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Biomedical subjects

S Erlinger

Publications and source records attributed to S Erlinger.

At least 199 records · Page 11Linked to original sources
PubMed1982

Effects of individual taurine-conjugated bile acids on biliary lipid secretion and sucrose clearance in the unanesthetized dog.

The effect of three taurine-conjugated bile acids on bile flow, induced biliary secretion of phospholipids and cholesterol, and the hepatobiliary clearance from plasma of sucrose and erythritol (two uncharged, nonmetabolizable permeability probe molecules) was assessed in the unanesthetized bile fistula dog under steady-state conditions. Synthetically prepared chenodeoxycholyltaurine, cholytaurine, or urological rate for randomized 90-min periods, and four 10-min samples of bile were taken at the end of each period. Induced bile flow (per mumoles of bile acid) was calculated to be about one-third higher with ursodeoxycholyltaurine than with the other bile acids. Induced phospholipid secretion was identical for all bile acids, but cholesterol secretion differed: the two dihydroxy taurine conjugates induced considerably more cholesterol per molecule bile acid or phospholipid than colyltaurine. Further, ursodeoxycholyltaurine induced significantly more cholesterol secretion than chenodeoxycholyltaurine. Erythritol clearances were identical for all bile acids, and sucrose clearance, although slightly higher for chenodeoxycholyltaurine than ursodeoxycholyltaurine, was similar for all three conjugated bile acids. The results indicate that, for these two 3,7-dihydroxy bile acids, the orientation of the 7-hydroxyl group on the steroid nucleus has a marked influence on cholesterol secretion into bile and bile flow but not on the apparent permeability of the hepatobiliary tree.

Animals↗
PubMed1982

Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat.

It has been reported that biliary secretion is the limiting step in the hepatic transport of bile acids by the hepatocyte from plasma to canalicular bile. The aim of the present study was to examine the role of conjugation in the transport process using ursodeoxycholate (UDCA) and tauroursodeoxycholate (TUDCA), two bile acid with low liver toxicity. Rats were given constant intravenous infusions of cholate (C), taurocholate (TC), UDCA, or TUDCA at progressively increasing rates. The biliary maximum secretory rate (SRm), in nmol . min-1 . 100 g body wt-1, for TC (1,835.2 +/- 135.5, mean +/- SE) was not significantly different from that of C (1,749.4 +/- 85.6). In contrast, the SRm for TUDCA (5,909.4 +/- 304.4) was approximately sevenfold that of UDCA (802.1 +/- 134.2), the difference being statistically significant (P less than 0.001). The SRm of UDCA in the presence of a taurine infusion (1,367 +/- 84.4) was higher than that of UDCA infused alone but still much lower than that of TUDCA. Phenobarbital sodium pretreatment did not increase SRm of UDCA alone or in the presence of a taurine infusion. These results suggest that in the rat 1) conjugation is the rate-limiting step in the overall transport of UDCA (and perhaps other bile acids) by the liver, and 2) the conjugation process itself is limiting, rather than the availability of taurine. They support the view that, although not mandatory for secretion into bile, conjugation of bile acids confers a biological advantage, possibly by increasing the solubility of the bile acid.

Animals↗
PubMed1982

Does Na+-K+-atpase have any role in bile secretion?

In this review, I have attempted to summarize the evidence supporting the view that Na+-K+-ATPase (the enzymatic basis for the sodium pump) plays a key role in bile secretion. First, experiments in the isolated perfused liver, in isolated and cultured hepatocytes, and more recently in hepatocyte membrane vesicles strongly suggest that bile acid uptake by the hepatocyte is a secondary active transport that is energized by the Na+ gradient maintained by the Na+-K+-ATPase. Thus, Na+-K+-ATPase appears important in coupling the energy from ATP to transport activity, resulting in the so-called bile acid-dependent bile flow. Second, experiments with liver plasma membranes have shown a correlation between Na+-K+-ATPase activity in these preparations and the so-called bile acid-independent bile flow. In view of the recognized sinusoidal-lateral localization of the Na+-K+-ATPase in the liver cells, several possibilities are proposed to explain how the enzyme activity could be coupled to ion transport and secretion into bile. These possibilities include Na+ movement from the intercellular space into the canalicular lumen through the paracellular pathway and movement of another ion using the Na+ gradient.

Animals↗
PubMed1982

Hepatic alterations during total parenteral nutrition in patients with inflammatory bowel disease: a possible consequence of lithocholate toxicity.

In order to understand the mechanism of hepatic abnormalities appearing during total parenteral nutrition, biliary bile acid composition and liver function tests were examined serially in 15 patients undergoing total parenteral nutrition for inflammatory bowel disease. In all 12 patients who underwent duodenal intubation before initiation of total parenteral nutrition, lithocholic acid accounted for less than 1% of total biliary bile acids. After 11-22 days of total parenteral nutrition, lithocholic acid accounted for 7%-15% of biliary bile acids in 5 patients and less than 1% of biliary bile acids in 10 patients. In the 5 patients with elevated levels of biliary lithocholic acid, serum alkaline phosphatase and aminotransferase activities rose progressively at serial determinations, the increase being significant after 2 wk of total parenteral nutrition. These results suggest that lithocholic acid may be involved in the hepatic lesions observed in patients undergoing total parenteral nutrition.

Adult↗
PubMed1982

Choleretic and diuretic properties of dihydroxydibutyl ether in the rat.

Dihydroxydibutyl ether (DDE) induces a choleresis and a diuresis in the rat. The stimulation of bile flow is immediate and dose-dependent; DDE appears to stimulate bile acid-independent flow of canalicular origin, because erythritol clearance increased in parallel to bile flow and choleresis occurs in the absence of an increased bile acid secretion. Increased bile flow may be accounted for by the osmotic activity of DDE and DDE metabolites excreted into bile, with an average increase in bile flow of 16 microliters/mumol of DDE (or DDE metabolites). Biliary secretion of DDE is limited with a maximal rate (biliary Tm) of 773 nmol.min-1.100 g b.wt.-1. The metabolic products of DDE in bile appear to be its mono- and diglucuronide conjugates inasmuch as DDE can be recovered after beta-glucuronidase incubation. DDE and a DDE glucuronide conjugate are also detected in the urine: there is an apparently linear relation between DDE (and DDE metabolites) excretion rate and increase in urinary flow (3.5 microliters/mumol of DDE or DDE metabolites). It is concluded that DDE stimulates choleresis and diuresis in the rat because the molecule and its glucuronide conjugates are secreted and concentrated in bile and urine.

Animals↗
PubMed1981

Cholestasis as a paraneoplastic manifestation of carcinoma of the kidney.

Two cases of hepatic paraneoplastic manifestations of carcinoma of the kidney are presented. In one, hepatosplenomegaly and abnormal liver function tests resolved following removal of the tumour. In the other, pruritus as a symptom of cholestasis was the presenting feature. Post-operatively a full blown cholestatic syndrome developed. Although their clinical presentations differed they may represent a spectrum of the same disease.

Adenocarcinoma↗
PubMed1981

Effects of troleandomycin administration on cholesterol 7 alpha-hydroxylase activity and bile secretion in rats.

Repeated administration of troleandomycin increased bile flow but decreased the biliary secretion of bile acids in rats. The increased bile flow was associated with a parallel increase in the biliary clearance of [14C]erythritol. Analysis of the relationship between bile flow and bile acid secretion indicated that, for any given rate of bile acid secretin, bile flow was higher in troleandomycin-treated rats than in control rats. The increased bile flow was associated with an increased activity of Na+,K+-adenosine triphosphatase in liver plasma membranes. The decreased bile acid secretion into bile was associated with a similar decrease in the bile acid pool size, a decreased bile acid synthesis rate and a decreased activity of microsomal cholesterol 7 alpha-hydroxylase. The concentration of bile acids in serum, the hepatic extraction ratio of [3H]taurocholate and its biliary transport maximum were not modified. It is concluded that repeated administration of troleandomycin increases the canalicular bile acid-independent flow but decreases the activity of cholesterol 7 alpha-hydroxylase, the synthesis, the pool size and the biliary secretion rate of bile acid in rats.

Animals↗
PubMed1980

Properties of Na+, K+-ATPase of liver plasma membranes in the hamster.

This study was designed to establish the properties of liver plasma membranes (LPM) Na+,K+-ATPase in the hamster and to determine whether a similar assay may be used to measure enzyme activity in the hamster and in the rat. Maximal Na+,K+-ATPase activity was obtained when the assay medium contained 5 mM Mg APT2- with or without 1 mM free Mg2+, 120 mM Na+, 12,5 mM K+. The incubation must be performed at 37 degrees C, pH 7.4. In the absence of free Mg2+, the saturation curve with respect to the substrate Mg ATP2- resulted in biphasic complex kinetics with a maximal activity at a substrate concentration of 5 mM. In the presence of 1 mM free Mg2+ activation of Na+,K+-ATPase and modification of the kinetics were observed: the biphasic curve tended to disappear and to become of the Michaelis-Menten type. The apparent Km for Mg APT2- was 0.36 mM and the Vmax 34.5 mumol.h-1.mg protein-1. In the presence of 10 mM free Mg2+ a decrease in the Vmax was observed without any effect on the apparent Km for Mg APT2-. It is concluded that the same incubation medium may be used to assay LPM N+,K+-ATPase from hamster and rat and that the addition of 1 mM free Mg2+ to the incubation medium is recommended to obtain Michaelis-Menten kinetics in order to eliminate complex kinetics due to the absence of free Mg2+.

Adenosine Triphosphate↗
PubMed1980

Effect of phalloidin on biliary lipid secretion in rats.

1. The effect phalloidin on bile acid, phospholipid and cholesterol secretion into bile was studied in rats with bile fistulae. 2. Phalloidin, when given for 7 days, induced a significant decrease in biliary cholesterol concentration and cholesterol saturation index. Bile acid and phospholipid concentration in bile remained unchanged. This effect was less marked in animals receiving the drug for 3 days, and not detectable in animals treated for 1 day. 3. These results provide circumstantial evidence for the hypothesis that microfilament dysfunction may lead to alterations in cholesterol secretion into bile.

Animals↗
PubMed1980

[Ineffectiveness of corticosteroids in cholestatic forms of chronic active hepatitis].

Four cases of chronic active hepatitis with cholestasis resembling primary biliary cirrhosis are reported. Two patients were women and two were men; their age ranged from 18 to 52 years. They had recurrent jaundice with pruritus, and, in two cases, xanthelasma or xanthomas. All patients had hyperbilirubinemia, a moderate increase in serum aspartate aminotransferase activity, an increase in serum alkaline phosphatase activity and immunoglobulins G levels. Hepatitis B surface antigen was present in one patient. Histological examination of the liver revealed active chronic hepatitis with cholestasis. Moderate doses of prednisone had no effect on clinical or biochemical signs in any of the patients.

Adolescent↗
PubMed1980

Influence of colchicine and phalloidin on bile secretion and hepatic ultrastructure in the rat. Possible interaction between microtubules and microfilaments.

The studies were carried out to examine the role of microtubules and microfilaments on bile secretion in the rat in vivo. Phalloidin (which causes irreversible polymerization of actin into microfilaments), administered at the dose of 50 microgram/100 g body wt during 3 days, caused an increase in the microfilamentous network around bile canaliculi; it induced a significant decrease both in basal bile flow, and in bile flow stimulated by sodium taurocholate, the major bile acid in the rat. Colchicine (which inhibits the polymerization of tubulin into microtubules), 3 hr after an injection of 0.2 mg/100 g body wt, caused the almost complete disappearance of microtubules in the hepatocytes; it did not modify basal bile secretion, but did induce a significant decrease in taurocholate secretion and taurocholate-stimulated bile flow after a bile-acid load, as well as a delayed plasma disappearance of the bile acid. Lumicolchicine, which is known to have no effect on tubulin, had no effect on bile secretion. The combined administration of phalloidin and colchicine caused both the increase of the pericanalicular microfilamentous network and the disappearance of microtubules; it induced a decrease in basal bile flow that was more marked than that observed with phalloidin alone, suggesting that the effects of the two drugs were not simply additive, but synergic. Although a toxic effect of colchicine could not be totally excluded, the results are compatible with the hypothesis that microtubules as well as microfilaments play a role in the excretion of a bile-acid load.

Alanine Transaminase↗
PubMed1979

Chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile in the dog.

Six dogs were given chenodeoxycholic acid, 200 mg/day for 15 days; gallbladder and hepatic bile samples were taken and biliary bile acids, phospholipids and cholesterol were compared to those of fourteen control dogs. It was found that: (1) the cholesterol saturation index of gallbladder bile was higher in treated dogs (0.12 +/- 0.06; m +/- SD) than in controls (0.07 +/- 0.01; P less than 0.05); the proportion of chenodeoxycholic acid in gallbladder bile was higher in treated dogs (27.8 +/- 12.5%) than in controls (4.5 +/- 1.9%; P less than 0.01); (2) in hepatic bile, the saturation index and proportion of chenodeoxycholic acid were significantly higher in treated dogs (respectively 0.13 +/- 0.03 and 21.6 +/- 8.8%) than in control dogs (respectively 0.07 +/- 0.01; P less than 0.01 and 4.6 +/- 2.2%; P less than 0.01). In the dog, chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile. It is concluded that the difference of effect of chenodeoxycholic acid in man and in the dog is not related to the duration of administration, but to a species difference.

Administration, Oral↗
PubMed1979

Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile.

To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.

Animals↗