Can dietary strategies in early life prevent childhood food allergy? A report from two iFAAM workshops.

Food allergy affects a small but significant number of children and adults. Food allergy is responsible for considerable morbidity and is the commonest cause of anaphylaxis in children. One of the aims of the European Union-funded "Integrated Approaches to Food Allergen and Allergy Risk Management" (iFAAM) project was to improve our understanding of the best way to prevent the development of food allergy. Groups within the project worked on integrating the current prevention evidence base as well as generating new data to move our understanding forward. This paper from the iFAAM project is a unique addition to the literature on this topic as it not only outlines the recently published randomized controlled trials (as have previous reviews) but also summarizes two iFAAM-associated project workshops. These workshops focused on how we may be able to use dietary strategies in early life to prevent the development of food allergy and summarized the range of opinions amongst experts in this controversial area.

Allergenicity assessment of Buchanania lanzan protein extract in Balb/c mice.

Tree nuts are among "Big Eight" and have been reported globally for causing allergy. Buchanania lanzan (Bl) is one of the major tree nuts consumed by Indian population. However, very little is known about B. lanzan's induced allergic manifestation. Therefore, evaluation of it's allergenic potential was undertaken. Bl-crude protein extract sensitized BALB/c mice sera were used to identify the allergic proteins by it's IgE binding capability. The major IgE binding proteins found with molecular weight of 11, 20, 23, 25, 48, 54, and 65 kDa. Specific IgE, specific IgG1, MCPT-1, PGD2 and histamine were assessed in mice sera. Enormous amount of mast cell infiltration was noted in different organs. The levels of Th1/Th2 transcription factors GATA-3, SOCS3 and STAT-6 were found upregulated, whereas T-bet was downregulated. Furthermore, elevated Th1/Th2 cytokine responses were observed in mice sera. All together, these reactions developed systemic anaphylaxis upon Bl-CPE challenge in sensitized BALB/c mice. In order to confirm the evidences obtained from the studies carried out in BALB/c, the investigation was extended to human subjects as well. Control subjects and allergic patients were subjected to skin prick test (SPT). Later sera collected from those positive to SPT along with controls were used for IgE immunoblotting. The study evaluated the allergic manifestation associated with Bl, and identified it's proteins attributing Bl-mediated allergy. This work may help in managing tree nuts mediated allergies especially due to Buchanania lanzan sensitization.

[Toxicological assessment of nanostructured silica. IV. Immunological and allergological indices in animals sensitized with food allergen and final discussioin].

This paper is the final in a series of publications on the assessment of subacute oral toxicity of nanostructured silica (SiO2). Preparation studied was a commercial nanopowder of SiO2, obtained by hydrolysis of tetrachlorosilane in the gaseous phase with the size of primary nanoparticles (NPs) of 5­30 nm. The experiment was conducted in 95 male Wistar rats weighing 150­180 g, divided into 6 groups numbering 25 (group 1), 26 (group 2), 11 (groups 3­6) of animals. The aqueous dispersion of SiO2 after sonication was administered to animals of groups 2, 4 and 6 for 28 days by intragastric gavage at a dose of 100 mg/kg of body weight per day. Animals of groups 1, 3, and 5 were treated with deionized water. On the 1st, 3d, 5th and 21st day of experiment the rats of groups 1, 2, 3 and 4 were sensitized intraperitoneally with hen's egg ovalbumin (OVA) adsorbed to aluminum hydroxide. Intravenous administration of the challenge dose OVA to rats in groups 1 and 2 was carried out on the 29th day. In the same period animals of groups 3­6 were bled for analysis of cellular immunity. There were evaluated the severity of systemic anaphylaxis reaction, the level of specific IgG antibodies to OVA in sensitized animals, state of erythrocytes, platelets and leukocytes of peripheral blood using standard methods. Using flow cytometry there were measured contents of lymphocyte populations of B-lymphocytes (CD45RA+), total T-lymphocytes (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), NKcells (CD161a+), phagocytic activity of polymorphonuclear leukocytes in respect of latex particles. Serum levels of TNFα and IL-10 cytokines were determined by ELISA. The result showed that NPs SiO2, at dose of 100 mg/kg body weight had no any marked effect on severity of active anaphylactic shock and level of specific antibodies. The changes in cellular immunity under the influence of nanomaterial had similar direction in sensitized and non-sensitized animals and were more pronounced in the latter. Based on the discussion of the results, together with data from previous publications it was concluded that oral maximum level without observable adverse effect (NOAEL) of nanostructured SiO2 is located below 100 mg/kg body weight.

Prevalence and outcome of allergic colitis in healthy infants with rectal bleeding: a prospective cohort study.

OBJECTIVES: Allergic colitis is often diagnosed clinically in healthy infants with rectal bleeding and often treated with costly hypoallergenic formula. The true prevalence of allergic colitis is unknown. We tested the hypothesis that allergic colitis is overdiagnosed in healthy infants with rectal bleeding. The authors also determined whether rectal bleeding in infants without allergic colitis would resolve without diet change. METHODS: For the purposes of this study, allergic colitis was defined histologically as colonic mucosa with >or= 6 eosinophils per high power field and/or eosinophils in colonic crypts or muscularis mucosae. We surveyed all 56 Ohio NASPGHAN members to determine standard practice regarding the evaluation of rectal bleeding in infants. In addition, infants

Human colonic anti-secretory activity of the potent NK(1) antagonist, SR140333: assessment of potential anti-diarrhoeal activity in food allergy and inflammatory bowel disease.

1. This in vitro study was designed to determine the potential use of the NK(1) antagonist, SR140333 as an anti-diarrhoeal treatment for food allergy or inflammatory bowel disease. The effect of various immune and neuronal stimuli on human colonic substance P (SP) release and the effect of SR140333 on subsequently stimulated mucosal ion transport was investigated. 2. Submucosal and sensory nerve fibre stimulation using electrical field stimulation (1 ms/7 Hz/7 V) and capsaicin (50 microM) respectively, mast cell activation by anti-IgE (1/250 dilution) and granulocyte stimulation using fMLP (50 microM) each released SP and evoked a secretory response. 3. SP and the NK(1) selective agonist, Sar-SP (0.1 - 1000 nM) stimulated an increase in colonic secretion which was antagonized by SR140333 (pD'(2)=6.7 and 7.25 versus SP and Sar-SP respectively). 4. SR140333, at a concentration that blocked NK(1)-mediated secretion (500 nM), also reduced the secretory response to both alphaIgE and capsaicin. This suggests a pathophysiologic role for NK(1) receptors. 5. Capsaicin evoked SP release was increased in tissue taken from Crohn's disease but not ulcerative colitis patients. The response to SP was however reduced by 70 and 89% respectively. 6. Mast cells and sensory afferents contribute to allergic diarrhoea. Since SR140333 reduced the secretory response to mast cell and afferent stimulation this compound may be particularly useful in reducing the symptoms of food allergy.

Gluten sensitivity of small intestinal mucosa in vitro: quantitative assessment of histologic change.

In view of the importance to the patient of demonstrating mucosal sensitivity to gluten we have quantitated morphologic change during organ culture of small bowel mucosa by measuring enterocyte height. In 27 normal controls the mean preculture enterocyte height was 28.3 micrometer +/- 1.8 (+/- 1 SD), decreasing to 25.6 micrometer +/- 1.9 and 26.1 micrometer +/- 2.0 after 24 h culture in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but there was no difference between culture with or without gluten. In 9 abnormal controls, the mean preculture enterocyte height was 27.0 micrometer +/- 2.7, decreasing significantly (p < 0.05) to 24.5 micrometer +/- 1.1 after 24 h culture without gluten, and to 25.4 micrometer +/- 2.3 with gluten (NS). In 17 untreated celiac patients, the mean preculture enterocyte height was 19.6 micrometer +/- 1.9 increasing significantly to 23.8 micrometer +/- 2.0 (p < 0.001) after 24 h culture without gluten but decreasing to 18.7 micrometer +/- 3.1 after 24 h culture with gluten (NS). There was a significant difference between culture with or without gluten (p < 0.001). In 21 treated celiac patients, the mean preculture enterocyte height was 28.1 micrometer +/- 1.9 decreasing to 25.4 micrometer +/- 2.0 and 24.2 +/- 1.9 in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but more importantly there was a significant decrease (p < 0.001) after culture with gluten compared with culture without gluten. These data indicate that it is possible to quantify morphologic change during organ culture and to demonstrate gluten-sensitivity not only in untreated, but also in treated celiac mucosa. These studies have important implications as regards the diagnosis and further investigation of the etiology of celiac disease.