Search PubMed⌕ Search

Biomedical subjects

W G Hardison

Publications and source records attributed to W G Hardison.

At least 55 records · Page 3Linked to original sources
PubMed1981

Nature of bile acid maximum secretory rate in the rat.

We studied the determinants of maximum bile acid secretory rate (SRm) in the rat. The choledochocaval fistula rat model manifested a bile acid secretory rate far in excess of the SRm previously reported for taurocholate in this species. We studied the ability of various bile acid solutions to maintain the high secretion rate in this model. Whole-rat bile, but not taurocholate in 2% albumin nor rat bile with bile acid content over 90% taurocholate, maintained secretion rate. We concluded that the mixture of bile acids in rat bile was the most important determinant of the high secretion rate and that the high rate was not due to a peculiarity of the model itself nor to the infusion of biliary lipids together with bile acids. Conventional determination of the SRm in the bile fistula rat confirmed this impression, with the least toxic bile acids manifesting the highest SRm. During infusion of taurocholate beyond the SRm, bile flow and bile acid secretion rate fell. This was accompanied only by scattered focal necrosis of single liver cells or of small aggregates of cells and not by any diffuse subcellular morphological change. We believe the maximum bile acid secretory rate is determined by toxicity of a specific bile acid for the secretory mechanism rather than by a limitation in transport receptor number as is usual with substances manifesting classical transport maxima. The high SRm of the 7 beta-hydroxy bile acid, ursodeoxycholic acid, is probably related to its very low toxicity. The high SRm in the choledochocaval fistula rat is probably related to the presence of 7 beta-hydroxy muricholic acids in the bile of this species.

Animals↗
PubMed1981

Bile acids modify alkaline phosphatase induction and bile secretion pressure after bile duct obstruction in the rat.

Bile acids induce synthesis of alkaline phosphatase by cultured hepatocytes. To test whether bile acids account for this enzyme's elevation during cholestasis, we developed an experimental model in which the content of the bile acid pool is controlled at the beginning of cholestasis. After depleting the bile acid pool by external biliary drainage, we obstructed bile flow in four groups of rats and then replenished the pool in three groups with taurocholate, taurochenodeoxycholate, or tauroursodeoxycholate, respectively, and replaced no bile acid in the fourth. Hepatic bile acid concentrations were elevated in all obstructed groups; however, the levels were higher in the groups that received bile acid replacement. Cholate was not metabolized, but both chenodeoxycholate and ursodeoxycholate were transformed to beta-muricholate. Although hepatic alkaline phosphatase activity rose in all obstructed animals, the levels achieved were higher in each group treated with bile acids than in the group that was not. Increases in plasma activities of alkaline phosphatase and 5'-nucleotidase occurred only after treatment with cholate or chenodeoxycholate. Bile secretion pressure was higher after ursodeoxycholate or no bile acid treatment but was lower after cholate or chenodeoxycholate replacement. Thus, all bile acids tested induced hepatic alkaline phosphatase to some degree, but only certain ones--those which reduced bile secretion pressure--released the enzyme into plasma. We conclude that, in the rat, the hepatic response to acute cholestasis is influenced by the composition of the intrahepatic bile acid pool and that various bile acids have significantly different effects on this response.

Alkaline Phosphatase↗
PubMed1980

Taurine transport by rat hepatocytes in primary culture.

Hepatic taurine concentration is 30--100 times that of plasma, suggesting an efficient taurine uptake mechanism in the hepatocyte. The characteristics of hepatic taurine transport were studied in primary cultures of adult rat hepatocytes. Taurine uptake was concentrative and linear for over 4 h. At taurine concentrations 2.5--100 microM, uptake was saturable with constants Km = 44 microM, V = 0.28 nmol/mg protein per min and EA = 13.2 kcal/mol. Uptake was inhibited 41% by incubation under N2 and was competitively inhibited by beta-alanine (Ki = 94 microM) and hypotaurine (Ki = 14 microM). Uptake was linearly dependent upon Na+ concentration from 0 to 140 mM. A second nonsaturable uptake process was identifiable only at taurine concentrations greater than 1 mM. This process was presumed to represent passive diffusion. At taurine concentrations existing in plasma, taurine enters the hepatocyte primarily by a single, Na+-dependent, carrier-mediated, oxygen-requiring transport process.

Animals↗
PubMed1979

Enterohepatic circulation rates of cholic acid and chenodeoxycholic acid in man.

The rate of enterohepatic cycling of cholic acid and chenodeoxycholic acid was determined in five male subjects. Pool sizes were measured by isotope dilution technique after intraduodenal administration of 14C-labelled cholic and chenodeoxycholic acid. The hourly hepatic secretion rate of bile acids was determined by an intestinal perfusion technique. From these data the cycling frequency was calculated. Chenodeoxycholic acid circulated on an average 1.34 (range, 1.13--1.57) times faster than cholic acid, probably because chenodeoxycholic acid to a larger extent than cholic acid is absorbed from the proximal small intestine and thus partly bypasses the hepaticoileal circuit. This difference in cycling rate may have methodological as well as physiological implications.

Bile Acids and Salts↗
PubMed1979

Effect of acute alterations in small bowel transit time upon the biliary excretion rate of bile acids.

The rate of biliary bile acid excretion is a product of bile acid pool size and enterohepatic cycling frequency. Cycling frequency, in turn, is determined by the time necessary for bile acid to travel from the ampulla of Vater to its small bowel absorptive site, from its absorptive site to the liver, and from the liver to the duodenum. In 10 subjects receiving constant intraduodenal infusion of an isocaloric formula containing the nonabsorbable markers polyethylene glycol and beta-sitosterol, the authors altered small intestinal transit time and measured the effect upon biliary bile acid excretion rate. Sorbitol (15% formula) shortened transit time by 38% and increased hourly bile acid excretion rate by 31%. Atropine (0.04 mg i.m. q 2 hr) increased transit time by 38% and decreased hourly bile acid excretion rate by 38%. Biliary excretion rates of cholesterol and of bilirubin, substances excreted in bile but not subject to enterohepatic circulation, did not change with changes in transit time. This suggests that sorbitol and atropine were not acting upon the biliary limb of the enterohepatic circulation but rather on the intestinal limb. The authors conclude that small bowel transit time is a major determinant of enterohepatic cycling frequency.

Aged↗
PubMed1979

Cholesterol and bile acid metabolism in moderately advanced, stable cirrhosis of the liver.

We have selected for this study a well-defined group of patients with moderately advanced but compensated alcoholic cirrhosis. They were well-nourished and had no ascites, varices, azotemia, or encephalopathy. Liver biopsy showed little or no necrosis and inflammation despite wide-spread fibrosis. Serum bilirubin, transaminase, alkaline phosphatase, albumin and globulins were essentially normal. Biochemical evidence for liver disease was restricted to modest elevation of BSP retention, gamma GTP, serum bile acid concentrations, and urinary bile acid excretion. Except for changes in the interrelationships among the three biliary lipids, they were generally spared the abnormalities of sterol metabolism described in other patients with more advanced, more active liver disease. Thus, striking abnormalities in the metabolism of cholesterol and bile acids probably require severe reductions in functioning hepatocellular mass, major portal-systemic shunting, high disease activity, or all three to become manifest.

Adult↗
PubMed1978

Importance of bicarbonate in bile salt independent fraction of bile flow.

The bile salt independent fraction (BSIF) of canalicular bile flow from the isolated rat liver perfused with bicarbonate-free perfusate is 50% of that from the liver perfused with bicarbonate-containing perfusate. HCO3-excretion is nearly eliminated and Na+ and Cl- excretion is reduced 50%. Replacement of HCO3- into perfusate increased bile flow by 0.3 microliter/g.min without changing bile acid excretion rate. 5.5-Dimethyl-2,4-oxazolidinedione (DMO) produced a similar effect. DMO was passively distributed between bile and plasma. The data indicate that a bicarbonate transport mechanism is responsible for production of up to 50% of the BSIF. Another weak acid, N-5[5-(2-methoxyethoxy)-2-pyrimidinyl]sulfamoylbenzene (glymidine), was rapidly excreted into bile and increased bile flow by over 2.0 microliter/g.min. Glymidine is probably excreted by an independent organic anion transport mechanism, and any effect on the bicarbonate transport mechanism is obscured. Canaliculus-enriched hepatocyte membrane fractions contained no HCO3-stimulated ATPase activity. Either this enzyme is unimportant in hepatocyte bicarbonate transport or transport occurs across membranes other than the bile canalicular membrane.

Adenosine Triphosphatases↗
PubMed1978

Hepatic taurine concentration and dietary taurine as regulators of bile acid conjugation with taurine.

Taurine concentration in liver biopsies taken from 20 patients undergoing cholecystectomy or laparotomy for obstructive jaundice correlated with percentage of taurine-conjugated bile acids in hepatic bile. In biliary obstruction, taurine concentrations in muscle did not parallel high hepatic taurine concentrations, suggesting selective hepatic taurine accumulation in biliary obstruction. In fasting subjects with an intact bile acid enterohepatic circulation, per cent taurine-conjugated bile acids in bile was the same as per cent taurine conjugation of bile acids by the liver. Ingestion of small amounts of taurine (250 mg) can increase the per cent taurine conjugation by the liver. Of 10 subjects, 7 increased per cent taurine conjugation of bile acids by the liver by 2.5 to 10% at 2 1/2 hr after intraduodenal taurine administration. We conclude that hepatic taurine concentration is a major determinant of per cent taurine conjugation of bile acids by the liver in man. In the fasting subject with an intact enterohepatic circulation, per cent taurine-conjugated bile acid in the bile acid pool is very close to the per cent taurine conjugation of bile acids by the liver. Hepatic bile acid conjugation pattern may differ from that of the bile acid pool as a result of taurine ingested with meals, but the deviation is small, and acute alteration of the per cent taurine conjugation in the bile acid pool does not occur.

Bile↗
PubMed1977

Influence of hepatic taurine concentration on bile acid conjugation with taurine.

In vitro, addition of taurine to liver homogenates increases the proportion of cholic acid conjugated with taurine. In the present study, the relation between hepatic taurine concentration and the proportion of infused sodium cholate conjugated with taurine was studied in the whole organ. The isolated perfused liver was studied to eliminate possible transfer of taurine to or from the large extrahepatic poosl present in vivo. During cholate infusion, the proportion of taurocholate excreted in bile decreased, and the proportion of glycocholate increased in a complementary fashion. Infusion of taurine with cholate prevented these changes. Hepatic taurine concentration, calculated from measured hepatic taurine concentrations before and at the end of cholate infusion, fell. Fall in proportion of total bile acid excreted as taurocholate was most rapid at low hepatic taurine concentrations between about 1.4 and 0.65 mumol/g liver. Hepatic taurine concentrations is a major determinant of the proportion of bile acid conjugated with taurine.

Animals↗