• Title/Summary/Keyword: 모델 쥐

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Pharmacological Profile of KR-31125, an Orally Active AT1 Receptor Antagonist (안지오텐신 수용체 리간드 KR-31125의 생체 내 활성에 관한 연구)

  • Lee, Sung-Hou
    • Journal of Life Science
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    • v.20 no.7
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    • pp.969-976
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    • 2010
  • In vivo studies of KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) were performed in pithed rats, conscious angiotensin II (AII) challenged normotensive rats, renal hypertensive rats (RHRs) and furosemide-treated beagle dogs. KR-31125 induced a non-parallel right shift in the dose-pressor response curve to AII ($ID_{50}$: 0.095 mg/kg) with a dose-dependent reduction in the maximum responses in pithed rats. Compared to losartan, this antagonistic effect was about 18 times more potent, presenting competitive antagonism. Other agonists such as norepinephrine and vasopressin did not alter the responses induced by KR-31125. Orally administered KR-31125 had no agonistic effect and dose-dependently inhibited the pressor response to AII with a slightly weaker potency ($ID_{50}$: 0.25 and 0.47 mg/kg, respectively) in the AII-challenged normotensive rat model, but with a more rapid onset of action than losartan (time to $E_{max}$: 30 min for KR-31125 and 6 hr for losartan). KR-31125 produced a dose-dependent antihypertensive effect with a higher potency than losartan in RHRs, and these effects were confirmed in furosemide-treated dogs where they presented a dose-dependent and long-lasting (>8 hr) antihypertensive effect with a rapid onset of action (time to $E_{max}$: 2-4 hr), as well as a 20-fold greater potency than losartan. These results suggest that KR-31125 is a potent, orally active $AT_1$ receptor antagonist that can be applied to the development of new diagnostic and research tools as an added exploratory potential of $AT_1$ receptor antagonist.

Evaluation on Effectiveness for Preventing Post Surgical Adhesion of Sodium Hyaluronate/Sodium Carboxymethyl Cellulose (HA/CMC) Membrane in Rat Cecum/Peritonium Model (쥐 맹장/복벽 찰과상 모델에서 Sodium Hyaluronate/sodium Carboxymethyl Cellulose 멤브레인의 수술 후 유착방지에 대한 유효성 평가)

  • Lee, Young-Moo;Lee, Young-Woo
    • Membrane Journal
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    • v.15 no.3
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    • pp.213-223
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    • 2005
  • We prepared an anti-adhesion membrane made of sodium hyaluronate/sodium carboxymethylcellulose (HA/CMC) and evaluated its effectiveness for adhesion prevention in a rat model. The anti-adhesion membrane was prepared by lyophilizing HA/CMC solution and cross-linking properly with 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC). In a cecum/abdominal wall abrasion model of Sprague-Dawley rat, cecal serosa and abdominal wall were abraded in $1\times2\;(cm^2)$ with a bone burr after peritoneal midline incision and sutured at 3 points around the injured surface. The denuded cecum was covered with HA/CMC membrane (experimental group), or nothing (control group) and apposed to the abdominal wall. Most of the control group represented 3 or more of adhesion grade at POD 7, 14, 21, and 28, whereas $60\~70\%$ of the experimental group was 2 or less of adhesion grade at 14, 21, and 28. It was similar in the adhesion strength. In a general manner, the adhesion grade and strength showed gradual increasing until POD 14, almost same or a little increasing POD 21, but decreasing POD 28. Also the control group was much higher in adhesion grade, strength, and area than the experimental group. It is expected that the anti-adhesion membrane will have a good clinical result in postoperative adhesion prevention.

Early hypothermia improves outcomes of cardiopulmonary resuscitation after cardiac arrest in acute myocardial infarction rat models (급성심근경색 쥐 모델의 심정지 후 조기 저체온 치료가 심폐소생술 결과에 미치는 효과)

  • Park, Jeong-Hyun;Im, Hee-Kyung;Kim, Jee-Hee;Lee, Young-Il
    • The Korean Journal of Emergency Medical Services
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    • v.20 no.2
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    • pp.7-19
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    • 2016
  • Purpose: To investigate the effect of early hypothermia on post-resuscitation myocardial recovery and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction(MI). Methods: Thoracotomies were performed in 10 male Sprague Dawley rats weighing 450-455g. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. Ninety minutes after arterial ligation, ventricular fibrillation was induced, cardiopulmonary resuscitation was subsequently performed before defibrillation was attempted. Animals were randomized to control group and experimental group(acute MI-normothermia)($32^{\circ}C$ for 4 hours). Duration of survival was recorded. Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured using echocardiography. Results: Myocardial function was significantly better in hypothermia group than the control group during the first 4 hours post-resuscitation. The survival time of the experimental group was greater than that of the control group(p<.050). Conclusion: This study suggests that early hypothermia can attenuate post-resuscitation myocardial dysfunction after acute myocardial function, and may be a useful strategy in post-resuscitation care.

Effect of Celecoxib, a Cyclooxygenase-2-specific Inhibitor, has no Effect on Chronically Maintained Neuropathic Pain in Rats (장기간 유지된 신경병증성 통증 흰쥐에서 선택적 COX2 억제제인 Celecoxib의 진통효과)

  • Park, Eun-Sung;Kim, Hyun-Jeong;Lee, Min-Ju;Lee, Ji-Yoon;Shin, Teo-Jeon;Seo, Kwang-Suk;Yum, Kwang-Won
    • Journal of The Korean Dental Society of Anesthesiology
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    • v.8 no.1
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    • pp.29-34
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    • 2008
  • 배경: 신경병증성 통증은 스테로이드, 아편유사제 등의 진통제에 잘 반응하지 않는다. 하지만 염증성 매개물질들이 신경병증성 통증의 발생에 관여한다는 보고가 있다. 특히 선택적 COX2 억제제인 celecoxib의 신경병증성 통증에 대한 효과에 관해서 상반된 연구결과가 존재한다. 본 연구는 신경병증성 통증 모델인 척추신경 결찰모델을 이용 기계적, 냉각 이질통 및 온도감각 과민현상의 발현에 celecoxib이 미치는 영향을 관찰하여 celecoxib의 항통각효과를 확인하고자 하였다. 방법: 30마리의 쥐를 이용 척추신경을 결찰하여 신경병증성 통증을 유도하였다 celecoxib (1, 10, 100, and 300 mg/kg)을 경구 투여하였고 총 30마리 중 12마리의 쥐에서 열, 기계적자극에 대해서 통각과민, 냉각자극에 의해 이질통이 발생하였다. 약물 투여 후 30, 60, 120, 180분 후 von Frey, 냉각자극검사, Hargreaves검사를 시행하여 쥐의 행동변화를 관찰하였다. 결과: 신경결찰 후 5일 후에 celecoxib의 용량에 관계없이 열, 기계적 자극에 의한 통각과민, 냉각 자극에 대한 이질통을 감소시키지 않았다(P > 0.05). 또한 celecoxib투여에 의한 장기간의 항 통각효과는 관찰되지 않았다(P > 0.05). 결론: celecoxib을 경구로 투여하였을 때 장기간 유지된 신경병증성 통증 흰쥐에서 약의 투여용량, 투여기간에 따른 항 통각작용은 관찰되지 않았다. 따라서 조직 손상후 발생된 장기간의 신경병증성 통증에 있어서 celecoxib은 효과가 없는 것으로 사료된다.

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Heterotopic Heart Transplantation in the Rat Model (쥐모델에서의 이소성의 심장이식)

  • Chung, Won-Sang;Jeon, Yang-Bin;Chun, Soon-Ho;Kim, Hyuk;Lee, Chul-Burm;Kim, Young-Hak;Jee, Heng-Ok;Seo, Jung-Kuk;Kong, Gu
    • Journal of Chest Surgery
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    • v.31 no.5
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    • pp.531-535
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    • 1998
  • In 1964, Abbott and Colleagues published the world's first heterotopic heart transplantation technique in the rat. Their method established circulation by end-to-end anastomoses of the graft's aorta and pulmonary artery to the recipient's abdominal aorta and Inferior Vena Cava(IVC), respectively. In 1966, Tomita et al altered Abbott's technique by employing end-to-side rather than end-to-end anastomoses, thus eliminating the hind leg paralysis that sometimes resulted from Abbott's technique. In order to prevent postsuture hemorrhage (since 7-0 silk suture was the finest available at that time), Tomita's aortic anastomosis was done with double up-and-down continuous suture technique. A single layer continuous anstomosis effected the pulmonary artery-IVC anastomosis. The availability of Nylon monofilament suture made it possible for Ono and Lindsey to use a single layer suture technique for the aortic end-to-side anastomosis in their modified rat heart transplantation. We observed survival time between control group and Immunosuppression(Cyclosporine administration, 10mg/Kg${\times}$4 times postoperatively) group after heterotopic heart transplantation in the rat model. The cyclosporine adminstration group survived longer than the control group, thus we concluded that cyclosporine was based on Immunosuppressive drugs.

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Effect of n-3 Fatty Acid Deficiency on Fatty Acid Composition in Brain, Retina and Liver Using a Novel Artificial Rearing System (인공 사육 동물 모델 시스템을 이용한 n-3 지방산 결핍이 쥐의 뇌, 망막, 간의 지방산 조성에 미치는 영향)

  • Lim, Sun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.4
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    • pp.466-475
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    • 2005
  • Docosahexaenoic acid (22:6n-3, DHA) is highly enriched in membrane of brain and retina, and plays an important role in maintaining an optimal function of the central nervous system. We investigated the effect of n-3 fatty acid deficiency on rat brain, retina and liver fatty acyl composition at two different ages (3 wks and 15 wks) under DHA deficient condition. Rat pups born to dams fed a diet with $3.1\%$ of total fatty acids as $\alpha-linolenic$ acid (LNA) were fed using an artificial rearing system either an n-3 deficient (n-3 Def) or n-3 adequate (n-3 Adq) diet. Both diets contained $17.1\%$ linoleic acid (LA) but the n-3 Adq diet also contained $3.1\%$ LNA. Rats consuming the n-3 Def diet showed a lower brain $(50\%\;in\;13\;wks\;and\;70\%\;in\;15\;wks,\;p<0.05)$ and retinal $(50\%\;in\;13\;wks\;and\;63\%\;in\;15\;wks,\;p<0.05)$ DHA than those on the n-3 Adq diet, which was largely compensated for by an increase in docosapentaenoic acid (22:5n-6, DPAn-6). In the liver of the n-3 Def group, the percentage of DHA decreased by $97\%$ at 3 wks of age with an apparent increase in DPAn-6 relative to the n-3 Adq group (p<0.05), while there was a $65\%$ lower liver DHA in n-3 Def group at 15 wks of age than the n-3 Adq group (p<0.05). Liver arachidonic acid (20:4n-6, AA) was increased at 3 wks of age but decreased at 15 wks of age in the n-3 Def group compared with n-3 Adq group (p<0.05). In conclusion, the replacement of DHA by DPAn-6 in brain and retina fatty acid composition may be related to the suboptimal function in spatial learning, memory and visual acuity. This artificial rearing method presents a first generation model for n-3 deficiency that is similar to the case of human nutrition that commonly employed two generation model.

The Effect of Complex Exercise Program of Diabetic Rats with Ischemic Brain Injury Model (허혈성 뇌손상 모델 당뇨쥐의 복합운동프로그램의 효과)

  • Kim, Dong-Hyun;Bang, Hyun-Soo
    • The Journal of Korean society of community based occupational therapy
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    • v.6 no.1
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    • pp.41-48
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    • 2016
  • Objective : We tried to know the improvement and neurological effect of diabetes when the complex exercise training was applied on diabetes that delayed the recovery of the ischemic brain injury. Methods : We performed this study in a animal lab which located in Gyengsangbukdo. We used 10 diabetes rats with ischemic brain injury, which is induced by STZ. We applied the complex exercise training on the rats for 4 weeks. We executed the maze test to confirm the recovery of the brain function and checked the blood sugar to know the improvement. Results : As a result of applying the complex exercise on diabetes rats with ischemic brain injury, there was a significant reduce of error and escape time in 3 weeks and 1 weeks, respectively. There was no difference of the blood sugar in control but there was a significant improvement in experiment group after applying the exercise training in 4 weeks. Conclusion : The senile disease like stroke and diabetes was increased currently. It is important for rehabilitation to improve the quality of life during the remainder of their life. In the study, we've known the improvement of diabetes and the recovery of the brain function when the complex exercise training was applied the rats with both diabetes and the ischemic brain injury.

A Naive Bayesian-based Model of the Opponent's Policy for Efficient Multiagent Reinforcement Learning (효율적인 멀티 에이전트 강화 학습을 위한 나이브 베이지만 기반 상대 정책 모델)

  • Kwon, Ki-Duk
    • Journal of Internet Computing and Services
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    • v.9 no.6
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    • pp.165-177
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    • 2008
  • An important issue in Multiagent reinforcement learning is how an agent should learn its optimal policy in a dynamic environment where there exist other agents able to influence its own performance. Most previous works for Multiagent reinforcement learning tend to apply single-agent reinforcement learning techniques without any extensions or require some unrealistic assumptions even though they use explicit models of other agents. In this paper, a Naive Bayesian based policy model of the opponent agent is introduced and then the Multiagent reinforcement learning method using this model is explained. Unlike previous works, the proposed Multiagent reinforcement learning method utilizes the Naive Bayesian based policy model, not the Q function model of the opponent agent. Moreover, this learning method can improve learning efficiency by using a simpler one than other richer but time-consuming policy models such as Finite State Machines(FSM) and Markov chains. In this paper, the Cat and Mouse game is introduced as an adversarial Multiagent environment. And then effectiveness of the proposed Naive Bayesian based policy model is analyzed through experiments using this game as test-bed.

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Pattern-Mixture Model of the Cox Proportional Hazards Model with Missing Binary Covariates (결측이 있는 이산형 공변량에 대한 Cox비례위험모형의 패턴-혼합 모델)

  • Youk, Tae-Mi;Song, Ju-Won
    • The Korean Journal of Applied Statistics
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    • v.25 no.2
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    • pp.279-291
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    • 2012
  • When fitting a Cox proportional hazards model with missing covariates, it is inefficient to exclude observations with missing values in the analysis. Furthermore, if the missing-data mechanism is not Missing Completely At Random(MCAR), it may lead to biased parameter estimation. Many approaches have been suggested to handle the Cox proportional hazards model when covariates are sometimes missing, but they are based on the selection model. This paper suggest an approach to handle Cox proportional hazards model with missing covariates by using the pattern-mixture model (Little, 1993). The pattern-mixture model is expressed by the joint distribution of survival time and the missing-data mechanism. In the pattern-mixture model, many models can be considered by setting up various restrictions, and different results under various restrictions indicate the sensitivity of the model due to missing covariates. A simulation study was conducted to show the sensitivity of parameter estimation under different restrictions in a pattern-mixture model. The proposed approach was also applied to mouse leukemia data.

Effects of a Pueraria lobata-root based combination supplement containing Rehmannia glutinosa and aerobic exercise on improvement of metabolic dysfunctions in ovariectomized rats (갱년기 모델 유도 흰 쥐에서 갈근과 지황 복합물 및 유산소 운동이 대사이상 개선에 미치는 영향)

  • Oh, Sang A;Ok, Hyang Mok;Kim, Hye Jin;Lee, Won Jun;Kwon, Oran
    • Journal of Nutrition and Health
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    • v.48 no.2
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    • pp.133-139
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    • 2015
  • Purpose: There is a fair amount of evidence indicating that increased risk of obesity and insulin resistance is associated with postmenopausal state, but can be modulated by diet and exercise. In this study, we explored whether a Pueraria lobata root-based supplement containing Rehmannia glutinosa (PR) and/or aerobic treadmill exercise can modify the metabolic changes associated with estrogen deficiency. Methods: Seventy rats were randomly assigned to the following groups for 8 weeks (n=10 per group): SHAM, sham-operated; PR0, ovariectomized (OVX) control; PR200, OVX with PR200 mg/kg B.W; PR400, OVX with PR400 mg/kg B.W; EPR0, OVX with exercise; EPR200, OVX with exercise and PR200 mg/kg B.W; EPR400, OVX with exercise and PR400 mg/kg B.W. Results: OVX induced significant increases in body weight, food intake, fat mass, LDL-cholesterol, and fasting blood glucose, confirming induction of menopausal symptoms. PR supplementation or exercise significantly suppressed the above mentioned changes through different regulatory elements in adipose tissue: PR supplement upregulated adiponectin gene expression and aerobic exercise upregulated adiponectin and insulin receptor gene expression and a combination of PR supplement and aerobic exercise showed an additive effect on adiponectin gene expression. Conclusion: Taken together, the results of this study suggest that PR supplement has a potential to provide health benefits in OVX rats through leptin and adiponectin secretion. In addition, the data suggest that combination of exercise and PR would have additive effects on metabolic dysfunction associated with estrogen deficiency.