Cetirizine inhibits gender-specific blood cell dynamics upon allergen contact in allergic rhinitis.

IgE-mediated inflammatory responses upon allergen contact in allergic rhinitis (AR) are associated with rapid alterations of circulating blood cell numbers detectable in a complete blood count (CBC). Aim of this study was to evaluate whether intake of antihistamines may modulate allergen-induced CBC dynamics in male and female patients. A total of N = 112 specific allergen challenges were performed in otherwise healthy AR subjects. Seventy-two (n = 72) subjects received placebo and forty (n = 40) received cetirizine (H1-receptor antagonist) per os prior to allergen exposure in a randomized, double-blind trial at the Vienna Challenge Chamber (VCC); a subgroup of twenty-five (n = 25) subjects received cetirizine and placebo on different study days (parallel group). Blood samples and symptom scores were taken at baseline and immediately after 6 h of airway challenge simulating ambient allergen contact. Female sex was associated with a pronounced circulating monocyte increase (p < .01) and male sex with an eosinophil decrease (p < .05) in the placebo group, but not in cetirizine treated subjects. The significant increase in segmented neutrophils (p < .001) and decrease in circulating erythrocytes (p < .01) upon allergen challenge was less prominent after cetirizine intake in both sexes. A more prominent thrombocyte increase in female subjects (p < .05) was noted upon allergen exposure, regardless of prior cetirizine intake. Cetirizine inhibited the mobilization of neutrophils, lymphocytes and decline in erythrocyte numbers, but did not affect thrombocyte increase upon allergen challenge. It further diminished gender-specific blood cell dynamics. Overall, as reflected in a simple CBC, cetirizine critically diminished immediate and late innate immune responses subsequent to allergen exposure.

Possible effect of landscape design on IgE recognition profiles of two generations revealed with micro-arrayed allergens.

The aim of this study was to investigate possible effects of landscape design on the IgE sensitization profile toward inhalant allergens in patients with respiratory allergy from Uzbekistan where green areas have been changed during the last two decades by a State program. Sera from two different generations of Uzbek (n=58) and, for control purposes, from two generations of Austrian (n=58) patients were analyzed for IgE reactivity to 112 different micro-arrayed allergen molecules by ImmunoCAP ISAC technology. Changes in molecular IgE sensitization profiles to pollen allergens in the young vs the middle-aged Uzbek population were associated with replanting, whereas those in the Vienna populations reflected natural changes in plant growth. Our data indicate that anthropologic as well as natural changes in the biome may have effects on IgE sensitization profiles already from one to another generation.

The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial.

BACKGROUND: CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D(2). The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. The objective of the present study was to determine the involvement of CRTH2 in promoting nasal and ocular symptoms in allergic subjects exposed to grass pollen. METHODS: A single centre, randomised, double-blind, placebo-controlled, two-way crossover study was conducted in 35 male subjects allergic to grass pollen comparing OC000459 200 mg bid with placebo for 8 days. Subjects were exposed to grass pollen (≥ 1400 grains/m(3)) for 6 h on the 2nd and 8th days of treatment and assessed for nasal symptoms, ocular symptoms, other symptoms, nasal secretion weight and rhinomanometry over the 6-h period. After a washout period of 3 weeks, subjects were switched to the alternative treatment for a further 8 days. The trial was registered on the clinical trials.gov database (Identifier NCT01448902). RESULTS: During the first treatment period, treatment with OC000459 significantly reduced both nasal and ocular symptoms in allergic subjects compared with placebo after challenge with grass pollen. A significant effect was observed on the 2nd day of dosing which was increased on the 8th day of dosing. The therapeutic effects of OC000459 persisted into the second treatment period despite a 3-week washout phase. The safety profile of OC000459 was similar to that of placebo. CONCLUSION: Treatment with OC000459 was well tolerated and led to a significant and persistent reduction in the symptoms of rhinoconjunctivitis.

Levocetirizine has a longer duration of action on improving total nasal symptoms score than fexofenadine after single administration.

AIMS: To compare the onset and duration of action of the new antihistamine levocetirizine with that of the second-generation antihistamine fexofenadine using the Vienna Challenge Chamber (VCC). The latter is an environment where subjects can be exposed to specific aeroallergens in controlled and reproducible conditions allowing for precise comparisons of anti-allergic drugs. METHODS: Ninety-four subjects received a single dose of levocetirizine 5 mg, fexofenadine 120 mg or placebo in a random order using a three-way cross-over design. On day 1, subjects were exposed to grass pollens (1500 grains/m(3)) in the VCC over a period of 4 h. Treatment was given 2 h after the start of challenge. On day 2, 22 h after drug intake, subjects were again exposed to pollens for 6 h. Specified symptoms were assessed by the subjects every 15 min using 5-point scales. The main efficacy parameter was the change from baseline in the Major Symptom Complex Score (MSCS = sum of rhinorrhea, sneezing, itchy nose and eyes). RESULTS: Baseline characteristics, including symptoms scores, were similar in the three study groups. During the first 2 h after drug intake both antihistamines achieved clinically relevant and significant (P < 0.001) improvements in symptom scores. Twenty-two to 24 h after drug intake, mean (SEM) MSCS reductions were: 1.9 (0.3) after placebo (baseline of 9.7), 3.8 (0.3) after fexofenadine (baseline of 9.9), and 5.1 (0.3) after levocetirizine (baseline of 9.8). Levocetirizine was significantly (P < 0.001) more effective than fexofenadine with a score difference of 1.3 (95% CI 0.7, 1.9). This was maintained until the end of the study (up to 28 h). CONCLUSIONS: A rapid onset of action in alleviating seasonal allergic rhinitis (SAR) symptoms of subjects exposed to grass pollens in the VCC was observed after levocetirizine and fexofenadine. Levocetirizine was more effective than fexofenadine at and later than 22 h after drug intake, an indication of the longer-duration of action of levocetirizine.

Light and transmission electron microscopy of the dorsal lingual epithelium of Pelusios castaneus (Pleurodira, Chelidae) with special respect to its feeding mechanics.

The ultrastructure of the dorsal lingual epithelium of the semi-aquatic West African mud turtle, Pelusios castaneus, is described. Our goal is to give additional information to previous studies of this species such as feeding pattern analysis and gross morphology. Tissue specimens were fixed in modified Karnovsky solution followed by osmium tetroxide, embedded in epoxy resin and observed using light and transmission electron microscopy. The dorsal tongue surface is covered with moderate papillae, which are coated by a stratified epithelium overlying a connective tissue core. Two epithelial regions can be differentiated, although differences are not very obvious: the apical area, where granular cells are more abundant than mucus cells, and the lateral area, where cell distribution is opposite. Within the epithelium, different layers are discernable on the basis of the cells' organelles, corresponding with a process of cell maturation and formation of different granules. These results together with data of previous studies of this species show that the ultrastructure of the lingual epithelium is similar to other turtles adapted to semi-aquatic environments; functional and morphological data indicate a generalist, being well but not highly adapted to feeding in an aquatic environment.

Morphology and function of the feeding apparatus of Pelusios castaneus (Chelonia; Pleurodira).

Feeding mechanics of vertebrates depend on physical constraints of the surrounding media, water or air. Such functions are inseparably combined with form. The aim of this study is to show this linkage for the pleurodiran freshwater turtle Pelusios castaneus and, additionally, to point out the major functional and biomechanical distinctions between aquatic and terrestrial feeding turtles as well as several intermediate forms. Gross morphological investigations of skull, hyoid, tongue, and connected musculature, as well as scanning electron microscopy of the tongue surface, show typical features of an aquatic feeder, e.g., strongly developed hyoid apparatus vs. a small tongue with only moderate papillae, and massive jaw and hyoid musculature. Additionally, the special function of the esophagus during feeding is investigated to elucidate the problems of a bidirectional feeder. The esophagus is highly distensible in order to store the excess water sucked in during feeding until the prey is fixed by the jaws. The distension is probably achieved by a coincidence of active (branchial horn) as well as passive (water) components. P. castaneus is a feeding generalist, and is well adapted to the aquatic medium in terms of its functional as well as morphological features.