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P Lees

Publications and source records attributed to P Lees.

At least 37 records · Page 2Linked to original sources
PubMed2002

Phenobarbitone concentrations in the hair, saliva and plasma of eight epileptic dogs.

Samples of plasma, saliva and hair were collected from eight dogs receiving phenobarbitone for idiopathic epilepsy. The concentrations of phenobarbitone in hair and plasma were correlated with the daily dose rate, and the concentrations in hair were also correlated with the concentration in plasma, the dose rate of the drug over the preceding six months and the ratio of the six-month dose to body surface area. The concentration of phenobarbitone in saliva was not correlated with either the concentration in plasma or the dose rate of the drug.

Animals↗
PubMed2002

Clinical efficacy and pharmacokinetics of carprofen in the treatment of dogs with osteoarthritis.

Six medium to large breed dogs with osteoarthritis were treated with 2 mg/kg of racemic carprofen, mixed with their morning feed, daily for 28 days. The treatment significantly (P < 0.01) reduced their mean lameness score, measured on a visual analogue scale, and there was a trend (P = 0.11) for the peak vertical forces exerted on a forceplate to be increased in the most severely affected limb. The plasma concentration-time relationships of the S(+) and R(-) enantiomers were studied for 24 hours after the first dose and after seven days and 28 days. There were no significant differences between the mean pharmacokinetic parameters measured on the three occasions, suggesting that carprofen was not accumulated and that tolerance to the drug did not develop. Although the pharmacokinetic parameters of the S(+) and R(-) enantiomers were generally very similar, there were wide variations both between and within dogs.

Administration, Oral↗
PubMed2002

Effects of carprofen (R and S enantiomers and racemate) on the production of IL-1, IL-6 and TNF-alpha by equine chondrocytes and synoviocytes.

Chondrocytes and synoviocytes harvested from the joints of healthy horses were maintained in tissue culture. Production of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in response to lipopolysaccharide (LPS), and the effects of addition of carprofen (racemate and R and S enantiomers) were determined. Lipopolysaccharide failed to stimulate TNF-alpha activity in both cell types but concentrations of IL-1 and IL-6 were both increased in a concentration and time-related manner. Both carprofen enantiomers and the racemic mixture attenuated the increase in IL-6 induced by LPS in synoviocytes, and S carprofen exerted a similar effect on chondrocytes. Neither enantiomer nor the racemate of carprofen suppressed the increase in IL-1 release produced by LPS in chondrocytes and synoviocytes. An action of carprofen to suppress IL-6 release might contribute to the actions which occur in vivo.

Animals↗
PubMed2002

Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate.

Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration-time curve (AUC) and elimination half-life (t(1/2)el) values were 9.99 and 10.11 microg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan-induced exudate, lipopolysaccharide-induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 microg h/mL after intravenous and 8.84, 8.53 and 8.52 microg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 microg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 microg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration-dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24-h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan-induced exudate and transudate) and 36 h (lipopolysaccharide-induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.

Animals↗
PubMed2002

Effects of anti-arthritic drugs on proteoglycan synthesis by equine cartilage.

The concentration-effect relationships of phenylbutazone, indomethacin, betamethasone, pentosan polysulphate (PPS) and polysulphated glycosaminoglycan (PSGAG), on proteoglycan synthesis by equine cultured chondrocytes grown in monolayers, and articular cartilage explants were measured. The effect of PSGAG on interleukin-1beta induced suppression of proteogycan synthesis was also investigated. Proteoglycan synthesis was measured by scintillation assay of radiolabelled sulphate (35SO4) incorporation. Polysulphated glycosaminoglycan and PPS stimulated proteoglycan synthesis in chondrocyte monolayers in a concentration-related manner with maximal effects being achieved at a concentration of 10 microg/mL. Polysulphated glycosaminoglycan reversed the concentration-related suppression of proteoglycan synthesis induced by interleukin-1beta. Neither PSGAG nor PPS exerted significant effects on radiolabel incorporation in cartilage explants. Betamethasone suppressed proteoglycan synthesis by both chondrocytes and explants at high concentrations (0.1-100 microg/mL), but the effect was not concentration-related. At low concentrations (0.001-0.05 microg/mL) betamethasone neither increased nor decreased proteoglycan synthesis. Phenylbutazone and indomethacin increased radiolabel incorporation in chondrocyte cultures but not in cartilage explants at low (0.1, 1 and 10 microg/mL), but not at high (20 and 100 microg/mL) concentrations. These findings may be relevant to the clinical use of these drugs in the treatment of equine disease.

Animals↗
PubMed2002

Pharmacodynamics and pharmacokinetics of phenylbutazone in calves.

Phenylbutazone (PBZ) was administered to six calves intravenously (i.v.) and orally at a dose rate of 4.4 mg/kg in a three-period cross-over study incorporating a placebo treatment to establish its pharmacokinetic and pharmacodynamic properties. Extravascular distribution was determined by measuring penetration into tissue chamber fluid in the absence of stimulation (transudate) and after stimulation of chamber tissue with the mild irritant carrageenan (exudate). PBZ pharmacokinetics after i.v. dosage was characterized by slow clearance (1.29 mL/kg/h), long-terminal half-life (53.4 h), low distribution volume (0.09 L/kg) and low concentrations in plasma of the metabolite oxyphenbutazone (OPBZ), confirming previously published data for adult cattle. After oral dosage bioavailability (F) was 66%. Passage into exudate was slow and limited, and penetration into transudate was even slower and more limited; area under curve values for plasma, exudate and transudate after i.v. dosage were 3604, 1117 and 766 microg h/mL and corresponding values after oral dosage were 2435, 647 and 486 microg h/mL. These concentrations were approximately 15-20 (plasma) and nine (exudate) times greater than those previously reported in horses (receiving the same dose rate of PBZ). In the horse, the lower concentrations had produced marked inhibition of eicosanoid synthesis and suppressed the inflammatory response. The higher concentrations in calves were insufficient to inhibit significantly exudate prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and beta-glucuronidase concentrations and exudate leucocyte numbers, serum thromboxane B2 (TxB2), and bradykinin-induced skin swelling. These differences from the horse might be the result of: (a) the presence in equine biological fluids of higher concentrations than in calves of the active PBZ metabolite, OPBZ; (b) a greater degree of binding of PBZ to plasma protein in calves; (c) species differences in the sensitivity to PBZ of the cyclo-oxygenase (COX) isoenzymes, COX-1 and COX-2 or; (d) a combination of these factors. To achieve clinical efficacy with single doses of PBZ in calves, higher dosages than 4.4 mg/kg will be probably required.

Administration, Oral↗
PubMed2002

Pharmacodynamics and enantioselective pharmacokinetics of racemic carprofen in the horse.

Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) values for R(-) and S(+)-carprofen of 117.4 and 22.6 microg h/mL (low dose carprofen) and 557.5 and 138.1 microg h/mL (high dose carprofen) respectively. Penetration of both enantiomers into exudate was slow and limited and passage into transudate was even lower. The pharmacodynamics of rac-carprofen was investigated at both the molecular level and in terms of the ability to suppress components of the tissue cage inflammatory response. Low dose carprofen produced only moderate and transient inhibition of serum thromboxane (Tx)B2 but failed to affect exudate prostaglandin (PG)E2 concentrations, whilst suppression of exudate leukotriene (LT)B4 and beta-glucuronidase was not significant. High dose carprofen produced greater and more persistent inhibition of serum TxB2 and virtually abolished exudate PGE2 synthesis. Some inhibition of LTB4 and beta-glucuronidase in exudate was also obtained. At both dosages rac-carprofen reduced the swelling produced by intradermal bradykinin injection but only high dose carprofen was anti-inflammatory as indicated by suppression of temperature rise over exudate tissue cages and neither dose affected leucocyte numbers in exudate. When considered in conjunction with previous data on carprofen, the present findings indicate that carprofen is not a selective inhibitor of cyclooxygenase (COX) isoenzymes, COX-1 and COX-2 in the horse, although it may show some preference for COX-2 inhibition. Because low dose carprofen, which is the clinically recommended dosage, produces minimal inhibition of COX, it is likely to achieve its therapeutic effects at least partially through other pathways, possibly including weak to moderate inhibition of 5-lipoxygenase and of enzyme release. The good safety margin of carprofen in clinical use might also be explained by weak COX inhibition and by other actions at the molecular level.

Animals↗
PubMed2002

Antigen challenge increases adherence of circulating neutrophils in horses with chronic obstructive pulmonary disease.

Activation of circulating neutrophils has been observed following challenge of horses with chronic obstructive pulmonary disease (COPD) and may facilitate the accumulation of these cells in the airways. In this study, no significant difference was observed between adherence to protein coated plastic of blood neutrophils from asymptomatic COPD-susceptible and normal horses stimulated by the mediators PAF, human recombinant (hr)IL-8 and hrC5a. Twenty-four hours after the start of a 7 h antigen challenge, adherence of unstimulated neutrophils from COPD-susceptible horses increased from 2.5 (0.5-4.1)% and 3.4 (0.6-6.6)% to 19.6 (16.9-20.3)% and 21.8 (10.6-23.1)% adherence for cells in medium containing 0.1% or 0.2% BSA, respectively; (median [range]; n = 4). Adherence of cells from normal horses remained unchanged. Addition of an anti-CD18 monoclonal antibody, H20A, inhibited the increase in adherence at 24 h by 96 (45-100)%, n = 3. The percentage of neutrophils in bronchoalveolar lavage fluid at 24 h increased from 1 (0-2) to 80 (65-94), (median (range), n = 4). These results suggest that antigen challenge results in exposure of circulating equine neutrophils to one or more factors that prime, or activate, these cells, which may enhance their recruitment to the lungs. Inhibition of circulating neutrophil activation may therefore represent a therapeutic target.

Animals↗
PubMed2001

Absence of mutations in the growth hormone (GH)-releasing hormone receptor gene in GH-secreting pituitary adenomas.

OBJECTIVE: GH-releasing hormone (GHRH) is a potent stimulator of somatotroph cell proliferation and GH secretion. GHRH acts via binding to a G-protein coupled receptor (GPCR) (GHRH-R), that activates adenylyl cyclase (AC) and increases growth and function of somatotroph cells. Indeed, a subset (30--40%) of somatotrophic adenomas contain somatic mutations of the GNAS1 gene that encodes the alpha subunit of the G-protein (G(s)alpha) that stimulates AC. As activating mutations of other GPCRs cause development of endocrine tumours, we hypothesized that somatic activating mutations of the GHRH-R might provide the molecular basis for somatotroph cell proliferation in a subset of human GH-secreting pituitary adenomas. DESIGN: We analysed genomic DNA isolated from 26 somatotrophinomas, 17 of which lacked activating mutations in the GNAS1 gene. We individually amplified via polymerase chain reaction all 13 coding exons and the exon-intron boundaries of the GHRH-R gene. We used denaturing gradient gel electrophoresis to search for abnormalities in exons 1 through 11. Abnormally migrating bands were subjected to direct sequencing. Exons 12 and 13, encoding for the intracellular C-terminal domain, were subjected to direct sequencing. RESULTS: Mutations were not detected in any of the tumours, but a rare polymorphism in codon 225 corresponding to the third transmembrane domain (V225I) was discovered. CONCLUSIONS: GHRH-R mutations are absent or rare in somatotrophinomas, and other mechanisms must explain the somatotroph cell proliferation in the adenomas that lack activating mutations in the GNAS1 gene.

Adenoma↗
PubMed2001

Differential inhibition of equine neutrophil function by phosphodiesterase inhibitors.

Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge, which may contribute to inflammation and lung damage. Inhibition of phosphodiesterase isoenzymes (PDEs) has been shown to attenuate human neutrophil functions including superoxide production, leukotriene (LT)B4 biosynthesis, enzyme and chemokine release. As equine neutrophils contain predominantly the isoenzyme, PDE4, the present study was undertaken to investigate the effects of rolipram, a PDE4 inhibitor, on equine neutrophil function. For comparison, the effects of the nonselective PDE inhibitor, theophylline, were examined. Cells from both normal horses and COPD horses in remission were used. Superoxide production was significantly inhibited by both rolipram [32.2 +/- 2.6 vs. 10.1 +/- 1.1 nmol/10(6) cells and 49.8 +/- 6.8 vs. 22.7 +/- 2.2 nmol/10(6) cells for normal and COPD susceptible horses, respectively, in response to 10(-7) M human recombinant (hr) C5a] and theophylline (19.0 +/- 0.6 vs. 10.2 +/- 0.6 nmol/10(6) cells and 24.3 +/- 2.1 vs. 10.7 +/- 0.9 nmol/10(6) cells for normal and COPD susceptible horses, respectively, in response to 10(-7) M C5a). However, superoxide production induced by serum treated zymosan was inhibited only by theophylline (10(-3) M). Neither hrC5a- nor platelet activating factor (PAF)-induced neutrophil adherence to fibronectin coated plastic was reduced by rolipram (10(-5) M). These results demonstrate that the effects of PDE inhibitors on equine neutrophils are both stimulus and function dependent. The PDE4 inhibitors may reduce neutrophil activation in vivo in horses with COPD.

Animals↗
PubMed2001

Pharmacokinetics and pharmacodynamics of danofloxacin in serum and tissue fluids of goats following intravenous and intramuscular administration.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of danofloxacin in goats and the concentrations required to induce bacteriostasis, bactericidal activity, and bacterial elimination. ANIMALS: 6 healthy British Saanen goats. PROCEDURE: Danofloxacin (1.25 mg/kg of body weight) was administered i.v. and i.m. in a cross-over design with 14 days between treatments. A tissue cage was used for evaluation of drug distribution into transudate and exudate. The ex vivo antibacterial activity of danofloxacin in serum, exudate, and transudate against a caprine isolate of Mannheimia haemolytica was determined. Pharmacokinetic and pharmacodynamic data were integrated to determine the ratio of the area under the concentration versus time curve to the minimum inhibitory concentration of danofloxacin (AUIC). RESULTS: Elimination half-lives of danofloxacin in serum were 4.67 and 4.41 hours after i.v. and i.m. administration, respectively. Volume of distribution was high after administration via either route, and bioavailability was 100% after i.m. administration. Rate of penetration into exudate and transudate was slow, but elimination half-lives from both fluids were approximately twice that from serum. Drug concentrations in serum, exudate, and transudate for 9 to 12 hours after administration induced marked ex vivo antibacterial activity. For serum, AUIC24h values required for bacteriostasis, bactericidal effect, and bacterial elimination were 22.6, 29.6, and 52.4, respectively. Similar values were obtained for exudate and transudate. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of danofloxacin pharmacokinetic and pharmacodynamic data obtained in goats may provide a new approach on which to base recommendations for therapeutic dosages.

Animals↗
PubMed2001

Pharmacodynamics and pharmacokinetics of ketoprofen enantiomers in sheep.

OBJECTIVE: To establish pharmacokinetic and pharmacodynamic properties of a racemic mixture and individual R(-) and S(+) enantiomeric forms of ketoprofen (KTP) in sheep and determine pharmacodynamic variables of KTP by pharmacokinetic-pharmacodynamic modeling. ANIMALS: 8 female Dorset crossbred sheep. PROCEDURE: A tissue cage model of inflammation was used. Carrageenan was administered into tissue cages. Time course of cyclooxygenase (COX)-2 inhibition was determined in vivo by measurement of exudate prostaglandin E2 (PGE2) concentrations. Time course of COX-1 inhibition was determined ex vivo by measurement of serum thromboxane B2 (TXB2) concentrations. In addition, plasma concentration-time course and penetration of KTP enantiomers into inflammatory exudate and transudate (noninflamed tissue cage fluid) were investigated. Four treatments were compared: placebo, racemic mixture (rac-KTP [3 mg/kg of body weight, IV]), S(+) KTP (1.5 mg/kg, IV),and R(-) KTP (1.5 mg/kg, IV). RESULTS: Both KTP enantiomers had elimination half-life and mean residence time measurements that were short and volume of the central compartment and steady state volume of distribution that were low. Clearance was rapid, particularly for R(-) KTP Elimination of both enantiomers from exudate was > 10 times slower than from plasma. Both rac-KTP and the individual enantiomers significantly inhibited serum TXB2 concentrations for 12 hours. Rac-KTP and S(+) KTP, but not R(-) KTP, also significantly inhibited PGE2 synthesis in exudate for 12 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Inhibition of serum TXB2 concentration and exudate PGE2 synthesis for similar time courses after S(+) KTP administration indicates that it is a nonselective inhibitor of COX in sheep.

Animals↗
PubMed2000

Phosphodiesterase activity in neutrophils from horses with chronic obstructive pulmonary disease.

Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge. Phosphodiesterase type4 (PDE4) inhibitors have been shown to attenuate human neutrophil activation. The aim of this study was to establish the PDE isoenzyme profile of equine neutrophils using isoenzyme selective inhibitors to determine if these compounds should be evaluated in horses with COPD. Total cAMP and cGMP dependent PDE activity was no different in neutrophils from normal (156.2+/-7.1 and 6.8+/-0.6 pmol/min/mg for cAMP and cGMP, respectively) and COPD susceptible horses (146.0+/-10.2 and 5.5+/-0.6 pmol/min/mg for cAMP and cGMP, respectively). The PDE4 inhibitors, CDP840 and rolipram, caused significant, concentration related and almost complete inhibition of PDE activity (IC(50) values=8.8+/-0.1 x 10(-9) and 7.3+/-0.2 x 10(-9)M for CDP840; 1.2+/-0.1 x 10(-6) and 1.1+/-0.1 x 10(-6)M for rolipram in normal and COPD susceptible horses, respectively). The inhibitory effects of the mixed PDE3/ PDE4 inhibitor, zardaverine were of similar magnitude and potency to rolipram. However, the limited inhibitory effects of the PDE3 inhibitor, siguazodan, suggest that zardaverine is acting primarily via PDE4 inhibition. These results indicate that PDE4 is the predominant isoenzyme present in the equine neutrophil and inhibition of PDE activity using selective PDE4 inhibitors may, therefore, modulate equine neutrophil activation in horses with COPD.

Animals↗
PubMed2000

Use of antibiotics in penetrating craniocerebral injuries. "Infection in Neurosurgery" Working Party of British Society for Antimicrobial Chemotherapy.

The Working Party was instituted to investigate the rationale of prophylactic and therapeutic antibiotic use in penetrating craniocerebral injuries (PCCI), and to make recommendations for current practice. A systematic review of papers on civilian and military PCCI over the past 25 and 50 years, respectively, was done via electronic databases and secondary sources, and data were evaluated. Guidelines on the removal of indriven bone or metal fragments only if further neural damage can be avoided were supported. However, no publications were identified where the data on infection or its treatment and prevention were complete or satisfactorily derived, and no controlled trials have been published. All studies were retrospective or anecdotal. Working Party recommendations are based on the data available and the professional experience and knowledge of the members. Broad-spectrum antibiotic prophylaxis is recommended for both military and civilian PCCI, Including those due to sports or recreational injuries.

Anti-Bacterial Agents↗
PubMed2000

Antibiotic treatment for animals: effect on bacterial population and dosage regimen optimisation.

Concern regarding antimicrobial resistance has led to proposals for the prudent use of antimicrobial agents. Whilst this is appropriate, it is not sufficient. This article proposes that dosage schedules should be developed to provide a basis for the rational use of antimicrobial drugs. This requires knowledge of resistance mechanisms and transfer, the biochemistry and structure of microorganisms and both the pharmacodynamics and pharmacokinetics of antimicrobial drugs. Dosage schedules should maintain concentrations at the site of infection in excess of MIC(90) for bacteriostatic drugs and bactericidal drugs acting primarily by time-dependent mechanisms whilst they should provide high AUIC and C(max)/minimum inhibitory concentration (MIC) values for agents acting mainly by concentration-dependent mechanisms. It is proposed that pharmacodynamic and population pharmacokinetic data should be integrated through use of the sigmoidal E(max) equation, together with mathematical modelling and appropriate statistical analyses, to take account of the natural variation in drug pharmacodynamics and pharmacokinetics.

Animal Diseases↗
PubMed2000

Influence of interleukin-1beta and hyaluronan on proteoglycan release from equine navicular hyaline cartilage and fibrocartilage.

Proteoglycan (PG) release, in response to recombinant human interleukin-1beta (rh-IL-1beta), was measured in cartilage explants obtained from the equine distal sesamoid bone (navicular bone). Fibrocartilage from the surface of the navicular bone apposing the deep digital flexor tendon and hyaline cartilage from the surface of the navicular bone articulating with the middle phalanx were labelled with 35SO4. Hyaline cartilage from the distal metacarpus was used as a control tissue. Following radiolabel incorporation, the three cartilage types were treated with rh-IL-1beta (100 U/mL) in the presence of hyaluronan (0.2, 2, 20, 200 and 2000 microgram/mL). rh-IL-1beta-Induced PG release was measured by scintillation assay of PG-bound radiolabel. Increases in PG release of 94% (P < 0.01), 101% (P < 0.05) and 122% (P < 0.05), in response to rh-IL-1beta, were noted in fibrocartilage, navicular hyaline cartilage and metacarpal hyaline cartilage, respectively. Hyaluronan (0.2 microgram/mL) significantly reduced rh-IL-1beta-induced PG release in metacarpal hyaline cartilage (P < 0.01). In fibrocartilage and navicular hyaline cartilage, hyaluronan did not reduce PG release and at some concentrations appeared to increase PG release, although this was not statistically significant. These experiments show that (i) fibrocartilage and hyaline cartilage of the navicular bone release PGs in response to rh-IL-1beta, and (ii) hyaluronan does not prevent rh-IL-1beta-induced breakdown of navicular bone cartilage.

Adjuvants, Immunologic↗