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Biomedical subjects

R W Foster

Publications and source records attributed to R W Foster.

At least 73 records · Page 4Linked to original sources
PubMed1985

Electrophysiological and other aspects of the relaxant action of isoprenaline in guinea-pig isolated trachealis.

In guinea-pig isolated trachealis isoprenaline (0.001-0.1 mumol l-1) caused concentration-dependent relaxation. Propranolol (1 mumol l-1) antagonized the effects of isoprenaline by more than 100 fold but did not modify the relaxant action of sodium nitrite. The tracheal relaxant actions of isoprenaline and ATP were unaffected by apamin (0.1 mumol l-1) but apamin profoundly antagonized the effects of noradrenaline and ATP on guinea-pig isolated taenia caeci. Tetraethylammonium (TEA; 8 mmol l-1) and procaine (5 mmol l-1) each evoked tracheal spasm but neither agent antagonized the isoprenaline-evoked relaxation of the trachealis. Trachealis exposed to K+-rich (120 mmol l-1) Krebs solution developed near-maximal tension. Both isoprenaline and sodium nitrite relaxed the K+-depolarized tissue though concentration-effect curves for both relaxants were moved to the right compared to those obtained in non-depolarized tissues. The maximal effect of sodium nitrite was markedly reduced. Intracellular electrophysiological recording showed that isoprenaline (0.01-1 mumol l-1) caused hyperpolarization and reduced or abolished slow wave discharge in trachealis muscle. These effects were accompanied by relaxation. Propranolol (1 mumol l-1) virtually abolished both the electrical and mechanical responses to isoprenaline (0.1 mumol l-1). Apamin (0.1 mumol l-1) did not alter the spontaneous electrical activity of trachealis cells or their electrical and mechanical responses to isoprenaline (0.1 mumol l-1). TEA (8 mmol l-1) caused depolarization and often increased slow wave amplitude and induced spike discharge. Isoprenaline (0.01 mumol l-1) failed to hyperpolarize TEA-treated trachealis cells. Higher concentrations of isoprenaline suppressed TEA-induced spasm, caused hyperpolarization and thereby increased slow wave or spike amplitude. Slow wave or spike frequency decreased as the hyperpolarization progressed but abolition of slow waves or spikes sometimes required more than 4 min exposure to isoprenaline. Procaine (5 mmol l-1) increased the amplitude of slow waves and induced spike discharge. Procaine markedly reduced the hyperpolarization induced by isoprenaline (0.1 and 1 mumol l-1) but had little effect on isoprenaline-induced relaxation. It is concluded that isoprenaline activates beta-adrenoceptors in guinea-pig trachealis and thereby evokes relaxation and hyperpolarization of the smooth muscle. The hyperpolarization does not involve the opening of apamin-sensitive K+-channels and it probably plays a supportive rather than a crucial role in the process by which isoprenaline-induced relaxation is achieved.

Action Potentials↗
PubMed1985

Some effects of nifedipine in guinea-pig isolated trachealis.

In trachealis depolarized by a K+-rich medium, nifedipine (0.001-1 mumol 1(-1) caused concentration-dependent antagonism of CaCl2-induced increase in tension, moving the CaCl2 log concentration-effect curve to the right and depressing the maximal response. In trachealis in normal Krebs solution, similar concentrations of nifedipine had marked antispasmogenic activity against the responses to potassium chloride (KCl) and tetraethylammonium (TEA). However, nifedipine had little, if any, antispasmogenic activity against the responses to acetylcholine or histamine. Nifedipine 1 mumol 1(-1) was tested for spasmolytic activity in tissues generating tension in response to the EC50 of acetylcholine, KCl or CaCl2. In producing spasmolysis nifedipine was most effective against CaCl2 and least effective against acetylcholine. Nifedipine (0.01-1 mumol-1) had little or no effect on the tone of trachealis in normal Krebs solution. Intracellular electrophysiological recording showed that nifedipine 1 mumol 1(-1) could abolish spontaneous slow wave activity. This was associated with very minor depolarization and little or no loss of mechanical tone. In tissues treated with TEA (8 mmol 1(-1) nifedipine abolished spike and slow wave discharge and reduced mechanical activity to the pre-TEA level. It is concluded that nifedipine prevents KCl- or TEA-induced spasm by inhibition of Ca2+ influx. Spasm evoked by acetylcholine or histamine and the maintenance of spontaneous tone depend largely on mechanisms for increasing the cytoplasmic concentration of free Ca2+ which are resistant to nifedipine.

Animals↗
PubMed1984

The application of irritant chemicals selectively to the skin of the leech ganglion/body wall preparation.

A technique is described for applying chemical irritants selectively to the skin of a superfused ganglion/body wall preparation of the horse leech, Haemopis sanguisuga. Details are given of the intracellular recording from sensory neurones of the effects of the irritant dibenzoxazepine and of mechanical stimulation. Dibenzoxazepine produced changes in the spontaneous firing pattern in the nociceptive cells of the leech but did not affect the response to mechanical stimulation of the skin in any type of sensory cell. It is possible that the system described could be used as a model of cutaneous excitation evoked by drugs or mechanical stimulation in higher animals.

Action Potentials↗
PubMed1984

Antagonism of Ca2+ and other actions of verapamil in guinea-pig isolated trachealis.

In trachealis bathed by a K+-rich, Ca2+-free physiological salt solution, calcium chloride (CaCl2) at 0.01 to 10 mmol l-1 evoked concentration-dependent spasm. Verapamil (0.1 to 10 mumol l-1) was an effective antagonist of CaCl2. Spasm evoked by acetylcholine, histamine, potassium chloride (KCl) and tetraethylammonium (TEA) was studied in trachealis bathed by normal Krebs solution. Verapamil (0.1 to 10 mumol l-1) markedly suppressed spasm evoked by KCl and TEA. In contrast the actions of acetylcholine and histamine were much less affected by verapamil. Spasm evoked by prostaglandin E2 was studied in trachealis bathed by Krebs solution containing indomethacin (2.8 mumol l-1). Verapamil (0.1 to 10 mumol l-1) had little or no effect against prostaglandin E2-induced spasm. Verapamil (0.1 to 10 mumol l-1) had relatively little effect on the tone of trachealis bathed by normal Krebs solution. In contrast bathing in Krebs solution lacking CaCl2 caused almost complete tone loss. Extracellular electrophysiological recording showed that verapamil (10 mumol l-1) suppressed not only TEA-evoked spasm but also TEA-evoked slow waves and spike potentials. Verapamil also abolished the transient period of slow wave activity associated with the spasm evoked by KCl. Intracellular electrophysiological recording showed that TEA-induced spike activity was resistant to tetrodotoxin (3 mumol l-1). However, verapamil (10 mumol l-1) abolished the tetrodotoxin-resistant spikes without increasing the resting membrane potential. It is concluded that verapamil suppresses TEA- or KCl-induced spasm, slow waves or spikes by inhibition of Ca2+ influx. Spasm evoked by acetylcholine, histamine and prostaglandin E2 depends on mechanisms for increasing the cytoplasmic concentration of free Ca2+ which are resistant to verapamil. The failure of verapamil markedly to depress tissue tone is consistent with the proposal that tone results from the activity of endogenous prostaglandins.

Acetylcholine↗
PubMed1984

Some features of the spasmogenic actions of acetylcholine and histamine in guinea-pig isolated trachealis.

Intracellular electrophysiological recording showed that acetylcholine (1 mumol l-1) and histamine (2 mumol l-1) depolarized trachealis cells and often increased the frequency of slow waves. Higher concentrations of these agents caused greater depolarization and abolition of slow waves. Marked depolarization was often associated with the appearance of electrical 'noise'. These electrical phenomena were accompanied by tonic tension development in a contiguous segment of trachea. Electrical 'noise' and tension evoked by high concentrations of acetylcholine or histamine could be dissipated by washing the agonist from the tissue. Acetylcholine-induced 'noise' was resistant to tetrodotoxin (3 mumol l-1) and to hexamethonium (1 mmol l-1). Neither acetylcholine (10-1,000 mumol l-1) nor histamine (2-200 mumol l-1) increased the lanthanum-resistant calcium fraction of muscle-containing strips of trachea. It is concluded that, while developing tension under the influence of acetylcholine or histamine, trachealis cells depolarize markedly but there is relatively little cellular influx of Ca2+.

Acetylcholine↗
PubMed1983

Evidence that the spasmogenic action of tetraethylammonium in guinea-pig trachealis is both direct and dependent on the cellular influx of calcium ion.

1 Tetraethylammonium (TEA, 1-8 mmol/l) evoked spasm of guinea-pig trachealis which was unaffected by atropine (1 mumol/l), mepyramine (1 mumol/l) or tetrodotoxin (3 mumol/l). 2 The spasm evoked by TEA was markedly suppressed in Ca2+-free Krebs solution while that evoked by acetylcholine was much less affected. 3 Extracellular electrical recording showed that exposure to Ca2+-free Krebs solution suppressed both spontaneous electrical slow wave activity of the trachea and the spasm and slow waves induced by TEA. These effects were reversible. 4 TEA (2 and 8 mmol/l) increased the lanthanum-resistant calcium fraction of trachea. 5 It is concluded that TEA acts directly on the smooth muscle of guinea-pig trachea, that the spasm and electrical slow waves evoked are Ca2+-dependent and that the cellular influx of Ca2+ is increased.

Animals↗
PubMed1983

The spasmogenic action of potassium chloride in guinea-pig trachealis.

Tissue bath experiments showed that potassium chloride (KC1) at 10-40 mmoll-1 evoked spasm of guinea-pig trachealis which was unaffected by atropine (1 mumoll-1), mepyramine (1 mumoll-1), tetrodotoxin (3 mumoll-1) or indomethacin (2.8 mumoll-1). Spasm evoked by KC1 was depressed in Ca2+-free Krebs solution or by exposure of tissues to LaCl3 (0.25-1 mmoll-1). Extracellular electrical recording showed that the spasm evoked by KCl 10 mmoll-1 was associated with promotion of electrical slow wave activity. Higher concentrations of KC1 abolished slow wave activity but caused further tension development. Intracellular recording confirmed the ability of KC1 10 mmoll-1 transiently to promote slow wave activity in individual trachealis cells. This action was associated with depolarization and tension development. Higher concentrations of KC1 evoked further tension development but slow waves were suppressed as the depolarization evoked by KC1 increased. KC1 (10-40 mmoll-1) increased the lanthanum-resistant calcium fraction of muscle-containing strips of trachea. It is concluded that KC1 acts directly on the smooth muscle of guinea-pig trachea. The spasmogenic action is associated with transient promotion of slow wave activity and a fall in resting membrane potential. The spasm involves the cellular influx of Ca2+ and is dependent on the presence of Ca2+ in the extracellular fluid.

Animals↗
PubMed1982

Cost-based reimbursement and prospective payment: reassessing the incentives.

Prospective payment is distinguished from the imposition of a regulatory ceiling on hospital costs. While a regulatory ceiling could potentially be effective in controlling expenditure growth, its success depends upon the political climate. Prospective payment, as a distinct financial policy, offers little cost-containment potential. It is appropriately evaluated in term of its effects on the distribution of risk between providers and third parties and on the trade-off between investment and current consumption.

Cost Control↗
PubMed1981

Some effects of chemical irritants on the membrane of the giant amoeba.

1 The effects of chemical irritants on the membrane potential and input resistance of the giant amoeba, Chaos carolinense, have been investigated. The membrane potential and input resistance were -111.5 mV and 8.6 M pi respectively. 2 In the resting state the cell membrane of Chaos carolinense was found to be impermeable to Na+ but permeable to K+. The distribution of K+ across the cell membrane conformed to a Donnan equilibrium with the resting membrane potential being the K+ equilibrium potential. 3 The chemical irritants dibenzoxazepine and its 2-chloro- and 3-chloro-analogues and o-chlorobenzylidene malononitrile produced a fall in input resistance but no change in membrane potential. It is suggested that these effects are caused by an increase in K+ permeability. 4 The potencies of a series of chemical irritants with respect to dibenzoxazepine were measured on the giant amoeba. These potencies did not reflect those found in mammalian preparations.

Amoeba↗
PubMed1979

Comparative evaluation of six techniques for determining the Michaelis-Menten parameters relating phenytoin dose and steady-state serum concentrations.

Using randomly generated data within set error limits, the Michaelis-Menten parameters Dmax and Km relating steady-state serum phenytoin concentrations (Css) and dose (D) were determined by 5 graphical techniques and an iterative computer fit to the hyperbolic equation. The best mean estimates of Dmax and Km were provided by the latter. Assuming the experimental error to be in Css the results indicate that the most reliable graphical technique is that based on the equation Css = Dmax Css/D - Km. However, considering its obvious simplicity and relative reliability the direct linear plot is recommended for clinical use.

Computers↗
PubMed1979

The effects of oestradiol benzoate, progesterone, relaxin and ovariectomy on cervical extensibility in the late pregnant rat.

Cervical extensibility increased from Day 16 to term in the pregnant rat. Following ovariectomy on Day 16 of pregnancy the cervix became as inextensible by Day 20 as that of non-pregnant animals. Fetal growth was maintained in rats ovariectomized on Day 16 if given oestradiol benzoate plus progesterone but cervical extensibility only increased to a small extent. Relaxin given to these animals further increased cervical extensibility, suggesting a role for this hormone.

Animals↗
PubMed1978

A study of the sympathomimetic action of guanethidine on the isolated anococcygeus muscle of the rat.

Guanethidine, acting on the rat isolated anococcygeus, causes adrenergic neurone blockade (slowly terminated by washing), noradrenaline potentiation and, with higher concentrations, spasm (both rapidly terminated by washing). 2 The spasm is an indirect sympathomimetic action, for it is sensitive to phentolamine and reserpine and shows tachyphylaxis. 3 The concentration of cocaine equieffective with the spasmogenic concentration of guanethidine as an inhibitor of noradrenaline uptake caused much less spasm. Moreover, it did not enhance noradrenaline efflux from anococcygeus loaded with (-)-[3H]-noradrenaline, as guanethidine did. 4 The spasm induced by guanethidine in excess of cocaine is due to guanethidine-evoked noradrenaline release.

Animals↗