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Biomedical subjects

P Lees

Publications and source records attributed to P Lees.

210 records · Page 12Linked to original sources
PubMedDate not supplied

Advances in anti-inflammatory therapy.

Anti-inflammatory drugs are widely used in veterinary practice to provide symptomatic relief of acute and chronic inflammatory conditions. Whilst much is already known about the properties of corticosteroid and non-steroidal anti-inflammatory drugs, new findings on their biology and pharmacokinetics continue to emerge. These are discussed, together with some possible novel therapeutic applications. Recent evidence, suggesting that morphine-like analgesic drugs may possess anti-inflammatory activity, is additionally presented. Knowledge of the pathways of formation, actions and interactions of the diverse range of mediators responsible for the pathophysiological changes underlying the inflammatory process is also increasing. Compounds are being developed which act selectively to block the formation or actions of these mediators and the potential of such agents as anti-inflammatory drugs is discussed. Although such compounds do not, at present, have veterinary applications, when used either alone, or in combination, some may prove to be potent and effective therapeutic agents.

Animals↗
PubMedDate not supplied

Development and characterisation of a model of bovine inflammation.

Two dialysis sacs each containing 50 ml dextran sulphate solution were implanted into the peritoneal cavities of five three month-old calves. One sac was inoculated with Pasteurella haemolytica or Streptococcus uberis and the second sac served as an uninoculated control. Samples of sac fluid removed after 0, four, six, eight, 15, 24, 36 and 48 hours and then at 24 hour intervals after inoculation revealed bacterial growth up to 9.0 log10 cfu ml-1 by two to three days after inoculation. Concentrations of 25 to 48 ng ml-1 of the inflammatory mediator prostaglandin E2 (PGE2) were detected six to 96 hours after inoculation, similar amounts being generated in sacs inoculated with either bacterium, but the concentrations in control sacs remained below 10 ng ml-4 over the seven day experiment. Post mortem, a tissue cast invested each of the inoculated sacs. Histologically, the reaction was an acute inflammatory response similar to that evoked by each bacterium in the target organ.

Animals↗
PubMedDate not supplied

Effect of antigen challenge on the activation of peripheral blood neutrophils from horses with chronic obstructive pulmonary disease.

The effect of antigen challenge on the state of activation of peripheral blood neutrophils from horses with chronic obstructive pulmonary disease (COPD) has been determined by measuring neutrophil superoxide anion formation. Prior to a seven-hour antigen challenge superoxide anion production by neutrophils from asymptomatic horses with COPD and normal horses in response to platelet activating factor (PAF) (with and without cytochalasin B), serum treated zymosan (STZ) and phorbol myristate acetate (PMA) was similar. Agonist-induced superoxide production by neutrophils from symptomatic COPD and normal horses remained unchanged five and 24 hours after antigen challenge. Interestingly, however, superoxide production by neutrophils from symptomatic COPD horses was significantly increased 24 hours after antigen challenge in the control samples for each agonist (basal superoxide production), a five-fold increase being measured in the presence of cytochalasin B. There was a small increase in superoxide production by neutrophils from normal horses but this only reached significance in one set of control samples. The change in activation state of circulating neutrophils during antigen challenge may facilitate the lung neutrophilia and subsequent tissue damage which occur in COPD.

Animals↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of fenleuton, a 5-lipoxygenase inhibitor, in ponies.

Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid metabolism, possess properties consistent with their involvement in a range of inflammatory diseases. In this study the pharmacokinetics and pharmacodynamics of the selective 5-lipoxygenase inhibitor, fenleuton, have been examined in the horse. Orally administered fenleuton (four 5 mg kg(-1) doses, given once daily) was absorbed from the gastrointestinal tract, and penetrated readily into tissue cage exudate, the ratio of the plasma:exudate AUC0-48h being 0.90+/-0.02 (n=6). Ionophore-stimulated leukotriene (LT) B4 synthesis, measured ex vivo in whole blood as immunoreactive LTB4, was significantly (P<0.05) inhibited throughout the 48 hour sampling period. Low levels of immunoreactive LTB4 were detected in transudate and these did not increase following addition of carrageenan to the tissue cages. Fenleuton had no significant inhibitory effect on exudate LTB4 concentrations. A reduction in carrageenan-induced skin swelling occurred, although this did not achieve statistical significance. The results obtained in this study suggest that fenleuton could be used to examine the role of LTs in inflammatory diseases of the horse.

Administration, Oral↗
PubMedDate not supplied

Inhaled leukotrienes cause bronchoconstriction and neutrophil accumulation in horses.

Leukotrienes have been shown to mimic many of the pathophysiological processes in allergic airway disease. In this study the bronchoconstrictor effect of inhaled LTD4, and radiolabelled neutrophil accumulation in response to inhalation of LTB4, have been examined in the horse. In separate studies, solutions of LTD4 and LTB4 were administered to the airways of normal animals by nebulisation. LTD4, but not LTB4, caused a dose-dependent increase in pleural pressure which was maximal at three to four minutes and had returned to baseline by 15 to 20 minutes. On a molar basis LTD4 was 305 to 970 times more potent than methacholine. LTB4 induced an early recruitment (15 minutes to 1 hour) to the lungs of radiolabelled neutrophils, which persisted for more than 5 hours in some animals. There was no effect on peripheral blood leucocyte counts or pleural pressure and neither LTB4, nor LTD4, affected respiratory rate. These results suggest that, if released during antigen challenge, LTB4 and LTD4 could contribute to the pathogenesis of equine COPD. In a small group of asymptomatic COPD horses these leukotrienes appeared to cause similar, but smaller, changes in lung function and neutrophil recruitment, which could suggest reduced responsiveness to these mediators.

Administration, Inhalation↗