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Biomedical subjects

R C Pirola

Publications and source records attributed to R C Pirola.

At least 55 records · Page 3Linked to original sources
PubMed1984

Chronic ethanol feeding causes accumulation of serum cholesterol in rat pancreas.

In a previous study, a rat model of ethanol-induced pancreatic steatosis was developed in which chronic ethanol feeding resulted in a twofold increase in pancreatic cholesteryl ester content. The studies reported here were performed in order to elucidate the mechanism of this cholesteryl ester accumulation. Rats were pair fed ethanol or control diets for 3 weeks. Ethanol feeding resulted in an increased accumulation of serum cholesterol in the pancreas. Ethanol feeding also resulted in increased in vitro incorporation of labeled acetate and mevalonate into the sterol moiety of pancreatic cholesteryl ester and increased incorporation of labeled acetate into its fatty acid component. These results suggest that chronic ethanol feeding causes pancreatic cholesteryl ester accumulation by affecting exchange of cholesterol between serum and pancreatic tissue.

Acetates↗
PubMed1983

Increased phospholipid synthesis in the stimulated rat and human pancreas.

Stimulation of the exocrine pancreas is associated with marked changes in pancreatic phospholipid metabolism. It has been previously established that de novo synthesis of phospholipids constitutes part of this "phospholipid effect". This study has demonstrated that in vitro stimulation of the rat pancreas utilising bethanecol and pancreozymin results in increased incorporation of labelled glucose into phosphatidyl inositol and, to a lesser extent, other phospholipids, suggesting increased de novo synthesis of these compounds. However, secretin which is believed to act via a different intracellular pathway, did not exert such an effect. The relevance of this animal model is indicated by the demonstration of increased incorporation of labelled glucose into phospholipids of human pancreas stimulated in vitro by bethanecol or sincalide (the active carboxy terminal octapeptide of pancreozymin).

Animals↗
PubMed1983

Pathogenesis of alcoholic pancreatitis.

The pathogenesis of alcoholic pancreatitis continues to be a puzzle. Of the many theories as to how alcohol might cause pancreatic damage, none satisfactorily explains why only a minority of alcoholics develop clinical pancreatitis. Hypertriglyceridemia and inherited factors could be important antecedents in some individuals, and high fat and protein diets may favour the development of the disease. Disturbances of the sphincter of Oddi have been postulated, but there are experimental and theoretical objections to the view that alcoholic pancreatitis generally results from sphincter dysfunction (obstruction-hypersecretion, biliary-pancreatic reflux and duodeno-pancreatic reflux). Biochemical studies of the effect of alcohol on pancreatic tissue have so far been relatively unrewarding. The most widely held view is that alcohol causes the deposition of protein in peripheral ducts leading to obstruction, inflammation and degeneration. However, it remains to be shown that these deposits are the cause rather than a result of pancreatic inflammation. Research might be facilitated by the development of a suitable animal model of the disease.

Adult↗
PubMed1982

Alcohol causes a fatty pancreas. A rat model of ethanol-induced pancreatic steatosis.

To develop an animal mode of alcoholic pancreatic steatosis, female Wistar rats were pair fed liquid diets, containing ethanol as 36% of calories or an isocaloric amount of carbohydrate for 3 weeks. Electron microscopic examination showed lipid vesicles localized principally at the bases of pancreatic acinar cells in the ethanol-fed rats. Ethanol feeding significantly increased pancreatic content of cholesteryl ester without changing levels of other lipids. Ethanol feeding enhanced labeled acetate, palmitate, oleate, and linoleate incorporation into cholesteryl ester. Therefore, increased esterification of cholesterol may, in part, explain the observed accumulation of cholesteryl ester.

Alcoholism↗
PubMed1981

Ethanol-induced changes in cardiac lipid metabolism.

The influence of ethanol on cardiac lipid metabolism has been investigated in the rat. Acute in vitro ethanol significantly stimulated the incorporation of 14C-1-acetate but not 14C-U-glucose into cardiac lipid in rats fed a diet free of ethanol for 3 weeks. Stimulation of incorporation was not uniform but was confined to the diglyceride and triglyceride fractions. This response of cardiac tissue lipid metabolism to acute ethanol was not observed in rats pair fed an isocaloric diet containing 36% of calories as ethanol. Chronic ethanol feeding significantly increased cardiac triglyceride content when compared with pair-fed controls. It also stimulated oxidation of labeled palmitate, but did not affect in vitro lipogenesis.

Animals↗
PubMed1980

Hemangioendothelial sarcoma of the liver associated with long-term estrogen therapy in a man.

An elderly male patient developed a hemangioendothelial sarcoma of the liver after 9 years of stilbestrol therapy. The latter had been commenced as treatment for presumed carcinoma of the prostate. However, the latter diagnosis was never established, even at a subsequent autopsy, and presumably this was the reason he survived and had such a long course of treatment. It is suggested that there was a causal relationship between the estrogen therapy and the development of the sarcoma. This suggestion is supported by the fact that one similar case has been reported, and by recent evidence that hemangioendothelial sarcoma may be associated with the long-term use of androgenic-anabolic steroids.

Aged↗
PubMed1980

Influence of ethanol on pancreatic lipid metabolism.

The influence of acute exposure to ethanol on rat pancreatic lipogenesis has been investigated. Marked alterations of in vitro pancreatic lipid metabolism were found with changes compatible with increased de novo triglyceride synthesis. Ethanol in vitro stimulated (U--14C) glucose incorporation into triglyceride, but inhibited incorporation into phosphatidyl choline. Prior exposure to ethanol did not further enhance these effects on labeled glucose incorporation. One hour after feeding ethanol at a dose of 378 mg/100 g body weight, (1--14C) acetate incorporation in vitro into pancreatic lipid was significantly increased. This increase was not uniform, but was confined to the free fatty acid, triglyceride, sphingomyelin, and phosphatidyl choline fractions. Similar observations were made when pancreatic tissue from saline-fed control animals was incubated in the presence of ethanol at a concentration of 3.4 mM. Prior exposure to ethanol enhanced this stimulatory effect, and tissue from the alcohol-fed animals incubated in the presence of ethanol incorporated more acetate label into all lipid fractions than tissue from alcohol-fed animals incubated without ethanol and from saline-fed animals incubated in the presence of ethanol.

Acetates↗
PubMed1976

Hypothesis: energy wastage in alcoholism and drug abuse: possible role of hepatic microsomal enzymes.

Hepatic microsomal drug oxidation appears to be an energy-wasteful process because it has no known link with energy-conserving mechanisms such as the synthesis of ATP, and in addition it requires the uncoupled oxidation of NADPH. It is postulated that this can appreciably alter the energy balance of the whole body under certain conditions. Such an imbalance would be favored by the repeated intake of drugs that induce hepatic microsomal enzymes and by the provision of ethanol as a major source of calories. The hypothesis is consistent with the changes in body weight in humans and animals after chronic ethanol intake. It is supported by observations of an increased oxygen consumption in rats given ethanol or barbiturates in doses that induce hepatic microsomal enzymes.

Alcoholism↗
PubMed1975

Acute and chronic effects of ethanol on intestinal lipid metabolism.

To assess the effects of ethanol on intestinal lipid metabolism, fatty acid oxidation and triacylglycerol synthesis were measured in intestinal slices incubated with ethanol. Ethanol, when used in concentrations likely to be achieved in the upper jejunum after moderate drinking, inhibited both palmitate and acetate oxidation, CO2 production and triacylglycerol synthesis, whereas it enhanced the esterification of fatty acid with ethanol. The concentrations required for the inhibitory effect were much higher than those needed to saturate enzyme systems known to participate in ethanol oxidation. In vivo administration of ethanol-containing diets produced persistent changes of the intestinal slices with respect to fatty acid oxidation and triacylglycerol synthesis. Acute intragastric administration of ethanol (3 g/kg) one hour prior to sacrifice, inhibited both processes in slices obtained from the jejunum, but not in those derived from the ileum. By contrast, chronic ethanol feeding increased the ability for fatty acid oxidation and triacylglycerol synthesis both in the jejunum and in the ileum. This stimulatory effect was associated with significant enhancement of palmitoyl-Co A synthetase activity, suggesting increased fatty acid activation. The inhibition by ethanol in high concentrations of intestinal fatty acid oxidation and triacylglycerol synthesis probably reflects epithelial cell damage; by contrast, prolonged administration of ethanol results in a persistent enhancement of lipid metabolism which may reflect the presence of a different cell population in the intestine.

Animals↗
PubMed1975

Energy wastage in rats given drugs that induce microsomal enzymes.

Metabolic efficiency was studied in rats given drugs known to induce hepatic microsomal enzymes. The presence of an increased metabolic rate was indicated by increases in oxygen consumption under various experimental conditions and by changes in body weight. The latter was not accounted for by increased losses of energy in excreta. The results support the hypothesis that hepatic microsomal enzyme induction can significantly alter the body's metabolic efficiency.

Aminopyrine↗
PubMed1973

Pathogenesis of postprandial hyperlipemia in rats fed ethanol-containing diets.

To study the mechanism of the increase in serum lipoproteins which occurs in rats fed alcohol chronically, and especially to assess the role of the intestine, the effects of acute and chronic ethanol administration on lymph and plasma lipids were compared in rats with and without intestinal lymph fistulae. In rats not previously given alcohol, the administration of one dose of a diet containing ethanol (3 g/kg) produced a significant increase in lymph flow, lipid output, and incorporation of dietary fat into lymph lipids when compared with the effects of a control diet containing isocaloric carbohydrate. However, no hyperlipemia developed after ethanol. By contrast, previous feeding of ethanol for several weeks modified the acute effects of ethanol on both lymph and serum lipids. Compared with control animals pair-fed with isocaloric carbohydrate-containing diets, rats which had been fed a diet with 36% of total calories as ethanol for 3-4 wk developed postprandial hyperlipemia when given a single dose of the ethanol-containing or even the ethanol-free diet. This was associated with an increased incorporation of labeled dietary fat and of intravenously injected [(3)H]lysine into plasma lipoproteins of d < 1.006. However, postprandial lymph flow and lipid output were not higher in rats fed alcohol chronically than in their pair-fed controls. Moreover, when rats with lymph fistulae were given intravenous (i.v.) infusions of lymph lipids (to substitute for the diverted intestinal lymph), the ethanol-fed animals still developed hyperlipemia. Incorporation of i.v. lysine into d < 1.006 plasma lipoproteins also remained significantly increased. Thus, under these conditions, alcoholic hyperlipemia does not result from changes in intestinal lymph lipids. Two main factors appear to be involved; the acute effects of ethanol on hepatic lipid metabolism and the development of an increased capacity for lipoprotein synthesis during chronic ethanol feeding. The latter most likely occurs in the liver and it is postulated that it is linked to the associated changes in the hepatic endoplasmic reticulum.

Animals↗