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R C Pirola

Publications and source records attributed to R C Pirola.

At least 19 recordsLinked to original sources
PubMed1992

Effects of ethanol, acetaldehyde and cholesteryl esters on pancreatic lysosomes.

Recent studies indicate that altered lysosomal function may be involved in the early stages of pancreatic injury. Chronic consumption of ethanol increases rat pancreatic lysosomal fragility. The aim of this study is to determine whether the lysosomal fragility observed after chronic ethanol consumption is mediated by ethanol per se, its oxidative metabolite acetaldehyde or cholesteryl esters (substances which accumulate in the pancreas after ethanol consumption). Pancreatic lysosomes from chow fed rats were incubated for 30 minutes at 37 degrees C with ethanol, acetaldehyde or phosphatidylcholine vesicles containing cholesteryl oleate. Lysosomal stability was then assessed by determination of: (a) Latency--that is, the per cent increase in lysosomal enzyme activity after addition of Triton X-100 and (b) Supernatant activity--that is, the proportion of lysosomal enzyme remaining in the supernatant after resedimentation of lysosomes. Acid phosphatase, N-acetyl glucosaminidase, beta-glucuronidase and cathepsin B were assayed as lysosomal marker enzymes. Lysosomes incubated with homogenising medium alone or equivalent volumes of phosphatidylcholine vesicles without cholesteryl oleate were used as controls. Cholesteryl oleate at concentrations of 15 and 20 mM increased pancreatic lysosomal fragility as shown by decreased latency and increased supernatant enzyme. In contrast, ethanol (150 mM) and acetaldehyde (5 mM) had no effect on lysosomal stability in vitro. These results suggest that increased pancreatic lysosomal fragility observed with ethanol may be mediated by cholesteryl ester accumulation rather than by ethanol or acetaldehyde.

Acetaldehyde↗
PubMed1991

Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis.

Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis.

Acute Disease↗
PubMed1990

Both ethanol consumption and protein deficiency increase the fragility of pancreatic lysosomes.

Both ethanol abuse and protein deficiency result in pancreatic injury. Moreover, these two variables frequently coexist. As lysosomal enzymes may play a role in the initiation of pancreatic injury, the aim of this study was to determine the effects of ethanol consumption and protein deficiency on pancreatic lysosomal stability. For 3 weeks, male Sprague-Dawley rats were match-fed (in groups of four) isocaloric amounts of one of the following liquid diets: (1) protein-sufficient diet, (2) protein-sufficient diet containing ethanol as 36% of the total energy, (3) protein-deficient diet, and (4) protein-deficient diet containing ethanol as 36% of energy. Pancreatic lysosomal stability was assessed by determining (a) latency, as indicated by the percentage increase in lysosomal enzyme activity in pancreatic homogenate induced by Triton X-100, and (b) by the percentage of lysosomal enzyme remaining in the supernatant after sedimentation of the lysosomal pellet from the pancreatic homogenate. Protein deficiency was associated with a decrease in latency and an increase in supernatant enzyme. Ethanol administration was associated with a decreased latency. Both protein-deficient and ethanol-fed animals exhibited higher pancreatic activities of cathepsin B, a lysosomal protease capable of activating trypsinogen. In addition, protein-deficient animals exhibited higher pancreatic activities of acid phosphatase, N-acetyl-glucosaminidase, and beta-glucuronidase. As lysosomal enzymes are postulated to play a role in the initiation of pancreatitis, these results suggest that ethanol consumption and protein deficiency may at least partly exert their toxic effects on the pancreas by altering pancreatic lysosomal stability and increasing the glandular content of cathepsin B.

Acetylglucosaminidase↗
PubMed1989

Alcohol-induced pancreatic injury (Part I). Unexplained features and ductular theories of pathogenesis.

The pathogenesis of alcoholic pancreatitis continues to be a puzzle. Classical theories of pathogenesis tend to overlook the dual nature of the disease, i.e., symptomatic acute attacks and chronic progressive parenchymal destruction. Furthermore, it is unknown why only a small minority of alcoholics develop clinical pancreatic injury. In addition, there is a lack of basic data concerning the natural history of the condition after cessation of alcohol consumption. The most widely accepted theory of pathogenesis postulates the deposition of protein plugs in peripheral pancreatic ducts as the initial lesion. However, it has not been established that these plugs are the cause rather than a result of pancreatic injury. The so-called "Big Duct" theories of pathogenesis (biliary-pancreatic reflux, duodeno-pancreatic reflux, and obstruction-hypersecretion) are confounded by a lack of agreement concerning the effect of alcohol on the sphincter of Oddi. Nutritional factors and heredity may be responsible for the selectivity of alcohol in this condition; in this regard, a number of dietary and HLA studies have been performed, but these have generally been inadequately controlled. Subcellular pancreatic injury (fat droplets, autophagic vacuoles, and mitochondrial lesions) has been observed in alcoholics without pancreatitis and in animals fed alcohol. In addition, ethanol feeding in animals has been shown to affect pancreatic cholesterol, phospholipid, and fatty acid metabolism as well as pancreatic content of digestive enzymes. Research is hampered by the lack of a suitable animal model of the disease.

Alcohol Drinking↗
PubMed1988

Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue.

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.

Acetates↗
PubMed1987

The incorporation of [myo-2-3H] inositol into phosphatidyl inositol of stimulated rat pancreas.

The 'phospholipid effect' involves agonist induced breakdown of phosphatidyl inositol (PI) or its phosphorylated derivates with increased incorporation of 32P or [myo-2-3H] inositol during resynthesis. In rat pancreas pancreozymin and bethanecol resulted in the standard dose dependent increased incorporation of 32P into PI which was paralleled by increased amylase secretion. By contrast the incorporation of [myo-2-3H] inositol into PI was significantly decreased by pancreozymin whereas bethanecol had no effect. However, pancreozymin caused a 30% decrease in labelled PI irrespective of whether it was prelabelled with 32P or [myo-2-3H] inositol. Thus in rat pancreas, pancreozymin resulted in the standard agonist induced breakdown of pre-labelled PI but inhibited the incorporation [2-3H-myo] inositol during the resynthetic phase.

Amylases↗
PubMed1986

Decrease in lipogenesis and glucose oxidation of rat adipose tissue after chronic ethanol feeding.

This investigation was performed to determine whether chronic ethanol feeding affects adipose tissue lipogenesis and glucose metabolism. Female Wistar rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 3 weeks. Chronic ethanol feeding resulted in a depression of adipose tissue lipogenesis as assessed by labeled glucose incorporation into glyceride glycerol and glyceride fatty acids. Glucose oxidation was also impaired after chronic ethanol feeding. Such changes may contribute to the postprandial hypertriacyglyceridemia observed in alcoholics.

Adipose Tissue↗
PubMed1985

Diet and drinking habits in relation to the development of alcoholic pancreatitis.

To determine whether increased intakes of fat and protein or particular drinking habits are associated with the development of alcoholic pancreatitis, a dietary study has been conducted. Patients with clinically evident alcoholic pancreatitis were compared with individuals with clinically evident alcoholic cirrhosis with respect to dietary and drinking habits before the onset of clinical illness. There was no significant difference between the two groups regarding intake of nutrients, drinking habits or type of alcoholic beverage consumed.

Adult↗
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↗
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↗