Allergic sensitization: screening methods

Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured

Artificial External Glottic Device for Passive Lung Insufflation

PURPOSE: For patients with neuromuscular disease, air stacking, which inflates the lungs to deep volumes, is important for many reasons. However, neuromuscular patients with severe glottic dysfunction or indwelling tracheostomy tubes cannot air stack effectively. For these patients, we developed a device that permits deep lung insufflations substituting for glottic function. MATERIALS AND METHODS: Thirty- seven patients with bulbar-innervated muscle weakness and/or tracheostomies were recruited. Twenty-three had amyotrophic lateral sclerosis, and 14 were tetraplegic patients due to cervical spinal cord injury. An artificial external glottic device (AEGD) was used to permit passive deep lung insufflation. In order to confirm the utility of AEGD, vital capacity, maximum insufflation capacity (MIC), and lung insufflation capacity (LIC) with AEGD (LICA) were measured. RESULTS: For 30 patients, MICs were initially zero. However, with the use of the AEGD, LICA was measurable for all patients. The mean LICA was 1,622.7±526.8 mL. Although MIC was measurable for the remaining 7 patients without utilizing the AEGD, it was significantly less than LICA, which was 1,084.3±259.9 mL and 1,862.9±248 mL, respectively (p<0.05). CONCLUSION: The AEGD permits lung insufflation by providing deeper lung volumes than possible by air stacking.ope

Effects of graded concentrations of supplemental selenium on selenium concentrations in tissues and prediction equations for estimating dietary selenium intake in pigs

The experiment was conducted to determine the effects of graded dietary selenium (Se) on organ weight and Se concentrations in tissues and to develop equations for estimating dietary Se intake in pigs. Sixteen barrows (initial body weight = 30.0 ± 2.6) were allotted to four dietary treatments including graded Se supplementations with 0, 1, 5, and 50 mg/kg of diet. The experimental diets fed to the pigs for 30 d, and then the pigs were euthanized, and the organs, muscle, and urine samples were collected. The hair and blood samples of pigs were collected on d 15 and 30. Equations were developed for predicting daily Se intake using the Se concentration in plasma, hair, liver, kidneys, muscle, or urine. For graded dietary Se concentrations, linear and quadratic effects on the final body weight, weight and relative weight of liver and kidneys were not observed. The Se concentration in plasma, hair, liver, kidneys, muscle, and urine were linearly and quadratically increased as dietary Se concentration increased (P  0.81, P < 0.001). The equations for estimating dietary Se intake using the Se concentration in the plasma, hair, or organ as an independent variable were significant (P < 0.05). In conclusion, the dietary Se concentration was well reflected in the Se concentration in the plasma, hair, liver, kidneys, and urine. The Se concentration in the plasma, hair, liver, and kidneys can be used as an independent variable for estimating the Se intake

Lower Expression of TLR2 and SOCS-3 Is Associated with Schistosoma haematobium Infection and with Lower Risk for Allergic Reactivity in Children Living in a Rural Area in Ghana

Inflammatory diseases such as atopic disorders are a major health problem in the Western world, but their prevalence is also increasing in developing countries, especially in urban centres. There is increasing evidence that exposure to a rural environment with high burden of compounds derived from parasites and microorganisms is associated with protection from atopic disorders. Since urbanisation is progressing at a rapid pace, particularly in less-developed nations, there is a need to understand the molecular processes that control the progress towards the development of allergic diseases in developing countries. In this study we have examined a population of school children living in a rural area of Ghana, where helminth (worm) infections are prevalent and associated with protection from skin reactivity to house dust mite. Blood samples were collected from these children and analysed for the expression levels of several genes involved in the development of a pro allergic immune system. The results point at a potential molecular link that might explain the negative association between schistosome infections and allergies

The development of TH2 responses from infancy to 4 years of age and atopic sensitization in areas endemic for helminth infections

BACKGROUND: Helminth infections and allergies are associated with TH(2) responses. Whereas the development of TH(2) responses and allergic disorders in pediatric populations has been examined in affluent countries, no or little data exist from low income regions of the world. The aim of this study is to examine factors influencing the development of TH(2) responses of children born in areas endemic for helminth infections and to relate these factors to atopic sensitization at 4 years of age. METHODS: Data were collected from pregnant mothers on helminth infections, education and socioeconomic status (SES). Total IgE, IL-5 in response to mitogen, and helminth antigens were measured in children at 2, 5, 12, 24 and 48 months of age. Skin prick testing (SPT) and allergen-specific IgE were determined at 4 years of age. RESULTS: Strong TH(2) responses were seen at 5 months of age and increased with time. Although maternal filarial infection was associated with helminth-antigen specific TH(2) responses, it was low maternal education or SES but not helminth infection, which was associated with the development of high total IgE and PHA-induced IL-5. At 4 years of age when allergen reactivity was assessed by SPT, the high general TH(2) responses did not translate into higher prevalence of SPT. The risk factor for SPT reactivity was low maternal education which decreased the risk of SPT positivity to allergens (adjusted OR, 0.32; 95% CI, 0.12 – 0.87) independently of maternal filarial infection which tended to reduce the child’s risk for being SPT positive (adjusted OR, 0.35; 95% CI, 0.07 – 1.70). CONCLUSIONS: In areas endemic for helminths, potent TH(2) responses were seen early in life, but did not translate into a higher SPT reactivity to allergens. Therefore, in many parts of the world TH(2) responses in general and IgE in particular cannot be used for diagnosis of allergic diseases

Contrasting Biogeographic and Diversification Patterns in Two Mediterranean-Type Ecosystems

The five Mediterranean regions of the world comprise almost 50,000 plant species (ca 20% of the known vascular plants) despite accounting for less than 5% of the world’s land surface. The ecology and evolutionary history of two of these regions, the Cape Floristic Region and the Mediterranean Basin, have been extensively investigated, but there have been few studies aimed at understanding the historical relationships between them. Here, we examine the biogeographic and diversification processes that shaped the evolution of plant diversity in the Cape and the Mediterranean Basin using a large plastid data set for the geophyte family Hyacinthaceae (comprising ca. 25% of the total diversity of the group), a group found mainly throughout Africa and Eurasia. Hyacinthaceae is a predominant group in the Cape and the Mediterranean Basin both in terms of number of species and their morphological and ecological variability. Using state-of-the-art methods in biogeography and diversification, we found that the Old World members of the family originated in sub-Saharan Africa at the Paleocene–Eocene boundary and that the two Mediterranean regions both have high diversification rates, but contrasting biogeographic histories. While the Cape diversity has been greatly influenced by its relationship with sub-Saharan Africa throughout the history of the family, the Mediterranean Basin had no connection with the latter after the onset of the Mediterranean climate in the region and the aridification of the Sahara. The Mediterranean Basin subsequently contributed significantly to the diversity of neighbouring areas, especially Northern Europe and the Middle East, whereas the Cape can be seen as a biogeographical cul-de-sac, with only a few dispersals toward sub-Saharan Africa. The understanding of the evolutionary history of these two important repositories of biodiversity would benefit from the application of the framework developed here to other groups of plants present in the two regions

TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of four inhibitors of the matrix metalloproteinases, which are capable of degrading most components of the extracellular matrix. However, in recent years, TIMP-1 has been recognised as a multifunctional protein, playing a complex role in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells and their genetically identical wild-type controls. For future studies, this cell system can be used to uncover the mechanisms and signalling pathways involved in the TIMP-1-mediated inhibition of apoptosis as well as to investigate the possibility of using TIMP-1 inhibitors to optimise the effect of conventional chemotherapy