thromboxane-b2 and Rhinitis--Allergic--Perennial

To observe the thromboxane (TX)B2 and cysteinyl leukotrienes (LTs) levels in the nasal lavage fluid of allergic rhinitis model and to observe the effect of desloratadine on the mediators.. In the positive control group, 8-12 week old male or female guinea pigs were intranasal sensitized and challenged with ovalbumin solution. The antihistamine treatment group was treated with desloratadine and the negative control group was sham-sensitized and sham-challenged. The nasal lavage fluid of each group was collected 5 hours after challenge and the levels of TXB2 and LTs in the nasal lavage fluid were measured.. In the positive control group, the TXB2 and LTs levels were the highest of the three groups and the desloratadine treated group had lower level (P < 0.05 and P < 0.01). The negative control showed the lowest level.. Our study demonstrated that in this model of allergic rhinitis, the levels of TXB2 and LTs in nasal lavage fluid increased dominantly after allergen challenge and desloratadine could inhibit the release of TXB2 and LTs, which implied that the therapeutic mechanism of desloratadine might contribute to the inhibitory effect on TXB2 and LTs production or release in allergic rhinitis subjects.

Topics: Animals; Female; Guinea Pigs; Histamine H1 Antagonists, Non-Sedating; Leukotrienes; Loratadine; Male; Nasal Lavage Fluid; Rhinitis, Allergic, Perennial; Thromboxane B2

Analysis of exhaled breath condensate is a method for noninvasive assessment of the lung. Condensate can be collected with a nose clip (subjects inhale and exhale via the mouth) or without it (subjects inhale via the nose and exhale via the mouth), but the mode of inhalation may influence condensate volume and mediator levels. We compared condensate volume and adenosine, ammonia, and thromboxane B2 levels in young healthy volunteers (n = 25) in samples collected for 10 minutes from subjects with or without a nose clip. Patients with allergic rhinitis (n = 8) were also studied to assess the effect of upper airway inflammation on mediator levels. Adenosine, ammonia, and thromboxane B2 levels were determined by HPLC, spectrophotometry, and radioimmunoassay, respectively. Volume of condensate was significantly higher without nose clip than that with nose clip (mean +/- SD, 2321 +/- 736 microl and 1746 +/- 400 microl, respectively; p = 0.0001). We found no significant difference in any mediator levels between these two collection modes in healthy volunteers, but adenosine showed a tendency to differ between oral and nasal inhalation in patients with allergic rhinitis. Our data indicate that whereas a greater volume of condensate can be obtained when subjects inhale through their noses, the mode of inhalation does not influence mediator levels in young healthy volunteers, but may affect these levels in patients with allergic rhinitis.

Topics: Adenosine; Adult; Ammonia; Bias; Breath Tests; Case-Control Studies; Constriction; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Inhalation; Linear Models; Male; Mouth; Nose; Rhinitis, Allergic, Perennial; Specimen Handling; Thromboxane B2; Tidal Volume; Time Factors; Vital Capacity

To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclooxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas thromboxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1-10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indomethacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.

Topics: Airway Resistance; Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Chromones; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Guinea Pigs; Histamine H1 Antagonists; Indomethacin; Leukotriene Antagonists; Nasal Mucosa; Ovalbumin; Phthalazines; Pyrilamine; Rhinitis, Allergic, Perennial; SRS-A; Thromboxane B2

Thromboxane A2 (TxA2) seems to play an important role in bronchial constriction and hypersensitivity in asthmatics. To study the role of TxA2 in allergic rhinitis, we investigated the levels of thromboxane B2 (TxB2), a stable metabolite of TxA2, in nasal lavage fluid from patients with allergic rhinitis and from actively sensitized guinea pigs after antigen challenge by radioimmunoassay (RIA). There was a significant (p < 0.05) rise in TxB2 levels soon after antigen challenge in nasal lavage fluid from both patients (36.4 +/- 7.5 pg/ml, mean +/- SE) and models (55.6 +/- 21.8 pg/ml). In some of the patients and models, there was an dual rise in TxB2 in the 10 hours after antigen challenge. There was a significant (p < 0.03) correlation between the patients whose levels of TxB2 were re-elevated and them whose nasal airway resistance showed dual rises. These results suggest that TxA2 may contribute to the nasal obstruction in later phase in allergic rhinitis.

Topics: Adult; Animals; Antigens; Disease Models, Animal; Female; Guinea Pigs; Humans; Male; Nasal Lavage Fluid; Nasal Obstruction; Radioimmunoassay; Rhinitis, Allergic, Perennial; Thromboxane A2; Thromboxane B2