Hepatic lesions of central pericellular fibrosis in morbid obesity, and after jejunoileal bypass.

Histologic findings in liver biopsy specimens obtained from 88 patients before and one and two years after end-to-end jejunoileal bypass are compared. In addition to the expected fatty changes, mild changes of centrilobular, pericellular fibrosis were present in the initial biopsies in 8.6%; a year later they had become apparent in 46%. Portal-central bridging developed in 6.8%, and early micronodular cirrhosis in 3.4%--always in those with central pericellular fibrosis. Electron-microscopic study of pre-bypass liver biopsies from eight addtional patients showed collagen and electron-dense material resembling basement membranes within the spaces of Disse in seven, although only four had light-microscopic evidence of minimal central pericellular fibrosis. The existence of these light- and electron- microscopic changes before jejunoileal bypass suggests that there is a lesion in morbid obesity that may be exacerbated during the first year after operation.

The effect of portacaval shunt on plasma lipids and tissue cholesterol synthesis in the dog.

Portacaval shunt (PCS) has been proposed as a therapy for hyperlipidemia; however, its lipid-lowering mechanism is unknown. In this study PCS was performed on ten mongrel dogs to measure its effect on plasma lipids and on the cholesterol synthesizing ability of the liver and intestines, the major indodenous cholesterol synthesizing tissues. Plasma was analyzed for total cholesterol (CHOL), triglycerides (TG), and the CHOL content of three plasma lipoprotein fractions. Jejunal, ileal, and hepatic cholesterol synthetic rates were determined by 14C-acetate incorporation to CHOL in tissue slices obtained at operation before PCS and 44 +/- 4.1 (S.D.) days after PCS. Plasma CHOL decreased by 18 +/- 7 (S.E.), 34 +/- 8 (S.E.), and 57 +/- 14 (S.E.) mg. per 100 ml. by 4, 6, and 16 weeks after PCS, respectively. TG decreased by 13 +/- 5 (S.E.), 27 +/- 5 (S.E.), and 30 +/- 9 (S.E.) mg. per 100 ml. at corresponding time intervals. Paired Student's test analysis of CHOL and TG changes are significant at the p less than 0.05 level. CHOL content of the three plasma lipoprotein fractions decreased correspondingly. Intestinal tissue CHOL synthesis rates changed only slightly. Hepatic synthetic rates increased by 30 to 40%; however, no synthetic rate changes were statistically significant at the p less than 0.05 level. PCS is associated with decreased in plasma CHOL [42% (see article)] AND TG [53% (see article)] in dogs up to 16 weeks following operation. Statistically significant changes in endogenous CHOL synthesis were not demonstrated by this study. The mechanism by which PCS affects plasma lipids in the dog is unknown as yet.

Hepatic veno-occlusive disease in a renal transplant patient receiving azathioprine.

Central vein phlebitis and occlusion developed in a patient who was receiving immunosuppressive therapy with azathioprine (Imuran) and prednisone after renal transplantation. He had been well for 1 year before evidence of liver disease was noted; once begun, it progressed to hepatocellular failure in spite of a change in immunosuppressants from azathioprine to cyclophosphamide. Several known causes of venoocclusive disease and the possible causes in this patient are discussed.

Polyenoic acid metabolism in cultured dissociated brain cells.

The incorporation of [1-(14)C]linolenate (18:3 n - 3) into cellular lipids of cultured dissociated brain cells was studied. During the initial phases of incubation, radioactivity was found in free fatty acids, diacylglycerols, triacylglycerols, and choline phosphoglyceride pools preferentially. Incorporation into the ethanolamine phosphoglyceride pool increased steadily and paralleled desaturation and chain elongation of 18:3 --> 20:3 --> 20:4 --> 20:5 --> 22:5 --> 22:6. From pulse-chase studies it was evident that the label of the highly polyunsaturated fatty acids in ethanolamine phosphoglycerides is constantly increased while the label in the fatty acids of choline phosphoglycerides decreased. Uptake of 18:3 by the cells was reduced by lowering incubation temperature, the triacylglycerol and ethanolamine phosphoglyceride pools being mainly affected. Lowering the incubation temperatures essentially abolished conversion of labeled 18:3 to the higher polyenoic acids. At intermediate temperatures, conversion of 18:3 to 20:5 n - 3 was still active, but conversion of 20:5 n - 3 to 22:6 n - 3 was abolished, suggesting that formation of 22:6 from 18:3 proceeds by at least two reactions distinguishable by their temperature dependency.

Monoglyceride modification of jejunal absorption of fatty acid in the rat.

The effect of increasing the intracellular pool of monoolein upon the subsequent uptake and esterification of oleic acid was investigated using in vitro rat jejunal slice techniques. The mucosal pool of monoglyceride was expanded by preincubation of jejunal slices in a monoglyceride-containing bile salt medium at a temperature close to 1 degrees C, which inhibited esterification. Subsequent incubation in micellar [(14)C]oleic acid was performed either at 37 degrees C or in the cold. Monoglyceride preincubation increased [(14)C]oleic acid uptake by about 60% without increasing incorporation of fatty acid into triglyceride. This was not due to inhibition of esterifying capacity nor to changes in oleic acid binding to a mucosal fatty acid-binding protein. It is suggested that under these experimental conditions monoglyceride may modify intracellular pools of fatty acid. However, when monoglyceride and fatty acid were preincubated together, mucosal esterification rates during subsequent incubation at 37 degrees C more than doubled. Implications of these data for present theories of rate-limiting steps in lipid absorption are discussed.