activity was examined for biochemical assessment of which the results are followed. Results: Participants showed as to behavioral change, tacrine application group was the most significantly responded, following tDCS application group. As to biochemical change, same as above, tacrine application group was the most significantly responded, following tDCS application group. Conclusion: From these results, confirm that tDCS application to rat with alzheimer's disease leads to positive effects on behavioral, cognitive function changes, and biochemical changes, lasting for certain period of time. This study, in particular, tDCS, which can change excitability of brain cells non-invasively, could provide basic data that is useful as a new treatment way for the patients with cognitive dysfunction.

Studies on Protective Effect of Bupleurum falcatum Extract (SHI-1909) against Experimental Inflammtory Bowel Disease Model (시호추출물 (SHI-1909)의 염증성 대장염 실험동물 모델에 대한 치료효과)

  • Cho, Seong-Wan;Kim, Young-Kwon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.10 no.3
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    • pp.613-619
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    • 2009
  • The Efficacy of SHI-1909 was investigated in comparision with predinisolone in acetic acid and Picrylsulfonic acid solution (TNBS)-induced rat inflammatory bowel disease (IBD) for 5 days. 7% Acetic acid and 5% TNBS solution were administered with polyethylene (P.E) tube inserted to rats intracolon, which causing colitis to the rats. The acetic acid and TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. We checked the inflammatory parameters like rat's weight, food intake quantity change during administration. After 5 days, we sacrificed the rats and checked the colon's length, ulcer and pathologic condition. Oral treatment with SHI-1909 resulted in significant recovery of macroscopic parameters like weight and diet intake change. Especially, SHI-1909 had a more potent effect than prednisolone on macroscopic colonic damage score. We can suggest that SHI-1909 could be a promising drug in the treatment of IBD.

Antitumor Activity of Salvia miltiorrhiza Herbal Extract in Rat Tumor Model (흰쥐의 종양에 대한 단삼 추출물의 항종양 활성)

  • Park, Hyun-Jeong;Ahn, Sang-Gun;Kim, Jeong-Sang
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.4
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    • pp.400-404
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    • 2007
  • The present study was carried out to investigate the antitumor activity of Salvia miltiorrhiza (SM) herbal extract in rat tumor model. We used a new tumor animal model for the invasion and metastasis of cancer using genetically k-ras-induced rat kidney cells (RK3E-ras). We observed tumor as early as 7 days after the injection of RK3E-ras cells in subcutaneous of Sprague-Dawley rats. All of the rats developed tumor mass at the inoculated site. After 7 days, the experimental groups were divided into two: saline control and injected with SM (200 mg/kg) groups. We investigated tumor's weight, size and hepatic metastasis of each group. Injection of SM herbal extract every other day for 14 days significantly inhibited tumor growth. Histologically, the tumors were undifferentiated carcinoma showing multifactorial necrosis and hemorrhage; also, the tumor invaded into hepatoportal region. Treatment with SM herbal extract caused significant inhibition of tumor cell proliferation. Our data showed that SM herbal extract is effective in controlling the tendency of tumor cell proliferation and metastasis by injection of RK3E-ras cells. These findings provided the potential value of SM as a novel antitumor agent candidate.

Effects of the Korean Medicinal Herbs for Treatment of Polycystic Ovary induced Rat Models: a Review (다낭성 난소 유발 rat에 단미 한약제가 미치는 영향에 관한 연구분석)

  • Bae, In-Suk;Kim, Eun-Seo;Nam, Eun-Young;Jung, Seung-Hyun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.31 no.1
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    • pp.122-137
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    • 2018
  • Objectives: This study is to review the effect of Korean medicinal herbs on treatment of polycystic ovary induced rat models reported in domestic & foreign journals. Methods: 7 electronic databases (Pubmed, CNKI, EMBASE, Oasis, RISS, CENTRAL, Koreankt) were searched with term as polycystic ovary, and study reports on polycystic ovary impairment with Korean medicinal herbs. After selecting several studies, the analysis was focused on items reflected in the Rotterdam criteria for diagnosis of polycystic ovary syndrome such as hyperandrogenism (HA), ovarian weight, the number of follicle cysts, estrous cycles, and etc. Results: 15 studies were reviewed. As a polycystic ovary induction material, estradiol valerate (EV) was used in 9 studies, testosterone propionate (TP) in 2 studies and dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), Poretsky's method and letrozole (LE) was used in rest 4 studies, respectively. Tribulus terrestris (TT), Nardostachys jatamansi (NJ), Lycii cortex (LC), Cinnamomum cassia kees (CCK) and Atractylodis macrocephalae koidz (AMK) produced statistically significant results related to hyperandrogenism. In ovarian weight, Silybum marianum (SM), AMK and Alllium sativum (AS) were statistically significant. In the the number of follicle cysts, SM and TT were statistically significant. In estrous cycles, AMK, NJ, TT and Coix lacryma-jobi (CL) were statistically significant. Conclusions: Based on the diagnosis criteria of Rotterdam, TT, NJ, AMK, SM, AS, and CL produced statistically significant results in rat model.

Cerebral Blood Flow Monitoring by Diffuse Speckle Contrast Analysis during MCAO Surgery in the Rat

  • Yeo, Chaebeom;Kim, Heejaung;Song, Cheol
    • Current Optics and Photonics
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    • v.1 no.5
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    • pp.433-439
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    • 2017
  • The rodent model has been used frequently to understand stroke pathophysiology, due to its low cost and the large spectrum of genetic strains available. Here, we present a diffuse speckle contrast analysis system (DSCA) with a $1{\times}2$ optical switch that was used to non-invasively assess cerebral blood flow (CBF) changes in the rat during intraluminal suturing for middle cerebral artery occlusion (MCAO) surgery. The blood flow index (BFI) in the left hemisphere was lower than that in the right hemisphere because the left middle cerebral artery was occluded. Furthermore, the performance of the DSCA system was compared with that of commercial laser Doppler flowmetry. The changes in the BFI measured by the two systems were correlated strongly. The DSCA system was less sensitive to motion artifacts and able to measure relatively deep tissue flow in the rat's brain. In conclusion, the DSCA system secured CBF monitoring during surgery in a rodent model without craniotomy.

Effects of Far Infrared on Nitric Oxide level at a rat model of Autoimmune Arthritis Induced (원적외선이 자가면역성 관절염 흰쥐모델의 산화질소정량에 미치는 영향)

  • Kim Jae Yoon;Park Kyu Hyun;Park Young Han;Kim Jin-Sang;Park Rae Joon
    • The Journal of Korean Physical Therapy
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    • v.14 no.2
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    • pp.65-73
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    • 2002
  • OBJECTIVE: This study was Far infrared(FIR) irradiating to a rat collagen-induced autoimmune arthritis and observed nitric oxide level of spine. METHODS: Type II collagen(CII) in adjuvant was injected into rats on day 0. The results showed that rats injected with CII plus adjuvant had signs of autoimmune arthritis on day 14. Thereafter, Far infrared(FIR) irradiation was begun on day 15. The rats were irradiated FIR twice per day for 20 min each time. RESULTS: Seven days later(Day 22), the level of NO at FIR irradiated group(FRG; Arth+FIR) was decreased more than FIR-non irradiated group(FNRG; Arth). Twenty-one days later(Day 36), the level of NO at FRG was more closed to the control group's NO level than the FNRG. CONCLUSION: These results indicated that Far infrared irradiating appears to reduce the nitric oxide level at a rat model of autoimmune arthritis induced.

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Hyperkinetic Rat Model Induced by Optogenetic Parafascicular Nucleus Stimulation

  • Moonyoung Chung;Young Seok Park
    • Journal of Korean Neurosurgical Society
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    • v.66 no.2
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    • pp.121-132
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    • 2023
  • Objective : The parafascicular nucleus (PF) plays important roles in controlling the basal ganglia. It is not well known whether the PF affects the development of abnormal involuntary movements (AIMs). This study was aimed to find a role of the PF in development of AIMs using optogenetic methods in an animal model. Methods : Fourteen rats were underwent stereotactic operation, in which they were injected with an adeno-associated virus with channelrhodopsin (AAV2-hSyn-ChR2-mCherry) to the lateral one third of the PF. Behavior test was performed with and without optical stimulation 14 days after the injection of the virus. AIM of rat was examined using AIM score. After the behavior test, rat's brain was carefully extracted and the section was examined using a fluorescence microscope to confirm transfection of the PF. Results : Of the 14 rats, seven rats displayed evident involuntary abnormal movements. AIM scores were increased significantly after the stimulation compared to those at baseline. In rats with AIMs, mCherry expression was prominent in the PF, while the rats without AIM lacked with the mCherry expression. Conclusion : AIMs could be reversibly induced by stimulating the PF through an optogenetic method.

Lamotrigine Decreased Hippocampal Damage and Improved Vascular Risk Markers in a Rat Model of Pentylenetetrazole Induced Kindling Seizure

  • Haggag, Basma S.;Hasanin, Amany H.;Raafat, Mona H.;Kawy, Hala S. Abdel
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.3
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    • pp.269-278
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    • 2014
  • Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.