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Kelly A Tappenden

Publications and source records attributed to Kelly A Tappenden.

17 recordsLinked to original sources
PubMed2006

Mechanisms of enteral nutrient-enhanced intestinal adaptation.

The role of enteral nutrients in maintaining small intestinal structure and function is well established. Evidence that enteral nutrients induce intestinal adaptation include the structural and functional gradient along the length of the healthy intestine, the atrophy and functional compromise induced by fasting and parenteral nutrition, and the enhanced adaptive capacity of the distal intestine following partial enterectomy. Key mechanisms contributing to enteral nutrient-induced intestinal adaptation include nonspecific luminal stimulation and that provided by specific nutrients, "functional workload" induced by polymeric nutrients, potential stimulation of pancreaticobiliary secretions, secretion of humoral mediators, and induction of intestinal hyperemia.

Adaptation, Physiological↗
PubMed2006

Formula-feeding reduces lactose digestive capacity in neonatal pigs.

The intestine of newborn pigs develops rapidly during the first days postpartum. We investigated if feeding milk replacer (infant formula) as an alternative to colostrum has compromising effects on nutrient digestive function in the neonatal period. Nineteen piglets born at term were assigned to one of four treatments: (1) newborn controls; (2) natural suckling for 24 h; (3) tube-fed formula for 24 h; (4) tube-fed porcine colostrum for 24 h. All three fed groups showed significant increases in small-intestinal and colonic weights, villous heights and widths, maltase and aminopeptidase A activities, and decreases in dipeptidylpeptidase IV activity, relative to newborn pigs. Following oral boluses of mannitol, lactose or galactose, formula-fed pigs showed significantly reduced plasma levels of mannitol and galactose compared with colostrum-fed pigs. Activity of intestinal inducible NO synthase and plasma levels of cortisol were significantly increased, whereas intestinal constitutive NO synthase and alpha-tocopherol were decreased in formula-fed pigs compared with colostrum-fed pigs. Although formula-fed pigs only showed minor clinical signs of intestinal dysfunction and showed similar intestinal trophic responses just after birth, as those fed colostrum, lactose digestive capacity was markedly reduced. We conclude that formula-feeding may exert detrimental effects on intestinal function in neonates. Formula-induced subclinical malfunction of the gut in pigs born at term was associated with altered NO synthase activity and antioxidative capacity.

Animals↗
PubMed2005

Induction of mucosal tolerance in Peyer's patch-deficient, ligated small bowel loops.

To explore the requirement for M cells and the Peyer's patch (PP) in induction of oral tolerance and address the potential in vivo role of intestinal epithelial cells as nonprofessional APCs, we have attempted to induce tolerance in mice with ligated small bowel loops without M cells and Peyer's patches. A 2-centimeter section of vascularized small bowel was spliced away from the gut without disruption of the mesenteric attachments. We introduced OVA directly into the lumen of the loop prior to footpad immunization. By excising segments of bowel that contain PPs in some mice and segments without patches in others, we could study the necessity of the M cell and the underlying patch versus epithelial cells in induction of mucosal tolerance. We show that OVA-specific T cell proliferation and serum antibody responses are reduced in mice that have previously been given OVA both in PP-containing loops and in loops without patches. Furthermore, both high- and low-dose tolerance could be induced in the absence of PPs. Low-dose tolerance is associated with bystander suppression and requires IL-10, which indicates active suppression and the induction of regulatory cells. These data suggest that there is a critical role for components of the mucosal immune system other than PPs in antigen sampling and induction of oral tolerance.

Animals↗
PubMed2005

Diet and age affect intestinal morphology and large bowel fermentative end-product concentrations in senior and young adult dogs.

The objective of this study was to determine the effects of age and diet on intestinal morphology and large bowel fermentative end-product concentrations in healthy dogs. Small intestinal villus width, height, and area, and small intestinal and colonic crypt depth were measured. Large bowel digesta samples were analyzed for ammonia, SCFAs, and branched-chain fatty acids (BCFAs). SCFAs are considered to be beneficial fermentative end-products in the intestine because they exert trophic effects on intestinal cells. Twelve senior (age = 11.1 y +/- 0.6 at baseline; 6 male, 6 female) and 12 young adult (age = 8 wk old at baseline; 6 male, 6 female) beagles were randomly assigned to 1 of 2 dietary treatments, an animal product-based diet (APB) and a plant product-based diet (PPB). Diets were fed for 12 mo. Jejunal (P = 0.03) and ileal (P = 0.02) villus height, and duodenal (P = 0.04) villus width were greater for dogs consuming the PPB diet. Young dogs had greater (P = 0.04) jejunal villus height, whereas senior dogs had greater (P < 0.001) colonic crypt depth. Ammonia concentrations decreased (P = 0.03) from proximal to distal colon and were higher in dogs consuming APB (P = 0.03). Age and treatment affected butyrate concentrations, with senior dogs (P = 0.04) and dogs consuming APB (P = 0.04) having higher concentrations. Both diet and age affected small and large intestinal morphology, and colonic fermentative end-product concentrations in dogs.

Animal Feed↗
PubMed2004

Genistein inhibits intestinal cell proliferation in piglets.

Currently 15% of U.S. infants are fed soy formulas that contain up to 14 mg of genistein equivalents/L. Our goal was to investigate the impact of dietary genistein on intestinal development. Piglets (n=8/group) were fed sow milk replacer (MR), MR+1 mg/L of genistein (LG), or MR+14 mg/L of genistein (HG) for 10 d. Formula intake, weight gain, and intestinal length and weight were similar in all groups. Average serum genistein concentration in the HG group was similar to that of soy formula-fed infants. No significant effects of genistein on enterocyte apoptosis, lactase, and sucrase activities or electrophysiologic measures were observed in jejunum or ileum. Jejunal and ileal villus heights were not significantly different, but the percentage of proliferating cell nuclear antigen-positive jejunal crypt cells in the HG was reduced 50% compared with that in MR and LG (p=0.001), indicating decreased proliferation. Enterocyte migration distance in the HG group tended to be 20% less (p=0.1) than LG or MR. Jejunal estrogen receptor beta mRNA expression in HG was half of that in LG (p=0.05), but neither was significantly different from MR. In conclusion, genistein at the level present in soy infant formula is bioactive in the small intestine and results in reduced enterocyte proliferation and migration. The lack of effect of genistein on nutrient transport and enzyme activity suggests that the impact of genistein is greater on proliferating versus differentiated intestinal cells.

Animal Feed↗
PubMed2004

Isolated soy protein consumption reduces urinary albumin excretion and improves the serum lipid profile in men with type 2 diabetes mellitus and nephropathy.

Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic patients with nephropathy, and to improve serum lipids. This study examined the effects of isolated soy protein consumption on urinary albumin excretion, serum lipids, plasma amino acids, and isoflavones in diabetic patients with nephropathy. Male patients (n = 14) with type 2 diabetes and nephropathy were followed in a crossover design for 7 mo. The study comprised two 8-wk intervention periods, placed between a 4-wk lead-in and two 4-wk washout periods. In the 2 intervention periods, 0.5 g/(kg. d) of the dietary protein was provided as either isolated soy protein (ISP) or casein, in random order. Blood and urine samples were collected at the beginning and end of each period. Data were analyzed by multiple linear regression for a repeated-measure design. ISP consumption led to changes of -9.5% in urinary albumin excretion (P < 0.0001), -0.45 in the total-to-HDL-cholesterol ratio (P < 0.05), -0.20 in the LDL-to-HDL cholesterol ratio (P < 0.05), and +4.3% in HDL cholesterol (P = 0.0040). Plasma arginine concentrations, the arginine-to-lysine ratio, and plasma isoflavone concentrations were higher after ISP consumption (P < 0.05). Urinary albumin excretion was negatively correlated with plasma total isoflavones (rho = -0.441), daidzein (rho = -0.326), and O-desmethylangolesin (rho = -0.389) (P < 0.05). The findings indicate that isolated soy protein consumption improves several markers that may be beneficial for type 2 diabetic patients with nephropathy.

Aged↗
PubMed2004

Neutrophil and small intestinal lymphocyte migration after Salmonella typhimurium infection: impact of fermentable fiber.

OBJECTIVES: Formula-fed infants have more episodes of acute diarrhea and intestinal infection than do breast-fed infants. Nutrient additions to infant formula that could confer some of the immune benefits of breast milk to formula-fed infants are currently under investigation. This study examined the impact of enteral formulas supplemented with fermentable substrates on small intestinal lymphocyte and neutrophil migration in piglets infected with Salmonella typhimurium. Small intestinal proinflammatory cytokine messenger RNA abundance and in vitro lipopolysaccharide-stimulated interleukin-6 release in whole blood were assessed. METHODS: Piglets were randomized to receive sow milk replacer formula supplemented with methylcellulose (control), soy polysaccharides (SPS) or fructooligosaccharides (FOS). On day 7, half of the piglets were infected with S. typhimurium. Intestinal lymphocyte, neutrophil and whole blood samples were obtained on day 14. RESULTS: After infection, there was decreased lymphocyte migration in the control group but not in the SPS and FOS groups. The SPS group had greater neutrophil migration compared with the control and FOS groups, regardless of infection. Small intestinal abundance of proinflammatory cytokine messenger RNA was not significantly changed by either infection or diet. Blood from the FOS group challenged with lipopolysaccharide for 2 hours exhibited decreased interleukin-6 production compared with blood from the control and SPS groups, regardless of infection. CONCLUSIONS: Supplementation of enteral formulas with SPS maintains the migratory function of small intestinal lymphocytes while increasing that of neutrophils.

Animals↗
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

Dietary lipids alter the effect of steroids on the transport of glucose after intestinal resection: Part I. Phenotypic changes and expression of transporters.

BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. This study was undertaken to assess the effect on D-glucose uptake of budesonide (Bud), prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids (PUFA). METHODS: In vitro ring uptake technique, Western blots, and Northern blots were performed. RESULTS: Bud increased the jejunal D-glucose uptake, and this effect was prevented by feeding PUFA. SGLT1 and Na+/K+ ATPase protein and mRNA abundance did not correlate with the change in the rate of uptake of glucose. CONCLUSIONS: (1) Bud increased the jejunal glucose uptake, (2) the activity of the sugar transporter does not correlate with the abundance of protein or their respective mRNAs, (3) th Bud effect on glucose uptake is prevented by feeding PUFA. Thus, the desired intestinal adaptive response after intestinal resection may be enhanced further by the administration of the locally acting steroid budesonide and by feeding a saturated compared with a polyunsaturated fatty acid diet.

Animals↗
PubMed2003

Dietary lipids alter the effect of steroids on transport of glucose after intestinal resection: Part II. Signalling of the response.

BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. Budesonide (Bud) increases the jejunal D-glucose uptake, and this effect is prevented through a polyunsaturated fatty acid (PUFA) diet. This study was undertaken to assess the possible signalling effect of budesonide, prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids. METHODS: Northern blots were performed. RESULTS: Steroids reduced the jejunal but not the ileal expression of proglucagon. Ornithine decarboxylase (ODC) expression was reduced in the jejunum. CONCLUSIONS: c-jun, ODC, and proglucagon may be involved in the adaptive response that occurs with steroids and variations in dietary lipids after intestinal resection.

Anastomosis, Surgical↗
PubMed2003

Glucagon-like peptide-2 and short-chain fatty acids: a new twist to an old story.

The nutritional regulation of intestinal adaptation extends beyond the route of nutrient administration as specific nutrients are known to mediate the adaptive response. Dietary carbohydrates are known to enhance intestinal adaptation in patients with short-bowel syndrome. This review discusses SCFA-induced adaptation in intestinal structure and function in adult rat and neonatal piglet models. Potential mechanisms relate to the salvage of energy as SCFA in the colon, direct mediation of intestinal adaptation by SCFA and stimulated release of glucagon-like peptide-2 (GLP-2) from enteroendocrine L cells by SCFA. Among the produced SCFA, butyrate appears to be responsible for increasing plasma GLP-2 concentration, in addition to the enterotrophic effects. Emerging evidence reveals that physiological concentrations of butyrate acutely upregulate the expression of key enterocyte-associated nutrient transporters. Focused experiments are needed to carefully identify the critical components of intestinal adaptation and yield conclusions regarding the relative contributions of SCFA and GLP-2 during the various phases of this process.

Adaptation, Physiological↗
PubMed2003

Altering dietary protein type and quantity reduces urinary albumin excretion without affecting plasma glucose concentrations in BKS.cg-m +Lepr db/+Lepr db (db/db) mice.

Protein restriction is used conventionally in the prevention and treatment of diabetic nephropathy. Recently, the use of soy protein instead of animal protein has been postulated as a new preventive and treatment option. The aim of this study was to determine the qualitative and quantitative effects of dietary protein on biomarkers of diabetic nephropathy in a Type 2 diabetes mellitus mouse model (BKS.cg-m +Lepr(db)/+Lepr(db) mice). Diabetic (+Lepr(db)/+Lepr(db)) and control (m+/m+) mice (n = 24/group) consumed one of four different diets ad libitum [20% casein, 20% soy protein, 12% casein or 12% soy protein (energy-based percentages)] from 35 +/- 4 d of age until termination (184-217 d of age). Blood and urine were collected throughout the study to measure biomarkers of diabetes and diabetic nephropathy. Kidney tissue was collected at the end of the study for weight. In diabetic mice, a 20% casein diet increased urinary albumin excretion to macroalbuminuric levels, whereas a 20% soy protein diet led to no major changes in urinary albumin excretion. Low protein diets (12%), independently of protein type, decreased urinary albumin excretion to low microalbuminuric levels. There were no significant differences in plasma glucose concentrations. These findings show lower urinary albumin excretion when a soy protein diet or a low casein diet is fed, suggesting a delay in the progression of diabetic nephropathy.

Albuminuria↗
PubMed2003

Fermentable fiber reduces recovery time and improves intestinal function in piglets following Salmonella typhimurium infection.

Diarrhea is a leading cause of morbidity and mortality in infants. The addition of fiber to infant formulas reduces recovery time following pathogenic infection in infants > 6 mo old, but effects on neonates are unknown. The hypothesis that fermentable fiber reduces infection-associated symptoms and enhances intestinal structure and function in neonates was examined. Piglets (2 d old) were randomly assigned to receive formula alone (control) or formula containing methylcellulose (MCEL), soy polysaccharides (SPS) or fructooligosaccharides (FOS) for 14 d. On d 7, piglets were further randomly assigned to receive an oral gavage of Salmonella typhimurium or serve as noninfected controls. S. typhimurium infection produced diarrhea in controls and MCEL groups, but not in the SPS and FOS groups. Postinfection physical activity was lower (P = 0.0001) in the controls than in all other groups. Ileal lactase activity was reduced (P < 0.05) following infection in the control group but not in the MCEL, SPS and FOS groups. Ileal mucosal barrier function, measured as resistance, was impaired by infection (P < 0.05) in the control and SPS groups, but was unaltered in the jejunum and colon. Total ion transport and basal short-circuit current were higher (P < 0.05) in jejunum than in ileum and colon, irrespective of diet or infection. SPS and FOS increased (P < 0.05) ileal glutamine transport relative to piglets fed MCEL, irrespective of infection. Because fermentable fiber enhances intestinal function and reduces the severity of S. typhimurium infection-associated symptoms, it may be a cost-effective way in which to reduce the severity of pathogenic infection-associated symptoms in infants.

Animals↗
PubMed2002

Provision of phosphorylatable substrate during hypoxia decreases jejunal barrier function.

OBJECTIVES: There is an emerging consensus that early enteral nutrition benefits the high-risk surgical patient. However, in patients with inadequate gastrointestinal perfusion, food in the intestine may increase the oxygen demand beyond that which can be satisfied by the available delivery, potentially leading to intestinal malfunction. The effect of metabolic substrate on gastrointestinal function during various oxygenation states was investigated. METHODS: Jejunal samples obtained from 32 male Sprague-Dawley rats (263 +/- Q15 g) were stripped of the muscularis, mounted in modified Ussing chambers, and randomized to be incubated in media equilibrated with one of four gas mixtures (95%, 75%, 50%, and 25% oxygen). After equilibration, fluorescent probes (4400 and 17 200 molecular weight [MW]) were added to the incubation media on the mucosal side. The rate of probe accumulation on the serosal side was determined before and after the addition of one of four substrates to the mucosal medium: mannitol (an osmotic control), glucose (which is transported, phosphorylated, and metabolized), 2-deoxyglucose (a glucose analog that is transported and phosphorylated but not metabolized), or 3-O-methylglucose (a glucose analog that is transported but not phosphorylated or metabolized). RESULTS: Lumenal glucose, 2-deoxyglucose, and 3-O-methylglucose increased permeation of the 4400-MW probe at all oxygen levels, whereas mannitol did not alter permeation in the 95% and 75% oxygen groups. Lumenal glucose increased (P < 0.05) the permeation rate of the 17 200-MW probe at all oxygen levels, whereas 2-deoxyglucose and 3-O-methylglucose did not increase the permeation rate of the 17 200-MW probe until oxygen was lowered to 75% and 50%, respectively. Regardless of substrate treatment, jejunal permeation of the 4400-MW (P < 0.001) and 17 200-MW (P < 0.05) probes increased in the 25% and 50% oxygen groups compared with the 75% and 95% oxygen groups. CONCLUSIONS: These initial results suggest that the provision of lumenal nutrients exacerbates the loss of gastrointestinal barrier function during hypoxia. Although the early provision of nutrients is an important intervention in acutely injured patients, care must be taken to ensure that gastrointestinal perfusion is adequate to allow substrate metabolism and prevent further compromise in gastrointestinal function.

3-O-Methylglucose↗
PubMedDate not supplied

Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets.

BACKGROUND: Supplementation of total parenteral nutrition (TPN) with a mixture of short-chain fatty acids (SCFA) enhances intestinal adaptation in the adult rodent model. However, the ability and timing of SCFA to augment adaptation in the neonatal intestine is unknown. Furthermore, the specific SCFA inducing the intestinotrophic effects and underlying regulatory mechanism(s) are unclear. Therefore, we examined the effect of SCFA supplemented TPN on structural aspects of intestinal adaptation and hypothesized that butyrate is the SCFA responsible for these effects. METHODS: Piglets (n = 120) were randomized to (1) control TPN or TPN supplemented with (2) 60 mmol/L SCFA (36 mmol/L acetate, 15 mmol/L propionate and 9 mmol/L butyrate), (3) 9 mmol/L butyrate, or (4) 60 mmol/L butyrate. Within each group, piglets were further randomized to examine acute (4, 12, or 24 hours) and chronic (3 or 7 days) adaptations. Indices of intestinal adaptation, including crypt-villus architecture, proliferation and apoptosis, and concentration of the intestinotrophic peptide, glucagon-like pepide-2 (GLP-2), were measured. RESULTS: Villus height was increased (p < .029) within 4 hours by supplemented TPN treatments. Supplemented TPN treatments increased (p < .037) proliferating cell nuclear antigen expression along the entire intestine. Indicative of an antiapoptotic profile, jejunal Bax:Bcl-w abundance was decreased (p = .033) by both butyrate-supplemented TPN treatments, and ileal abundance was decreased (p = .0002) by all supplemented TPN treatments, regardless of time. Supplemented TPN treatments increased (p = .016) plasma GLP-2 concentration at all time points. CONCLUSIONS: Butyrate is the SCFA responsible for augmenting structural aspects of intestinal adaptations by increasing proliferation and decreasing apoptosis within 4 hours postresection. The intestinotrophic mechanism(s) underlying butyrate's effects may involve GLP-2. Ultimately, butyrate administration may enable an infant with short-bowel syndrome to successfully transition to enteral feedings by maximizing their absorptive area.

Adaptation, Physiological↗