A case of novobiocin-induced jaundice is described in which the main feature was elevated unconjugated bilirubin in the serum. No evidence of hemolysis or hepato-cellular failure was demonstrated.The effect of novobiocin on serum bilirubin was studied by administering 2 g. of the drug daily in four divided oral doses for two days. An increase in serum unconjugated bilirubin was nearly always observed in the normal subjects and in patients with cirrhosis of the liver. This rise was particularly significant in three patients with hemolytic anemia and in two patients with Gilbert's disease. After an oral dose of 500 mg. the BSP clearance was decreased after one hour and it was close to normal after three hours. Since hemolysis is not responsible for this elevation of serum unconjugated bilirubin, the novobiocin-induced hyperbilirubinemia appears to be due to a direct effect of the drug upon the liver.

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PubMedDate not supplied

Hepatocyte bile secretion: current views and controversies.

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PubMedDate not supplied

Measurement of serum alpha 1-acid glycoprotein and alpha 1-antitrypsin desialylation in liver disease.

To determine whether the presence of circulating desialylated glycoproteins reflect the existence and/or the severity of liver disease, 73 patients were evaluated with liver biopsies, conventional liver function tests, and the measurement of the degree of desialylation of two glycoproteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT). A combination of two immunological methods, available as routine laboratory tests, was used for the determination of the desialylation of alpha 1-AGP and alpha 1-AT. The severity of liver disease was assessed by a clinical classification depending upon the presence or absence of four complications (jaundice, ascites, hepatic encephalopathy, and weight loss). The presence of serum desialylated alpha 1-AGP did not allow detection of mild liver disease, but asialo alpha 1-AGP (and to a lesser extent of asialo-alpha 1-(AT) correlated with the severity of liver disease. The sensitivity of desialylated alpha 1-AGP in detection of severe liver disease was 65%, and its specificity was 80%.

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PubMedDate not supplied

A new method to measure portal and hepatic blood flow using taurocholate in the rat.

Hepatic artery and portal vein blood flows were assessed separately in anesthetized rats using radiolabeled taurocholate. The ratio of portal vein blood flow to total hepatic blood flow was calculated from measurements of taurocholate concentrations of portal vein, hepatic artery and hepatic vein, and of taurocholate hepatic extraction ratio. Animals were administered [14C]taurocholate intraperitoneally as a label of the taurocholate pool 24 hr before the experiments. In steady-state conditions, serum [14C]taurocholate activities were used as an index of taurocholate relative concentration and the hepatic extraction ratio of taurocholate was estimated using [3H]taurocholate infused into the systemic blood stream. Total hepatic blood flow was estimated by the Fick's principle using indocyanine green. The mean hepatic blood flow was 13.9 ml X min-1 (S.E. 1.9), and the mean ratio of portal blood flow to hepatic blood flow was 72.2% (S.E. 6.7). It is concluded that taurocholate may be used to assess separately portal venous and hepatic arterial blood flow in the rat.

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PubMedDate not supplied

Franco-Belgian cooperative study of ursodeoxycholic acid in the medical dissolution of gallstones: a double-blind, randomized, dose-response study, and comparison with chenodeoxycholic acid.

A double-blind randomized, multicenter study was carried out to determine the efficacy and safety of ursodeoxycholic acid (UDCA) at 4 doses of 2.1 to 16.2 mg X kg-1 X day-1, and chenodeoxycholic acid (CDCA) at the dose of 16.9 mg X kg-1 X day-1, in 197 patients treated for up to 1 year for radiolucent gallstones in functioning (opacified) gallbladders. There was confirmed complete dissolution in 5.9% of patients receiving UDCA at the dose of 2.1 mg X kg-1 X day-1, 18.9% in those receiving 4.2, 28.9% in those receiving 8.4, 14.6% in those receiving 16.2, and 20.0% in patients receiving CDCA. Partial (over 50%) or complete dissolution occurred in 29.4% of patients receiving 2.1 mg X kg-1 X day-1 of UDCA, 37.8% of those receiving 4.2, 55.2% in those receiving 8.4, 48.7% in those receiving 16.2, and 50.0% in patients receiving CDCA. Complete dissolution occurred significantly more frequently in small (less than 5 mm in diameter) than in large (5 to 15 and more than 15 mm) stones. There was no significant influence of treatment on serum cholesterol and triglycerides in any of the groups. Serum aminotransferases remained normal (or lower than twice the upper normal limit) in all patients treated with UDCA. Diarrhea leading to cessation of treatment occurred in 5% of patients receiving UDCA, but was significantly less frequent than in those receiving CDCA. These results confirm that, within a 1-year period, UDCA is equally effective and induces diarrhea less frequently than CDCA, with an optimal dose (8 mg X kg-1 X day-1) approximately twice lower than that of CDCA.

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PubMedDate not supplied

Long-term maintenance of taurocholate uptake by adult rat hepatocytes co-cultured with a liver epithelial cell line.

Taurocholate (TC) uptake by adult rat hepatocytes co-cultured with other rat liver epithelial cells (RLEC) was studied comparatively to hepatocytes in primary culture. Cells were cultured on Petri dishes for desired times prior to measuring their ability to transport TC. TC uptake was linear for 150 sec in both culture conditions. In hepatocytes cultured alone, the initial rate of TC uptake at an extracellular concentration of 100 microM was 0.19 +/- 0.02 nmole per min per 10(6) cells after 48 hr of culture and decreased by 75% after 4 to 6 days. In hepatocytes co-cultured with RLEC, the rate of uptake at 48 hr (0.31 +/- 0.01 nmole per min per 10(6) cells) was significantly higher than in hepatocytes cultured alone (p less than 0.01); in addition, TC uptake remained stable at an average rate of 0.17 +/- 0.01 nmole per min per 10(6) cells for up to 56 days. No detectable uptake was found in RLEC cultured alone. TC uptake exhibited both saturable (Vmax = 0.30 +/- 0.03 nmole per min per 10(6) cells and Km = 42.6 +/- 4.4 microM) and nonsaturable components. These kinetic parameters were similar to those previously reported in isolated hepatocytes and in short-term cultured hepatocytes. TC uptake exhibited sodium dependence and was significantly reduced when extracellular sodium was replaced by lithium and sucrose, or in the presence of 1 mM ouabain. After 18 days of co-culture, TC uptake had qualitatively the same characteristics as at 48 hr, with a saturable and a nonsaturable component.(ABSTRACT TRUNCATED AT 250 WORDS)

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