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[Diagnostic significance of determining gamma-glutamyltranspeptidase and alkaline phosphatase activity in blood serum and bile in viral hepatitis B and in bile duct inflammation].

Diagnostic importance of gamma-glutamyl transpeptidase and alkaline phosphatase activities estimation in bile was demonstrated during inflammation of biliary ducts and gallbladder. Activation of these enzymes in B-bile in cholecystitis and in B- and C-bile--in cholecystocholangitis enabled to perform topical diagnosis. Correlation between the enzymatic activity in bile and blood allowed to diagnose acute viral hepatitis B and its combination with inflammation of biliary cuts.

Acute Disease↗

Histological analysis of liver parenchyma and choledochal wall, and external diameter and intraluminal pressure of the common bile duct in controls and patients with common bile duct stones with and without acute suppurative cholangitis.

The purpose of this prospective controlled study was to determine the changes in intraluminal pressure and diameter of the common bile duct in a total of 121 bile patients with choledocholithiasis, and the consequences of these alterations for choledochal mucosa and liver histology. In fact, the reflux of bacteria from the obstructed biliary tract into the bloodstream is responsible for producing the clinical syndrome of acute suppurative cholangitis. Group I (26 patients) served as controls, Group II (50) had choledocholithiasis with clear green bile, and Group III (45) were patients with acute suppurative cholangitis with pus in the biliary tract. Ultrasonography revealed gallstones in all the patients. The external diameter of the common bile duct in patients with choledocholithiasis and acute suppurative cholangitis was significantly greater than in those of the other groups. Patients with acute suppurative cholangitis also had a higher intraluminal pressure than those of Groups I or II.

Acute Disease↗

[Reconstruction of the bile ducts after complex injury of the gallbladder and the bile ducts after blunt abdominal trauma in a dog].

Solitary injuries of the gall bladder and the bile ducts are very seldom and dangerous. The prognosis of such injuries depends of the delay until the diagnosis is made and of the method of the bile ducts reconstruction. Several methods have been described; we present a method of reconstruction of the bile ducts after cholecystectomy with a bilio-digestive anastomosis with following advantages: no tension on the anastomosis, possibility of several anastomoses on the same jejunal loop, exact adaptation of the mucosa and elimination of the reflux of intestinal contain in the bile ducts with a long and isoperistaltic Roux-loop.

Animals↗

Bile peritonitis from a cholecystohepatic bile ductule: an unusual complication of cholecystectomy.

A case is presented of postoperative bile peritonitis from an accessory cholecystohepatic bile ductule after cholecystectomy for acute cholecystitis. Accessory bile ductules (ducts of Luschka) are occasionally encountered in the gallbladder fossa but do not drain directly into the gallbladder fundus. Nevertheless, they may be injured during surgery and may go unrecognized. When recognized intraoperatively, ligation is acceptable; however, when they are actively leaking bile and are greater than 2 mm in diameter, repair of injured cholecystohepatic ducts may be indicated. This case serves to reemphasize one argument for the routine placement of drains after cholecystectomy for acute cholecystitis.

Bile Ducts, Intrahepatic↗

Individual serum bile acid concentrations in normo- and hyperlipoproteinemia as determined by mass fragmentography: relation to bile acid pool size.

Combined gas-liquid chromatography-mass spectrometry with specific ion monitoring (mass fragmentography) has been used for assay of cholic acic (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) in human serum. Deuterium-labeled C and D were used as internal standards. The relative standard deviation of duplicate samples was 3, 4, and 7% for C, CD, and D, respectively. The variation within the same individual in the fasting state was small, while the day-to-day variation was greater, especially for the dihydroxy bile acids. In normal control subjects (n = 24), the fasting serum concentration of C averaged 184 +/- 24 ng/ml (mean +/- SEM), and that of CD and D 526 +/- 62 and 407 +/- 44 ng/ml, respectively. Patients with type IIa hyperlipoproteinemia (n = 32) displayed low values of serum bile acids, with a C concentration of 121 +/- 11 ng/ml (P less than 0.01 vs. controls). A similar pattern was seen in patients with a type IIb lipoprotein pattern (n = 10). Subjects with type IV hyperlipoproteinemia (n = 32) showed serum bile acid levels within the normal limits. No relationship to age, sex, or body weight was seen in any of the patient subgroups. Bile acid kinetics were determined with an isotope dilution technique using 14C-labeled C and CD under steady state conditions in control subjects and patients with type IIa and type IV hyperlipoproteinemia. The serum concentration of C correlated significantly to its pool size in control subjects and in patients with type IIa hyperlipoproteinemia but not in patients with type IV. The serum level of CD was not related to CD pool size in any of the subgroups. The data obtained are discussed in relation to present concepts of the enterohepatic circulation. It is suggested that the intestinal content of C in the fasting state is proportional to the total C pool size. The possibility of a defective intestinal uptake of C in some patients with type IV hyperlipoproteinemia is raised.

Bile Acids and Salts↗

Enzymatic determination of faecal bile acids. A simple test for bile acid malabsorption.

A simple method for total faecal bile acid (FBA) determination was carried out. This test involves a 72 hour stool collection, homogenization and FBA determination by means of an enzymatic-fluorimetric method (3 -Hydroxysteroid-dehydrogenase). The reliability of this test was discussed. FBA levels were tested in twelve healthy volunteers. In addition, two patients with bile acid malabsorption syndrome due to terminal ileitis and one patient with cholegenic diarrhoea caused by biliocolonic fistula were examined. The mean +/- SD of FBA values in healthy subjects was 0.49 +/- 0.3 g/72 hours. However, all patients tested show a marked increase of FBA levels. In conclusion the present method for bile acid determination in the faeces seems to be a useful tool in the diagnosis of bile acid malabsorption syndrome and in cholegenic diarrhoea.

3-Hydroxysteroid Dehydrogenases↗

Regression of bile duct damage and bile duct proliferation in the non-rearterialized transplanted rat liver is associated with spontaneous graft rearterialization.

The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 +/- 1.29; 1 week, 20.44 +/- 1.76; 4 weeks, 15.46 +/- 3.14), bile ducts/ductules (1 week, 4.88 +/- 1.07; 4 weeks, 7.20 +/- 2.42), and connective tissue (4 weeks, 4.02 +/- 1.66; 6 months, 14.94 +/- 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 +/- 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 +/- 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher (P < .02) than control (0.25 mL/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison study between fasting total serum bile acid and post prandial bile acid in hepatic diseases: a preliminary study.

Fasting bile acid, two-hour post prandial bile acid and other liver function tests (Bili, AST, ALT, ALB, Glob, ALP) were measured in 22 normal and 28 liver diseased patients. In normal volunteers, the mean value of fasting total serum bile acid (FTBA) and postprandial serum bile acid (PTBA) were 3.08 mumole/L (S.D. 1.65) range 0.21-6.26 mumol/L, and 8.07 mumole/L (S.D. 2.99) range 4.06-15.65 mumole/L. Comparison between FTBA, PTBA and other liver function tests in various liver diseases from this study the PTBA was not statistically significant superior to FTBA. Therefore, it is not necessary to do the PTBA at this time until more data is available.

Bile Acids and Salts↗

Mechanism of ketoconazole-induced elevation of individual serum bile acids in the rat: relationship to the effect of ketoconazole on bile acid uptake by isolated hepatocytes.

Ketoconazole, an imidazole derivative, has been implicated in a number of hepatic dysfunctions. The aim of the present study was to determine the effect of in vivo treatment of rats with ketoconazole on individual serum bile acid levels and the in vitro effects of ketoconazole on the hepatocellular uptake of two bile acids and two other model substrates transported by liver cells. Male Sprague-Dawley rats were treated i.p. with a single injection of ketoconazole of 25 mg/kg (n = 4) or 50 mg/kg (n = 4); the control group (n = 4) received the vehicle only at a dose of 1 ml/kg. Blood samples were collected at 4 hr after dosing. With high-performance liquid chromatography, the serum was assayed for individual serum bile acids. At the higher dose, ketoconazole produced a significant increase in serum levels of cholic acid, taurocholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid and taurochenodeoxycholic acid compared with the control group (P < .05). Cholic acid, taurocholic acid and chenodeoxycholic acid levels were significantly raised in rats treated with the lower dose. In vitro, ketoconazole strongly inhibited the hepatocellular uptake of [14C]cholic acid, [14C]taurocholic acid and [3H]ouabain but not [14C]2-aminoisobutyric acid, which indicated that the effect is relatively specific. The kinetics of inhibition were competitive and the inhibition constants for taurocholate and ouabain were 6 and 1 microM, respectively. Ketoconazole inhibited by both Na(+)-dependent taurocholate uptake and stimulated bile acid countertransport of preloaded hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Minimal bile acid malabsorption and normal bile acid breath tests in cystic fibrosis and acquired pancreatic insufficiency.

This study was undertaken because of reports of a marked increase in fecal bile acid excretion by children with cystic fibrosis. We attempted to confirm this finding by performing [1-14C]cholylglycine breath tests and by measuring fecal bile acid and fat excretion in patients with cystic fibrosis and acquired pancreatic insufficiency. Studies were done when patients were taking pancreatic enzymes (Cotazym) and also without medication. 14CO2 excretion in breath was normal in patients with acquired pancreatic insufficiency and even lower in cystic fibrosis, both with and without Cotazym therapy. Fecal bile acid excretion was slightly elevated in both groups without Cotazym and became normal with Cotazym in patients with acquired pancreatic insufficiency. Steatorrhea was present in both patient groups and improved during Cotazym therapy. Bile acid malabsorption in cystic fibrosis and acquired pancreatic insufficiency is minimal and probably not clinically important.

Adult↗

Value of routine intraoperative cholangiography in detecting aberrant bile ducts and bile duct injuries during laparoscopic cholecystectomy.

A prospective study was performed to determine the frequency and type of bile duct abnormalities, and to determine whether routine use of intraoperative cholangiography during laparoscopic cholecystectomy might aid in the prevention of bile duct injuries. Overall, anatomical aberrations of the bile ducts were found in 98 (19 per cent) of 513 cholangiograms. The most common anomalies were at the hepatic confluence and constituted different types of right hepatic subsegmental ducts draining separately into the biliary tree (n = 43, 8.4 per cent), either close to the cystic duct or directly into the cystic duct. Three bile duct injuries (0.5 per cent) occurred during the study period. These results show that routine intraoperative cholangiography is feasible and provides valuable information about the anatomy of the biliary tract, thereby improving the safety of laparoscopic cholecystectomy. If an injury to the biliary tract occurs early during operation, the cholangiogram allows the surgeon to detect the injury, to make a prompt repair and thereby reduce the morbidity associated with a delayed diagnosis. Routine use of intraoperative cholangiography is strongly recommended.

Acute Disease↗

Comparison of bile acid binding to sinusoidal and bile canalicular membranes isolated from rat liver.

Simon et al. (J. Clin. Invest., 70 (1982) 401) studied cholate binding to crude liver plasma membrane vesicles and suggested that the binding may represent mainly the binding to the receptor (carrier) on the canalicular membrane. This hypothesis was supported by finding a good correlation between the number of cholate binding sites on liver plasma membrane and the maximal rate of biliary secretion (Tm) for taurocholate. We studied bile acid binding to sinusoidal and canalicular membrane vesicles isolated from rat liver by a rapid filtration technique. Scatchard analysis of the saturation kinetics showed both [3H]cholate and [3H]chenodeoxycholate bind to two classes of binding site on each membrane. However, little difference was observed between the binding to sinusoidal and canalicular membrane vesicles for each bile acid (cholate, Kd1 = 10.4 and 19.8 microM, n1 = 31.0 23.6 pmol/mg protein, Kd2 = 1.32 and 1.73 mM, n2 = 13.1 and 23.4 nmol/mg protein; and chenodeoxycholate, Kd1 = 0.207 and 0.328 microM, n1 = 36.7 and 27.4 pmol/mg protein, Kd2 = 1.16 and 2.26 mM, and n2 = 20.6 and 24.2 nmol/mg protein; numbers show the mean values sinusoidal and canalicular membrane vesicles, respectively). Chenodeoxycholate binding to sinusoidal membrane vesicles was markedly inhibited by cholate but not by Rose bengal, an organic anion dye. These studies indicate that both membranes (sinusoidal and canalicular membrane vesicles) have two kinds of binding site for bile acids, although no clear difference in the binding properties was observed between the two membranes. Consequently, the cholate binding Simon detected may represent the binding not only to canalicular membrane vesicles but also to sinusoidal membrane vesicles.

Animals↗

Bile acid feeding induces cholangiocyte proliferation and secretion: evidence for bile acid-regulated ductal secretion.

BACKGROUND & AIMS: We have shown that taurocholate (TC) and taurolithocholate (TLC) interact in vitro with normal cholangiocytes, increasing DNA synthesis, secretin receptor (SR) gene expression, and adenosine 3',5'-cyclic monophosphate (cAMP) synthesis. To further extend these in vitro studies, we tested the hypothesis that bile acids (BAs) directly stimulate cholangiocyte proliferation and secretion in vivo. METHODS: After feeding with TC or TLC (1% for 1-4 weeks), we assessed the following in vivo: (1) ductal proliferation by both morphometry and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and measurement of [3H]thymidine incorporation; and (2) the effect of secretin on bile secretion and bicarbonate secretion in vivo. Genetic expression of H3-histone and SR and intracellular cAMP levels were measured in isolated cholangiocytes. RESULTS: After BA feeding, there was an increased number of PCNA-positive cholangiocytes and an increased number of ducts compared with control rats. [3H]Thymidine incorporation, absent in control cholangiocytes, was increased in cholangiocytes from BA-fed rats. In BA-fed rats, there was increased SR gene expression (approximately 2.5-fold) and secretin-induced cAMP levels (approximately 3.0-fold) in cholangiocytes, which was associated with de novo secretin-stimulated bile flow and bicarbonate secretion. CONCLUSIONS: These data indicate that elevated BA levels stimulate ductal secretion and cholangiocyte proliferation.

Animals↗

[Determination of index of the transcutaneous electrostimulation effect on the liver and bile ducts based on micellar structure and lithogenicity of bile in patients with the exterior drainage of the common duct].

Kept under clinical observation were 78 patients under common bile duct drainage for mechanical jaundice of the nontumor genesis. In all patients, micellarity and lithogenicity of the hepatic bile (fraction "C") were studied postoperatively, with an individual selection having been carried out of the index of transcutaneous electrostimulation effect on the hepatobilliary system. An effective modality has been elaborated for treatment and prophylaxis of hepatic insufficiency, correction of micellarity and lithogenicity of bile in the early postoperative period in patients with mechanical jaundice of the nontumor genesis, that can be recommended for use in the health care practice.

Bile↗

[Bile acids in the process of canalicular bile formation].

This review summarizes the current knowledge of the role of bile acid in the canalicular bile secretion: its membrane transport in hepatocyte; molecular mechanisms and pathways of its regulatory effects on membrane transporters; the role of its hydrophobicity in membrane transporter regulation; hepatocyte necrosis and apoptosis at cholestasis induced by hydrophobic bile acids; the possible mechanisms of protective effects of ursodeoxycholic acid in cholestatic impairment of the liver.

Animals↗

The infiltration of bile duct carcinoma along the bile duct wall.

The infiltration of extrahepatic bile duct carcinoma along the bile duct wall was studied in 29 resection cases. Histologically, spreading took place by mucosal infiltration in one case, mucosal and transmural in three, and transmural in 25. The average microscopic infiltrating distance from the gross margin of the tumor (ID) was 16.8 mm towards the liver, 6.5 mm towards the duodenum. The ID of the infiltrating type in the gross appearance of the tumor and the ID of the tubular adenocarcinoma in the histological cellular type tended to be long. The severer the invasion of the carcinoma to the lymphatic vessels, the longer the ID. The result indicated that most bile duct carcinomas have a tendency for long infiltration along the wall. An exceedingly wide resection involving hepatectomy is advisable for treatment.

Adenoma, Bile Duct↗

Morphologic structure of bile canaliculi after bile duct ligation in the rat. A time-course study.

Changes in bile canaliculi (BCs) after bile duct ligation (BDL) are heterogeneous throughout the liver lobule. Male Wistar rats were killed five hours, 20 hours, four days, or eight days after BDL, and BCs were counted according to their shape (1, normal; 2, elongated with microvilli; 3, dilated, devoid of microvilli; or 4, filled with blebs). Compared with controls, the number of BCs doubled after BDL, less than 10% of the BCs were of type 3. As time elapsed, the ratios of types 3 and 4 increased; however, their combined ratio always was below 50%, and remained stable between days 4 and 8. Bilirubin levels peaked between days 2 and 4, then remained stable. The heterogeneous changes in BCs could be explained by the heterogeneous tightness of tight junctions. Decrease in cell size and increase in the size of BC branches could favor contact between bile and blood.

Aged↗