Background Insects have become increasingly interesting as alternative nutrient sources for feeding humans and animals, most reasonably in processed form. Initially, some safety aspects — among them allergenicity — need to be addressed. Objective To reveal the cross-reactivity of shrimp-, mite- and flies-allergic patients to different edible insects, and further to assess the efficacy of food processing in reducing the recognition of insect proteins by patients' IgE and in skin prick testing of shrimp-allergic patients. Methods IgE from patients allergic to crustaceans, house dust mite or flies was evaluated for cross-recognition of proteins in house cricket Acheta domesticus (AD), desert locust Schistocerca gregaria (SG) and Yellow mealworm Tenebrio molitor (TM). Changes in IgE-binding and SPT-reactivity to processed insect extracts were determined for migratory locust ( Locusta migratoria , LM), after different extraction methods, enzymatic hydrolysis, and thermal processing were applied. Results IgE from patients with crustacean-allergy shows cross-recognition of AD, SG and stable flies; house dust mite allergics' IgE binds to AD and SG; and the flies-allergic patient recognized cricket, desert locust and migratory locust. Cross-reactivity and allergenicity in SPT to LM can be deleted by conventional processing steps, such as hydrolysis with different enzymes or heat treatment, during the preparation of protein concentrates. Conclusion The results show that crustacean-, HDM- and stable flies-allergic patients cross-recognize desert locust and house cricket proteins, and crustacean-allergic patients also flies proteins. Furthermore, this study shows that appropriate food processing methods can reduce the risk of cross-reactivity and allergenicity of edible insects.
Both humans and their most important domestic animals harbor IgE and a similar IgE receptor repertoire and expression pattern. The same cell types are also involved in the triggering or regulation of allergies, such as mast cells, eosinophils or T-regulatory cells. Translational clinical studies in domestic animals could therefore help cure animal allergies and at the same time gather knowledge relevant to human patients. Dogs, cats and horses may spontaneously and to different extents develop immediate type symptoms to pollen allergens. The skin, nasal and bronchial reactions, as well as chronic skin lesions due to pollen are in principle comparable to human patients. Pollen of various species most often causes allergic rhinitis in human patients, whereas in dogs it elicits predominantly eczematous lesions (canine atopic dermatitis), in horses recurrent airway obstruction or hives as well as pruritic dermatitis, and in cats bronchial asthma and so-called cutaneous reactive patterns (eosinophilic granuloma complex, head and neck pruritus, symmetric self-induced alopecia). In human allergy-specific IgE detection, skin tests or other allergen provocation tests should be completed. In contrast, in animals IgE and dermal tests are regarded as equally important and may even replace each other. However, for practical and economic reasons intradermal tests are most commonly performed in a specialized practice. As in humans, in dogs, cats and horses allergen immunotherapy leads to significant improvement of the clinical symptoms. The collected evidence suggests that canines, felines and equines, with their spontaneous allergies, are attractive model patients for translational studies.
Predictive preventive personalized medicine Liver cancer is the fifth most common form of cancer worldwide [1], with an incidence rate almost equals the mortality rate and ranks 3 rd among causes of cancer related death [2]. The coexistence of two life threatening conditions, cancer and liver cirrhosis makes the staging challenging. However, there are some staging systems, e.g. the Barcelona staging system for Hepatocellular carcinoma (HCC) [3], that suggest treatment options and management. Whereas diagnosis in early stages gives hope for a curative outcome, the treatment regime for around 80 % [2] of the patients classified as severe stages only gears towards palliation [4]. An intra-arterial radiation approach, radioembolisation (RE) is ubiquitously applied as one of palliative approaches. Although, in general RE shows promising results in intermediate and advanced stage HCC [5], individual treatment outcomes are currently unpredictable. Corresponding stratification criteria are still unclear. We hypothesised that individual radioresistance/radiosensitivity may play a crucial role in treatment response towards RE strongly influencing individual outcomes. Further, HCC represents a highly heterogeneous group of patients which requires patient stratification according to clear criteria for treatment algorithms to be applied individually. Multilevel diagnostic approach (MLDA) is considered helpful to set-up optimal predictive and prognostic biomarker panel for individualised application of radioembolisation. Besides comprehensive medical imaging, our MLDA includes non-invasive multi-omics and sub-cellular imaging. Individual patient profiles are expected to give a clue to targeting shifted molecular pathways, individual RE susceptibility, treatment response. Hence, a dysregulation of the detoxification pathway (SOD2/Catalase) might indicate possible adverse effects of RE, and highly increased systemic activities of matrix metalloproteinases indicate an enhanced tumour aggressiveness and provide insights into molecular mechanisms/targets. Consequently, an optimal set-up of predictive and prognostic biomarker panels may lead to the changed treatment paradigm from untargeted "treat and wait" to the cost-effective predictive, preventive and personalised approach, improving the life quality and life expectancy of HCC patients. Keywords: Market access, Value, Strategy, Companion diagnostics, Cost-effectiveness, Reimbursement, Health technology assessment, Economic models, Predictive preventive personalized medicine Achieving and sustaining seamless "drug -companion diagnostic" market access requires a sound strategy throughout a product life cycle, which enables timely creation, substantiation and communication of value to key stakeholders [1, 2]. The study aims at understanding the root-cause of market access inefficiencies of companies by gazing at the "Rx-CDx" co-development process through the prism of "value", and developing a perfect co-development scenario based on the literature review and discussions with the ...
BackgroundClassical methods of gene product analysis such as binding assays (e.g., ELISA, protein chip technology) are generally time-consuming, lab-intensive, less sensitive, and lack high-throughput capacity. In addition, all existing methods used to measure proteins necessitate multiple divisions of the original sample and individual tests carried out for each substance, with an associated cost for each test.MethodTogether with a small biotech company, we developed a new and innovative analytical detection system based on homogenous time-resolved fluorescence (HTRF) technology. Our system facilitates the development of immune assays that measure selective different analytes such as selected biomarkers in a small sample volume at less than 20 min with a much higher sensitivity compared to common binding assay systems such as enzyme-linked immunosorbent assay (ELISA). Recent advances of the application of this novel detection system combine the power of miniaturization, microfluidics, better linear range, and faster quantification.ResultsThe power of the HTRF technology offers great promise for point-of-care clinical testing and monitoring of many important analytes such as disease-specific biomarkers in the nanogram level in different human body fluids such as CSF, blood, serum, plasma, and saliva. The linear dynamical range of our HTRF assay was determined between 2.5 and 100 ng/mL. Precision and accuracy calculated for inter- as well as intra-assays was less than ± 10 %. Intra-assay and inter-assay precision for high, medium, and low analyte concentrations show mean CV values less than ± 10 %. Intra- and inter-assay accuracy for all three concentrations show mean recovery values of 80–120 %.ConclusionThe aim of this work is to describe the development and establishment of this novel HTRF system that allows the very fast detection and quantification of biomarkers in different human body fluids. Furthermore, a specific antibody combination that assures a specific binding of the correct refolded autoimmune IgG is evaluated.
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