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PubMedDate not supplied

Liver functional analysis by total bile acid level of C-tube bile after hepatectomy.

BACKGROUND/AIMS: In order to predict liver failure which can lead to death after hepatectomy, a sensitive and specific indicator is needed for liver function. Transcystic duct tube (C-tube) drainage after hepatectomy is thought to be useful in decreasing postoperative complications. METHODOLOGY: Conventional serum liver function tests, and total bile acid (TBA) and total bilirubin (T.Bil) concentration levels of bile from a C-tube in 11 hepatectomized patients who underwent C-tube drainage were compared on postoperative day 2 (Day 2) and postoperative day 7 (Day 7). RESULTS: When serum liver function tests were improving between Day 2 and Day 7, the TBA concentration in bile was increasing in contrast to a decreasing T.Bil concentration. On Day 7, TBA concentrations in the bile in patients without liver cirrhosis or with low ICGR15 values were higher than those in patients with liver cirrhosis or with high ICGR15 values, whereas there were no significant differences between T.Bil bile concentrations in the two groups on Day 7, that is, the measurement of TBA bile concentration might be a faster and more accurate parameter for liver function than that of T.Bil bile concentration. CONCLUSIONS: TBA bile concentration obtained from C-tubes was a useful liver function indicator after hepatectomy.

Aged↗
PubMed1990

Relationship between the newly identified bile acid binder and bile acid oxidoreductases in human liver.

Gel filtration fractions of human hepatic cytosol obtained from an autopsy liver were examined for elution of bile acid oxidoreductases. Several enzymes including 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 3-ketosteroid reductase, and dihydrodiol dehydrogenase eluted mainly in the 30,000-40,000 Mr fractions known to contain the newly identified bile acid binder (Stolz, A., Sugiyama, Y., Kuhlenkamp, J., and Kaplowitz, N. (1984) FEBS Lett. 177, 31-35). These enzyme activities could be resolved into six peaks of dihydrodiol dehydrogenase activity on chromatofocusing, some of which also had oxidoreductase activity with bile acids. Using equilibrium dialysis, the major lithocholate-binding activity was found to coelute with 3 beta-HSD, completely separate from 3 alpha-HSD. Reexamination of the surgical liver specimen originally used to purify the bile acid binder confirmed these results. The peak fraction from chromatofocusing, which exhibited the bulk of binding activity with bile acids, had 3 beta-HSD activity, whereas other fractions had 3 alpha-HSD. Anti-serum to the previously purified binder identified a single 36-kDa protein in both liver specimens and exclusively in the chromatofocusing fractions containing both the binding and 3 beta-HSD activity. However, upon further purification of the binder from this fraction, 3 beta-HSD activity was separated from the binder, but the homogeneous protein retained dihydrodiol dehydrogenase activity. Thus, in contrast to the rat in which the major bile acid binder is identical to 3 alpha-HSD, in human liver the bile acid binder is distinct from 3 alpha-HSD and copurifies with a different oxidoreductase that has dihydrodiol dehydrogenase activity but no activity with bile acids.

3-Hydroxysteroid Dehydrogenases↗
PubMed1987

Taurine increases bile acid pool size and reduces bile saturation index in the hamster.

There is evidence that increased availability of taurine enhances the proportion of taurine-conjugated bile acids in bile. To explore the possibility that taurine treatment could also influence hepatic cholesterol and bile acid metabolism, we fed female hamsters for 1 week and measured both the biliary lipid content and the microsomal level of the rate-limiting enzymes of cholesterol and bile acid synthesis. In these animals the cholesterol 7 alpha-hydroxylase activity was significantly greater in respect to controls (P less than 0.05). The total HMG-CoA reductase activity, as well as that of the active form, was similarly increased. The stimulation of 7 alpha-hydroxycholesterol synthesis was associated with an expansion of the bile acid pool size in taurine-fed animals. Taurine feeding was observed to induce an increase in bile flow as well as in the rate of excretion of bile acids, whereas the secretion rate of cholesterol in bile was decreased. As a consequence, the saturation index was significantly lower in taurine-fed animals (P less than 0.05). The possible mechanisms through which taurine exhibits the modification of the enzyme activities and of the biliary lipid composition are discussed.

Animals↗
PubMed1980

Bile acids and bile alcohols of bullfrog.

Gallbladder bile of the bullfrog, Rana cetesbeiana was found to contain a number of minor bile acids and bile alcohols in unconjugated forms. The following bile acids and bile alcohols were identified by combined gas-liquid chromatography-mass spectrometry: cholic acid, allocholic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-24-methyl-5 beta-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 alpha-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 alpha-cholestan-27-oic acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholestan-27-oic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 alpha-cholestan-24-one, and 3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one. These minor constituents of the bile may represent intermediates in the biosynthetic pathway of bile acids and bile alcohols in the bullfrog.

Animals↗
PubMed1980

Metabolism of individual molecular species of phosphatidylcholine in the liver subcellular membranes and bile. Origin of bile phosphatidylcholine.

Membrane fractions, particularly microsomes and bile canalicular membranes, isolated from rat liver were examined, in order to elucidate the site of a subpool of phosphatidylcholine destined for bile in the liver cell which was demonstrated in a previous paper (Kawamoto, T., Okano, G. and Akino, T. (1980) Biochim. Biophys. Acta 619, 20--34). 1. The bile canalicular membranes isolated from rat liver were not contaminated by other membranes when examined by membrane marker enzymes, and showed typical membrane structure, when examined by electron microscopy. The activity of DCPcholine : diacylglycerol cholinephosphotransferase was almost absent from the bile canalicular membranes and acyl CoA : 1-acyl-sn-glycero-3-phosphocholine acyltransferase activity was 17% of that found in the microsomes. 2. The molecular class composition of phosphatidylcholine was similar in the bile canalicular membranes and microsomes. The proportion of palmitoyl and stearoyl species in the major molecular classes was also similar in both membrane types. 3. In the in vivo experiments with [2-(3H)]glycerol, the specific radioactivity of phosphatidylcholine and its species such as palmitoyl-linoleoyl species in the bile canalicular membranes were significantly higher than that in other membranes. When compared with the specific radioactivity of phosphatidylcholine species in bile that in the bile canalicular membranes was also distinctly higher.

Animals↗
PubMed1979

[Bile acids in duodenal juice of infants and children. Normal values, lognormal distribution, and age-dependence of the total quantity and the distribution of bile acids (author's transl)].

43 gastroenterologically healthy infants and children were investigated during the basic secretion period and after the injection of secretin/pankreozymin in order to establish the total quantity and also the distribution of the secreted bile acids. The total concentration and quantity were enzymatically determined while column and thin-layer chromatography were utilized to separate the bile into 34 different bile acids. Quantified results for bile salts were read directly from the thin-layer sheet with the help of a Chromatogram-Spectrophotometer Zeiss KM 3. While the total quantity of bile acids was found to be independent of age, the composition of bile changed during the first years of life. The percentage of cholic acids decreased from 50% in infants to 35% in older children. At the same time, deoxycholic acids went up from 3% to 13%, and chenodeoxycholic acids increased by 5%. The percentage of glycine and taurine conjugated bile salts, however, remained constant after to the second month of life, the former at 58% and the latter at 35%. In comparison, rather small amounts of unconjugated acids and sulfates were secreted, 0,5% and 6% respectively. The latter were distributed in the same sequence as the nonsulfated bile acids. Lithocholic acids (2,6%) and ursodeoxycholic acids (4,3%) were regularly present in the intestinal secretion.

Age Factors↗
PubMed1995

[Conjugated bile acid profiles in serum, urine, and bile of patients with primary biliary cirrhosis under the ursodeoxycholic acid treatment].

We studied the conjugated bile acid profiles (sulfate, glucuronide, and nonsulfate-nonglucuronide) in serum, urine, and bile of 12 patients with primary biliary cirrhosis (PBC) before and under the ursodeoxycholic acid therapy (UDCA, 600mg/day, 6-8 months). Serum total bile acid concentration in those patients without the UDCA therapy was several times higher than those of healthy volunteers, and the percentage of sulfate to total bile acid was 24.8%. After the UDCA therapy, serum total bile acid concentration increased making a progression of Scheuer's stage. In patients with stage I-III, the percentage of sulfate to total was 13.7-65.0% (32.5%, mean), and that of glucuronide to total was 6.6-43.3% (24.0%). Then, the sum of sulfate and glucuronide conjugates was more than 50% to total. Although in patients with stage IV, serum total bile acid level rose markedly, the percentages of sulfate and glucuronide highly reduced. In urine of patients with stage I-III, a large amount of sulfate and glucuronide was found and the percentage of both conjugates was more than 65% of total. On the other hand, sulfate and glucuronide conjugates were only minor component in bile. Based on these data, we might be led to the following conclusion: (1) in patients with PBC (stage I-III), sulfated conjugates of serum bile acid are not minor component, (2) the increased UDCA in serum of patients with PBC during the UDCA treatment might be more easily extracted into urine as sulfate and glucuronide UDCA.

Aged↗
PubMed1994

A unique rat model of bile ductular hyperplasia in which liver is almost totally replaced with well-differentiated bile ductules.

A novel rat model was developed in which furan combined in a unique synergistic manner with bile duct ligation to induce replacement of most of liver with well-differentiated hyperplastic bile ductules. Multiple tissue sections of liver from Fischer 344 male rats first subjected to a bile duct ligation and 1 week later given furan by gavage at 45 mg/kg body weight, once a day, five times weekly for 5 to 6 weeks, exhibited a mean percent of bile ductule tissue per total liver section area of 72.6 +/- 16.3% compared to control values of 20.0 +/- 4.2% for bile duct-ligated rats that received corn oil by gavage instead of furan and 11.9 +/- 3.1% for rats that were given a sham operation followed by furan. This dramatic difference was also reflected by the very high mean gamma-glutamyl transpeptidase specific activity of liver homogenates from the bile duct-ligated/furan-treated rats, which was approximately 8 x 10(3) nmoles p-nitroaniline/mg protein/hour versus values of approximately 2 x 10(3) for bile duct-ligated/corn oil control, approximately 1 x 10(3) for sham-operated/furan-treated control, and 44.9 for untreated rat. The data presented support a potentially powerful experimental model for investigating bile ductular cell functions, differentiation, and proliferation.

Animals↗
PubMed1993

Resolution of liver biopsy alterations in three siblings with bile acid treatment of an inborn error of bile acid metabolism (delta 4-3-oxosteroid 5 beta-reductase deficiency).

Identical male twins and their brother, cholestatic from birth, with delta 4-3-oxosteroid 5 beta-reductase deficiency, were studied by serial liver biopsy. Spectrometry documented defective primary bile acid synthesis and markedly increased levels of atypical oxo and allo bile acids in urine and serum. Hepatocellular cholestasis and giant-cell transformation resolved in parallel with clinical and biochemical recovery during oral bile acid administration. In the twins, portal fibrosis stabilized at a mild level; they are well as 5-yr-olds at this writing. Follow-up biopsy in their brother at 8 mo was normal, and he is doing well at 3 yr of age. Hepatic ultrastructural alterations in all three were characterized by abnormalities of bile canaliculi including small bile plugs, diverticulae and latticelike elaborations of hepatocellular membranes adjacent to bile canaliculi that were shown to have resolved completely on subsequent biopsies. Eight additional cases have been detected on urine screening; only two of these patients have survived, on bile acid therapy. Early diagnosis and treatment improves the prognosis of this otherwise lethal inborn error of bile acid synthesis.

Bile Acids and Salts↗
PubMed1992

A simple method for bile duct anastomosis and interval bile collection in the liver-transplanted rat.

A mini T-tube is introduced for the bile duct anastomosis of rat liver transplantation as well as interval bile collection. The validity of the T-tube was evaluated in 14 liver-transplanted rats and compared to 14 rats using traditional stent for bile duct anastomosis. Changes of biliary tree after the T-tube anastomosis were examined by T-tube cholangiography on sample rats at 4 days and at 4 months after liver grafting. Additionally, bile volumes and rates of bile salt secretion were compared in the continuously flowing cannula and the chronic T-tube fistula in normal rats. The results show that the mini T-tube facilitates bile duct anastomosis and study of bile secretion after liver transplantation in rats without increase in surgical difficulty or interference of biliary enterohepatic circulation.

Anastomosis, Surgical↗
PubMed1999

Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats.

BACKGROUND & AIMS: Dihydroxy bile acids induce a bicarbonate-rich hypercholeresis when secreted into canalicular bile in unconjugated form; the mechanism is cholehepatic shunting. The aim of this study was to identify a xenobiotic that induces hypercholeresis by a similar mechanism. METHODS: Five organic acids (sulindac, ibuprofen, ketoprofen, diclofenac, and norfloxacin) were infused into rats with biliary fistulas. Biliary recovery, bile flow, and biliary bicarbonate were analyzed. Sulindac transport was further characterized using Tr(-) rats (deficient in mrp2, a canalicular transporter for organic anions), the isolated perfused rat liver, and hepatocyte membrane fractions. RESULTS: In biliary fistula rats, sulindac was recovered in bile in unconjugated form and induced hypercholeresis of canalicular origin. Other compounds underwent glucuronidation and were not hypercholeretic. In the isolated liver, sulindac had delayed biliary recovery and induced prolonged choleresis, consistent with a cholehepatic circulation. Sulindac was secreted normally in Tr(-) rats, indicating that its canalicular transport did not require mrp2. In the perfused liver, sulindac inhibited cholyltaurine uptake, and when coinfused with cholyltaurine, induced acute cholestasis. With both basolateral and canalicular membrane fractions, sulindac inhibited cholyltaurine transport competitively. CONCLUSIONS: Sulindac is secreted into bile in unconjugated form by a canalicular bile acid transporter and is absorbed by cholangiocytes, inducing hypercholeresis. At high flux rates, sulindac competitively inhibits canalicular bile salt transport; such inhibition may contribute to the propensity of sulindac to induce cholestasis in patients.

Animals↗
PubMed1999

Risk of bile duct carcinogenesis after excision of extrahepatic bile ducts in pancreaticobiliary maljunction.

BACKGROUND: A reflux of pancreatic juice into the biliary tract caused by pancreaticobiliary maljunction (PBM) has been considered important in the development of biliary tract carcinogenesis in choledochal cysts. We excised extrahepatic bile ducts in patients with choledochal cysts to terminate the reflux of pancreatic juice. We investigated whether this surgery could stop the development of the residual bile duct carcinoma. METHODS: Fifty-six patients with a diagnosis of PBM with choledochal dilatation underwent surgical excision of extrahepatic bile ducts. We applied a person-year method to compare the relative risks (observed number/expected number) of biliary tract carcinoma before and after surgery. RESULTS: In 3 patients, bile duct carcinoma developed in residual dilated segments 19 years 6 months, 8 years 8 months, and 2 years 5 months, respectively, after surgery. Although the relative risk in the post-surgery group was slightly decreased by surgery, it was still high compared with that of the general population. CONCLUSIONS: The incidence of bile duct carcinoma is still high, even after excision of extrahepatic bile ducts in PBM patients with choledochal dilatation. For these patients, careful long-term follow-up is necessary, especially after operations that leave the dilated bile ducts, such as cases of Todani's type IV-A.

Adolescent↗
PubMedDate not supplied

Temporary bile diversion in cats with experimental extrahepatic bile duct obstruction.

The use of a cholecystostomy catheter for temporary bile diversion was investigated in four cats with experimentally induced extrahepatic bile duct obstruction. Eighteen days after ligation of the common bile duct, a 6.5 F accordion catheter was placed in the gallbladder with a 22 g Hawkins needle-guide system through a paracostal incision. Biochemical parameters and fasting serum bile acids were monitored for 16 days. There were significant decreases in mean total bilirubin, aspartate aminotransferase, and fasting serum bile acids within 72 hours of bile diversion, and in mean alanine aminotransferase within 96 hours. Attitude and appetite improved, and the catheter was tolerated well. Positive bile cultures developed in three cats. Histologic changes in the gallbladder included mucosal ulcerations, a mixed inflammatory cellular infiltration, and fibrosis of the submucosa.

Alanine Transaminase↗
PubMed1992

A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.

Imaging of biliary strictures may suggest malignancy but cytology can provide a tissue diagnosis. The aim of this study is to compare the diagnostic value of brush cytology and bile cytology. Thirty two patients (20 males, 12 females, median age 66 years, range 31-84) with biliary strictures at endoscopic retrograde cholangio pancreatography (24) or percutaneous transhepatic cholangiography (8) had bile cytology and brush cytology. Brushings were taken using a modified Geenan cytology brush (6 Fr gauge, Wilson Cook) passed alongside a guide wire placed through the stricture. Bile was aspirated after insertion of an internal/external catheter or an endoprosthesis. Bile and brushings were examined by one experienced cytologist (AD) and was reported as positive or negative for malignant cells. Twenty nine patients had malignant strictures. Sixteen were confirmed by histology and 13 had malignancy suggested by clinical follow up. Three patients had resection of histologically benign strictures. The overall sensitivity of brush cytology (17 of 29 positive, 59%) was significantly greater than bile cytology (seven of 29 positive, 24%) (p < 0.01) as was the diagnostic accuracy (63 v 31%, p < 0.01). None of the patients had positive bile cytology with negative brush cytology. There were no procedure related complications and the average sampling time once the guide wire had been inserted was less than five minutes. It is concluded that brush cytology is more sensitive than bile cytology and with the technique described is safe and rapid.

Adult↗
PubMed2001

Use of a fluorescent bile acid to enhance visualization of the biliary tract and bile leaks during laparoscopic surgery in rabbits.

BACKGROUND: We set out to determine whether intravenously administered cholylglycylaminofluorescein (CGF), a fluorescent bile acid, would enhance the visualization of the biliary tract and bile leaks in rabbits undergoing laparoscopic cholecystectomy (LC). METHODS: CGF was infused at doses of 1, 5, and 10 mg/kg b.w. Biliary recovery was determined spectrophotometrically (six rabbits). For LC (seven rabbits), a blue (fluorescein) filter was attached to the light source, and a fluorescein-emission filter was attached to the charge coupled device (CCD) camera. The biliary tract and bile leak (made by incising the gallbladder) was observed under standard and fluorescent illumination. RESULTS: Apple-green fluorescence appeared in 2 min and persisted for 30-60 min, enhancing visualization of bile duct anatomy as well as the bile leak. Biliary recovery of CGF at 90 min was high (86-96% of the infused dose). CONCLUSION: In rabbits, CGF is secreted quantitatively in bile, induces biliary fluorescence, and enhances visualization of the bile ducts and bile leaks when viewed with appropriate filters.

Animals↗
PubMed2005

Hepatoprotective bile acid 'ursodeoxycholic acid (UDCA)' Property and difference as bile acids.

Ursodeoxycholic acid (UDCA) is a bile acid, which is present in human bile at a low concentration of only 3% of total bile acids. It is a 7beta-hydroxy epimer of the primary bile acid chenodeoxycholic acid (CDCA). UDCA is isolated from the Chinese drug 'Yutan' a powder preparation derived from the dried bile of adult bears. For centuries, Yutan has been used in the treatment of hepatobiliary disorders. In Japan, it has also been in widespread use as a folk medicine from the mid-Edo period. In Japan, not only basic studies such as isolation, crystallization, definition of the chemical structure and establishment of the synthesis of UDCA have been conducted but clinical studies have been conducted. First reports on the effects of UDCA in patients with liver diseases came from Japan as early as 1961. In the 1970s, the first prospective study of patients with gallbladder stones treated with UDCA demonstrating gallstone dissolution was reported. In late 1980s, a number of controlled trials on the use of UDCA in primary biliary cirrhosis (PBC) were reported. Since then, a variety of clinical studies have shown the beneficial effect of UDCA in liver disease worldwide. To date, UDCA is utilized for the treatment of PBC for which it is the only drug approved by the U.S. Food and Drug Administration (FDA). In recent years, with the advent of molecular tools, the mechanisms of action of bile acids and UDCA have been investigated, and various bioactivities and pharmacological effects have been revealed. Based on the results of these studies, the bioactive substances in bile acids that are involved in digestive absorption may play important roles in signal transduction pathways. Furthermore, the mechanisms of action of UDCA is evidently involved. We reveal the physicochemical properties of UDCA as bile acid and overview the established pharmacological effects of UDCA from its metabolism. Furthermore, we overview the current investigations into the mechanism of action of UDCA in liver disease.

Journal Article↗
PubMed2002

Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump.

The bile salt export pump (BSEP or ABCB11) mediates the adenosine triphosphate-dependent transport of bile salts across the canalicular membrane of the hepatocyte. Mutations in the corresponding ABCB11 gene cause progressive familial intrahepatic cholestasis type 2. The aim of this study was to investigate the regulation of human ABCB11 gene transcription by bile salts. First, a 1.7-kilobase human ABCB11 promoter region was cloned. Sequence analysis for possible regulatory elements showed a farnesoid X receptor responsive element (FXRE) at position minus sign180. The farnesoid X receptor (FXR) functions as a heterodimer with the retinoid X receptor alpha (RXRalpha) and can be activated by the bile salt chenodeoxycholic acid (CDCA). Luciferase reporter gene assays showed that the ABCB11 promoter is positively controlled by FXR, RXRalpha, and bile salts in a concentration-dependent manner. Mutation of the FXRE strongly represses the FXR-dependent induction. Second, endogenous ABCB11 transcription regulation was studied in HepG2 cells, stably expressing the rat sodium-dependent taurocholate transporter (rNtcp) cells. ABCB11 expression was induced by adding bile salts to the culture medium, and this effect was maximized by combining it with cotransfection of rFxr and hRXRalpha. Reducing endogenous FXR levels using RNA interference fully repressed the bile salt-induced ABCB11 expression. In conclusion, these results show that FXR is required for the bile salt-dependent transcriptional control of the human ABCB11 gene and that the cellular amount of FXR is critical for the level of activation of ABCB11 transcription.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Dissolution of human cholesterol gallstones in bile salt/lecithin mixtures: effect of bile salt hydrophobicity and various pHs.

BACKGROUND: Unconjugated bile salts currently available for gallstone dissolution are poorly effective. We evaluated in vitro the litholytic potency of taurine-amidated bile salts against human cholesterol gallstones. METHODS: Seventy radiolucent gallstones with similar size and composition (cholesterol content, 70.1 +/- 0.9%) from a single patient were incubated in model biles composed of 100 mM of either taurochenodeoxycholate (TCDC), taurocholate (TC), taurohyodeoxycholate (THDC) or tauroursodeoxycholate (TUDC) and of 45 mM egg yolk lecithin in saline buffered with tris/HCl (at pHs 7 and 8) or phosphate (at pHs 4 and 6). Biles (total lipids, 10 g/dl; cholesterol saturation, 99%) were incubated at 37 degrees C for 40 days. Gallstones were periodically weighed and returned to the dissolution vials, and the biliary cholesterol concentration was monitored. RESULTS: Model biles remained optically clear during the initial 48 h of incubation. Then, biles containing THDC and TUDC, but not those with TC and TCDC, became progressively turbid until, after several days, a white precipitate surrounded the residual stone. Abundant liquid crytalline droplets were observed at polarizing microscopy in biles containing TUDC and THDC. Gallstone dissolution was closely related to cholesterol solubilization and decreased in the order TCDC > THDC > or = TC > TUDC, being highest at pH 8. At the physiologic pH of 7 THDC was more litholythic than TC. CONCLUSIONS: In vitro, the litholytic potency of bile salts on cholesterol gallstones primarily depends on their hydrophobicity. THDC is a new potential gallstone-dissolving agent, deserving in vivo studies.

Cholagogues and Choleretics↗