In vitro and in vivo binding of phenylbutazone and related drugs to equine feeds and digesta.

In vitro and in vivo studies of phenylbutazone binding to equine ingesta and digesta were undertaken. In vitro binding to chopped hay and powdered pony nuts in buffer solutions at 37 degrees C was found to be time-, concentration- and pH-dependent. Percentage binding generally increased with time, decreased with concentration and varied with buffer pH in an unpredictable manner.

Prediction of the duration of hospitalization in patients with respiratory syncytial virus infection: use of clinical parameters.

To assess the possibility that clinical data available at the time of hospital admission for patients with respiratory syncytial virus infection could predict the length of hospitalization without antiviral therapy, the charts of all 102 patients admitted with laboratory documented respiratory syncytial virus infection during 1982 to 1985 were reviewed. Two thirds (65) of the patients remained hospitalized greater than three days. Prolonged hospitalization could have been predicted for 40 of the 65 patients (61.

Fetal breathing movements are not a reliable predictor of continued lung development in pregnancies complicated by oligohydramnios.

Fetal breathing activity was monitored by ultrasonography in 14 patients with oligohydramnios (4 with fetal anuria and 10 with premature rupture of the membranes). 45 patients with intact membranes, with normal amniotic fluid volume, and matched for gestational age were the controls. Fetal breathing movements were seen in all 8 patients who died in the perinatal period with a necropsy diagnosis of lung hypoplasia.

MHC antigen expression in sequential biopsies from cardiac transplant patients--correlation with rejection.

Class I induction on the myocardium of transplanted heart was investigated with regard to its temporal relationship to rejection episodes, how it is affected by anti-rejection therapy and whether it is dependent upon the presence of a T cell infiltrate in the biopsy. Sequential cardiac biopsies (total 114) from 11 patients from the time of transplant to 1 year after transplant were studied using immunocytochemical techniques. The effect of different immunosuppressive regimens on MHC antigen expression was also studied.

Physiological, biochemical and haematological effects on horses of a phenylbutazone paste.

Five matched pairs of horses were used to investigate the biochemical, haematological and general clinical effects of a new dosage schedule of a phenylbutazone paste administered under controlled feeding conditions. One group of horses received a loading dose (8.8 mg/kg) on day 1, followed by doses of 3.

Cyclosporin A inhibits mitogen-activated but not phorbol ester-activated locomotion of human lymphocytes.

Human blood lymphocytes acquire locomotor capacity during 24 hr culture with mitogens such as monoclonal anti-CD3 antibodies, phytohaemagglutinin (PHA), or Staphylococcus aureus Cowan strain (SAC). Activation of locomotor capacity by these agents is blocked by the presence of cyclosporin A (greater than or equal to 10 ng per ml), as measured by inhibition of the development of morphological polarization of the cells in culture and inhibition of their capacity to invade collagen gels. The response to OKT3 is inhibited by lower doses of cyclosporin than the responses to SAC or PHA.

Measurement of flunixin in equine inflammatory exudate and plasma by high performance liquid chromatography.

An accurate and reliable method for the separation of flunixin from, and measurement in, equine inflammatory exudate and plasma by high performance liquid chromatography has been developed. Flunixin can be detected in concentrations as low as 0.05 micrograms/ml using an ultraviolet spectrophotometric detector at 285 nm.

Applications of equine models of acute inflammation. The Ciba-Geigy Prize for Research in Animal Health.

The development of reproducible models of acute inflammation in which inflammatory heat is easily quantified and from which inflammatory exudate is readily harvested has facilitated studies in the horse of the actions of steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Blockade of the synthesis of eicosanoids and suppression of inflammatory heat by clinical dose rates of NSAIDS suggests a causal link between the two events and provides further evidence for a role of these compounds in acute equine inflammation. The tendency for enolic and carboxylic acids NSAIDS to accumulate in inflammatory exudate may account for the duration of action of these compounds in inhibiting exudate eicosanoid synthesis and the data confirm clinical experiences with these drugs.

Inflammation: a clinical perspective. The Ciba-Geigy Prize for Research in Animal Health.

The cardinal signs of acute inflammation have been recognised for almost 2000 years, but it is only in the last hundred years that significant progress has been made in understanding the underlying cellular response. Our knowledge of the chemical messengers which regulate and in some cases lead to persistence of the inflammatory process is, as yet, incomplete, but it is hoped that further research at this level will lead to the development of more effective therapeutic agents.

Development of equine models of inflammation. The Ciba-Geigy Prize for Research in Animal Health.

Two experimental models of acute non-immune inflammation have been developed to enable studies of the biochemical composition and cellular content of exudates to be undertaken. Both are based on the creation of a mild, reproducible and reversible inflammatory reaction, which is free from uncontrolled incidental factors and which causes minimal distress to the experimental animals. The polyester sponge model involves the insertion of small polyester sponge strips soaked in sterile carrageenan solution into subcutaneous neck pouches and their serial removal.

Metabolism, excretion, pharmacokinetics and tissue residues of phenylbutazone in the horse.

The pharmacokinetics, metabolism, excretion and tissue residues of phenylbutazone (PBZ) in the horse were studied following both intravenous and oral administration of the drug at a dose rate of 4.4 mg/kg. A 72-hour blood sampling schedule failed to demonstrate a third exponential phase; the plasma disposition following intravenous injection being described by a two compartment open model, with the following elimination phase parameters: beta = 0.

Actions of BW540C in an equine model of acute inflammation: a preliminary study.

An equine model of acute non-immune inflammation has been developed to facilitate studies of the inflammatory process and the actions of novel anti-inflammatory drugs. Five polyester sponge strips soaked in sterile 2% carrageenin solution were placed in subcutaneous pouches prepared under local anaesthesia in the necks of conscious ponies. Serial removal of the strips and harvesting of the exudate enabled studies to be made of the cellular, biochemical and mediator aspects of the localised, acute inflammation, and the heat generated by the lesion was monitored by infra-red thermometry.

OKT3-activated locomotion of human blood lymphocytes: a phenomenon requiring contact of T cells with Fc receptor-bearing cells.

The OKT3 antibody activates locomotion of human blood T lymphocytes as measured by polarization assays and invasion of collagen gels. The proportion of motile cells increases during a period of 24-48 hr of culture, even following only a brief initial contact with OKT3. The motile cells are the growing population.

Use of a novel non-steroidal anti-inflammatory drug in the horse.

In a two-part cross-over experiment in six ponies, an acute inflammatory reaction was generated by injecting carrageenin solution into subcutaneously-implanted tissue-cages lined with fibrovascular granulation tissue. In each part of the cross-over, half of the ponies received a novel phenylpyrazoline anti-inflammatory agent (BW540C) orally and half received a placebo treatment. BW540C inhibited platelet cyclo-oxygenase for 24 h but the reductions in exudate eicosanoid concentrations were less pronounced.

The effects of ischaemia, lysophosphatidylcholine and palmitoylcarnitine on rat heart phospholipase A2 activity.

Phospholipase A2 activity was studied in the isolated rat heart following coronary artery ligation. In both the homogenate and mitochondrial fractions phospholipase A2 activity was significantly depressed at 20 min post ligation in the ischaemic region only. This is at a time of peak lysophospholipid concentration and severity of arrhythmias.

Calcium channel blocking properties of amlodipine in vascular smooth muscle and cardiac muscle in vitro: evidence for voltage modulation of vascular dihydropyridine receptors.

Amlodipine was twice as potent as nifedipine at inhibiting Ca2+-induced contractions in depolarised rat aorta (IC50 1.9 nM vs. 4.

Effects of a phenylbutazone paste in ponies: model of acute nonimmune inflammation.

In a 12-day treatment schedule, 5 ponies were given orally a paste formulation of phenylbutazone (PBZ) and 5 matched ponies were given equivalent doses of a placebo paste. On day 12, a mild, nonimmune inflammatory reaction was induced subcutaneously in the neck of each pony by inserting sterile, polyester sponge strips soaked in a 2% carrageenan solution. Exudate was collected at 4, 8, 12, and 24 hours by serial removal of sponges.

Absorption of phenylbutazone from a paste formulation administered orally to the horse.

The absorption pattern of phenylbutazone was studied in five horses during administration of the drug in a paste formulation on days 1, 5, 8 and 12 of a 12-day dosing schedule. Since two or more plasma concentration peaks were usually obtained following each oral dose, it was concluded that phasic absorption was a particular feature of the oil:water formulation of the product. Possible causes of this unusual absorption pattern are discussed and the therapeutic implications of both phasic absorption and the recorded values of Cmax, tmax and AUC024 for phenylbutazone and its active metabolite oxyphenbutazone are considered.

Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse.

The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation.