Biliary excretion of dye was evaluated in three normal and one mutant Corriedale sheep (characterized by depressed biliary transport of many organic anions) during infusion of unconjugated sulfobromophthalein (BSP) and its preformed glutathione conjugate (BSP-GSH). Maximal dye excretion rates in bile in normal sheep were higher when BSP-GSH rather than BSP was administered. In confirmation of earlier studies, dye excretion in bile was markedly depressed in the mutant animal. However, movement of unconjugated BSP from liver cells into bile remained relatively intact whereas transport of conjugated BSP compounds was virtually absent. Preservation of unconjugated dye entry into bile suggests the presence of a transport mechanism for unconjugated BSP which is preserved in mutant sheep and is distinct from that involved in BSP-GSH excretory transport. Renal clearance of conjugated BSP compounds was greater than of unconjugated BSP and clearance values were comparable in the normal and mutant sheep. Thus, no excretory defect comparable to that present in liver was identifiable in the kidney.

Animals↗

PubMedDate not supplied

Bone disease in primary biliary cirrhosis: increased bone resorption and turnover in the absence of osteoporosis or osteomalacia.

The role of vitamin D in hepatic osteodystrophy was examined. Eleven unselected patients with primary biliary cirrhosis (PBC) were assessed for disorders of mineral and vitamin D metabolism. Six were not receiving supplementary vitamin D, and five were being treated with oral vitamin D (50,000 IU daily). Serum levels of 25-hydroxyvitamin D were normal in all patients receiving oral therapy and in 4 of 6 untreated patients. Levels of serum 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D were normal or near normal in all patients. Studies were repeated after 6 months of therapy with parenteral vitamin D2 (100,000 IU i.m. monthly) in 7 patients. Initial bone histomorphometry revealed no evidence of osteomalacia or osteoporosis. However, the bone resorption surface of trabecular bone was increased. This abnormality was no longer present on repeat bone biopsies obtained after parenteral vitamin D therapy, and bone formation had decreased. In addition, trabecular bone volume remained normal in the face of the lower rate of bone formation. Increased bone resorption surface in the absence of osteoporosis or osteomalacia has not been previously described in PBC. Improvement in this bone parameter, associated with the finding of a decrease in the formation of bone and in hydroxyproline excretion in urine after parenteral vitamin D, suggests that increased turnover may be an early feature of the bone disease which complicates PBC and that parenteral vitamin D may retard the rate at which hepatic osteodystrophy develops in chronic cholestatic liver disease.

Adult↗

PubMedDate not supplied

Sinusoidal endothelial cells from normal guinea pig liver: isolation, culture and characterization.

Guinea pig nonparenchymal hepatic cells were isolated by enzymatic digestion and subsequent separation on a 17.5% metrizamide gradient. Endothelial cell and Kupffer cell-enriched fractions were separated by centrifugal elutriation. Viability of both cell fractions was approximately 80%. Endothelial cells were cultured on a substratum of guinea pig liver collagen and 1% gelatin (1:1). Freshly isolated and cultured sinusoidal endothelial cells contained Factor VIII R:antigen, angiotensin I converting enzyme activity, and they synthesized prostaglandins characteristic of other endothelial cells. Sieve plates were identified in both freshly isolated and cultured cells. Fresh endothelial cells and Kupffer cells formed Fc receptor-mediated rosettes with IgG-opsonized sheep red blood cells, but cultured endothelial cells did not. Only Kupffer cells demonstrated Fc and C3 receptor-mediated phagocytosis. These methods for isolating and culturing sinusoidal endothelial cells should permit further functional assessment of endothelial cells and their interrelationship with other sinusoidal lining cells.

Animals↗

PubMedDate not supplied

The immunologic diagnosis of chronic active "autoimmune" hepatitis: distinction from systemic lupus erythematosus.

We have evaluated the immunologic characteristics often associated with systemic lupus erythematosus in a series of patients with a variety of different liver diseases. Antibody to double-stranded DNA as measured by the Farr assay was detected frequently in patients with various forms of liver disease. No patient with liver disease, including those with a presumed immunologic etiology, was found to have antibody to double-stranded DNA using more specific assays. Other immunologic phenomena such as the presence of immunofluorescent staining at the dermal-epidermal junction in the lupus band test, circulating immune complexes and the presence of antinuclear antibody were present in a number of patients with different forms of liver disease. The absence of antibody to double-stranded DNA in patients with liver disease suggests that there may be a true immunologic distinction between systemic lupus erythematosus and chronic active ("lupoid") hepatitis.

Adult↗

PubMedDate not supplied

The effect of glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine in intact rats.

The effect of hepatic glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine was assessed in fed male Sprague-Dawley rats. Within 30 min of i.p. administration of either diethylmaleate or phorone, hepatic glutathione fell approximately 75 to 80% and remained depressed for the ensuing 120 min. [14C]Aminopyrine was i.p. administered 30 min after the glutathione-lowering agents (zero time) and exhaled 14CO2 was collected at 15-min intervals for the next 120 min. Parameters of 14CO2 exhalation including peak exhalation rate, cumulative exhalation from 0 to 120 min and the elimination rate constant were all impaired in glutathione-depleted rats. Metabolism of the [14C]methyl groups involves N-demethylation with formation of formaldehyde, oxidation to formate and conversion to 14CO2. Glutathione depletion did not affect CO2 evolution from i.p. administered formate or bicarbonate. The glutathione-dependent step presumably involves either or both generation of formaldehyde or its subsequent oxidation to formate.

Aminopyrine↗