Oral exposure to diabetes-promoting food or immunomodulators in neonates alters gut cytokines and diabetes.
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Disease development in diabetes-prone BB rats is modified by the type of diet fed after weaning. The aim of this investigation was to determine whether exposure during the first week of life to antigens from a known diabetes-promoting diet (NIH-07) could modify diabetes incidence and, if so, to what extent this occurs via alterations in systemic T-cell reactivity, gut cytokines, or islet infiltration. Diabetes-prone BB (BBdp) rats were hand-fed twice daily between age 4 and 7 days with vehicle, a hydrolyzed casein (HC)-based infant formula, Pregestimil (PG), PG + cereal-based NIH-07 diet, PG + lipopolysaccharides (LPS) or PG + LPS + silica. After weaning, they were fed either an NIH-07 diet or a semipurified HC (diabetes-retardant) diet until 150 days. In separate studies, 5-day-old BBdp rat pups were administered the aforementioned treatments, and expression of intestinal mRNA for gamma-interferon (IFN-gamma) or transforming growth factor-beta (TGF-beta) was quantified using reverse transcriptase-polymerase chain reaction. The effect of early oral treatment with NIH-07 or PG on systemic T-cell reactivity was evaluated using footpad swelling delayed-type hypersensitivity (DTH) and the popliteal lymph node assay. Oral exposure of neonates to a complex mixture of antigens from the diabetes-promoting diet delayed onset of diabetes (79 vs. 88 days) and prevented disease in approximately one-third of animals. A similar protective effect was seen for neonatal exposure to wheat gluten in animals subsequently weaned onto a semipurified wheat gluten diet. By contrast, LPS-treated neonates displayed more severe insulitis and developed diabetes at an increased rate, which was significantly suppressed by co-administration of silica particles. The protective effect of early exposure to diabetogenic diets was not associated with significant reduction of islet infiltration, and there was no impact on the DTH response to food antigens. However, whereas diabetes-resistant BBc rats developed systemic tolerance to NIH-07 antigens fed chronically, BBdp rats did not. The lack of effect of the early oral antigen regimen on the DTH reaction in the footpad, a classic Th1-mediated reaction, suggests little effect on systemic T-cell reactivity. However, local effects were observed in the small intestine. Oral exposure to diabetes-promoting food antigens or LPS downregulated the Th1 cytokine IFN-gamma and decreased the IFN-gamma/TGF-beta ratio. Thus, oral exposure to diabetes-promoting food antigens and immune modulators in neonates can modify diabetes expression in association with changes in local cytokine balance in the gut. (+info)
Comparison of an amino acid mixture and protein hydrolysates in treatment of infants with phenylketonuria.
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This study compares three feeding regimens for infants with phenylketonuria diagnosed by neonatal screening. Group 1 (five children) received Minafen (Cow & Gate) until they weighed twice their birthweights; Aminogran (Allen & Hanbury) was then added to the feeds in increasing amounts and replaced Minafen at between 8 and 10 months of age. Group 2 (five children) received Aminogran from the neonatal period. Group 3 (five children) received Minafen until they weighed twice their birthweights; Cymogran (Allen & Hanbury) was then added in increasing amounts and replaced Minafen at between 8 and 10 months of age. In all three groups growth was normal and control of phenylalanine levels satisfactory. During the first few months of life the Aminogran regimen proved more complicated and caused more practical difficulties than the regimens starting with Minafen. Later in the first year, when mixed feeding was introduced, and particularly when the bottle was exchanged for the cup, Aminogran had advantages over Cymogran because of its low calorie content, small bulk, and less unpleasant taste. At this age feeding problems were fewer and easier to manage with Aminogran than with Cymogran. A method of using Aminogran in the management of such problems is described. For these reasons, the regimen fed group 1, in which Minafen is used initially and then replaced by Aminogran, is preferred to the other two. (+info)
Effects of peptides derived from dietary proteins on mucus secretion in rat jejunum.
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The hypothesis that dietary proteins or their hydrolysates may regulate intestinal mucin discharge was investigated in the isolated vascularly perfused rat jejunum using an enzyme-linked immunosorbent assay for rat intestinal mucins. On luminal administration, casein hydrolysate [0.05-5% (wt/vol)] stimulated mucin secretion in rat jejunum (maximal response at 417% of controls). Lactalbumin hydrolysate (5%) also evoked mucin discharge. In contrast, casein, and a mixture of amino acids was without effect. Chicken egg albumin and its hydrolysate or meat hydrolysate also did not modify mucin release. Interestingly, casein hydrolysate-induced mucin secretion was abolished by intra-arterial TTX or naloxone (an opioid antagonist). beta-Casomorphin-7, an opioid peptide released from beta-casein on milk ingestion, induced a strong mucin secretion (response at 563% of controls) that was inhibited by naloxone. Intra-arterial beta-casomorphin-7 also markedly increased mucin secretion (410% of controls). In conclusion, two enzymatic milk protein hydrolysates (casein and lactalbumin hydrolysates) and beta-casomorphin-7, specifically, induced mucin release in rat jejunum. The casein hydrolysate-induced mucin secretion is triggered by a neural pathway and mediated by opioid receptor activation. (+info)
Safety of a new extensively hydrolysed formula in children with cow's milk protein allergy: a double blind crossover study.
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BACKGROUND: Formulae for infants with cow's milk protein allergy (CMA) should be based on extensively hydrolysed protein. 'Extensively' however is not strictly defined. Differences in molecular weight and peptide chain length may affect its clinical outcome. We studied the safety of a new extensively hydrolysed casein based formula (Frisolac Allergycare: FAC) for children with IgE mediated CMA. METHODS: Thirty children, aged 1.5 - 14.8 years old (median 4.9 years) with persistent CMA were enrolled in this double-blind reference product (Nutramigen: NUT) controlled crossover study. All had positive skin prick tests (SPT) and IgE mediated allergy, showing immediate reactions after ingestion of small amounts of milk. Twenty-five children also had positive radio allergen sorbent tests (RAST) to cow's milk. Formulae provided consisted of 80% elementary formula in combination with 20% reference or test product. Crossover periods lasted for two weeks. From both products molecular weight (MALDI-TOF method and HPLC) and peptide chain length distribution (adapted Edman degradation) were determined. RESULTS: Maximum molecular weights of NUT and FAC are 2.1 and 2.56 kDa, respectively. The contribution of free amino acids and small peptides <0.5 kDa is 46% for FAC and 53% for NUT. About 50% of the protein fraction of both products consists of peptides longer than four amino acids. Three children did not complete the study. The other children all tolerated FAC very well; no adverse reactions were reported. CONCLUSIONS: The new extensively hydrolysed casein-based formula (FAC) can safely be used in children with IgE mediated cow's milk allergy. (+info)
Sweet and sour preferences during childhood: role of early experiences.
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We investigated the effects of early experience on sweet and sour preferences in children. Eighty-three children were divided into four groups based on the type of formula fed during infancy and age. By using a forced-choice, sip-and-swallow procedure, we determined the level of sweetness and sourness preferred in juice. Children who were fed protein hydrolysate formulas, which have a distinctive sour and bitter taste and unpleasant odor, preferred higher levels of citric acid in juice when compared to older children who were fed similar formulas. No such difference was observed between the groups for sweet preference. However, the level of sweetness preferred in juice was related to the sugar content of the child's favorite cereal and whether the mother routinely added sugar to their foods. These data illustrate the wide variety of experiential factors that can influence flavor preferences during childhood. (+info)
The use of protein hydrolysate improves the protein intestinal absorption in undernourished mice infected with Schistosoma mansoni.
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Patients residing in endemic areas for schistosomiasis in Brazil are usually undernourished and when they develop the hepatosplenic clinical form of the disease should usually receive hospital care, many of them being in need of nutritional rehabilitation before specific treatment can be undertaken. In the mouse model, investigations carried out in our laboratory detected a reduced aminoacid uptake in undernourished animals which is aggravated by a superimposed infection with Schistosoma mansoni. However, in well-nourished infected mice no dysfunction occurs. In this study, we tried to improve the absorptive intestinal performance of undernourished mice infected with S. mansoni by feeding them with hydrolysed casein instead of whole casein. The values obtained for the coefficient of protein intestinal absorption (cpia) among well-nourished mice were above 90% (either hydrolysed or whole protein). In undernourished infected mice, however, the cpia improved significantly after feeding them with hydrolysed casein, animals reaching values close to those obtained in well-nourished infected mice. (+info)
Statistical characterization of ion trap tandem mass spectra from doubly charged tryptic peptides.
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Collision-induced dissociation (CID) is a common ion activation technique used to energize mass-selected peptide ions during tandem mass spectrometry. Characteristic fragment ions form from the cleavage of amide bonds within a peptide undergoing CID, allowing the inference of its amino acid sequence. The statistical characterization of these fragment ions is essential for improving peptide identification algorithms and for understanding the complex reactions taking place during CID. An examination of 1465 ion trap spectra from doubly charged tryptic peptides reveals several trends important to understanding this fragmentation process. While less abundant than y ions, b ions are present in sufficient numbers to aid sequencing algorithms. Fragment ions exhibit a characteristic series-specific relationship between their masses and intensities. Each residue influences fragmentation at adjacent amide bonds, with Pro quantifiably enhancing cleavage at its N-terminal amide bond and His increasing the formation of b ions at its C-terminal amide bond. Fragment ions corresponding to a formal loss of ammonia appear preferentially in peptides containing Gln and Asn. These trends are partially responsible for the complexity of peptide tandem mass spectra. (+info)
Treatment of children with phenylketonuria using a phenylalanine-free protein hydrolysate (Albumaid XP).
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Albumaid XP, a phenylalanine-free protein hydrolysate, was used for treatment of five phenylketonuric infants born between January, 1970, and September, 1972. The results were compared with those obtained from the five infants most recently treated with Lofenalac in our clinic prior to 1970. Treatment was begun by 2 months of age in all instances. Satisfactory physical growth and mental development were achieved using either Albumaid XP or Lofenalac, and there were no major differences in the outcomes with either treatment. The two protein sources may be used interchangeably for treatment of phenylketonuria. (+info)