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Biomedical subjects

E Lebenthal

Publications and source records attributed to E Lebenthal.

At least 127 records · Page 7Linked to original sources

Cholecystokinin: a factor responsible for the enteral feedback control of pancreatic hypertrophyphy.

Chronic diversion of pancreatic and biliary secretions away from the proximal small intestine results in pancreatic hypertrophy in adult rats. Serum levels of cholecystokinin (CCK) were measured in age-matched control and surgically diverted rats at various times after operation by a radioimmunoassay method that was specific for the sulfated form of CCK. The concentration of CCK was markedly increased in bypassed rats as compared with controls. The increases in circulating CCK in bypassed rats was substantiated by a bioassay method that measured physiologically active CCK. The degree of pancreatic hypertrophy and the increase in CCK levels both progressed with time up to 23 days after surgery. Linear regression analysis showed an apparent direct correlation between pancreatic weights and serum CCK levels (r = 0.99). Feeding bypassed rats with diets containing various pancreatic and biliary supplements did not abolish the hyperplastic response of their pancreata. However, feeding with diets supplemented with bile partially suppressed the increase in serum CCK levels, while a diet containing Cotazyme and bile completely suppressed this increase. The discrepancy between serum CCK levels and the degree of pancreatic hypertrophy in the supplemented bypassed rats was further demonstrated by the lack of correlation using linear regression analysis (r = 0.33). The observed pancreatic hypertrophy in the absence of high serum levels of CCK in the bypassed rats fed bile and Cotazyme supplements suggests that serum hypertrophic factors other than CCK may also be involved in the enteral feedback regulation of pancreatic growth.

Animals↗

Physiological factors controlling release of enterokinase from rat enterocytes.

The quantitative release of enterokinase from isolated rat enterocytes following treatment with taurocholate-taurodeoxycholate, papain, chymotrypsin, elastase, carbamylcholine, and cholecystokinin-octapeptide was examined. Alkaline phosphatase and lactate dehydrogenase activities were evaluated simultaneously to check for specificity. Bile salts promoted a concentration-dependent release of all enzymes. Concomitantly, bile salts also led to cell destruction in proportion to the amount of enzymes released. Proteases caused the release of enterokinase and alkaline phosphatase with no concomitant increase of lactate dehydrogenase or cell lysis. At equal concentrations, papain released more enzymes than chymotrypsin and elastase. Chymotrypsin and elastase, however, led to higher ratios of enterokinase to alkaline phosphatase found in the media and suggested a selective release of enterokinase (EK) over that of alkaline phosphatase. Bile salts and pancreatic proteases together seem to have an additive effect of the release of EK. Carbamylcholine and cholecystokinin-octapeptide had no effect on enzyme release. These results suggested that pancreatic proteases are involved in the release of enterokinase by a selective action. Bile salts may also play a role through a nonselective detergent effect.

Alkaline Phosphatase↗

Effect of fat and carbohydrate composition on the gastric emptying of isocaloric feedings in premature infants.

The gastric emptying of six infant feedings (20 kcal/oz; whey to casein ratio, 60:40) with varying fat and carbohydrate composition was studied. Feedings contained either predominantly long-chain triglycerides (94%) or predominantly medium-chain triglycerides (94%) as the fat and lactose, glucose, or glucose polymers (Polycose) as the carbohydrate. Eleven premature infants were fed 22 ml/kg body wt of all six feedings over a 3-4-day period, and the volume of gastric contents was measured every 20 min using polyethylene glycol 4000 as the marker. Analysis of variance demonstrated that the use of medium-chain triglycerides resulted in faster gastric emptying than long-chain triglycerides (p less than 0.001). Analysis of variance and Tukey's test showed that use of glucose polymers instead of glucose resulted in less volume of gastric contents at 40 min (p less than 0.05). Use of glucose polymers instead of lactose resulted in less volume of gastric contents at 60 and 80 min (p less than 0.05). Gastric emptying can be altered by changes in nutrient composition. The difference between medium-chain and long-chain triglycerides was more pronounced than the differences between the carbohydrates studied. Feedings with medium-chain triglycerides may be more suitable than long-chain triglycerides in patients with delayed gastric emptying.

Dietary Carbohydrates↗

Pancreatic and intestinal digestive enzymes in post-weanling rats with hypothalamic obesity.

Male Sprague-Dawley rats received bilateral electrolytic lesions in the ventromedial hypothalamic nuclei (VMNL rats) at the age of 31 days; sham-lesioned rats served as controls. For 28 post-operative days all animals self-selected from three synthetic diets, each high in carbohydrate, fat and protein, respectively. Following this, half of the VMNL rats and half of the controls were switched to lab chow for 14 days. Body weights were comparable among the groups, but linear growth was greatly reduced and body fat (Lee Index) was elevated in VMNL rats, irrespective of diet. In the sham-lesioned controls, the synthetic diets reduced most parameters of exocrine pancreatic activity. In VMNL rats, in contrast, pancreatic parameters were unaffected by the synthetic diet. The data suggest that VMN lesions disinhibit the exocrine pancreas. In contrast, most parameters of intestinal activity were not influenced by VMN lesions.

Animals↗

Digestibility of native and modified starches: in vitro studies with human and rabbit pancreatic amylases and in vivo studies in rabbits.

The effects of cooking and chemical modification of purified starches on the relative rates and extent of their hydrolysis were studied in vitro by using purified human and rabbit pancreatic amylases. Comparison was made with an in vivo study of postprandial glucose and insulin response in adult rabbits. Uncooked starches showed negligible hydrolysis in vitro, whereas cooking (10 min, 100 degrees C) increased both the rate and extent of hydrolysis of all starches. Soluble potato starch was the most and potato amylose the least hydrolyzed. Unmodified tapioca and waxy corn starch were hydrolyzed at the same rate and to the same extent as soluble potato starches. In most cases chemical modification did not change the rate and extent of hydrolysis of the starches. Minor differences between human and rabbit pancreatic amylase exist, but there is a general resemblance between the two amylases in their starch-hydrolyzing properties (correlation coefficient = 0.90; P less than 0.001). The in vivo study showed that uncooked starches elicited no detectable glucose and insulin responses, whereas all the cooked starches except amylose caused glucose and insulin responses comparable to the response seen when feeding glucose. Chemically modified starches (especially waxy corn acetylated distarch adipate) seemed to promote a faster rate of absorption, but the total glucose response (i.e., for the entire 180-min duration) was similar for modified starches and their unmodified counter-parts. The in vivo results showed an overall qualitative similarity to the in vitro results but presented a quantitative difference in the magnitude of the responses for various starch preparations. A good correlation exists between the in vitro and in vivo results (correlation coefficient = 0.84; P less than 0.01). This indicates that the action of pancreatic amylases is an important determinant in the digestion and absorption of these carbohydrates.

Amylases↗

Impact of digestion and absorption in the weaning period on infant feeding practices.

Weaning is a transition period in which solid and table foods replace milk or formula. Such a shift involves not only a change in the texture but also the nutrient constituents in the diet of the infant. Appropriate dietary changes, although known to affect the physiologic and biochemical function of the gastrointestinal tract in adults, have not been established clearly in infants. The relationship between diet and gastrointestinal development during the weaning period is explored. New concepts such as alternate pathways for digestion and absorption during infancy and the possible effects of new feeding modalities such as total parenteral nutrition and elemental diet are discussed. The influence of exogenous factors such as malnutrition and diseases on the development of the gastrointestinal function, particularly that of the small intestinal brush border hydrolytic enzymes and exocrine pancreatic enzymes, are also reviewed because of their potential influence on the weaning process.

Age Factors↗

Normal pancreatic and intestinal enzymes in hypophagic growth-retarded rats that received dorsomedial hypothalamic lesions shortly after weaning.

Male weanling Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats). Sham-operated rats served as controls. After being fed lab chow for two postoperative weeks, the animals were divided into four groups. One group of DMNL rats and controls received a high-caloric diet (high-fat diet, chocolate chip cookies, 32% sucrose solution, potato chips and marshmallows), whereas another group of DMNL rats and controls continued to receive lab chow. The experiment was terminated on the 185th postoperative day. In accordance with previous findings, DMNL rats, irrespective of diet, were lighter and shorter than controls. In addition, DMNL rats fed junk food were lighter than DMNL rats fed lab chow, and junk-fed controls weighed as much as chow-fed controls. Both DMNL rats and controls fed junk food were also shorter and showed higher carcass fat than their chow-fed counterparts. Also, DMNL rats fed junk food had less carcass fat than junk-fed sham-operated controls, whereas in accordance with previous findings, there was no difference between chow-fed DMNL rats and chow-fed sham-operated controls. Irrespective of diet, DMNL rats ate less calories than their respective sham-operated controls. Both absolute and percent pancreas weight and protein/pancreas were unaffected in DMNL rats but were reduced in both junk-fed groups in comparison with their chow-fed counterparts. Both concentrations and contents of pancreatic trypsinogen, amylase and lipase were unaffected in DMNL rats but total activities of all three enzymes were dramatically reduced in the junk-fed compared with the chow-fed DMNL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of caloric density on gastric emptying in premature infants.

The role of caloric density in the regulation of gastric emptying has been well documented in adults but studied to only a limited extent in young infants. Ten premature infants were each fed 22 ml/kg formula (Similac Special Care), at concentrations of 24, 20, 13, and 6.5 Cal/oz, as well as one feeding of distilled water. The volume of gastric contents was measured at 20-minute intervals by the double-aspiration technique using the marker polyethylene glycol 4000. Analysis of variance demonstrated a significant inhibition of gastric emptying related to increasing caloric density (P less than 0.001) when evaluated over the entire time of measurement. By 20 minutes, significant differences (P less than 0.01) were present between 0 and 6.5, 6.5 and 13, and 13 and 20 Cal/oz. A volume difference between 20 and 24 Cal/oz (P less than 0.05) was present only at 80 minutes. Despite the inhibition of emptying, higher caloric density feedings were associated with emptying of more calories over comparable periods (P less than 0.001). Regulation of gastric emptying by caloric density in premature infants is qualitatively similar to that in adults.

Bottle Feeding↗

Induction of enterokinase in the rat small intestine following hypersecretion of trypsinogen by chronic trypsin inhibitor feeding.

The interrelationship between trypsin/trypsinogen and enterokinase (EK) was studied in rats following induction of trypsinogen hypersecretion by various agents. Both soybean trypsin inhibitor and para-aminobenzamidine increased intraluminal tryptic activities to a level about twice that found in the control rats. This resulted in an increase in the mucosal and the intraluminal contents of EK in the rat small intestine. On the other hand, in cholecystokinin-treated rats, although there was an increase of intraluminal trypsin, the increase was about 80% less than in the inhibitor-fed rats. Under this condition, there was no effect on the mucosal or the intraluminal EK. These results suggested that substantial increase in intraluminal trypsin/trypsinogen levels (two-fold over control) will increase the mucosal and the intraluminal concentrations of EK in the rat small intestine. Our observation extends previous reports that a decreased level of trypsin/trypsinogen, such as in pancreatic insufficiency, leads to a decrease in mucosal EK. These observations, when taken together, strongly support the modulating role of intraluminal trypsin/trypsinogen levels in controlling the EK concentrations in the small intestine.

4-Aminobenzoic Acid↗

Pancreatic growth and enzyme profiles in weanling rats with normophagic hypothalamic obesity.

Weanling male rats with ventromedial hypothalamic lesions (VMNL rats) and sham-operated controls were killed 1, 2, 4, and 5 weeks postoperatively. The VMNL rats developed normophagic hypothalamic obesity in the presence of normal body weight and reduced linear growth. In both VMNL and control rats, pancreatic weight and protein content increased with time but were lower in the lesioned animals. Pancreatic DNA content was arrested in VMNL rats and remained so during the remainder of the experiment. The only significant enzyme changes (trypsinogen, amylase, and lipase) were evident in higher trypsinogen concentration in VMNL rats during 2 and 4 weeks after lesion production. In view of previous data on both hypophysectomized and VMNL rats and the known role of the ventromedial hypothalamic nucleus in neuroendocrine and neuroautonomic function, it is speculated that the changes observed here are in part due to disruption of neuroendocrine and in part due to disturbance of neuroautonomic control systems.

Amylases↗

Chemical adrenalectomy by aminoglutethimide and the pancreas in suckling rats.

The role of corticosterone in the development of pancreatic enzymes of suckling rats was studied through a partial and transient blockade of steroidogenesis by aminoglutethimide. Rats were injected with aminoglutethimide the night before their 14th day of age. Ten hours later they showed a transient decrease of serum total corticosterone level as compared with rats injected only with the vehicle. At 34 and 58 h after injection, their corticosterone levels returned to that of control rats. Pancreatic weight, protein, DNA contents, and total activities of amylase, lipase, and trypsinogen were depressed only in the aminoglutethimide-treated pups 34 h after injection. These pancreatic parameters returned to the control level 58 h after injection. Hydrocortisone given to another group of rats completely abolished the effect of aminoglutethimide on the pancreas. Thus, a transient suppression of serum corticosterone level caused a delay in the developmental accumulation of pancreatic exocrine enzymes that resumed only after the serum corticosterone returned to the control level. These results further confirm that corticosterone is an important modulator of pancreatic enzyme development in the rat.

Adrenal Glands↗

Effect of chronic reserpine treatment on the pancreases of neonatal rats.

Chronic reserpine treatment of adult rats results in the accumulation of pancreatic enzymes and reduction of their discharge. These changes are reminiscent of those in cystic fibrosis. Since the majority of cystic fibrosis patients have their pancreatic dysfunction manifested in childhood, we studied chronic reserpine treatment in rat pups. Four-day-old rat pups were given reserpine (50 micrograms/kg intraperitoneally) or vehicle daily until sacrifice. The reserpine group showed significant decreases in body weights at 14 and 21 days of age. Pancreatic weights were also decreased but were of normal weight or increased when normalized against body weights. At 14 and 21 days of age, pancreatic concentrations of amylase, lipase, and trypsinogen showed no difference between reserpine and control pups. At both ages, pancreatic contents of all three enzymes were generally less in the treated pups, but were found to be similar when corrected for body weights. Hydrocortisone treatment of 14-day-old pups caused precocious accumulation of pancreatic enzymes in both reserpine and control groups. Intestinal contents of lipase, trypsin, and amylase were decreased in the reserpine pups at 14 days of age and reached a more significant level at 21 days of age; these data suggest a decrease in the secretion of pancreatic enzymes. Dispersed acini from 14-day-old pups showed a reduced capacity to release amylase as stimulated by carbachol or the octapeptide of cholecystokinin. The results suggested that chronic reserpine treatment of pups in the suckling period did not cause significant disturbance of the developmental accumulation of pancreatic enzymes. A definite inhibition of exocrine secretion was found with reserpine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

Effect of inflammatory bowel disease on absorption and disposition of prednisolone.

The pharmacokinetics and bioavailability of prednisolone after doses of oral prednisone and intravenous prednisolone were determined in seven patients receiving corticosteroids for treatment of inflammatory bowel disease in active disease and remission. Prednisone absorption and conversion to the active form of prednisolone was complete in both disease phases. Pharmacokinetic parameters for total and free (unbound) prednisolone did not differ significantly between disease phases. Differences in protein binding were observed between active disease and remission with the fractional binding of prednisolone to plasma proteins decreased in active disease. This may be accounted for by decreased plasma albumin concentrations in active disease. Alpha 1-acid glycoprotein concentrations were significantly higher in active disease but did not contribute to the overall binding of prednisolone.

Adolescent↗