A dominance of Mu class glutathione transferases within the equine tapeworm Anoplocephala perfoliata.

The most common equine tapeworm, Anoplocephala perfoliata, has often been neglected amongst molecular investigations and has been faced with limited treatment options. However, the recent release of a transcriptome dataset has now provided opportunities for in-depth analysis of A. perfoliata protein expression. Here, global, and sub-proteomic approaches were utilized to provide a comprehensive characterization of the A. perfoliata soluble glutathione transferases (GST) (ApGST). Utilizing both bioinformatics and gel-based proteomics, GeLC and 2D-SDS PAGE, the A. perfoliata 'GST-ome' was observed to be dominated with Mu class GST representatives. In addition, both Sigma and Omega class GSTs were identified, albeit to a lesser extent and absent from affinity chromatography approaches. Moreover, 51 ApGSTs were localized across somatic (47 GSTs), extracellular vesicles (EVs) (Whole: 1 GST, Surface: 2 GSTs) and EV depleted excretory secretory product (ESP) (9 GSTs) proteomes. In related helminths, GSTs have shown promise as novel anthelmintic or vaccine targets for improved helminth control. Thus, provides potential targets for understanding A. perfoliata novel infection mechanisms, host­parasite relationships and anthelmintic treatments.

Correlation between airway inflammation and loss of deep-inhalation bronchoprotection in asthma.

BACKGROUND: One of the characteristic features of the hyperresponsive airway smooth muscle in asthma is the loss of deep-inhalation bronchoprotection and bronchodilation. The airway of individuals with asthma is also characterized by inflammation. OBJECTIVE: To evaluate whether the loss of deep-inhalation bronchoprotection is correlated with the degree of inflammation in the asthmatic airway. METHODS: Eighteen study participants performed 2 methacholine challenges (identical doses), 1 with deep inhalations and 1 without, separated by at least 24 hours. Airway inflammation was evaluated by measurement of fraction of exhaled nitric oxide (FE(NO)) and induced sputum eosinophils. RESULTS: A significant negative correlation was found between the degree of deep-inhalation bronchoprotection and airway inflammation when measured by FE(NO) (P = .02, r = .54, n = 18) and by percentage of eosinophils (P = .002, r = .76, n = 12). A significant positive correlation was also found between the FE(NO) and percentage of eosinophils (P = .009, r = .68, n = 12). CONCLUSIONS: Deep-inhalation bronchoprotection was significantly impaired in individuals with greater airway inflammation. This finding suggests that therapy directed at decreasing airway inflammation may promote the recovery of normal deep-inhalation bronchoprotection.

Difference between dosimeter and tidal breathing methacholine challenge: contributions of dose and deep inspiration bronchoprotection.

BACKGROUND: Two bronchoprovocation methods are widely used. Compared to the tidal breathing method, the dosimeter method delivers approximately half the dose and involves five deep inhalations. Both the lower dose and the bronchoprotective deep inhalations contribute to the lesser airway response of the dosimeter. OBJECTIVE: To determine the relative role of dose and deep inspiration in the difference between the two methods. METHODS: Subjects with asthma (n = 24) underwent three methacholine challenges: a dosimeter challenge, a 2-min tidal breathing challenge (twice the dose), and a modified 2-min tidal breathing challenge (twice the dose plus five deep inhalations). RESULTS: The dosimeter method produced a nonsignificantly lower response than the modified tidal breathing method (p = 0.14). Both deep inhalation methods produced significantly less response than did the standard tidal breathing method (p = 0.011). In the 12 subjects with the most mild airway hyperresponsiveness (AHR), the differences between the deep inhalation method and the tidal breathing method were greater (p = 0.007). By contrast, deep inhalations produced no effect in the 12 subjects with greater AHR; the two tidal breathing methods produced identical results, while the dosimeter produced less response than either (p = 0.033). Six current asthmatics with mild airway responsiveness (tidal breathing method) had negative dosimeter methacholine challenge results. CONCLUSIONS: In subjects with moderate airway responsiveness, the difference between the methods is due to the difference in dose, whereas in subjects with mild AHR, deep inhalations had a large effect overwhelming the dose effect and producing false-negative methacholine challenge results in 25% of the subjects.