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Biomedical subjects

M A Bray

Publications and source records attributed to M A Bray.

At least 37 records · Page 2Linked to original sources
PubMed1987

Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis.

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhibitors concurrently with the antibiotic.

Ampicillin↗
PubMed1984

Leukotrienes reduce nociceptive responses to bradykinin.

The biotransformation of arachidonic acid leads to two important groups of inflammatory mediators, the leukotrienes and the prostaglandins. Hyperalgesic effects have been demonstrated for prostaglandins in a variety of animal models but the effects of leukotrienes on inflammatory pain are less well documented. Using the isolated rabbit ear model of algesia we have shown that perfusion of the ear with the leukotrienes B4, C4 and D4 (10(-8)-10(-7) M) causes a reversible, dose- and time-dependent reduction of the reflex fall in systemic blood pressure and the "head flick" response induced by injection of bradykinin (400 ng), without affecting similar responses induced by the neurotransmitter acetylcholine. The antagonistic effect of leukotrienes on the algesic action of bradykinin could be reversed by the leukotriene antagonist FPL55712 (2 micrograms/ml). This result implies that the leukotrienes may have a desensitizing effect on the nociceptor during an inflammatory response in contrast to the pain threshold-lowering action of the E- and I-type prostaglandins.

Acetylcholine↗
PubMed1984

Retinoids are potent inhibitors of the generation of rat leukocyte leukotriene B4-like activity in vitro.

Several retinoids (tretinoin, retinol, retinal, retinyl acetate, etretinate and RO 10-1670) were tested in vitro for their ability to inhibit the generation of the leukocyte chemotactic factor leukotriene B4 (LTB4) from calcium ionophore-stimulated rat PMN in vitro. LTB4 activity was measured in vitro via bioassay using rat PMN aggregation and chemokinesis. Tretinoin, retinol, RO 10-1670 and retinal were active inhibitors of LTB4 generation with ID50S (microM) of 0.55-1.5, 5.9-6.5, 4.8-5.9 and 19-28.4 respectively whilst retinyl acetate and etretinate were inactive. Inhibition of the generation of LTB4 by tretinoin was confirmed by reverse phase-high pressure liquid chromatography. These results are discussed in the context of retinoid treatment of skin diseases such as psoriasis where inhibition of neutrophil accumulation during retinoid treatment has been reported.

Animals↗
PubMed1983

The effect of parasitization by Leishmania mexicana mexicana on macrophage function in vitro.

Macrophages infected with amastigotes of Leishmania mexicana mexicana as compared to normal macrophages show decreased migration both randomly and through a 5 microns pore in response to a known chemotaxin, an increased ability to pinocytose and an increased bactericidal ability. Unless very heavily parasitized their ability to phagocytose is unaltered. Parasitized macrophages are unaltered in their ability to secrete extracellularly lysosomal enzymes, prostaglandins and lysozyme in response to known stimuli, or to kill target cells in an antibody dependent cell mediated cytotoxicity assay.

Animals↗
PubMed1982

Neutrophil aggregating and chemokinetic properties of a 5,12,20-trihydroxy-6,8,10,14-eicosatetraenoic acid isolated from human leukocytes.

Suspensions of human peripheral blood leukocytes were incubated with arachidonic acid and calcium ionophore A23187. Acidic lipid extracts were purified by silicic acid chromatography and reversed phase high performance liquid chromatography. A polar metabolite with an ultraviolet absorption spectrum identical to that of leukotriene B4 was identified by gas chromatography and mass spectrometry as a 5,12,20-trihydroxy-6,8,10,14-eicosatetraenoic acid. The data indicated that this compound was the 20-hydroxy metabolite of leukotriene B4. The compound showed chemokinetic activity towards human polymorphonuclear leukocytes and aggregating activity towards rat peritoneal polymorphonuclear leukocytes. Its activity was greater than that of 5-hydroxy-6,8,11,14-eicosatetraenoic acid but less than that of leukotriene B4. It is concluded that the 15,12,20-trihydroxyeicosatetraenoic acid may play a role as a mediator of inflammatory reactions.

Calcimycin↗
PubMed1982

Leukotriene B4: an inflammatory mediator with vascular actions in vivo.

Leukotriene B4 (LTB4) is a 5, 12-dihydroxy derivative of arachidonic acid generated by a variety of inflammatory cells via the lipoxygenase enzyme system. In vitro leukotriene B4 is a potent chemotactic and aggregatory agent; enhances neutrophil complement receptors; stimulates membrane calcium changes and causes contraction of lung parenchyma. In vivo LTB4 is a potent stimulator of vascular permeability in rats, rabbits, guinea-pigs and man particularly in the presence of a vasodilator such as PGE2. LTB4 causes a profound transient neutropenia and massive accumulation of neutrophils when injected into the dermis (rabbit and man), skin chambers (rabbit and man) or body cavities (guinea-pig, rat).

Animals↗
PubMed1981

Aggregation of polymorphonuclear leucocytes (PMNs) by leukotriene B4: effects of cyclooxygenase products and metabolic inhibitors.

Leukotriene B4 isomer III (LTB4) stimulates the aggregation of rat PMNs in vitro. The effects of deoxyglucose, iodoacetate, dinitrophenol, cyclohexamide, colchicine, prostaglandins and thromboxane B2 (TXB2) on aggregation were examined. The results demonstrate that, first, aggregation is an active process, the energy being supplied by glycolysis and not mitochondrial respiration. The response can be elicited in the absence of extracellular glucose. Synthesis of protein does not occur during aggregation. An intact microtubular system is required for the expression of a full aggregation response. Prostaglandins E1, E2, F2 alpha and TXB2, products of the cyclooxygenase pathway of arachidonic acid metabolism, partially inhibit LTB-4 induced aggregation by a mechanism which has not yet been elucidated. The prostaglandins and TXB2 themselves do not promote aggregation.

Alprostadil↗
PubMed1981

Leukotriene B4: an inflammatory mediator in vivo.

Leukotriene B4 (LTB4 isomer III), which promotes the movement and aggregation of leucocytes in vitro also stimulates the chemo-attraction of leucocytes and their adherence to vascular endothelium in vivo. These effects were observed directly in the hamster cheek pouch preparation and on histological examination of sections from the rabbit mesentery. Intravenous injection of LTB4 (isomer III) into the rabbit resulted in a profound but transient neutropenia. Intradermal injection of LTB4 (isomer III) in the rabbit produced a rapid accumulation of neutrophils and this effect was also observed in skin chambers applied over abrasions on the rabbit back or the human forearm.

Animals↗
PubMed1981

Isomers of leukotriene B4 possess different biological potencies.

Rat elicited polymorphonuclear leucocytes (PMNs), when exposed to the ionophore A23187, release three isomers of leukotriene B4. The three isomers have been purified and tested for their ability to induce the chemokinesis of human PMNs in vitro, the aggregation of rat PMNs in vitro and changes in vascular permeability in rabbit skin in vivo in the presence of PGE2. The results demonstrate that all three isomers are biologically active and that the enzymatically produced isomer, in which the conjugated triene contains one cis and two trans double bonds, is more potent than the two diastereoisomers of LTB4 which contain all trans double bonds in the conjugated triene and which are produced by non-enzymatic hydrolysis.

Animals↗
PubMed1981

Prostaglandin generation by separated human blood mononuclear cell fractions.

Prostaglandins (PGs) have been widely implicated as modulators of immuno-inflammatory reactions. The cellular source of such immunoregulatory PGs has generally been thought to be the macrophage/monocyte, however several workers have suggested that adherent T-lymphocytes may be involved. We have attempted to resolve this question and have assayed PGE2 and thromboxane B2 release by purified sub-populations of human blood lymphocytes. Separated lymphocyte populations produce little PGEs when compared to monocytes and we concluded that the levels of PGs generated could be explained by monocyte contamination. In conclusion, we feel that the monocyte/macrophage acts as the source of immunoregulatory prostaglandins.

Cell Adhesion↗
PubMed1981

Leukotriene B4: a mediator of vascular permeability.

1 Intradermal injection of leukotriene B4 (LTB4) or prostaglandin E2 (PGE2), 1 to 100 ng per skin site produced little or no change in plasma exudation in the rabbit, guinea-pig and rat. 2 Intradermal injection of LTB4 or PGE2 together with bradykinin (500 ng) resulted in a significant potentiation of the plasma exudation produced by bradykinin alone in the rabbit and guinea-pig. 4 LTB4 (1 to 10 ng) had no effect on blood flow in the rabbit skin, in contrast to PGE2 which was a potent vasodilator in this species. 5 It is concluded that LTB4 is a mediator of vascular permeability and that this effect can only be observed in the presence of a vasodilator such as PGE2.

Animals↗