In vivo allergen tachyphylaxis in guinea pig lung is mediated by endogenous prostaglandin E biosynthesis

Self Cite

We present a noninvasive and highly sensitive system for measuring lung function in small animals. It is based on a two-chambered body plethysmography. Head and body chambers are separated by a cuff around the head of the animal. Aerosols for pharmacologic investigations are generated. Breathing-dependent changes in pressure and/or volume are registered, the signals are digitized. All data are processed in an IBM compatible PC/AT. A multitasking real time operation system shows the signals on line. A special software offers seven different lung function parameters (compressed air, airway resistance, thoracic gas volume, maximal flow rates, tidal volume, breathing frequency, I/E ratio). The results are presented as graph and text documents. Result files are submitted to calculation by standard soft ware. The computer-aided handling allows the simultaneous performance of up to nine pharmacological tests.

Section: Documentation and Statisticsmentioning

confidence: 99%

Noninvasive Analysis of Lung Function in Small Animals: Compressed Air, Thoracic Gas Volume, Airway Resistance, Maximal Flow Rates, Tidal Volume, Breathing Frequency, l/E Ratio

Dorsch¹,

Hess²

1992

Self Cite

“…All tests are performed according to a randomized crossover pro tocol [7]: groups of 10-14 animals were divided into two subgroups and treated cither with the test material or control solutions. One week later the tests were repeated.…”

Section: Inhalation Challenge In Guinea Pigsmentioning

confidence: 99%

Antiasthmatic Effects of <i>Galphimia glauca</i>, Gallic Acid, and Related Compounds Prevent Allergen- and Platelet-Activating Factor-Induced Bronchial Obstruction as well as Bronchial Hyperreactivity in Guinea Pigs

Dorsch

Bittinger

Kaas

et al. 1992

Self Cite

A methanolic extract from Galphimia glauca (320 mg/kg, orally) inhibited acute bronchial reactions to allergen (ovalbumin, 10 mg/ml) and platelet-activating factor (PAF, 1 μg/ml) inhalation challenges, but not to histamine or acetylcholine in spontaneously breathing guinea pigs. Furthermore, the PAF-induced bronchial hyperreactivity was markedly reduced. Gallic acid and related compounds as well as the flavonoid, quercetin, were identified as active compounds. Gallic acid, methyl gallate and quercetin showed significant effects after a single oral dose of 45 mg/kg, tetragalloyl quinic acid after 5 mg/kg. Continuous treatment of the animals with one certain fraction (GG II, 3 days, 3 × 2 mg/kg) containing all active compounds reduced allergen- and PAF-induced bronchial reactions by more than 70%.

“…Therefore, this model may be more physiologically representative of the clinical situation than those using a single highconcentration challenge with antigen. Recently, several studies have been reported on modulation of 'desensitization' in vivo using pulmonary responses in sensitized guinea pigs [15][16][17][18]. Our method of re peated, leukotriene-mediated contractions of isolated lung appears well suited to further evaluate the phar macologic control of lung contractions and the me chanisms of desensitization in actively sensitized, an tigen-challenged tissues.…”

mentioning

confidence: 99%

Repeatable Antigen-Induced Contractions of Isolated Guinea Pig Lung Strips Are Mediated by Leukotriene

Robichaud¹,

Webster²,

Thueson³

1986

Lung strips from actively sensitized guinea pigs were repeatedly contracted by antigen (ovalbumin, OA) challenge in the presence of the antihistamine (H₁) mepyramine. At lower concentrations of OA, hourly challenges gave reproducible and consistent responses. High-concentration OA resulted in desensitization, with two to six contractions being very weak. The antigen concentration affected not only the force of contraction, but other parameters including the time to peak effect, the protraction of the peak effect, and the repeatability of the force and time to peak. Low concentrations of OA induced a response which peaked by 6–8 min and decreased by about 30% after 15 min, while high-concentration OA resulted in a contraction which peaked later and did not relax. These data suggest that different ‘early’ and ‘late’ mediators may be involved depending on the ‘activation state’ or the mechanisms that predominate in the contraction response as a result of the amount of stimulation by antigen. Leukotriene apparently mediates the peak and the 15-min contraction since both were inhibited completely by FPL-55712 (IC₅₀ = 8 μM) or NDGA (IC₅₀ = 5 μM). These repeated, leukotriene-mediated contractions of isolated lung may mimic the clinical situation (chronic exposure to low amounts of antigen) of allergic disease and may be used to study the modulation of lung responses and desensitization phenomena.