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Biomedical subjects

D F Biggs

Publications and source records attributed to D F Biggs.

At least 37 records · Page 2Linked to original sources
PubMed1985

Does capsaicin cause reflex bronchospasm in guinea-pigs?

Capsaicin given intravenously (i.v.) into the vena cava or intra-arterially (i.a.) into the aortic arch of anesthetized guinea-pigs induced dose-dependent increases in pulmonary-flow resistance (R) and dynamic thoracic elastance (E). Threshold doses were 0.5-1.0 micrograms/kg body weight; greater than 8.0 micrograms/kg induced tachyphylaxis. These responses to capsaicin, i.v. or i.a., were similar after decentralization, bilateral vagotomy, or glossopharyngealotomy, and after autonomic blockers (mecamylamine, atropine, mepyramine, and bethanidine). Morphine significantly reduced responses to capsaicin but had no effect on responses to substance P (SP). Naloxone did not reverse the inhibitory effect of morphine, and neither reduced nor enhanced capsaicin-induced increases. Of the two antagonists to SP examined (given i.v.), [D-Pro2,D-Trp7,9]SP had no effect on SP-induced increases but abolished capsaicin-induced increases in R, though without affecting increases in E, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP reduced increases in R induced by both SP and capsaicin but had no effect on increases in E. Capsaicin (2.0-32.0 micrograms/kg i.v. or i.a.) had no bronchospastic effect in guinea-pigs given this drug (50.0 mg/kg s.c.) 7 days earlier. We conclude that in guinea-pigs--unlike other species--capsaicin causes bronchospasm without stimulating any afferent receptors in a centrally mediated bronchospastic reflex arc.

Animals↗
PubMed1985

Mechanisms of action of sodium cromoglycate.

The effects of sodium cromoglycate (SCG) on cardiovascular and pulmonary responses to phenylbiguanide, capsaicin, and vagal stimulation were studied in anesthetized guinea pigs. Phenylbiguanide had no bronchospastic activity but induced reflex changes in arterial blood pressure which were reduced or abolished by SCG. Capsaicin induced nonreflex bronchospasm, and decreases in arterial blood pressure that were unaffected by SCG. Sodium cromoglycate, given before or after atropine, had no effect on the bronchospasm and cardiovascular responses to unilateral or bilateral stimulation of the vagus nerves. We conclude that SCG may influence both the afferent and efferent pathways of responses to drugs.

Animals↗
PubMed1984

Low-dose methotrexate kinetics in arthritis.

Twelve patients with either rheumatoid or psoriatic arthritis were injected with a 10-mg bolus dose of methotrexate (MTX) either intramuscularly (n = 6) or intravenously (n = 6) and the MTX concentration in their sera was determined by radioimmunoassay. MTX concentration--time data fitted triexponential equations. Doses injected intramuscularly were rapidly and completely absorbed. There were no significant intergroup differences in drug mean t 1/2, volume of distribution, and total body clearance. In nine patients serum MTX concentrations remained above the suggested critical level of 0.01 mumol throughout the 24-hr study irrespective of the route of administration, but MTX did not cumulate in the serum. We conclude that the behavior of low doses of MTX in patients with arthritis closely resembles the pattern in patients receiving intermediate and high doses for the treatment of neoplasia.

Absorption↗
PubMed1984

Direct and indirect actions of histamine on airway smooth muscle in guinea pigs.

Studies in guinea pigs showed that some forms of drug-induced bronchospasm are reflexogenic involving afferents in the glossopharyngeal nerve. At least two pathways appear to be involved. One pathway contains H1 receptors and is blocked by mepyramine and sodium cromoglycate (SCG), and its pharmacological characteristics are similar to those of active reflex vasodilation. The other appears to involve peripheral muscarinic receptors. The findings also indicate that SCG may act on efferent as well as afferent pathways.

Airway Resistance↗
PubMed1981

The mechanism of the bronchoconstriction induced by unilateral orthodromic stimulation of the carotid sinus nerves.

Unilateral stimulation of carotid sinus nerve afferents at 2 and 4 V produced pulse duration-dependent reflex bronchoconstriction which was unaffected by midcervical, bilateral vagotomy. The bronchoconstriction consisted of two pharmacologically distinct components. One component was blocked by atropine or atropine methiodide, and other was blocked by either mepyramine or disodium cromoglycate. Combinations of atropine or atropine methiodide with mepyramine or disodium cromoglycate completely eliminated bronchoconstrictor responses to nerve stimulation. These data indicate that two separate bronchoconstrictor reflexes, possibly resembling serotonin- and diazoxide-induced reflex bronchoconstriction are activated by stimulation of afferent fibers in the carotid sinus nerves.

Airway Resistance↗
PubMed1980

The effects of diazoxide on total lung resistance in the anesthetized paralyzed guinea-pig.

The initial effects of diazoxide on dynamic pulmonary compliance (CL) and flow resistance (RL) were measured in paralyzed, anesthetized guinea-pigs. Diazoxide (10, 20 or 40 mg/kg) caused a dose-related increase in RL and decrease in CL. The increase in RL could be selectively abolished by glossopharyngealotomy or decentralization, and by pretreatment with mepyramine (0.1 mg/kg) or disodium cromoglycate (10 mg/kg). Pretreatment with indomethacin (0.1 mg/kg) or acetylsalicylic acid (1 mg/kg) selectively eliminated the decreases in compliance observed after diazoxide. It is concluded that diazoxide initially constricts both large (RL) and small (CL) airways. The constriction of the large airways may involve a release of histamine, whereas the constriction of the small airways may be mediated by a prostaglandin or prostaglandin-like substance.

Airway Resistance↗