• Childhood Kidney Diseases
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• v.6 no.1
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• pp.85-91
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• 2002

Purpose: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-${\beta}1$. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-${\beta}1$. Materials and Methods : Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-${\beta}1$ in renal tissue- conditioned media was measured by ELISA. Results : Masson- trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson- trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-${\beta}1$ concentration among the groups. Conclusion: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-${\beta}1$ expression. (J Korean Soc Pediatr Nephrol 2002 ;6 : 85-91)

• Journal of Oriental Neuropsychiatry
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• v.28 no.1
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• pp.25-38
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• 2017

Objectives: The study aims were to evaluate the Anti-stress and Sleep-inductive effects of Yunjogyosim-tang (YJGS) in rats induced by Chronic Mild Stress (CMS). Methods: 25 healthy Rats were randomly divided into 5 groups; Normal, CMS (Control), YJGS 50, YJGS 100, and YJGS 200. All rats except the normal group were exposed to random stress conditions like water deprivation, empty bottles, forced runs on the treadmill, etc. according to the timetable of CSM for 3 weeks. After a week starting the experiment, Rats in YJGS 50, YJGS 100, and YJGS 200 groups were fed orally once a day for 2 weeks. Blood samples were taken afterward from each rat for analysis of Complete blood count, AST, ALT, and glucose levels. Corticosterone, serotonin, and melatonin were measured by ELISA kit. BDNF and $TNF-{\alpha}$ were measured by RT-PCT. Results: 1. Corticosterone levels were lower in YJGS 50, and YJGS 200 groups compared to the control group. 2. Serotonin levels were lower in the YJGS 100 and YJGS 200 groups compared to the control group. 3. Melatonin levels were higher in the YJGS 50 group compared to the control group. 4. Activity levels were higher in the BDNF, and YJGS 50 groups compared to the control group. 5. In the Activity of $TNF-{\alpha}$, YJGS 50 group showed a significant decrease compared to the control group. 6. In the Glucose content, YJGS 50, YJGS 100, and YJGS 200 groups showed a significant decrease compared to the control group. 7. When analyzing leukocytes, monocytes were found to be increased in YJGS 100 and YJGS 200 groups compared to the control group. 8. When analyzing red blood cells, more changes occurred to erythrocytes and thrombocytes in the YJGS 50 and YJGS 200 groups than in the control group. Hemoglobin was significantly increased in the YJGS 100 group and platelet levels were significantly increased in all experimental groups compared with the control group. Conclusions: These results suggest that Yunjogyosim-tang has anti-stress and sleep-inductive effects on rats induced by CMS.

• Journal of Society of Preventive Korean Medicine
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• v.3 no.2
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• pp.151-170
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• 1999

This study was to investigate the metal accumulation from SipJeonDaeBo-Decoction to rat blood of Sprague Dawley. 1. There were no significance in body weight, water dose feed ingestion quantity, liver, kidney, brain, bone weights between the control and the experimental groups. Under the experiment with drinking waters was no metal ${\sim}\;0.65mg/L$ detected. Metal level within feed found 0.0001-376.983mg/kg. 2. In the pack of SipJeonDaeBo-decoction, there detected no metal ${\sim}2.086mg/L$ 3. After P.O(per os) SipJeonDaeBo-decoction, As is detected $2.390{\pm}0.812mg/kg$ in blood; Cd $0.001{\pm}0.001mg/kg$, Co $0.003{\pm}0.001mg/kg$, Cr $0.432{\pm}0.234mg/kg$, Cu $1.013{\pm}0.373mg/kg$, Fe $426.293{\pm}114.842mg/kg$, no Hg, Mn $0.109{\pm}0.082mg/kg$, Ni $0.122{\pm}0.068mg/kg$, Zn $3.584{\pm}1.270mg/kg$. 4. The concentration of Hazardous heavy metal (As, Cd, Co, Cr, Hg, Ni, Pb) within blood control group is searched $0.488{\pm}0.138\;mg/l$; experiment I group $0.432{\pm}0.080mg/l$, experiment II group $0.588{\pm}0.213mg/l$. In the concentration of non hazardous heavy metal(Cu, Fe, Mn, Zn) control group $101.409{\pm}6.832mg/l$; experiment I group $96.062{\pm}5.732\;mg/l$, experiment II group $125.139{\pm}044.820mg/l$. 5. Correlation among every metal in blood Zn and Cr was 0.87956 ; Cd and As -0.02316, Pb and As -0.08738, Ni and As 0.07824, Mn and As 0.07824, Mn and Cd 0.04999. Briefly under the injection of SipJeonDaeBo-decoction, this study was defined within safety in blood level by P.O. during 10 days.

• Applied Biological Chemistry
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• v.48 no.4
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• pp.358-363
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• 2005

Effects on the feeds of streptozotocin-induced diabetic rats with a giant embryonic rice on lipid peroxides level and antioxidative enzyme activites in plasma and liver tissues were investigated. Along with the experimental periods, all animals in diabetic groups had a lower increase rate in body weight than the normal control group. A giant embryonic rice-fed group showed a inhibition in the decrease of body weight, and a increase in feed intake compared to the normal control group. The organ weights of the diabetic control group were heavier than those of the normal control while rice-fed groups including the giant embryonic rice-fed group were found to have lower organ weights, and its blood sugar level was found to be lower than those of the normal group. Lipid peroxides of the giant embryonic rice-fed animals showed a lower lipid peroxidation values compared to that of the diabetic control group. Plasma vitamin A and E concentrations of the diabetic control group were significantly decreased compared to the normal control while those of the giant embryonic rice-fed group were found to be significantly higher than those of the diabetic control. Of the hepatic antioxidative enzymes, SOD activity of the giant embryonic rice-fed group was higher than that of the diabetic control group. Taken these together, low lipid peroxidation values and, in contrast, high antioxidative enzyme activities were thought to be a cause for decreasing hepatic oxidative damages.

• Applied Microscopy
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• v.23 no.1
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• pp.139-163
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• 1993

Background: It has been well established and is now no longer a controversial issue that ischemia produces a series of inflammatory reactions and the ischemic myocardium cannot survive without adequate restoration of coronary flow, ie, reperfusion. Nevertheless, controversies that intravascular pluggings (IVP) by polymorphonuclear leukocytes (PMNs) or platelets may cause contractile dysfunction in ischemia and even in repefusion still remain. Accordingly, we attempted to examine the intravascular plug fomation as well as the ultrastructural changes in myocytes and microvessels and to determine the relation among them. Methods: 1) Human (n= 10, 39-63 years of age; 3 females and 7 males): left ventricular myocardium (LVM) was biopsied from chronic ischemic heart disease patient during bypass surgery. 2) Calf (Holstein-Friesian species, n=4): Circumflex branch of the left coronary artery (LCx) was occluded (ischemia) for 45 minutes and recanalized (reperfusion) for 3 and 6 hours, respectively and LVMs were biopsied after occlusion and recanalization, respectiverly. 3) Rat (Sprague-Dawley species, n=20): Left coronary artery (LCA) was occluded for 20 minutes and recanalized for an hour as the method described by Selye et al., (1960) and hearts were removed after occlusion and recanalization, respectively. 4) Pig (landrace type, n=7): Anterior ascending branch of the left coronary artery (LAD) was coccluded for 45 minutes and recanalized for 2 hours and LVMs were biopsied after occlusion and recanalization, repectively. All of the LVMs were routinely prepared for transmissiom electron microscopy. Rseults: In human, most of the LVM showed irreversible ultrastructural changes in myocytes and frequent IVPs by PMNs or platelets without any significant correlation with age or sex. In the animal LVM, myocytes showed reversible ultrastructural changes with slight variations in accordance with the species, duration of ischemia and reperfusion or site of biopsy, however, injuries were more severe in the subendocardial myocytes and IVPs by PMNs or platelets were frequently observed. Ultrastructural changes in the myocytes seemed to be gradually improved by recanalization, howerver, IVPs were still observed after recanalization. Conclusion: These results suggest that microvessels are more resistant to ischemic insult than the myocytes themselves and IVP by PMNs and platelets may play an important role to produce ischemic or reperfusion injuries. Thus, it is favorable that angioplasty is preceded by thrombolysis and it is likely that restoration of myocardial function requires relarively long period of time even after recanalization.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.65-72
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• 1982

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.37-45
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• 1981

The importance of thyroid hormones for the survival of rats in the cold is along-established fact. Hypothyroid animals are unable to survive in a cold environment. It was also reported that acute exposure of rats, guinea pigs and rabbits to cold produced an increased secretion of TSH and thereby thyroid hormone secretion within 10 to 30 min, but this increase of thyroid activity disappeared quite rapidly during warming. However, in human study no significant difference was found in the concentration of $T_4$, TSH and cortisol between summer and winter. But plasma $T_3$ concentration was increased significantly in winter in 56 adult men. On the other hand, it has been also known that catecholamines are important in the maintenance of body temperature of rat exposured to cold. Abundant evidences suggest that the sympathetic nervous system is involved in the activation of nonshivering thermogenesis and that thyroid hormone metabolism and secretion are influenced by catecholamines and consequently by the activity of the sympatheticadrenal system. Many of the metabolic effects of catecholamines are associated with an increase in the level of cAMP mediated through activation of adenylate cyclase which converts ATP to cAMP. Other studies have shown that thyroid hormones affect the amount of adenylate cyclase present in the adipose tissue. On the other hand. it was also reported that a particulate cAMP phosphodiesterase activity in fat cells was modulated by the action of thyroid hormones. The objective of the present study was to determine the interaction between thyroid activity and cyclic nucleotides during acute exposure to cold. Albino rats weighing around 200 g were used as the experimental animal. The room temperature group was kept at $25^{\circ}C$ and the cold-exposured group was kept at $4^{\circ}C$ for 1 week or 2 weeks. Each group was subdivided into three subgroups; control, KI, and MTU group. At the end of experiment the animals were etherized and blood was taken from abdominal aorta for $T_4,\;T_3$ and cyclic nucleotides. The determinations of $T_3,\;T_4$ and cyclic nucleotides were carried out with a radioimmunoassay(RIA) method. The results were summerized as followings. 1) A significant increase of thyroid weight was observed in rats exposured to cold for 2 weeks. Furthermore, in rats administered MTU while to exposure to cold the thyroid weight was also increased significantly. 2) After 2 weeks $T_3$ concentration in the plasma of cold-exposured rats was significantly increased in KI group and MTU group as well as in control group. On the contrary, after 2 weeks of cold exposure $T_4$ level was decreased in control group. 3) In the case of cyclic nucleotides, plasma cAMP was increased in the control group after 1 or 2 weeks of cold exposure. However, cAMP level in plasma was rather significantly decreased in KI group and MTU group as well as in control group.

• Journal of the Korean Applied Science and Technology
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• v.34 no.3
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• pp.443-450
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• 2017

This study was done to investigate the protective effects of ethanol extract puerariae radix(Pr) on carbon tetrachloride($CCl_4$) intoxicated rats. Male sprague Dawley rats(200~210g)was used. experimental groups were divided into normal group, $CCl_4$-control group, and ethanol extract $CCl_4$-treated group. $CCl_4$-treated groups were injected with $CCl_4$ 0.6mg/kg.b.w(i.p). The activities of Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Alkaline phosphatase(ALP), Glutamyltranspeptidase(${gamma}$-GT), Lactate dehydrogenase(LDH) in extract pretrated group was significantly decreased(p<0.05) compared to the $CCl_4$-control group. The contents of triglyceride, cholesterol and lipid peroxide were significantly decreased(p<0.05). whereas content of HDL-choresterol was significantly increased.(p<0.05). In addition, activities of hepatic catalase(CAT), glutathione peroxidase(GSH-Px) in the extract pretreated rats were significantly decreased(p<0.05) compared to the $CCl_4$-control group. but the content of glutathione(GSH) was significantly increased(p<0.05). These results suggest that extract of puerariae radix(Pr) has hepatoprotective effect in the $CCl_4$-intoxicated rats.

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.872-880
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• 2001

The purpose of this study was to investigate the effects of glucuronic acid on antioxidative defense system and recovery of muscle fatigue in rat artier aerobic exercise. Sprague-Dawley male rats weighing 150 $\pm$ 10g were randomly assigned to one normal(N) group and three exercise training groups. Exercise training groups were classified into glucuronic acid free intubation group(T group), 250mg glucuronic acid/kg bw intubation group(TU group), and 500 mg glucuronic acid/kg bw intubation group(2TU group) according to glucuronic acid supplementation level. The glucuronic acids were administered to rats by oral intubation before exercise training. The experimental rats in exercise training groups(T, TU and 2TU) were exercised on glucuronic acid supplementation or rats in normal group were confined in cage for 4 weeks. And rats were sacrificed with an overdose of pentobarbital injection just after running. Liver xanthine oxidase(XOD) activities were not significantly different among four groups. The activity of superoxide dismutase(SOD) in T group was no significant difference from N group, but those of TU and 2TU groups were increased by 9% and 18%, respectively, compared with that of T group. Liver glutathione peroxidase(GSHpx) activites of T and TU groups showed a similar tendency to that of normal group, but increase 17% in 2TU group compared with normal group. The ratio of GSH/GSSG in liver of T group was lower than that of normal group, but those of TU and 2TU groups were a similar tendency to that of normal group. Contents of thiobarbituric acid reactive substance(TBARS) in T group was increased by 47%, compared with that of normal group but those of TU group and 2TU group were lower 27% and 35%, respectively, compared with that of T group. The contents of glycogen in soleus muscle significantly lower in all three trained exercise groups than that of normal group, but there were no significant differences among the trained exercise groups. Contents of hepatic glycogen in T group were decreased 27% compared with those of normal group while those of TU and 2TU groups were the same as normal group levels. The contents of serum lactic acid in T group were increased 240% of normal group, but hose of TU and 2TU groups were decreased 38%, 39%, respectively, by glucuronic acid supplementations, compared with that of T group. In conclusion, the effects of glucuronic acids in exercise training rats would appear to reduce peroxidation of tissue as an antioxidative defense mechanism and promote recovery of muscle fatigue.

• Journal of Nutrition and Health
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• v.35 no.1
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.