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At least 793 records · Page 44Linked to original sources
PubMed2005

Effects of hydrophobic and hydrophilic bile salts on gallstone growth and dissolution in model biles.

UNLABELLED: Cholesterol crystallization is a prerequisite for gallstone formation and growth, whereas dissolution of crystallized cholesterol forms the basis of nonsurgical therapy. Crystallization has been studied in detail, but dissolution mechanisms and effects of gallstones are largely unknown. METHODS: We evaluated gallstone growth or dissolution, cholesterol crystallization and lipid distribution into various phases, in model biles with low or intermediate phospholipid contents (crystal-containing left two-phase or central three-phase zones), and with high phospholipid or low cholesterol contents (crystal-free right two-phase or bottom one-phase zones). RESULTS: In model biles with added gallstones plotting in left two-phase and central three-phase zones, gallstone masses increased, whereas crystallization in the aqueous phase was less than without gallstones (P<0.001). In biles plotting in the right two-phase zone, gallstone masses decreased, depending on bile salt hydrophobicity (TUDC>TC>TCDC: P<0.001). In biles plotting in the bottom one-phase zone containing TC or TCDC, gallstone masses increased. In contrast, gallstone masses decreased in case of TUDC with preferential distribution of cholesterol into emerging vesicles. CONCLUSIONS: Our findings suggest competition between gallstone surface and surrounding aqueous phase for precipitation of cholesterol in crystal-containing zones. Different gallstone dissolution mechanisms may exist for TUDC and TCDC.

Bile↗
PubMed2001

Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump.

Biliary excretion of certain bile acids is mediated by multidrug resistance associated protein 2 (Mrp2) and the bile salt export pump (Bsep). In the present study, the transport properties of several bile acids were characterized in canalicular membrane vesicles (CMVs) isolated from Sprague--Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBR) whose Mrp2 function is hereditarily defective and in membrane vesicles isolated from Sf9 cells infected with recombinant baculovirus containing cDNAs encoding Mrp2 and Bsep. ATP-dependent uptake of [(3)H]taurochenodeoxycholate sulfate (TCDC-S) (K(m)=8.8 microM) and [(3)H]taurolithocholate sulfate (TLC-S) (K(m)=1.5 microM) was observed in CMVs from SD rats, but not from EHBR. In addition, ATP-dependent uptake of [(3)H]TLC-S (K(m)=3.9 microM) and [(3)H]taurocholate (TC) (K(m)=7.5 microM) was also observed in Mrp2- and Bsep-expressing Sf9 membrane vesicles, respectively. TCDC-S and TLC-S inhibited the ATP-dependent TC uptake into CMVs from SD rats with IC(50) values of 4.6 microM and 1.2 microM, respectively. In contrast, the corresponding values for Sf9 cells expressing Bsep were 59 and 62 microM, respectively, which were similar to those determined in CMVs from EHBR (68 and 33 microM, respectively). By co-expressing Mrp2 with Bsep in Sf9 cells, IC(50) values for membrane vesicles from these cells shifted to values comparable with those in CMVs from SD rats (4.6 and 1.2 microM). Moreover, in membrane vesicles where both Mrp2 and Bsep are co-expressed, preincubation with the sulfated bile acids potentiated their inhibitory effect on Bsep-mediated TC transport. These results can be accounted for by assuming that the sulfated bile acids trans-inhibit the Bsep-mediated transport of TC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1979

Daily fluctuation of cholestatic enzymes in bile and its relationship to the total bile salts concentration.

The activities of alkaline phosphatase (AP), gamma-glutamyl-transpeptidase and leucine aminopeptidase as well as the total bile salt concentration (Tbs) were measured in bile specimens collected spontaneously at 7 and 11 a.m. and 4 and 9 p.m. from the 3rd-9th postoperative day of 16 patients with T-tube insertion. The general trend for all cholestatic enzymes to increase or decrease was in some way related to the total bile salt concentration. The best correlation was found between AP and Tbs (r = 0.48). It is suggested that the enterohepatic circulation of bile salts may lead to the delivery of membrane-bound cholestatic enzymes into the bile canaliculi without damage to the hepatocyte.

Alkaline Phosphatase↗
PubMed1987

Bile duct carcinoma in a focal dilatation of the intrahepatic bile duct.

A 40 year old male with bile duct carcinoma arising in a localised dilatation of the intrahepatic bile duct is presented. The patient presented with recurrent upper abdominal pain, fever and jaundice. Computed tomography showed a localised duct dilatation and ultrasound clearly demonstrated a tumor mass arising within the bile duct. At surgery, papillary adenocarcinoma was confirmed. This case suggests that the tumour arose from the pre-existing cyst. A localised dilatation of the bile duct on computed tomography and ultrasound may harbour a bile duct carcinoma.

Adult↗
PubMed1997

Isolated hepatocyte couplets and bile duct units--novel preparations for the in vitro study of bile secretory function.

Studies of the mechanisms of bile formation have been facilitated by the development of in-vitro models that enable the transport functions of hepatocytes and bile duct epithelial cells to be analyzed in isolation. Isolated hepatocyte couplets represent a primary bile secretory unit that retain secretory polarity. Isolated bile duct units are intact polarized segments of interlobular bile duct segments. Both preparations can be maintained in short term culture, respond appropriately to choleretic agonists and facilitate a variety of functional applications.

Animals↗
PubMed1997

Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities.

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.

Antiviral Agents↗
PubMed1982

Abnormalities of bile acids in serum and bile from patients with myotonic muscular dystrophy.

1. Serum bile acids in seven patients with adult type myotonic dystrophy and 22 normal persons were quantitatively analysed by gas-liquid chromatography and gas chromatography-mass spectrometry for cholesterol, gamma-glutamyltransferase and bilirubin. There was no bile obstruction in any patient. 2. Dexoycholic acid values in all mothers of patients with congenital type myotonic dystrophy were three times (2.1 mumol/l) that of the control (0.7 mumol/l). 3. Uncommon bile acids were detected in the patients' sera. One of them appeared to be dihydroxymono-oxocholanic acid, having a longer side chain. Another one appeared to be dihydroxycholanic acid, with a steroid-nucleus structure similar to chenodeoxycholic acid and with a longer side chain. 4. Biliary bile acids from three patients and one normal person were also analysed, and this revealed a remarkable decrease in ursodeoxycholic acid in the patients. 5. The presence of bile acid abnormality in patients with myotonic muscular dystrophy is proposed.

Adolescent↗
PubMed2003

Bile composition in inflammatory bowel disease: ileal disease and colectomy, but not colitis, induce lithogenic bile.

BACKGROUND: Inflammatory bowel disease is a risk factor for gall-bladder stones, but there is controversy about the composition of these stones and whether such patients develop lithogenic bile. METHODS: In 54 gallstone-free inflammatory bowel disease patients and 13 non-inflammatory bowel disease patients with cholesterol-rich gallstones, we measured the biliary cholesterol saturation indices, nucleation times and bilirubin concentrations, and determined the bile acid composition and molecular species of phosphatidylcholine, in gall-bladder bile. RESULTS: Patients with Crohn's colitis or ulcerative colitis had less saturated bile (mean cholesterol saturation index, 0.9) and longer nucleation times (median, 21 days) than those with ileal Crohn's disease (1.5; 14 days) or those who had undergone colectomy (1.6; 5 days). In patients with ileal Crohn's disease, the mean biliary bilirubin concentration was two- to three-fold higher than that in the other groups, and was associated with a decrease in the percentage of biliary deoxycholate and an increase in the percentage of ursodeoxycholate, compared with disease controls, but phosphatidylcholine species were similar. CONCLUSIONS: Patients with small bowel Crohn's disease, or who have undergone colonic resection, have supersaturated bile and an increased risk of cholesterol gallstone formation. In patients with ileal disease, the presence of high biliary bilirubin concentrations and low percentage of deoxycholic acid may also favour the formation of mixed, pigment-rich, gallstones.

Adult↗
PubMed2003

Effect of the dimeric bile acid analogue S 0960, a specific inhibitor of the apical sodium-dependent bile salt transporter in the ileum, on the renal handling of taurocholate.

The effect of the dimeric bile acid analogue S 0960 (CAS 142974-51-4), a specific inhibitor of the apical sodium-dependent bile salt transporter (ASBT) in the ileum, on kidney function was studied by clearance experiments in anesthetized rats. Additional experiments were performed on proximal tubular cells freshly isolated from rat kidney cortex and enriched by nycodenz density gradient centrifugation. The clearance studies, which were performed after a 5 h bile duct ligation, revealed a marked rise of the 3H-taurocholate clearance (from 85.4 +/- 15.7 to 371.1 +/- 86.0 microliters/min 100 g b.w., p < 0.05) and a considerable fall of the fractional tubular 3H-taurocholate reabsorption (from 90.2 +/- 1.72 to 68.2 +/- 7.50%, p < 0.05) after S 0960 at a dose of 10 mg/kg i.v. whereas the glomerular filtration rate did not significantly change (from 919 +/- 165 to 1055 +/- 162 microliters/min/100 g b.w.). Isolated proximal tubular cells showed a significant accumulation of 3H-taurocholate. The 3H-taurocholate cell/bath concentration ratio amounted to 3.34 +/- 0.17 at a 3H-taurocholate bath concentration of 3 x 10(-7) mol/l. LiCl (10(-3) mol/l), which is known to inhibit sodium-dependent transport processes in the kidney, markedly diminished cellular 3H-taurocholate uptake (by 65.8%) whereas probenecid (CAS 57-66-9, 10(-4) mol/l), the classical inhibitor of the basolateral organic acid transporter in the kidney, did not significantly affect 3H-taurocholate uptake. This finding indicates that transport of taurocholate by the basolaterally located organic acid transporter is not involved in the uptake process. The kinetic studies revealed an apparent K(m) value of 31 mumol/l and a Vmax value of 6.7 mumol/l cell water/min for tubular 3H-taurocholate uptake. At concentrations > 30 mumol/l S 0960 virtually completely inhibited cellular 3H-taurocholate uptake. 3H-taurocholate uptake was half-maximally inhibited at a S 0960 concentration of 5.8 mumol/l. The results of this functional study are in line with recent molecular evidence that the apical sodium-dependent bile salt transporters in kidney and ileum are identical and demonstrate that S 0960 is a potent inhibitor of the apical sodium-dependent taurocholate transporter in the kidney which augments the renal clearance of 3H-taurocholate. Compounds such as S 0960 may be of special therapeutical value in patients with extrahepatic cholestasis and elevated levels of plasma bile acids.

Animals↗
PubMed1996

Calcium supplementation modifies the relative amounts of bile acids in bile and affects key aspects of human colon physiology.

Use of calcium supplements has increased dramatically in recent years yet little is known about the effect of calcium supplementation on colon physiology. We supplemented 22 individuals with a history of resected adenocarcinoma of the colon, but currently free of cancer, with 2000 or 3000 mg calcium for 16 wk. The effects of supplementation on duodenal bile acids and important fecal characteristics including total fecal output, wet and dry weight, pH, bile acids (in solids and in fecal water), and concentrations and total excretion of calcium, magnesium, phosphates (organic and inorganic), unesterified fatty acids and total fat were determined. Calcium supplementation significantly decreased the proportion of water in the stool (P = 0.03), doubled fecal excretion of calcium (P = 0.006), and increased excretion of organic phosphate (P = 0.035) but not magnesium. Calcium supplementation significantly decreased the proportion of chenodeoxycholic acid in bile (P = 0.007) and decreased the ratio of lithocholate to deoxycholate in feces (P = 0.06). The concentration of primary bile acids in fecal water decreased after 16 wk Ca supplementation. Together with other reports of a "healthier" bile acid profile with respect to colon cancer when changes such as those observed in this study were achieved, these results suggest a protective effect of calcium supplementation against this disease.

Adenocarcinoma↗
PubMed1992

The effect of bile duct ligation and bile diversion on FK506 pharmacokinetics in dogs.

Mongrel or beagle dogs were submitted to bile duct ligation, or to extraenteric biliary diversion by means of choledochoureterostomy. The kinetics of intravenously administered FK506 was not changed from control status two weeks after bile duct ligation, but the bioavailability of orally administered FK506 was nearly quadrupled. Following oral administration, the absorption of FK506 was highly variable. The results indicate that in dogs FK506 is absorbed from the intestine just as efficiently in the absence of enteric bile and in presence of exogenous bile salt supplement when compared with its absorption in presence of normal bile drainage. These findings with FK506 are different from those with cyclosporine after biliary obstruction or diversion and will have important practical as well as experimental ramifications.

Animals↗
PubMed2006

Restoration of bile ducts in drug-induced vanishing bile duct syndrome due to zonisamide.

Prolonged drug-induced cholestasis may be due to destruction and disappearance of bile ducts, sometimes referred to as vanishing bile duct syndrome. Although some of these cases progress to fibrosis, cirrhosis, and liver failure, others improve with time. We report a case of a 35-year-old man who developed vanishing bile duct syndrome after ingestion of zonisamide, an antiepileptic drug that is also prescribed for weight loss. His liver biopsy showed complete absence of bile ducts 3 weeks after starting treatment. There was no ductular reaction. The drug was stopped and a follow-up biopsy 3 months later showed strands of intermediate hepatobiliary cells at the periphery of the portal tracts that extended into lobules; these structures lacked lumina and expressed biliary cytokeratins, CK7 and CK19. A third biopsy, 7 months later, showed the presence of ductules with lumina located within portal tracts. Intermediate hepatobiliary cells were rare; although sparse clusters of hepatocytes with membrane staining for CK7 were present. Cholestasis and levels of bilirubin improved over time. The histologic features in this case document the sequence of events in restoration of the biliary tree after loss of bile ducts, which seems to be a process of maturation of intermediate hepatobiliary cells that arise from a proliferative compartment at the porto-hepatic interface.

Adult↗
PubMed2006

Preservation of bile ductules mitigates bile duct loss.

The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection. The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining. Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.

Adolescent↗
PubMed1976

In vitro effect of free bile acids on the bile canalicular membrane phospholipids in the rat.

Liver cell plasma membranes of male rats were isolated and separated into two fractions, one rich in bile canalicular membranes (BCM) and the other comprising the rest of the plasma membrane (PM). Aliquots of BCM, PM, and microsomes were incubated with deoxycholic, chenodeoxycholic, or cholic acid at bile acid - membrane phospholipid mole ratios up to 100, and the phospholipid solubilization from the PM and from microsomes was linear and apparently nonselective, while that from BCM was biphasic and distinctly selective. Phosphatidyl choline and phosphatidyl ethanolamine made up 90% of the phospholipids solubilized from the BCM at a bile acid - membrane phospholipid mole ratio sufficient to solubilize about 50% of the total phospholipids of the BCM. Of particular interest was the observation that the molecular species and fatty acid composition of the phospholipids solubilized from the BCM under these experimental conditions were similar to those of bile obtained from the same animal, and were quite unlike those solubilized at higher bile acid - phospholipids mole ratios. The data are discussed in terms of the mechanism of the biliary secretion of phospholipids.

Animals↗
PubMed2003

Bile acid regulation of hepatic physiology: III. Bile acids and nuclear receptors.

Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Recent studies reveal that bile acids also are signaling molecules that activate several nuclear receptors and regulate many physiological pathways and processes to maintain bile acid and cholesterol homeostasis. Mutations of the principal regulatory genes in bile acid biosynthetic pathways have recently been identified in human patients with hepatobiliary and cardiovascular diseases. Genetic manipulation of key regulatory genes and bile acid receptor genes in mice have been obtained. These advances have greatly improved our understanding of the molecular mechanisms underlying complex liver physiology but also raise many questions and controversies to be resolved. These developments will lead to early diagnosis and discovery of drugs for treatment of liver and cardiovascular diseases.

Animals↗
PubMed1997

Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter.

Although bile acid transport by bile duct epithelial cells, or cholangiocytes, has been postulated, the details of this process remain unclear. Thus, we performed transport studies with [3H]taurocholate in confluent polarized monolayers of normal rat cholangiocytes (NRC). We observed unidirectional (i.e., apical to basolateral) Na+-dependent transcellular transport of [3H]taurocholate. Kinetic studies in purified vesicles derived from the apical domain of NRC disclosed saturable Na+-dependent uptake of [3H]taurocholate, with apparent Km and Vmax values of 209+/-45 microM and 1.23+/-0.14 nmol/mg/10 s, respectively. Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na+-dependent taurocholate-cotransporting polypeptide and rat ileal apical Na+-dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT. Northern blot analysis demonstrated that the size of the ASBT transcript was identical in NRC, freshly isolated cholangiocytes, and terminal ileum. In situ RT-PCR on normal rat liver showed that the message for ASBT was present only in cholangiocytes. Immunoblots using a well-characterized antibody for the ASBT demonstrated a 48-kD protein present only in apical membranes. Indirect immunohistochemistry revealed apical localization of ASBT in cholangiocytes in normal rat liver. The data provide direct evidence that conjugated bile acids are taken up at the apical domain of cholangiocytes via the ASBT, and are consistent with the notion that cholangiocyte physiology may be directly influenced by bile acids.

Animals↗
PubMed1985

Bile duct lesions and diminution in number of intrahepatic bile ducts in asymptomatic primary biliary cirrhosis.

Morphological changes of interlobular bile ducts in asymptomatic or symptomatic primary biliary cirrhosis (PBC) and chronic hepatitis with ductal lesions were investigated. It was supposed that bile duct lesions found in PBC and chronic hepatitis could be distinguished histologically. There were identical epithelial changes between symptomatic PBC and asymptomatic one, but granulomas were more often found in asymptomatic PBC than in symptomatic PBC. Numbers of interlobular bile ducts per portal tract and the rates of portal tracts without interlobular duct in asymptomatic PBC were intermediate between symptomatic PBC and chronic hepatitis. Serial sections revealed that some bile ducts were able to be followed by ductules in asymptomatic PBC. From these results, numbers of interlobular bile ducts are undoubtedly decreased in asymptomatic PBC but not so much as in symptomatic one. This observation may be attributable partially for taking asymptomatic course.

Aged↗
PubMed1988

Beta-glucuronidase activity related to bacterial growth in common bile duct bile in gallstone patients.

Beta-glucuronidase activity in the bile may be of importance in the etiology of pigment gallstones. This enzyme is of hepatic or bacterial origin. We have described a method to measure the activity of bacterial beta-glucuronidase in human bile, using 4-nitrophenyl-beta-D-glucopyranosiduronic acid as substrate. The method was used to measure the beta-glucuronidase activity in the bile from 51 patients with gallstone disease. This activity was related to the presence of beta-glucuronidase-producing bacteria in the bile. Escherichia coli, Bacteroides species, and Clostridium perfringens were the only species found to produce beta-glucuronidase. Patients with beta-glucuronidase-producing bacteria had on an average significantly higher enzyme activity in the bile than patients without such bacteria (p less than 0.01). The limitations of using artificial substrates in this type of studies are discussed.

Aged↗