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Experimental Model of Cardiac Xenograft, Mouse Heart to Rat. (이종이형의 심장이식의 실험적 모델)

  • Kim, Byung-Il;Sohn, Sang-Tae;Shin, Sung-Ho;Chung, Won-Sang;Kim, Hyuk;Kim, Young-Hak;Kang, Jung-Ho;Jee, Heng-Ok;Lee, Chul-Burm;Seo, Jung-Kuk
    • Journal of Chest Surgery
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    • v.32 no.1
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    • pp.1-4
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    • 1999
  • Background: The transplantation of organs between phylogenetically disparate or harmonious species has invariably failed due to the occurrence of hyperacute rejection or accerelated acute rejection. But, concordant cardiac xenograft offer us an opportunity to study xenotransplantation in the absence of hyperacute rejection. Current therapeutics for the prolongation of survival of rodent concordant xenotransplantation are not ideal with many regimens having a high mortality rate. Cyclosporine A & Mycophenolate Mofetil are new immunosuppresive agent which has been shown to be effective at prolonging survival of allograft, as purine synthesis inhibitor. Material and Method: We used white mongrel rats as recipient and mice as donor, divided 4 groups(n=6), control group(Group 1) has no medication or pretreatment, Group 2 has splenectomy as pretreatment 7∼10 days before transplantation, Group 3 has Cyclosporine A treatment group, Group 4 has combined treatment of Cyclosporine A & Mycophenolate Mofetil(RS 61443). We compared survival time. Reuslt: We can't find significant difference of survival time between each groups. Conclusion: We concluded that rejection of cardiac xenograft was different from rejection of allograft, and new immunossuppresive Agent(Mycophenolate Mofetil, Cyclosporine A) was not effective for prolongation of survival time after cardiac xenograft.

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Effects of vitamin C on the formation of aflatoxin B1-DNA adduct in rat livers treated with radiation and aflatoxin B1 (Vitamin C가 방사선과 Aflatoxin B1을 처리한 흰쥐의 간세포에서 Aflatoxin B1-DNA Adduct 형성에 미치는 영향)

  • Kim, Soyoung;Kim, Hansoo;Kang, Jin-Soon
    • Food Science and Preservation
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    • v.21 no.5
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    • pp.747-756
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    • 2014
  • The objective of this study was to examine the effects of vitamin C on the formation of aflatoxin $B_1$ ($AFB_1$)-DNA adduct and $AFB_1$-induing cellular oxidative damage in rat livers treated with radiation and $AFB_1$. Six-week-old male Sprague-Dawley rats were randomly divided into five groups: the control group, the $AFB_1$-treated group, the group treated with $AFB_1$ and vitamin C, the group treated with X-ray and $AFB_1$, and the group treated with X-ray and $AFB_1$ with vitamin C. On the first day of the experiment, only one dose of X-rays was exposed to the entire liver at 1,500 cGy. Next, vitamin C was injected at 10 mg/kg body weight via intraperitoneal injection, followed an hour later by the administration of 0.4 mg/kg of $AFB_1$ via intraperitoneal injection. These treatments were administered every three days for 15 days. On the 16th day, the animals were sacrificed. The $AFB_1$ contents of the rat sera were determined via indirect competitive ELISA. In the quantitative analysis of $AFB_1$ in the rat sera via ELISA, $5.17{\pm}0.34ng/mL$ of $AFB_1$ was detected in the $AFB_1$-treated groups, but the amount decreased more significantly to $3.23{\pm}0.76ng/mL$ in the groups treated with $AFB_1$ and vitamin C (p<0.01) than in the $AFB_1$-treated groups. The effect of vitamin C on $AFB_1$-DNA adduct formation was determined via ELISA. The values of $AFB_1$-DNA adduct formation were $9.38{\pm}0.41ng/mL$ in the $AFB_1$-treated groups, but the amount decreased more significantly to $5.28{\pm}0.32ng/mL$ in the groups treated with $AFB_1$ and vitamin C (p<0.01) than in the $AFB_1$-treated groups. Immunohistochemistry revealed that the accumulation of the $AFB_1$ was not observed in the normal liver tissue (G1). The $AFB_1$-positive materials were observed in the central vein and the portal vein of the liver tissue from the $AFB_1$(G2) treatment or the X-ray and $AFB_1$(G4) co-treatment, but the $AFB_1$-positive materials were observed weakly in the group treated with vitamin C (G3 and G5). These results indicate that vitamin C had ameliorating effects on the $AFB_1$ accumulation of liver tissue.

Effect of Chitosan-Trimer on the Prevention of Postoperative Intraperitoneal Adhesion Formation in Rats (랫트에서 Chitosan-Trimer가 복강유착에 미치는 영향)

  • Kwon, Eun-ju;Jang, Kwang-ho;Jang, In-ho
    • Journal of Veterinary Clinics
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    • v.18 no.3
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    • pp.257-264
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    • 2001
  • This study was performed to investigate the effects of chitosan-trimer (CT) on the prevention of postoperative adhesion formation in the rate model. All animals divided into PBS (control), 1% CT, 3% CT, and chitin treated group. The mean adhesion score in 1% CT group (1.03$\pm$0.63), 3% CT group (0.64$\pm$0.53) and chitin group (1.67$\pm$0.71) was found to be lower than that in control group (2.07$\pm$0.81). More favorable adhesion prevention was achieved in 3% CT group (0.64$\pm$0.53) in comparison with the control group, 1% CT group, and chitin group without any hemorrhagic complications. A statistically significant difference was observed in adhesion formation between control group and 3% CT group (p<0.001). In control group, 44 of 45 sites (97.7%) formed adhesions between the intestine defects. In contrast, 3% CT was effective in reducing the incidence of adhesion formation to 17 to 45 sites (62.2%) (p<0.05). The locations of adhesions were observed in serosa-serosa (60%), serosa-mesentery (13.3%), serosa-connective tissue of testis (10%), omentum-liver (10%), serosa-omentum (3.3%), serosa-cecum (3.3%), and serosa-incision (0%). On the results of histological analysis, grade of inflammation and fibrosis at the sites of postoperative peritoneal adhesion formation were not significantly different in all groups. But, 3% CT showed the lowest score of inflammation and fibrosis. In 3% CT group, the rate of increase of plasma fibrinogen was significantly lower compared with that in control group from pre-operation to 10 days later (p<0.05). There were no appreciable difference in the CBC, leukocyte differential counts and total protein concentrations among four groups. In conclusion, our data suggested that CT should be effective on reducing adhesion formation in experimental rat models. The results also showed that 3% CT does not adversely affect normal wound healing and healthy recovery after operation.

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Acute Kidney Injury Models: Focus on the Therapeutic Effects of Stem Cell in Preclinical Approach (줄기세포 연구를 위한 급성신장손상 모델)

  • Nam, Hyun-Suk;Woo, Jae-Seok;Woo, Heung-Myong
    • Journal of Veterinary Clinics
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    • v.27 no.5
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    • pp.533-539
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    • 2010
  • Stem cell-based therapy is under intensive investigation to treat acute renal failure (ARF). The purpose of this study was to evaluate available ARF models, and suggest a model appropriate to therapeutic evaluation of the stem cells in preclinical approach by determining the optimum concentration of nephrotoxic agents and duration of ischemia induction. Three different types of available acute kidney injury (AKI) animal models were analyzed using rats: Cisplatin (saline, 5 and 7.5 mg/kg, IP) or glycerol (saline, 8 and 10 ml/kg, IM)-induced nephrotoxicity as toxic models and ischemia-induced (sham, 35 and 45 minutes) nephropathy as an ischemic model. The relevance and applicability to investigate especially the regenerative ability of stem cells were evaluated regarding morphology, renal function and survival at this time point. In the point of renal function, 10 ml glycerol/kg and 7.5 mg cisplatin/kg model in toxic models and 45 min model in ischemia models showed significant decrease for the longer observation time compared to 8 ml glycerol/kg, 5 mg cisplatin/kg and the 35 min ischemia models, respectively. All groups were observed no mortality except 45 min-ischemia model with 50% survival. Histological significant alterations including cast formation in the tubular lumen, tubular necrosis and apoptosis were revealed on the second day in either ischemiaor glycerol-induced models, and on day 5 in cisplatin-induced models. The results indicate that ischemia 35 min-, cisplatin 7.5 mg/kg- and glycerol 10 ml/kg-induced AKI would be ideal animal models to monitor a outcome parameter related to the therapeutic effects on renal function with noninvasive techniques in the same animal at multiple time points. Our findings also suggest that the best time points for the functional or histological interpretation of renal will be on day 2 in both glycerol- and ischemia-induced AKI models and on day 5 in cisplatin-induced AKI.

Effect of gender on the pharmacokinetics and metabolite formation of sulfamethazine in the rabbit (토끼의 성차가 sulfamethazine의 약동학 및 대사산물 생성에 미치는 영향)

  • Yun, Hyo-in;Park, Il-hyun
    • Korean Journal of Veterinary Research
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    • v.32 no.1
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    • pp.35-39
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    • 1992
  • SMZ is one of the most widely used antibacterial agents in veterinary medicine. It is also used as a growth promotant in many species of domestic animals There are marked species differences in its metabolism and pharmacokinetics. However, its pharmacokinetic and metabolism in rabbits. which are ragarded not only as good laboratorty animals hut also as good economical animals in its own, are lacking. Sex-differences in drug metabolism are well recognized in wide range of animal species including rats. Males are known to he more active than females. It is also know that there are Significant differences in the direction of metabolic pathways. But recently, female goats are reported to be more active in the metabolie capacity of SMZ than the other sex by Dutch researchers at Utrecht. Therefore, it is not easy to make general conclusicn of having higher SMZ metal-die capacity in the male compared to the opposite sex in every animal species. In this regard, the study on metabolic pattern of SMZ in rabbits, which are regarded as hervivorous, is of interest because the dietary habbits of rabbit are comparable to thai of goal, NEW Zealand White rabbits of each sex were given SMZ(35mg/kg) as a bolus injection into the marginalean, vein in order to study its pharmacokinetic profiles(using plasma) anc metabolic pattem(24h urine) as specified in the methods anc materials. 1. In the rabbit, the major metabolic pathway of SMZ was the acetylation(the formation of $N_4AcSMZ$). There were hydroxylation pathways(50HSMZ, $6CH_2OHSMZ$) as well, in the metabolism of SMZ in the rabbit, but minor pathways. 2. No sex differences in the metabolic direction of SMZ and its metabolites formation were found from the urinary excreted metabolites of SMZ out of 24h collected urine. 3. The concentration-time curves of SMZ(35mg/kg, iv) in the plasma compartment were fitted to a one-compartment open model when using a computer program(NONLIN). There was also no difference in the pharmacokinetic pattem of SMZ between two sexes. 4. The emergence of $N_4AcSMZ$ metabolized from SMZ was very fast in the plasma of the rabbit The elimination of $N_4AcSMZ$ was prolonged as compared to that of the parent drug Vie found no sex difference in the elimination pattern of $N_4AcSMZ$ in the rabbit.

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Antioxidant Effect of Mul-kimchi on Hepatic Tissue of Rats Fed with High Cholesterol Diet (키토산-아스코베이트 첨가 물김치의 고콜레스테롤 식이 흰쥐 간 조직에 대한 항산화효과)

  • Beik, Kyung-Yeun;Kim, Mee-Jung;Kim, So-Ja;Yang, Jae-Ho;Kim, Soon-Dong
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.3
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    • pp.178-185
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    • 2006
  • This study was to investigate the effect of 0.1% chitosan-ascorbate (CA) prepared with different molecular weight (223, 746, 1,110 and 2,025 kDa) of chitosan on the changes in antioxidant activity of mul-kimchi during storage at $10^{\circ}C$ for 20 days. Animal experiments were divided to 5 groups; normal control group (NC), high cholesterol diet group (HC), high cholesterol diet mul-kimchi diet group (HCKC), high cholesterol diet and CA2025 containing mul-kimchi administrated group (HCCA), and high cholesterol diet and 1/2 concentrated CA containing mul-kimchi administrated group (HC2CA). Mul-kimchi juice was administered 0.5 mL per 100 g body weight once a day and fed for 5 weeks. Electron donating activity of the 20 days-stored mul-kimchi with 0.1% CA showed higher activity (84.74~89.13%) than those of control and ascorbic acid mul-kimchi (35.04 and 75.04%). Superoxide dismutase activities of the kimchijuice with CA were higher in the higher molecular of chitosan. In the animal experiments, the average body weight of the HCCA and HC2CA group were lower 6.9% and 8.4% than that of HC control group, respectively. Hepatic glutathione content in HCCA and HC2CA group was increased 22.5% and 9.1% as compared to HC group. Hepatic glutathione S-transferase activities were significantly increased in the HCCA (219.9%) and HC2CA group (153.8%) compared to NC group. Hepatic superoxide dismutase activity was highest in the HCCA group, and the activities in CA groups were higher than those of NC and HC group.

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The Toxicological Pathologic Study of Amanita muscaria in Sprague-Dawley Rat (Amanita muscaria 경구투여 시 Sprague-Dawley Rat에서의 독성병리 연구)

  • Kim, Jin;Kim, Hyeong-Jin;Kim, So-Jung;Kim, Byeong-Soo;Kim, Sang-Ki;Park, Byung-Kwon;Park, Young-Seok;Cho, Sung-Dae;Jung, Ji-Won;Nam, Jeong-Seok;Choi, Chang-Sun;Lee, Seung-Ho;Jung, Ji-Youn
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1152-1158
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    • 2009
  • For the toxicological pathologic study of amanita muscaria, we have investigated single and repeated dose toxicity in Sprague-Dawley (SD) rats. Single dose toxicity study was identified as catalepsy, incline and tail pinch methods (control 0 mg/kg, low 3.3 mg/kg, middle 16.5 mg/kg, high 33.0 mg/kg). Repeated dose toxicity study was carried out in blood tests, serum tests and histopathological methods. Neurotoxicity - muscle paralysis, and convulsion and loss of movement - was observed at 33.0 mg/kg group in the single dose toxicity study. Dysfunction of liver and kidney were shown in the repeated oral administration of the amanita muscaria at 3${\sim}$4 weeks. Serum chemistry results revealed a marked increase of LDH [Lactate Dehydrogenase (3181.5 IU/L; normal 230-460 IU/l)], ALT [Alanine transaminase (124.0 IU/l; normal <40 IU/l)] but the kidney was normal. Histopathological results show interstitial edema and tubular epithelial necrosis in the kidney. These results suggest that amanita muscaria has a neurotoxic effect and causes dysfunction of liver and kidney in the SD rat.

Effects of Fermented Dandelion (Taraxacum coreanum) Extract on Male Climacteric Syndrome (흰민들레 발효추출물의 남성 갱년기 개선에 대한 효과)

  • Lee, Hak Su;Baek, Yeon Su;Kim, Ye Seul;Kim, Hyun Pyo
    • Journal of Life Science
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    • v.26 no.9
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    • pp.1063-1073
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    • 2016
  • Male climacteric syndrome, andropause, or testosterone deficiency syndrome (TDS) is one of the new health issues in elderly men. It is a natural phenomenon that happens with age in men, which is clinically characterized by a decline in levels of serum testosterone resulting in a significantly decreasing of physical and mental activities. The aim of this study was to investigate the putative alleviative effects of dandelion extract on the symptoms of TDS by increasing serum testosterone levels and compare the efficacy between dandelion extract (DE) and fermented dandelion extract (FDE). After daily intake of DE and FDE for 4 weeks, serum testosterone levels, muscles of vastus lateralis, forced swimming time, total sperm counts, and motile sperm counts were significantly increased in older rats (22 weeks). Additionally, SHBG, epididymal fat pad, total serum cholesterol and triglyceride were significantly decreased in DE and FDE fed groups. However, PSA levels were not different among all groups. Furthermore, DE and FDE enhanced the expression of genes related to testosterone biosynthesis in TM3 Leydig cells. Overall, these positive effects on andropause were greater in FDE compared to DE. These results suggest the potential of FDE as a safe and efficacious natural material for recovering testosterone levels and reducing andropause symptoms.

The Influence of 5-Fluorouracil Administration Mode on the Expression of Phospholipase C and Ras Oncoprotein Associated with Regeneration of Rat Intestinal Mucosa Following Radiation (방사선 조사후 백서 공장 점막의 재생과정에서 5-fluorouracil 투여가 phospholipsse C 와 ras 암유전자단백의 발현에 미치는 영향)

  • Park Kyung Ran;Lee Chung Sik;Kim Sung Sook;Lee Young Han;Ryu Sung Ho;Suh Pann-Ghill
    • Radiation Oncology Journal
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    • v.12 no.3
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    • pp.271-284
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    • 1994
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in transmembrane signal transduction. PLC-${\gamma}1$ acts as the intracellular effector in signal transduction for cellular proliferation and differentiation. Ras oncoprotein is also involved in cell growth. We determined the biological significance of PLC and ras oncoprotein in regeneration following radiation and the effect of different modes of administration of 5-FU. Materials and Methods : To determine the effect of the administration mode of 5-FU on the regeneration of intestinal mucosa of rats following radiation, we compared the expression of PLC and ras oncoprotein in six groups. Group I had no treatment. Group II received radiation(8 Gy) only. Group III received radiation(8 Gy) and 5-FU(150mg/kg) continuous intravenous (iv) infusion for 12 hours. Group IV received radiation(8 Gy) and 5-FU(750mg/kg) iv bolus injection. Group V received only 5-FU(150mg/kg) continuous iv infusion for 12 hours, Group VI received only 5-FU (150mg/kg) iv bolus injection. Through immunoblotting and immunohistochemistry, we examined the expression of PLC and ras oncoprotein in rat jejunum at 96 hours after radiation or 5-FU administration and at 120 hours after radiation and 5-FU adminstration. We also investigated the histological findings using hematoxylin and eosin stain. Results : In the immunohistochemistry study, PLC-${\gamma}1$ expression was the highest in group III followed by groups II and VI in that order and was weakly positive in groups V and VI. PLC-${\gamma}1$ was hardly detected in the control group. The expression of ras oncoprotein was the same as the PLC-${\gamma}1$ expression for all groups. These results were confirmed by the histological findings regarding the mucosal regeneration. In the immunoblotting analysis, PLC-${\gamma}1$ expression was the highest in group III followed by group IV and II in that order. This difference between the immunoblotting and immunohistochemistry study was due to the high expression of PLC-${\gamma}1$ on the damaged surface epithelium rather than to its expression in the regeneration region as observed in the immunohistochemistry study for group IV. The expression of PLC-${\delta}1$ was positive only in group V and VI, which received both radiation and 5-FU, and the expression of PLC-${\beta}1$ was negligible for all groups. Conclusion : These results suggest that PLC-${\gamma}1$ mediated signal transduetion and ras oncoprotein may have a significant role in mucosal regeneration after radiation, and that continuous iv infusion of 5-FU may induce active regeneration in intestinal mucosa following radiation. In addition, the expression of PLC-${\delta}1$ in combined group of radiation and 5-FU implies that PLC-${\delta}1$ may be involved in signal transduction mediated by concerted action between radiation and 5-FU.

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Effect of Achyranthis Radix and Drynariae Rhizoma Extracts on Antioxidant Activity and Antioxidant Enzymes (우슬과 골쇄보의 추출물이 항산화 활성 및 항산화 효소 대사에 미치는 효과)

  • Kang, Mi Young;Lee, Soo Hyun;Lee, Sang Won;Cha, Sun Woo;Song, Jae Lim;Lee, Sang Chul
    • Korean Journal of Plant Resources
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    • v.28 no.5
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    • pp.600-607
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    • 2015
  • In vitro and in vivo experiments using Achyranthis radix and Drynariae rhizoma extracts were conducted. Antioxidant properties were analyzed and the effects on bone, glucose and lipid metabolism were investigated. Drynariae rhizoma (64.67%) obtained higher DPPH radical scavenging activity compared to Achyranthis radix (19.03%). Similar results were obtained in the reducing power. No differences were observed on the ABTS radical scavenging ability and SOD. In contrast, Achyranthis radix (77.60%) has higher chelating ability compared to Drynariae rhizoma (46.21%). In vivo experiments revealed higher plasma TBARS in OVX-DR than in OVX-AR. Opposite result was seen in erythrocyte TBARS. Hepatic, nephritic and erythrocyte enzymes were considered for the antioxidant enzyme activities. GSH-Px and PON of hepatic enzymes were higher in OVX-AR. While the CAT and GR were higher in OVX-DR. SOD, GSH-Px, GR and PON of nephritic enzymes of OVX-DR were higher compared to OVX-AR. Almost similar values were obtained in CAT using both extracts. The OVX treated rats obtained higher CAT and GR in the erythrocyte enzymes compared to SHAM. The SOD of erythrocyte enzymes in OVX-DR was higher compared to OVX-AR. On the other hand, the GSH-Px was higher in OVX-AR.