Release of Mast Cell Tryptase into Saliva: A Tool to Diagnose Food Allergy by a Mucosal Challenge Test?

Background: Our aim was to examine whether measurement of the saliva mast cell tryptase (MCT) concentrations before and after a mucosal challenge test with the offending food would be helpful in diagnosing food allergy. Methods: We performed a retrospective analysis of 44 food challenge tests performed in 38 patients between 2006 and 2009. Patients with a suspected history of food allergy chewed the food until they developed symptoms or until the amount of time known from the patients' history to usually be required for the provocation of symptoms had passed. In 5 patients, saliva samples for the measurement of MCT were collected at minutes 0, 1, 4, 8, 11, and 16 after the first onset of symptoms. The remainder of the patients only had samples taken before chewing and 4 min after the end of the test period. Results: During repeated measurements, MCT peaked about 4 min after the onset of symptoms (p = 0.028). During 33 of the 44 tests (75.0%), we observed oral symptoms during testing; after 25 of the 33 (75.8%) tests evoking symptoms, the saliva MCT concentration increased. The MCT increase was negative in all other tests where no oral symptoms could be provoked. Conclusions: The measurement of saliva MCT 4 min after the onset of symptoms may be helpful to diagnose food allergy. Because of numerous confounding variables, however, a negative saliva MCT increase does not exclude food allergy. Copyright (C) 2011 S. Karger AG, Base

Rezension: Raymond Geuss: Kritik der politischen Philosophie - eine Streitschrift

Der Buchtitel ist Programm: Raymond Geuss, 1946 in Indiana (USA) geboren und seit 2007 Professor für Philosophie in Cambridge (GB), kritisiert in seiner schmalen Abhandlung Klassiker der (politischen) Philosophie – etwa Kant, Rawls oder Nozick – in scharfem, zum Teil auch polemischem Tonfall. Ihren Theorien unterstellt Geuss einen verfehlten Realismus und setzte ihnen einen eigenen, realistischen Ansatz der politischen Philosophie entgegen. Seiner Idee einer politischen Philosophie liegen vier Thesen zugrunde, welche Raymond Geuss bereits in der Einleitung vorstellt. Die Thesen lauten: Erstens: Die politische Philosophie muss realistisch sein. Dies bedeutet für Geuss, dass die politische Philosophie nicht von einem fiktiven Ideal ausgehen, sondern sich mit den realen Motivationen der Menschen oder der tatsächlichen Beschaffenheit von Institutionen beschäftigen soll. Zweitens: In der Politik geht es in erster Linie ums Handeln und um die Kontexte des Handelns. Drittens: Politik ist immer historisch verortet, also immer kontext- und zeitabhängig. Viertens: Politik ist eher ein Handwerk oder eine Kunst als eine reine Theorieanwendung. Zudem wendet er sich gegen all jene Theoretiker, die in der Tradition Kants stehen und dabei Theorien mit universellem Anspruch aufstellen, die beinhalten, Politik sei angewandte Ethik

Comparison of the antioxidant potential in urine, saliva and skin

Aim: Free radicals, oxidative stress and their possible consequences for health are becoming increasingly important in modern medicine. Reactive species influence the organism, potentially causing oxidative cell damage. They can be produced by exogenous sources, or be a product of a variety of not only physiological metabolic processes, such as immune response, but also pathological processes. The antioxidant protection system protects the organism from oxidative damage caused by reactions producing an excess of free radicals. The analysis of antioxidant potential (AOP) is therefore becoming increasingly important for the diagnosis of individual vitality

The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization

Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics. Among them was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose knockdown and knockout led to short circadian periods. TNPO1 was found in endogenous clock protein complexes and particularly binds to PER1 regulating its (but not PER2's) nuclear localization. While PER1 is also transported to the nucleus by the classical, Importin beta-mediated pathway, TNPO1 depletion slowed down PER1 nuclear import rate as revealed by fluorescence recovery after photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated nuclear import may constitute a novel input pathway of how cellular redox state signals to the clock, since redox stress increases binding of TNPO1 to PER1 and decreases its nuclear localization. Together, our RNAi screen knocking down import carriers (but also export carriers) results in short and long circadian periods indicating that the regulatory pathways that control the timing of clock protein subcellular localization are far more complex than previously assumed. TNPO1 is one of the novel players essential for normal circadian periods and potentially for redox regulation of the clock

Comparison of a group-delivered and individually delivered lifestyle-integrated functional exercise (LiFE) program in older persons: a randomized noninferiority trial

Background: The Lifestyle-Integrated Functional Exercise (LiFE) program is effective in improving strength, balance, and physical activity (PA) while simultaneously reducing falls in older people by incorporating exercise activities in recurring daily tasks. However, implementing the original LiFE program includes substantial resource requirements. Therefore, as part of the LiFE-is-LiFE project, a group format (gLiFE) of the LiFE program has been developed, which will be tested regarding its noninferiority to the individually delivered LiFE in terms of PA-adjusted fall incidence and overall cost-effectiveness. Methods: In a multi-centre, single-blinded noninferiority trial, an envisaged sample of N = 300 participants (> 70 years; faller and/or confirmed falls risk; community-dwelling) will be randomized in either LiFE or gLiFE. Both groups will undergo the same strength and balance activities as well as PA promotion activities and habitualization strategies as described in the LiFE programme, however, based on different approaches of delivery: During the 6-month intervention phase, LiFE participants will receive seven home visits and two telephone calls; in gLiFE, the program will be delivered in seven group sessions and also two telephone calls. Main outcomes are a) fall incidence per PA and b) incremental cost-effectiveness ratio comparing costs and quality-adjusted life years between the two interventions. Secondary outcomes include PA behaviour, motor performance, health status, psychosocial status, program evaluation, and adherence. Measurements will be conducted at baseline, 6-month and 12-month follow-up; evaluation of intervention sessions and assessment of psychosocial variables related to execution and habitualization of LiFE activities will be made during the intervention period as well. Discussion: Compared to LiFE, we expect gLiFE to (a) reduce falls per PA by a similar rate; (b) be more cost-effective; (c) comparably enhance physical performance in terms of strength and balance as well as PA. By investigating the economic and societal benefit, this study will be of high practical relevance as noninferiority of gLiFE would facilitate large-scale implementation due to lower resource usage. This would result in better reach and increased accessibility, which is important for subjects with a history of falls and/or being at risk of falls. Trial registration ClinicalTrials.gov NCT03462654. Registered on March 12, 2018

Detrimental effects of an inhaled phosphodiesterase-4 inhibitor on lung inflammation in ventilated preterm lambs exposed to chorioamnionitis are dose dependent

Background: Treatment of bronchopulmonary dysplasia in preterm infants is challenging due to its multifactorial origin. In rodent models of neonatal lung injury, selective inhibition of phosphodiesterase 4 (PDE4) has been shown to exert anti-inflammatory properties in the lung. We hypothesized that GSK256066, a highly selective, inhalable PDE4 inhibitor, would have beneficial effects on lung injury and inflammation in a triple hit lamb model of Ureaplasma parvum (UP)-induced chorioamnionitis, prematurity, and mechanical ventilation. Methods: Twenty-one preterm lambs were surgically delivered preterm at 129 days after 7 days intrauterine exposure to UP. Sixteen animals were subsequently ventilated for 24 hours and received endotracheal surfactant and intravenous caffeine citrate. Ten animals were randomized to receive twice a high (10 μg/kg) or low dose (1 μg/kg) of nebulized PDE4 inhibitor. Results: Nebulization of high, but not low, doses of PDE4 inhibitor led to a significant decrease in pulmonary PDE activity, and was associated with lung injury and vasculitis, influx of neutrophils, and increased proinflammatory cytokine messenger RNA levels. Conclusion: Contrary to our hypothesis, we found in our model a dose-dependent proinflammatory effect of an inhaled highly selective PDE4 inhibitor in the lung. Our findings indicate the narrow therapeutic range of inhaled PDE4 inhibitors in the preterm population

Prognostic impact of <i>CEBPA </i>mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIP InDel), frameshift InDel or nonsense mutations inducing translational stop (bZIP STOP) or single base-pair missense alterations (bZIP ms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIP InDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIP InDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIP InDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIP InDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIP ms). (Figure presented.)</p

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants

Micronutritional supplementation with a holoBLG-based FSMP (food for special medical purposes)-lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect

Background: Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model. Methods: Binding of iron-catechin into BLG was confirmed by spectroscopy and docking calculations. Serum IgE binding of children allergic or tolerating milk was assessed to loaded (holo-) versus empty (apo-) BLG and for human mast cell degranulation. BLG and Bet v 1 double-sensitized mice were orally treated with the holoBLG or placebo lozenge, and immunologically analysed after systemic allergen challenge. Human PBMCs of pollen allergic subjects were flow cytometrically assessed after stimulation with apoBLG or holoBLG using catechin-iron complexes as ligands. Results: One major IgE and T cell epitope were masked by catechin-iron complexes, which impaired IgE binding of milk-allergic children and degranulation of mast cells. In mice, only supplementation with the holoBLG lozenge reduced clinical reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen presentation. In allergic subjects, stimulation of PBMCs with holoBLG led to a significant increase of intracellular iron in circulating CD14+ cells with significantly lower expression of HLADR and CD86 compared to their stimulation with apoBLG. Conclusion: The FSMP lozenge targeted antigen presenting cells and dampened immune activation in human immune cells and allergic mice in an antigen-non-specific manner, thereby conferring immune resilience against allergic symptoms