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Biomedical subjects

G Paumgartner

Publications and source records attributed to G Paumgartner.

At least 271 records · Page 15Linked to original sources

Case report: chenodeoxycholic acid therapy of intrahepatic radiolucent gallstones in a patient with Caroli's syndrome.

A 28-year-old man with intrahepatic cystic dilatations of the biliary tree (Caroli's syndrome) which contained multiple radiolucent gallstones was treated with 1 g of chenodeoxycholic acid per day. He had undergone cholecystectomy 4 years and surgical exploration of the common bile duct with papillotomy 2 years prior to chenodeoxycholic acid therapy. While no decrease in the number of stones could be detected by retrograde cholangiography 2 years after papillotomy, most of the stones had disappeared after 2 years of treatment with chenodeoxycholic acid.

Adult↗

[Does cholestyramine impair the bioavailability of prednisolone?].

Measurements of plasma prednisolone concentrations in two patients who received orally 37.5 and 75 mg of the drug respectively showed no differences when 8 g of cholestyramine was given with the corticosteroid. Thus, no influence of cholestyramine on the bioavailability of orally administered prednisolone could be demonstrated.

Biological Availability↗

[Detection of 3 beta-hydroxy-5-cholenoic acid in human amniotic fluid].

Studies of the bile acids of human meconium suggest that a fetal pathway of bile acid synthesis exists which leads to formation of 3beta-hydroxy-5-cholenoic acid, a bile acid not found in serum of healthy pregnant women. To obtain additional support for this hypothesis, cholic, chenodeoxycholic, and 3beta-hydroxy-5-cholenoic acid were measured in amniotic fluid specimens from 18 pregnant women without liver disease. The finding of a considerable percentage of 3beta-hydroxy-5-cholenoic acid (mean: 34 molar %; range 3-71 molar % of total bile acids) in amniotic fluid strengthens the hypothesis that a fetal pathway of bile acid synthesis exists which begins with oxidation of the cholesterol side chain.

Adolescent↗

Effects of bile and bile acids on cultured human fibroblasts.

Impaired healing induced by leakage of bile has been postulated as one factor responsible for complications after reconstructive bile duct surgery. The cytotoxicity of human bile and its major bile acids on cultured human fibroblasts was therefore studied by evaluation of their effects on cell morphology and growth, on synthesis and secretion of 35SO4-mucopolysaccharides and on release of a lysosomal enzyme. Normal human fibroblasts derived from a standard culture strain (MRC-5) were grown to confluence and exposed to: (1) sterile human T-tube bile, (2) a mixture of bile acids resembling that of human bile, or (3) various concentrations of the glycine- and taurine conjugates of cholic, chenodeoxycholic or deoxycholic acid. Medium containing whole bile (total bile acid concentration 0.25, 0.75 or 1.6 mmol/l) exerted time and dose dependent cytotoxic effects on morphology and growth and release of lysosomal enzyme. Synthesis and secretion of 35SO4-mucopolysaccharides were markedly inhibited. The bile acid mixture exhibited the same time and dose dependent effects. The conjugates of deoxycholic acid were found to be the most toxic of the individual bile acids studied.

Bile↗

Relationship between bile flow and Na+, K+-adenosinetriphosphatase in liver plasma membranes enriched in bile canaliculi.

The relationship between bile flow and Na+,K+-ATPase activity in liver plasma membranes enriched in bile canaliculi was studied in rats treated with ethinyl estradiol, phenobarbital, or 20-methyl cholanthrene. In comparison with controls (1.49+/-0.12 microliter/min per g liver), bile flow was significantly diminished by ethinyl estradiol, increased by phenobarbital, and unchanged by 20-methyl cholanthrene or the solvent, propanediol (0.92+/-0.31, 2.50+/-0.21, 1.62+/-0.18, and 1.64+/-0.30 microliter/min per g liver, respectively). The corresponding values for canalicular Na+,K+-ATPase activity were 80.7+/-19.2, 50.0+/-18.4, 231.7+/-42.6, 82.7+/-30.7, and 143.6+/-55.3 micronmol Pi/h per g liver. Canalicular Na+,K+-ATPase activity was significantly correlated (r=0.785, n=31) with bile flow. These findings support the hypothesis that a fraction of bile flow is related to Na+,K+-ATPase activity and canalicular Na+ transport.

Adenosine Triphosphatases↗

[Physiology of bile formation (author's transl)].

Generation of bile flow in humans depends mainly on two transport mechanisms of the hepatocyte. One of these is responsible for secretion of bile acids, the other for transport of sodium into the bile canaliculi. Accordingly, a bile acid dependent fraction of hepatocytic bile can be distinguished from a bile acid independent fraction. Many endogenous and exogenous substances, including x-ray contrast media, are secreted into hepatocytic bile by more or less specific transport systems. The bile produced by the liver cells is then modified by admixture of ductular bile and by reabsorptive processes in the biliary passages and in the gallbladder. Increased knowledge about these mechanisms represents one of the requirements for progress in oral and intravenous cholangiography.

Animals↗

Bile acids in serum and bile of infants with cholestatic syndromes.

The concentration of individual bile acids in serum was measured in 18 neonates and infants with various cholestatic conditions (extrahepatic biliary atresia, neonatal hepatitis syndrome, chronic intrahepatic cholestasis and posthemolytic cholestasis). The cholate/chenodeoxycholate ratio in serum was smaller than one in all patients with neonatal hepatitis syndrome or extrahepatic biliary atresia, cholestatic conditions which were accompanied by signs of liver cell injury. It was greater than one in the patients with chronic intrahepatic cholestasis. Administration of cholestyramine to patients with patent extrahepatic bile ducts decreased the total concentration bile acids in serum and elevated the cholate/chenodeoxycholate ratio. Thus, cholestyramine administration may be of diagnostic value for evaluation of bile duct patency in cholestasis of infancy. Differences between the bile acid pattern in serum and bile were observed. Thus, the cholate/chenodeoxycholate ratio was always higher in bile than in serum. 3beta-hydroxy-5-cholenoic acid found in serum was not detectable in bile. This finding suggests that impairment of biliary excretion rather than increased hepatic synthesis is responsible for elevation of this monohydroxy bile acid in serum.

Bile↗

Determination of bile acid concentration in human amniotic fluid for prenatal diagnosis of intestinal obstruction.

Bile acid concentration was measured in amniotic fluid obtained for standard indications from 11 healthy pregnant women without polyhydramnios (28 to 42 weeks of gestation) and from 9 patients with polyhydramnios (28 to 38 weeks of gestation). Two of the latter women delivered infants with intestinal obstruction distal to the papilla of Vater, a condition that causes regurgitation of bile into the amniotic fluid. In the women without polyhydramios, the total bile acid concentration ranged from 1.4 to 2.4 micronmol/liter. In the seven patients with polyhydramnios not associated with fetal intestinal obstruction, the bile acid concentration in amniotic fluid was not significantly different (0.9 to 1.9 micronmol/liter). By contrast, the bile acid concentration in amniotic fluid specimens from the two patients with polyhydramnios who gave birth to children with intestinal obstruction was considerably elevated (30.3 to 83.1 micronmol/liter). These findings suggest that determination of bile acid concentration in amniotic fluid permits prenatal diagnosis of intestinal obstruction distal to the papilla of Vater.

Amniotic Fluid↗

[Serum concentration of digitalis glycosides as a therapeutic guide].

The concentration of digitalis glycosides in serum may serve as a useful guide in adjusting digitalis glycoside dosage to individual needs. Radio-immunological determination of digoxin is mainly indicated when patients with renal failure, hypothyroidism or hyperthyroidism or elderly subjects are treated with digoxin, when signs of digitalis intoxication are present or when patient compliance has to be assessed. However, factors which alter myocardial sensitivity to digitalis glycosides must be considered in the interpretation of serum concentrations of digitalis glycosides.

Digitalis Glycosides↗

Kinetics of hepatic uptake of unconjugated bilirubin.

1. The uptake of bilirubin was studied in the perfused rat liver by a multiple-indicator dilution technique employing the three-compartment model of Goresky. 2. The kinetics of hepatic bilirubin uptake could be described by the Michaelis-Menten equation. 3. The maximal uptake velocity (V max.) and the apparent half-saturation constant (Km) were 4-4 +/- 0-5 nmol s-1 g-1 of liver and 58 +/- 16 nmol/g of liver respectively, indicating that the hepatic uptake system for bilirubin under normal conditions is operating far below saturation. 4. Sodium taurocholate did not compete with bilirubin for hepatic uptake. 5. These findings are consistent with the concept that carrier-mediated transport is responsible for hepatocellular uptake of bilirubin and that bilirubin and bile acids enter the hepatocyte via separate pathways.

Animals↗

Uptake of bile acids by perfused rat liver.

The uptake of 14C-labeled cholic, taurocholic, and chenodeoxycholic acid by the perfused rat liver was studied to characterize the mechanism responsible for hepatic uptake of bile acids. A rapid-injection multiple indicator-dilution technique and the three-compartment model of Goresky were employed. The kinetics of hepatic uptake of the three bile acids could be described by the Michaelis-Menten equation. The maximal uptake velocities (Vmax) were 24.9 +/- 2.2 (mean +/- SD), 20.8 +/- 1.2, 1.2, and 11.4 +/- 0.9 nmol/s-g liver for cholic, taurocholic, and chenodeoxycholic acid, respectively. The corresponding apparent half-saturation constants (Km) were 526 +/- 125, 258 +/- 43, and 236 +/- 48 nmol/g liver. Competitive inhibition could be demonstrated between cholate and taurocholate as well as between cholate and chenodeoxycholate. Substitution of 94% of the Na+ in the perfusion medium decreased the Vmax and the apparent Km of taurocholate uptake by 68 and 55%, respectively. These findings are consistent with the hypothesis that bile acids are taken up into the hepatocyte by Na+-dependent carrier-mediated transport.

Animals↗

Inhibition of bile formation by high doses of taurocholate in the perfused rat liver.

Sodium taurocholate was administered to the in situ perfused liver of male Sprague Dawley rats at various rates below (57 and 114 nmol/min -g liver) and above (228 and 456 nmol/min -g liver) its biliary transport maximum (Tm) to study its effect on bile formation. As expected, bile flow increased with increasing dose until maximal bile salt excretion was reached. By contrast, during taurocholate infusions exceeding the taurocholate-Tm, bile flow and bile salt excretion decreased. Under those conditions, a given bile salt excretion was associated with a smaller volume of bile. A relationship between these effects and the concentration of taurocholate in the perfusate (160 to 860 nmol/ml) was suggested by the observation that bile formation returned toward normal when the taurocholate concentration was lowered by exchange of the perfusate.

Animals↗

Biliary lipid composition in early childhood.

The biliary lipid composition was studied in 11 children without hepatic or gastrointestinal disease who ranged in age from 15 to 54 months. The molar percentages of cholesterol, bile acids and phospholipids in the biliary lipid mixture averaged 5.0 +/- 1.1; 80 +/- 6.1 and 15 +/- 6.2%, respectively. Cholic, chenodeoxycholic, deoxycholic and ursodeoxycholic acid comprised 48; 45; 4 and 3% of total bile acids, respectively. A comparison of the lipid composition with data reported in the literature for the adult reveals that the molar percentage of cholesterol is relatively low in early childhood. This could be one of the factors which is responsible for the low incidence of cholesterol gallstones in this age group.

Adult↗