Effect of Dietary Lipids (Soybean Lecithin and Triacylglycerol) on Hepatic F-Actin Microfilaments in Cyclosporine A-Treated Rats

We studied and quantified the effect of cyclosporine A on hepatic F-actin on bile canalicular and basolateral membranes in rats fed either soybean lecithin, triacylglycerol-enriched diet, or low-fat diet by means of confocal laser scanning microscopy imaging. The phalloidin–FITC staining of F-actin was quite normal in the lecithin–cyclosporine A group but decreased significantly in the other cyclosporine A-treated groups (by 40% and 25% of control in triacylglycerol–cyclosporine A and cyclosporine A groups, respectively). The alteration of F-actin by cyclosporine A, related to cholestasis evidenced by a decrease in bile salt secretion, was prevented by dietary soybean lecithin and amplified by dietary soybean triacylglycerol.     

A network model of glomerular function

A model has been developed to establish the determinants of glomerular function by means of a network analysis. The topological and dimensional parameters of the capillary network were obtained by reconstructing the lobular structures of two Wistar rat glomeruli. Calculation of the hydrostatic pressure drop from the afferent to the efferent extremity of the network () was based on the concept of the additional pressure drop per red cell in single-file flow, or, in multiple-layer flow, on in vitro experimental data relating apparent viscosity of blood to dynamic hematocrit and capillary radius. Partition of red cells at bifurcations was calculated as a function of the velocity ratio within the branches. The micropuncture data obtained in Munich-Wistar rats at distal pressure disequilibrium (net ultrafiltration pressure greater than 0) were used to establish the validity of the model. ε was found to be 3.1%. The efferent ultrafiltration pressure was close to the value predicted from the micropuncture data. At distal pressure disequilibrium, 100% of the glomerular surface area was utilized for filtration. In this case, the mean integrated ultrafiltration pressure and the filtration coefficient were close to the values reported by R. C. Blantz, F. C. Rector, Jr., and D. W. Seldin ((1974) Kidney Int.6, 209–225) using the single-tube model of W. M. Deen, C. R. Robertson, and B. M. Brenner ((1972) Amer. J. Physiol.223, 1178–1183). The hydraulic conductance was estimated between 0.046 and 0.09 μl sec^?1 mm Hg^?1 cm^?2S.A. but was dependent on the value chosen for the glomerular surface area.     

Esophageal-atrial fistula

We report an unusual case of an esophageal-atrial fistula in a patient with CREST (calcinosis, Raynaud's phenomenon, esophagitis, sclerodactyly, telangiectasia) variant of scleroderma. An ulcer in Barrett's esophagus perforated into the left atrium and led to systemic embolization and cerebral abscess. A review of similar reports of esophageal-atrial fistula reveals a symptom complex that includes chronic esophageal pathology, gastrointestinal bleeding, and neurological signs. An antemortem diagnosis has never been made.     

Inhibition of Na+/H+ exchange in the rat is associated with decreased ursodeoxycholate hypercholeresis, decreased secretion of unconjugated urodeoxycholate, and increased ursodeoxycholate glucuronidation

In the perfused rat liver, ursodeoxycholate in high dose produces an HCO3- -rich hypercholeresis which we have shown previously to be inhibited by replacement of perfusate Na+ with Li+ or by addition of amiloride (or amiloride analogues). In the present studies, we have determined whether such inhibition is associated with altered ursodeoxycholate biotransformation. Under control conditions, ursodeoxycholate infusion produced a 3.7-fold increase in bile flow and a 9.2-fold increase in biliary HCO3- output. By thin-layer chromatography, ursodeoxycholate radioactivity in bile was present in unconjugated form (15%) or as glycine or taurine amidates. Glucuronide conjugates of ursodeoxycholate accounted for less than 1% of biliary bile acids. Li+/Na+ substitution decreased ursodeoxycholate-stimulated bile flow and HCO3- secretion by greater than 90%, but decreased recovery of ursodeoxycholate and metabolites by only 25%. Amiloride or amiloride analogues decreased ursodeoxycholate-stimulated choleresis and HCO3- output by 38%-76%, yet did not cause decreased recovery of ursodeoxycholate and metabolites. Inhibition of the hypercholeresis was associated with a decrease in unconjugated ursodeoxycholate to less than 2% of total biliary bile acids, a striking increase in ursodeoxycholate glucuronides, and a reciprocal decrease in glycine and taurine amidates. With Li+/Na+ substitution, the predominant metabolites were a mixture of the 24-ester and the 3-aketal (ethereal) glucuronide (29%), and amidation with glycine appeared to be selectively inhibited; with amiloride or its analogues, only the 3-ethereal glucuronide was formed (20%-60% of biliary bile acids), and both taurine and glycine amidation were inhibited. Thus, maneuvers that decrease Na+/H+ exchange inhibit ursodeoxycholate hypercholeresis and cause replacement of unconjugated ursodeoxycholate in bile by its glucuronide. The secretion of unconjugated ursodeoxycholate, a lipophilic bile acid, appears to be necessary for hypercholeresis induced by high-dose ursodeoxycholate infusion.