The hormone, 1,25-dihydroxyvitamin D3 (1,

Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors with diverse actions including adipocyte differentiation and lipid metabolism. Recent studies have revealed anti-inflammatory activities, but the majority of these studies have been performed in monocyte/macrophages. In these studies, we investigate the effects of PPAR ligands in murine mitogen-activated splenocytes. Ciglitazone, a PPARgamma ligand, consistently decreased IFN-gamma and IL-2 production by mitogen-activated splenocytes and had modest effects on splenocyte proliferation. The effects of WY14,643, a representative of the fibrate class of PPARalpha ligands, on splenocyte proliferation and IL-2 levels are less marked than those observed with the PPARgamma ligand. In addition, treatment with WY14,643 and other fibrates led to marked increases in supernatant concentrations of IL-4. However, treatment with a potent and specific PPARalpha ligand (GW7,647) did not augment IL-4. Also, WY14,643 induced IL-4 expression in splenocytes from PPARalpha knockout mice, suggesting that the fibrate effect on IL-4 was largely through a PPARalpha-independent mechanism. This increase in IL-4 was associated with and causatively related to augmented expression of CD23 by CD45R/B220(+) cells. We also demonstrate that PPARgamma gene expression is up-regulated in T cells by mitogen activation, that it is positively regulated by IL-4 and WY14,643, and that it is blocked by anti-IL-4. Finally, we demonstrate that WY14,643 can modestly augment IL-4 promoter activity in a PPARalpha-independent manner. In concert, these findings support the roles of PPAR ligands in modulating inflammatory responses involving lymphocytes but also establish potent effects of the fibrate class of PPARalpha ligands on IL-4 expression that are receptor independent.

Colic (abdominal pain) is a common cause of mortality in horses. Change in management of horses is associated with increased colic risk and seasonal patterns of increased risk have been identified. Shifts in gut microbiota composition in response to management change have been proposed as one potential underlying mechanism for colic. However, the intestinal microbiota in normal horses and how this varies over different seasons has not previously been investigated. In this study the faecal microbiota composition was studied over 12 months in a population of horses managed at pasture with minimal changes in management. We hypothesised that gut microbiota would be stable in this population over time. Faecal samples were collected every 14 days from 7 horses for 52 weeks and the faecal microbiota was characterised by next-generation sequencing of 16S rRNA genes. The faecal microbiota was dominated by members of the phylum Firmicutes and Bacteroidetes throughout. Season, supplementary forage and ambient weather conditions were significantly associated with change in the faecal microbiota composition. These results provide important baseline information demonstrating physiologic variation in the faecal microbiota of normal horses over a 12-month period without development of colic.

Laparotomy during winter and summer months was associated with increased likelihood of SSI but there was no effect of surgery performed outside normal working hours. This information assists in identifying horses at high risk of SSI and informing development of preventive strategies.

The findings of the present study have relevance to horses in the UK, Ireland and USA.

The general aim of the present study was to test whether there are differences in the occlusal design of the ruminant selenodont molar, and by examining correlations between tooth form and diet, improve our understanding of the function of the selenodont molar within the Bovidae. Twenty-six species of bovid ruminants were grouped into the three feeding types established by Hofmann (1968) ± i.e. browsers, grazers and intermediate feeders. The characteristics of the shape, number, width and length of the enamel ridges were found to correlate with the hypothesized function of the molar occlusal surface. These follow the principles applied to non-bovid species where adaptation of the occlusal surface has been investigated in some detail. Thirteen characteristics of the occlusal surface were scored. ANOSIM results reject the null hypothesis that there are no differences in the selenodont molar occlusal surface. SIMPER results showed that all the characteristics scored contributed to the differences between groups, and crown height was not explaining the major dissimilarity between feeding groups. Differences in enamel ridge characteristics between feeding types suggest that food is being processed in essentially different ways by the browsers and grazers. Intermediate feeding species cluster within the other feeding types, depending on what the major component of the diet is. The grouping produced by the MDS, based on dental characters, closely agrees with Hofmann's classi®cation based on gut structure.

SummaryReasons for performing study: To determine risk factors involved in survival to hospital discharge of cases of synovial sepsis. Objectives: Investigate pre-, intra-and post operative factors involved in short-term survival of horses undergoing endoscopic treatment for synovial sepsis. Study design: Retrospective case series. Methods: Clinical data were obtained for horses (>6 months old) undergoing endoscopic surgery as part of management for synovial sepsis over a 7-year period in a single hospital population. Descriptive data were generated for pre-, intra-and post operative variables. Multivariable logistic regression analysis was used to develop 3 models related to presurgical, surgical and post surgical stages of management with outcome defined as survival to hospital discharge. Results: Two hundred and fourteen horses were included. In Model 1 (preoperative variables), increased preoperative synovial fluid total protein (TP) was associated with nonsurvival (OR 0.88, 95% CI 0.83-0.94, P<0.001) whereas the presence of a wound on admission was associated with survival (OR 4.75, 95% CI 1.21-18.65, P = 0.02). Model 2 (intraoperative variables) revealed that factors associated with decreased survival were anaesthetic induction outside of normal working hours (OR 0.36, 95% CI 0.15-0.88 P = 0.02) and presence of moderate/severe synovial inflammation at surgery (OR 0.28, 95% CI 0.12-0.67, P = 0.004). Model 3 (post operative variables) showed that increased post operative synovial fluid TP (OR 0.94, 95% CI 0.90-0.98, P = 0.013) and undertaking more than one endoscopic surgery for treatment (OR 0.19, 95% CI 0.05-0.70, P = 0.005) were associated with nonsurvival. Cut-off values for predicting survival were 55-60 g/l for preoperative and 50-55 g/l for post operative TP measurements. Conclusions: This study has identified factors associated with altered likelihood of survival to hospital discharge following endoscopic surgery for synovial sepsis. Prognosis for survival to hospital discharge can be based on evidence from this study at the key stages of management of horses with synovial sepsis.

Changes in management of the surgical colic patient over the last 30 years have resulted in considerable improvement in post operative survival rates. However, post operative complications remain common and these impact negatively on horse welfare, probability of survival, return to previous use and the costs of treatment. Multiple studies have investigated risk factors for post operative complications following surgical management of colic and interventions that might be effective in reducing the likelihood of these occurring. The findings from these studies are frequently contradictory and the evidence for many interventions is lacking or inconclusive. This review discusses the current available evidence and identifies areas where further studies are necessary and factors that should be taken into consideration in study design.