From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "
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Introduction: The kinetics of protein oxidation, monitored in breath, and its contribution to the whole body protein status is not well established. Objectives: To analyze protein oxidation in various metabolic conditions we developed/validated a 13C-protein oxidation breath test using low enriched milk proteins. Method/Design: 30 g of naturally labeled 13C-milk proteins were consumed by young healthy volunteers. Breath samples were taken every 10 min and 13CO2 was measured by Isotope Ratio Mass Spectrometry. To calculate the amount of oxidized substrate we used: substrate dose, molecular weight and 13C enrichment of the substrate, number of carbon atoms in a substrate molecule, and estimated CO2-production of the subject based on body surface area. Results: We demonstrated that in 255 min 20% ± 3% (mean ± SD) of the milk protein was oxidized compared to 18% ± 1% of 30 g glucose. Postprandial kinetics of oxidation of whey (rapidly digestible protein) and casein (slowly digestible protein) derived from our breath test were comparable to literature data regarding the kinetics of appearance of amino acids in blood. Oxidation of milk proteins was faster than that of milk lipids (peak oxidation 120 and 290 minutes, respectively). After a 3-day protein restricted diet (~10 g of protein/day) a decrease of 31% ± 18% in milk protein oxidation was observed compared to a normal diet. Conclusions: Protein oxidation, which can be easily monitored in breath, is a significant factor in protein metabolism. With our technique we are able to characterize changes in overall protein oxidation under various meta-bolic conditions such as a protein restricted diet, which could be relevant for defining optimal protein intake under various conditions. Measuring protein oxidation in new-born might be relevant to establish its contribution to the protein status and its age-dependent development.
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From Pubmed: " BACKGROUND: Antigen-specific immunotherapy (AIT) is a promising therapeutic approach for both cow's milk allergy (CMA) and peanut allergy (PNA), but needs optimization in terms of efficacy and safety. AIM: Compare oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and determine the dose of allergen needed to effectively modify parameters of allergy. METHODS: Female C3H/HeOuJ mice were sensitized intragastrically (i.g.) to whey or peanut extract with cholera toxin. Mice were treated orally (5 times/week) or subcutaneously (3 times/week) for three consecutive weeks. Hereafter, the acute allergic skin response, anaphylactic shock symptoms and body temperature were measured upon intradermal (i.d.) and intraperitoneal (i.p.) challenge, and mast cell degranulation was measured upon i.g. challenge. Allergen-specific IgE, IgG1 and IgG2a were measured in serum at different time points. Single cell suspensions derived from lymph organs were stimulated with allergen to induce cytokine production and T cell phenotypes were assessed using flow cytometry. RESULTS: Both OIT and SCIT decreased clinically related signs upon challenge in the CMA and PNA model. Interestingly, a rise in allergen-specific IgE was observed during immunotherapy, hereafter, treated mice were protected against the increase in IgE caused by allergen challenge. Allergen-specific IgG1 and IgG2a increased due to both types of AIT. In the CMA model, SCIT and OIT reduced the percentage of activated Th2 cells and increased the percentage of activated Th1 cells in the spleen. OIT increased the percentage of regulatory T cells (Tregs) and activated Th2 cells in the MLN. Th2 cytokines IL-5, IL-13 and IL-10 were reduced after OIT, but not after SCIT. In the PNA model, no differences were observed in percentages of T cell subsets. SCIT induced Th2 cytokines IL-5 and IL-10, whereas OIT had no effect. CONCLUSION: We have shown clinical protection against allergic manifestations after OIT and SCIT in a CMA and PNA model. Although similar allergen-specific antibody patterns were observed, differences in T cell and cytokine responses were shown. Whether these findings are related to a different mechanism of AIT in CMA and PNA needs to be elucidated."
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Weipermeaat is een reststroom vanuit de zuivelindustrie en heeft op basis van zijn samenstelling een lage waarde in de veevoermarkt maar biedt wel perspectieven voor de basischemie: het bevat grote hoeveelheden suikers (lactose). Eén van de mogelijke manieren om de waarde van het weipermeaat te vergroten is middels fermentatie richting biobased building blocks zoals ethanol. De gist Kluyveromyces marxianus kan efficiënt lactose omzetten in ethanol waarbij tevens single cell protein (SCP) wordt geproduceerd. In dit project zal een haalbaarheidsstudie worden uitgevoerd waarin oplossingen worden onderzocht voor de bestaande praktische uitdagingen bij de productie van ethanol op weipermeaat waaronder een hoge zoutconcentratie. Ook zal er onderzoek gedaan worden naar de toepassing van bijproducten. Op basis van de resultaten zal een evaluatie van de business case plaatsvinden waarbij zowel ethanol productie als de verhoging van de nutritionele restwaarde door SCP-productie wordt meegenomen. In het samenwerkingsverband is deskundigheid aanwezig in de hele keten vanaf de weipermeaat reststromen (Looop BV) en fermentatie met gisten (HAN BioCentre) tot aan toepassing (Beethanol BV en de Fachhochschule Münster). Het project zal deels worden uitgevoerd door studenten vanuit de HAN University of Applied Science.
