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  • 1
    ISSN: 1420-908X
    Keywords: Airway hyperresponsiveness ; ZD2138 ; Zileuton ; 5-lipoxygenase ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of two 5-lipoxygenase (5LO) inhibitors, ZD2138 or Zileuton, on acute, inflammatory responses to aerosolizedAscaris suum (Ag) were determined in atopicMacaca fascicularis monkeys. Monkeys (n=6 each group) were dosed with vehicle, 3 or 10 mg/kg ZD2138, or 30 mg/kg Zileuton (p.o.). Both ZD2138 or Zileuton significantly inhibited ex vivo LTB4 production in Ca2+ ionophore-stimulated whole blood from these same monkeys (n=6 each group) by 45.5% (3 mg/kg ZD2138), 82.5% (10 mg/kg ZD2138) and 84.3% (30 mg/kg Zileuton). ZD2138 (10 mg/kg) reduced bronchoalveolar lavage (BAL) LTE4 levels (65.1% inhibition), BAL neutrophils (88.9% inhibition), and IL-6 (54.0% inhibition) 4h post Ag. Zileuton inhibited these responses and also reduced BAL levels of IL-8 (73.4% inhibition). A second study was performed to evaluate the effects of ZD2138 on chronic Ag-induced responses. Treatment with ZD2138 did not prevent pulmonary inflammation or the development of airway hyperresponsiveness (AHR). Based upon these results, 5LO inhibition significantly reduced ex vivo LTB4 and in vivo LTE4 production as well as several acute inflammatory responses to Ag in the lung. However, ZD2138 did not inhibit more chronic responses following multiple Ag exposure.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 45 (1996), S. 239-245 
    ISSN: 1420-908X
    Keywords: Airway hyperresponsiveness ; Monkey ; Anti-histamine ; β-agonist ; Steroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The following study was performed to further characterize a primate model of asthma using classes of drugs that target allergy (pyrilamine, cetirizine), are bronchodilators for the treatment of asthma (salbutamol, salmeterol) or are anti-inflammatory (dexamethasone). These drugs were examined for their ability to inhibit acute, antigen-induced bronchoconstriction, the development of airway hyperresponsiveness (AHR) and the infiltration of leukocytes into the lungs of atopic cynomolgus monkeys (Macaca facsicularis) using a 10-day, multiple antigen (Ag) challenge protocol. All compounds except dexamethasone and cetirizine significantly (p〈0.05) reduced acute, Ag-induced bronchoconstriction (salbutamol: 74.2%, salmeterol: 52.6%%, pyrilamine: 62.4% inhibition) compared to vehicle control trials. Only dexamethasone and salmeterol prevented the development of AHR to methacholine challenge by 90.4±6.81% and 85.7±5.61% respectively. Dexamethasone significantly reduced the Ag-induced increase in BAL eosinophils by 85.9±8.53%. Cetirizine reduced the eosinophil response in 5 of 6 monkeys and salmeterol demonstrated a trend towards reduced eosinophil increases after multiple Ag challeng, but neither of these were statistically significant. These results further illustrate the utility of this model in predicting compound effects against several relevant functional endpoints that are consistent with the effects of similar classes of compounds in humans.
    Type of Medium: Electronic Resource
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