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Biomedical subjects

J Morley

Publications and source records attributed to J Morley.

At least 109 records · Page 6Linked to original sources
PubMed1989

The effect of prophylactic anti-asthma drugs on PAF-induced airway hyperreactivity.

Intravenous injection of platelet activating factor (PAF) in anesthetized guinea pigs induces non-selective airway hyperreactivity. This response to PAF was reduced in a dose-dependent manner by systemic administration of established prophylactic anti-asthma drugs (ketotifen, cromoglycate, aminophylline and glucocorticosteroids) and by competitive antagonists of PAF. These inhibitory effects could not be accounted for by antagonism of histamine (H1), serotonin or peptidoleukotrienes receptors; parasympatholytic activity; cyclo-oxygenase or lipoxygenase inhibition; mast cell stabilization; or bronchodilatation. Infusion or injection of PAF to induce airway hyperreactivity in the guinea pig may provide a prospective test for prophylactic anti-asthma drugs.

Animals↗
PubMed1989

The effect of prophylactic anti-asthma drugs on PAF-induced platelet accumulation in the thorax of the guinea pig.

Intravenous infusion of platelet activating factor (PAF) causes an accumulation of platelets within the thorax of the guinea pig that is accompanied by increased sensitivity of the airways to spasmogens. A crystal scintillation detector has been used for measurement of intrathoracic accumulation of 111Indium-labeled platelets during responses to PAF. PAF-antagonists inhibit development of airway hyperreactivity, do not diminish platelet accumulation in response to an intravenous infusion of PAF. It is therefore concluded that intrathoracic platelet accumulation per se is not the determinant of increased airway reactivity.

Airway Resistance↗
PubMed1989

Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs.

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.

Animals↗
PubMed1989

Ketotifen in the prophylaxis of extrinsic bronchial asthma. A multicenter controlled double-blind study with a modified-release formulation.

In a placebo controlled double-blind multicenter trial, 245 patients with bronchial asthma (131 male and 124 female patients) between 6 and 51 years of age were treated in two parallel groups. A slow-release oral formulation containing 2 mg of ketotifen or placebo was administered daily for a duration of 12 weeks. Over a period of four weeks before the study, 94 percent of the patients had asthmatic attacks. 78 percent had cough, and 62 percent had nasal symptoms. In the group treated with slow-release oral ketotifen, there were 3.9 asthmatic attacks (range, 0 to 20) per week, and in the placebo group, there were 2.9 (range, 0 to 12) (mean values during four weeks prior to start of treatment). At the end of treatment, asthmatic attacks were significantly reduced in the group treated with slow-release oral ketotifen compared with placebo. Significant reduction was also evident for cough and sputum production, as well as nasal discharge and obstruction; however, slow-release oral ketotifen did not significantly improve pulmonary function indices when compared to placebo. The use of concomitant medication (beta-sympathomimetic drugs) was also significantly reduced in the group receiving slow-release oral ketotifen. The overall efficacy assessed by the investigators was "very good" and "good" in 76 percent of the group receiving slow-release oral ketotifen and 30 percent in the group receiving placebo (p less than 0.001). Tolerability rated by the investigators was "very good" and "good" in 90 percent of the group with slow-release oral ketotifen and in 96 percent of the group with placebo (p less than 0.10). The most frequent side effects were "mild" and "moderate" sedation, sleepiness and drowsiness reported in 44 percent of the patients receiving slow-release oral ketotifen and in 26 percent of the patients receiving placebo. This difference was statistically significant (p less than 0.01).

Adolescent↗
PubMed1988

Pharmacological evaluation of prophylactic anti-asthma drugs by reference to the pathological sequelae of exposure to allergen or platelet activating factor.

Exposure of guinea-pigs to platelet activating factor (PAF) induces airway hyperreactivity and causes an influx of eosinophils into the airways. These effects are inhibited by the established prophylactic anti-asthma drugs; cromoglycate, aminophylline, glucocorticosteroids and ketotifen, whereas other drug categories, with the exception of PAF-receptor antagonists, are ineffective.

Allergens↗
PubMed1988

Accumulation of platelets and eosinophils in baboon lung after paf-acether challenge. Inhibition by ketotifen.

Intratracheal administration of platelet-activating factor (paf-acether) induced transient bronchoconstriction in baboons. Using an automated isotopic monitoring system, we found that intratracheal administration of paf-acether also elicited transient accumulation of platelets labeled with 111In oxine within the pulmonary vasculature after the increase in maximal peak inspiratory pressure. Bronchoalveolar eosinophilia were inhibited by prophylactic administration of the antiasthma drug ketotifen but not by pyribenzamine, suggesting that the effects of ketotifen are unrelated to H-1 receptor antagonism. Platelet accumulation was not affected by ketotifen or pyribenzamine. This study suggests that paf-acether may be a mediator of the eosinophil recruitment in bronchial asthma and that inhibition of this phenomenon by ketotifen may contribute to the therapeutic efficacy of this drug.

Animals↗
PubMed1987

Delayed-onset synergism between leukotriene B4 and prostaglandin E2 in human skin.

The time-course of cutaneous inflammatory responses to LTB4 and PGE2 both alone and in combination has been studied in 10 healthy volunteers. LTB4 induced a transient wheal and flare response in some subjects, maximal at 15 minutes and succeeded by an erythematous, indurated lesion at 2-4 hours. PGE2 elicited a wheal and erythema response which resolved within 1-2 hours. Combination of LTB4 and PGE2 produced acute wheal and erythema responses which did not differ significantly from the summation of responses to the individual constituents of the mixture or from responses to a two-fold increase in the concentration of either component. Wheal and erythema responses persisted, however, with significant potentiation of responses 4 hours after injection. As both leukotrienes and prostaglandins are generated in acute allergic reactions, the effects of these mediators in combination could contribute to persisting and late-onset responses to allergen, in both the skin and lung. In particular, sustained responses to the combination of LTB4 and PGE2 might be important in the pathogenesis of inflammatory skin diseases such as psoriasis.

Adult↗
PubMed1986

Bronchial hyper-reactivity: recent preclinical developments.

Airway hyper-reactivity has been recognized, if not commented upon, for many decades; however, it was the use of allergen inhalation as a clinical test that focused attention upon this aspect of asthma. In allergic asthma, an association has been drawn between inflammatory events, as manifested by the late-onset reaction to allergen, and increased reactivity of airway smooth muscle. The recognition that IgE-dependent processes determine such changes has led to extensive speculation as to pathogenic mechanism underlying the events, with the mast cell being prominent in most schemes. However, no mast cell constituent has been shown to elicit long-lasting inflammatory changes appropriate to asthma nor smooth muscle hyperplasia. Furthermore, it is now clearly evident that selective mast cell stabilising drugs do not prevent development of airway hyper-reactivity that is associated with responses to allergen. Recent pre-clinical studies have implicated platelet activating factor (PAF) as a mediator central to asthma exacerbation; with cells such as platelets, macrophages and eosinophils serving as a source of this material in IgE dependent allergic reactions. The appreciation that PAF can account for acute manifestations of airway hyper-reactivity and for persisting changes of airway function (not only in acute allergic events, but also in acute and chronic non-allergic processes) may have major therapeutic implications. Established prophylactic anti-asthma drugs (i.e. cromoglycate, ketotifen, theophylline and glucocorticosteroids) inhibit such pulmonary pathology, whereas beta-adrenoceptor agonists intensify the hyper-reactivity that follows exposure of pulmonary tissue to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗