Biomedical subjects

F M Cunningham

Publications and source records attributed to F M Cunningham.

78 records · Page 5Linked 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

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

Equine peripheral blood mononuclear cells proliferate in response to tetanus toxoid antigen.

It has been reported that equine peripheral blood mononuclear cells (PBMNs) do not proliferate in response to tetanus toxoid (TT) (Frayne and Stokes 1995, Research in Veterinary Science 59, 79-81). Here we demonstrate that lymphocyte proliferation responses to TT, which are characteristic of a recall antigen, may be achieved under certain culture conditions. Given that TT vaccination is routinely applied to many horses, TT is a suitable antigen for the investigation of cellular immune responses by peripheral blood mononuclear cells in the horse.

Animals↗

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↗

PubMedDate not supplied

Ceftriaxone administered once or twice a day for treatment of bacterial infections of childhood.

Twenty-six children received a single daily intravenous dose of ceftriaxone, 50 mg/kg, for a variety of bacterial infections including abscess (5), cellulitis (5), periorbital cellulitis (5), bacteremia without focus (4), osteomyelitis (2), pneumonia (2), pyelonephritis (2) and otitis media (1). Organisms isolated from infectious foci were Staphylococcus aureus (9), Streptococcus pneumoniae (6), Streptococcus pyogenes (3), Escherichia coli (2); and Haemophilus influenzae type b, nontypable H. influenzae, Group B streptococcus, Pasteurella multocida, Haemophilus parainfluenzae and satelliting streptococcus (1 each). Microbiologic cure was achieved in 20 of 22 (91%) infections and clinical cure in 25 of 26 (96%). Fifteen possible adverse reactions occurred in 34 patients evaluable for drug safety; most were mild and self-limited. Neutropenia developed in two patients necessitating discontinuation of ceftriaxone in one, followed by prompt resolution. Seventeen children received ceftriaxone, 75 mg/kg/day, in two divided doses for a similar variety of infections. Bacteriologic and clinical cure rates of 100 and 94%, respectively, were demonstrated. Leukopenia developed in one patient and resolved when ceftriaxone was discontinued. Once a day dosing of ceftriaxone in pediatric patients provides greater ease of administration combined with efficacy equal to that achieved with a divided dosage schedule.

Adolescent↗