P.A. Harris

Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies

This study described a scoring system for the assessment of apparent neck adiposity and evaluated morphometric measurements for assessment of neck and overall adiposity. Twenty-one barren Thoroughbred mares, 13 Arabian geldings and 75 Welsh, Dartmoor, or crossbred pony mares, were clinically examined and blood samples analysed for insulin, glucose, leptin, and triglycerides. Bodyweight (BW), height, length, girth and abdominal circumferences, neck length, neck crest height and neck circumference were measured, and body condition scores (BCS) and cresty neck scores (CNS) were rated. Girth:height ratio had the strongest associations with BCS (r(s)=0.64, P<0.001 in horses; r(s)=0.83, P<0.001 in ponies) and blood variables, such as leptin (r(s)=0.39, P=0.024 in horses; r(s)=0.68, P<0.001 in ponies). Crest height and neck circumference:height ratio had the strongest association with CNS (r(s)>0.50, P<0.01) and blood variables, such as insulin (r(s)0.40, P<0.05). Cresty neck score was useful in the assessment of neck crest adiposity and had physiological relevance, as demonstrated by associations with blood variables. Girth:height was the most suitable morphometric for assessment of overall adiposity, and either crest height or neck circumference:height was a suitable morphometric for assessment of apparent neck adiposity.

Biological actions of curcumin on articular chondrocytes

OBJECTIVES Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA.

Risk factors associated with equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark

REASONS FOR PERFORMING STUDY The prevalence (up to 93% in Thoroughbred racehorses) and severity of equine gastric ulceration syndrome (EGUS) has been associated with type of training and differing management practices. However, there have been few studies to confirm these findings in nonracehorses in Europe. OBJECTIVES To investigate the prevalence of EGUS in a population of Danish horses, during winter when the horses had been housed and fed for at least 8 weeks and to analyse the influence of feed, work level and environment on the risk of EGUS of > or = grade 2 in severity. METHODS A total of 201 horses, not in active race-training, were evaluated, representing 23 different stables from all 5 regions within Denmark. All horses were considered to be healthy and not on medical treatment for EGUS. Endoscopically observed ulcer lesion scores were based on the number present (0-4) and severity (0-5). Univariate and multivariable mixed effects logistic regression models were developed using EGUS score as the dependent variable. An ulceration severity score of > or = 2 was regarded as being clinically significant. Separate models were developed for horses with ulcers in either the glandular or nonglandular regions of the stomach graded > or = 2 (EGUS > or = 2) and for those horses that had nonglandular ulcers graded > or = 2 (NG > or = 2). RESULTS In this population, 53% (107/201) of horses were graded as having EGUS > or = 2 with 95 (47%) horses having NG > or = 2. Three variables were significantly (P<0.05) associated with EGUS > or = 2: straw being the only forage available; exceeding 2 g/kg bwt of starch intake/day or >1 g/kg bwt/meal; and water not being available in the turn out paddock. Risk of NG > or = 2 significantly increased when straw was the only forage available, 1 g/kg bwt of starch/meal was exceeded, water was not available in the turnout paddock and the interval between forage feeding was >6 h. CONCLUSION AND POTENTIAL RELEVANCE This study has confirmed that components of the diet, readily modifiable, may have an important impact on the risk of EGUS in the nonracehorse. Differences in the multivariable models produced for all ulcers and nonglandular ulcers support differences in the aetiology of ulcers in different locations of the stomach.

Identification of equine cecal bacteria producing amines in an in vitro model of carbohydrate overload.

ABSTRACT Acute laminitis has been associated with the overgrowth of gram-positive bacteria within the equine hindgut, causing the release of factor(s) leading to ischemia-reperfusion of the digits. The products of fermentation which trigger acute laminitis are, as yet, unknown; however, vasoactive amines are possible candidates. The objectives of this study were to use an in vitro model of carbohydrate overload to study the change in populations of cecal streptococci and lactobacilli and to establish whether certain species of these bacteria were capable of producing vasoactive amines from amino acids. Cecal contents from 10 horses were divided into aliquots and incubated anaerobically with either corn starch or inulin (fructan; both at 1 g/100 ml). Samples were taken at 6-h intervals over a 24-h period for enumeration of streptococci, lactobacilli, and gram-negative anaerobes by a dilution method onto standard selective growth media. The effects of the antibiotic virginiamycin (1 mg/100 ml) and calcium hydrogen phosphate (CaHPO4; 0.3 g/100 ml) were also examined. Fermentation of excess carbohydrate was associated with increases in numbers of streptococci and lactobacilli (2- to 3.5-log unit increases; inhibited by virginiamycin) but numbers of gram-negative anaerobes were not significantly affected. A screening agar technique followed by 16S rRNA gene sequence analysis enabled the identification of 26 different bacterial strains capable of producing one or more vasoactive amines. These included members of the species Streptococcus bovis and five different Lactobacillus spp. These data suggest that certain bacteria, whose overgrowth is associated with carbohydrate fermentation, are capable of producing vasoactive amines which may play a role in the pathogenesis of acute laminitis.

Targeting Matrix Metalloproteinases in Inflammatory Conditions

The matrix metalloproteinases (MMPs) and their endogenous regulators, the tissue inhibitors of MMPs (TIMPs) are responsible for the physiological remodelling of the extracellular matrix (ECM) in healthy connective tissues. MMPs are also involved in the regulation of cell behaviour via the release of growth factors and cytokines from the substrates they cleave, increasing the magnitude of their effects. Excess MMP activity is associated with ECM destruction in various inflammatory conditions, such as osteoarthritis (OA), while MMP under-activity potentially impairs healing by promoting fibrosis and preventing the effective removal of scar tissue. Both direct (TIMPs, small molecule MMP inhibitor drugs, blocking antibodies and anti-sense technologies) and indirect (glucocorticoids and non-steroidal anti-inflammatory drugs, statins, anti-sense technologies and various phytochemicals) strategies for MMP inhibition have been proposed and investigated. The strategy of MMP inhibition for degenerative and neoplastic diseases has been relatively unsuccessful due to undesired sequelae, often caused by non-selectivity of the MMP inhibition method. Therapeutic strategies for MMP-related conditions ideally should regulate MMP activity in order to maintain the optimum balance between MMPs and TIMPs. By avoiding complete inhibition it may be possible to prevent the complications of MMP over- and under-activity. Furthermore, MMP sub-type specificity is critical for minimising detrimental off-target effects that have been observed with broad-spectrum MMP inhibitors. Any potential MMP inhibitor or modulator must be subjected to rigorous pharmacokinetic, toxicity and safety studies and data obtained using in vitro models must be verified in clinically relevant animal models before therapeutic use is considered.

Matrix metalloproteinases in inflammatory pathologies of the horse.

The extracellular matrix (ECM) of connective tissue is constantly being remodelled to allow for growth and regeneration. Normal tissue maintenance requires the ECM components to be degraded and re-synthesised in relatively equal proportions. This degradation is facilitated by matrix metalloproteinases (MMPs) and their proteolytic action is controlled primarily by the tissue inhibitors of metalloproteinases (TIMPs). Both MMPs and TIMPs exist in a state of dynamic equilibrium, with a slight excess of one or the other depending on the need for either ECM breakdown or synthesis. Long-term disruption to this balance between MMPs and TIMPs will have pathological consequences. Matrix metalloproteinases are involved in a number of diseases in mammals, including the horse. Excess MMP activity can cause ECM destruction, as seen in the lamellar basement membrane in laminitis and the articular cartilage in osteoarthritis. Matrix metalloproteinase under-activity can potentially impede healing by preventing fibrinolysis in fibrotic conditions and the removal of scar tissue in wounds. Matrix metalloproteinases also degrade non-ECM proteins and regulate cell behaviour via the release of growth factors from the substrates they cleave, increasing the scope of their effects. This review looks at the involvement of MMPs in equine health and pathologies, whilst exploring the potential consequences of therapeutic intervention.

Effect of nutritional antioxidant supplementation on systemic and pulmonary antioxidant status, airway inflammation and lung function in heaves-affected horses

An oxidant/antioxidant imbalance in favour of oxidants has been identified as playing a decisive role in the pathogenesis of chronic inflammatory airway diseases. Nutritional antioxidant supplementation might reduce oxidative damage by enhancement of the antioxidant defence, thereby modulating inflammatory processes. In a placebo-controlled, blind study, it was tested whether a dietary antioxidant supplement administered for 4 weeks would improve lung function and reduce airway inflammation in heaves-affected horses. Eight horses in clinical remission of heaves were investigated at rest and after a standardised exercise test before and after treatment with an antioxidant supplement (consisting of a mixture of natural antioxidants including vitamins E and C and selenium from a variety of sources) or placebo (oatfeed pellets without additive). Pulmonary function and exercise tolerance were monitored; systemic and pulmonary lining fluid uric acid, glutathione and 8-epi-PGF(2alpha) were analysed, and bronchoalveolar lavage (BAL) cytology and inflammatory scoring of the airways were performed. The antioxidant treatment significantly improved exercise tolerance and significantly reduced endoscopic inflammatory score. Plasma uric acid concentrations were significantly reduced, suggesting downregulation of the xanthine-dehydrogenase and xanthine-oxydase pathway. Haemolysate glutathione showed a nonsignificant trend to increase, while plasma 8-epi-PGF(2alpha) remained unchanged. Pulmonary markers and BAL cytology were not significantly affected by antioxidant supplementation. The present study suggests that the antioxidant supplement tested modulated oxidant/antioxidant balance and airway inflammation of heaves-affected horses.

The prevalence and anatomical distribution of equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark

REASONS FOR PERFORMING STUDY The prevalence (up to 93% in Thoroughbred racehorses) and severity of equine gastric ulceration syndrome (EGUS) have been correlated with the type of training and associated management practices. However, there have been few reports to confirm these findings in nonracehorses in Europe. OBJECTIVES To describe the prevalence, anatomical distribution, severity and number of gastric ulceration lesions in a population of Danish pleasure horses; and to investigate differences for groups based on age, breed type and workload. METHODS A total of 201 horses not in active race-training, age 7 months-27 years, were evaluated, representing 23 different stables from all 5 regions of Denmark. These horses were considered to be healthy by the owner and not on veterinary treatment for EGUS. Endoscopically observed ulcer lesion scores were based on the number present (0-4) and severity (0-5). The presence or absence of ulcers in the glandular and/or nonglandular regions of the stomach was recorded and which site the most severe ulcers were found. RESULTS The prevalence of EGUS severity score > or = 2 was 53%. The most severe lesions were commonly observed at the margo plicatus. Although older horses were not more likely to be affected by clinically significant EGUS they were more likely to have lesions in both the glandular and nonglandular regions. Differences in location of EGUS lesions were identified in different age groups, breed types and in horses exposed to different levels of work. CONCLUSION AND POTENTIAL RELEVANCE This study confirms that gastric ulceration can be prevalent in a group of apparently clinically normal horses, not in intensive work. Further investigation of reasons for differences in EGUS location between different populations may aid toward the development of novel preventive measures.

Breed differences in insulin sensitivity and insulinemic responses to oral glucose in horses and ponies of moderate body condition score

Breed-related differences may occur in the innate insulin sensitivity (SI) of horses and ponies, an important factor believed to be associated with the risk of laminitis. The aim of this study was to measure the glucose and insulin responses of different breeds of horses and ponies in moderate body condition to a glucose-containing meal and to compare these responses with the indices of SI as determined by a frequently sampled intravenous glucose tolerance test (FSIGT). Eight Standardbred horses, 8 mixed-breed ponies, and 7 Andalusian-cross horses with a mean ± SEM BCS 5.0 ± 0.3 of 9 were used in this study. Each animal underwent an oral glucose tolerance test (OGTT) in which they were fed a fiber-based ration (2.0 g/kg BW) containing 1.5 g/kg BW added glucose, as well as a standard FSIGT with minimal model analysis. The glucose response variables from the OGTT were similar between groups; however, the peak insulin concentration was higher in ponies (94.1 ± 29.1 μIU/mL; P = 0.003) and Andalusians (85.3 ± 18.6; P = 0.004) than in Standardbreds (21.2 ± 3.5). The insulin area under the curve was also higher in ponies (13.5 ± 3.6 IU · min · L(-1); P = 0.009) and Andalusians (15.0 ± 2.7; P = 0.004) than in Standardbreds (3.1 ± 0.6). Insulin sensitivity, as determined by the FSIGT, was lower in Andalusians (0.99 ± 0.18 × 10(-4)/[mIU · min]) than in Standardbreds (5.43 ± 0.94; P < 0.001) and in ponies (2.12 ± 0.44; P = 0.003) than in Standardbreds. Peak insulin concentrations from the OGTT were negatively correlated with SI (P < 0.001; rs = -0.75). These results indicate that there are clear breed-related differences in the insulin responses of horses and ponies to oral and intravenous glucose. All animals were in moderate body condition, indicating that breed-related differences in insulin dynamics occurred independent of obesity.

Insulin sensitivity and glucose dynamics during pre-weaning foal development and in response to maternal diet composition.

Nutritional management of animals during pregnancy can affect glucose and insulin dynamics in the resulting offspring through influences on fetal development. Additionally, high starch feeding in mature horses is associated with reduced insulin sensitivity and an increased risk for diseases such as obesity and laminitis. However, no study has yet evaluated the effect of feeding a high starch diet to pregnant mares on glucose and insulin dynamics in their offspring. Twenty late-gestation mares maintained on pasture were provided two-thirds of digestible energy requirements from isocaloric, isonitrogenous low starch (LS, n=10) or high starch (HS, n=10) feed. Their foals were assessed with an insulin-modified frequently sampled intravenous glucose tolerance test at 5, 40, 80, and 160 d of age. Baseline glucose concentrations, insulin sensitivity, and insulin-independent glucose clearance in 5-d foals were all greater than values observed in mature horses and declined towards mature values as foals reached 160 d of age. Baseline glucose concentrations were all within normal range, but higher in foals born from HS mares through 80 d of age. Insulin sensitivity was not different between dietary groups until a trend for lower insulin sensitivity in HS foals emerged at 160 d of age. These data are the first to characterize decreasing insulin sensitivity and glucose tolerance in Thoroughbred foals from 5 to 160 d of age. This study also presents the first data examining glucose and insulin dynamics in developing foals in response to maternal high starch diet.