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Biomedical subjects

H Sankaran

Publications and source records attributed to H Sankaran.

At least 19 recordsLinked to original sources
PubMed1994

Induction of malnutrition in chronic alcoholism: role of gastric emptying.

Epidemiological studies reveal that chronic alcoholics exhibiting liver disease are generally malnourished. Experimental studies unequivocally demonstrate that incidence of malnutrition cannot be avoided in animals fed liquid diets containing high concentrations of alcohol. Furthermore, ingestion of additional amounts of macronutrients by such chronically alcoholic animals prevents or regresses alcohol-induced adverse effects despite a continuous intake of high amounts of alcohol. It is thus apparent that high amounts of alcohol intake and malnutrition are necessary factors to produce adverse effects in chronic alcoholism. The mechanism by which malnutrition manifests in chronic alcoholism is, however, not clear. Recent studies have demonstrated, a) an inverse relationship between alcohol and non-alcohol energy intake and its impact on alcohol-induced effects in chronically alcoholic rats, b) a synergism between malnutrition and high doses of alcohol intake in the induction of alcoholemia, and c) that chronic alcoholemia significantly prolongs the delay in gastric emptying. Data obtained from these studies enable us to hypothesize that abnormal prolongation of gastric emptying in alcoholics with chronic alcoholemia may play a major role in the initiation of macronutrient deficiencies leading eventually to the induction of malnutrition.

Alcoholism↗
PubMed1994

Unsaturated fat and low energy intake induce whereas an increment in energy intake ameliorates fatty liver during prolonged alcohol consumption by rats.

Two groups of rats were fed liquid diets containing 35% of energy as fat and either 36 or 26% of energy as alcohol to examine the effect of fat and energy intake on alcoholic fatty liver production. After 4 wk, five rats in each group were killed for analysis of liver triglyceride concentration, and then the alcohol diets fed to remaining rats were switched. All remaining rats were killed for hepatic triglyceride determination after another 4 wk. Rats initially fed the 36% alcohol diet or those switched to this diet ingested less energy, exhibited alcoholemia and slow growth, and developed fatty livers. Rats initially fed the 26% alcohol diet or those switched to this diet ingested significantly more energy, high amounts of alcohol and fat, exhibited low alcoholemia and faster growth than when they were fed the 36% alcohol diet. Fatty liver was absent in rats fed the 26% alcohol diet but was induced when they were fed the 36% alcohol diet. Fatty liver in rats initially fed the 36% alcohol diet regressed completely when the rats were switched to the 26% alcohol diet. Additional studies employing 36% alcohol diets containing 35% of energy as fat, derived from either corn oil or olive oil, revealed that unsaturated fat and not specifically linoleate plays a role in the induction of fatty liver. Thus, nutritional factors regulate the induction or regression of fatty liver and alcoholemia in alcoholic rats.

Alcoholism↗
PubMed1994

Effect of caloric content and composition of a liquid meal on gastric emptying in the rat.

We examined the effect of caloric content and substrate composition on gastric emptying in conscious Sprague-Dawley rats using gastric radioscintigraphy. Three-milliliter volumes of normal saline, glucose, casein hydrolysate, or intralipid containing 0, 1, 2, 3, or 6 kcal labeled with 99mTc-diethylenetriaminepentaacetic acid were given intragastrically. Gamma-camera imaging and computer analysis allowed construction of gastric emptying curves constructed over many time points for each emptying study. There was no difference in the half-emptying times (t1/2) between different substrates with equal calories, and increasing calories significantly prolonged gastric emptying for all substrates. Emptying occurred in a linear fashion with meals containing calories. With 3-ml meals containing 2, 3, or 6 kcal, the rate of delivery of calories to the duodenum is constant regardless of substrate or change in caloric content. We conclude that the rate of caloric delivery to the small intestine with gastric infusion of 1-6 kcal is relatively constant despite differences in total caloric load, substrate composition, and osmolarity.

Animals↗
PubMed1992

Carbohydrate intake determines pancreatic acinar amylase activity and release despite chronic alcoholemia in rats.

Adverse effects observed in alcoholic rats are often attributed to alcohol per se. Alcoholic liver damage, however, can be avoided by modulating nutritional factors despite high blood alcohol concentrations. Hence, we examined the effect of blood alcohol concentration on pancreatic enzyme activity and release. Three liquid diets containing 36 and 18% of total energy derived from alcohol and protein, respectively, were fed. Each alcohol diet contained 11, 21 or 31% of energy from carbohydrate, and the fat concentration was appropriately adjusted. The control groups of rats (fed an isoenergetic liquid diet without alcohol) and the alcoholic groups of rats were maintained for 2 wk. The three groups of alcoholic rats consumed 13.3 +/- 2.3, 13.3 +/- 2.2 and 13.2 +/- 1.9 g/kg of alcohol daily, and their corresponding blood alcohol levels were 41.5 +/- 4.3, 55.4 +/- 8.9 and 44.6 +/- 2.2 mmol/L. Pancreatic acinar amylase activity in alcoholic rats was proportional to carbohydrate ingested, despite high blood alcohol concentrations; chymotrypsin and trypsin activities were unchanged. Acinar enzyme activities in control rats were similar. Furthermore, cholecystokinin-octapeptide-stimulated amylase release in alcoholic rats corresponded with the amylase concentration in acini, whereas stimulated trypsin output was unaltered in both control and alcoholic rats. These results demonstrate that neither alcohol ingestion nor high blood alcohol concentration affects the activities of pancreatic proteases and that the changes in the activity and release of amylase are related to the intake of carbohydrate.

Alcoholism↗
PubMed1989

Reversal by glucose of pancreatic amylase insufficiency in chronic alcoholic rats.

Carbohydrate consumption regulates pancreatic amylase synthesis in rats. The Lieber-DeCarli 36% alcohol diet employed in chronic alcohol studies and the isocaloric control diet contain 11 and 47% of total calories from carbohydrates, respectively. Young rats fed ad libitum the 36% ethanol diet for 2 weeks obtained 1.2 g/day of carbohydrate, whereas those pair-fed with control diet received 5.8 g/day. Rats fed the 36% ethanol diet and given an intramuscular injection of a solution of 1.5 g of glucose daily for 2 weeks received twofold greater amounts of carbohydrate than saline-injected controls (2.7 versus 1.2 g). These changes in carbohydrate intake produced proportionate changes in pancreatic amylase levels. The secretory responses to cholecystokinin-octapeptide (CCK8) of acini from control and glucose-injected rats were significantly higher compared with those in the saline-injected or noninjected alcohol groups. The blood alcohol levels in glucose-injected rats were markedly reduced compared with other alcohol groups (71.7 versus 274.9 mg/dl) despite similar amounts of ethanol ingestion daily (2.4 g) in the three groups. In vitro experiments with acini from rats fed a nutritionally optimal diet revealed that high pharmacologic concentrations of ethanol, while inducing basal secretion, inhibited CCK8-stimulated amylase secretion. These results indicate that: (a) the amount of alcohol consumption does not correlate with either the levels of blood alcohol or of pancreatic amylase; (b) the carbohydrate availability in rats regulates pancreatic amylase levels despite significant levels of alcohol in blood; (c) blood alcohol levels observed in vivo may not affect synthetic and secretory processes of amylase in pancreatic acini.

Alcoholism↗
PubMed1989

Regulation of pancreatic amylase by dietary carbohydrate in chronic alcoholic rats.

The nutritional adequacy of dietary ingredients is essential for optimal food consumption and growth of animals. Dietary carbohydrate levels regulate pancreatic amylase synthesis. Ethanol diets with 36% of total calories from ethanol and 11% from carbohydrate are nutritionally inadequate, whereas a 26% ethanol diet made isocaloric to the 36% alcohol diet by the addition of maltose-dextrins provides all nutrients in amounts recommended for normal growth. Young rats fed the modified ethanol diet for 3 months consume 101.4 ml of diet daily compared to 66.5 ml by those on the 36% ethanol diet. Increased food consumption results in (a) similar amounts of alcohol consumption (3.6 vs. 3.3 g/day), (b) a threefold enhancement in carbohydrate intake (5.1 vs. 1.7 g/day), and (c) a normal growth rate (6.7 vs. 3.1 g/day). Both the acinar content of amylase (20.2 +/- 0.3 micrograms/mg of protein) and the acinar response to cholecystokinin-octapeptide in 36% ethanol diet-fed rats are significantly reduced compared to those of 26% ethanol diet-fed rats (34.1 +/- 5.6 micrograms/mg of protein). These results confirm (a) the nutritional adequacy of the 26% ethanol diet compared to the 36% ethanol diet, and (b) that carbohydrate inadequacy, and not ethanol consumption per se, is the primary cause of pancreatic amylase insufficiency in chronic alcoholic rats.

Alcoholism↗
PubMed1986

Increased pancreatic acinar content and secretion of cationic trypsinogen following 30-day continuous ethanol intoxication in rats.

The effects of sustained, high blood alcohol levels (216 +/- 120 mg/100 ml, S.D.) for 30 days on cholecystokinin (CCK)-mediated pancreatic exocrine function were studied in a rat model that achieves both maximally controlled, optimal nutrition and high alcohol intake (approximately 40.5% of total calories). In alcohol-fed rats, basal plasma levels of immunoreactive cationic trypsinogen (ICT) were reduced by 50% (P less than 0.05), but intravenous doses (0-30 IDU/kg/hr; 1 IDU = approximately 62.5 ng CCK-8) of cholecystokinin octapeptide (CCK-8) resulted in a 3-fold greater maximal concentration of ICT and an 80% steeper slope of the dose-response curve compared to those of pair-fed control animals. Basal plasma levels of amylase were not different in the two groups at basal conditions and did not change significantly following CCK-8 administration. In vitro studies with isolated pancreatic acini have shown that basal secretion of ICT into the media was similar in the two groups. However, ICT secretion in response to CCK-8 (30-3000 pM) was 2-fold greater in alcohol-fed rats than in pair-fed controls, resulting in a CCK-8 EC50 which was about half that of controls. On the contrary, the basal and maximal amylase secretion from acini isolated from alcohol-fed rats was reduced by 67 and 43%, respectively, causing a reduction in the magnitude of the response curve with almost identical EC50 and slopes. Despite the marked alterations in CCK-stimulated enzyme secretion, radioiodinated CCK-33 binding to receptors on acini isolated from both control and alcohol-fed rats was similar. Cellular concentrations of ICT and amylase, however, revealed similar patterns of alterations: 2 to 3-fold increase in ICT and 70% reduction in amylase in alcoholic acini compared to controls. These results indicate that the inverse changes in amylase and ICT secretions following continuous ethanol administration are probably due to differential effects on enzyme synthesis.

Alcoholism↗
PubMed1986

Interaction of enkephalins and des-tyrosyl-enkephalins with synaptosomal plasma membrane vesicles: enkephalin binding and inhibition of proline transport.

Leucine- and methionine-enkephalins inhibit the Na+-dependent transport of proline into plasma membrane vesicles derived from synaptosomes. Glycine transport is weakly inhibited by enkephalins whereas there is no inhibition of transport of glutamic acid, aspartic acid, or gamma-aminobutyric acid. The inhibition of proline uptake is observed with des-tyrosyl-enkephalins but not with morphine, dynorphin(1-13), or beta-endorphins. Furthermore, enkephalin-induced inhibition of proline transport is not antagonized by naloxone. [Leu]enkephalinamide and modified [Leu]enkephalins with greater selectivity for the delta-subclass of enkephalin binding sites are less effective than [Leu]enkephalin in the inhibition of proline transport. Specific binding of [3H]Leu-enkephalin to the plasma membrane vesicles is demonstrated, and des-Tyr-[Leu]enkephalin competes with Leu-enkephalin for [Leu]enkephalin binding sites. The similarity in the concentrations of des-Tyr-[Leu]enkephalin required to compete for specific [Leu]enkephalin binding and to inhibit proline transport suggests that a specific subclass of enkephalin binding sites, distinguished by their recognition of both the enkephalins and their des-tyrosyl derivatives, may be associated with the synaptic proline transport system.

Amino Acids↗
PubMed1986

Effect of Bt2cGMP on action of cholecystokinin in isolated perfused rat pancreas.

We have examined the effects of Bt2cGMP on cholecystokinin stimulation of pancreatic exocrine secretion in the isolated perfused rat pancreas. Bt2cGMP produced a concentration-dependent inhibition of the stimulatory effects of cholecystokinin octapeptide (CCK-8, 100 pM) on both pancreatic juice flow and enzyme secretion. Adding 1 mM Bt2cGMP rapidly and completely abolished CCK-8-stimulated pancreatic juice and enzyme secretion. Adding 500 microM Bt2cGMP for 10 min at the termination of 1 nM of CCK-8 infusion caused an immediate and persistent inhibition of the residual response. In contrast, treatment with C-terminal CCK antiserum I had no influence on the residual response. To account for the ability of Bt2cGMP to function as a competitive antagonist of the action of CCK and the ability of the nucleotide to inhibit the residual stimulation caused by CCK, we feel that Bt2cGMP hindered the binding of CCK not only by reducing the association rate constant for hormone binding but also accelerating the dissociation rate.

Amylases↗
PubMed1985

Cholecystokinin-induced secretion and synthesis of amylase and cationic trypsinogen by pancreatic acini isolated from rats given an ethanol diet.

Effects of chronic alcohol intake on secretion and synthesis of amylase and cationic trypsinogen (CT) were studied with pancreatic acini isolated from male Sprague-Dawley rats fed a Lieber-DeCarli ethanol or control diet for 30 days. Pancreatic acini were incubated in a media containing increasing concentrations of cholecystokinin octapeptide (CCK-8: 0-1000pM) followed by addition of [3H]leucine. Amylase and CT secreted in the media and those labeled in acini were quantitated. Basal and CCK-stimulated secretion of CT was not different in alcoholic and control groups. On the other hand, a dose-response curve of CCK-stimulated amylase secretion from alcoholic acini was markedly reduced with both basal and maximal secretion decreased to only 40% of controls. Basal incorporation of [3H]leucine into amylase was reduced by 70% in alcoholic acini compared to controls while that into CT was not different in the two groups. CCK-8 exhibited a biphasic effect on [3H]leucine incorporation into both enzymes in alcoholic acini: low concentrations of CCK-8 (less than 100pM) increased the incorporation whereas high concentrations (greater than 100pM) decreased it. However, in control acini, CCK-8 induced progressive suppression of the incorporation into these enzymes, the pattern of which was similar to that previously observed in fasted rats (Am. J. Physiol. 241:G116-G112, 1981). This difference in the response pattern resulted in significantly higher rates of CCK-8 induced incorporation into CT in alcoholic acini. These results suggest that the differences observed may possibly be attributable not only to alcohol intake but also to the differences in carbohydrate intake and in temporal patterns of diet consumption.

Amylases↗
PubMed1985

Irreversible inhibition by acetaldehyde of cholecystokinin-induced amylase secretion from isolated rat pancreatic acini.

Acetaldehyde inhibited both amylase secretion induced by maximal concentrations (300 pM) of cholecystokinin octapeptide and the binding of radioiodinated cholecystokinin to receptors on isolated rat pancreatic acini. This inhibition was concentration dependent (10 mM to 1 M for amylase secretion and 100 mM to 1 M for binding). However, a correlation between the two inhibitory effects could not be obtained. Furthermore, the inhibitory effects were not reversible. Acetaldehyde did not alter the basal amylase secretion between 6 and 45 mM concentrations. However, 60, 100 and 300 mM acetaldehyde significantly decreased basal amylase secretion; no significant change in amylase secretion was observed at 600 mM and 1 M. Higher concentrations of acetaldehyde produced a 2- to 10-fold increase in basal amylase secretion. 51Cr release from prelabeled acini revealed no significant cell membrane damage between 10 and 600 mM acetaldehyde. These data suggest that acetaldehyde inhibition of cholecystokinin-induced amylase secretion is intracellularly mediated.

Acetaldehyde↗