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P Vadas

Publications and source records attributed to P Vadas.

84 records · Page 5Linked to original sources
PubMed1983

Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock.

This study examined the role of plasma phospholipase A2 (PLA2) in the mediation of the hypotension associated with experimental endotoxin shock in rabbits. Endotoxin shock was induced in rabbits, and mean arterial blood pressure and plasma PLA2 levels were monitored. Serial plasma PLA2 determinations over 5 h showed an 11-fold increase in circulating enzyme activity, and the rise in circulating enzyme activity was directly related to the fall in mean arterial blood pressure. Pretreatment of rabbits with glucocorticoids abrogated the hypotensive effect of endotoxin, and also inhibited a rise in plasma PLA2 activity. To determine if the rise in PLA2 activity was simply a mechanistically unrelated epiphenomenon, the effect of infusion of exogenous PLA2 (purified from the blood of rabbits in endotoxin shock) was investigated. Infusion of the exogenous enzyme into normal rabbits caused a fall in mean arterial blood pressure, and the rate of fall of blood pressure paralleled that induced by endotoxin itself. Treatment of the PLA2-active fraction, prior to infusion with the PLA2 inhibitor, p-bromophenacyl bromide, protected against this hypotensive effect. These data are consistent with the postulate that the endotoxin-induced release of massive amounts of PLA2 into the systemic circulation in rabbits contributes significantly to the hypotension associated with septic shock.

Animals↗
PubMed1982

The efficacy of anti-inflammatory agents with respect to extracellular phospholipase A2 activity.

The effects of steroidal and non-steroidal anti-inflammatory agents on extracellular phospholipase A2 (PLA2) activity were investigated. Enzyme release was inhibited by 5 x 10(-8) M dexamethasone but not by indomethacin, whereas the soluble extracellular enzyme was inactivated by mepacrine but not by dexamethasone or indomethacin. PLA2, released into the interstitium by activated macrophages is both pro-inflammatory and vasoactive. The anti-inflammatory efficacy of steroidal and non-steroidal drugs may partially reside in their ability to inhibit the release of PLA2, or inactivate preformed extracellular PLA2 in chronically inflamed sites.

Animals↗
PubMed1982

The appearance and significance of phospholipase A2 in lymph draining tuberculin reactions.

Popliteal and prefemoral lymphatics of sheep were cannulated, and lymph was collected before and during the course of responses to PPD and concanavalin A. Hyperemia-inducing activity (HIA) and phospholipase A2 (PLA2) were released into lymph in response to antigenic stimulation, whereas lymph plasma draining unstimulated lymph nodes had consistently little or no detectable HIA and PLA2 activity. HIA appeared in the lymph efferent to the stimulated node at a time when blood flow to the responding node was enhanced. While the appearance of HIA did not directly correlate with changes in lymphocyte output, lymph protein concentration, or lymph flow rates, there was, however, a statistically significant correlation between HIA and PLA2 levels in lymph plasma, suggesting that extracellular PLA2 may contribute to the vasoactivity in lymph and thereby modulate blood flow to areas of antigenic stimulation. Vasoactive lymph, injected into rabbits, induced hyperemia via an indomethacin-sensitive pathway, since the induction of hyperemia was abrogated by pretreatment of injection sites with indomethacin. The extracellular release of PLA2 in response to inflammatory stimuli may represent an amplification mechanism for the generation of high levels of prostaglandins found in lymph draining stimulated nodes.

Animals↗
PubMed1982

The production of plasminogen activator by afferent but not efferent lymph cells emigrating from chronic granulomatous lesions in sheep.

Subcutaneous granulomas were induced in sheep by injecting Freund's adjuvant. At varying times thereafter afferent and efferent lymphatics draining the granulomas were cannulated. Lymph was collected for periods up to several days or weeks from either normal skin or from inflammatory lesions 15 to 120 days after the initiation of the lesions. The fibrinolytic activity of cells and cell culture medium in which cells were grown was assayed by using 125I-fibrin plates. No detectable enzyme activity was found from normal afferent, normal efferent, or stimulated efferent lymph cells. Afferent granuloma cells produced a plasminogen-dependent, DFP inhibitable protease activity that was dependent on the cell concentration and the incubation time. Results of cell separation techniques such as sedimentation velocity, adherence on fibrin plates, and Sephadex G-10 fractionation showed that the large, macrophage-like cell population in afferent lymph was secreting the plasminogen activator. The lymph cells collected from lesions 1 to 2-mo-old were more active than an equivalent number of cells collected from earlier or later lesions. When tuberculin was injected directly into lesions the lymph cells that appeared in the subsequent 1 to 2 days produced more enzyme per cell. The relationship between plasminogen activator and other possible mediators that appear in either the cells or plasma of afferent lymph is discussed.

Animals↗
PubMed1980

Secretion of a hyperemia-inducing moiety by mitogen or glycogen stimulated mononuclear inflammatory cells of sheep and rabbit.

A nonlymphokine mediator of hyperemia has been shown to be secreted by both rabbit peritoneal exudate cells stimulated with 5% glycogen and by concanavalin A treated cells from afferent lymph of sheep. This mediator is not stored in an active form in cells, but is either activated or synthesized de novo in response to antigenic or mitogenic stimuli. Secretion of the mediator is inhibited by culturing cells in the presence of dexamethasone but not indomethacin. However, expression of the activity is inhibited by pretreatment of the assay animals with indomethacin, suggesting a two-step induction of hyperemia. A similar mediator was found to be secreted by sheep and rabbit alveolar lavage cells, and rat peritoneal exudate cells. The presence of this hyperemia-inducing activity from diverse species suggests a fundamental role in controlling blood flow. Alteration of blood flow may modulate delivery of blood-borne cells and factors to sites of chronic inflammation.

Animals↗
PubMedDate not supplied

Measurement of blood flow and vascular permeability changes in response to 12-O-tetradecanoyl-phorbol-13-acetate and to asbestos fibers.

The hyperemia (increased blood flow) and vascular permeability changes induced in rabbit skin by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate and by asbestos fibers have been quantitated. The resultant hyperemia, measured with radiolabeled microspheres, was inhibited in both cases by steroidal and nonsteroidal anti-inflammatory drugs. Since the inflammatory responses resulting from exposure to these agents might be important for the subsequent development of neoplasms, it is proposed that such a specific and quantitative technique be used to analyze the components of these inflammatory responses in more detail.

Administration, Topical↗