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Bronchial asthma is a disease with many unsolved problems and despite an increased availabili ty of anti-asthma drugs, morbidi ty and mortality from this disease are not improving. It is now recognized that asthma should be considered as a chronic inflammatory disease of the lung resulting in bronchial hyperreactivity and subsequent symptoms. The mechanisms underlying airways inflammation and bronchial hyperreactivity have now become a focal point of research in the quest for knowledge about how the management of this disease can be improved. Platelet activating factor (PAF-acether AGEPC) is a naturally occurring ether-linked phospholipid discovered in 1972 associated with IgE mediated allergic responses which has potent effects on platelet activation. PAF is now recognized as a molecule having a diverse range of biological effects relevant to allergic inflammation and asthma including the abili ty to induce long lasting airway inflammation and associated increases in bronchial reactivity. Certain activities of PAF are known to be secondary to platelets activation raising the possibility that this blood element plays a role in the pathogenesis of asthma.
List of contents
Platelets: Activation and Production.- Platelets: Some historical background.- Platelet activation. An overview.- Platelet production by the lung.- Platelet Activating Factor.- Metabolic origin and fate of platelet activating factor.- Properties of PAF relevant to asthma.- Effect of platelet activating factor on histamine release from rat mast cells.- PAF and airway hyperreactivity. Prospects for novel prophylactic anti-asthma drugs.- The role of PAF-acether in anaphylaxis demonstrated with the use of the antagonist BN 52021.- Platelet Activation in Asthma.- Evidence for platelet activation in allergic asthma.- Platelet abnormalities in asthma. Do they exist in humans?.- Lack of PAF release in allergen-induced asthma.- Bleeding time and PAF-acether induced platelet aggregation in atopy.- Platelets in bronchoalveolar lavage from asthmatic patients and allergic rabbits with allergen-induced late phase responses.- Platelet kinetics in stable asthmatic patients.- Aspirin-Induced Asthma.- Platelet activation by IgE and aspirin.- Metabolites of arachidonic acid in the lung.- Eicosanoids and aspirin-sensitive asthma.- Pharmacological attempts to modulate leukotriene synthesis in aspirin-induced asthma.- Evidence of PAF release and platelet activation in analgesics-asthma-syndrome.- Pharmacological Modulation of Bronchial Hyperreactivity and Asthma.- New concepts in the pathogenesis of bronchial hyperresponsiveness.- Effects of BN 52063 on PAF-acether induced weal and flare reaction in man.- Effects of the PAF antagonist CV 3988 on PAF-induced changes in mucus secretion and in respiratory and circulatory variables in ferrets.- Effect of the PAF antagonist SRI 63-441 on the allergic response in awake dogs with natural asthma.
