Abstract: BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.

Abstract: Abstract Across the globe, wildlife populations and their behaviours are negatively impacted by people. Protected areas are believed to be an antidote to increasing human pressures but even they are not immune to the impact of anthropogenic activities. Areas that have been set aside for the protection of wildlife therefore warrant more attention when investigating the impact of anthropogenic pressures on wildlife. We use cheetahs Acinonyx jubatus as a case study to explore how a large carnivore responds to anthropogenic pressures inside wildlife areas. Using GPS-collar data we investigate cheetah space use, both when moving and stationary, and movement parameters (speed and turn angles) in relation to human disturbance, distance to human settlement, livestock abundance and livestock site use inside wildlife areas. Space use was negatively influenced by human disturbance, resulting in habitat loss and fragmentation and potentially reducing landscape permeability between neighbouring wildlife areas. Cheetahs were also less likely to stop in areas where livestock numbers were high, but more likely to stop in areas that were frequently used by livestock. The latter could reflect that cheetahs are attracted to livestock however, cheetahs in the study area rarely predated on livestock. It is therefore more likely that areas that are frequently used by livestock attract wild herbivores, which in turn could influence cheetah space use. We did not find any effects of people and livestock on cheetahs? speed and turn angles which might be related to the resolution of the data. We found that cheetahs are sensitive to human pressures and we believe that they could be an indicator species for other large carnivores facing similar challenges. We suggest that further research is needed to determine the levels of anthropogenic pressures needed to maintain ecological integrity, especially inside wildlife areas.

Abstract: The stimuli that elicit thirst were studied in four ponies. Nineteen hours of water deprivation produced an increase in plasma protein from 67 +/- 0.1 g/litre to 72 +/- 2 g/litre, a mean (+/- se) increase in plasma sodium from 139 +/- 3 to 145 +/- 2 mmol/litre and an increase in plasma osmolality from 297 +/- 1 to 306 +/- 2 mosmol/litre. Undeprived ponies drank 1.5 +/- 0.9 kg/30 mins; 19 h deprived ponies drank 10.2 +/- 2.5 kg/30 mins and corrected the deficits in plasma protein, plasma sodium and plasma osmolality as well as compensating for the water they would have drunk during the deprivation period. In order to determine if an increase in plasma osmolality would stimulate thirst, 250 ml of 15 per cent sodium chloride was infused intravenously. The ponies drank when osmolality increased 3 per cent and when plasma sodium rose from 136 +/- 3 mmol/litre to 143 +/- 3 mmol/litre. Ponies infused with 15 per cent sodium chloride drank 2.9 +/- 0.7 kg; those infused with 0.9 per cent sodium chloride drank 0.7 +/- 0.5 kg. In order to determine if a decrease in plasma volume would stimulate thirst, ponies were injected with 1 or 2 mg/kg bodyweight (bwt) frusemide. Plasma protein rose from 68 +/- 2 g/litre pre-injection to 75 +/- 2 g/litre 1 h after 1 mg/kg bwt frusemide and to 81 +/- 1 g/litre 1 h after 2 mg/kg bwt frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Reasons for performing the study: Similar to human decubitus ulcers, local high pressure points from ill-fitting saddles induce perfusion disturbances of different degrees resulting in tissue hypoxia and alteration in sweat production. Objective: To relate the different clinical manifestations of saddle sores to the magnitude of saddle pressures at the location of the withers. Methods: Sixteen horses with dry spots after exercise (Group A) and 7 cases presented with acute clinical signs of saddle pressure in the withers area (Group B) were compared with a control group of 16 sound horses with well fitting saddles (Group C). All horses underwent a saddle pressure measurement at walk, trot and canter. Mean and maximal pressures in the area of interest were compared between groups within each gait. Results: Mean pressures differed significantly between groups in all 3 gaits. Maximal pressure differed between groups at trot; at walk and canter, however, the only significant difference was between Group C and Groups A and B, respectively, (P>0.05). Mean and maximal pressures at walk in Group A were 15.3 and 30.6 kPa, in Group B 24.0 and 38.9 kPa and in Group C 7.8 and 13.4 kPa, respectively; at trot in Group A 18.1 and 43.4 kPa, in Group B 29.7 and 53.3 kPa and in Group C 9.8 and 21.0 kPa, respectively; and at canter in Group A 21.4 and 48.9 kPa, in Group B 28.6 and 56.0 kPa and in Group C 10.9 and 24.7 kPa, respectively. Conclusion: The study shows that there is a distinguishable difference between the 3 groups regarding the mean pressure value, in all gaits.

Abstract: REASONS FOR PERFORMING STUDY: Force transmission under an English saddle (ES) at walk, trot and canter is commonly evaluated, but the influence of a side saddle (SS) on the equine back has not been documented. HYPOTHESIS: Force transmission under a SS, with its asymmetric construction, is different from an ES in walk, trot and canter, expressed in maximum overall force (MOF), force in the quarters of the saddle mat, and centre of pressure (COP). The biomechanics of the equine back are different under a SS compared to ES. METHODS: Thirteen horses without clinical signs of back pain ridden in an indoor riding school with both saddles were measured using an electronic saddle sensor pad. Synchronous kinematic measurements were carried out with tracing markers placed along the back in front of (withers, W) and behind the saddle (4th lumbar vertebra, L4). At least 6 motion cycles at walk, trot and canter with both saddles (ES, SS) were measured. Out of the pressure distribution the maximum overall force (MOF) and the location of the centre of pressure (COP) were calculated. RESULTS: Under the SS the centre of pressure was located to the right of the median and slightly caudal compared to the COP under the ES in all gaits. The MOF was significantly different (P<0.01) between saddles. At walk, L4 showed significantly larger (P<0.01) vertical excursions under the ES. Under the SS relative horizontal movement of W was significantly reduced (P<0.01) at trot, and at canter the transversal movement was significantly reduced (P<0.01) . In both trot and canter, no significant differences in the movement of L4 were documented. CONCLUSIONS AND POTENTIAL RELEVANCE: The results demonstrate that the load under a SS creates asymmetric force transmission under the saddle, and also influences back movement. To change the load distribution on the back of horses with potential back pain and as a training variation, a combination of both riding styles is suitable.