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Biomedical subjects

P A Coppo

Publications and source records attributed to P A Coppo.

5 recordsLinked to original sources
PubMed1988

Inhibition of granulocyte function by steroids is not limited to corticoids. Studies with sex steroids.

Noting that corticosteroid doses required for protection in shock models exceeded those required to saturate glucocorticoid receptors in mammalian cells, we postulated a nonspecific physicochemical effect of steroids upon the cell membrane, and therefore tested three noncorticoid steroids for their effects on granulocyte function. All three (conjugated equine estrogen, a synthetic progestogen, and a synthetic androgen) behaved in manner analogous to corticoids at similar concentrations, inhibiting granulocyte aggregation, chemotaxis, and chemiluminescence, as well as binding to the granulocytes of the synthetic oligopeptide agonist f-Met-Leu-Phe. Estrogen was further shown to reduce granulocyte membrane fluidity, assessed by electron paramagnetic resonance. We propose that the unique effects of extremely high-dose corticosteroids are not mediated via the glucocorticoid receptor, but result rather from physicochemical effects of the drugs upon the membranes of effector cells.

Adrenal Cortex Hormones↗
PubMed1983

Complement activation by trichophyton rubrum.

The role of complement in infections by dermatophytes is unknown. Therefore we evaluated the ability of the dermatophyte Trichophyton rubrum to activate complement in vitro. Aliquots of human plasma that had been incubated with T. rubrum were examined for evidence of complement activation. Following incubation, the total hemolytic complement activity of plasma fell 76%. Further, each T. rubrum incubation led to obvious C3 conversion and generation of polymorphonuclear leukocyte (PMN) aggregating activity. Plasma that had complement activity depleted by heat (56 degrees C x 30 min) or 10 mM EDTA failed to develop C3 conversion or PMN aggregating activity. Complement activation was not affected when the classical complement pathway was selectively blocked by MgEGTA. These studies indicate that T. rubrum can activate the complement system by the alternative pathway. The consequent generation of anaphylatoxins, chemotaxins, and opsonins might be important both in host defense against dermatophytic infections and in the inflammatory reactions mediated by them.

Animals↗
PubMed1982

Anisodamine inhibits thromboxane synthesis, granulocyte aggregation, and platelet aggregation. A possible mechanism for its efficacy in bacteremic shock.

Anisodamine hydrochloride is a vasoactive drug produced in the People's Republic of China that appears efficacious in clinical and experimental bacteremic shock, and about whose mode of action little is known. Suspecting that the drug might work by inhibition of platelet or granulocyte aggregation, or both, we tested it in these systems. Anisodamine proved a modest inhibitor of granulocyte aggregation and a powerful inhibitor of platelet aggregation; thromboxane synthesis was inhibited in anisodamine-treated platelets, further suggesting that the biochemical mode of action might be inhibition of cyclo-oxygenase or thromboxane synthetase.

Animals↗
PubMed1982

Synergy among agents inhibiting granulocyte aggregation.

Recent evidence suggests complement (C) -stimulated granulocytes (PMNs) are important in a variety of diseases, including shock and myocardial infarction (MI). Corticosteroids inhibit PMN response to C and show promise in some studies of shock and MI, but their use has not become routine for several reasons. Synergy was sought among agents inhibiting PMN aggregation in vitro in response to activated C: methylprednisolone (MP), with a 50% inhibitory dose (AD50) of 0.6 mg/ml; ibuprofen (IBU), with AD50 of 1.0 mg/ml, and betahistine (BH), with AD50 of 1.6 mg/ml. Simultaneous use of all three agents produced 3.4-fold synergy; 3-fold synergy obtained between IBU + MP and IBU + BH, while 1.5-fold synergy was noted between MP + BH. Further, MP and IBU were at least additive in inhibiting .O2- generation by FMLP-stimulated PMNs and in blocking directed migration. In a preliminary in vivo test of this finding, cats were given MP and IBU--in known individually ineffective doses--immediately prior to coronary artery ligation. Neither MP nor the low dose of IBU chosen limited the size of the resultant MI, while both agents together reduced MI size by 42%. Synergy among these agents suggests that they inhibit PMN function of distinct cellular mechanisms (as yet not elucidated). Further, early in vivo results encourage speculation that such synergy might ultimately be exploited clinically, although such speculation must presently be regarded as preliminary.

Betahistine↗