• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.51-61
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• 2002

Purpose: The most common causes of neonatal cholestasis are neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA). Since neonatal cholestasis presents with variable expression of same pathologic process and has similar clinical, biochemical, and histologic features between EHBA and idiopathic neonatal hepatitis (NH), differential diagnosis is often difficult. We reviewed the differences of clinical characteristics and laboratory data to find out any correlation between the results of $Tc^{99m}$ DISIDA scan and presence of acholic stool. Methods: Between June 1993 and January 2001, total 29 infants younger than 4 month-old underwent $Tc^{99m}$ DISIDA scan. Their biochemical tests and clinical course were reviewed retrospectively. Results: Patients who had negative intestinal activity on $Tc^{99m}$ DISIDA scan showed acholic stool and revealed higher serum direct bilirubin and urine bilirubin level. 18.2% of patients with acholic stool showed intestinal activity on $Tc^{99m}$ DISIDA scan and 81.8% of them did not. All the patients without acholic stool showed positive intestinal activity on $Tc^{99m}$ DISIDA scan. The result of $Tc^{99m}$ DISIDA scan and the presence of acholic stool showed high negative correlation (r :-0.858). Patients with acholic stool and negative intestinal activity on $Tc^{99m}$ DISIDA scan showed higher serum total bilirubin level. Patients without acholic stool and positive intestinal activity on $Tc^{99m}$ DISIDA scan showed higher serum level of ALT. Conclusion: Patients with acholic stool and negative intestinal activity showed high correlation, but 18.2% of patients with acholic stool showed positive intestinal activity. So operative cholangiogram or transcutaneous liver biopsy should be performed for confirmation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2185-2190
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• 2013

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

• Journal of the Korean Chemical Society
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• v.42 no.3
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• pp.266-276
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• 1998

Cholesterol supersaturation in bile, which causes gallstone formation, is the result of low bile acid secretion or high cholesterol secretion. The quantitative analysis of cholesterol, bile acids and sterols which are precursors of cholesterol have been used to examine the changes in bile component. We described a simple, sensitive and reproducible method for simultaneous determination of cholesterol, five bile acids and seven sterols in human bile juices and gallstones by capillary column gas chromatography-mass spectrometry (GC/MS). Clinical samples were hydrolyzed by alcoholic KOH, extracted twice (pH 14 and 1) and derivatized to trimethylsilyl (TMS) ether with $MSTFA/NH_4I$ (N-methyl-N-trimethylsilyltrifluoroacetamide/ammonium iodide) mixture in order to be detected on the GC/MS. The good quality control data were obtained through within-a-day and day-to-day test (RSD values were 1.72-13.79, 0.68-14.10, respectively) and the recovery range of them was 73.56-96. 95 Using this method, biliary and gallstone compositions in the patients with intrahepatic stones were analyzed. The amounts and its relative distribution of cholesterol, bile acids and sterols showed different pattern in bile juices and gallstones.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1751-1758
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• 2015

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters ($p{\leq}0.001$). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverr-iniinfected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively ($p{\leq}0.001$). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism.

• The Korean Journal of Nuclear Medicine
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• v.26 no.1
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• pp.86-94
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• 1992

Quantitative analysis of gallbladder emptying is important in diagnosis of motility disorder of gallbladder and in studies of biliary physiology. However, the normal range of gallbladder ejection fraction (GBEF) has not been determined yet and the best method for stimulating the gallbladder to contract has not been elucidated adequately. The purpose of this study was to compare the gallbladder emptying effect of the fatty meal ingestion with that of the continuous infusion of cholecystokinin (CCK) and to establish the normal GBSF values of normal subjects. Quantitative hepatobiliary scan with $^{99m}Tc-DISIDA$ after a fatty meal was performed for 22 normal healthy volunteers. Among them, 10 subjects repeated the test with a fatty meal. Again, for 7 subjects quantitative heaptobiliary scan with an infusion of CCK (sincalide) at a rate of 20 ng/kg/hr for 45 minutes was performed repeatedly. The results were as follows. 1) With a fatty meal, the mean GBEF was $89.6{\pm}8.2%$ in 22 normal subjects, and there was no difference between subjects. 2) With a continuous infusion of CCK, the mean GBEF was $62.4{\pm}16.6%$ in 7 normal subjects, and there was a significant difference between subjects(p<0.05). 3) The reproducibility of GBEF by a fatty meal was significantly higher than by an infusion of CCK (p < 0.05). 4) The mean GBEF by a fatty meal was significantly higher than that by an infusion of CCK (p < 0.05). We concluded that a fatty meal is superior to a continuous infusion of CCK for inducing gall-bladder contraction because that induces more complete emptying and the response is more reproducible and constant.

• The Korean Journal of Pesticide Science
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• v.11 no.4
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• pp.217-221
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• 2007

In order to elucidate the behavior of the fungicide hexaconazole (1-(6-chloro-3-pyrldyhnethyl)N-nitroimidazolidin-2-ylideneamine) in carp (Cyprinus carpio L.), carps were exposed to [$^{14}C$]hexaconazole at a predicted environmental concentration (PEC) of 0.32 mg $L^{-1}$ for 4 days under static conditions. Hexaconazole in water was absorbed into carps to reach the maximum concentration 2 days after exposure. The amounts of the [$^{14}C$]hexaconazole and its metabolites absorbed in gall were much higher than those in the other organs and especially those in gall 2 days after exposure were 25 and 67 times higher than those in liver and kidney, respectively, strongly suggesting that biliary excretion involving enterohepatic recirculation could be an import route for the elimination of hexaconazole absorbed in carps.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.299-304
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• 2014

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

• The Korean Journal of Pharmacology
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• v.2 no.2
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• pp.23-33
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• 1966

Hexachlorophene was reported previously to have a powerful parasiticidal effects on Clonorchis sinensis in vitro and in vivo, but the mechanism of its effect was not known. In the present report it was observed that there was an influence of hexachlorophene on the oxygen consumption, the glycolysis, the glycogenesis and the protein synthesis of C. sinensis. A hundred mg. of C. sinensis collected from the biliary tracts of the infested rabbits was incubated in 2 ml of K.R.P. medium with vavious concentration of hexachlorophene, $glucose-1-C^{14}$ and $glycine-1-C^{14}$ in a 25 ml incubation flask with central well. The oxygen consumption was observed by Warburg manometer, the glycogenolysis by measurement of radioactivities of extracted glycogen and protein from C. sinensis incubated with $C^{14}-glucose$ or$C^{14}-glycine$. 1) The oxygen consumption by C. sinensis was markedly inhibited during all stages of incubation in concentration of $10^{-4}$ and $10^{-5}g/ml$ of hexachlorophene, but in $10^{-6}$, slightly increased initially and gradually decreased after 3 hours of incubation. 2) Hexachlorophene inhibited the glycolysis by C. sincnsis markedly in the concentration of $10^{-4}$, $10^{-5}$, $10^{-6}$ and $10^{-7}g/ml$. 3) The protein synthesis by C. sinensis from glycine was inhibited in the concentration of $10^{-5}$, $10^{-6}$ and $10^{-7}g/ml$ of hexachlorophene. 4. The glycogen synthesis by C. sinensis in each concentration of $10^{-4}$, $10^{-5}$ and $10^{-6}g/ml$ of hexachlorophene was inhibited markedly. The speed of inhibition was more rapid in high concentration than in low, and in low concentration even the glycogen itself which had synthesized in their stage in their body was consumed in later stage. 5) The effects of oxygen consumption, glycolysis and glycogen synthesis were not influenced in the concentration of $10^{-5}g/ml$ of chloroquine phosphate, whereas hexachlorophene and dithiazanine inhibited markedly in same concentration, and the former was more potent than the latter.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.328-334
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• 1997

Pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), was studied using radioimmunoassay (RIA) and $^{125}I$-DWP401 in rats. When DWP401 was adm inistered i.v. at doses of 50 and 500 mcg/kg, the plasma DWP401 disappeared biiexponentially with terminal half life of 4.7 and 92.8 min. The $C_{max}$ and $T_{max}$ after s.c. administration of ti at doses of 50 and 500 ${\mu}g$/kg were determined to be 23.6 and 17.5 ng/ml at 50 ${\mu}g$/kg, and 261.4 ng/ml and 36.8 min, respectively. Both the total urinary and biliary recoveries of intact DWP401 2343 very low (<0.4%), probably due to its extensive degradation in the body. the concentration ratio of DWP401 between the organ and plasma decreased especially in the liver and kidney as the dose and time after the dose increased. For example, the liver/plasma and kidney/plasma concentration ratio of DWP401 at 2.5 min after i.v. doses of 50 ${\mu}g$/kg were comparable and much larger than unity. But, the ratio at 2.5 min after i.v. doses of 500${\mu}g$/kg was much larger in the kidney that in than in the liver. These results suggest that the systemic administration of DWP401 might be subject to rapid and extensive clearance from circulation within several hour after main distrbution to liver and kidney.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.335-344
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• 1997

The absorption, distribution and excretion of $^{14}C$ labeled YH1885 {5,6-Dimethyl-2(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydroc hloride), a new proton pumpinhibitor, were investigated in rats after a single administration of $^{14}C$-YH1885. 1. After intravenous administration of 5mg/kg, the blood level of radioactivity declined in a biphasic fashion with the mean terminal elimination half-life of 12.4hr. 2. After oral administration of 20mg/kg, the maximum blood level of radioactirity was reached at 4.0hr in female rats. The blood level of radioactivity-time profiles in male and female rats were similar, and the absorptionof $^{14}C$-YH1885 was not affected by food. 3. Appproximately 89% and 1% of radioactivity of the total dose were excreted in feces and urine, respectively. 4. Biliary excretion of radioactivity was 47.9% of the dose. Enterohepatic circulation of radioactivity was 49.6%. 5. Radioactivity was excreted maily into feces via bile. 6. The concentration of radioactivity in most tissues reached the peak level at 4.0hr after dosing, and then declined. Autoradiograms of male rats showed that the radioactivity levlels in the fat, harder's gland, liver and G-Itract were higher than those in the other tissues and the elimination of radioactivity from fat and liver was slow. 7. Autoradiograms of a pregnant rat showed that radioactivity was transferred to mammary gland, placenta and fetus. The radioactivity level in the mammary gland was higher than that in the blood.