Amylase-Trypsin Inhibitors in Wheat and Other Cereals as Potential Activators of the Effects of Nonceliac Gluten Sensitivity.

Nonceliac gluten sensitivity (NCGS) is a gluten-related gastrointestinal disorder distinct from celiac disease (CD) and gluten allergy that is not easy to diagnose due to the lack of biomarkers. It is characterized by intestinal symptoms and extraintestinal manifestations with the consumption of gluten-containing foods. In contrast to CD, NCGS patients do not present a genetic predisposition or intestinal villi atrophy. Recent studies question the proinflammatory triggering activity of α-gliadin fraction contained in wheat, since it has been demonstrated that the amylase-trypsin inhibitors (ATIs) exert a strong activating effect on the innate immune response. We aimed to analyze the role of ATIs in the activation of innate immunity and in the development of the symptoms characteristic of NCGS. A systematic literature search was made using databases such as MEDLINE, SciELO, Science Direct, and Scopus, with focus on key words such as "amylase-trypsin inhibitors," "wheat," "gluten," and "celiac." Many studies are available on the structure, inhibition mechanism, and immune system effects of ATIs, mainly focused on IgE-mediated reactions. Recently, with the increase of NCGS interest, has increased the literature on the capacity of ATIs contained in wheat to activate the innate immune system. Literature published to date questions the relationship between activation of the innate immune system and gluten in NCGS. ATIs may have acted as interfering contaminant of gluten and appear as potential activator of innate immunity in NCGS patients. In view of their potential impact, more interventional studies are needed to demonstrate the proinflammatory effect of ATIs.

Motivations for avoiding wheat consumption in Australia: results from a population survey.

OBJECTIVE: To assess the prevalence of and explanations for wheat avoidance, including reported symptoms, diagnoses and information sources influencing the decision to avoid wheat, and to investigate potential psychological predictors of this behaviour. DESIGN: Cross-sectional population survey. SETTING: The study was conducted in Australia, using a nationwide postal omnibus survey. SUBJECTS: Adults aged 18 years and over (n 1184; 52·9% female) selected at random from the Australian Electoral Roll. RESULTS: With cases of stated and suspected coeliac disease (1·2%) excluded, 7·3% of the sample reported adverse physiological effects, predominantly gastrointestinal, that they associated with wheat consumption. Few among this group (5·7%) claimed a formally diagnosed intolerance or allergy requiring avoidance of wheat-based foods. Symptomatic wheat avoidance was highly correlated with dairy avoidance and predicted by gender (female), lesser receptiveness to conventional medicine and greater receptiveness to complementary medicine, but not by neuroticism, reasoning style or tendency to worry about illness. CONCLUSIONS: The data indicate that many adult Australians are consciously avoiding consumption of wheat foods, predominantly without any formal diagnosis. Reported symptoms suggest a physiological but not allergenic basis to this behaviour. Questions to be answered concern whether symptoms are attributed correctly to wheat, the agents (wheat components, dietary factors or additives) and physiological mechanism(s) involved, the nutritional adequacy of avoiders' diets, and the clinical and psychosocial processes that lead a substantial number of adults to avoid consuming wheat (or any other dietary factor) apparently independently of a medical diagnosis.

Use of Triticum aestivum in open wound healing: a clinical, pathological, and tensiometric assessment in the rabbit model / Uso de Triticum aestivum na cicatrização de feridas: um ensaio clínico, histopatológico e tensiométrico em coelhos

While Triticum sp. has been shown to act in wound healing, stimulating collagen synthesis by fibroblasts, the use of this plant extract has yet to be assessed in vivo, in commercially viable presentations. This study used rabbits and assessed, on days seven, 14, and 21, the presence or absence of granulation tissue and epithelialization, histopathological structures, and scar quality through the breaking and tension strength. Treatments, performed for 21 days, were aqueous extract of T. aestivum at a concentration of 2mg/mL (group I) and 10mg/mL (group II) and a nonionic cream (control group). We demonstrate that the formation of granulation tissue was not significantly different between treatments. In the analysis of epithelial tissue, wounds in group II differed from other treatments by day 7. On days 14 and 21 there was no significant clinical difference between groups. In the histopathological evaluation, scar quality and rupture strength did not differ between the groups in the studied period. In the tension strength evaluation, group I differed from the others, presenting a higher tension strength overall. The studied treatments did not differ regarding healing evolution of the skin wounds, but T. aestivum extract, at 2mg/mL, presents better results in the tension strength evaluation...

O extrato de trigo (Triticum sp.) vem sendo usado na cicatrização de feridas por estimular a síntese de fibroblastos, entretanto a sua aplicabilidade in vivo em apresentações comercialmente viáveis ainda tem de ser demonstrada. Neste estudo, avaliaram-se feridas cutâneas de coelhos tratadas com extrato aquoso de T. aestivum quanto à presença de tecido de granulação e epitelização, estruturas histológicas, qualidade cicatricial, além de ensaio tensiométrico. As feridas foram tratadas diariamente, por 21 dias, com diferentes concentrações do extrato (grupo I = 2mg/mL; grupo II = 10mg/mL) ou apenas o veículo (grupo controle = creme não iônico), e avaliadas nos dias sete, 14 e 21. A formação de tecido de granulação não diferiu entre os tratamentos. A epitelização aconteceu em menor tempo em feridas do grupo II, mas aos 14 dias já não havia diferença neste parâmetro. Na avaliação histopatológica, a qualidade cicatricial e a força de ruptura não diferiram no período estudado, entretanto a resistência tensiométrica das feridas do grupo I foi maior que a dos demais tratamentos. Dessa forma, conclui-se que, mesmo não havendo diferença na evolução cicatricial de feridas tratadas ou não com extrato aquoso de T. aestivum, o uso desse composto, a 2mg/mL, resultou em tecidos cicatriciais mais resistentes à tração...

Review article: coeliac disease, new approaches to therapy.

BACKGROUND: Coeliac disease is managed by life-long gluten withdrawal from the diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Novel therapeutic approaches are needed to supplement or even replace the dietary treatment. AIM: To review recent advances in new therapeutic options for coeliac disease. METHODS: A literature search was performed on MEDLINE, EMBASE, Web of Science, Scopus, DDW.org and ClinicalTrials.gov for English articles and abstracts. The search terms used included, but not limited to, 'Celiac disease', 'new', 'novel', 'Advances', 'alternatives' and 'Drug therapy'. The cited articles were selected based on the relevancy to the review objective. RESULTS: Several new therapeutic approaches for coeliac disease are currently under development by targeting its underlying pathogenesis. Alternative therapies range from reproduction of harmless wheat strains to immunomodulatory approaches. Some of these therapies such as enzymatic cleavage of gluten and permeability inhibitors have shown promise in clinical studies. CONCLUSIONS: Gluten-free diet is still the only practical treatment for patients with coeliac disease. Novel strategies provide promise of alternative adjunctive approaches to diet restriction alone for patients with this disorder.

Infant and childhood diet and type 1 diabetes risk: recent advances and prospects.

Type 1 diabetes is a chronic autoimmune disease characterized by a preclinical period of autoimmunity. It is well accepted that both genetic and environmental factors contribute to disease risk. Given that type 1 diabetes, and its preclinical autoimmunity, appear early in life, infant and childhood diet have been implicated as potential initiating exposures in the etiology of the disease. Several publications in the past year have provided further evidence for existing hypotheses regarding the roles of wheat, cow's milk, omega-3 fatty acids, and the maternal diet during pregnancy. However, inconsistencies in findings between studies suggest the need for collaboration and standardization of study methods to move forward in research in this area. One such example of this is the TEDDY (The Environmental Determinants of Diabetes in the Young) study, which is an international, multicenter birth cohort study with standardized recruitment, dietary collection methodologies, and analytic approaches.

Wheat flour allergy: an entire diagnostic tool for complex allergy.

Wheat proteins are involved in respiratory allergy, contact allergy and food allergy. Wheat allergens involve in these pathologies are well-known. However, establishment of wheat allergy diagnostic can be sometimes difficult on account of the complex allergenic composition of skin prick test (SPT) solutions of wheat flour. Therefore, we have studied specific IgE reactivity from patient sera with wheat food allergy, and characterized allergenic composition of wheat SPT solutions by specific antibodies directed to wheat allergens. The results showed that 20 of the 25 sera analyzed contained specific IgE to at least one wheat protein fraction. Among positive sera, 75% have specific IgE to water/salt soluble fraction, 85% to native gluten fractions and 65% to wheat isolate fraction. The results showed also that SPT solutions of wheat flour contained major food allergens from each allergenic fraction. These results highlighted the importance of using fractions, which constitute the whole wheat allergenic pattern, during specific IgE reactivity analyses. Moreover, we have observed that wheat isolate extract (results of food industrial process) contained not only modified allergens (neo-allergens) involve of specific food allergy to wheat isolate but also some native allergens involve in wheat food allergy. Thus, these results showed the importance to use, for wheat in vivo diagnosis together wheat SPT solutions (gluten extract and wheat isolate) in order to differentiate wheat food allergy to specific wheat isolate allergy.

Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests.

BACKGROUND: Eosinophilic esophagitis (EE) is a recently described disorder identified in patients with symptoms suggestive of gastroesophageal reflux disease (GERD) but unresponsive to conventional reflux therapies. Therapies have included corticosteroids, elemental diet, and diet restriction. We report our experience with skin prick and atopy patch testing and food elimination diets in patients diagnosed as having EE. OBJECTIVE: To identify food antigens that cause EE and the characteristics of patients who respond to food elimination vs those who are unresponsive. METHODS: Patients diagnosed as having EE had restricted diets based on skin prick and atopy patch testing results. Additional biopsies were performed after 4 to 8 weeks of restricted diet. Demographics, atopic tendencies, and food antigens were identified retrospectively in our food allergy database. RESULTS: A total of 146 patients diagnosed as having EE were evaluated with skin prick and atopy patch testing. Thirty-nine patients had unequivocal demonstration of food causing EE, with normalization of biopsy results on elimination and reoccurrence on reintroduction. An additional 73 patients, for a total 112 (77%) of 146 patients, had resolution of their EE as demonstrated by biopsy results. Fifteen (10%) of 146 patients were nonresponders manifested by no significant reduction in esophageal eosinophils despite restricted diet based on skin prick and atopy patch testing. Egg, milk, and soy were identified most frequently with skin prick testing, whereas corn, soy, and wheat were identified most frequently with atopy patch testing. CONCLUSION: In more than 75% of patients with EE, both symptoms and esophageal inflammation can be significantly improved with dietary elimination of foods. Skin prick and atopy patch testing can help identify foods in most patients.

What safety measures need to be taken in oral food challenges in children?

BACKGROUND: Food allergens are often accused of causing numerous ailments. This is particularly true for the pediatric population, where the incidence of food allergy is four times as high as in adults. As food challenges may provoke life-threatening reactions, intensive safety measures need to be taken during provocation, and prompt medical intervention may become necessary. METHODS: We retrospectively evaluated 349 oral challenges in 204 children with atopic dermatitis, looking for criteria to help the physician decide which patients need medical intervention. RESULTS: A total of 178 (51%) oral food challenges with the four allergens (cow's milk [CM], hen's egg [HE], wheat, and soy) showed a positive clinical reaction. Of these, 120 (67%) needed medical intervention. In 42 (35%) cases, intervention was parenteral, and oral medication was given in 78 (65%) cases. There was a strong positive correlation (90%) between the level of specific IgE and the need for medical intervention (> or = 17.50 kU/l for CM, wheat, and soy; > or = 3.50 kU/l for HE). Patient history of food allergy was an indicator of the need for medical intervention (P = 0.01). A positive patient history and a high level of specific IgE were significantly (P=0.003) associated with parenteral medication in HE. CONCLUSIONS: Patient history of food allergy is a reliable indicator of the need for medical intervention in the cases of CM, wheat, and soy regardless of the level of specific IgE. With HE, a positive patient history plus a high level of specific IgE significantly indicates the need for parenteral medication. On the basis of our results, we recommend establishing intravenous access in children with a level of specific IgE of > or = 17.50 kU/l (CAP class 4) to CM and wheat, or with specific IgE of > or =3.50 kU/l (CAP class 3) to HE.

Lead and cadmium contents in cereals and pulses in north-eastern China.

It is known that, unlike Japanese, Koreans or southern Chinese who depend on rice as a major source of energy for daily life, people in north-eastern China rely not only on rice, but on wheat and other cereals and to a lesser extent also on pulses. Cereal and pulse samples were collected from open markets in north-eastern China, and analyzed by inductively-coupled plasma spectrometry (ICP-MS) for two potentially hazardous heavy metals--lead (Pb) and cadmium (Cd). The average Pb level in cereals (31.3 ng Pb/g as a geometric mean) and that of pulses (25.7 ng Pb/g) were similar to each other with no significant difference. Among the cereals, Pb contents were higher in foxtail millet (54.3 ng/g) and lower in maize (35.4 ng Pb/g; grain and flour in combination), wheat flour (28.8 ng Pb/g) and rice flour (22.7 ng Pb/g). Lead levels in two important types of pulses, kidney bean and soybean (24.6 and 30.8 ng Pb/g, respectively), were comparable to the levels in rice and wheat. In contrast, Cd levels were substantially higher in pulses (55.7 ng Cd/g) than in cereals (9.2 ng Cd/g), and among the pulses, Cd in soybean (55.7 ng Cd/g) was significantly higher than that in kidney bean (23.8 ng Cd/g). The possible public health implication of the Pb and Cd levels, especially the high Pb level in foxtail millet (54.3 ng Pb/g) and the high Cd level in soybean (73.5 ng Cd/g), is discussed.

Calcium intakes in individuals on diets for the management of cows' milk allergy: a case control study.

Three hundred and twenty-three individuals with self-reported food allergy were recruited by media advertisements. Questionnaire information was collected on all respondents. Chocolate (57%), milk (47%), wheat (36%) and food additives (35%) were the most frequently implicated foods. The most frequently reported symptoms were itching (43%), skin rash (43%) and tiredness (43%). Food avoidance was the most common form of food allergy diagnosis (33%) with only 8% of respondents reporting food challenge in food allergy diagnosis. Self-diagnosis was reported by 34% of respondents with 29% and 24% reporting diagnosis by a general practitioner or a homeopath, respectively. Twenty-four per cent of respondents 'always' avoided and a further 57% 'nearly always' avoided the implicated food(s). A group of 38 adults with self-reported 'milk allergy' was selected for further study. Dietary assessments, using the dietary history method, were carried out on this subgroup and on age-, sex- and occupation-matched controls. The results of the dietary assessments revealed that the 'milk allergy' group had significantly higher intakes of fibre, beta-carotene, vitamin C, vitamin E, iron and folic acid (P < 0.05) and significantly lower intakes of calcium (P < 0.002) in comparison to controls. Eighteen per cent of the group used milk alternatives. Thirty-four per cent of the 'milk allergy' group took calcium-containing supplements. Even after calcium supplementation, the mean calcium intake of those who completely avoided milk was unacceptably low (441 mg/d).

Studies on the aetiology of coeliac disease: no evidence for lectin-like components in wheat gluten.

In an approach to examine the lectin-hypothesis in the pathogenesis of coeliac disease, the presence of lectin-like components in three wheat gluten preparations known to induce coeliac disease, gliadin, Frazer fraction III and an acetic acid/ethanol extract of gluten, was investigated. Lectin-like components in these wheat gluten preparations were traced in binding studies employing a variety of model glycoproteins glycosylated with the different types of N-linked oligosaccharides, i.e., those of the high mannose-, complex- and hybrid-type. Binding affinity of wheat proteins to these glycoproteins was analyzed by affinity dotting and blotting techniques and was compared to that of the well characterized lectins Galanthus nivalis agglutinin, Concanavalin A and wheat germ agglutinin. Though the three wheat gluten preparations exhibited binding reactivity for distinct model glycoproteins, no correlation was found between the type of N-glycosylation of the model glycoproteins and their binding capability to the different wheat gluten preparations. Moreover, binding of the three gluten preparations to the model glycoproteins could not be inhibited by competitive saccharides (methyl-alpha-D-mannopyranoside, N-acetyl-D-glucosamine, mannan). Enzymatic deglycosylation of the ligand glycoproteins with endo-beta-N-acetylglucosaminidase H (Endo H, EC 3.2.1.96) or peptide N-glycosidase F (PNGase F, EC 3.5.1.52) abolished their binding reactivity for the plant lectins, but did not affect binding of the wheat gluten preparations. These results give no evidence for the presence of lectin-like components in wheat gluten preparations and do question the 'lectin hypothesis' of coeliac disease.

[Idiopathic nephrotic syndrome and food hypersensitivity. Value of an exclusion diet]. / Syndrome néphrotique idiopathique et hypersensibilité alimentaire. Valeur des régimes d'éviction.

A case of idiopathic nephrotic syndrome (INS) evolving since more than 7 years with 4 successive corticosensitive relapses is reported. At the time of a 5th relapse corticosteroid treatment was refused by the parents and evolution went on without any spontaneous tendency to remission. Three months later, allergy tests detected various sensitizations, especially for food allergens. An antiallergic treatment including dietary exclusions induced a complete and durable remission. Five similar cases are reported. These facts, compared to data from the literature, indicate the possible role of food hypersensitivity in INS. Its mechanism has been discussed; the possible part of a lymphocyte activation has been emphasized.

IgE antibodies to foods are not a feature of cystic fibrosis.

It has been suggested that patients with cystic fibrosis have abnormal immune responses to foods. We have measured IgE antibodies to inhalants and foods (by RAST) in 105 patients with cystic fibrosis aged between 8 months and 28 years. Serum IgE was elevated (greater than 180 kU/l) in 21 patients. In 43, IgE antibodies were detected in serum. The majority of positive results were with house-dust mite, grass pollen or Aspergillus. Only four of the patients had a positive RAST to a food--one to milk, one to wheat and two to egg. On the basis of high serum IgE or positive RAST results, 44.8 per cent of the patients were atopic and the frequency of atopy was age-related, being higher in patients aged 4 years or more. However, the presence of food antibodies was unrelated to age. This study confirms the high prevalence of atopy in patients with cystic fibrosis but unequivocally demonstrates that the presence of IgE antibodies to foods in their serum is rare.

Food intolerance: a major factor in the pathogenesis of irritable bowel syndrome.

Specific foods were found to provoke symptoms of irritable bowel syndrome (IBS) in 14 of 21 patients. In 6 patients who were challenged double blind the food intolerance was confirmed. No difference was detected in changes in plasma glucose, histamine, immune complexes, haematocrit, eosinophil count, or breath hydrogen excretion produced after challenge or control foods. Rectal prostaglandin E2 (PGE2), however, increased significantly, and in a further 5 patients rectal PGE2 correlated with wet faecal weight. Food intolerance associated with prostaglandin production is an important factor in the pathogenesis of IBS.

Food allergies and migraine.

60 migraine patients completed elimination diets after a 5-day period of withdrawal from their normal diet. 52 (87%) of these patients had been using oral contraceptive steroids, tobacco, and/or ergotamine for an average of 3 years, 22 years, and 7.4 years respectively. The commonest foods causing reactions were wheat (78%), orange (65%), eggs (45%), tea and coffee (40% each), chocolate and milk (37%) each), beef (35%), and corn, cane sugar, and yeast (33% each). When an average of ten common foods were avoided there was a dramatic fall in the number of headaches per month, 85% of patients becoming headache-free. The 25% of patients with hypertension became normotensive. Chemicals in the home environment can make this testing difficult for outpatients. Both immunological and non-immunological mechanisms may play a part in the pathogenesis of migraine caused by food intolerance.