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Biomedical subjects

A M White

Publications and source records attributed to A M White.

At least 55 records · Page 3Linked to original sources
PubMed1982

Fibrin, red cell and platelet interactions in an experimental model of thrombosis.

1 Insertion of a cotton thread into an arteriovenous shunt of an anaesthetized rat causes an increase in the weight of the thread due to deposition of thrombus. 2 The thrombus formed was of the venous (red) type, being sensitive to heparin, yet possessed important characteristics of an arterial thrombus, in that it was dependent on platelets and on rate of blood flow. 3 Thromboxane synthetase inhibitors had no effect on thrombus deposition. 4 Cyclo-oxygenase inhibitors did not significantly depress thrombus formation at doses which inhibited platelet function ex vivo. 5 Compounds which can modify the release or action of adenosine 5' -diphosphate partly inhibited thrombus formation. 6 A depression in clotting factor levels induced by sodium warfarin led to a highly significant reduction in thrombus formation at doses which caused a prolongation of prothrombin clotting time.

Animals↗
PubMed1982

Subcellular localization of 111In in human and rabbit platelets.

In order to examine the subcellular distribution of 111In in 111In-oxine-labeled human and rabbit platelets, we employed a hypothetical grain technique of EM autoradiography analysis. The results indicate that in the rabbit 111In was concentrated within the platelet dense bodies, particularly when the platelets had been labeled in a plasma-free system. Under comparable conditions of labeling, human platelets appeared to accumulate almost all the radiolabel within the cytosol. Using inhibitors of 5-hydroxytrptamine (5-HT) uptake, i.e., cloimipramine, ouabain, sodium fluoride, p-chloromercuribenzoate, and reserpine, we were unable to demonstrate an active uptake process in either species. Both collagen and thrombin were able to cause dose-dependent release of radioactivity from the labeled rabbit platelets only. In the case of collagen, this mimicked endogenous 5-HT release and was inhibited by indomethacin. These results and their implications are discussed.

Animals↗
PubMed1981

The effects of two different dosage regimens of sulphinpyrazone on platelet function ex vivo and blood chemistry in man.

When sulphinpyrazone (either 200 mg q.d.s. for 7 days or 400 mg b.d.s. for 5 days) was administered to human volunteers, inhibition of platelet function was observed ex vivo. The inhibitory effect was measured by the increase in the concentration of sodium arachidonate required to cause platelet aggregation and a decrease in the biosynthesis by the platelets of malondialdehyde from added sodium arachidonate. ADP-induced primary platelet aggregation was statistically significantly inhibited only on 1 day of the two studies. The inhibitory effect did not correlate with the plasma concentrations of unchanged sulphinpyrazone nor with its sulphone metabolite but correlated with the plasma concentration of the thioether metabolite (r = 0.577, p less than 0.001). Platelet count, plasma fibrinogen, beta-thromboglobulin, urea and creatinine concentrations were not changed by the drug but there was a clinically insignificant increase in bleeding time in all but one subject.

Bleeding Time↗
PubMed1980

Sulfinpyrazone: a review of its pharmacological properties and therapeutic use.

Sulfinpyrazone1 has long been recognised as a potent uricosuric agent, but has more recently been studied extensively as a platelet inhibitor and antithrombotic agent. It is active in man following oral administration and has been reported to be effective in reducing the incidence of transient ischaemic attacks, thromboembolism associated with vascular and cardiac prostheses, recurrent venous thrombosis, arteriovenous shunt thrombosis and sudden cardiac death following myocardial infarcton. Sulfinpyrazone has not been demonstrated to be effective in preventing or reducing the risk of stroke or death in patients with cerebrovascular disease with a recent history of cerebral or retinal ischaemioc attacks. The normal total dose of sulfinpyrazone as an antithrombotic agent is 800mg daily. The drug has been used continuously for up to 4 years with no serious adverse reactions or laboratory abnormalities. There has been no apparent diminution of effect with time. Sulfinpyrazone is not a substitute for conventional anticoagulant agents (e.g. the coumarin derivatives) in the treatment of venous thrombosis, but is an important drug for the treatment of conditions associated with arterial thrombosis and possibly for the prophylaxis of recurrent venous thrombosis.

Animals↗
PubMed1980

Inhibition of thrombocytopenic episodes caused by the Arthus reaction, the sub-lethal Forssman reaction and ADP.

Through the use of 51Cr-labelling about 50% of circulating platelets were shown to be permanently removed from the circulation subsequent to the Arthus reaction but not after the sub-lethal Forssman reaction or the repeated injection of ADP to guinea pigs. Oral administration of ticlopidine inhibited the transient thrombocytopenia caused by ADP. Cyclooxygenase inhibitors including sulphinpyrazone and its thioether metabolite inhibited the thrombocytopenia of the Arthus reaction but only sulphinpyrazone effectively inhibited the thrombocytopenia of the sub-lethal Forssman reaction.

Adenosine Diphosphate↗
PubMed1979

A modified non-radioisotope method for measurement of platelet production time.

Platelet production time (PPT), based on the measurement of malondialdehyde (MDA) production prior to and after the intake of acetylsalicylic acid (ASA), was determined in 20 healthy subjects. High MDA levels were produced by stimulating platelet lipid peroxidation with arachidonic acid, resulting in a reliable, sensitive and accurate technique. PPT correlated well with platelet survival time measured by 51Cr autologous labelled platelets when both methods were used simultaneously in the same patients. This modified non-radioisotope method might serve as a useful aid in the diagnosis of platelet disorders, thromboembolic diseases associated with increased platelet consumption and for the evaluation of drugs affecting platelet function.

Aspirin↗
PubMed1979

A study of the relationship between ex vivo and in vivo effects of sulphinpyrazone in the guinea pig.

In guinea pigs, sodium arachidonate-induced platelet aggregation ex vivo proved a more sensitive method for detecting drug-related effects after the administration of sulphinpyrazone than collagen-induced platelet aggregation. It was possible to detect inhibition of platelet aggregation after giving sulphinpyrazone orally in a single dose of 3 mg/kg. Excellent correlation was achieved between ex vivo and in vivo inhabition of platelet function with sulphinpyrozone using the Arthus reaction. The results are consistent with the formation, in the guinea pig of metabolites more potent than the parent molecule.

Administration, Oral↗
PubMed1978

The relationship between cyclic adenosine 3', 5' - monophosphate and biochemical events in rat skin after the induction of epidermal hyperplasia using hexadecane.

Sequential changes in skin metabolism have been studied in a model system of epidermal hyperplasia and hyperkeratinization induced by the application of n-hexadecane to shaved rat skin. The epidermal accumulation of glycogen typical of the hyperplastic response has been correlated with an increase in glycogenesis and a decrease in glycogenolysis. DNA synthesis was increased by 6 h after the start of hexadecane treatment and reached a maximum after one day. The concentration of skin cyclic AMP fell immediately after hexadecane application and subsequently rose to give a prolonged increase. Use of the combined topical application of hexadecane and the anti-inflammatory drugs triamcinolone acetonide, hydrocortisone and indomethacin showed that the hexadecane-induced changes in DNA synthesis and glycogen metabolism were linked to the initial fall in cyclic AMP concentration. The significance of the biphasic change in cyclic AMP levels is discussed as a possible system of control for the development and maintenance of hyperplasia.

Administration, Topical↗
PubMed1977

The binding of topically applied glucocorticoids to rat skin.

The epidermis of rat skin was shown to be the major site of accumulation of label after the topical application of [3H]-cortisol, [3H]-corticosterone and [3H]-triamcinolone acetonide. However, incubation of the skin in vitro in a way which ensured contact only between the dermal side of the skin and the steroid showed preferential accumulation of label from [3H]-cortisol and [3H]-corticosterone in the epidermis whereas label from [3H]-triamcinolone acetonide appeared evenly spread in the dermis and epidermis. The affinity of corticosterone to soluble proteins in skin homogenates was greater than that of cortisol as measured by displacement binding and correspondingly glucose uptake into the skin in vitro was inhibited for 18 hr after a single application of corticosterone but was not inhibited by cortisol.

Administration, Topical↗
PubMed1976

The existence of a glyconeogenic pathway in rat skin.

The existence of a glyconeogenic pathway in rat skin has been demonstrated by measurement of three of the key glyconeogenic enzymes, fructose 1,6-bisphosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase, and by studies on the incorporation in vitro of carbon from pyruvate and alanine into skin glycogen.

Alanine↗