Dechra Pharmaceuticals (United Kingdom)

Reasons for performing studyClodronic acid (CA) is a bisphosphonate which inhibits bone resorption through inhibition of formation/dissolution of hydroxyapatite crystals and by direct cellular effects on osteoclasts. The study was conducted to assess the short‐ and long‐term effectiveness of CA for the control of lameness associated with navicular syndrome.ObjectivesTo demonstrate the effectiveness of CA in navicular syndrome.Study designRandomised, multi‐centre, double‐masked, placebo controlled field trial in client‐owned horses.MethodsHorses with unilateral or bilateral forelimb lameness (AAEP lameness scale grade ≥2); positive anaesthesia of the distal palmar digital nerve(s); radiographic evidence of navicular syndrome and the absence of other causes of lameness were eligible for enrolment. Horses were randomised to treatment groups in a 3:1 ratio of CA to saline control. Treatment was administered once via intramuscular injection at 1.2 mg/kg bwt (maximum 765 mg CA or 15 ml saline). Efficacy was assessed by comparing lameness grades before and after treatment.Results146 horses of various breeds were enrolled at 6 sites in Germany and US. At 8 weeks, horses in the CA group had a significantly higher success rate than horses in the control group (least squares mean 74.72% vs. 3.30%; P = 0.0028). Efficacy was sustained through 180 days in 66% of horses. Adverse events were few and considered to be mild and transient.ConclusionsClodronic acid was safe and effective in navicular syndrome.Ethical animal research: Owners gave informed consent for their horses’ inclusion in the study. Sources of funding: Dechra Ltd. Competing interests: The late Dr Frevel was a consultant to Omnimedic GbR, which has applied for a patent for the use of clodronic acid for navicular syndrome. Dr Poole is employed by Dechra.

BackgroundThe effects of trilostane on key hormones and electrolytes over 24 hours in dogs with pituitary‐dependent hyperadrenocorticism (PDH) are unknown.ObjectivesTo determine the plasma concentration of cortisol, endogenous adrenocorticotropic hormone (ACTH), aldosterone, sodium, potassium, and ionized calcium concentrations, and plasma renin activity over a 24‐hour period after administration of trilostane to dogs with well‐controlled PDH.AnimalsNine dogs (mean age 9.3 ± 0.67 years, mean weight 31.9 ± 6.4 kg) with confirmed PDH.MethodsProspective study. Thirty days after the first administration of trilostane, blood samples were taken at −30, 0 (baseline), 15, 30, 60, and 90 minutes, and 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after administration of trilostane and plasma concentration of cortisol, endogenous ACTH, aldosterone, sodium, potassium, ionized calcium, and renin activity were determined.ResultsCortisol concentrations decreased significantly (P < .001) 2–4 hours after trilostane administration. From baseline, there was a significant (P < .001) increase in endogenous ACTH concentrations between hours 3–12, a significant increase (P < .001) in aldosterone concentration between hours 16–20, and a significant (P < .001) increase in renin activity between hours 6–20. Potassium concentration decreased significantly (P < .05) between hours 0.5–2.Conclusion and Clinical ImportanceTreatment with trilostane did not cause clinically relevant alterations in plasma aldosterone and potassium concentration. Results suggest that in dogs with PDH, the optimal time point for an ACTH‐stimulation test to be performed is 2–4 hours after trilostane dosing. Future studies are necessary to establish interpretation criteria for a 2‐ to 4‐hour postpill ACTH‐stimulation test.

A 53-year-old woman with chronic plaque psoriasis treated with adalimumab (antitumour necrosis factor (anti TNF) α therapy) for 10 months presented with an 8 week history of hyperesthesia in a ‘glove and stocking’ distribution and clumsiness on walking. Nerve conduction studies confirmed the clinical diagnosis of a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). She was admitted and treated with intravenous immunoglobulin and oral steroids and made an excellent recovery. To our knowledge, this is the first published report of CIDP associated with anti TNF α therapy given to treat psoriasis.

The link between the fermentation of carbohydrate in the equine large intestine and the development of acute laminitis is poorly understood. Absorption of endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one experimental model of laminitis, but does not cause laminitis when administered alone. Thus, the potential role of endotoxin is unclear. Platelet activation has previously been demonstrated in the developmental stage of laminitis. Equine platelets are more sensitive than leukocytes to activation by endotoxin, and can be activated directly by LPS in the low pg/ml range, activating p38 MAP kinase and releasing serotonin (5-HT) and thromboxane. The objectives of this study were firstly to determine whether endotoxin and platelet activation could be measured in the plasma of horses in the developmental phase of laminitis induced with oligofructose. Secondly, the time course of events involving platelet activation and platelet-derived vasoactive mediator production was investigated. Laminitis was induced in six Standardbred horses by the administration of 10 g/kg bwt of oligofructose. Plasma samples were obtained every 4 h, and platelet pellets were obtained by centrifugation. LPS was measured using a kinetic limulus amebocyte lysate assay, and platelet activation was assessed by Western blotting for the phosphorylated form of p38 MAP kinase. Plasma 5-HT was assayed by HPLC with electrochemical detection and thromboxane B 2 was measured by radioimmunoassay. Clinical signs of laminitis and histopathologic changes were observed in lamellar sections from five of the six horses. Onset of lameness was between 20 and 30 h after the administration of oligofructose. LPS increased above the limit of detection (0.6 pg/ml) to reach a peak of 2.4 ± 1.0 pg/ml at 8 h. TNFα was also detectable in the plasma from 12 to 24 h. There was a time-dependent increase in platelet p38 MAPK phosphorylation, which peaked at approximately 12 h (3.8 ± 1.3 fold increase); plasma 5-HT and thromboxane increased steadily after this time (2.9 ± 0.6 and 11.3 ± 5.0 fold increases, respectively). These data indicate that small quantities of endotoxin may move into the circulation from the large intestine after the sharp decrease in pH that occurs as a result of carbohydrate fermentation. Correlating these findings with in vitro studies suggests that LPS may primarily activate platelets, leading indirectly to the activation of leukocytes. Therefore, endotoxin may contribute in the initiation of the early inflammatory changes observed in experimental models of acute laminitis.

The efficacy of top-dress antiinflammatory drugs ultimately depends on a patient's willingness to consume treated feed. The current study compares the palatability of two phenylbutazone top-dress formulations (Equipalazone Powder, Dechra Pharmaceuticals, and Pro-Dynam, VetXX, Ltd.) and a suxibuzone top-dress formulation (Danilon Equidos, Janssen Animal Health). Results of a three-period, crossover study on 18 healthy horses showed that Pro-Dynam was significantly less palatable, with significantly less consumption of treated feed compared with either Equipalazone Powder or Danilon Equidos. There was no statistically significant difference in terms of consumption of treated feed and palatability scores between Equipalazone Powder and Danilon Equidos.