Biomedical subjects

P Lees

Publications and source records attributed to P Lees.

At least 55 records · Page 3Linked to original sources

PubMed2000

Effects of polysulfated glycosaminoglycan and hyaluronan on prostaglandin E2 production by cultured equine synoviocytes.

OBJECTIVE: To investigate effects of the anti-arthritic agents hyaluronan and polysulfated glycosaminoglycan (PSGAG) on inflammatory metabolism in cultured equine synoviocytes. SAMPLE POPULATION: Synoviocytes cultured from samples obtained from the metacarpophalangeal joints of 4 horses. PROCEDURE: Equine synoviocytes were grown in monolayer culture. Synoviocytes were stimulated with lipopolysaccharide (LPS) and simultaneously treated with various concentrations of hyaluronan or PSGAG for 48 hours. Three hyaluronan preparations were compared. Prostaglandin E2 (PGE2) concentrations in culture medium were measured, using radioimmunoassay. RESULTS: The highest concentrations of hyaluronan and PSGAG tested inhibited PGE2 production. CONCLUSIONS AND CLINICAL RELEVANCE: Clinically achievable concentrations of hyaluronan and PSGAG inhibited PGE2 synthesis by cultured equine synoviocytes. This anti-inflammatory action may be a mechanism through which these agents exert anti-arthritic effects. The effect was obtained at concentrations that can be achieved by use of intra-articular, but not systemic, administration of hyaluronan or PSGAG.

Adjuvants, Immunologic↗

PubMed2000

The influence of mechanical loading on isolated chondrocytes seeded in agarose constructs.

Articular cartilage is subjected to dynamic compressive loading during normal activity which influences chondrocyte metabolism through various mechanotransduction pathways. A well characterised and reproducible model system, involving chondrocytes embedded in agarose gel, has been used to investigate the effects of mechanical compression on chondrocytes, isolated from full depth cartilage or separately from the superficial and deep zone tissue. The role of nitric oxide as a mediator of mechanical-induced effects has also been studied. Chondrocytes were isolated, separately, from full depth, superficial and deep zone cartilage and seeded in 3% agarose constructs. Dynamic compressive strain was applied to the constructs using a range of frequencies (0.3, 1 and 3 Hz). Glycosaminoglycan synthesis, cell proliferation and nitrite production were assessed. In further experiments, constructs were compressed in the presence of 1 mM L-NAME or 10 microM dexamethasone. Glycosaminoglycan synthesis by full depth chondrocytes was affected by compressive strain in a frequency dependent manner. Dynamic strain at all frequencies induced an increase in [3H]-thymidine incorporation. Glycosaminoglycan synthesis by deep zone cells was affected by the strain regimes in a similar fashion to full depth cells, while superficial cells exhibited a similar proliferative response to full depth cells. Dynamic compression inhibited nitrite production, the effect being reversed by L-NAME. Compression induced stimulation of [3H]-TdR incorporation was reversed by L-NAME. These studies demonstrate that glycosaminoglycan synthesis and proliferation are influenced by the dynamic strain regimes in a distinct manner. Indeed the data suggest that these processes occur in different chondrocyte sub-populations. It may be speculated that nitric oxide acts as a mediator of mechanotransduction processes affecting proliferation primarily in the superficial cell sub-population.

Agar↗

PubMed1999

Agonist-induced adherence of equine neutrophils to fibronectin- and serum-coated plastic is CD18 dependent.

Adherence to vascular endothelium and extracellular matrix proteins is a pre-requisite for neutrophil accumulation at sites of inflammation. In this study, equine neutrophil adherence to fibronectin and autologous serum-coated plastic in response to PAF, hrIL-8, hrC5a and PMA has been measured. In addition, the mechanisms involved have been investigated using monoclonal antibodies (MoAbs) against the beta2 integrin CD18. PAF and hrC5a caused similar, concentration dependent, increases in adherence to fibronectin- and serum-coated plastic (maximum responses 19 +/- 4% and 19 +/- 3% for PAF and 15 +/- 4% and 16 +/- 2% for hrC5a on fibronectin- and serum-coated plastic, respectively). Adherence in response to PMA, although not reaching a maximum over the time course studied, was of a similar magnitude on the two surfaces (41 +/- 1% and 38 +/- 2% with 10(-7) M PMA on fibronectin- and serum-coated plastic, respectively). In contrast, the maximum adherence caused by hrIL-8 was significantly lower on fibronectin- than on serum-coated plastic (9 +/- 3% vs. 17 +/- 2%; 10(8) x M hrIL-8). Pre-incubation with MoAbs against CD18 (H20A and 6.5E) caused concentration related inhibition of stimulus-induced adherence to both fibronectin- and serum-coated plastic. Equine neutrophil adherence in response to PAF, hrIL-8, hrC5a and PMA therefore appears to be mediated by a CD18 dependent mechanism.

Animals↗

PubMed1999

Metabolic kinetics of proteoglycans by embryonic chick sternal cartilage in culture.

Explant cultures of embryonic chick sternum have been widely studied, but the kinetics of biosynthesis of proteoglycans by this tissue in culture has not been characterized. Caudal cartilaginous portions of 16-day-old embryonic chick sterna were cultured for 8 days. Histological examination showed that the fresh cartilage contained morphologically homogenous chondrocytes, which were embedded in a uniform extracellular matrix. After culture for 8 days, the histological appearance of the explant remained unchanged but the tissue increased in size with time as indicated by a progressive increase in DNA content and in the content of glycosaminoglycan and collagen. Rates of degradation and release from the tissue of proteoglycans labeled in ovo with 35S were first order during culture, as were the unlabeled proteoglycans. Proteoglycan synthesis was high during the first 2 days of culture, and this then gradually decreased from this high level during the following 2 days. Synthesis was then maintained at a constant level for the remainder of the culture period. After culture for 2 and 7 days, the proteoglycans synthesized by the explants were identical to the preexisting proteoglycans in hydrodynamic size, glycosaminoglycan chain size, and ability to form aggregates. These findings suggest that the embryonic chick sterna maintained a stable cartilage phenotype during the extended culture periods. The initial rapid rate of matrix turnover was probably attributable to an adaptation of the tissue to ex ovo culture conditions and the subsequent maintenance of cellular activities at a lower level indicated the establishment of a steady-state rate of metabolism.

Animals↗

PubMed1999

A pharmacodynamic and pharmacokinetic study with vedaprofen in an equine model of acute nonimmune inflammation.

The pharmacodynamics and enantioselective pharmacokinetics of vedaprofen were studied in six ponies in a two period cross-over study, in which a mild acute inflammatory reaction was induced by carrageenan soaked sponges implanted subcutaneously in the neck. Vedaprofen, administered intravenously at a dosage of 1 mg/kg, produced significant and prolonged inhibition of ex vivo serum thromboxane B2 (TXB2) synthesis and short-lived inhibition of exudate prostaglandin E2 (PGE2) and TXB2 synthesis. Vedaprofen also partially inhibited oedematous swelling and leucocyte infiltration into exudate. Vedaprofen displayed enantioselective pharmacokinetics, plasma concentrations of the R(-) enantiomer exceeding those of S(+) vedaprofen. The plasma concentration ratio, R:S, increased from 69:31 at 5 min to 96:4 at 3 h and plasma mean AUC values were 7524 and 1639 ng x h/mL, respectively. Volume of distribution was greater for S(+) vedaprofen, whilst elimination half-life (t(1/2beta)) and mean residence time were greater for R(-) vedaprofen. The penetration of vedaprofen into inflammatory exudate was also enantioselective. For R(-) and S(+) vedaprofen maximum concentration (Cmax) values were 2950 and 1534 ng/mL, respectively, and corresponding AUC values were 9755 and 4400 ng x h/mL. Vedaprofen was highly protein bound (greater than 99%) in both plasma and exudate. The significance of these data for the therapeutic use of vedaprofen is discussed.

Animals↗

PubMed1999

Pharmacokinetics of carprofen enantiomers in equine plasma and synovial fluid - a comparison with ketoprofen.

Carprofen is a Non Steroidal Anti-Inflammatory Drug (NSAID) which is widely used for the treatment of musculoskeletal disorders in horses. The commercial preparation is a racemic mixture of two enantiomers (R and S carprofen). We used HPLC to measure plasma and synovial fluid R and S carprofen concentrations following a single intravenous (i.v.) dose, and computer modelling to determine the pharmacokinetic parameters of the enantiomers in these two body fluids. A comparison was made with results from an identical experiment using ketoprofen. The plasma elimination half lives of R and S carprofen were 20 and 16 times longer than those of R and S ketoprofen, and clearance was considerably slower for carprofen than ketoprofen. Plasma R carprofen concentrations were higher than S carprofen concentrations throughout the 48-h period. Ketoprofen was no longer detectable in synovial fluid after 5 h (S enantiomer) or 12 h (R enantiomer), whereas synovial fluid carprofen concentrations did not peak until 12 h and were still detectable at 48 h. Synovial fluid concentrations of both carprofen enantiomers were significantly lower than plasma concentrations, probably due to high plasma protein binding which could limit transfer through the synovial membrane. Our results indicate significant differences between carprofen and ketoprofen and between the two carprofen enantiomers.

Animals↗

PubMed1999

Enantiospecific pharmacokinetics and pharmacodynamics of ketoprofen in sheep.

Pharmacokinetic and pharmacodynamic parameters were established for the enantiomers of the 2-arylpropionic acid (APA) nonsteroidal anti-inflammatory drug (NSAID), ketoprofen (KTP). Each enantiomer was administered separately (1.5 mg/kg) and in a racemic mixture (3 mg/kg) intravenously (i.v.) to a group of eight sheep in a four-way, four-period cross-over study using a tissue cage model of inflammation. Plasma disposition of each KTP enantiomer was similar following separate administration of the pure compounds compared to administration of the racemic mixture. S(+)KTP volume of distribution (Vd(area)) was higher and clearance (ClB) faster than those of R(-)KTP. S(+) and R(-)KTP achieved relatively low concentrations in exudate and transudate. Unidirectional limited chiral inversion of R(-) to S(+)KTP was demonstrated. After R(-)KTP administration S(+)KTP was detected in plasma, but not in either exudate or transudate. Pharmacokinetic/pharmacodynamic (PK/PD) modelling of the data could not be undertaken following R(-)KTP administration because of chiral inversion to S(+)KTP, but the pharmacodynamic parameters, calculated maximum effect (Emax), concentration producing 50% effect (EC50), Hill's coefficient (N), rate constant of elimination of drug effect from the compartment (KeO) and mean equilibration half-life (t1/2KeO) were determined for S(+)KTP after administration of the racemic mixture as well as the pure compound.

Animals↗

PubMed1999

In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen.

The effects of hyaluronan and carprofen (both racemic mixture and separate R and S enantiomers) on proteoglycan (PG) synthesis by equine cultured chondrocytes and cartilage explants were examined. Hyaluronan stimulated PG synthesis in both cell and explant cultures. The concentration-response curve of the latter was bell-shaped. Racemic carprofen and R and S enantiomers also stimulated PG synthesis, although concentration-response relationships varied for each preparation and high concentrations inhibited synthesis. It was concluded that (a) hyaluronan exerts a stimulatory effect on PG synthesis at low concentrations and (b) stimulatory effects of carprofen on PG synthesis are, to some degree, enantioselective with the carprofen S-enantiomer exerting the greatest effect. Hyaluronan and carprofen are used clinically despite incompletely understood mechanisms of action. These results suggest (a) hyaluronan and carprofen might exert an anti-arthritic action through stimulation of PG synthesis and (b) there is possible justification for therapeutic administration of enantiomeric rather than racemic carprofen.

Adjuvants, Immunologic↗

PubMed1999

Effects of R and S enantiomers and a racemic mixture of carprofen on the production and release of proteoglycan and prostaglandin E2 from equine chondrocytes and cartilage explants.

OBJECTIVE: To examine effects of carprofen (enantiomers and a racemic mixture) on the metabolism of equine chondrocytes. SAMPLE POPULATION: Cartilage from clinically normal horses. PROCEDURE: Effects of carprofen on proteoglycan neosynthesis, glycosaminoglycan (GAG) release and prostaglandin (PG) E2 production by unstimulated chondrocyte monolayers and cartilage explants were examined, as were similar variables in monolayers and explants exposed to carprofen and recombinant human interleukin 1beta (IL-1). Carprofen (enantiomers and racemic mixture) was used alone or along with IL-1 on monolayers and explant cultures. Medium was collected 48 to 96 hours later, and cartilage was digested. Proteoglycan synthesis was assessed as the amount of 35S-labeled proteoglycan in medium and digested cartilage. Total GAG content of the medium and digested cartilage was measured, and proteoglycan degradation was calculated. Radioimmunoassay was used to measure PGE2 production. RESULTS: Carprofen significantly decreased PGE2 production by unstimulated chondrocytes and antagonized an IL-1-induced increase in PGE2 production. Carprofen significantly increased proteoglycan synthesis in unstimulated monolayers and explants. Concurrently, there was a decrease in GAG release by explants. Use of IL-1 significantly decreased proteoglycan synthesis, but the highest concentrations of carprofen partially reversed this effect in chondrocyte monolayers. CONCLUSIONS: Carprofen had a potentially beneficial effect on proteoglycan metabolism of equine chondrocytes. This effect was sufficiently strong at the highest concentrations to overcome inhibitory effects of IL-1 on proteoglycan synthesis. Carprofen also inhibited PGE2 production by unstimulated and IL-1-stimulated chondrocytes. Carprofen induced these enantiomer-specific effects. CLINICAL RELEVANCE: Use of carprofen in osteoarthritic horses may induce beneficial changes in articular cartilage matrix.

Animals↗

PubMed1998

Dynamic mechanical compression influences nitric oxide production by articular chondrocytes seeded in agarose.

Nitric oxide (NO) has been implicated in the inhibition of cell proliferation in cytokine and lipopolysaccharide (LPS)-stimulated chondrocytes and is known to be influenced by physical forces in several tissues. In this study, a well-characterized model system utilizing bovine chondrocytes embedded in 3% agarose constructs has been used to investigate the effect of dynamic strain at 0.3, 1, or 3 Hz on NO production. LPS induced a significant increase in nitrite levels, which was reversed by both L-NAME and dexamethasone. Dynamic compressive strain produced a significant reduction in nitrite production. The effect was partially blocked by L-NAME but unaffected by dexamethasone. L-NAME also reversed dynamic compression-induced stimulation of [3H]-thymidine incorporation. NO appears to be a constituent of mechanotransduction pathways which influence proliferation of bovine chondrocytes seeded within agarose constructs. The inhibitor experiments also infer that alterations in cNOS activity primarily determine the response.

Animals↗

PubMed1998

Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation.

Injections of mild irritants intradermally (carrageenan, zymosan and dextran) and intracaveally (carrageenan) in a tissue cage model of inflammation were used in studies of the pharmacodynamics and pharmacokinetics of tolfenamic acid administered intramuscularly in calves. Inhibition of serum thromboxane (TX)B2 and inflammatory exudate prostaglandin (PG)E2 were used as indicators of the magnitude and time course of blockade of cyclo-oxygenase isoforms COX-1 and COX-2, respectively. Single doses of 2, 4 and 8 mgkg-1 tolfenamic acid partially inhibited irritant-induced rises in skin temperature (non-dose dependently) and skin oedema (dose-dependently). These doses also markedly inhibited serum TXB2 synthesis and the duration of inhibition was dose-related. A dose of 2 mgkg-1 tolfenamic acid also attenuated skin temperature rise over carrageenan-injected tissue cages, and markedly inhibited exudate PGE2 synthesis, even though drug penetration into both exudate and tissue cage transudate was limited. Tolfenamic acid pharmacokinetics were characterized by a relatively short tmax (0.94-2.04 h), a high estimated Vdarea (1.79-3.20 Lkg-1), an estimated t1/2 beta of 8.01-13.50 h and Cl beta of 0.142-0.175 Lkg-1h-1. The actions of tolfenamic acid in inhibiting PGE2 synthesis and in attenuating two of the cardinal signs of inflammation (heat and swelling) suggest that a dosage of 2 mgkg-1 administered intramuscularly should be effective clinically as an anti-inflammatory agent.

Animals↗

PubMed1998

Effect of the 5-lipoxygenase inhibitor, fenleuton, on antigen-induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease.

The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on three occasions and fenleuton (4 days oral dosing 5 mg/kg) pre-treatment on one occasion. Three horses received fenleuton prior to the second challenge and three horses received the drug prior to the fourth antigen challenge. Changes in radiolabelled neutrophil distribution, lung function and peripheral leucocyte counts were monitored on each occasion for 7 h following the start of antigen challenge. Antigen challenge caused an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. Neither response was affected by fenleuton pre-treatment. Mean maximal changes in pleural pressure (delta Pplmax) and respiratory rate were also unaffected by fenleuton pre-treatment. However, in the two horses which responded to antigen-challenge with a particularly marked increase in delta Pplmax (> 15 cm H2O), prior administration of fenleuton reduced the response by 64 and 63%. These results suggest that 5-lipoxygenase inhibitors warrant further investigation as bronchodilators in equine COPD.

Animals↗

PubMed1997

Pulsed electromagnetic fields preserve proteoglycan composition of extracellular matrix in embryonic chick sternal cartilage.

The influence of pulsed electromagnetic fields (PEMF) on proteoglycan composition in cartilage extracellular matrix has been investigated. Day 16 embryonic chick sternal cartilage was explanted to culture and exposed for 3 h per day for 2 days to a repetitive single-pulse PEMF with frequency of 15 Hz and peak magnetic field of 1.25 G. PEMF treatment did not affect cell proliferation, as indicated by [3H]thymidine incorporation, but significantly stimulated the retention of glycosaminoglycans in the explants and reduced the release of glycosaminoglycans into the media. Determination of incorporation of [35S]sulfate and [3H]N-acetylglucosamine into proteoglycans in vitro and breakdown of in ovo labelled [35S]sulfated proteoglycans in vitro showed that PEMF treatment significantly suppressed the synthesis of proteoglycans and the degradation of both newly synthesized and pre-existing proteoglycans. Sepharose CL-2B chromatography demonstrated that PEMF did not affect either the size distribution of newly synthesized and pre-existing [35S]sulfated proteoglycans or their ability to aggregate with hyaluronate. Sepharose CL-6B chromatography followed by cellulose acetate electrophoresis revealed that the chain length and degree of sulfation of [35S]sulfated glycosaminoglycans were identical in control and PEMF-treated cultures. It is concluded that PEMF treatment preserved extracellular matrix integrity of cultured cartilage explants by down-regulating proteoglycan synthesis and degradation in a co-ordinated manner without affecting their gross structural nature.

Animals↗

PubMed1997

Hospital activity. Barred facts.

Barcode technology is applicable to a number of crucial management issues in the NHS, including internal efficiency, contract pricing and the effectiveness of care. Its enormous potential lies in the ability to record in detail over a number of dimensions such as time, staff group, patient type, and cost. But the effort involved is considerable. Projects have to be actively managed, users have to be willing participants and data has to be analysed. Where short cuts have been sought, projects have failed to deliver their full potential. The data is merely a means to an end, but a very powerful one. It brings together people who may normally work independently, and the process of collecting barcode data is a perfect mechanism for bringing together the patient, the professional and the purse strings.

Electronic Data Processing↗

PubMed1997

Enantioselective behaviour of drugs used in domestic animals: a review.

The chirality of drugs, with particular reference to agents used in veterinary medicine, is reviewed. Basic concepts of chirality and aspects of the methodology for the separation of enantiomers are considered. Chiral compounds are in common use in animals and their pharmacological actions and side-effects (pharmacodynamics) and absorption into and fate within the body (pharmacokinetics) are of fundamental importance; pharmacodynamic and pharmacokinetic properties of enantiomeric pairs commonly differ and this has major implications for their effective and safe therapeutic use. As examples of the particular significance of chirality in veterinary medicine, the following drug classes are reviewed; benzimidazole anthelmintics, cloprostenol, verapamil, ketamine, halogenated hydrocarbon anaesthetics and 2-arylpropionic acid anti-inflammatory drugs. The implications of chirality for drug product development and approval by registration authorities are discussed.

Anesthetics↗

PubMed1997

Pharmacology of the 5-lipoxygenase inhibitors BAY Y 1015 and BAY X 1005 in the horse.

Calcium ionophore A23187 induced time and concentration dependent production of immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro. Time dependent production of immunoreactive LTB4 by equine neutrophils and immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5-lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015, produced concentration dependent inhibition of ionophore-induced LTB4 synthesis by equine whole blood (mean +/- SEM IC50s n = 5; 6.14 +/- 0.28 microM vs. 12.30 +/- 0.75 microM for BAY Y 1015 and BAY X 1005, respectively) and neutrophils (mean +/- SEM IC50s n = 5; 0.003 +/- 0.001 microM vs. 0.045 +/- 0.021 microM for BAY Y 1015 and BAY X 1005, respectively) and LTC4 synthesis by equine eosinophils (mean +/- SEM IC50s n = 5; 0.0036 +/- 0.0002 microM and 0.108 +/- 0.023 microM for BAY Y 1015 and BAY X 1005, respectively) in vitro. In all three assays, BAY Y 1015 was more potent than BAY X 1005, and for both compounds much higher concentrations were required to inhibit LT synthesis by whole blood compared to isolated neutrophils and eosinophils. Plasma concentration-time relationships and pharmacokinetic parameters for BAY Y 1015 administered intravenously and orally to six horses at a dosage of 10 mg/kg in a two period cross-over study were established. The study also evaluated the anti-inflammatory properties of BAY Y 1015 and its ability to inhibit ex vivo whole blood LTB4 synthesis and in vivo LTB4 synthesis in a tissue cage model of acute inflammation. At this dosage, BAY Y 1015 failed to significantly inhibit immunoreactive LTB4 synthesis or the oedema produced by intradermal injection of the mild irritant, carrageenan.

Administration, Oral↗

PubMed1997

Phenylbutazone pharmacokinetics and bioavailability in the dromedary camel (Camelus dromedarius).

Phenylbutazone was administered intravenously and intramuscularly at a dosage rate of 4.4 mg/kg to a group of 6 female camels in a two-period crossover study. After intravenous (i.v.) administration, disposition was characterised by a two-compartment open model, with a low volume of distribution (0.174 l.kg-1), and distribution and elimination half-lives of 0.43 and 12.51 h, respectively. After intramuscular (i.m.) dosing absorption was relatively rapid with absorption half-time and time of maximal concentration values of 1.14 and 3.95 h, respectively. Plateau concentrations of phenylbutazone in plasma were obtained between 2 and 12 h and mean bioavailability was 97%, although this was subject to wide inter-animal differences. Plasma concentrations of the phenylbutazone metabolite, oxyphenbutazone, were low after iv dosing and generally undetectable after im administration, indicating that it is unlikely to contribute significantly to the pharmacological effects produced by phenylbutazone administration. An indication was obtained that phenylbutazone inhibited the ex vivo synthesis of serum thromboxane B2 (TxB2) for 24h after i.v. dosing, but this finding requires confirmation.

Animals↗

PubMed1997

Nitric oxide production by equine articular cells in vitro.

Recent research in several species has suggested nitric oxide (NO) as a mediator of articular cartilage damage and an inhibitor of cartilage matrix neosynthesis. This study investigated NO production by cultured equine articular chondrocytes in response to 2 arthritogenic molecules, namely lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta), and compared NO production by cultured equine synoviocytes stimulated with LPS. Synoviocytes exhibited a low basal level of NO synthesis (measured as nitrite, a NO metabolite) that was neither significantly increased nor decreased by exposure to LPS. Basal NO synthesis by synoviocytes was not significantly reduced by competitive inhibitors of nitric oxide synthase (NOS). In contrast, chondrocytes treated with LPS or IL-1 beta synthesised nitrite in a dose-related manner. Inhibitors of NOS suppressed nitrite production to below the basal levels of release of unstimulated cells. Dexamethasone, an inhibitor of induction of the inducible isoform of NOS (iNOS), reduced nitrite synthesis by LPS-stimulated chondrocytes. Western blot analysis revealed expression, in response to LPS, of protein in the same molecular weight range as iNOS identified in other species. This work demonstrates that equine chondrocytes have the capacity to synthesise NO, although its exact roles in cartilage metabolism have yet to be determined.

Animals↗