Biomedical subjects
Publications and source records attributed to J C Pector.
A promoting effect of portocaval anastomosis in a triphasic model of rat hepatocarcinogenesis is demonstrated since after initiation and selection premalignant lesions and hepatocellular carcinomas increase. This demonstrates that chronic administration of an exogenous compound is not the only way to promote cancer development.
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Male adult obese (fa/fa) Zucker rats with high hypertriglyceridemia and hyperinsulinemia, and mild hypercholesterolemia were submitted to a portacaval shunt in order to examine the effects of this shunt on blood lipids and lipid synthesis. Sham-operated pair-fed obese (fa/fa) Zucker rats, obese (fa/fa) Zucker rats fed ad libitum, and lean (Fa/?) littermates fed ad libitum served as controls. In fa/fa rats 3 wk after portacaval shunt, fasting serum values of triacylglycerol (-70%) and cholesterol (-43%) were lower and plasma total glucagon was higher (+68%) than in pair-fed sham-operated fa/fa controls. In the same rats 4 wk after portacaval shunt and while fed ad libitum, serum protein was reduced by 22%, plasma pancreatic glucagon was 100% higher, and the hyperinsulinema was not modified. At that time, the wet weight of the liver and its total content in DNA, RNA, protein, and glycogen was decreased by 43%, 22%, 34%, 39%, and 60%, respectively. The in vivo incorporation of 3H2O into liver fatty acids was 76% lower and that into liver cholesterol eas 43% lower, per total organ, while the labeling of glyceride fatty acids was not modified in epididymal adipose tissue when compared with pair-fed fa/fa Zucker rats. In conclusion, portacaval shunting lowered blood triacylglycerol and cholesterol levels in fa/fa rats, and this was due, at least partially, to reduction in hepatic lipogenesis and cholesterologenesis.
Male rats underwent either portacaval shunt or portacaval transposition; in both cases, sham-operated pair-fed rats served as controls. Three weeks after a portacaval shunt, fasting serum values of glucose (-35%) and cholesterol (-24%) were lower, and fasting plasma glucagon was higher (+65%). The wet weight of the liver and its total content in DNA, RNA, and protein decreased by 43, 40, 43, and 48%, respectively. The supernatant of liver obtained after centrifugation at 700 g incorporated less [1-14C]acetate (-56%) into fatty acids and less [1-14C]acetate (-94%) and [2-14C]mevalonate (-37%) into cholesterol. The activity of acetyl CoA carboxylase was reduced by 56%. The in vivo incorporation of [3H]H2O into liver fatty acids was 83% lower and that into liver cholesterol was 39% lower than in pair-fed controls. Several of the preceding parameters, including in vitro and in vivo labeling of hepatic fatty acids and cholesterol, were found to be mostly normal in rats with portacaval transposition. These data suggest that the reduction of fatty acid and cholesterol biosynthesis in the liver of rats with portacaval shunt was due to the reduction of total hepatic blood flow rather than to the diversion of portal blood constituents.
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Male rats were submitted for 3 wk either to portacaval shunt or to portacaval transposition. In both cases, sham-operated pair-fed rats served as controls. After an overnight fast, insulinemia was similar in all groups, but glucagonemia was significantly higher (by 65%) and serum glucose significantly lower (by 35%) in rats with a portacaval shunt. The lipid metabolism of epididymal adipose tissue was studied in vitro, as well as in vivo. In rats with a portacaval shunt, in vitro lipogenesis from [U-14C]glucose, [1-14C]acetate, or 3H2o was 60-80% lower than in sham-operated pair-fed controls. Twice as much in vitro basal lipolysis could be determined. In addition, in vivo lipogenesis from 3H2O was markedly decreased (6 times). By contrast, in rats with portacaval transposition, in vitro lipogenesis was higher (by 80-140%) and basal lipolysis lower (by 63%) than in pair-fed controls. Thus, even when the nutritional state was taken into consideration, the type of portal diversion was the determining factor in influencing lipid metabolism in epididymal adipose tissue.
This test has been previously described and is used routinely by the authors since 1960. The method is based on the alternate arterial blood distribution between skin and muscle of a limb, depending on modifications in the vasomotor tone. Skin temperature, arteriography and progression speed of the contrast medium are measured simultaneously. The test shows the morphology of the arterial lesion. It measures vasomotor reserve by these parameters, especially the skin temperature, before and after administration of pentothal. Results are rated as good, average and poor. The authors have compared this test, performed before surgery, to the results of lumbar sympathectomy and found an excellent correlation. Late result of lumbar sympathectomy can thus be foreseen by means of this test provided no new organic lesion interferes with the hemodynamics of the limb.
The effects of portacaval anastomosis and portacaval transposition on colloidal radiogold fractional clearance and on hepatic cytochrome P-450 level were compared in the rat. Colloidal radiogold fractional clearance was significantly lower in rats with portacaval anastomosis (0.556 +/- 0.188 min-1 (mean +/- 1 SD)) than in sham-operated animals (0.842 +/- 0.151 min-1); hepatic cytochrome P-450 level was likewise lower in the former (0.60 +/- 0.14) nmol/mg of microsomal proteins) than in the latter (0.83 +/- 0.12 nmol/mg of microsomal proteins). Colloidal radiogold fractional clearance was not different in rats with portacaval transposition (0.808 +/- 0.201 min-1) and in sham-operated animals (0.798 +/- 0.064 min-1); hepatic cytochrome P-450 level was significantly lower in the former (0.55 +/- 0.07 nmol/mg of microsomal proteins) than in the latter (0.76 +/- 0.17 nmol/mg of microsomal proteins). If colloidal radiogold clearance is assumed to be an index of liver blood flow, these results suggest that portacaval anastomosis induces a decrease, and portocaval transposition produces no change, in liver blood flow. It is concluded that the decrease in hepatic cytochrome P-450 level in the rat with portacaval anastomosis is not merely the consequence of reduced blood flow, but rather results from deprivation of a substance or substances present in portal blood and contributing to maintenance of the cytochrome level.
Fractional clearance of colloidal gold particles (k), liver weight and hepatic cytochrome P-450 were measured in rats with portacaval shunt and in rats with portacaval shunt plus arterialization of the hepatic stump of the portal vein. The effects of enzyme induction by phenobarbital was studied in both groups. Total arterialization of the liver provides a probably normal hepatic blood flow and seems to protect the liver from post-shunt atrophy. Nevertheless, in both arterialized and shunted rats, the cytochrome P-450 concentration was significantly lower than in controls. The same results were obtained after treatment by phenobarbital. These findings suggest that normal hepatic blood flow and oxygen supply are not the main determinant of a normal activity of the hepatic microsomal biotransformation system. Substances present in portal blood would probably be necessary in maintaining hepatic cytochrome P-450 level.
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