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Biomedical subjects

E Lebenthal

Publications and source records attributed to E Lebenthal.

At least 91 records · Page 5Linked to original sources

Antigliadin antibodies detected by enzyme-linked immunosorbent assay as a marker of childhood celiac disease.

Using an enzyme-linked immunosorbent assay (ELISA) assay, we studied the sera of 17 patients with celiac disease and 114 control subjects for the levels of IgG and IgA antigliadin antibodies. As a group, the patients with celiac disease had significantly higher levels of antigliadin antibodies of both IgG and IgA classes (p less than or equal to 0.001). However, there was a significant overlap of values, resulting in respective sensitivities and specificities of 88% and 90% for IgG antigliadin antibodies, and 73% and 65% for IgA antigliadin antibodies. The combined use of both IgG and IgA antigliadin antibody levels produced a sensitivity of 86% and a specificity of 90%. A gluten-free diet in celiac patients did not seem to affect these results. We conclude that the antigliadin antibody ELISA assay cannot be used as a definitive diagnostic test for celiac disease. The small-bowel biopsy remains the principal diagnostic method; the ELISA assay should, at best, be considered a screening test for this disease.

Antibodies↗

Feeding the premature and compromised infant: gastrointestinal considerations.

We have presented the current concepts of gastrointestinal ontogeny--the various factors governing the ontogeny of the gastrointestinal tract and the interaction and intricate relationship between different determinants. It is only through a better understanding of the development of the gut and the various factors affecting it that pediatric gastroenterologists are able to design nutritional support strategies for managing very young and compromised neonates.

Digestive System↗

Disorders of carbohydrate digestion and absorption.

The carbohydrate malabsorptive syndromes are frequently seen by pediatricians. The congenital deficiency states are quite rare, but adult type hypolactasia and lactose intolerance following rotavirus infection are recognized with increasing frequency by primary care physicians. Therapy for these disorders involves identification of the offending carbohydrate, removal of the carbohydrate from the diet, and exclusion of other entities that may result in carbohydrate malabsorption but not respond to its removal from the diet. Prognosis for both the primary and secondary carbohydrate malabsorption syndromes is excellent. Compliance with diets for those pediatric patients who will require lifelong therapy remains problematic.

Dietary Carbohydrates↗

Thyroxine effect on exocrine pancreatic development in rats.

Thyroxine and glucocorticoids both play important roles in regulating the development of mammalian tissues. The mechanisms by which they modulate the developmental process is not fully understood. Furthermore, the interaction between the effects of two hormones on the pancreas has not been studied in detail. To investigate these issues, we studied the effect of thyroxine and/or corticosterone on the development of the exocrine pancreas in normal and adrenalectomized rats. Daily injection of thyroxine (0.1 micrograms/g body wt) to pups starting at day 5 of age resulted in precocious increases of exocrine enzymes in the pancreata of these pups. Hypothyroid pups, induced by propylthiouracil, exhibited suppression of development of their pancreatic exocrine enzymes. Replacement of thyroxine or corticosterone alleviated the suppression of exocrine enzyme development in these pups. Rat pups, who underwent adrenalectomy at 5 days of age, had undetectable plasma corticosterone and exhibited similar suppression of pancreatic enzyme development. Injection of thyroxine or corticosterone alone to adrenalectomized pups led to normal development of exocrine pancreatic enzymes. When both thyroxine and corticosterone were given together to adrenalectomized pups, their pancreatic enzyme levels were found to increase to values above those of pups treated with thyroxine or corticosterone alone. We conclude that thyroxine has both direct and indirect modulatory roles in the development of the rat exocrine pancreas. Normal development of the exocrine pancreas depends on both intact adrenal and thyroid function in the rat.

Adrenalectomy↗

Interaction of malnutrition and difluoromethylornithine-induced intestinal mucosal damage: degree of severity and subsequent recovery.

The interaction between malnutrition and exposure to a mucosal damaging agent, difluoromethylornithine (DFMO), was examined by monitoring the small-intestinal changes in weanling rats. Malnutrition as induced by the expanded-litter method resulted in severe reduction in body weights in the expanded litters as compared to normal litters. Subsequent treatment of malnourished and well-nourished pups with DFMO for 7 days resulted in decreases in small-intestinal weights and enzyme contents. A 2 factors (well-nourished and malnourished) by 2 factors (DFMO-treated and nontreated) analysis of variance showed no interaction between malnutrition and DFMO treatment in terms of food intake, total mucosal protein, and contents of enterokinase, leucine aminopeptidase and sucrase. Very slight and insignificant interactions (p less than or equal to 0.2) were found for body weights, intestinal weights and total DNA content. Only one parameter studied, the maltase content, showed significant interaction between malnutrition and DFMO treatment (p less than 0.05). Three weeks after the withdrawal of DFMO, essentially all the changes caused by DFMO recovered. But those changes caused by malnutrition did not, such that the malnourished group, whether treated with DFMO or not, still remained significantly less than the control group in their small-intestinal parameters. Analysis of variance showed no interaction between malnutrition and DFMO treatment in the recovery phase. The results suggest that malnutrition is a more important factor in determining the intestinal damage and that malnutrition in the immediate postnatal period does not increase the sensitivity of the small intestine to the damaging effect of DFMO.

Animals↗

Long-term pancreatic-biliary diversion in the rat: persistent loss of mucosal enterokinase, with reinduction by delayed oral pancreatic biliary supplementation.

Diversion of pancreatic-biliary (PB) secretions in rats for 23 days led to loss of enterokinase (EK) activity in bypassed segments of the small intestine. Simultaneous oral trypsinogen and bile salt (TB) supplements prevented the loss of EK activity. To study the temporal course of events after PB diversion and to determine if the loss of EK is reversible, PB diversion was performed in rats by surgical transposition of the 4-cm segment of duodenum including the ampulla of Vater to a point 30 cm distal to its original site. Bypassed and control (sham- and nonoperated) rats fed standard rat chow were sacrificed at 10, 23, and 45 days after surgery. One bypassed group was fed standard chow for 23 days and then chow supplemented with TB until sacrifice at 45 days. At sacrifice, the intestines were divided into segment 1 (the bypassed proximal 30 cm) and segment 2 (the 30 cm distal to the bypass). In segment 1, EK disappeared almost completely by 10 days and remained at the same low levels at both 23 and 45 days (p less than 0.05). No significant changes in EK levels were found at any time in segment 2 distal to the bypass. Mucosal disaccharidase activity in segment 1 increased or showed no change. In rats with delayed TB supplementation, EK activity in segment 1 returned almost to control levels at the time of sacrifice. The results confirm the importance of PB secretions in the maintenance of EK activity. The effects of bypass on EK are both enzyme- and site-specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vitamin D deficiency, pancreatic and small intestinal enzyme development in rats.

Maternal vitamin D deficiency has been shown to lead to reduced body weights in developing rat pups. To evaluate the effects of vitamin D deficiency alone both in dams and pups during the perinatal age on the ontogeny of gastrointestinal enzymes, female weanling rats (3 weeks of age) were divided into three groups. Groups I and II were fed a control (vitamin-D-replete) diet. Group II were fed a vitamin-D-deficient diet. Six weeks afterward they were mated with normal male rats while continuing on their respective diets until sacrifice. Only rats that delivered their pups on the same day from each group were brought into the study. Litter sizes of groups I and II were adjusted to 10, while group III was adjusted to 13 such that the rate of growth paralleled that of group II. At 19 days after birth, all dams and pups were sacrificed. There were no differences in the calcium and phosphorus contents in breast milk obtained from dams of each group. The serum calcium concentration of pups from group II (vitamin-D-deficient) was lower than the other groups. Body weights of pups from groups II and III were significantly lower than those of group I. The mucosal weight, total mucosal protein, mucosal DNA, sucrase, and maltase activities from groups II and III were similar, but lower than group I. Pancreatic weight, total pancreatic protein, DNA, amylase, and lipase activities from groups II and III were also similar, but lower than group I. Vitamin D deficiency was confirmed in both dams and pups from group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The effect of cholecystokinin-octapeptide, insulin, glucagon, triiodothyronine, and epidermal growth factor on amylase activity in fetal pancreas in vitro.

To evaluate the possible role of various hormones on fetal pancreas development, late gestational fetal rat pancreata (20 days) were cultured in a serum-free medium for 6 days in the presence of cholecystokinin-octapeptide (CCK-8), epidermal growth factor, triiodothyronine, or glucagon with or without dexamethasone. In the absence of any added hormone, the tissue amylase activity declined very rapidly. Epidermal growth factor alone (4.10(-7) M) could not preserve the amylase activity, whereas triiodothyronine (0.1 microM) and glucagon (4 micrograms/ml) had a deleterious effect that was prevented by the addition of DXM (3.10(-6) M). In the presence of CCK-8 (2.10(-11) M) 50 and 30% of the amylase activity was maintained on the 2nd and the 4th day of culture, respectively. The CCK-8 effect was dose dependent and was inhibited by asperlicin (10 microM). The combination of CCK-8 and dexamethasone maintained more than 80% of the amylase activity in the fetal pancreas explants through 4 days of culture. Fetal pancreas cultured in this optimal medium and treated with streptozotocin (10(-7) M) during the 1st day of culture showed a significantly lower tissue amylase activity on the 4th and 6th days than those not treated with streptozotocin. The streptozotocin effect was attenuated when insulin (0.1 U/ml) was added. These data suggest that, in addition to the well-known effect of glucocorticoid on enzyme activities in the fetal pancreas, two additional hormones, CCK and insulin, could play a role in the modulation of pancreatic amylase activity in the fetal rat.

Amylases↗

The effect of postnatal development on the adherence of nonfimbriated and fimbriated Salmonella typhimurium to isolated small intestinal enterocytes.

The adherence of radiolabeled fimbriated (S 7471 OF) and nonfimbriated (S 7471 N) Salmonella typhimurium to small intestinal rat enterocytes was examined during postnatal development. The fimbriated strain invariably adhered in higher numbers than the nonfimbriated strain during all periods of development. The capability of enterocytes to bind Salmonella increased significantly during postnatal development and reached adult levels at weaning time (21 days of age). Bacterial adherence to enterocytes was similar if the cells were isolated from the proximal or the distal small intestine. Early weaning of pups did not affect the capability of enterocytes to bind Salmonella. Pretreatment of isolated enterocytes from adult animals with rat's milk before exposure to Salmonella had no effect on the level of bacteria that adhered per enterocyte. Conversely, pretreatment of Salmonella with rats' milk before binding to enterocytes from adult animals also did not alter the level of bacteria adhered per enterocyte. These results suggest an age-dependent, postnatal development of available receptors for S. typhimurium on rat enterocytes. The acquisition of these receptors is not affected by mother's milk and is unaltered by early weaning.

Aging↗

Regulation of rat pancreatic glucocorticoid receptors by thyroxine during development.

The effect of T4 on the development of pancreatic glucocorticoid receptors was studied in normal and adrenalectomized rat pups. Daily injection of T4 (0.1 microgram/g BW) to intact pups starting 3 days before death at 10, 15, and 20 days of age resulted in a precocious increase in pancreatic glucocorticoid-binding capacities. Intact pups made hypothyroid by propylthiouracil feeding exhibited lower glucocorticoid-binding capacities in their pancreata. Scatchard analysis demonstrated an increase in the number of glucocorticoid-binding sites in the pancreata of T4-treated intact rats compared to that in normal intact rats. In hypothyroid groups the number of glucocorticoid-binding sites was much lower than that in normal intact rats. The Kd values, however, were unchanged in hypothyroid, hyperthyroid, and control groups. Rat pups who underwent adrenalectomy at 12 days of age had undetectable plasma corticosterone levels and showed an increase in their pancreatic glucocorticoid-binding capacity 3 days after operation. Replacement of corticosterone resulted in a binding level similar to that in the sham-operated group. However, injection of T4 alone to adrenalectomized pups led to a further increase in pancreatic glucocorticoid-binding capacity above that due to adrenalectomy alone. When both T4 and corticosterone were given together to adrenalectomized pups their pancreatic glucocorticoid-binding capacities increased to levels above those in the adrenalectomized group, but lower than those in pups receiving T4 alone. Our results suggest that T4 modulates the development of rat pancreatic glucocorticoid receptors and, at least in part, acts via pathways independent of adrenal function.

Adrenalectomy↗

Nutritional assessment of children with short-bowel syndrome receiving home parenteral nutrition.

Serial nutritional assessments using arm anthropometry, computed tomography of the thigh, and serum biochemical indexes during an eight-month period were performed on nine children with short-bowel syndrome receiving home parenteral nutrition. The mean patient age at the beginning of the study was 3.0 years. In anthropometric measurements, the mean body weight of our test population did not deviate from that of the normal population. Most patients were below the normal median for height. The mean midarm muscle area was 114% of the normal median, and the mean midarm fat area was 98% of the normal median. The mean weight and height velocities were 148% and 122% of the standard, respectively. Retinol-binding protein values, albumin levels, and total lymphocyte counts of the patients were low, while levels of aspartate aminotransferase and alanine aminotransferase were slightly elevated. Midarm muscle and fat compartment sizes were highly correlated with thigh muscle and fat compartment sizes, as demonstrated by computed tomography. Our results demonstrate that children with short-bowel syndrome receiving home parenteral nutrition can maintain normal growth characteristics and extremity compartment sizes.

Anthropometry↗

Effect of difluoromethyl ornithine (DFMO) on small intestine of adult and weanling rats.

Oral feeding of DL-difluoromethyl ornithine (DFMO) (2% in water ad libitum) for 14 days has no detectable effect on the small intestine of adult rats. Similar feeding of DFMO to weanling rat pups caused diarrhea in three to four days accompanied by a decrease in food consumption and body weight compared to age-matched controls. Significant decreases in small intestinal mucosal weight, total protein, DNA, enterokinase, leucine amino peptidase, sucrase, and maltase contents were observed in the DFMO-treated group four days after treatment. Extending the treatment to seven days led to a more severe reduction in these parameters. Villous atrophy of the mucosa was demonstrable by light microscopy and morphometric measurements. The mucosa of the DFMO-treated rat pups showed a reduction in total thickness and villous height but no change in crypt depth. A significant reduction in villus-crypt ratio was also seen. Changes in small intestinal mucosal parameters were not due to a decrease in food intake since pair-fed, age-matched rat pups showed no biochemical changes compared to control pups. DFMO-treated weanling rats showed less than 5% of ornithine decarboxylase (ODC) activity when compared to age-matched control animals. The effects observed on the small intestinal mucosa are presumably due to inhibition of ornithine decarboxylase activities by DFMO which prevents the proliferation, regeneration, and maturation of epithelial cells. The relative insensitivity of the adult rat small intestine to DFMO treatment suggests a lesser dependence of its intestinal mucosa to ODC activities.

Age Factors↗

Developmental changes of glucocorticoid receptors in the rat pancreas.

Glucocorticoids are known to play a role in the maturation of the exocrine pancreas. The exact mechanism of glucocorticoid action in pancreatic ontogeny is, however, not clear. The present study characterized and quantitated the binding of [3H]dexamethasone to cytosol fractions from pancreata of rats at various ages. Trunk blood samples from these rats were also checked for levels of free and bound corticosterone. Specific and saturable bindings for dexamethasone were found in pancreatic cytosol fractions from newborn suckling and adult rats. Competition studies showed a preference for steroids with glucocorticoid activity. Specific binding was relatively low in pancreatic cytosol from newly born and 1-day old pups. A significant rise was seen after day 15. Cytosolic binding capacities were greatest from pancreata obtained from pups at weaning (3rd to 5th weeks). Values then declined toward the adult level. Scatchard analysis revealed a single class of binding sites with a dissociation constant (Kd) of 7.3 (+/- 1.1) X 10(-8) M and number of binding sites equalled to 1.29 (+/- 0.18) X 10(-13) mole/mg of cytosolic protein in adult rat pancreas. Pancreata from 25- and 15-day old rats had Kds of 3.4 (+/- 0.8) X 10(-8) M and 2.7 (+/- 0.7) X 10(-8) M with the number of binding sites equal to 1.77 (+/- 0.21) X 10(-13) mole/mg protein and 1.31 (+/- 0.16) X 10(-13) mole/mg protein respectively. Total plasma corticosterone concentration was low before day 10. It rose significantly by day 15, peaked at day 25, and then declined after weaning. About 5-15% of corticosterone during weaning and about 20-30% before and after weaning were in the free form. The peak level of dexamethasone binding corresponded to an increase in the plasma corticosterone level during weaning. This suggests a close relationship between plasma corticosterone levels and pancreatic glucocorticoid receptors. Both may, therefore, play a role in pancreatic development in the rat.

Aging↗

Maternal dietary restriction during pregnancy and lactation: effect on digestive organ development in suckling rats.

To examine the relative effects of maternal malnutrition during pregnancy and lactation on development of the pancreas and small intestine in suckling pups, rats were restricted to 50% of control (C) intake beginning at day 5 of pregnancy. Immediately after birth, some litters were exchanged such that some C dams were suckling pups born to 50%-restricted dams (C/50) and vice versa (50/C). Other litters were allowed to stay with their own mothers, which received a control or restricted diet as during pregnancy (C/C and 50/50). Pups nurtured by restricted dams had reduced body weights, intestinal lengths, hepatic and pancreatic weights, and specific activities of pancreatic lipase and small intestinal brush border sucrase and maltase. Small intestinal lactase levels were higher in the groups of pups from mothers restricted during lactation. In nearly all cases, the 50/C group was the most severely affected while the C/50 group was intermediate between the C/C and 50/50 groups.

Amylases↗

Effect of hydrocortisone on the maturation of cholecystokinin (CCK) binding and CCK stimulated amylase release in pancreatic acini of neonatal rats.

Neonatal rat pancreata are not responsive to stimulation by cholecystokinin (CCK) and this has been shown to be due primarily to low binding of CCK to pancreatic acinar cells of rats of this age group. To see if hydrocortisone has any effect on the maturation of CCK binding and enzyme secretion, day-old rat pups were injected three times intraperintoneally with hydrocortisone at a dose of 5 mg/100 g body weight per dose and sacrificed 48 h after the first injection. Control age-matched pups were injected with 0.9% saline at the same volume and schedule as the hydrocortisone injected pups. The pancreatic weight, protein, and DNA contents were found to be significantly lower in the pups from the hydrocortisone-treated group than in the pups from the control group. The protein content per unit weight of DNA, however, was not different between the two. The maximal output of amylase under stimulation by 3 X 10(-10) M CCK was significantly higher in the dispersed acini prepared from the hydrocortisone-treated group as compared to dispersed acini prepared from the control (575 +/- 50 vs. 390 +/- 40% when expressed as a percentage of basal release). The maximal binding to 125I-BH-CCK was also significantly higher in the dispersed acini from the hydrocortisone group when compared to the dispersed acini from the control group (2.6 +/- 0.5 vs. 1.4 +/- 0.4%). Hydrocortisone, therefore, induces the precocious maturation of the secretory apparatus of the pancreatic acini, specifically the increase in capacity to bind and the greater responsiveness of the acini to CCK.

Amylases↗

Nutrition and exocrine pancreatic function in infancy: effects of total parenteral nutrition and first degree malnutrition.

Thirty-six infants suffering from gastrointestinal diseases during infancy were evaluated for exocrine pancreatic function by means of the pancreozymin-secretin test. Duodenal fluid volume, protein content, and content and peak-specific activity of amylase, lipase, and trypsin were determined following intravenous administration of either pancreozymin (CCK) or secretin. Seven infants receiving long-term parenteral nutrition and 17 infants receiving oral feedings and exhibiting first-degree malnutrition in association with chronic diarrhea underwent testing. Results were compared to those of a group of 12 age-matched infants with chronic diarrhea and weight loss. Four patients receiving total parenteral nutrition (TPN) suffered from severe short bowel syndrome and three had intractable diarrhea of infancy. The total duration of TPN ranged from 1.5-12 months, and the period of exclusive TPN in the absence of oral feedings ranged from 1-4 months. The heights, weights, and weight-for-height relationships were at or above the fifth percentile for all seven infants. The weight-for-height relationship of each patient in the control group was above the fifth percentile, while that of all malnourished infants was below the fifth percentile. No significant difference was found in the volume of fluid collected following either CCK or secretin administration. The content and concentration of amylase and lipase were lower in those patients receiving TPN. The levels were statistically significant (p less than 0.05) following secretin administration. In contrast, the peak-specific activity and total trypsin content, as well as protein content, was not significantly different in patients receiving TPN, controls, and malnourished patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗