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At least 487 records · Page 27Linked to original sources
PubMed2001

Visualization of the transport of primary and secondary bile acids across liver tissue in rats: in vivo study with fluorescent bile acids.

BACKGROUND/AIMS: Lysyl fluorescein conjugated bile acid analogues (LFCBAA) closely parallel their natural counterparts. To assess LFCBAA as a tool for the visualization of bile acid transport within liver tissue. METHODS: Wistar rats were administered physiological concentrations of the primary bile acid analogue cholyllysyl fluoroscein (CLF) and of the secondary bile acid analogue lithocholyllysyl fluorescein (LLF) and serial liver biopsies were taken at fixed intervals. Both compounds were also injected retrogradely into the biliary tree. Frozen sections were examined by fluorescence microscopy. RESULTS: Both CLF and LLF were rapidly taken up from sinusoidal blood but differed significantly in their hepatic handling. CLF was rapidly transported into bile, whereas LLF transport was slower and produced significantly more bile duct fluorescence. LLF clearance showed a lobular gradient with last remaining bile acid being confined largely to zone 3. Both compounds were avidly taken up by cholangiocytes after injection intravenously or retrogradely into the biliary tree. CONCLUSIONS: Visualization of LFCBAA by fluorescence microscopy may yield further information regarding hepatobiliary bile acid localization during studies of physiological and pathological mechanisms involved in transport of bile acids. The presence of both compounds within cholangiocytes strongly suggests that they may undergo a degree of chole-hepatic recirculation.

Animals↗
PubMed2000

Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones.

BACKGROUND AND AIMS: There is limited information available on the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on hepatic and biliary cholesterol metabolism in patients with gallstones. The aims of this study were to determine the effect of simvastatin on the regulatory elements of cholesterol metabolism that determine the concentrations of cholesterol in plasma and bile. METHODS: Thirty-one gallstone patients were enrolled in the study; 17 were treated with 20 mg simvastatin daily for 3 weeks prior to cholecystectomy and 14 served as controls. Samples of blood, liver, gall-bladder bile and bile from the common bile duct (CBD) were collected and analysed. RESULTS: The plasma cholesterol (-30%), triacylglycerol (-23%) and low-density lipoprotein (LDL) cholesterol (-42%) concentrations were significantly lowered by simvastatin treatment, as was the plasma lathosterol: cholesterol (-70%), which reflects whole-body cholesterol synthesis. Despite these changes, the hepatic LDL receptor protein and LDL receptor activity in circulating mononuclear cells were similar in both groups. There were no differences in the plasma phytosterol: cholesterol, which reflects the intestinal cholesterol absorption capacity or in the activity of hepatic acyl-coenzyme A: cholesterol acyltransferase. There were however, lower cholesterol concentrations in CBD (-68%) and gall bladder (-41%) bile, and decreased lithogenic (-47%) and bile acid hydrophobicity (-22%) indices of CBD bile in the simvastatin group. CONCLUSIONS: These data indicate that simvastatin reduced plasma and biliary cholesterol levels primarily by reducing cholesterol synthesis. The reduction in CBD bile lithogenicity and bile acid hydrophobicity by simvastatin suggests that this agent may be useful for people who have early stages of cholesterol gallstone development and in whom a choleretic effect is required.

Adult↗
PubMed1985

Bile composition and bile acid pool size. Comparison after truncal, selective, and highly selective vagotomy.

We studied biliary lipid composition and bile acid pool size in 29 patients surgically treated for duodenal ulcer. Fourteen were examined both before and after surgery, the rest postsurgically only. They were divided into three groups according to type of vagotomy. With duodenal fluid obtained via nasogastric tube, we determined bile acid pool size, bile concentrations, and lithogenic index. We found no significant differences in bile composition and bile acid pool size among the three types of vagotomy, postsurgically. However, patients studied before surgery, compared with the entire post-vagotomy group, had a significant increase in relative cholesterol content and lithogenic index, most pronounced in the truncal vagotomy group. Bile acid pool size was also increased postsurgically. Vagotomy may predispose to gallstone development by increasing the bile's relative cholesterol concentration and thus the lithogenic index. However, the slightly expanded bile acid pool size may improve cholesterol solubility in certain patients.

Bile↗
PubMed1997

Purification of a newly identified alkaline sphingomyelinase in human bile and effects of bile salts and phosphatidylcholine on enzyme activity.

The hydrolysis of sphingomyelin (SM) generates important signals regulating cell proliferation and apoptosis. Acid and neutral sphingomyelinases (SMase) have been identified and their biological effects intensively studied. We recently found in human bile a novel alkaline SMase that may have important roles in hepatobiliary diseases. In this work, we purified the enzyme and studied the factors influencing enzyme activity. Purification steps included Sephadex G25, diethylaminoethyl (DEAE)-Sepharose, Sephacryl S-200, and sphingosylphosphorylcholine (SPC) affinity chromatographies. A single protein of 92 kd was obtained with the specific enzyme activity increased 1,154-fold. The enzyme specifically hydrolyzed SM to ceramide, had a weaker activity against phosphatidylcholine (PC), and no activity against either phosphatidylethanolamine (PE) or p-nitrophenyl phosphate. Its optimum pH was 9.0 and its Vmax and Km were 45 micromol/h/mg and 2.5 x 10(-5) mol/L, respectively. The enzyme activity was dependent on concentration and structure of bile salts. Both trihydroxy and dihydroxy bile salts at concentrations up to their critical micellar concentrations activated the alkaline SMase, trihydroxy bile salts being more potent than dihydroxy ones. The side chain of trihydroxy bile salts was also important. Taurocholate (TC) was most effective in activating SMase, followed by glycocholate (GC), and cholate. 3-((3-cholamidopropyl)dimethylammonio)-propanesulfonate (CHAPS) alone had no effect on SMase activity but inhibited TC-induced activation of SMase. PC competitively inhibited bile alkaline SMase activity, with the 50% inhibition occurring at a PC/SM ratio of approximately 28. In conclusion, we purified a novel alkaline SMase from human bile and found that its activity is dependent on the levels of two major biliary components: PC and bile salts.

Bile↗
PubMed1978

Bile lipid composition and bile acid pool size in diabetes.

Since the prevalence of gallstones is higher in diabetics than in controls and since cholelithiasis is often associated with supersaturated bile, we measured bile lipid composition and bile acid pool size in 8 patients with juvenile diabetes, 16 with maturity-onset diabetes, and 10 control subjects. Bile lipid composition was expressed as "saturation index." In the maturity-onset diabetics the saturation index (1.60 +/- 0.45 SDM) was significantly higher (P less than 0.005) than that in the controls (0.82 +/- 0.20) and in patients with juvenile diabetes (0.75 +/- 0.24). The absolute values for biliary bile acid concentration were significantly lower (P less than 0.01) in the maturity-onset diabetics than in the other two groups. There were no differences in either the proportion of the individual biliary bile acids or the size of the bile acid pool between the three groups. The results suggest that the incidence of cholelithiasis in diabetes is associated with the secretion of a supersaturated bile only in the maturity-onset subgroup.

Adult↗
PubMed1991

Ion-pair high-performance liquid chromatography of bile salt conjugates: application to pig bile.

The high-performance liquid chromatographic separation and quantitation of conjugated bile salts from pig bile is reported. Synthetic standards and bile samples were chromatographed on a C18 reversed phase column using acetonitrile/water/tetrabutyl ammonium phosphate as an isocratic mobile phase at a flow rate of 1 mL/min. Detection of the ion-pairs was at 214 nm. The method permits efficient separation of all conjugated pig biliary bile salts without prior modification or treatment of the samples. Analysis of 12 pig biles showed that 85% of the bile salts are conjugated to glycine. The three main conjugated bile salts were glyco-3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid (GHC), glyco-3 alpha,7 alpha-dihydroxy-5 beta-cholanoic acid (GCDC), and glyco-3 alpha,6 alpha-dihydroxy-5 beta-cholanoic acid (GHDC). Glyco-3 alpha-hydroxy-6-oxo-5 beta-cholanoic acid (G3 alpha 6oxo), tauro-3 alpha,7 alpha-dihydroxy-5 beta-cholanoic acid (TCDC), tauro-3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid (THC), and tauro-3 alpha,6 alpha-dihydroxy-5 beta-cholanoic acid (THDC) were found to contribute each for 4 to 5% to the total. An excellent correlation was found between the sum of conjugated bile salts quantitated by high-performance liquid chromatography (HPLC) and values obtained by conventional enzymatic assay. Simplicity, efficiency and relative rapidity of the method render it suitable for routine analyses.

Animals↗
PubMed1993

High performance liquid chromatographic determination of free and conjugated bile acids in serum, liver biopsies, bile, gastric juice and feces by fluorescence labeling.

Separation and measurement of commonly occurring free and conjugated bile acids in serum, liver biopsies, bile, gastric juice and feces have been successfully accomplished using high performance liquid chromatography with fluorescence labeling. Free and conjugated bile acids were extracted from pretreated samples using Sep-Pak C18 cartridges and then fractionated on a piperidinohydroxypropyl Sephadex LH-20 column. Free and glycine conjugated bile acids were labelled with 4-bromomethyl-7-methoxycoumarin. Taurine conjugated bile acids were hydrolysed with cholylglycine hydrolase prior to derivatization with 4-bromomethyl-7-methoxycoumarin. Labelled bile acids were eluted using an acetonitrile/methanol/water gradient on an ultrasphere ODS column. The eluate was monitored by a fluorophotometer at 360 nm (excitation) and 410 nm (emission). Linearity was obtained between 50 and 400 nmol. Recoveries from serum, gastric juice and feces were greater than 87%. This is therefore a sensitive method for the precise quantification of bile acids in serum, liver biopsies, bile, gastric juice and feces.

Bile↗
PubMed1988

Ileal excretion of bile acids: comparison with biliary bile composition and effect of ursodeoxycholic acid treatment.

The amount of bile acid excreted via an ileostomy at the end of the ileum should give an estimate of the amount of bile acid transported to the colon. In the present study, 8 patients with ileostomies at the end of the ileum but without disease or resection of the small intestine excreted 1690 +/- 205 mumol/day (mean +/- SEM) of bile acids from the ileostomies. In comparison with duodenal bile, cholic acid was increased at the end of the ileum and chenodeoxycholic acid decreased; in addition, bile acid sulfates were increased and bile acid glucuronides were decreased. When ursodeoxycholic acid, a bile acid that decreases biliary cholesterol saturation and dissolves gallstones, was administered at a dose of 500 mg to each subject, 59% +/- 8% (mean +/- SEM) of this bile acid was excreted within 24 h from the ileostomies. It is apparent from these studies that absorption of ursodeoxycholic acid from the small intestine is slower than previously anticipated and involves the entire small intestine and probably also the colon.

Adult↗
PubMed2002

Three hypotheses linking bile to carcinogenesis in the gastrointestinal tract: certain bile salts have properties that may be used to complement chemotherapy.

The literature for the proliferative effect of bile acids on the GI tract has been reviewed and three hypotheses developed regarding their carcinogenicity. Considered as a unit, the GI tract is protected from this carcinogenicity in different ways in the esophagus, stomach, small bowel and colon. Uncharged BAs can enter the esophageal epithelial cells by reflux of gastroduodenal juices in humans, and in animals by surgical alteration of the GI tract or by adding bile concentrate to the diets, and this can initiate GERD and eventually cancer. Acid suppressant therapy used to treat GERD patients, converts stomach pH to >4. This will remove the charges on conjugated bile acids allowing them entry into the epithelium thus casting doubt on the efficacy of acid suppression. From these observations, we postulate that (a) uncharged BA in daily contact with the esophagus can cause GERD and eventually cancer. This might explain the cancers obtained by Fein et al. (b) Clinical trials designed to test the effectiveness of acid suppressants will be meaningless since up to approximately 87% of these patients (in one study) have bile in their refluxate, and this, combined with acid suppressants, will initiate carcinogenesis. (c) Bile reaching a colon made sterile by antibiotics or other means, will not be deconjugated and so, with pKa's of 2 and 4, will be uncharged and therefore can easily enter the colonic cells where the pH is >6. This should be of some concern, especially on a high-fat diet when more bile enters the colon. A group of physicians noted that approximately 47% of patients with esophageal cancers also had some form of colon cancer and postulated that an etiological factor in the environment was responsible. Could this factor be bile? Reactions of certain bile salts with epithelial cells suggest a useful role for them in chemotherapy. Experiments to test hypotheses a, b and c are presented in the addendum.

Animals↗