• Archives of Pharmacal Research
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• v.25 no.5
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• pp.655-663
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• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

• Korea journal of population studies
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• v.6 no.1
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• pp.43-69
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• 1983

This study was conducted to make the life tables from specific causes of death in Korea. Both "Life tables of Korea in l978-79" and "the statistics on causes of death statistics in 1980" issued by Economic Planning Board were used as source of data for this study. Among the 58, 187 death certificates reported to the concerned authorities, 39, 801 causes were drawn for the purpose of this study. As a result, it is revealed that two thirds of men in Korea died from these 10 major causes of death. The summarized results are as follows: 1. According to recent statistics, 10 major causes of death in 1980 were shown in the order of 1) malignant neoplasms, 2) cerebrovascular disease, 3) accidents and adverse effects, 4)hypertensive disease, 5) ischaemic heart disease and heart attack, 6) chronic liver disease and cirrhosis, 7) tuberculosis, 8) pneumonia, bronchitis, emphysema and asthma, 9) suicide, 10) diabetes mellitis. 2. The major causes of death in Korea were very similar to those of developed countries such as West Germany, Denmark and Japan. This means that our pattern of death causes is almost approaching to that of developed countries. 3. Our crude death rate in 1980 was on the line of 6.6 per 1, 000 people. This is very low level, compared with 12.1 in West Germany and 10.0 in Denmark, however, our age sepcific death rate was on the verge of doubled level in each age category as to that of West Germany, Denmark and Japan. The fact tells us that our death rate is very high yet, especially in young and prime adult age, and the proportion of the aged is quite low. 4. Average ages of people died from malignant neoplasms, cerebro vascular diseases and hypertensive diseases were 63.1, 66.6, 67.3 respectively, however, that of accidents and adverse effect was only 42.5. This shows that accidents occur indifferently from age. 5. In the curve of eventual death probability, the curve of malignant neoplasms was the highest of all curves before 60 in age. However, the probability curve of eventually dying from accidents and adverse effects tends to decline with age. 6. In this study five life tables from major causes of death (four leading causes of death and of tuberculosis) were constructed for 1979. These life tables are reflecting accurately the effects of age distribution on the specific cause of death. In the surviving curje of these tables we can see that the curve of accidents is adversely related to age. While curves of neoplasms, hypertension and tuberculosis are not diminishing before 40 in age, they are going sharply downward after 50 in age.ard after 50 in age.

• Korea journal of population studies
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• v.16 no.2
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• pp.65-83
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• 1993

The purpose of this study is estimate limits of Korean life expectancy at birth by 'Gompertz growth curse Model', 'Cause-Elimination Model' and Multidimensional models of Senescencee and Mortality'. Data used in Gompertz curve were obtained from all life tables published from 1905 to 1990 in Korea, and life expectancies at birth of eighteen groups were selected at five-year interval in consideration of time-series changes. Data used in Cause-Elimination Model are 'Cause of Death statistics in 1991' published in 1992 by National Bureau of Statistics of Korea and 'life table of 1989' published in 1990 by National Bureau of Statistics, Economic Planning Board of Korea. The materials are all classifiable death data, 119, 253 cases of male and 82, 420 cases of female, which is from 1991 Causes of Death statistics. The cases of death analyzed belong to one of 8 categories; i.e., Infectious and Parasitic Diseases(001-139; with notation of Infectious Diseases), Malignant Neoplasms(140-208), Hypertensive Diseases(401-405), Ischemic Heart Dieases and Diseases of Pulmonary Circulation and Other Forms of Heart Diseases(410-429;with notation of Heart Disease), Cerebrovascular Diseases(430-438), Chronic Liver Diseases and Cirrhosis(571; with notation of Liver Diseases), Injury and Poisoning(800-999) and all other disease. Data used in 'Multidimensional models of senescence and mortality' were life table of 1989 published by National Bureau of statistics, Economic Planning Board of Korea and life table of 1970, 1978-79, 1983, 1985 and 1987. The major findings may be summarised as follows: 1. Estimate equations of Gompertz growth curve using life expectancy at birth during the 1905-1990 period are as the following. Male : y = 88.047697 $\times$ $0.199690^{0.903381x}$ Female : y = 95.632828 $\times$ $0.199690^{0.903381x}$ Limits of life expectancy at birth, which were estimated by Gompertz growth curve, are 88.05 for male and 95.63 for female. 2. The effect on life expectancy at birth eliminationg all causes death is 14.04 years(for male) and 10.86 years(for female). Astonishingly, eliminating the malignant neoplasms increase life expectancy at birth by 2.85 years for male 2.03 years for female in 1991. In table 8 we show the effect on life expectancy at birth of separately eliminating each of the 8 categorical causes of death. The theoretical limit to life expectancy by Cause-Elimination Model is 80.96 for male and 85.82 for female. 3. If the same rate of delay [0.376 year(male), 0.435 year(femable) per calendar year] continued, then life expectancy at birth would reach 74.82(male) years and 84, 10(female) years in 2010. With 14.04-years(male) and 10.86-years(female) effect attributable in 2010 would be 88.86 years(male) and 94.96(femable) years. 4. 'Multidimensional models of senescence and death' permits calculations of the value of the attribution coefficient (B), percent of loss per year of physiologic function. The results of Ro and B during the 1970-1989 period are listed in table 9. Estimate of limit to Korean life expectancy at birth by 'Multidimensional models of senescence and death' is 99.47 years for male and 104.74 years for female in 1989.

• Journal of Sasang Constitutional Medicine
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• v.15 no.1
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• pp.90-108
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• 2003

Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) has been developed as prescriptions for the Soyeumin constitution. The hepatoprotective effect of the water extract of Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) was investigated against carbon tetrachloride (CCl4)-induced hepatic damage. A single intra-peritoneal injection of CCl4 produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) 500 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with CCl4-treated control group. Treatment of rats with CCl4 led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from CCl4 administration were inhibited by the pretreatment with Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SG1) extract. These results suggest that Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract can be useful as a hepatoprotective agent. And the effect of NO modulation by NO synthesis or precursors, and Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang (SGT) water extract was researched on chronic liver damage induced by CCl4 administration. It was observed that endogenous NO protected the liver from lipid peroxidation, fibrosis, and damage. Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract showed the hepatoprotective effect on the chronic liver cirrhosis model and relationship with NO modulation.

• Korean Journal of Plant Resources
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• v.28 no.5
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• pp.635-640
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• 2015

Nonalcoholic fatty liver disease (NAFLD) is a kind of liver inflammation caused by an accumulation of fat in the liver. Patients with NAFLD have an increased risk to develop liver fibrosis, which leads to cirrhosis. To investigate hepatoprotective effects of Agrimonia eupatoria L (A. eupatoria), oleic acid-induced NAFLD in HepG2 cells was used and A. eupatoria was fractionated with ethanol (EtOH), n-hexane, dichloromethane (CH₂Cl₂), ethyl acetate (EtOAc), n-butanol (BuOH), and H₂O. Cells treated with the EtOAc fraction showed the highest lipid accumulation inhibiting effect. A. eupatoria also suppressed triglyceride accumulation and inhibited expression of lipid marker gene, such as a peroxisome proliferator activated receptor γ (PPAR-γ). Moreover, another marker, mRNA expression level of peroxisome proliferator activated receptor α (PPAR-α) was significantly increased by in a dose-dependent manner. These results suggest that A. eupatoria is a potent agent for the treatment of NAFLD.

• YAKHAK HOEJI
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• v.40 no.5
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• pp.550-557
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• 1996

One of therapeutics in liver disease (morbus wilson) is D-penicillamin (D-pen: D-3-mercapto-valin). Especially the cross-linking of collagen molecules could be inhibited by D-pe n in extracellular space. In this study we investigated the antifibrotic effects of D-pen in rats that were induced the liver fibrosis by bile duct ligation and scission (BDL/S). Rats were treated for 4 weeks with D-pen after BDL/S operation or sham operation. The balance between fibrogenesis-marker (PNIIIP) and the fibrolysis-maker (PNIVP) were observed in sera by RIA (radioimmunoassay), and the parameter of collagen deposition in liver tissue (hydroxyproline: HYP) was measured by colorimetry. The weight of liver in BDL/S operated group was increased significantly in compared with sham operation group (15.2g${\pm}$1.1, vs 11.9g${\pm}$3.9: p<0.005, p<0.05). The rats group treated by D-pen showed the lower level of PNIIIP (6.7ng/ml${\pm}$1.5, vs 9.5ng/ml${\pm}$2.8) and the higher value of PIVCP (14.0ng/ml${\pm}$1.9, vs 7.9ng/ml${\pm}$1.5) in sera that compared to untreated rats. The content of HYP was decreased by 141% in BDL/S with D-pen treated group than that of it in BDL/S group. No correlation was revealed between collagen parameters in sera and HYP in liver tissue of BDL/S operated and D-pen treated rats. The group treated with D-pen showed the lower value of clinical biochemistry parameters (GOT: glutamate oxalacetate transaminase, Total-Bilirubin) in compared with only BDL/S operated rats, but the value of GPT (glutamate pyruvate transaminase) and Alkaline phosphatase in two BDL/S groups was nearly same. In the histological finding, we observed mild bile duct proliferation, weak inflammation and fibrosis in BDL/S with D-pen treated group, but BDL/S operated group showed the formation of septum (island of hepatocytes), massive bile duct proliferation. This result represents that the BDL/S operation induces liver fibrosis (cirrhosis) in 4 weeks, and D-pen inhibits the synthesis of collagen weakly and stimulates the degradation of collagen in the extracellular space. We conclude that the monitoring of PNIIIP, PIVCP in sera is useful parameter for screening of antifibrotic effect, and D-pen delay the liver fibrosis.

• Korean Journal of Clinical Laboratory Science
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• v.38 no.3
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• pp.208-211
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• 2006

Microalbuminuria is most frequently caused by kidney damage from diabetes. Moreover, many other conditions can lead to kidney damage, such as high blood pressure, heart failure, cirrhosis, or systemic lupus erythematosus (SLE). The measurement of the microalbumin in urine may be useful for the early diagnosis or as a predictor of nephropathy in diabetes. The most common method for getting a quantitative measurement of urinary protein relies on a 24-hour urine collection. The result of this method is accurate. But 24hr urine collection is difficult to obtain and variations in volume are frequent. Also the patients complain about urine collection. We tried to measure reference values for microalbumin using fasting urine and compare them with the albumin/creatinine ratio using 24hr urine. The concentrations of microalbumin in fasting urine and 24hr urine were $7.1{\pm}3.8mg/L$, $5.7{\pm}2.9mg/L$ (r=0.61, p=0.27), respectively. The albumin/creatinine ratios using fasting urine and 24hr urine were $8.7{\pm}4.2{\mu}g/mg$, $8.7{\pm}4.0{\mu}g/mg$ (r=0.76, p=0.88), respectively. This study indicated that the measurement of microalbumin in fasting urine was an easy and simple method for early diagnosis or to predict nephropathy in diabetes. Thus, setting up the reference value using fasting urine may be useful in the screening test for the diabetic nephropathy patients instead of using the 24hr albumin excretion rate (AER).

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.39-50
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• 2002

Hepatitis B viral infection which affect about 10% of Korean population manifests asymptomatic carrier, chronic hepatitis and liver cirrhosis and even associates with hepatocellular carcinoma. Clinical manifestations induced by hepatitis B virus vary depending on the degree of immune response by cytotoxic T cells against viral epitope-presenting liver cells. Since hepatitis B virus presents high rate of mutaton that might change the presented epitope and eventually alter immune response, viral mutations, especially in promoters and enhancers, have an important implication in hepatic inflammation and viral replication. To identify mutations related to the hepatic inflammation, we investigated sequence variations of hepatitis B viral promotor regions in the presence or absence of symptoms in hepatitis B carriers. For this, sera from persistently hepatitis B virus-infected mother-child pairs were collected. After PCR amplifiation of all hepatitis B viral promoters (C promoter, S1 promoter, S2/S promoter, X promoter) using serum DNA from each pair, viral promotors were sequenced by automatic sequencer and then sequence data were analyzed by ClustalW. In most cases, the dominant type of maternal virus was transmitted to the child. However, in some children, some new host specific viral variants could be observed in Cp, S1p and S2/Sp. The mutations in C promoter did not seem to be vertically transmitted but arose in new host independently after the wild type had been transmitted. Enhancer I containing X promoter revealed high host specific variations as has been reported before. Two S promoters, S1p and S2/Sp, have shown some point mutations in children, but no deletion mutations were detected as in chronic hepatitis patients in whom deletion mutations are frequently found. In conclusion, the children with the vertically transmitted hepatitis B virus mostly retain the dominant type virus that had been transmitted. However, host specific variants tended to accumulate over time, possibly as clinical symptoms develop.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.2
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• pp.178-184
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• 1999

Purpose: The aims of this study were to evaluate the clinical manifestations and prognosis of the syndromic and nonsyndromic intrahepatic bile duct paucity (IHBDP). Methods: We studied histology of 42 infants with neonatal cholestasis. Fourteen patients were diagnosed as IHBDP. We evaluated the clinical manifestations, courses and prognosis retrospectively. Results: Underlying disease of the 42 infants with neonatal cholestasis were biliary atresia in 23, intrahepatic bile duct paucity in 14 (Alagille syndrome in 4 and nonsyndromic IHBDP in 10), neonatal hepatitis in 5 infants. The mean ratio of the bile ducts per portal tract was 0.087 (range: 0~0.5). The manifestations in 4 patients with Alagille syndrome demonstrated as follows: characteristic face in 3, chronic cholestasis in 4, posterior embryotoxon in 2, vertebral anomalies in 2, peripheral pulmonary stenosis in 2. One of 4 patients of Alagille syndrome improved cholestasis and the other 3 patients were remained their cholestasis and growth retardation. All patients of the nonsyndromic IHBDP were idiopathic. Seven out of 8 patients of nonsyndromic IHBDP showed improvement of cholestasis, and one patient received liver transplantation due to cirrhosis. Conclusion: This study suggested that IHBDP should be considered in the differential diagnosis of neonatal cholestasis. The outcome of idiopathic IHBDP was better than predicted.

• Journal of Yeungnam Medical Science
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• v.18 no.1
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• pp.51-58
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• 2001

Background: Cholestatic hepatitis is failure of bile to reach the duodenum with hepatocellular damage and no demonstable obstruction of the major bile ducts. The prognosis is usually good with recovery in less than 4 weeks after withdrawal of the offending drug. However, a prolonged course lasting over 3 months is possible and, in rare cases, progression to ductopenia with development of a vanishing bile duct syndrome occurs. A differential diagnosis with other causes of Chronic liver disease is needed. Materials and Methods: From January 1991 through January 2000, 14 patients diagnosed as cholestatic hepatitis by liver biopsy were included. The possible causative drug, clinical features, laboratory findings, and progression of cholestatic hepatitis were evaluated. The semiquantitative study of liver lesions was performed by two independent observers. Results: Causes of cholestatic hepatitis are 5 cases of oriental medicine, 3 cases of anti-tuberculosis medication, 1 case of ticlopidine and antibiotics and 4 cases of unknown causes. The clinical features of cholestatic hepatitis were jaundice, itching, urine color change, and general weakness. During 6 to 30 months, LFT of 5 patients showed prolonged elevation. Elevated total cholesterol ${\geq}$250 mg/dL in 6 patients, pheripheral blood eosinophilia in 5 patients, auto-antibody positive in 6 patients were observed respectively. The biopsies showed intralobular bilirubinostasis with a mixed portal inflammatory infiltration. Conclusion: In cholestatic hepatitis, durations of abnormal LFT are variable regardless of causative drugs. If cholestatic hepatitis progresses toward chronic course, viral hepatitis, primary biliary cirrhosis, and autoimmune hepatitis should be differentially diagnosed and sequential liver biopsies are needed.