Biomedical subjects

Barbara Stoll

Publications and source records attributed to Barbara Stoll.

28 records · Page 2Linked to original sources

PubMed2003

Total parenteral nutrition adversely affects gut barrier function in neonatal piglets.

Sepsis is the most common morbidity in preterm infants, who often receive total parenteral nutrition (TPN). We hypothesized that gut barrier function is compromised in TPN-fed compared with enterally fed newborn piglets (ENT pigs). Colostrum-deprived newborn pigs were implanted with jugular venous and bladder catheters under general anesthesia. Pigs were either administered TPN (n = 15) or fed formula (ENT pigs, n = 15). After 6 days, pigs were gavaged a solution of mannitol, lactulose, and polyethylene glycol 4000 (PEG 4000) and urine was collected for 24 h. At 7 days, small bowel samples were assayed for myeloperoxidase activity, morphometry, and tight junction protein abundance. Intestinal contents and peripheral organ sites were cultured for bacteria. Urinary recovery (%dose) of mannitol (53 vs. 68) was lower, whereas that of lactulose (2.93 vs. 0.18) and PEG 4000 (12.78 vs. 0.96) were higher in TPN vs. ENT pigs, respectively (P < 0.05). Incidence of translocation was similar in TPN and ENT pigs. Myeloperoxidase activity was increased in TPN vs. ENT pigs in the jejunum (P < 0.001) and was weakly correlated with lactulose (R2 = 0.32) and PEG 4000 (R2 = 0.38) recovery. Goblet cell counts did not change, but intraepithelial lymphocyte numbers decreased with TPN. Only claudin-1 protein abundance was increased in the TPN group. We conclude that TPN is associated with impairment of neonatal gut barrier function as measured by permeability but not translocation.

Animals↗

PubMed2003

Intestinal lysine metabolism is driven by the enteral availability of dietary lysine in piglets fed a bolus meal.

Previous steady-state continuous-feeding studies have shown that the gut mucosa removes substantial amounts of both dietary and systemic amino acids. However, enteral nutrition is often given under non-steady-state conditions as a bolus meal, and this has been shown to influence systemic metabolism. Therefore, our aim was to quantify the relative metabolism of dietary and systemic lysine by the portal-drained viscera (PDV) under non-steady-state conditions after a single bolus meal. Five 28-day-old piglets implanted with arterial, venous, and portal catheters and with an ultrasonic portal flow probe were given an oral bolus feeding of a milk formula containing a trace quantity of intrinsically 15N-labeled soy protein and a continuous intravenous infusion of [U-13C]lysine for 8 h. Total lysine use by the PDV was maximal 1 h after the meal (891 micromol x kg(-1) x h(-1)) and was predominantly of dietary origin (89%), paralleling the enteral delivery of dietary lysine. Intestinal lysine use returned to a low level after 4 h postprandially and was derived exclusively from the arterial supply until 8 h. Cumulative systemic appearance of dietary lysine reached 44 and 80% of the ingested amount 4 and 8 h after the meal, respectively, whereas the PDV first-pass use of dietary lysine was 55 and 32% of the intake for these two periods, respectively. We conclude that the first-pass utilization rate of dietary lysine by the PDV is directly increased by the enteral lysine availability and that it is higher with a bolus than with continuous oral feeding.

Adaptation, Physiological↗

PubMed2003

GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1.

BACKGROUND & AIMS: Our aim was to determine whether the intestinotrophic effects of GLP-2 are mediated by acute up-regulation of intestinal substrate utilization in TPN-fed piglets. METHODS: Twenty-four 12-day-old pigs, fitted with a portal flow probe and carotid, jugular and portal catheters, were fed by TPN for 7 days. On day 8, a group of pigs (n = 8) was infused intravenously with saline (control) for 4 hours and then with GLP-2 (500 pmol x kg(-1) x hour(-1), GLP-2) for 4 hours. (2)H-glucose and (13)C-phenylalanine were infused to estimate their kinetics and protein turnover. Another group (n = 8) received consecutive intravenous infusions of saline, GLP-2, and GLP-2 plus N(G)-Nitro-L-arginine methyl ester (L-NAME, 50 micromol x kg(-1) x hour(-1)) for 4 hours each. RESULTS: GLP-2 acutely increased portal-drained visceral (PDV) blood flow rate (+25%) and intestinal blood volume (+51%) in TPN-fed piglets. GLP-2 also increased intestinal constitutive nitric oxide synthase (NOS) activity and endothelial NOS protein abundance. GLP-2 acutely increased PDV glucose uptake (+90%) and net lactate production (+79%). Co-infusion of GLP-2 plus L-NAME did not increase either PDV blood flow rate or glucose uptake. GLP-2 increased PDV indispensable amino acid uptake by 220% and protein synthesis by 125%, but did not decrease protein breakdown or phenylalanine oxidation. CONCLUSIONS: We conclude that in TPN-fed neonatal pigs, GLP-2 acutely stimulates intestinal blood flow and glucose utilization, and this response is nitric oxide-dependent. These findings suggest that GLP-2 may play an important physiological role in the regulation of intestinal blood flow and that nitric oxide is involved in GLP-2 receptor function.

Amino Acids↗

PubMed2003

Parenteral nutrition results in impaired lactose digestion and hexose absorption when enteral feeding is initiated in infant pigs.

BACKGROUND: Preterm infants often receive total parenteral nutrition (TPN) before enteral feeding. Although TPN has been linked to mucosal atrophy, its effects on intestinal digestion, absorption, and metabolism are unknown. OBJECTIVE: Our aim was to determine the effects of TPN on rates of intestinal nutrient absorption and metabolism in infant pigs after initiation of enteral feeding. DESIGN: Piglets were surgically implanted with catheters in the carotid artery, jugular vein, portal vein, and duodenum; an ultrasonic blood flow probe was inserted in the portal vein. Piglets were given TPN (TPN group) or enterally fed formula (enteral group) for 6 d. On day 7, both groups were enterally fed a milk-based formula, and the net portal absorption and metabolism of enteral [(2)H]glucose and [(13)C]leucine were measured. RESULTS: After enteral feeding began, portal blood flow increased by 27% and 41% above the basal rate in the enteral and TPN groups, respectively; oxygen consumption remained lower in the TPN group. During enteral feeding, the net portal absorption of glucose was lower in the TPN group and that of galactose was not significantly different between the groups; lactate release was higher in the TPN group. Portal absorption accounted for only approximately 37% of galactose intake in both groups. The TPN group had lower net portal absorption of arginine, lysine, threonine, and glycine. The portal absorption of dietary leucine was not significantly different between the groups; the arterial utilization and oxidation of leucine were significantly lower in the TPN group. CONCLUSION: Short-term TPN results in decreased lactose digestion and hexose absorption and increased intestinal utilization of key essential amino acids when enteral feeding is initiated in piglets.

Amino Acids, Essential↗

PubMed2003

Glucagon-like peptide 2: a key link between nutrition and intestinal adaptation in neonates?

This paper reviews the evidence from recent studies in young piglets to examine the hypothesis that glucagon-like peptide 2 (GLP-2) is a physiologically relevant hormonal signal linked to the intestinal adaptation associated with enteral nutrition in neonates. Observations that support the hypothesis include, 1) the GLP-2 secretory response to enteral nutrition is functional as early as late gestation, 2) parallel changes in intestinal growth and circulating GLP-2 occur in response to the quantity and composition of enteral nutrition after birth, and 3) the acute temporal changes in intestinal metabolism and circulating GLP-2 concentrations in response to enteral nutrition are generally coincident. In contrast, however, the lack of intestinal trophic responses to both pharmacological GLP-2 concentrations in the fetus and weanling pigs, and to physiological GLP-2 concentrations in neonates raises doubts concerning the physiological relevance of GLP-2 as a enterally mediated trophic signal. A more definitive test of this hypothesis will require further studies that assess the intestinal metabolic response to enteral nutrition using experimental approaches that block GLP-2 action.

Adaptation, Physiological↗

PubMed2002

Key nutrients and growth factors for the neonatal gastrointestinal tract.

The nutritional support of gastrointestinal growth and function is an important consideration in the clinical care of neonatal infants. In most health infants, the provision of either breast milk or formula seems to support normal intestinal mucosal growth, but the most significant advantages of breast milk may be for host defense or gut barrier-related functions that are involved in reducing infection. The specific effects of various milk-borne growth factors on key mucosal immune and barrier functions are likely to provide valuable new clues to the advantages of human milk. A substantial number of preterm, low-birth weight babies or those suffering from compromised intestinal function, however, often cannot tolerate oral feedings and instead receive TPN. The consequences of TPN on gastrointestinal function and how this contributes to morbidity of these infants warrants further study, with respect to both clinical and basic research questions. Although enteral nutrition seems to be a critical stimulus for intestinal function, the minimal amounts and composition of nutrients necessary to maintain specific intestinal functions remain to be established. The experimental tools exist to start defining the specific nutrient requirements for the infant gut and some of these nutrients are known (e.g., glutamate, glutamine, and threonine). Peptide growth factors and gut hormones clearly play a role in gut growth and in several ways mediate the trophic actions of enteral nutrition. Although a number of these growth factors are good candidates for therapeutic use, their clinical application in the management of gastrointestinal insufficiency and disease has been slow. The emergence of GLP-2 as a trophic peptide that seems to target the gut is a promising candidate on the horizon.

Amino Acids↗

PubMed2002

The high metabolic cost of a functional gut.

BACKGROUND & AIMS: Animal studies have shown that more than half of the dietary protein intake is used by the gut and that a large proportion of this utilization is devoted to (glyco-)protein synthesis. Recycling of these secretions may play a critical role in the regulation of overall dietary amino acid bioavailability. METHODS: Four piglets (age 32 days, 8-10 kg) bearing portal, arterial, and duodenal catheters and a portal flow probe were infused with a complete diet via the duodenum for 12 hours, followed by 12 hours of fasting. The portal balance of glucose and amino acids was measured throughout the 24-hour period. The animals also received duodenal and intravenous infusions of different lysine and threonine tracers. Measurements of intestinal tracer utilization and reappearance in the portal blood were used to calculate intestinal amino acid utilization and recycling. RESULTS: From 0 to 6 hours, one third of the protein intake appeared in the portal blood. As feeding continued, the portal glucose balance (60% of intake) was constant, but the net amino acid portal balance became progressively more positive. Significant net amino acid absorption continued for at least 6 hours after the cessation of feeding. Over 24 hours, 52% of the dietary protein intake appeared in the circulation and one third of this derived from recycled intestinal secretions. CONCLUSIONS: Intestinal recycling of amino acids contributes significantly to their systemic availability and may be a critical factor in amino acid nutrition.

Absorption↗

PubMed2002

Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants.

OBJECTIVE: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD). STUDY DESIGN: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups. CONCLUSIONS: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention.

Anti-Inflammatory Agents↗

PubMed2002

Net portal absorption of enterally fed alpha-ketoglutarate is limited in young pigs.

Our aim was to quantify the intestinal metabolic fate of dietary alpha-ketoglutarate (AKG). Female pigs (n = 6; 21 d old) were implanted with arterial, venous, portal and gastric catheters and an ultrasonic portal flow probe and fed a corn and soybean meal-based diet. On the day of the experiment, the pigs received a 4-h intragastric infusion of sodium AKG at a rate equivalent to 0, 2.5, 5 or 10% of dietary intake. The net portal AKG balance of the control and 2.5% treatments did not differ and were not different from zero. However, the net portal AKG balance of both the 5 [163 micro mol/(kg. h)] and 10% [159 micro mol/(kg. h)] treatments were greater (P < 0.05) than the control. Despite significant net AKG absorption at the 5 and 10% levels, the net portal appearance represented only 10.8 and 6.7%, respectively, of the enteral input. The net portal appearances of glutamate, glutamine, ammonia and the branched-chain amino acids were not affected by dietary AKG level. We conclude that the absorption of dietary AKG is limited in young pigs and does not change the net portal balance of amino acids or ammonia.

Amino Acids↗

PubMedDate not supplied

Feeding an elemental diet vs a milk-based formula does not decrease intestinal mucosal growth in infant pigs.

BACKGROUND: We previously showed that the level of enteral nutrient intake determines the rate of intestinal growth in piglets. Our objective was to determine whether providing enteral nutrition in the form of elemental nutrients (glucose, amino acids, lipid [ED]) rather than cow's milk formula (lactose, protein, lipid [FORM]) reduces small intestinal growth and lactase activity. METHODS: Three-week-old piglets were fed either ED (n = 7) intragastrically or FORM (n = 6) orally for 6 days. RESULTS: Intestinal protein and DNA masses, villus height, and crypt depth were not different in ED and FORM pigs. Crypt cell proliferation, measured by in vivo bromodeoxyuridine labeling, was significantly (p < .05) higher (+37%) in ED than in FORM pigs. Rates of mucosal protein synthesis (%/d), measured by in vivo 2H-leucine incorporation, were higher (p < .05) in ED than FORM (147 vs 89) pigs. Circulating concentrations (pmol/L) of the intestinotrophic peptide, glucagon-like peptide-2 (GLP-2), were also higher (p < .05) in ED than in FORM (148 vs 87) pigs. The mean lactase-specific activity (micromol/min/g) in proximal and distal segments was higher (p < .05) in FORM than in ED (124 vs 58) pigs. CONCLUSIONS: We conclude that intestinal mucosal growth and villus morphology are similar in pigs fed ED and FORM, despite higher cell proliferation and protein synthesis rates and lower lactase activity with ED. This implies that elemental diets may be as trophic as polymeric formulas to simultaneously provide nutrition and a stimulus for intestinal growth during bowel rest.

Animals↗