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Biomedical subjects

L A Heitlinger

Publications and source records attributed to L A Heitlinger.

33 records · Page 2Linked to original sources

Glucose flux from dietary disaccharides: all sugars are not absorbed at equal rates.

Considerable discrepancies exist in the literature regarding the rates of glucose absorption from the common dietary disaccharides, lactose, maltose, and sucrose. This study compared the unidirectional flux of glucose derived from dietary disaccharides with that of their constituent monosaccharides in vitro. Lactose-stimulated short-circuit current (Isc) and mucosal-to-serosal flux (Jm----s) were lower than that of an equimolar glucose-galactose mixture and were phlorizin inhibitable. Maltose- and glucose-stimulated Isc were similar, but Jm----s of glucose derived from the hydrolysis of maltose was lower than that of free glucose. Sucrose-stimulated Isc and Jm----s were similar to that of an equimolar glucose-fructose mixture. Isc and Jm----s of glucose from both maltose and sucrose were phlorizin and acarbose inhibitable. We conclude that the rate of glucose uptake from disaccharides is less than or equal to that of free glucose and is dependent on the glucose source. We speculate that regulation of glucose uptake from disaccharides can occur at three sites: the hydrolytic enzyme, the glucose transporter, and the tight junctions.

Absorption↗

Human intestinal disaccharidase activities: correlations with age, biopsy technique, and degree of villus atrophy.

The relationship between intestinal morphology, disaccharidase activity, and disaccharide absorption is controversial. A retrospective study of 798 consecutive biopsies was performed to determine whether disaccharidase activities varied by subject age, biopsy technique, and degree of villus atrophy. Lactase activity was inversely correlated with age in the absence or presence of villus atrophy; sucrase, maltase, and palatinase activities did not correlate with age. Biopsies obtained by capsule or endoscopy had similar disaccharidase activities. In subjects 24 months of age or younger, the degree of mucosal injury was inversely correlated with lactase activity. In subjects older than 24 months, the degree of mucosal injury was inversely correlated with maltase and, to a lesser extent, lactase activities. The data suggest that disaccharidase activities in mucosal biopsies, whether obtained by endoscopy or capsule, are diminished in the presence of mucosal injury and correlate inversely with the degree of injury.

Adolescent↗

Failure to conserve lactose and glucose polymers during frozen storage of fecal specimens: methods for preservation.

Freezing is often used to retard bacterial enzymatic activity in fecal specimens collected to quantify specific carbohydrates. The effectiveness of freezer storage on preservation of lactose and glucose polymers was assessed. The data showed that more than 50% of lactose that was added to fecal supernatants that were stored without treatment for more than 50 days at -20 degrees C was lost. Adjustment of pH with HCl (pH 4.9), with HgCl2 (pH 6.3 or 5.85), or with NaOH (pH 10) improved carbohydrate preservation (P less than 0.0004). Storage of the supernatants of fecal homogenates lessened the loss of carbohydrate compared with the total homogenates (P less than 0.001). In supernatants, degradation occurred via simple hydrolysis; in homogenates, degradation occurred by hydrolysis and fermentation to a variety of end-products. Unprocessed fecal specimens that were frozen for months, then retrieved and incubated with lactose or glucose polymers showed extensive fermentative capacity. Cumulatively, the data indicate that enzymatic activity in feces is not halted by storage in the freezer, even if bacteria have been filtered from the stool.

Animals↗

Digestion, absorption, and fermentation of carbohydrates.

Newborn infants born after a term gestation appear to have an adequate capacity for small intestinal digestion and absorption of carbohydrate. Premature infants do not have a mature level of intestinal lactase activity. Apparently, in the premature infant, colonic fermentation serves an important, if not the only major route, for lactose carbon absorption, and it also appears that signs of fermentation activity such as increased BH2 are not indicative of disease. Important questions remaining in the premature infant relate to developmental aspects of colonic fermentative activity, effects of systemic antibiotic treatment on colonic salvage, the effects of various fermentation pathways on energy balance, the capacity for absorption of sugars, SCFA, and electrolytes by colonic epithelia, and the effects of fermentation products on metabolism and on the mucosal cells of the intestine or colon. Research addressing these questions may have relevance in the following areas: further development of formula diets for healthy premature infants and for patients of all ages with intestinal or colon dysfunction; the effects of colonic disease or surgical resection; the nutritional or clinical effects of dietary fiber; and the effects of antibiotic therapy on intestinal and colon function.

Animals↗

Effects of graded alpha-glucosidase inhibition on sugar absorption in vivo.

The effect of inhibition of disaccharidases on the degree of absorption of glucose, lactose, and sucrose was examined utilizing an in vivo model in the rat. Acarbose, a competitive alpha-glucosidase inhibitor was utilized to selectively inhibit small intestinal mucosal enzymes. Adult rats (250-350 g body weight) were the subjects of intraduodenal bolus infusion experiments with either sugar alone or sugar plus acarbose. All sugars were infused at a dose of 0.5 g/kg body weight. Portal venous blood glucose was determined at 30-min intervals from 0 to 150 min. Glucose (monosaccharide) and lactose (beta-galactoside) absorption were not altered by the presence of acarbose. In contrast, sucrose (alpha-glucosidase) absorption was significantly diminished in the presence of acarbose. Sucrose absorption in the presence of increasing acarbose doses (0.7-5.6 mg/kg body weight) was depressed in a dose-dependent fashion. Linear regression analysis revealed a high degree of correlation between residual sucrase activity and area under blood glucose curve (r = 0.9837). Similar degrees of correlation were found between acarbose dose and area under blood glucose curve (r = -0.9322), and between residual sucrase activity and acarbose dose (r = -0.9695). These data confirm that acarbose is a selective alpha-glucosidase inhibitor that does not affect monosaccharidase transport. In the presence of acarbose, alpha-glucosidase absorption is diminished in a dose-dependent fashion. Postprandial glucose rise following an alpha-glucosidase meal seems to be determined, in the presence of graded acarbose inhibition, by residual mucosal alpha-glucosidase activity.

Acarbose↗

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↗

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↗

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 development of the gastrointestinal tract on infant feeding.

We have described the developmental pattern of the gastrointestinal tract under optimal conditions (i.e., low risk pregnancy and normal labor and delivery at term). The tissues do not develop simultaneously, and morphologic and functional development are not concurrent. An important consideration is the effect of suboptimal or even adverse conditions on the developmental sequence and attainment of maturity. Malnutrition during both the prenatal and postnatal periods may restrict the morphologic and biochemical development of the gastrointestinal tract. Dietary modifications have been shown to alter the developmental pattern of intestinal and pancreatic enzymes in animal models. Drugs and hormonal therapy given during pregnancy and early infancy have been known to cause developmental defects, but the specific effects on the gastrointestinal tract have not been evaluated. For further understanding of digestibility of nutrients and absorption in the perinatal period, these departures from the normal development of the gastrointestinal tract and the mechanisms by which these potential effects occur remain to be described. In view of these undetermined factors, in the case of intolerance or unavailability of milk from the natural mother, feedings should be individualized, with attention to direct measurement of enzyme concentrations, balance studies, or both, especially in the case of extreme prematurity or unusual requirements.

Dietary Carbohydrates↗

Enzymes in mother's milk and their possible role in digestion.

Human breast milk contains many enzymes, some of which may assist in digestion; other enzymes may have other diverse functions. The loci and regulation of milk enzyme synthesis remain to be elucidated, but multiple loci and complex hormonal regulation seem to be likely. In a similar fashion, multiple mechanisms of protein release have been described, but stimulus secretion coupling has not been directly demonstrated. The possible physiologic importance of milk as compensatory mechanisms for the relatively limited digestive capabilities of young infants is but one of many reasons why breast milk should not be heated, if possible, prior to feeding.

Amylases↗

Mammary amylase: a possible alternate pathway of carbohydrate digestion in infancy.

Mammary amylase is a possible alternate pathway of digestion of glucose polymers and starches, that is most important in early infancy when pancreatic amylase is low or absent in duodenal fluid and responds poorly to stimuli. Human breast milk contains 1000-5000 units of amylase/liter. In order to evaluate the likelihood that a significant proportion of mammary amylase activity would withstand passage through the stomach, purified and unpurified mammary amylase were exposed to acid and pepsin in vitro to simulate the gastric environment found in young infants. Both purified and unpurified enzymes were stable at pH 7.5 with little or no activity lost after 4 h, and approximately 80% retained at 6 h. When incubated at pH 3.5, one-third of unpurified enzyme activity was retained for 6 h; in contrast, the purified enzyme was acid labile losing 80% by 2 h. Addition of bovine serum albumin or breast milk proteins to purified enzyme protected the activity. When unpurified enzyme was exposed to a stepwise decline in pH from 6.5 to 3.5 over 4 h, 50% of the original activity was retained. Unless the concentration was greater than or equal to 3750 units/ml, the addition of varying concentrations of pepsin to defatted breast milk incubated at pH 3.5 did not affect any greater decay of enzyme activity despite evidence of peptic digestion of proteins in the reaction mixture. This study supports the possibility that ingested mammary amylase could retain a significant proportion of its original activity after exposure to acid and pepsin in the stomach of young infants.

Amylases↗

Relationship of endomysial antibodies to jejunal mucosal pathology: specificity towards both symptomatic and asymptomatic celiacs.

Serum immunoglobulin A class antibodies reactive to the endomysial lining of the smooth muscle bundles of the gastrointestinal tract have recently been reported to be specific and sensitive indicators of celiac disease (CD). A total of 203 subjects were examined for serum endomysial antibodies (EmA) and in 103 small bowel biopsies were obtained. EmA were detected in 43 cases including 26 CD patients evaluated during the gluten challenge phase of diagnosis by European Society for Pediatric Gastroenterology and Nutrition criteria, 11 of 53 symptomatic patients, and 6 asymptomatic family members. All patients with detectable antibody at the time of biopsy exhibited grade III-IV villous atrophy. Disaccharidase activities performed in 19 cases revealed severe deficiencies. EmA were not detected in 160 subjects including 42 infants and children with chronic nonspecific diarrhea. Eighteen of these possessed grade II-III villous atrophy with moderate disaccharidase deficiency and 24 were found to have normal histology and enzymes. The EmA were also not detected in 3 CD patients who were well maintained on a gluten-free diet for greater than 1 year and 25 asymptomatic family members exhibiting normal histology and enzymes. An additional 90 infants and children with other gastrointestinal and liver diseases were also negative for the serum EmA. Fourteen of these patients underwent biopsies and were demonstrated to have normal histology.

Adolescent↗

Rectal myopathy in chronically constipated children.

We examined full-thickness rectal biopsies from 30 children who had chronic constipation, including 5 children with constipation associated with clinical symptoms of intestinal pseudo-obstruction. Biopsies from 9 patients who required colonic interposition and from 7 with Hirschsprung's disease were used as controls. Tissues were evaluated for muscularis mucosae thickness (in mm), for absolute circular and longitudinal muscle layer thicknesses and their ratio, and for the intensity of neural vasoactive intestinal peptide (VIP) immunohistochemical staining. Atrophy of the rectal musculature with focal muscle fiber vacuolation or muscle fiber disappearance was found in all children with chronic constipation. Muscularis mucosae thickness was increased (P < .01) and the circular-to-longitudinal muscle ratio was decreased in the constipation group, with the greatest degree of atrophy being demonstrated in the circular layer. Two of the patients had additional biopsies up to 9 years after the first that illustrate progressive myopathic changes over time. This study demonstrates muscular atrophy in the rectum of children with chronic constipation. Besides primary idiopathic disease, potential etiologies include chronic distention, denervation, functional obstruction from obstipation, alteration in gut hormones, and toxic, ischemic, or neural injury.

Adolescent↗