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D A Willoughby

Publications and source records attributed to D A Willoughby.

At least 19 recordsLinked to original sources
PubMed1979

Potassium permanganate induced calcergy: a model to study the effects of drugs on hydroxyapatite crystal deposition.

Hydroxyapatite crystal deposition is thought to play a role in the inflammatory episodes of osteoarthritis. A plaque of hydroxyapatite crystals was produced by local subcutaneous injection of a potassium permanganate solution. Transmission electron microscopy with X-ray energy spectroscopy was used to identify the crystal deposits as hydroxyapatite. The effects of dexamethasone, indomethacin, ethane 1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diposphonate (Cl2MDP) on the development of the apatite plaque was studied. EHDP strongly inhibited the apatite deposition. Cl2MDP slowed the natural resorption of the apatite plaque. Dexamethasone and indomethacin failed to affect the crystal deposition process. The results suggest that EHDP could inhibit crystal deposition in the osteoarthritic joint and that Cl2MDP might have a role in slowing apatite crystal shedding from osteoarthritic cartilage and so reduce the synovitis seen in Osteoarthritis.

Animals↗
PubMed1979

The role of kallikrein in leukocyte migration inhibition.

Previous studies from this department have established the presence of leukocyte migration inhibition activity in acute nonimmune inflammatory rat pleural exudates, induced by different irritants, which involved coagulation phenomenon. In the present investigation we present evidence for a role of kallikrein in the leukocyte migration inhibition phenomenon exhibited by acute pleural exudate in rates depleted of kininogens by intravenous injection of cellulose sulfate.

Animals↗
PubMed1979

Leukocyte migration inhibition activity of nonimmune acute inflammatory pleural exudate.

Material with leuckocyte migration inhibition (LMI) activity has been demonstrated in various types of nonimmunologically induced acute pleural inflammatory exudates. This activity is present in inflammatory cell-free exudate and appears to involved the deposition of fibrin around the migrating leukocyte, resulting in "cell-trapping." This is supported by the fact that removal or inhibition of fibrin formation leads to loss of exudate LMI activity. Both fibrinogen and complement as well as vitamin K-dependent clotting factors appear to be required for LMI activity. The mechanism involved in the LMI reaction and its significance in nonimmune and cell-mediated immune inflammation are discussed.

Animals↗
PubMed1979

A comparison of coumarin and levamisole on parameters of the inflammatory response.

Three experimental animal models have been used in the studies on the stimulatory effect of coumarin and levamisole. Both coumarin and levamisole increases cell coverage on subcutaneous implanted glass coverslip in mice. An increase in intracellular phosphatase activity was also observed. Stimulated mouse peritoneal cells when treated in vivo with coumarin or levamisole and then cultured in vitro showed increases acid phosphatase secretion (both extracellular and intracellular) as compared to control. Coumarin reduced the primary lesion of adjuvant-induced arthritis in rats. However, it potentiates the secondary lesions. Levamisole has no effect on the primary lesion but potentiates the secondary lesions. There was an increase in spleen and adrenal weights which correlate well with the severity of the secondary lesions. Increase in liver weight was only observed in coumarin-treated animals, an observation which suggests that coumarin may be a powerful mononuclear phagocytes system stimulant. The similarities and differences between coumarin and levamisole in their mode of action will be discussed.

Acid Phosphatase↗
PubMed1979

Studies on cell motility in inflammation. I. The chemotactic activity of experimental, immunological and non-immunological, inflammatory exudates.

The accumulation of leucocytes at the site of inflammation may be brought about by chemotaxis or proliferation in the extravascular tissues. The present paper focuses on the chemotactic properties of different types of experimental inflammatory pleural exudates, using a modified Boyden chamber. The time-course of carrageenan-induced exudate chemotactic activity for polymorphs was maximal at 4 h, thereafter diminishing towards 24 and 48 h. Chemotactic activity for mononuclear cells remained unchanged throughout the 4--48 h time-course. Heating the exudates to 56 degrees C for 1 h partially reduced chemotactic activity. These results correlate well with the migration of polymorph and mononuclear cells into the pleural cavity during carrageenan-induced pleurisy. The potency of polymorph and mononuclear cell chemotactic activity of different exudates was of the following order: carrageenan greater than calcium pyrophosphate greater than reverse passive Arthus greater than dextran. The results are discussed in order to elucidate the differences between the underlying mechanisms responsible for leucocyte accumulation in different types of inflammatory reaction.

Animals↗
PubMed1979

Studies on cell motility in inflammation. II. The in vivo effect of anti-inflammatory and anti-rheumatic drugs on chemotaxis in vitro.

Two systems were used to test the effect of anti-inflammatory and anti-rheumatic drugs on chemotactic activity of cell-free exudates and also on the chemotactic responsiveness of exudate leucocytes. (1) Inflammatory cell-free exudates from treated rats were tested for their chemotactic activity on exudate leucocytes from untreated rats. (2) Polymorph and mononuclear cells from treated rats were tested for their responsiveness to the chemotactic activity of cell-free exudates from untreated rats. Levamisole, coumarin and D-penicillamine were ineffective in (1) and (2). Colchicine reduced chemotaxis of polymorphs in both systems (1) and (2), whereas no effect was observed on mononuclears. Naproxen was more effective in reducing the chemotaxis of polymorphs compared with mononuclears in systems (1) and (2). In contrast, indomethacin and dexamethasone reduced the chemotaxis of both polymorph and mononuclear cells in systems (1) and (21. Of the drugs tested dexamethasone exhibited the highest potency. These results emphasize the necessity for studying both cellular and humoral factors in the evaluation of the action of anti-inflammatory drugs on chemotaxis.

Animals↗
PubMed1979

Cyclic adenosine 3', 5'-monophosphate and the mechanism of action of three common anti-inflammatory drugs.

1 The effects of indomethacin, dexamethasone and colchicine on cyclic adenosine 3', 5'-monophosphate (cyclic AMP) concentration in leucocytes during a crystal-induced pleurisy in rats were studied. 2 Each of the drugs significantly increased leucocyte cyclic AMP content within 3 h of the injection of crystals. 3 By 6 h, leucocyte cyclic AMP levels returning toward control levels and could not be sustained at the higher level by an additional administration of the respective anti-inflammatory drug.

Animals↗
PubMed1978

[Origin of a mitogrenic factor for cultivated macrophages (IMF: Inflammatory Mitogenic Factor) found in exudates of non-specific acute inflammation].

The mitogenic activity of inflammatory exudate obtained from irradiated Rats is reduced. After transfer of bone marrow syngeneic cells into irradiated Rats this mitogenic activity is further decreased, while after transfer of thymic cells it is increased. It is postulated that the mitogenic activity of inflammatory exudate could be related to thymic cells and that T lymphocytes may be involved in non specific-inflammatory reactions.

Acute Disease↗
PubMed1978

Induction of macrophage DNA synthesis in vitro by non-immunological inflammatory exudates: effect of irradiation and thymus or bone marrow cell reconstitution.

An acute inflammatory exudate possesses mitogenic activity in that it is able to induce both DNA synthesis and proliferation of macrophages in vitro. This activity is reduced however if the inflammatory exudate is obtained from irradiated rats (900 r). Transfer of bone marrow syngeneic cells into irradiated rats does not reverse this reduction. On the contrary the decrease of mitogenic activity is more pronounced. On the other hand transfer of thymic syngeneic cells not only restores the mitogenic activity of inflammatory exudate from irradiated rats but increases it. Transfer of both types of cell together fully restores the mitogenic activity of inflammatory exudate. It is postulated that the mitogenic activity of inflammatory exudate could be related to thymic cells and that T lymphocytes may be involved in non-specific inflammatory reactions.

Animals↗
PubMed1978

The leucocoyte disappearance reaction in non-immune acute inflammation.

Injection of a variety of irritants (saline, ovalbumin, compound 48/80 and powdered glass) into the rat pleural cavity induced the disappearance of pleural leucocytes during the first two hours of the reaction. This phenomenon, termed the leucocyte disappearance reaction (LDR), was suppressed by treatment with the anticoagulants heparin and warfarin. The in-vitro incubation of normal, or inflammatory pleural leucocytes resulted in the deposition of dense interconnecting meshwork of fibrin only upon addition of fibrinogen to the culture medium. It is suggested from these results that the LDR is related to the clotting system, involving leucocyte-derived enzyme(s) analogous to those of the clotting system (e.g., tissue thromboplastin), which convert fibrogen to fibrin, resulting in cell-trapping and subsequent "disappearance" of pleural leuococytes. Similarities were observed betweeen the LDR in non-immune inflammation and the macrophage disappearance reaction of cell-mediated immunity. The significance of these phenomena in the inflammatory process, both immune and non-immune, is discussed.

Animals↗
PubMed1978

Inflammation.

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Capillary Permeability↗
PubMed1977

The identification of particulate matter in biological tissues and fluids.

Sections, 1-2 micron thick, of Araldite embedded tissue were prepared to provide a link between optical and electron microscopy for the identification of crystals. This technique permits examination of individual particles by means of polarising light microscopy, electron microscopy, X-ray energy spectroscopy and electron diffraction. It provides a reliable method for routine and research studies. It has led to the positive identification of individual crystals of calcium pyrophosphate dihydrate and hydroxyapatite in synovial fluids. The method can be applied to the identification of other particulate matter in a variety of biological specimens.

Aged↗
PubMed1977

The relation of cyclic AMP levels to phagocytosis and enzyme release in acute inflammation in vivo.

The effect of altering endogenous leucocyte cyclic AMP levels on phagocytosis and lysosomal enzyme release was studied in vivo. Acute pleural exudates were produced in rats using either calcium pyrophosphate dihydrate crystals or rat serum. Despite marked increases in leucocyte cyclic AMP concentration produced by injection of dibutyryl cyclic AMP and theophylline, there was no reduction in crystal phagocytosis or in enzyme discharge.

Acid Phosphatase↗
PubMed1977

The value of multifactorial screening for anti-inflammatory activity as shown by coumarin.

Different types of acute inflammatory pleural reactions have been used as a means of detecting the anti-inflammatory potential of a particular drug coumarin. The latter had some type of activity in all the reactions. However, whereas coumarin inhibited leucocyte accumulation induced by dextran it had no effect on the volume of fluid exudate. Conversely, coumarin reduced the volume of exudate in the Arthus reaction whereas the cellular infiltrate remained unaltered. Leucocytes from dextran-induced exudate (predominantly polymorphs) removed from animals pretreated with coumarin showed marked inhibition of migration in vitro. This correlated well with the suppression by coumarin of the dextran-induced leucocyte response in vivo. Coumarin administered in vivo was also shown to stimulate phagocytosis of latex by mouse peritoneal macrophages in vitro. These findings are discussed with respect to the evaluation of anti-inflammatory drug activity and to the mode of action of coumarin.

Animals↗