• Journal of Korean Ophthalmic Optics Society
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• v.7 no.1
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• pp.39-43
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• 2002

This study was investigated the anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus by using Chorioallantoic membrane (CAM) and rat cornea. First experiment, the fertilized chicken eggs were kept in a humidified egg incubator at $37^{\circ}C$. After 4 days incubation, about 3 ml of albumin was aspirated from eggs with an hypodermic needles through a small hole drilled at the narrow end of the eggs, and the shell membrane on the floor of the air sac was peeled away. Embryos with chorioallantois of 3~5 mm in diameter were employed for the assay of antiangiogenic activity. Retinoic acid was used as a positive control for this experiment. After 48 h of treatment. branching pattern of blood vessels below coverslip containing retinoic acid ($10{\mu}g/egg$) was dramatically decreased. A simiar angiogenic inhibition was observed in the CAM treated with $50{\mu}g/egg$ of Cnidium omcinale Makino and Tabanus bovinus extracts. Second experiment, rat corneal neovascularization was induced by suturing (one stitch) the cornea with 10-0 nylon, and terramycin was applied on the cornea for I week to prevent corneal inflammation. In the cornea of rats untreated with herbal extracts, numerous vessels were usually seen invading the cornea by day 2 or 3 after suture, and reaching the lesion area within 5~6 days. Corneal neovascularization was gradually increased and peaked at 3 weeks. In contrast to this, herbal extracts conspicuously inhibited the angiogenesis, Oral administration of herbal extracts (20 mg/kg body weight/day) for 4 weeks significantly inhibited the rat corneal angiogenesis induced by suture, and the length of blood vessels in herbal medicine-treated rat cornea was conspicuously lower than that in control animals. A similar phenomenon was also observed in the rat cornea treated with thalidomide (200 mg/kg body weight/day). These findings indicate the anti-angiogenic properties of Cnidium officinale Makino and Tabanus bovinus, suggesting that these properties may be one of the pharmacological mechanisms underlying the anti-tumor and anti-metastatic activities of herbal extracts tested in this study.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.197-203
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• 2005

Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$ $2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.7
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• pp.1095-1101
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• 2003

This study was carried out to investigate the effect of Gastrodiae Rhizoma (G. Rhizoma) on blood pressure-lowering in spontaneously hypertensive rats (SHR) fed high-fat diet supplemented with 10% (w/w) of lard during the experimental period of 8 weeks. Forty of male SHR weighing approximately 100 g were randomly divided into eight groups; A: negative control (lard 10%), B: positive control (lard 10% ＋ basal diet ＋ 5 brix water extract), C: lard 10% ＋ 1% G. Rhizoma powder, D: lard 10%＋5% G. Rhizoma powder, E: lard 10%＋2 brix 50% ethanol extract, F: lard 10%＋10 brix 50% ethanol extract, G: lard 10%＋2 brix water extract, H: lard 10% ＋ 10 brix water extract. A gain in weight did not differ significantly among dietary groups, but a little higher in control groups than in G. Rhizoma dietary groups. Except for spleen, weights of liver, kidney and testis are significantly different among dietary groups. Serum total cholesterol concentration was markedly higher in control groups than in G. Rhizoma groups (p<0.05), however, there was no significant difference in serum triglyceride. Except for negative control (A) and group D, serum HDL concentration was significantly higher in G. Rhizoma groups (p<0.05). On the other hand, serum LDL concentration was significantly higher in two control groups (A, B) and markedly lower in E and G groups of hot water extract of G. Rhizoma (p<0.05). Reference systolic blood pressure (BP) showed average 185.7$\pm$5.8 mmHg for 4 weeks after feeding high-fat diet, and the pressure was measured on every 7 days intervals after feeding of G. Rhizoma diet. Comparing with reference BP before feeding of G. Rhizoma diet, the groups of 50% ethanol (E, F) and water (G) extracts on BP level after 28 days were shown to be reduced at 16.8, 20.2 and 11.7 mmHg, respectively. When the pressure (187 mmHg) of group A was considered as 100%, the reduction rate of BP in group F was 11% (20.5 mmHg). These results indicated that the groups treated with ethanol extracts of G. Rhizoma showed to have lower blood pressure level compacred to the groups treated with whole powder or water extracts of G.Rhizoma in SHR fed with high-fat diet.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.6
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• pp.758-763
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• 1999

The protective effects of sea tangle (Laminaria japonica) extract and fucoidan components on the attack of oxygen radicals in kidney were studied, Sprague-Dawley (SD) male rats (210 $\pm$ 5 g) were with fed experimental diets of Dasi-Ex group (sea tangle extract powder of $4.0\%$ added to control diet), Euco-I, II and III groups (fucoidan powder of 1, 2 and $3\%$, respectively, added to Dasi-Ex group) for 45 days, Hydroxyl radical formations were significantly decreased ($10\~15\%$ and $15\~30\%$) in mitochondria and microsomes of Dasi-Ex and Fuco-I, II, III groups compared with control group. Hydrogen peroxide formations were also significantly decreased ($10\~15\%$) in microsomes of Dasi-Ex and Fuco-I, II, III groups compared with control group. Significant differences in mitochondrial basal oxygen radical (BOR) and microsomal induced oxygen radical (IOR) formations of Dasi-Ex and Fuco-I groups could not be obtained, but mitochondrial BOR and microsomal IOR formations were significantly decreased ($12\~15\%$ and $13\~14\%$) in Fuco-II and III groups compared with control group. BOR formations were significantly decreased ($12\~25\%$) in microsomes of Dasi-Ex and Fuco-I, II, III groups, and IOR formations were also significantly decreased ($10\~15\%$) in mitochondria of Fuco-I, II, III groups compared with control group, Significant differences in mitochondrial Mn-SOD activities of Dasi-Ex group could not be obtained, but mitochondrial Mn-SOD activities were dose-dependently increased by $8\%,\;16\%$ and $36\%$ in Fuco-I, II and III groups compared with control group, Mn-SOD activities an microsome were significantly increased about $20\%$ in Dasi-Ex group, while they were remarkably increased about $40\%$ in Fuco-I, II and III groups compared with control group. lipid peroxide contents were significantly decreased about $15\%$ and $15\~25\%$ in mitochondria and microsomes of Fuco-II and III groups. Membrane fluidities resulted in marked increases ($20\~35\%$ and $17\~24\%$) in mitochondria and microsomes of Dasi-Ex and Fuco-I, II and III groups. These results suggest that administrations of fucoidan added to sea tangle may play a pivotal role in attenuating attack of oxygen radicals in kidney.

• 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.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.51-56
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• 1996

The objectives of this study is to find out mechanism of vasodilating effects of ANP in 2K-1C renovascular hypertensive rat aorta and to compare with those of normotensive rat aorta. In 2K-1C renovascular hypertensive rat, average arterial blood pressure and plasma renin activity were higher than in normotensive rat. In 2K-1C renovascular hypertensive rat aorta, NE sensitivity was more increased and maximal contraction of aorta by NE was higher than those of normotensive rat aorta. ANP inhibited NE-induced contraction in both 2K-1C renovascular hypertensive and normotensive rat aorta, concentration-dependently. However, ANP was less effective for relaxing NE-induced contraction in 2K-1C renovascular hypertensive rat aorta than in normotensive rat aorta. ANP inhibited $^{45}Ca^{2+}$ uptake induced by NE in both 2K-1C renovascular hypertensive and normotensive rat aorta. From these results. inhibition of $Ca^{2+}$ influx may be one of the vasodilating mechanism of ANP in 2K-1C renovascular hypertensive rat aorta. Although the potency of ANP in relaxing NE-induced contractions was attenuated, the efficacy of ANP was not changed in 2K-1C renovascular hypertensive rat aorta compared with that of ANP in normotensive rat aorta. Abbreviations: ANP, Atrial natriuretic peptide; 2K-1C, 2-kidney 1 clip; NE, norepinephrine; SHR, Spontaneously hypertensive rat; DOC, Deoxycorticosterone; EDTA, Ethylenediaminetetra-acetic acid; PSS, Physiological salt solution; TRIS, tris(hydroxymethyl) aminomethane

• Journal of Veterinary Clinics
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• v.22 no.1
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• pp.16-20
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• 2005

The purpose of this study was to compare the antiangiogenic effects of As₄O/sub 6/ to those of As₂O₃ on the rat corneal micropocket model induced by VEGF. 20 ng VEGF impregnated pellets were used for angiogenic inducer on the rat cornea micropocket assay in this study. After ophthalmoscopic examination, Sprague-Dawley rats with normal cornea were implanted VEGF pellet. Total 60 eyes were used in this study. Control group only received VEGF pellet, As₂O₃ group followed oral administration of As₂O₃ at a dose of 50 mg/kg per day after VEGF pellet implantation and As₄O/sub 6/ group followed oral administration of As₄O/sub 6/ at a dose of 50 mg/kg per day after VEGF pellet implantation were classified. The eyes were examined under a surgical microscope daily on postoperative from day 3 to day 9 after pellet implantation. The number, length, clock hour of vascularization, and area of vessels in As₄O/sub 6/ group were significantly less evident than those of control group and As₂O₃ group (P < 0.05). In conclusion, As₄O/sub 6/ had better antiangiogenic effects on the new vessel induced by VEGF in the rat cornea.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.138-143
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• 2009

Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.468-475
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• 2005

Transmyocardial revascularization (TMR) in end stage ischemic heart disease results in variable clinical responses. We investigated the acute effect of early reperfusion and the angiogenesis after formation of the transmyocardial channel in a transplanted rat heart model with acute myocardial infarction. Material and Method: In the 30 transplanted hearts we induced acute myocardial infarction by ligating the proximal left coronary artery and inserted a porous 22G intravenous cannula into the left ventricle. After ten minutes of reperfusion, we removed the cannula. At every stage, we recorded the heart rate, QRS size, and left coronary arterial blood flow using the electrocardiogram and Doppler. One week later the rats were sacrificed and evaluated for the patency of intramyocardial channels and the angiogenesis. Result: The heart rates after ligation and after cannula insertion were $239.1\pm61.7,\;235.8\pm58.0bpm$ respectively, and they were statistically significantly slower than that of before ligation, $277.6\pm40.3bpm\;(p=0.017,\;p=0.007\;respectively)$. QRS sizes before ligation, after ligation, and after cannula insertion were $3.6\pm3.3mm,\;2.8\pm3.3 mm,\;and\;2.4\pm2.2mm,$respectively, and there was no significant difference in the three groups. Doppler findings after ligation showed that average peak and mean values of coronary perfusion were significantly decreased from $2.11\pm0.17kHz,\;1.25\pm0.22kHz\;to\;0.83\pm0.15kHz,\;0.38\pm0.11kHz$(p<0.05 respectively). After insertion of the porous cannula, the average peak and mean values of coronary perfusion were $0.61\pm0.05kHz\;and\;0.33\pm0.05 kHz$ respectively, but there was no statistically significant change compared to values after ligation. In all cases except one, pathologic findings showed no patent channels in the acute stage, however, one case showed the angiogenesis. Conclusion: We confirmed that TMR in a rat heart transplant model did not show blood flow through the channel in the acute stage. However, reperfusion effect in some cases had a potential for angiogenesis.