• Title/Summary/Keyword: ANIMAL MODEL

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Establishment of a Radiation-Induced Fibrosis Model in BALB/c Mice (BALB/c 마우스를 이용한 방사선섬유증 모델 확립)

  • Ryu, Seung-Hee;Lee, Sang-Wook;Moon, Soo-Young;Oh, Jeong-Yoon;Yang, Youn-Joo;Park, Jin-Hong
    • Radiation Oncology Journal
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    • v.28 no.1
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    • pp.32-38
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    • 2010
  • Purpose: Although radiation-induced fibrosis is one of the common sequelae occurring after irradiation of skin and soft tissues, the treatment methods are not well standardized. This study aimed to establish the skin fibrosis mouse model by fractionated radiation for the further mechanism studies or testing the efficacy of therapeutic candidates. Materials and Methods: The right hind limbs of BALB/c mice received two fractions of 20 Gy using a therapeutic linear accelerator. Early skin damages were scored and tissue fibrosis was assessed by the measurement of a leg extension. Morphological changes were assessed by H&E staining and by Masson's Trichrome staining. TGF-${\beta}1$ expression from soft tissues was also detected by immunohistochemistry and PCR. Results: Two fractions of 20 Gy irradiation were demonstrated as being enough to induce early skin damage effects such as erythema, mild skin dryness, dry and wet desquamation within several weeks of radiation. After 13 weeks of irradiation, the average radiation-induced leg contraction was $11.1{\pm}6.2mm$. Morphologic changes in irradiated skin biopsies exhibited disorganized collagen and extracellular matrix fibers, as well as the accumulation of myofibroblasts compared to the non-irradiated skin. Moreover, TGF-${\beta}1$ expression in tissue was increased by radiation. Conclusion: These results show that two fractions of 20 Gy irradiation can induce skin fibrosis in BALB/c mice accompanied by other common characteristics of skin damages. This animal model can be a useful tool for studying skin fibrosis induced by radiation.

Beneficial Effects of Acanthopanax senticosus Extract in Type II Diabetes Animal Model via Down-Regulation of Advanced Glycated Hemoglobin and Glycosylation End Products (제2형 당뇨 동물모델에서 가시오가피 추출물의 당화혈색소 및 최종당화산물 억제를 통한 혈당조절 효과)

  • Kwon, Han Ol;Lee, Minhee;Kim, Yong Jae;Kim, Eun;Kim, Ok-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.929-937
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    • 2016
  • The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

The Usefulness and Safety of Natural Stent in a Canine Model of Tracheal Stenosis (Nd-YAG laser를 이용한 기관협착 동물모델에서 Natural 스텐트의 안전성 및 유효성 -Dumon 스텐트와의 비교 실험-)

  • Kim, Ho-Joong;Koh, Won-Jung;Suh, Gee-Young;Chung, Man-Pyo;Kim, Jhin-Gook;Suh, Soo-Won;Kwon, O-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.4
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    • pp.431-438
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    • 2002
  • Background : In order to investigate the usefulness and safety of Natural Stent, we performed this study in a canine model of tracheal stenosis induced using Nd-YAG laser. Materials and Methods : After tracheal stenosis was induced in 12 Mongrel dogs using Nd-YAG laser, either Dumon (n=6) or Natural (n=6) stent was inserted into the trachea. To assess the degree of stent migration and mucostasis, bronchoscopy was performed every week for 4 weeks, after which all stents were removed. One week after stent removal, tracheal stenosis was evaluated by bronchoscopy. Results : The degree of stent migration was not different between the dogs with Dumon stent ($3.0{\pm}0.8$) and those with Natural ($2.0{\pm}1.0$), nor was the degree of mucostasis, at Dumon ($1.7{\pm}0.5$) and Natural Stent ($1.5{\pm}0.6$), respectively. One week after stent removal, the degree of tracheal stenosis was not different between the Dumon ($1.5{\pm}0.5$) and the Natural group ($1.0{\pm}0.4$). In addition, there was no death and the degree of tracheal stenosis remained always within the safe limit (less than 2.0) in all animals. Conclusion : In a canine model of tracheal stenosis induced using Nd-YAG laser, the usefulness and safety of Natural Stent were similar to those of Dumon Stent. A clinical trial is necessary to document the usefulness and safety of Natural Stent in patients with tracheal stenosis.

The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury (주산기 저산소성 허혈성 뇌손상에서 항세포자멸사를 통한 mycophenolic acid의 신경보호 효과)

  • Kim, Ji Young;Yang, Seung Ho;Cha, Sun Hwa;Kim, Ji Yeun;Jang, Young Chae;Park, Kwan Kyu;Kim, Jin Kyung;Chung, Hai Lee;Seo, Eok Su;Kim, Woo Taek
    • Clinical and Experimental Pediatrics
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    • v.50 no.7
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    • pp.686-693
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    • 2007
  • Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

Attenuation of Renal Ischemia-Reperfusion (I/R) Injury by Ascorbic Acid in the Canine Nephrotomy (개의 신장에 있어서 Ascorbic Acid에 의한 허혈/재관류 손상의 감소에 관한 연구)

  • Kim, Jong-Man;Lee, Jae-Yeon;Jeong, Seong-Mok;Park, Chang-Sik;Kim, Myung-Cheol
    • Journal of Veterinary Clinics
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    • v.27 no.5
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    • pp.553-558
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    • 2010
  • The purpose of this study was to investigate the effects of premedicated ascorbic acid and hepa-saline irrigation/aspiration on attenuation of ischemia-reperfusion (I/R) injury and recovery of renal function in canine nephrotomy model. In the canine model, nine mixed dogs were subjected to renal nephrotomy with premedicated ascorbic acid and hepa-saline irrigation-aspiration (treatment group 2), and only hepa-saline irrigation-aspiration (treatment group 1). The level of renal function and antioxidant enzymes after nephrotomy were measured. And the expression pattern of TNF-${\alpha}$ and INF-${\gamma}$ was examined in the renal tissue at $7^{th}$ day after nephrotomy. BUN and creatinine levels significantly decreased in the treatment group 1 and 2 compared to that of control group at the $3^{rd}$, 5th and $7^{th}$ day after reperfusion (p < 0.05). And, there was significant difference between treatment group 1 and 2 at the $3^{rd}$ day after reperfusion (p < 0.05). The activities of antioxidant enzymes in plasma was significantly increased in the treatment group 1 and 2 compared to that of control group at the $3^{rd}$, $5^{th}$ and $7^{th}$ day after reperfusion (p < 0.05). And, there was significant difference between treatment group 1 and 2 at the $3^{rd}$ day after reperfusion (p < 0.05). TNF-${\alpha}$ was decreased and INF-${\gamma}$ was increased in treatment groups. The result of this study suggested that irrigation-aspiration has effects on attenuation of renal ischemia-reperfusion injury, and the exogenous ascorbic acid has a role in the attenuation of renal ischemia-reperfusion injury and recovery of renal function in canine nephrotomy model.

The Correlations of Parameters Using Contrast Enhanced Ultrasonography in the Evaluation of Prostate Cancer Angiogenesis (전립선암쥐모형의 신생혈관생성의 평가를 위해 시행된 역동적 조영 증강 초음파에서 얻은 변수간의 상관성연구)

  • Hwang, Sung Il;Lee, Hak Jong;Kim, Kil Joong;Chung, Jin-haeng;Jung, Hyun Sook;Jeon, Jong June
    • Ultrasonography
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    • v.32 no.2
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    • pp.132-142
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    • 2013
  • Purpose: The purpose of this study is to investigate the correlations of various kinetic parameters derived from the time intensity curve in a xenograft mouse model injected with a prostate cancer model (PC-3 and LNCaP) using an ultrasound contrast agent with histopathologic parameters. Materials and Methods: Twenty nude mice were injected with human prostate cancer cells (15 PC-3 and five LNCaP) on their hind limbs. A bolus of $500{\mu}L$ ($1{\times}10^8$ microbubbles) of second-generation US contrast agent (SonoVue) was injected into the retroorbital vein. The region of interest was drawn over the entire tumor. The time intensity curve was acquired and then fitted to a gamma variate function. The maximal intensity (A), time to peak (Tp), maximal wash-in rate (washin), washout rate (washout), area under the curve up to 50 sec ($AUC_{50}$), area under the ascending slope ($AUC_{in}$), and area under the descending slope ($AUC_{out}$) were derived from the parameters of the gamma variate fit. Immunohistochemical staining for VEGF and CD31 was performed. Tumor volume, the area percentage of VEGF stained in a field, and the count of CD31 (microvessel density, MVD) positive vessels showed correlation with the parameters from the time intensity curve. Results: No significant differences were observed between the kinetic and histopathological parameters from each group. MVD showed positive correlation with A (r=0.625, p=0.003), washin (r=0.462, p=0.040), $AUC_{50}$ (r=0.604, p=0.005), and $AUC_{out}$ (r=0.587, p=0.007). Positive correlations were also observed between tumor volume and $AUC_{50}$ (r=0.481, p=0.032), washin (r=0.662, p=0.001), and $AUC_{out}$ (r=0.547, p=0.012). Washout showed negative correlations with MVD (r=-0.454, p=0.044) and tumor volume (r=-0.464, p=0.039). The area percentage of VEGF did not show any correlation with calculated data from the curve. Conclusion: MVD showed correlations with several of the kinetic parameters. CEUS has the potential for prediction of tumor vascularity in a prostate cancer animal model.

Relationship between Bone Morphological Microstructure and Inflammatory Markers in Growing Mice Fed a High Fat Diet (고지방식이 공급에 따른 성장기 마우스의 골의 형태학적 미세구조와 염증지표 변화)

  • Kim, Mi-Sung;Lee, Hyun-A;Kim, Ok-Jin;Sohn, Cheong-Min
    • Journal of Nutrition and Health
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    • v.44 no.6
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    • pp.481-487
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    • 2011
  • Obesity not only reduces bone mineral density but also increases inflammatory markers. Therefore, we examined the change in inflammatory markers and morphological microstructure of the bones using a mouse model fed a high-fat diet. C57BL/6J 4-week-old male mice were divided into a control group (n = 6) and a experimental group (n = 6); the control group was provided with 10% Kcal fat diet, and the high-fat diet group was provided with 45% Kcal fat diet for 12 weeks using the free provision method. Blood was analyzed for inflammatory markers, and micro-computed tomography was used to measure the morphological microstructure of the femoral bone. The weight increases in the control group and high-fat diet group were $5.85{\pm}1.84g$ and $16.06{\pm}5.64g$, respectively (p < 0.01), glucose was $115.00{\pm}16.88mg/dL$ and $188.33{\pm}13.29mg/dL$ (p < 0.01), and triglycerides were $65.00{\pm}6.19mg/dL$ and $103.33{\pm}8.02mg/dL$ (p < 0.05) respectively. Leptin and interleukin (IL)-6 were significantly higher in the high-fat diet group than that in the control group (p < 0.01). As a result of a biochemical index analysis of bone metabolism, osteocalcin tended to be lower in the high-fat diet group, whereas CTx was significantly higher in the high-fat diet group compared to that in the control group (p < 0.01). The thickness of the bony trabecula was significantly narrower in the high-fat diet group than that in the control group (p < 0.05), and the gap in the bony trabecula was significantly wider in the high-fat diet group than that in the control group (p < 0.05). IL-6 and the gap in the bone trabecula, which was a morphological microstructure of the bones, showed a positive correlation (p < 0.05). Taken together, inducing obesity through a high-fat diet in mice during the growth phase caused a change in bone microstructure and was correlated with the inflammation index. Accordingly, restriction of excessive fat intake may be needed to suppress the inflammatory reactions and promote normal bone formation.

Development of Anti-Aging Products (Anti-Wrinkle) like Epidermal Growth Factor(EGF) Materials using Supercritical Heat-Treated Extract Radish (초임계 열처리된 무 성분을 이용한 상피세포성장인자(EGF) 유사소재 개발 및 광노화(주름개선) 효과)

  • Kim, Hyun Kyoung
    • The Journal of the Convergence on Culture Technology
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    • v.4 no.3
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    • pp.197-207
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    • 2018
  • The radish skin and radish greens (mucheong) are an edible part of the radish. But they are removed before eating the radish and used as a byproduct or an animal feed material because of their tough and rough texture. This study was conducted to investigate the effect of supercritical heat-treated radish-extract on UV-induced Hos: HRM-2 wrinkled mouse animal model on anti-aging wrinkles. Supercritical heat-treated radish-extract was applied on the back of seven-weeks old HRM-2 mice. The effect of HRE on skin thickness, elasticity and wrinkle formation of the mice was observed by using UVB lamp to induce melanogenesis and wrinkle formation. As the result, increased depth of wrinkles was observed in the negative control group in comparison to the normal group. In contrast, decreased depth of wrinkles was observed in the radish-extract-free group compared to the negative control group. In the study of the effect of radish-extract on wrinkle-formation related gene expression and protein what protein expression, MMP-2 and MMP-2 gene expression significantly increased in the negative control group compared to the normal group. The gene expression reduced independence to the mass of radish-extract treated. Similar to quantitative results of mRNA expression, the expression of MMP-2 protein increased as a result of UVB-irradiation. The MMP-2 expression was inhibited in dependence to the mass of radish-extract treated. In conclusion, the supercritical heat-treated radish-extract has an effect on improving skin wrinkles not only when it is applied to the skin but also when orally ingested. Thus, it can be effectively used as a composition to health functional products. Thereafter, we can also conclude that radish, a food that does not show any side-effects even upon long-term intake, can reduce wrinkle formation as well as improve skin elasticity when taken regularly for a long period.

Effect of Buan Mulberry on Metabolic Improvement in Streptozotocin-Induced Diabetic Rats (Streptozotocin으로 유발된 당뇨쥐의 신진대사 증진에 대한 부안 오디의 효과)

  • Lee, Ju-Taek;Ryu, Jae-Sung;Kwak, Dong-Hoon;Park, Yun-Jum;Kang, Seong-Sun;Kim, Pyoung-Jun;Hwang, Kyung-A;Choo, Young-Kug
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1750-1757
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    • 2010
  • This study was designed to evaluate the anti-diabetic effects of Buan mulberries by using an insulin-dependent diabetes mellitus animal model. Several studies have shown that mulberries have metabolism-improving, antioxidant, and lipid-lowering properties in rats with streptozotocin (STZ)-induced diabetes. In this study, Sprague-Dawley male rats were randomly assigned to 1 normal control group and 5 STZ-induced diabetes groups: rats that had STZ-induced diabetes and did not receive any agents (diabetic group; negative control), rats that had STZ-induced diabetes and received insulin (insulin group; positive control), rats that had STZ-induced diabetes and received 0.5% mulberry extract (0.5% mulberry group), rats that had STZ-induced diabetes and received 1.0% mulberry extract (1.0% mulberry group), and rats that had STZ-induced diabetes and received 2.0% mulberry extract (2.0% mulberry group). Mulberry extracts were administered to the diabetic animals for 4 weeks. The rats that received mulberry extracts showed lower body weights and insulin levels, as well as higher kidney weights, blood glucose levels, urine quantities, and water intake in comparison with the normal controls. Further, the insulin concentrations in the mulberry-fed animals were higher than those in the diabetic group, and the kidney weights, blood glucose levels, urine quantities, and water intake in the mulberry-fed animals were lower than the corresponding values in the diabetic controls. These results suggest that mulberry may be an effective functional food to prevent diabetes-related complications.

Study on the Optimum Range of Weight-Age Data for Estimation of Growth Curve Parameters of Hanwoo (한우의 체중 성장곡선 모수 추정을 위한 체중 측정 자료의 최적 범위에 관한 연구)

  • Cho, Y.M.;Yoon, H.B.;Park, B.H.;Ahn, B.S.;Jeon, B.S.;Park, Y.I.
    • Journal of Animal Science and Technology
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    • v.44 no.2
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    • pp.165-170
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    • 2002
  • Mature weight (A) and rate of maturing (k) estimated by nonlinear regression were studied to determine the optimum age range over which the estimate of growth curve parameters can be estimated. The weight-age data from 1,133 Hanwoo bulls at Hanwoo Improvement Center of N.A.C.F. were used to fit the growth curve using Gompertz model. All available weight data from birth to the specific age of months were used for the estimation of parameters: the six specific ages used were 12, 14, 16, 18, 20 22 and 24 months of age. The mean estimates of mature weight (A) were 966.5, 1,255.9, 1,126.2, 916.5, 842.2, 780.9 and 767.0kg for ages 12 through 24 months, respectively. The mean estimates of mature weight (A) to 22 and 24 months of age were not different from each other. However, they were different from the estimates based on the data to other ages. Mean estimates of rate of maturing (k) were 3.362, 3.595, 3.536, 3.421, 3.403, 3.409 and 3.411 for ages 12 through 24 months, respectively. The mean estimates of maturing rate (k) for ages 18 through 24 months of age were not significantly different from each other. However, they were different from the estimates based on the data to other ages. Correlations among estimates of A at various ages showed the highest value of 0.93 between 22 and 24 months. Correlations among estimates of k at various ages were highest ranging from 0.91 to 0.99 among 18 to 24 months. The correlations between A and k were positive and tended to decrease with the increase of the age from 0.84 for the age of 12 months to 0.10 for the age of 24 months. Thus, the estimates of growth curve parameters, A and k, suitable for genetic studies can be derived from accumulated Hanwoo bulls after 22 months of age.