Journal of Physiology & Pathology in Korean Medicine
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v.23
no.4
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pp.799-804
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2009
Kamikaekyuk-tang(KMKKT), a formula of ten Oriental herbs, was orientally designed to promote vital energy, to remove blood stasis, and to decrease inflammation for treating cancers. KMKKT and its component had potent antiandrogen and androgen receptor activities in prostate cancer and also inhibited angiogenesis induced by basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells and suppressed the tumor growth in LLC-bearing mice, and liver metastasis of colon 26-L5 cancer cells, suggesting a potent cancer preventive agent. Nevertheless, there is no safety study of KMKKT before clinical trial so far. Thus, in the current study, we investigated the toxicity about ethanol-extracted KMKKT. Male and female Spraque Dawley (SD) rats were given orally by KMKKT at 250, 500, and 1000 mg/kg for 4 weeks. Mortality, clinical signs and measured change of body weight, food consumption and water consumption were observed. In addition, we performed ophthalmologic, urinary, hematological, blood serum biochemical and histopathological examination. Any general toxicity was not found in KMKKT treated group. Also, there were no significant differences in the parameters such as body weight, food consumption and water consumption, a lot of urine and blood factor levels except WBC, MCHC and Ca level compared with control group. Although WBC and MCHC were elevated in female rats and Ca level was decreased in male rats, these were within normal ranges. Finally, we determined that maximum tolerated dose (MTD) was 1000 mg/kg and no observed adverse effect level (NOAEL) was 500 mg/kg. Taken together, these results demonstrated that KMKKT is very safe to SD rats.
Lee Chang-Woo;Lee Myong-Lyoll;Kim Hwan-Mook;Yoon Won-Kee;Kim Seung-Hwan;Son Hwa-Young;Kim Hyoung-Chin
Toxicological Research
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v.20
no.3
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pp.263-272
/
2004
This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.
5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn s disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or $CHCl_3$/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at $37^{\circ}C$. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at $37^{\circ}C$. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.
This study was conducted to investigate the subacute transdermal toxicity of Syndella gel, a new topical drug containing deproteinized dialysate of calf's blood and micronomicin sulfate in Sprague-Dawley rats. Three doses (1.97, 3.94, 7.88 g/kg) of Syndella gel was daily treated transdermally to male and female rats for 30 days. No death was occurred in either control or treated rats. No significant toxic clinical signs and body weight change were not observed at any doses in the male or female rats treated. There were no significant alterations in hematologic and biochemical parameters in both sexes, however slight increase of potassium concentration was observed in 3.94g/kg and 7.88 g/kg female groups. No significant necrotic changes were not observed in examined organs. This study showed that up to 7.88g/kg Syndella gel did not induce subacute transdermal toxicity.
The membranes of mitochondria and chloroplasts contain a number of pigments that can act as endogenous sensitizers to produce activated oxygen species, most efficiently in blue light, which, in turn, attack functional targets in membranes. Therefore, intense blue light from the sun can exert various adverse effects on the functional and structural integrity of the membranes: one of the biochemical events of these negative effects could be the oxidative degradation of the unsaturated fatty acid constituents of membrane polar lipid. It may be assumed that as a strategy to avoid the light induced fatty acid degradation in membranes plant cells, responding to high intensity blue light, change the fatty acid compositions of membrane lipid in such that more-unsaturated fatty acid constituents are replaced by lessunsaturated fatty acid constituents. The results obtained in the present study, most importantly the measurements of double bond index of membrane polar lipid in concert with other measurements such as light quaility-dependent membrane peroxidation and the activities of membrane-bound proteins, seem to support this assumption.
Lee, Seungjun;Choi, Hyun-Ah;Lee, Woo-Kyun;Lee, Jong Yeol;Jeon, Seong Woo;Kim, Joonsoon
Journal of Environmental Impact Assessment
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v.23
no.3
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pp.197-207
/
2014
In this study, the functional priority of wetlands was determined through analysis of previous research. To determine relative importance, three processes were performed. First, quantitative values from the case studies were normalized. Second, non-quantitative values were prioritized based on standard criteria. Third, equal weight was applied as long as there was no special consideration regarding a particular value's disproportionate priority in the research. Finally, results were grouped into large, medium, and small classes.In this study, the functions of the medium class were found to be the most significant, in the following order of priority: water supply and ground water recharge; culture and recreation; biodiversity; product; water quality control; flood control; erosion control; moderation of climate change; and provision of biochemical matter. To verify these results, we compared our findings with those of an assessment that used the Rapid Assessment Method (RAM) on the same type of study area. Whereas this comparison indicated some correlations by the culture, water storage, and genetic sustainability functions, it suggested a lack of such relationship by the water purification and flood prevention functions.
Na, Chun-Soo;Hong, Cheol Yi;Na, Dae-Seung;Kim, Jin Beom;Yoon, Sun Young;Lee, Sang-Bum;Dong, Mi-Sook
Korean Journal of Pharmacognosy
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v.44
no.1
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pp.83-90
/
2013
The aim of this study was to evaluate the effect of hot water extract of peduncle obtained from Hovenia dulcis Thunb (HD) which is commercially developed for the protective effect on the alcoholic hepatotoxicity, on the endurance capacity for weight loaded forced swimming mice. The swimming times to exhaustion in mice fed 100 and 200 mg/kg HD for 2 weeks were prolonged 3.6 and 3.7 fold, and for 4 weeks 1.9 and 2.7 fold compared with each vehicle control ($42.8{\pm}20.5$ min and $67.7{\pm}47.8$ min, for 2 and 4 weeks), respectively. Blood biochemical parameters for ALT, AST, creatinine and BUN were not significantly different between from HD fed or control mice. Although HD fed mice swam over 2 fold longer time than vehicle control mice at 4 weeks, blood biomarkers of physical fatigue such as glucose, triglyceride and free fatty acid, lactate were not significant different and even tended to ameliorate. Hepatic lipid peroxidation and SOD activity did not significantly change in HD fed- and vehicle control exhausted swimming mice at 2 or 4 weeks. However, catalase activity in HD-fed mice was significantly increased in a dose-dependent manner compared with vehicle control mice. The present study indicates that HD improved physical fatigue and exercise performance in mice. Therefore, it has a potential for the pharmacological effect of anti-fatigue.
Fifty-four, mixed-sex, halothane-carrier crossbred (Yorkshire${\times}$Landrace) pigs with an average initial BW of $108.2{\pm}0.8$ kg were randomly allotted to one of three dietary treatments for 5 d before slaughter: i) a control corn-soybean meal finisher diet devoid of supplemental magnesium; ii) a diet supplemented with 1.5 g/kg of elemental Mg from magnesium acetate; and iii) a diet supplemented with 1.5 g/kg of elemental Mg from magnesium sulfate heptahydrate. Serum creatine kinase (CK), lactate and glucose were analyzed at slaughter. Muscles from longissimus (LM) were packaged and stored to simulate display storage for muscle lactate and glycogen determinations at 0, 1, 2, 3, and 4 d. Mg supplementation reduced (p<0.05) serum CK and lactate concentration, but had no effect (p>0.05) on serum glucose. Daily change of muscle lactate concentration linearly increased (p<0.01), while glucose concentration linearly decreased (p<0.05) as storage time increased in all treatments. However, dietary Mg acetate and Mg sulfate supplementation in pigs elevated (p<0.05) muscle glycogen and reduced (p<0.05) muscle lactate concentrations, especially during the first 2 d of display, compared with pigs fed the control diet. This study suggests that short-term feeding of magnesium acetate and magnesium sulfate to heterozygous carriers of the halothane gene has beneficial effects on stress response and pork quality by improving blood and muscle biochemical indexes.
This study was intended to evaluate the overall effects of nutritional education on adults having two or more symptoms of chronic degenerative disease. A nine week nutritional education program was provided for 65 adults with chronic diseases. We assessed the changes in dietary knowledge, eating behavior and socio-psychological factors. When we evaluated the nutrient intakes of the subjects, their energy intake was 79.4% of the Korean Recommended Dietary Allowances (RDA). Their dietary intake of other nutrients was also below the RDA level except for Vitamin C. Their knowledge of dietary therapy was slightly improved after the implementing of nutritional education. The dietary behavior of ‘night snacks before sleep’was significantly improved. While the overall fear due to disease was significantly increased, self-efficacy was not improved. Self-efficacy for eating “three regular meals” and “choosing fruit, vegetable and grain” were significantly decreased. Family support for “buying food which is good for my health” was also significantly increased, whereas “advises me to eat appropriate foods for health” was decreased. Biochemical analysis indicated that blood levels of triglyceride, cholesterol and blood pressure improved after nutrition education. Therefore, we concluded that nutritional education program for people with chronic degenerative diseases could change the diet therapy knowledge, dietary behavior, and the fear due to disease, support from family and behavior intention toward the direction to improve the chronic disease condition. However, it did not improve self-efficacy. Our study also indicated that nutritional education strategies to improve self-efficacy should be an important aspect in a long term education plan for patients to establish desirable eating habits.
Liver functions in diffuse parenchymal liver disease such as cirrhosis of the liver depend largely on the effective hepatic blood flow rather than on the individual cell functions. Clinical methods of measuring the hepatic blood flow were developed recently by the application of colloidal disappearance rate. In order to correlate the radiogold disappearance rate to conventional biochemical liver function tests, 21 normal subjects and 80 cases of cirrhosis of the liver were studied with both methods. The results are summarized as following: 1. The validity of external counting method to measure the blood disappearance rate of colloidal radiogold was confirmed by in vitro counting of the serial blood samples. 2. The blood disappearance rate of collidal radiogold was essentially the same. as the liver uptake rate of colloidal radiogold in normal and cirrhotic subjects with various degrees of functional disturbance. And it seemed there was no serious extrahepatic removal of the colloidal radiogold. 3. The disappearance rate of colloidal radiogold was not significantly changed by the posture change, but was enhanced by ingestion of 500 ml of water. 4. The disappearance rate of colloidal radiogold was not influenced by single dose of Telepaque, while BSP retention was increased after Telepaque. 5. The mean disappearance half time of colloidal radiogold in normal subjects was $2.49{\pm}0.391$(S.D.) minutes. The mean normal disappearance rate constant (K value) was $0.285{\pm}0.0428$(S.D.)/minute. 6. The colloidal radiogold disappearance half time was abnormally prolonged (over 3.2 min.) in $87.7{\pm}3.68$(S.D.) % of cirrhotic subjects. 7. In patients of liver cirrhosis the blood disappearance rate of colloidal radiogold correlated well to serum albumin and globulin levels and BSP retention which were considered to reflect functions of hepatic parenchymal cells. There was, however, no correlation between colloidal disappearance rate and thymol turbidity test, serum glutamic pyruvic transaminase, and serm alkaline phosphatase activities. The latters were considered to be associated with the activity of liver disease.
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