Abstract: Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice.

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: The Federation Equestre Internationale has permitted the use of altrenogest in mares for the control of oestrus. However, altrenogest is also suspicious to misuse in competition horses for its potential anabolic effects and suppression of typical male behaviour, and thus is a controlled drug. To investigate the pharmacokinetics of altrenogest in horses we conducted an elimination study. Five oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose interval of 24 h. Following administration blood and urine samples were collected at appropriate intervals. Altrenogest concentrations were measured by liquid chromatography-tandem mass spectrometry. The plasma levels of altrenogest reached maximal concentrations of 23-75 ng/mL. Baseline values were achieved within 3 days after the final administration. Urine peak concentrations of total altrenogest ranged from 823 to 3895 ng/mL. Twelve days after the final administration concentrations were below the limit of detection (ca 2 ng/mL).

Abstract: INTRODUCTION: The connection between morphologic changes of the spine and the intensity of training has been assessed for a number of sport activities. The influence of horseback riding on the spine has only rarely been evaluated. The aim of our study was to evaluate to what degree horseback riders suffer from back pain and whether there is an association between this parameter and the category i. e. the intensity of horseback riding. Furthermore we wanted to judge whether riding may have a positive effect on pre-existent back pain. METHODS: 508 horseback riders (63.2 % females; 36.8 % males) competing in either dressage, showjumping or vaulting were interviewed using a questionnaire. Apart from biometric data, the intensity with which riding was performed and the localisation and intensity (VAS) of back pain was assessed. Furthermore, in the case of existing back pain, riders were asked whether different riding disciplines and paces changed the intensity of pain. RESULTS: 300 dressage riders (59.1 %), 188 showjumpers (37.0 %) and 20 vaulters (3.9 %) with an average age of 33.5 Jahre (12 – 77 years) were questioned. The incidence of back pain was 72.5 %. A significant correlation between back pain and riding discipline respectively gender or riding level could not be found. Discrepancies in VAS-score for dressage riders (3.95 +/- 0.13), show jumpers (4.10 +/- 0.16) and vaulters (3.76 +/- 0.5) were marginal and not significant (p > 0.05). Overall 58.7 % resp. 15.2 % reported to have pain in the lumbar i.e cervical spine. Despite the fact that a large fraction of dressage riders claimed to have problems in these spine areas with 57.7 % resp. 68.8 %, this finding was not significant compared to the other riding disciplines. While 61.6 % of dressage riders reported an improvement of their back pain when riding, this was only the case in 40.9 % of show jumpers. CONCLUSION: Compared to the general population, a high incidence of back pain is found among riders. A significant correlation between the intensity of riding or the riding discipline and frequency or severity of back pain could not be found. For riders with pre-existent back pain the pace “walk” seems to have a positive influence on pain intensity.