Feeding driet chicory root to pigs decrease androstenone accumulation in fat by increasing hepatic 3β hydroxysteroid dehydrogenase expression

The present study investigated the in vivo effect of chicory root on testicular steroid concentrations and androstenone metabolizing enzymes in entire male pigs. Furthermore, the effect on skatole and indole concentrations in plasma and adipose tissue was investigated. The pigs were divided into two groups; one receiving experimental feed containing 10% dried chicory root for 16 days before slaughter, the control group was fed a standard diet. Plasma, adipose and liver tissue samples were collected at slaughter. Plasma was analyzed for the concentration of testosterone, estradiol, insulin-like growth factor 1 (IGF-1), skatole and indole. Adipose tissue was analyzed for the concentration of androstenone, skatole and indole, while the liver tissue was analyzed for mRNA and protein expressions of 3β-hydroxysteroid dehydrogenase (3β-HSD), sulfotransferase 2A1 and heat-shock protein 70 (HSP70). The results showed that the androstenone concentrations in the adipose tissue of chicory fed pigs were significantly (p < 0.05) lower and indole concentrations were higher (p < 0.05) compared to control fed pigs. Moreover the chicory root fed pigs had increased mRNA and protein expression of 3β-HSD and decreased HSP70 expression (p < 0.05). Testosterone and IGF-1 concentrations in plasma as well as skatole concentrations in adipose tissue were not altered by dietary intake of chicory root. It is concluded that chicory root in the dietreduces the concentration of androstenone in adipose tissue via induction of 3�-HSD, and that these changes were not due to increased cellular stress

Dexamethasone in horses

Equine athletes and companion horses are commonly treated with glucocorticoids such as dexamethasone. Care of sick or injured animals is vital for the animal welfare. To protect the integrity of equine sport, legal therapeutic substances are regulated during competition. The overall aim of this thesis was to provide quantitative information of dexamethasone exposure and response in Standardbreds and to relate this information to medication and anti-doping methodology. Dexamethasone-21-isonicotinate suspension administered intramuscularly and dexamethasone sodium phosphate solution administered both intravenously and intra- articularly were used in experiments. Dexamethasone was quantified in plasma, urine and synovial fluid by means of UHPLC-MS/MS. Cortisol response, IL-1β response, joint circumference response, local skin temperature response and lameness response were used as biomarkers. Dexamethasone plasma- and synovial fluid concentration-time courses were characterised by means of compartment modelling. The response-time courses were described by fitting a turnover model with an inhibitory function to experimental biomarker response data. Dexamethasone exposure was described in plasma and synovial fluid. In the Standardbreds studied, median dexamethasone plasma clearance was 0.51 L∙h-1∙kg-1 and median volume of distribution (at steady state) was 1.58 L∙kg-1. The median half-life in plasma and synovial fluid was 2.4 h and 1.3 h, respectively. After intramuscular administration of dexamethasone-21-isonicotinate, mean terminal half-life was 39 h due to slow release into plasma from the injection site. The dexamethasone concentration was 4- to 15-fold higher in urine than in plasma. A circadian cortisol baseline was described using a cosine function and cortisol response was characterised. Median potency value and for cortisol response in plasma was 0.039 ng∙mL-1 and the efficacy value was 0.92. Dexamethasone inhibited lameness and synovial fluid IL-1β release at doses lower than the approved. The median calculated synovial fluid concentration that suppressed lameness response by 50 % was 17 ng∙mL-1. The tentative potency value for IL-1β response was 19 ng∙mL-1. The information provided in this thesis can be used to improve future medication protocols and anti-doping controls which could improve animal welfare

Return to play after thigh muscle injury in elite football players: implementation and validation of the Munich muscle injury classification

Background: Owing to the complexity and heterogeneity of muscle injuries, a generally accepted classification system is still lacking. Aims To prospectively implement and validate a novel muscle injury classification and to evaluate its predictive value for return to professional football. Methods: The recently described Munich muscle injury classification was prospectively evaluated in 31 European professional male football teams during the 2011/2012 season. Thigh muscle injury types were recorded by team medical staff and correlated to individual player exposure and resultant time-loss. Results: In total, 393 thigh muscle injuries occurred. The muscle classification system was well received with a 100% response rate. Two-thirds of thigh muscle injuries were classified as structural and were associated with longer lay-off times compared to functional muscle disorders (p<0.001). Significant differences were observed between structural injury subgroups (minor partial, moderate partial and complete injuries) with increasing lay-off time associated with more severe structural injury. Median lay-off time of functional disorders was 5–8 days without significant differences between subgroups. There was no significant difference in the absence time between anterior and posterior thigh injuries. Conclusions: The Munich muscle classification demonstrates a positive prognostic validity for return to play after thigh muscle injury in professional male football players. Structural injuries are associated with longer average lay-off times than functional muscle disorders. Subclassification of structural injuries correlates with return to play, while subgrouping of functional disorders shows less prognostic relevance. Functional disorders are often underestimated clinically and require further systematic study

Nitrofurantoin plasma- and urine exposure in eight healthy beagle dogs following standard nitrofurantoin dosing regimen

Bacterial cystitis is common in dogs and is usually treated with antibiotics. Nitrofurantoin is used for treatment of bacterial cystitis in humans and might provide a feasible treatment option in dogs. The aim of this study was to investigate the nitrofurantoin plasma concentration-time course and potential adverse effects in dogs. Nitro-furantoin (4.4-5.0 mg/kg) was administered orally to eight healthy beagles every 8 h for five days before repeated plasma and urine samples were collected. An additional four beagles served as untreated controls. The nitrofurantoin plasma and urine concentrations were measured using ultra high precision liquid chromatography coupled to tandem mass-spectrometry and further analysed using a non-compartmental pharmacokinetic model. In plasma, the median C-max was 2.1 mu g/mL, t(max) was 2 h, the terminal rate constant was 0.9 per h and the terminal half-life was 0.8 h. In urine, median C-max was 56 mu g/mL, t(max) was 1 h and the terminal half-life was 4.3 h. No adverse effects were observed clinically or in haematology or biochemistry. The data presented in this study combined with in vitro sensitivity data from common urine pathogens and the lack of observed adverse effects suggest that nitrofurantoin in a standard dosing regimen could be effective in sporadic bacterial cystitis treatment in dogs. Further clinical studies are highly warranted to verify the effectiveness in clinical cases

In vivo joint synovial fluid disposition of a novel sustained-release formulation of diclofenac and hyaluronic acid in horses

Intra-articular administration of sustained-release anti-inflammatory drugs is indicated in horses suffering from joint inflammation, but no such drugs are labelled for veterinary use. To obtain initial data on synovial disposition and safety of a new sustained-release formulation of diclofenac (SYN321) in the joints of horses, an experimental interventional study of elimination and side effects of intra-articular administration of SYN321 was conducted. Nine clinically sound horses were included in the study, and SYN321 was administered by the intra-articular route. Dose ranges and sampling intervals were established in a pilot study with two horses, and then applied in a main study involving seven horses treated in the fetlock joint. Diclofenac was detected above lower limit of quantification (LOQ: 0.5 ng/ml) in synovial fluid throughout the study period (14 days), and below LOQ (0.1 ng/ml) in plasma after 4 days and in urine after 14 days. No obvious clinical side effects were detected. Clinical examination and objective lameness evaluation suggested that SYN321 has potential as a local joint NSAID treatment with sustained release in horses, but further studies on synovial fluid exposure, safety and clinical efficacy are warranted

Plasma atropine concentrations associated with decreased intestinal motility in horses

IntroductionAtropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Materials and methodsEight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. ResultsAtropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg center dot h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 mu g/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. ConclusionThe IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 mu l of 1% atropine sulfate per drop or less may be used to lower the risk further