SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Allergic conjunctivitis

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Mast cells have gained notoriety based on their detrimental contributions to IgE-mediated allergic disorders. Although mast cells express the vitamin D receptor (VDR), it is not clear to what extent 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) or its predominant inactive precursor metabolite in the circulation, 25-hydroxyvitamin D3 (25OHD3), can influence IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo.

Concepts: Asthma, Allergic conjunctivitis, Anaphylaxis, Cell biology, Allergy, Vitamin D, Immune system, Mast cell

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Allergen immunotherapy is the only disease-modifying treatment for allergic diseases. Sublingual immunotherapy (SLIT) in liquid and tablet form has been used by clinicians in Europe for years, but has only recently gained popularity and approval in the United States. In 2014, the US Food and Drug Administration approved 3 SLIT tablets for the treatment of allergic rhinitis, with or without allergic conjunctivitis. Immunotherapy treatment strategies for the polysensitized patient vary between the United States and Europe. This variation hinges upon whether the polysensitized patient is truly polyallergic. Polysensitization is the positive response to 2 or more allergens on skin prick testing or in vitro specific-IgE testing. Polyallergy is the symptomatic clinical response to 2 or more allergens. In this review, we discuss the use of SLIT in the United States with a focus on treating the polyallergic patient with SLIT.

Concepts: Allergic conjunctivitis, Tablet PC, Allergen immunotherapy, United States, Allergology, Immunology, Asthma, Allergy

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The primary side effects associated with 0.1% brimonidine tartrate (BT) ophthalmic solution with sodium chlorite are allergic conjunctivitis, blepharitis, and conjunctival hyperemia. However, cornea-related side effects are rare. In this study, we report 2 similar cases in which corneal neovascularization, corneal infiltration, and corneal opacity developed after BT eye-drop use.

Concepts: Brimonidine, Eye, Keratitis, Blepharitis, Conjunctiva, Allergic conjunctivitis, Ophthalmology, Conjunctivitis

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Mast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends.

Concepts: Epigenetics, Allergic conjunctivitis, Posttranslational modification, Asthma, Immune system, Allergy, Mast cell, Histone

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At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell-deficient mice and their circadian variations were lost in mast cell-deficient mice reconstituted with bone marrow-derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80-induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell-mediated allergic reactions.

Concepts: Allergic conjunctivitis, DNA, Asthma, Gene, Histamine, Allergy, Mast cell, Immune system

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The incidence of food allergies has increased dramatically during the last decade. Recently, probiotics have been studied for the prevention and treatment of allergic disease.

Concepts: Allergic conjunctivitis, Eczema, Gut flora, Immune system, Food allergy, Mast cell, Asthma, Allergy

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Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.

Concepts: Allergic conjunctivitis, Immune system, Signal transduction, Asthma, Enzyme, Tyrosine kinase, Allergy, Mast cell

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Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells.

Concepts: Asthma, Allergic conjunctivitis, Cell biology, Mast cell, Immune system, Allergy

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Atopic dermatitis comorbidities extend well beyond the march to allergic conditions (food allergy, asthma, allergic rhinitis, allergic conjunctivitis, and eosinophilic esophagitis), suggesting both cutaneous and systemic immune activation. In reviewing atopic dermatitis comorbidities, Councilors of the International Eczema Council found a strong pattern of immune activation in peripheral blood and the propensity to both skin and systemic infections. Associations with cardiovascular, neuropsychiatric, and malignant diseases were increasingly reported, but confirmation of their link with atopic dermatitis requires longitudinal studies. Given the possibility of atopic dermatitis-related systemic immune activation, future investigations of new interventions should concurrently examine the impact on these comorbidities.

Concepts: Inflammation, Allergic conjunctivitis, Atopy, Food allergy, Eczema, Immune system, Asthma, Allergy