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Biomedical subjects

W Paul

Publications and source records attributed to W Paul.

At least 109 records · Page 6Linked to original sources
PubMed1984

Synergistic interaction between prostaglandins and PAF-acether in experimental animals and man.

Platelet activating factor (PAF-acether) is released from a variety of inflammatory cell types and has properties appropriate to a mediator of allergy and inflammation. Here, we have examined the interaction between PAF-acether and the prostaglandins, PGE2 and ZK 36374 (a stable analogue of prostacyclin, PGI2) in the skin of guinea-pigs and human volunteers. PGE2 and ZK 36374 significantly potentiated increased plasma protein extravasation induced by PAF-acether in guinea-pigs, assessed by extravasation of I-125-HSA. In addition, PGE2 significantly potentiated the ability of PAF-acether to elicit acute wheal (volume) and flare responses in human skin. The inflammatory properties of PAF-acether should not be considered in isolation since this phospholipid interacts synergistically with prostaglandins which are recognised as modulators of inflammation.

Animals↗
PubMed1984

Inflammatory characteristics of platelet activating factor (PAF-acether) in human skin.

The phospholipid PAF-acether is released from a range of inflammatory cell types and, in experimental animals, has properties appropriate to a mediator of inflammation. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early weal and flare response was succeeded, in a proportion of subjects, by an area of late-onset erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time-course and dose-response relationship of the early response has been determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. PAF-acether should therefore be considered as a potential mediator of both acute and persisting inflammation in man.

Adult↗
PubMed1984

Platelet-activating factor: a possible mediator of the dual response to allergen?

Certain allergic asthmatic patients exhibit a dual response in the lung following bronchial challenge with the appropriate allergen. Often this is paralleled by a cutaneous dual response when the antigen is injected intradermally. The mechanisms underlying such phenomena are not established, but some evidence suggests that the late response is a consequence of the early response. Since platelet activation has been observed following antigen challenge in asthmatic subjects, we have studied the ability of platelet activating factor (PAF-acether, AGEPC) to induce cutaneous inflammatory responses in man. In a time course study over 24 hr, PAF-acether produced a biphasic response: an immediate weal and flare reaction, which resolved within 1-2 hr and was followed some 3-6 hr later by a delayed reaction in which erythema associated with hyperalgesia was evident. These observations suggest that PAF-acether should be considered in the context of allergic asthma as a possible mediator of the dual response to allergen.

Adult↗
PubMed1984

Platelets and bronchospasm.

The intrathoracic accumulation of radiolabelled platelets and concomitant changes in airway resistance have been recorded continuously in anaesthetised guinea pigs. Platelet-activating factor (PAF-acether) and antigen (in sensitised animals) elicited dose-related intrathoracic accumulation of platelets that could be associated with an increase in airway resistance. Maximal increases in airway resistance preceded maximal increases in platelet accumulation. Low doses of antigen could elicit substantial platelet accumulation, without detectable changes in lung function. It is concluded that physical obstruction of the pulmonary vasculature is not the sole determinant of platelet-dependent bronchoconstriction.

Airway Resistance↗
PubMed1984

Beta-adrenoceptor agonist responses in the skin and lungs of asthmatic subjects.

Concomitant intradermal injection of salbutamol inhibits histamine-induced weal volume in the skin of atopic asthmatic subjects and the degree of this inhibition (index of beta-adrenergic effect in the skin) correlates with the bronchodilator effect of inhaled salbutamol in the same subjects (index of beta-adrenergic effect in the lung).

Adrenergic beta-Agonists↗
PubMed1984

PAF-acether-induced plasma exudation in rat skin is independent of platelets and neutrophils.

The ability of Paf-acether to induce increased plasma protein extravasation (IPPE) was assessed in the skin of rats by measuring extravasation of 125I-bovine serum albumin. Paf-acether elicited dose-dependent IPPE with a threshold of 0.04 pmol and a maximum at 4.5 nmol, with an effective concentration (EC50) of 23 pmol. The EC50 of the 1-0-ester Paf-acether analog was 1.5 nmol whereas 2-lyso Paf-acether was ineffective in inducing IPPE. Serotonin and histamine were respectively 100 and 1,00-fold less potent than Paf-acether. High doses of Paf-acether also resulted in a dose related accumulation of III-indium oxine labeled platelets. Ultrastructural and radioisotopic studies showed that Paf-acether-induced IPPE was not dependent upon platelet accumulation. In addition, platelet release products were ruled out in this phenomenon, since a "cocktail" of indomethacin, methysergide and pyrilamine-maleate failed to significantly reduce Paf-acether-induced IPPE. Neutrophils were not involved in Paf-acether -induced IPPE since nitrogen mustard-treated animals presented with IPPE not significantly different from controls. Finally, the specificity of Paf-acether on IPPE formation was demonstrated by its complete prevention by prior intravenous injection of Paf-acether (6 ug/kg), but not of Paf-acether analogs, histamine or serotonin.

Animals↗
PubMed1983

A comparative study of PGI2 and two analogues (FCE 21292 and FCE 21258) in vitro and in vivo.

Two analogues of PGI2, FCE 21258 (5E-13,14-didehydro-carboprostacyclin) and FCE 21292 (5E-13,14-didehydro-20-methyl-carboprostacyclin) have been evaluated in comparison with PGI2 in different in vitro and in vivo screening tests. The rank order of potency was PGI2 greater than FCE 21292 greater than FCE 21258 in the following tests: potentiation of bradykinin-induced increased plasma protein extravasation in the guinea pig skin, inhibition of guinea pig platelet aggregation in vivo where the duration of action of FCE 21292 was longer than that of PGI2, lowering of mean systemic arterial pressure in conscious normotensive and spontaneously hypertensive rats and inhibition of rabbit platelet aggregation in vitro. In the relaxation of bovine coronary artery in vitro the rank order of potency was FCE 21292 greater than PGI2 greater than FCE 21258.

Animals↗
PubMed1983

Inflammatory actions of platelet activating factor (Pafacether) in guinea-pig skin.

Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pigs by means of radioisotopic marker techniques. Intradermal injection of Paf-acether elicited increased plasma protein extravasation (IPPE) (0.2-200 pmol/site), platelet accumulation (PA) (20-200 pmol/site) and red blood cell accumulation (RBCA) (200 pmol/site), whereas lyso-Paf (up to 2 nmol/site) was inactive in all these respects. Following intradermal injection, the IPPE responses to Paf-acether (2 and 20 pmol/site) were complete within 15 and 30 min respectively, although in response to 200 pmol/site, IPPE was detectable up to 1.5 h. The PA and RBCA responses to Paf-acether (200 pmol/site) were complete within 1 h. IPPE induced by Paf-acether (3 pmol/site) was potentiated by concomitant intradermal injection of a cutaneous vasodilator prostaglandin E2 (PGE2, 1 nmol/site) and inhibited by the beta-adrenoceptor agonist, isoprenaline (4.5 nmol/site) or the alpha-adrenoceptor agonist, phenylephrine (6 nmol/site). Such observations are consistent with Paf-acether effecting increased vessel wall permeability. Intradermal injection of PGE1 (3 nmol/site) significantly reduced PA in response to Paf-acether (200 pmol/site), whilst significantly enhancing IPPE. This dissociation of increased vascular permeability from PA is consistent with Paf-acether eliciting IPPE via a platelet-independent mechanism. These results indicate that a direct effect on vessel wall permeability contributes to the inflammatory response to Paf-acether in guinea-pig skin. It is suggested that Paf-acether is a potential mediator of allergy and inflammation.

Alprostadil↗
PubMed1983

Comparative study on the distribution of alpha- and gamma-hexachlorocyclohexane in the rat with particular reference to the problem of isomerization.

Blood levels and tissue distributions of alpha-, beta-, gamma- and delta-hexachlorocyclohexane (HCH) were studied following oral administration of alpha-HCH and gamma-HCH to rats. Following administration of alpha-HCH, there was no evidence of beta-HCH, gamma-HCH or delta-HCH, nor could transformation into alpha-HCH, beta-HCH or delta-HCH be detected after exposure to gamma-HCH. After eight weeks of administration, tissue retention of alpha-HCH was 10-20 times greater than that of gamma-HCH. gamma-HCH was eliminated to a much greater extent than alpha-HCH from the tissues, and in particular from fatty tissue. alpha-HCH accumulated in fat and brain, while gamma-HCH showed very low affinity for lipid.

Animals↗
PubMed1982

An in vivo model for studying platelet aggregation and disaggregation.

A simple minimally invasive technique has been developed for the continuous monitoring of 111-Indium labelled homologous platelets in the thoracic (C1) and abdominal (C2) regions of experimental animals. The effects of the aggregatory agents adenosine diphosphate (ADP), collagen and platelet activating factor (PAF) and the anti-aggregatory agent, prostacyclin (PGI2) have been studied in the guinea-pig. Administration of ADP, collagen or PAF produces an increase in counts in C1, a decrease in counts in C2, and hence an increase in the ratio C1/C2. The rise in C1/C2 is more protracted after collagen administration than after ADP or PAF. PGI2 (50-500 ng/kg) reduces the response to ADP. The present technique is both simple, reproducible and although the present experiments are in the presence of heparin, the technique remains functional in the presence of minimal heparin, thus making it a suitable method for studies of platelet function and the evaluation of anti-aggregatory agents in vivo.

Abdomen↗
PubMed1982

Evidence in man of synergistic interaction between putative mediators of acute inflammation and asthma.

The two-component hypothesis of acute inflammation postulates that the acute inflammatory response depends on both increased local blood flow and increased microvascular permeability: the validity of this concept has previously been established in animals and was tested here in man. A mixture of the mediators prostaglandin E2 and bradykinin produces a larger cutaneous wheal (volume) response than can be accounted for either by summation of the responses to the individual substances or by the slopes of their dose-response curves. This enhanced response is inhibited by noradrenaline (consistent with the vasoconstrictor property of noradrenaline) and by salbutamol (consistent with the anti-permeability property of salbutamol). These observations indicate that the two-component hypothesis of acute inflammation applies to man as well as animals; this finding is important in the evaluation of the role of putative mediators in the pathogenesis of asthma and other diseases in which inflammation plays a part.

Acute Disease↗