Biomedical subjects

Jan Elnif

Publications and source records attributed to Jan Elnif.

6 recordsLinked to original sources

PubMed2006

Diet- and colonization-dependent intestinal dysfunction predisposes to necrotizing enterocolitis in preterm pigs.

BACKGROUND & AIMS: Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs. METHODS: Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1-2 days of age. RESULTS: Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects. CONCLUSIONS: A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of Clostridium perfringens.

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PubMed2005

Preterm birth makes the immature intestine sensitive to feeding-induced intestinal atrophy.

Preterm birth and formula feeding predispose to small intestinal dysfunction, which may lead to necrotizing enterocolitis (NEC). In piglets, we tested whether the physiological and environmental transitions occurring at birth affect the response of the immature intestine to enteral feeding. Pig fetuses (106 days gestation, term = 115 days) were prepared with esophageal feeding tubes and fed either sow's colostrum (n = 8) or infant formula (n = 7) in utero. After 24 h of oral feeding, the pig fetuses were delivered by cesarean section and their gastrointestinal morphology and function were compared with those of preterm newborn (NB) littermates that were not fed (n = 8) or fed colostrum (n = 7) or formula (n = 13) for 24 h after birth. Before birth, both colostrum and formula feeding resulted in marked increases in intestinal mass, brush-border enzyme activities, and plasma glucagon-like peptide 2 concentrations, to levels similar to those in NB colostrum-fed piglets. In contrast, NB formula-fed piglets showed reduced intestinal growth, decreased brush-border enzyme activities, and intestinal lesions, reflecting NEC. NB formula-fed pigs also showed impaired enterocyte endocytotic function and decreased antioxidative capacity, whereas brush-border enzyme mRNA levels were unaltered, relative to NB colostrum-fed pigs. Our results indicate that the feeding-induced growth and enzyme maturation of the immature intestine are not birth dependent. However, with a suboptimal diet (milk formula), factors related to preterm birth (e.g., microbial colonization and metabolic and endocrine changes) make the immature intestine sensitive to atrophy and development of NEC.

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PubMed2003

Activities of gastric, pancreatic, and intestinal brush-border membrane enzymes during postnatal development of dogs.

OBJECTIVE: To measure activities of digestive enzymes during postnatal development in dogs. SAMPLE POPULATION: Gastrointestinal tract tissues obtained from 110 Beagles ranging from neonatal to adult dogs. PROCEDURE: Pepsin and lipase activities were measured in gastric contents, and amylase, lipase, trypsin, and chymotrypsin activities were measured in small intestinal contents and pancreatic tissue. Activities of lactase, sucrase, 4 peptidases, and enteropeptidase were assayed in samples of mucosa obtained from 3 regions of the small intestine. RESULTS: Gastric pH was low at all ages. Pepsin was not detected until day 21, and activity increased between day 63 and adulthood. Activities of amylase and lipase in contents of the small intestine and pancreatic tissue were lower during suckling than after weaning. Activities of trypsin and chymotrypsin did not vary among ages for luminal contents, whereas activities associated with pancreatic tissue decreased between birth and adulthood for trypsin but increased for chymotrypsin. Lactase and gamma-glutamyltranspeptidase activities were highest at birth, whereas the activities of sucrase and the 4 peptidases increased after birth. Enteropeptidase was detected only in the proximal region of the small intestine at all ages. CONCLUSIONS AND CLINICAL RELEVANCE: Secretions in the gastrointestinal tract proximal to the duodenum, enzymes in milk, and other digestive mechanisms compensate for low luminal activities of pancreatic enzymes during the perinatal period. Postnatal changes in digestive secretions influence nutrient availability, concentrations of signaling molecules, and activity of antimicrobial compounds that inhibit pathogens. Matching sources of nutrients to digestive abilities will improve the health of dogs during development.

Aging↗

PubMed2002

Preterm birth affects the intestinal response to parenteral and enteral nutrition in newborn pigs.

Maturation of gastrointestinal (GI) function in neonates is stimulated by enteral nutrition, whereas parenteral nutrition induces GI atrophy and malfunction. We investigated whether preterm birth alters the GI responses to parenteral and enteral nutrition. Pigs were delivered either preterm (107 d gestation) or at term (115 d gestation) and fed total parenteral nutrition (TPN) or enteral sow's milk (ENT) for 6 d after birth. Immaturity of the preterm pigs was documented by reduced blood pH, oxygen saturation and neutrophil granulocyte function, impaired intestinal immunoglobulin G uptake from colostrum, and altered relative weights of visceral organs (small intestine, liver, spleen, pancreas, and adrenals). For both ages at delivery, increases occurred in pancreatic weight (30-75%) and amylase activity (0.5- to 13-fold) after birth, but much more in ENT than in TPN pigs (P < 0.05). Six days of TPN feeding was associated with reduced intestinal weight for both delivery groups (60% of values in ENT, P < 0.001), but only in term TPN pigs was the weight lower than at birth (-20%, P < 0.05). Likewise, it was only in term TPN pigs that intestinal maltase activity increased, compared with ENT, and the absorption of glucose and proline decreased. Only in preterm pigs did TPN feeding increase lactase activity (+50% compared with ENT, P < 0.05). For both delivery ages, the mRNA of lactase-phloridzin hydrolase and sodium-coupled glucose transporter 1 were increased in TPN, compared with ENT. In conclusion, the trophic effect of enteral vs. parenteral nutrition on the GI tract is also present after preterm birth, but the postnatal maturation of many GI functions is modified, compared with term birth. The effects of nutritional regimen on the maturation of the gut epithelium in neonates depend on gestational age at birth.

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PubMed2002

Prenatal development of gastrointestinal function in the pig and the effects of fetal esophageal obstruction.

Maturation of the fetal gastrointestinal tract (GIT) is influenced by both luminal stimuli (e.g. swallowed fluid) and hormonal factors (e.g. endogenous cortisol release). The aims of the present study were 1) to investigate GIT growth and maturation during the last 20% of gestation in pigs (term = 114 +/- 2 d), and 2) to investigate the effect of esophageal ligation, to prevent fetal swallowing, at 80% to 91% gestation. In normal fetuses, marked increases occurred during late gestation in body weight (+95%), relative intestinal weight (+79%, g kg(-1) body weight), activity of some digestive enzymes (1.5- to 10-fold), and absorption of glucose and intact proteins (3- to 6-fold). Fetuses with ligated esophagi had lowered body weight (-20%), reduced intestinal weight (-43%), aminopeptidase A activity (-24%), and glucose absorption (-27%), while lactase, sucrase, and dipeptidylpeptidase IV activities were increased (+40-50%), compared with sham-operated fetuses (all p < 0.05). Other parameters of GIT function remained unchanged by esophageal obstruction (absorption of amino acids and immunoglobulin, activity of chymosin, amylase, trypsin, chymotrypsin, maltase, aminopeptidase N -- all expressed per gram GIT tissue). Ligated fetuses had elevated cortisol levels, which is known to stimulate fetal GIT maturation. We conclude that the rapid development of GIT function in late gestation is diminished by esophageal obstruction, mainly due to slower GIT growth and not inhibition of normal functional development of enterocytes.

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PubMed2002

Glucagon-like peptide 2 enhances maltase-glucoamylase and sucrase-isomaltase gene expression and activity in parenterally fed premature neonatal piglets.

Exogenous glucagon-like peptide 2 (GLP-2) mimics the stimulatory effect of enteral nutrition on intestinal mucosal growth in preterm neonatal pigs. Little is known about its effects on small intestinal function. In this study, we investigated whether the trophic actions of GLP-2 and enteral nutrition are paralleled by effects on small intestinal function. Cesarean-delivered piglets (92% of gestation) were given either a parenteral nutrient infusion [total parenteral nutrition (TPN), n = 7], TPN + human GLP-2 (25 nmol/kg/d, n = 8), or enteral nutrition (ENT, n = 6) for 6 d. Gene expression (mRNA) and activities of lactase phlorizin hydrolase (LPH), maltase-glucoamylase (MGA), sucrase-isomaltase (SI), aminopeptidase N (ApN), and A (ApA) and dipeptidyl peptidase IV (DPP IV) were measured. Both GLP-2 and enteral nutrition increased mucosal weight (+30-40%, p < 0.05) relative to TPN. GLP-2 stimulated jejunal MGA and SI mRNA abundance and activity levels but did not change LPH in parenterally fed pigs (p < 0.05). Enteral nutrition decreased jejunal LPH and MGA mRNA abundance and activity and increased ileal ApN, ApA, and DPP IV activities relative to TPN (p < 0.05). We conclude that GLP-2 and enteral nutrition exert different effects on intestinal enzyme function despite similar effects on intestinal growth. In addition, the effects of GLP-2 on intestinal function in these parenterally fed, premature neonatal pigs differed from those previously reported for similarly fed term neonates.

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