Background: This study was designed to develop a Korean version of the heparin-coated vascular bypass shunt by using a physical dispersing technique. The safety and effectiveness of the thrombo-resistant shunt were tested in experimental animals. Material and Method: A bypass shunt model was constructed on the descending thoracic aorta of 21 adult mongrel dogs(17.5-25 kg). The animals were divided into groups of no-treatment(CONTROL group; n=3), no-treatment with systemic heparinization(HEPARIN group; n=6), Gott heparin shunt (GOTT group; n=6), or Korean heparin shunt(KIST group; n=6). Parameters observed were complete blood cell counts, coagulation profiles, kidney and liver function(BUN/Cr and AST/ ALT), and surface scanning electron microscope(SSEM) findings. Blood was sampled from the aortic blood distal to the shunt and was compared before the bypass and at 2 hours after the bypass. Result: There were no differences between the groups before the bypass. At bypass 2 hours, platelet level increased in the HEPARIN and GOTT groups(p<0.05), but there were no differences between the groups. Changes in other blood cell counts were insignificant between the groups. Activated clotting time, activated partial thromboplastin time, and thrombin time were prolonged in the HEPARIN group(p<0.05) and differences between the groups were significant(p<0.005). Prothrombin time increased in the GOTT group(p<0.05) without having any differences between the groups. Changes in fibrinogen level were insignificant between the groups. Antithrombin III levels were increased in the HEPARIN and KIST groups(p<0.05), and the inter-group differences were also significant(p<0.05). Protein C level decreased in the HEPARIN group(p<0.05) without having any differences between the groups. BUN levels increased in all groups, especially in the HEPARIN and KIST groups(p<0.05), but there were no differences between the groups. Changes of Cr, AST, and ALT levels were insignificant between the groups. SSEM findings revealed severe aggregation of platelets and other cellular elements in the CONTROL group, and the HEPARIN group showed more adherence of the cellular elements than the GOTT or KIST group. Conclusion: Above results show that the heparin-coated bypass shunts(either GOTT or KIST) can suppress thrombus formation on the surface without inducing bleeding tendencies, while systemic heparinization(HEPARIN) may not be able to block activation of the coagulation system on the surface in contact with foreign materials but increases the bleeding tendencies. We also conclude that the thrombo-resistant effects of the Korean version of heparin shunt(KIST) are similar to those of the commercialized heparin shunt(GOTT).
The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.
Purpose: The prognosis of neonates with cholestasis is not clear. Some factors, such as high peak bilirubin levels and liver histologic findings have been claimed to affect the prognosis adversely. Our study aims to define which factors influence the prognosis of neonatal intrahepatic cholestasis. Methods: Retrospective reviews of the medical records were performed in 32 cases with neonatal intrahepatic cholestasis, who were admitted to Department of Pediatrics, Pusan National University Hospital from July 1995 to July 2002. Neonates were classified into 2 groups according to the duration of elevated serum alanine aminotransferase (ALT) levels more or less than 6 months. The data, such as biochemical, histopathologic and radiologic findings, were compared in both groups. Biochemical data included mean peak level of serum ALT, total bilirubin, direct bilirubin, and alkaline phosphatase. Histologic parameters related to lobular architecture, fibrosis, inflammatory infiltration and degenerative features of hepatocytes were arbitrary estimated on a scale of 1 to 3. Results: There were 19 males and 13 females, whose mean age was 48 days (14~77 days). The peak serum ALT levels were higher in the poor outcome group. Ductular proliferation and portoportal bridging were more severe in the poor outcome group. But the degree of multinucleated hepatocytes, hepatocellular swelling and canalicular plug did not appear to be significantly related to the long-term outcome. The DISIDA scintigraphy by visualization time of gall bladder and intestine was not useful in predicting outcome of neonatal intrahepatic cholestasis. Conclusion: Neonates who have intrahepatic cholestasis with high serum ALT levels, severe ductular proliferation and portoportal bridging in the liver biopsy specimen should be carefully followed up because they may have a poor prognosis.
This study was conducted to investigate the hepatoprotective effects of fermented Smilax china leaf ethylacetate extracts by Aspergillus oryzae on carbon tetrachloride-induced liver injury in mice. Experimental mice were divided into four groups (five mice/group) (NC; normal control group, CB; basic diet supplemented before $CCl_4$ treatment group, NS ; basic diet mixed with 0.5% Smilax china leaf ethyl acetate extract supplemented before $CCl_4$ treatment group, FS; basic diet mixed with 0.5% fermented Smilax china leaf ethyl acetate extract supplemented before $CCl_4$ treatment group) fed for 4 weeks each. In the $CCl_4$-treated groups (CB, NS and FS) compared with the NC group, liver weights, activities of alanine aminotransferase, aspartate aminotransferase, xanthine oxidase and aldehyde oxidase, contents of triglycerides, total cholesterol and LDL-cholesterol in serum, and hepatic lipid peroxide levels increased, whereas body weight gain and contents of glutathione and HDL-cholesterol decreased. Furthermore, in the FS groups compared with the NS and CB groups, increased or decreased indicators by $CCl_4$ treatment significantly decreased or increased, respectively. This study suggests that fermented Smilax china L. leaf extracts may regulate xanthine oxidase and aldehyde oxidase inhibitory activities and hepatoprotective effects due to flavonoid aglycone derived from its glycoside in leaves of Smilax china by fermentation of A. oryzae.
The antioxidant activity and protective effects of a hot water extract from the Stauntonia hexaphylla fruit (WESHF) were investigated in vitro and in vivo. The total polyphenol and flavonoid contents of WESHF were $16.13{\pm}0.27mg$ gallic acid equivalent/g and $4.7{\pm}0.80mg$ catechin equivalent/g, respectively. In addition, the DPPH radical-scavenging activity ($SC_{50}$) and the Oxygen Radical Absorbance capacity of WESHF were $63.62{\pm}4.10{\mu}g/ml$ and $90.63{\pm}5.29{\mu}M$ trolox equivalent/g, respectively. The hepatoprotective effect of WESHF against hydrogen peroxide-induced oxidative damage was investigated. $H_2O_2$-induced liver damage on HepG2 cells was prevented by $200{\mu}g/ml$ of WESHF. Furthermore, to investigate the protection mechanism of WESHF on hydrogen peroxide-induced cytotoxicity in HepG2 cells, pre-treatment with $200{\mu}g/ml$ of WESHF significantly attenuated a decrease in the activities of CAT, SOD, GR, and GPx. The hepatoprotective activity of WESHF was evaluated in an experimental model of hepatic damage induced by acetaminophen (APAP). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased in the livers of mice treated with 200 mg/kg of WESHF compared to the APAP-treated group. The lipid peroxidation level, which increased after APAP administration, was significantly reduced in the WESHF group. In addition, histological examinations of the liver showed the same protective effect of WESHF treatment. Based on these findings, it is suggested that WESHF has potent hepatoprotective effects, and the mechanism that causes this type of protection could be related to antioxidant pathways.
Shim, Yoon Hee;Cho, Su Jin;Rhyu, Jung Hyun;Hong, Young Mi
Clinical and Experimental Pediatrics
/
v.48
no.10
/
pp.1082-1089
/
2005
Purpose : Abdominal obesity is encountered as a risk factor for cardiovascular diseases. However, the anthropometric cut-off value to estimate the cardiovascular risk, has not been suggested. This study was designed to find the relationship between the abdominal fat and various parameters of obesity to find the cardiovascular risk factors related to abdominal obesity and to establish practical methods to measure them. Methods : Twenty seven obese Korean adolescents of moderate to severe degree and 22 healthy adolescents were enrolled. The body mass index(BMI), arm circumference and skinfold thickness were measured. Furthermore, blood lipid, sugar, insulin and four different cytokines' levels were checked and the distribution of body composition was measured by bioelectrical impedance analysis. The subcutaneous and intra-abdominal fat thickness by abdominal ultrasonography(US) and the total and intra-abdominal fat area by abdominal computerized tomography(CT) were measured in the obese group. Results : The most accurate method to measure abdominal fat in children is abdominal CT and the fat mass measured by bioelectrical impedance was strongly correlated with it(r=0.954). It was also correlated with arm circumference, fat thickness measured by abdominal US, BMI, aspartate aminotransferase(AST), alanine aminotransferase(ALT) and triglyceride level. Conclusion : Abdominal CT is the most accurate method to measure intra-abdominal fat, and it can be replaced by abdominal US for cost effectiveness. The screening methods that can be used at school or in outpatient basis include bioelectrical impedance, waist/hip ratio, and arm circumference. The cardiovascular risk factors include leptin, triglyceride and insulin level.
Kim, Tai Sung;Hur, Tae Hyung;Lim, Sun Jeong;Bin, Joong Hyun;Hahn, Seung Hoon;Kim, So Young;Kim, Hyun Hee;Lee, Wonbae
Clinical and Experimental Pediatrics
/
v.51
no.4
/
pp.396-400
/
2008
Purpose : The study was performed to assess the distribution of the diseases associated with nonspecific reactive hepatitis (NRH) for the past 10 years and to evaluate the change in the level of AST and ALT, and the difference by several variable factors. Methods : From January 1997 to December 2006, 646 patients had elevated liver enzymes among 22,763 patients admitted to the Holy Family Hospital. We analyzed the difference in the age distribution, the period of elevated levels of AST and ALT, the resolution period, the peak value, the daily resolution value of AST and ALT, the sexual differences and the difference in several disease entities. One hundred and ninety-seven patients not confirmed as NRH or lost during follow-up were excluded. Results : The prevalence rate of NRH was 2.84%. When compared to AST, ALT showed longer period of morbidity and resolution and the peak value was also higher in ALT. The male and female ratio showed significant value of 1.63:1. The morbid and resolution periods of AST and ALT between males and females were longer periods in males. The most prevalent disease entities were respiratory and gastrointestinal infections. Between the respiratory and the gastrointestinal diseases, the highest level of AST and ALT was observed in the respiratory disease. Conclusion : NRH is a common disease that occurs in 2.84% of the admitted pediatric patients. However, the pathogenesis and the progress of the disease have not been well known due to the lack of generalized information. Further research is necessary in the future.
Hong, Young Mi;Song, Young Whan;Kim, Hae Soon;Park, Hae Sook;Min, Jung Hae;Jung, Jo Won;Kim, Nam Su;Noh, Chung Il
Clinical and Experimental Pediatrics
/
v.52
no.10
/
pp.1109-1118
/
2009
Purpose : Metabolic syndrome (MS), characterized by obesity and insulin resistance, elicits risk factors such as hyperlipidemia, hypertension, and glucose intolerance with additive effects on atherosclerosis, leading to cardiovascular diseases. The purposes of this study were to evaluate the prevalence of MS among overweight and obese adolescents and to investigate the impact of obesity on the cardiovascular system. Methods : In all, 684 adolescents were included in the study. Blood pressure, body mass index (BMI), fasting blood glucose, total cholesterol, triglyceride, low-density-lipoprotein (LDL)-cholesterol, high-density-lipoprotein (HDL)-cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and high-sensitive C-reactive protein (hs-CRP) were measured in the patients with a BMI of >85 percentile. Brachial-ankle pulse wave velocity (BaPWV) and ankle brachial index were measured using Vascular Profiler (VP)-1000. Results : MS was confirmed in 19.5% of the overweight and obese adolescents and 50.8% of the obese adolescents. The systolic and diastolic blood pressure, height, weight, fat mass, %fat, BMI, obesity index, and waist circumference were higher in the overweight and obese adolescents with MS. Moreover, the triglyceride, AST, ALT, and hs-CRP levels were higher, whereas HDL-cholesterol level was significantly lower in this group. The overweight and obese adolescents with MS showed shorter diastolic and systolic times, higher heart rate and BaPWV, and longer E-wave deceleration time by echocardiography. Conclusion : Overweight and obese adolescents showed characteristic MS features such as hypertension and hyperlipidemia. Thus, obese adolescents predisposed to MS should be provided early treatment for obesity.
Journal of the Korean Society of Food Science and Nutrition
/
v.43
no.6
/
pp.807-813
/
2014
The objective of the present study was to investigate the protective effects of anthocyanin-enriched extract from radiation-induced blackberry (Rubus fruticosus L.) mutant (${\gamma}$-B201) against carbon tetrachloride ($CCl_4$)-induced liver injury in Spargue-Dawley (SD) rats. The in vivo results show that ${\gamma}$-B201 attenuated the levels of serum aspartate aminotransferase, alanine aminotransferase, and liver lipid peroxidation in $CCl_4$-treated SD rats. Histopathological examination of rat livers showed that ${\gamma}$-B201 reduced the incidence of liver lesions induced by $CCl_4$. Moreover, ${\gamma}$-B201 prevented DNA damage in $CCl_4$-treated SD rats. Furthermore, administration of ${\gamma}$-B201 significantly increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), in $CCl_4$-treated rat livers. In conclusion, the present study suggests that ${\gamma}$-B201 blackberry extract protects the liver from $CCl_4$-induced hepatic damage through an antioxidant mechanism. Therefore, ${\gamma}$-B201 blackberry may be functional food material for human health.
Journal of the Korean Society of Food Science and Nutrition
/
v.46
no.9
/
pp.1035-1044
/
2017
This study was carried out to investigate the effects of freeze-dried garlic powder (FDGP) on the lipid metabolism in rats fed a high fat-cholesterol (HFC) diet for 4 weeks to induce hyperlipidemia. The rats were divided into the following four experimental groups: normal diet group (NC), HFC diet group (HFC), HFC+FDGP 5 mg/100 g body weight (BW) group (FGT-1), and HFC+FDGP 15 mg/100 g BW group (FGT-2). Body weight gains and food efficiency ratios were significantly lower in the FGT groups compared to the HFC group, and the food intake was not significantly different in all experimental groups. Serum total lipid, triglyceride, and total cholesterol levels were significantly lower in the FGT groups compared to the HFC group. Total lipid content of the FGT-2 group was reduced by about 9% and 12% compared to the FGT-1 group and HFC group, respectively. The FGT groups also showed about 10% reductions low density lipoprotein (LDL)-cholesterol, atherogenic index (AI), and cardiac risk factor (CRF) compared to the HFC group. Liver function index (alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) and lipid components were significantly lower in the FGT groups compared to the HFC group. Thiobarbituric acid reactive substances content of serum and liver tissue was reduced in the FGT groups compared to the HFC group, and was lower in the FGT-2 group compared to the FGT-1 group in serum. Antioxidant activities in serum and liver tissue were in the order of FGT-2> FGT-1> HFC group, significantly. In conclusion, FDGP effectively reduced the lipid components of serum and liver tissue. Feeding FDGP did not increase high density lipoprotein-cholesterol, but reduced LDL-cholesterol content, AI and CRF, especially. This shows that FDGP, will be effective in preventing and improving cardiovascular diseases such as arteriosclerosis and hyperlipidemia.
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