Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis.

BACKGROUND: Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR). METHODS: Twenty-four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid. RESULTS: Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment. CONCLUSIONS: Anti-IL-33 antibody has a therapeutic potential for experimental AR.

The essential and ancillary role of glutathione in Saccharomyces cerevisiae analysed using a grande gsh1 disruptant strain.

A grande gsh1 disruptant mutant of Saccharomyces cerevisiae was generated by crossing a petite disruptant to a wild-type grande strain. This strain was relatively stable, but generated petites at an elevated frequency, illustrating the ancillary role of glutathione (GSH) in the maintenance of the genetic integrity of the mitochondrial genome. The availability of the grande gsh1 deletant enabled an evaluation of the role of GSH in the cellular response to hydrogen peroxide independent of the effects of a petite mutation. The mutant strain was more sensitive to hydrogen peroxide than the wild-type strain but was still capable of producing an adaptive stress response to this compound. GSH was found to be essential for growth and sporulation of the yeast, but the intracellular level needed to support growth was at least two orders of magnitude less than that normally present in wild-type cells. This surprising result indicates that there is an essential role for GSH but only very low amounts are needed for growth. This result was also found in anaerobic conditions, thus this essential function does not involve protection from oxidative stress. Suppressors of the gsh1 deletion mutation were isolated by ethylmethanesulfonate mutagenesis. These were the result of a single recessive mutation (sgr1, suppressor for glutathione requirement) that relieved the requirement for GSH for growth on minimal medium but did not affect the sensitivity to H(2)O(2) stress. Interestingly, the gsh1 sgr1 mutant generated petites at a lower rate than the gsh1 mutant. Thus, it is suggested that the essential role of GSH is involved in the maintenance of the mitochondrial genome.

Effects of alpha-toxin of Staphylococcus aureus on the ciliary activity and ultrastructure of human nasal ciliated epithelial cells.

OBJECTIVE: The in vitro effects of staphylococcal alpha-toxin on ciliary activity were investigated at different concentrations and exposure times. STUDY DESIGN: Ciliated epithelial cells of the sphenoid sinus were taken from patients operated on for pituitary tumors. Video-computerized analysis technique and transmission electron microscopy were used to analyze the effects of the toxin on ciliary activity. METHODS: Ciliary beat frequency (CBF) was measured in four different concentrations of alpha-toxin including 0.1, 1, 10, and 50 microg/mL. CBF was measured at 2, 4, 6, 12, 24, and 48 hours after administration of the toxin. To observe reversibility of the reduced ciliary activity, after 24-hour incubation in the media containing 10 microg/mL of alpha-toxin, the media were replaced with alpha-toxin-free media. The tissues were also processed for transmission electron microscopy to observe ultrastructural changes of the epithelial cells. RESULTS: CBF increased significantly at 2-hour incubation and then decreased significantly after 12-hour incubation in 10 microg/mL of alpha-toxin (P< .05, repeated-measures ANOVA). The transmission electron microscopic findings showed mitochondrial swelling and a slight protrusion of the plasma membrane of the cilia. In toxin-free media, loss of ciliary activity was not recovered. CONCLUSIONS: CBF increased at first, but with increasing incubation time ciliary movements decreased gradually and stopped eventually. This loss of CBF may be an irreversible change associated with ultrastructural changes in the mitochondria and the plasma membrane of the cilia.

The development of a decision support system for diagnosing nasal allergy.

This paper deals with the problem of improving the capability of the medical decision support system (MDSS) for diagnosing nasal allergy by integrating the previously developed expert system with the neural network approach. Three knowledge acquisition methods were used to develop the expert system: statistical, rule-based, and the combined approach. Among the three, a combined approach showed the best prediction rate based on discriminant analysis. Using the results of a combined approach as input values, the neural network was developed using back-propagation method. Unlike the expert system, the neural network system provides the resulting allergy status in probabilistic terms. Managerial as well as legal issues were also discussed in this paper.