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Biomedical subjects

Troy A Scribner

Publications and source records attributed to Troy A Scribner.

3 recordsLinked to original sources

Experimental gastrointestinal allergy enhances pulmonary responses to specific and unrelated allergens.

BACKGROUND: Gastrointestinal allergy often precedes or coexists with respiratory allergy. OBJECTIVE: We hypothesized that established experimental gastrointestinal allergy would prime for the development of allergic respiratory responses. METHODS: BALB/c mice were sensitized with ovalbumin (OVA) in the presence of aluminum potassium sulfate and then subjected to intragastric saline or OVA challenges. After the development of allergen-induced gastrointestinal allergy, mice were intranasally exposed to either saline, OVA, or a neoaeroallergen house dust mite (HDM) extract. Airway inflammation (eg, bronchoalveolar lavage fluid cellularity, cytokine levels, and OVA-specific antibody levels) and airway responsiveness to methacholine exposure were assessed after intranasal allergen exposure. RESULTS: A single intranasal exposure to OVA induced significantly more airway inflammation in intragastric OVA-challenged mice compared with that seen in intragastric saline-treated mice. Kinetic analysis revealed that the observed amplification of lung inflammation was sustained for up to 12 days after the last intragastric OVA challenge after resolution of blood eosinophilia. When mice with gastrointestinal allergy were repeatedly challenged with HDM in the respiratory tract, they experienced enhanced airway inflammation, including bronchoalveolar lavage fluid eosinophilia and increased IL-13 levels. CONCLUSION: Taken together, our results demonstrate that OVA-induced gastrointestinal allergy enhances not only allergic airway responses to OVA but also to HDM, an unrelated aeroallergen. CLINICAL IMPLICATIONS: Experimental gastrointestinal allergy primes for responses to allergens in the respiratory tract, enhancing antigen-specific antibody and T(H)2 cytokine production, airway inflammation, and airway hyperresponsiveness.

Allergens↗

Rapid venom immunotherapy update.

PURPOSE OF REVIEW: This paper will review new indications for the administration of rapid or ultrarush venom immunotherapy and the advantages of pretreatment with antihistamines. RECENT FINDINGS: Rapid and ultrarush venom immunotherapy protocols have been successfully employed to achieve protective maintenance venom doses rapidly. These have been associated with systemic reactor rates as low as 5-7%. Recently, rapid venom immunotherapy protocols have been successfully employed to reach ultra-high maintenance doses for patients not previously protected with standard maintenance doses (i.e. 100 micro g). There is also evidence that pretreatment with antihistamines before venom injections during rapid venom immunotherapy may reduce the numbers and severity of injection-related systemic reactions, as well as improve long-term outcomes in preventing subsequent resting systemic reactions in the field. SUMMARY: Pretreatment with antihistamines should be considered in patients receiving rapid or ultrarush venom injections. Ultrarush or rapid immunotherapy regimens compare favorably with conventional modified rush protocols in terms of side-effects, and may be considered in order to achieve higher but effective maintenance venom doses in those rare patients who are treatment failures.

Animals↗

Mast cells are required for experimental oral allergen-induced diarrhea.

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.

Allergens↗