Influence of dietary protein and carbohydrate on phenytoin metabolism in man.
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Biomedical subjects
Publications and source records attributed to C Balabaud.
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Liver atrophy is a main feature in rats with a porto caval shunt. Histological studies revealed small size hepatocytes. Ultrastructural differences between periportal and centrolobular zones were noticed, in particular, the dilatation of the nuclear envelope and of the rough endoplasmic reticulum which appeared dilated, desorganized and sometimes without ribosomes, was more pronounced in the periportal zone. Hepatocytes of this zone might be more sensitive to the decrease of O2 and/or hepatotrophic factors.
In the rat after food intake, whether during the dark or light period, bile flow increases. Food intake seems to be a major factor in the circadian rhythm of bile secretion.
Phenylbutazone, a well-known enzyme inducer, at a dose of 80 mg . kg-1 once daily for 8 days increases liver weight and bile flow expressed per g of liver (p less than 0.01). The bile salt secretory rate is not increased.
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The contribution of hepatocytes of different acinar zones to bile salt transport and to the secretion of the BSNDF was studied in the rat. Changes in the removal of 14C-taurocholate from blood, in the biliary secretion of taurocholate, and in canalicular flow were determined after damage of the periportal (acinar zone 1) or centrilobular (acinar zone 3) areas by allyl alcohol or bromobenzene, respectively. The extent of cell necrosis was quantitated by light microscopy, and the quality of the intracellular damage was assessed by electron microscopy. After either periportal or centrilobular damage, surviving cells responded to an intravenous infusion of taurocholate by secreting bile salts into bile at a rate similar to controls. However, following the administration of 14C-taurocholate at high concentrations and as a single bolus, the rate of removal of this isotope from blood was slower than in controls. Both experiments suggested that periportal and centrilobular hepatocytes had the capability for bile salt transport. Consequently, since the concentration of bile salts in sinusoidal blood at each zone determines the relative contribution of hepatocytes to bile salt transport, periportal cells probably transport the largest amount of bile salts reaching the acinus. Canalicular bile flow, on the other hand, decreased following centrilobular cell damage, and this was associated with a high concentration of bile salts in bile. This suggested that at bile salt loads near physiological concentrations, the predominant contribution of centrilobular hepatocytes is to the secretion of the BSNDF.
The bile salt-nondependent fraction of canalicular bile water has been measured by the extrapolation to zero of the regression line representing the relationship between bile flow and bile salt secretion. This extrapolation assumes that the secretion of bile salts whatever their concentration, carries the same amount of water per molecule. The purpose of this study was to test this assumption. Rats were depleted of bile salts by a bile fistula and infused with sodium taurocholate at rates varying from 30 to 500 mmumol/min. Bile salt secretion was linear with bile salt infusion at any concentration. Values of bile flow and bile salt secretion were grouped according to bile salt concentration, and regression lines calculated. The slopes of the regression lines changed from 0.090 at bile salt concentrations below 10 mM to 0.012 at bile salt concentrations between 30 and 45 mM, (p less than 0.001). These results indicate that the relationship between bile flow and bile salt secretion in the rat cannot be represented by only one regression line. Consequently, the rate of secretion of the bile salt-nondependent fraction of canalicular bile water cannot be measured by the extrapolation of this single regression line.
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In rats the bile flow and the estimated bile acid independant flow (BAIF) were significantly lower at 17.00 h than at 08.00 and 24.00 h. The decrease in BAIF paralleled the decrease in liver weight. Bile acid excretion was not different.
Hepatic blood flow was measured in the unanesthetized rabbit using the clearance technique of 198Au and 125I RB. The values are: 71.82 +/- 16.24 ml-min-1-kg-1 for 198Au, and 60.21+/-9.94 ml-min-1-kg-1 for 125I RB (P less than 0.01). The overestimation of HBF with colloidal gold is probably due to extra splanchnic sequestration which has been estimated to be 15+/-3%. The week extraction of RB limits the use of this dye for measurements of HBF. HBF is easier to measure with 198 Au.
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In five rats with congenital portacaval shunt, liver atrophy, hyperplastic foci in the periportal zone, atrophic hepatocytes in the centrolobular zone, well-preserved hepatocyte ultrastructure with abundant rough endoplasmic reticulum, packed mitochondria and numerous peroxisomes were observed as in surgical portacaval shunt. However, portal triads were abnormal in contrast to surgical shunt. In large portal triads, hepatic arteries were prominent, bile ducts numerous and portal veins were lacking. Instead, small or large capillaries were seen in the portal tracts usually at the periphery. These capillaries appeared to be in continuity with nearby sinusoids presenting the ultrastructural characteristics of capillaries. These observations suggest that absence of the portal vein is compensated by formation of neocapillaries. It is assumed that these capillaries originate from periportal sinusoids and are necessary to distribute blood to all sinusoids and form a reservoir to lower arterial pressure.
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Perisinusoidal fibrosis of the liver was discovered in a 22 year-old woman with idiopathic thrombocytopenic purpura requiring splenectomy. No etiology of fibrosis could be found. As shown by immunocytochemistry, collagen types I, III, IV, laminin, and fibronectin were increased. Under electron microscopy, numerous collagen bundles and fragments of basement membrane-like material were demonstrated. Perisinusoidal cells loaded with lipids showed several of the characteristics of fibro/myofibroblasts, while the activity and number of Kupffer cells were apparently increased. The exact mechanism of fibrosis in this case remains unknown but it is likely that platelet destruction and/or Kupffer cell hyperactivity played a role.
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