Search PubMed⌕ Search

Biomedical subjects

S Sanjar

Publications and source records attributed to S Sanjar.

At least 37 records · Page 2Linked to original sources

Viewpoint: untoward effects of beta-adrenoceptor agonists in asthma.

Beta-adrenoceptor agonists are potent and selective relaxants of airway smooth muscle. They produce symptomatic bronchodilatory effects and are the most widely used therapy in asthma. In patients with asthma, they usually effect a reduction of airway resistance, but there have been several reports of episodes of increased airway obstruction, arterial hypoxaemia and even death associated with such therapy. "Anomalous or paradoxical bronchospasm" are appropriate terminologies to describe this unexpected phenomenon. Five mechanisms have been proposed to account for anomalous responses to these substances: 1) reactive myogenic tone; 2) metabolic products with spasmogenic activity; 3) adrenoceptor tachyphylaxis; 4) increased inflammatory burden; and 5) induction of airway hyperreactivity. Following a review of the relative merits of each proposal, it is concluded that increased inflammatory burden and induction of airway hyperreactivity, alone or in combination, provide the most plausible explanation for paradoxical bronchospasm.

Adrenergic beta-Agonists↗

In vivo method for the assessment of platelet accumulation.

Platelets labeled with 111Indium have been injected intravenously into anesthetised guinea pigs, and intrathoracic content of 111Indium-labeled platelets has been monitored continuously using a microcomputer-based system (AIMSplus). Dose-effect relationships have been described for ADP, collagen, and PAF, and effects of drugs upon selected responses illustrate the potential of this test system for routine in vivo screening of agents that may inhibit aggregation of platelets.

Adenosine Diphosphate↗

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↗

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↗

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↗

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↗