• Archives of Pharmacal Research
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• v.28 no.3
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• pp.330-334
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• 2005

The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 $\mu$mol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance ($CL_b$) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane ($CL_{exc}$) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent V$_{max}$ and $CL_{linear}$, but the $K_m$ for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.3 no.1
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• pp.63-67
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• 2000

Purpose: Biliary atresia, one of the major causes of neonatal cholestais, is an idiopathic, serious disorder, affecting the newborn that results in complete obstruction of biliary tract. Successful reestablishment of bile flow is dependent on early surgical intervention, early diagnosis is imperative. The authors evaluate the utility of Tc-99m-labeled diisoprpyliminodiacetic acid (DISIDA) hepatobiliary scintigraphy in the diagnosis of biliary atresia. Methods: From January, 1995 to August, 1999, total 60 patients with neonatal cholestasis underwent Tc-99m DISIDA hepatobiliary scintigraphy at Asan Medical Center. Results: The undelying causes of neonatal cholestasis were biliary atresia in 14, neonatal hepatitis in 33, intrahepatic bile duct paucity in 9, and total parenteral nutrition induced cholestasis in 4. All patient with biliary atresia were interpreted correctely in DISIDA hepatobiliary scintigraphy, showing 100% sensitivity. Of the 46 patients with neonatal hepatitis and other causes, 37 patients had intestinal radioactivity showing 80% specificity. Conclusion: Visualization of DISIDA in the intestinal tract indicates patency of the biliary ducts and excludes the diagnosis of biliary atresia. But the absence of intestinal excretion on the DISIDA hepatobiliary scintigraphy dose not necessarily indicate biliary atresia.

• The Korean Journal of Nuclear Medicine
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• v.22 no.2
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• pp.181-185
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• 1988

Since hepatocyte clearance, leading edge parencymal transit time and biliary excretion can be evaluated separately with hepatobiliary scan using $^{99m}Tc-DISIDA$, hepatobiliary scan may be useful in differentiating intrahepatic cholestasis from extrahepatic cholestasis. Excretory liver function was analysed in 13 healthy subjects and 11 patients with clinically suspected hepatocellular disease and 9 patients with extrahepatic biliary obstruction confirmed by surgery, radiological and clinical evidence. Indices of total liver activity (% TLA), liver parechymal uptake (% LPU), heart pool clearance (% HPC) and liver-heart rate (% LHR) were calculated from time activity curve over heart and liver. Compared with healthy subjects, significant reduction (p<0.05) in total liver activity (% TLA) and liver-heart rate (% LHR) was observed in all patients group. But no useful indices was demonstrated in differentiating hepatocellular disease from extrahepatic biliary obstruction.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.1
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• pp.1-11
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• 2016

Cholestasis results from impairment in the excretion of bile, which may be due to mechanical obstruction of bile flow or impairment of excretion of bile components into the bile canaliculus. When present, cholestasis warrants prompt diagnosis and treatment. The differential diagnosis of cholestasis beyond the neonatal period is broad and includes congenital and acquired etiologies. It is imperative that the clinician differentiates between intrahepatic and extrahepatic origin of cholestasis. Treatment may be supportive or curative and depends on the etiology. Recent literature shows that optimal nutritional and medical support also plays an integral role in the management of pediatric patients with chronic cholestasis. This review will provide a broad overview of the pathophysiology, diagnostic approach, and management of cholestasis beyond the neonatal and infancy periods.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.969-972
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• 2002

The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats during acute inflammation (AI) was investigated. AI was induced by an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as a model OC since it is largely excreted into bile, and is neither metabolized nor binds to proteins in the body. When TBuMA was administered intravenously to AI rats at a dose of 6.6 $\mu$mole/kg, the AUC was increased, while biliary excretion (i.e., cumulative amount and apparent clearance) was decreased compared to normal rats. When TBuMA was administered intravenously to AI rats at a constant rate (i.e., a bolus injection at a dose of 1.5 $\mu$mole/kg followed by a constant infusion at a rate of 1.5 $\mu$mole/kg/hr for 165 min), steady-state concentrations of plasma and liver concentrations of TBuMA were increased significantly, while in vivo hepatic uptake (amount) and canalicular excretion (clearance) were decreased. These results are consistent with a hypothesis in which both the sinusoidal uptake of TBuMA into hepatocytes via the OCT1 and the canalicular excretion of the compound from hepatocytes via the P-gp are decreased by LPS-induced AI.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.101-107
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• 2002

We experienced two cases of Rotor syndrome in brothers who were a 13 year-old boy and an 11 year-old boy, respectively. They presented with icteric scleras for a few months. Their common laboratory characteristics were as follows: Direct bilirubin was more increased than indirect bilirubin, but aminotransferases were normal. Plasma indocyanine green (ICG) test revealed hepatic excretory defect: plasma ICG concentrations 15 minutes after intravenous injection were 80.45% and 78.28%, respectively. 99mTc-DISIDA Hepatobiliary scan showed that severely decreased hepatic extraction with mild cardiac blood pool, markedly delayed biliary excretion in both intra- & extra- hepatic bile ducts, delayed visualization of gall bladder, and markedly delayed intestinal biliary passage. Needle liver biopsy showed normal hepatic histology without pigmentation.

• The Korean Journal of Nuclear Medicine
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• v.29 no.4
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• pp.492-496
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• 1995

To evaluate the usefulness of hepatic uptake in neonatal jaundice, Tc-99m-DISIDA cholescintigraphy was reviewed for 13 infants with prolonged mired jaundice and no demonstrable excretion into bowel,even after 24hr. Five patients proved to have biliary atresia. The remainder had neonatal hepatitis. There was no distinct differentiation of the hepatic uptake of tracer at 5 and 10 minutes between biliary atresia and neonatal hepatitis. The consideration of hepatic uptake rate of the tracer is not useful in differentiating neonatal hepatitis from biliary atresia.

• The Korean Journal of Nuclear Medicine
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• v.5 no.1
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• pp.49-64
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• 1971

The radioactive $^{131}I$-rose bengal serial scintiphotography was performed in 62 patients with the hepatobiliary diseases and in 20 normal subjects. This approach permitted visualization of the hepatic uptake of $^{131}I$-rose bengal from the circulation and its excretion into the biliary trees and the intestines. In some of these patients, gallbladder function was examined, using eggs as a gallbladder constrictor. The time of maximum hepatic uptake was well correlated to the conventional biochemical liver function tests. In addition to $^{131}I$-rose bengal scintiphotography, $^{198}Au$-colloid scintiphotography was also performed to make comparison of these two tests. The results obtained were as follows: 1. In normal subjects, the maximum hepatic uptake of $^{131}I$-rose bengal occurred at $23{\pm}2.9$ minutes, the initial hepatic excretion at $34{\pm}5.1$ minutes, the visualization of the gallbladder at $29{\pm}5.7$ minutes and the intestinal visualization at $54{\pm}25.8$ minutes. The radioactivity in the gallbladder decreased to $10.7{\pm}5.0%$ one hour after the ingestion of eggs. 2. In the patients with cirrhosis of the liver, there was a delayed and decreased hepatic uptake. The maximun hepatic upake occurred at $43{\pm}12.9$ minutes. The differences in the results of uptake between the cirrhotic and the normal group were statistically significant. The initial hepatic excretion occurred at $60{\pm}18.5$ minutes and had tendency of delaying compared with the normal controls. The gallbladder was visualized in 13 of 16 cases (81%) and its visualization occurred at $49{\pm}14.6$ minutes with a tendency to be delayed compared with the normal controls. The intestinal visualization occurred at $63{\pm}15.8$ minutes and its delaying tendency was somewhat more prominent. 3. In patients with hepatitis, the maximum hepatic uptake occurred at $59{\pm}21.4$ minutes and was significantly delayed. The initial hepatic excretion occurred at $82{\pm}34.3$ minutes and the results revealed a delaying tendency. The gallbladder was visualized in 15 of 20 cases (75%) at $57{\pm}18.7$ minutes, which was significantly delayed. The Intestinal visualization was noted in all cases with marked delay. 4. In patients with obstructive jaundice, the maximum hepatic uptake was noted at $83{\pm}14.7$ minutes, showing the most significant delay. The hepatic excretion into biliary trees and intestines was not entirely noted in all cases except the only one case with gallbladder visualization. 5. In patients with cholelithiasis, the maximum hepatic upake and the initial hepatic excretion were slightly delayed with mean times of $39{\pm}11.2\;and\;48{\pm}17.1$ minutes respectively. The visualization of the gallbladder was demonstrated in 10 of 17 cases (59%) and occurred at $52{\pm}25.6$ minutes with a slight delay. The intestinal visualization occurred at $67{\pm}47.7$ minutes and was slightly delayed. $^{131}I$-rose bengal in the gallbladder remained high, $49.3{\pm}21.3%$, which suggested quantitatively decreased power of gallbladder constriction. 6. The time of the maximum hepetic uptake was correlated well to BSP retention and serum alkaline phosphatase ativity. However, the maximum hepatic uptake had no definite correlation with serum albumin, serum globulin, TTT, serum cholesterol, SGPT or SGOT. 7. In the diagnosis of the hepatobiliary diseases with jaundice, $^{131}I$-rose bengel serial scintiphotography has proved to be more useful than $^{198}Au$-colloid scintiphotography. With these results, it could be justified that $^{131}I$-rose bengal scintiphotography is an excellent diagnostic aid for dynamic hepatobiliary function studies in the clinical practice.

• Korean Journal of Clinical Pharmacy
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• v.3 no.2
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• pp.163-168
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• 1993

The influence of cimetidine pretreatment(100mg/kg, single i.p.) on the hepatic blood flow was investigated using pharmacokinetic parameters of indocyanine green(ICG) in the rat on the basis of hepacc perfusion-limited model. ICG(1mg/kg) was respectively administered via femoral and portal vein to the control and to the cimetidine-pretreated rats. The rate constant K12, K20 and the systemic clearance(CLt) of ICG were significantly(p<0.05) decreased ill the cimetidine-pretrea-to(B rats, but no significant diffirences were observed in hematocrit and liver weight. The biliary excretion rates of ICG were also decreased regardless of the route of administration in the cimetidine-pretreated rats. And also the hepatic blood flow in rats was decreased about $16\%$ by cimetidine. It may be concluded that the decreased hepatic blood flow with cimetidine mainly contributed to the decreased hepatic uptake and the decreased systemic clearance of ICG.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.4
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• pp.511-513
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• 2004

Effects of the dietary supplementation of Codonopsis lanceolata root on triglyceride and cholesterol levels in the serum, liver, breast muscle and bile in male Cobb$\times$Cobb chicks were investigated. The chicks (15-42 days old) were fed diets supplemented with 0, 0.25 and 0.5% Codonopsis lanceolata root. No differences were observed in body weight, feed conversion ratio, gall bladder weight or abdominal fat deposition among the control group and the two treatment groups. Liver weights were higher in chicks fed a 0.5% Codonopsis lanceolata diet than in those fed the control diet (p<0.05). However, serum levels of both glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were not different among the three groups. Broiler chicks fed either 0.25% or 0.5% dietary Codonopsis lanceolata root showed decreased serum levels of triglyceride, total cholesterol and low density lipoprotein cholesterol compared to the control group (p<0.05). Supplementation with either 0.25% or 0.5% dietary Codonopsis lanceolata root decreased the triglyceride and total cholesterol levels in liver and breast muscle compared to the control group (p<0.05). Biliary cholesterol increased by 15% in chicks fed 0.5% dietary Codonopsis lanceolata root, suggesting that the biliary excretion of cholesterol had been elevated by dietary Codonopsis lanceolata root (p<0.05). In conclusion, these results indicate that dietary Codonopsis lanceolata root can decrease triglyceride and cholesterol levels in the serum, liver and breast muscle of broilers.