Site of anti-inflammatory action of dexamethasone in rabbit skin.

Systemic pretreatment of rabbits with dexamethasone results in a time-dependent inhibition of oedema responses caused by intradermal injection of both 'direct-acting' and 'neutrophil-dependent' stimuli. Local injection of actinomycin D, an inhibitor of RNA synthesis, inhibits this effect. Our studies suggest that a major action of dexamethasone in this model may be a local inhibition of increased permeability of the vascular endothelium.

Characterization of Gaddum's substance R.

1. When the isolated small intestine of the rat is perfused via the mesenteric artery, an oxytocic principle (Gaddum's substance R) is released which is detectable in the perfusate after 30 min and is present in samples collected 8 h later. 2.

Circulating autoantibodies to recombinant lipocortin-1 in asthma.

One of the postulated mechanisms of corticosteroid action is through the de novo synthesis and release of lipocortins. We assayed circulating antibodies to lipocortin-1 in sera obtained from normal (n = 67) and asthmatic (n = 57) subjects using an ELISA technique. Asthmatic subjects with a wide range of severity, with the mildest needing only occasional inhaled beta-agonist therapy to the most severe needing maintenance oral corticosteroid treatment, were recruited from our Asthma Clinic and classified into five categories according to the need of therapy.

Antipyretic actions of human recombinant lipocortin-1.

The effect of human recombinant lipocortin-1 (hrLC-1) on the pyrogenic actions of the synthetic polyribonucleotide polyinosinic:polycytidylic acid (poly I:C) has been studied in conscious rabbits. Poly I:C (2.5 micrograms kg-1) given i.

The presence of autoantibody to recombinant lipocortin-I in patients with psoriasis and psoriatic arthritis.

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kDa protein, lipocortin-I. Anti-lipocortin-I antibodies (ALA) were measured by enzyme-linked immunosorbent assay (ELISA) in 23 patients with plaque-type psoriasis alone (NAP), in 21 patients with psoriasis and arthritis (PA), and in 67 healthy controls. Only two of 23 NAP patients had elevated ALA, whereas six of 21 PA patients had raised levels of ALA (P = 0.

The detection of lipocortins 1, 2 and 5 in central nervous system tissues from Lewis rats with acute experimental allergic encephalomyelitis.

The calcium and phospholipid-binding proteins lipocortins 1, 2 and 5 have been detected, by electrotransfer and immunoblotting techniques, in central nervous system (CNS) tissues of control Lewis rats and animals with experimental allergic encephalomyelitis (EAE). The cerebellum and spinal cord content of lipocortins 2 and 5 remained unchanged throughout the development of EAE but the amounts of the steroid-inducible protein lipocortin 1 increased in samples from pre-diseased and adjuvant-treated rats and were further enhanced in tissues from clinically sick and convalescent animals. The significance of these findings is discussed in conjunction with the ongoing changes in pathology which occur during the progression of EAE.

An assay for the assessment of lipocortin 1 levels in human lung lavage fluid.

The physiological function of the lipocortins, proteins which are thought to be glucocorticoid-regulated, is unclear. An improved assay for lipocortins might help to elucidate their role. A rapid and specific sandwich enzyme-linked immunosorbent assay (ELISA) for lipocortin 1 with a working range of 1-2000 ng/ml and an interrun coefficient of variation of less than 10% is described and used in this pilot study to quantify human lipocortin 1 for the first time in acellular bronchoalveolar lavage fluid (BALF), and in media conditioned by BAL cells, from control patients and those with pulmonary sarcoidosis.

Anti-inflammatory lipocortin 1 production by peripheral blood leucocytes in response to hydrocortisone.

The presence and amount of the anti-inflammatory protein lipocortin 1 was determined in plasma and peripheral blood leucocytes by a highly specific, enzyme-linked immunosorbent assay. Within 120 min of a single intravenous dose of 100 mg hydrocortisone, the intracellular concentrations of lipocortin 1 in peripheral monocytes in 7 of 8 healthy men increased by a median of 225% (range 129-507%) compared with pretreatment levels, and mononuclear cell-surface lipocortin increased by a median of 224% (range 76-483%). Placebo injections had no effect.

An image processing approach to characterizing choroidal blood flow.

Indocyanine green (ICG) dye angiography has made possible routine visualization of choroidal blood flow in the human eye; however, to date, its clinical utility has been limited. An overlying layer of densely pigmented tissue and the complex, multilayered vascular structure of the choroid combine to produce angiographic images of low contrast which are difficult to interpret. Conventional image processing can enhance individual images of the blood vessels, but this approach contributes no information about the dynamics of blood flow.

Detection of lipocortin 1 in human lung lavage fluid: lipocortin degradation as a possible proteolytic mechanism in the control of inflammatory mediators and inflammation.

Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 (Lc 1; 37 kDa), in human lung lavage supernatants. In lavage fluid from healthy volunteers, a higher percentage (greater than 70%) of the detected Lc 1 was in its native form, compared to that from patients with abnormal lungs.

Perinatal ocular physiology and ROP in the experimental animal model.

In order to overcome the scarcity of premature human ocular tissues and the enormous obstacles to direct examination of immature human ocular vasculatures, a number of animal models have been employed by investigators in order to study various aspects of ROP. A variety of factors may influence selection of the particular model used, but ultimately it is the faithfulness with which the model mimics human ROP that is most important. The validity of the models has been and remains a controversial subject, but evidence appears strong in favor of the beagle puppy model for studying physiology of the ocular vasculatures during perinatal development.

Pulsatile flow in the choroidal circulation: a preliminary investigation.

A preliminary investigation has been made of choroidal blood flow using a computer-aided image analysis approach to interpretation of indocyanine green (ICG) dye choroidal angiograms. The goal of the study was to characterise blood flow through the choroidal arteries vs. choroidal capillaries and veins.

Lipocortin.

In this short article the author has attempted to review some of the areas of lipocortin research which are currently of interest. The area has become an extraordinary complex one with many conflicting claims in the literature, on the other hand there are enough interesting leads in the work that has already been done to encourage further research into this fascinating family of membrane-based regulatory molecules.

Autoantibodies to recombinant lipocortin-1 in rheumatoid arthritis and systemic lupus erythematosus.

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kD protein, lipocortin-1. Autoantibodies to lipocortin-1 were measured by enzyme linked immunosorbent assay (ELISA) in 90 healthy subjects and in 63 patients with rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE), 26 with polymyalgia rheumatica, and 13 with chronic airways disease. Sixteen patients with RA receiving prolonged, high steroid doses (prednisolone greater than 7.

A study of phospholipase A2-induced oedema in rat paw.

The inflammaogenic action of four extracellular phospholipases A2 was tested in the rat paw oedema model. Subplantar injection of microgram amounts of the venom phospholipases A2 from Vipera russeli, Naja mocambique mocambique and honey bee, or the porcine enzyme produced a rapid but transient oedematous response. The venom enzyme from Vipera was the most potent in this respect, the pancreatic enzyme the least.

Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test.

Human recombinant lipocortin 1 has been tested for anti-inflammatory activity in a conventional model of acute inflammation. Microgram amounts of the protein, locally administered, inhibited edema of the rat paw when induced by subplantar injections of carrageenin: the ED50 was 10-20 micrograms per paw, and inhibition (maximum of 60-70%) was not dependent upon an intact adrenal cortex. Doses of lipocortin that produced approximately 50% inhibition in the carrageenin test were inactive against edema elicited by bradykinin, serotonin, platelet-activating factor-acether, or dextran, whereas edema caused by Naja mocambique venom phospholipase A2 was strongly inhibited by lipocortin.

The effects of the anti-glucocorticoid RU 38486 on steroid-mediated suppression of experimental allergic encephalomyelitis (EAE) in the Lewis rat.

Lewis rats, sensitised for the autoimmune condition EAE received a range of doses of the steroid dexamethasone at various times post-inoculation in an attempt to modify the clinical course of the disease. Depending upon the dosing regime employed microgram quantities of the steroid were sufficient to significantly inhibit the clinical development of EAE and milligram doses of the drug completely suppressed the emergence of disease. Administration of the potent anti-glucocorticoid RU38486 to sensitised animals intensified the clinical course of EAE and reversed the steroid-induced inhibition of the disease.