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Biomedical subjects

R W Bury

Publications and source records attributed to R W Bury.

48 records · Page 3Linked to original sources
PubMed1979

Assay of flucytosine (5-fluorocytosine) in human plasma by high-pressure liquid chromatography.

The use of the antifungal agent flucytosine has been associated with dose-related hepatotoxicity and bone marrow depression, and measurement of plasma concentrations is useful in determining dosage schedules. The present study describes a rapid, simple, and sensitive high-pressure liquid chromatographic analysis of plasma flucytosine which may be completed within 30 min of receipt of a plasma sample. Sample preparation is minimal and merely involves precipitation of plasma protein before injection onto a reverse-phase column. The method is accurate and reproducible and yields results comparable to or perhaps slightly superior to those obtained by conventional microbiological assay. The value of the procedure for routine use is enhanced by the freedom from interference by a large range of medications administered concurrently with flucytosine.

Chromatography, High Pressure Liquid↗
PubMed1977

Cardiovascular effects of synthetic substance P in several species.

In dogs anaesthetised with chloralose, infusion of synthetic substance P into the femoral artery caused marked elevation of femoral arterial blood flow which was well sustained during the infusion period. Doses less than 59 fmol/kg/min increased femoral arterial flow only, but larger doses caused transient hypotension accompanied by tachycardia. The administration of substance P by i.v. and intravertebral (i.vert.) arterial routes caused hypotension and tachycardia of similar pattern and magnitude to those produced by intrafemoral (i.f.) arterial infusion of equivalent doses. I.v. injection of substance P into rats and rabbits caused qualitatively similar cardiovascular effects to those in dogs, but higher doses were required for threshold responses. Substance P had little effect on the spontaneously beating isolated guinea-pig heart. Like many other vasodilator substances in vivo, substance P caused constriction of the isolated perfused ear vein from the rabbit. The results suggest that the major cardiovascular effect of synthetic substance P is vasodilatation and that a direct action on vascular smooth muscle is involved.

Animals↗
PubMed1977

The stability of synthetic substance P in blood.

Experiments with synthetic substance P incubated in whole blood show that apart from a moderate loss of activity immediately on exposure of the peptide to whole blood, it is inactivated slowly in this tissue, approximately 25% of control activity remaining after 30 min incubation. Incubation with plasma did not result in the degradation of substance P. The attenuation of substance P activity in blood may be due to enzymatic destruction within erythrocytes.

Animals↗
PubMed1977

Substance P: its pharmacology and physiological roles.

The recent identification and synthesis of the endecapeptide substance P has renewed interest in this naturally occurring compound. The original substance P of Euler and Gaddum was a mixture of biologically active substances, some of which were peptides. The peptide component was responsible for gut-contracting, hypotensive and sialogogic properties attributed to substance P. For almost 40 years following its discovery, substance P resisted isolation and purification. Even the most highly active preparations were heterogeneous and there was a divergence of results from experiments using preparations which were partially purified by different techniques. Nevertheless much of the early work on the distribution and pharmacology of crude substances P has been confirmed using the synthetic endecapeptide and has stimulated research towards the elucidation of a possible functional role for substance P. Most proposed functions have been highly speculative but, at present, evidence is accumulating in support of a physiological role for substance P as a neurotransmitter in sensory pathways.

Animals↗
PubMed1976

Biological activity of C-terminal partial sequences of substance P.

Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog, isolated guinea pig ileum, and the isolated rabbit ear vein. The tripeptide and tetrapeptide possessed weak vasodilator properties only but no activity was detected on the other less sensitive preparations. The pentapeptide produced appreciable spasmogenic and vasoactive effects. Sequences of six or more C-terminal amino acids were able to elicity activity at comparable doses to that of the parent endecapeptide; however, the activity did not increase regularly with the chain length. In each assay preparation the octapeptide was the most potent peptide. It was twice as potent as substance P on a molar basis in the guinea pig ileum but the enhancement of activity beyond that of substance P was less pronounced in the vascular preparations.

Amino Acid Sequence↗
PubMed1976

The effects of metoclopramide in modifying the response of isolated guinea-pig ileum to various agonists.

Metoclopramide has a dual effect on intestinal smooth muscle. Low concentrations of metoclopramide cause potentiation of the responses to substance P, acetylcholine, histamine and barium chloride on the guinea-pig ileum. Higher concentrations produce a depression of smooth muscle responses which is characteristic of the tertiary amine local anesthetics. Neural pathways are involved in the mechanism of potentiation, since the enhancement of the responses to the agonists is abolished by tetrodotoxin. Atropine partially antagonizes the potentiating effect of metoclopramide implying that activation of muscarinic receptors is a contributing factor, but this does not fully explain the potentiation.

Acetylcholine↗
PubMed1976

Interactions between local anesthetics and spasmogens on the guinea-pig ileum.

The effect of various local anesthetics and other substances known to modify calcium fluxes in cells, on submaximal responses of guinea-pig ileum to substance P, acetylcholine, histamine and barium chloride was determined. Procaine caused a dose-related depression of the response to all the agonists but the response to substance P was far less susceptible to this depression. Lidocaine, bupivacaine, pramoxine and W 6211 also caused a lower degree of attenuation of the response to substance P than the responses to acetylcholine, histamine and barium chloride. Verapamil caused a dose-related depression of responses to all the agonists equally. The use of calcium-free solutions abolished responses to substance P, acetylcholine and histamine. The response to barium chloride was less affected by calcium withdrawal but was reduced markedly. In the presence of 10 mM lanthanum chloride, the response to all the agonists was abolished. The relative resistance of the substance P responses to antagonism by local anesthetics suggests that different and more efficient channels for calcium entry into the smooth muscle cell are involved.

Acetylcholine↗
PubMedDate not supplied

A [14C]phenacetin breath test to measure hepatic function in man.

Phenacetin, a high-clearance drug, was labeled as [14C-ethyl]phenacetin and used in a breath test of hepatic function. 14CO2 appeared rapidly in breath such that more than 30% of the administered radioactivity was expired in 2 hr. For all means of expression used to describe the appearance of 14CO2 in breath, normal controls and hospitalized patients without liver disease were clearly separated from cirrhotic subjects with moderate and severe liver damage. The phenacetin breath test was validated by the close correlation of 14CO2 appearance with the disposition of the parent compound examined after its intravenous administration, and by demonstration that the rate-limiting step in 14CO2 generation from labeled phenacetin occurred proximal to 14CO2 generation from [14C]acetate given intravenously. Correcting for the actual volume of CO2 exhaled by control and cirrhotic subjects did not increase the sensitivity of the test. The phenacetin breath test has potential as a simple procedure to quantitate hepatic metabolism of drugs, particularly those mediated by cytochrome P448.

Acetates↗
PubMedDate not supplied

Area estimation in pharmacokinetic studies using a hand-held programmable calculator.

A short program for area analysis in pharmacokinetic studies using the Hewlett-Packard HP41C hand-held programmable calculator is described. Area under the concentration-time curve is calculated firstly within defined time limits and then with extrapolation to infinite time using the slope constant of the terminal phase. Input of concentration-time data is simple and there is no limit on the number of time-concentration co-ordinates which can be entered for area calculation.

Computers↗
PubMedDate not supplied

A pharmacological investigation of synthetic substance P on the isolated guinea-pig ileum.

1. The pharmacological properties of synthetic substance P have been studied on the guinea-pig ileum and compared with those of acetylcholine and other agonists. 2. The effects of synthetic substance P in the presence of atropine, hexamethonium, mepyramine and certain of the drugs which antagonize serotonin are in close agreement with those reported for the naturally occurring peptide. 3. The spasmogenic action of substance P is not mediated by cholinergic mechanisms or release of prostaglandins, and does not appear to involve release of serotonin. The inability of tetrodotoxin to attenuate responses to substance P suggests that its spasmogenic action is not elicited through neural mechanisms. Thus, it is likely that substance P acts directly on the smooth muscle of the ileum. 4. Since substance P is present in the brain and can depolarize neurones, it may be a neurotransmitter. A screening of various centrally acting drugs, whose mechanisms of action are unclear, was undertaken to seek possible interactions with substance P. Pimozide was the most potent in depressing responses to substance P but none of the drugs caused the specific antagonism which would assist in elucidating a possible physiological role for substance P.

Amitriptyline↗
PubMedDate not supplied

An assessment of the usage of the plasma theophylline assay service in a teaching hospital.

A four-week assessment of all inpatients who had been prescribed theophylline therapy was carried out at a major Australian teaching hospital. A total of 49 theophylline assays was requested for 36 of 116 patients who were prescribed theophylline. Only 38 (78%) assays were ordered for appropriate indications and at appropriate times. In 26 of the 34 appropriately requested assays that could be followed-up, appropriate action was judged to have been taken on receipt of the assay result. Of the 80 patients who were prescribed theophylline for whom theophylline assays were not ordered, 19 might have benefited from the performance of an assay. It is concluded that the theophylline assay service is not being used optimally.

Australia↗