A partial estrogen receptor agonist with strong antiatherogenic properties without noticeable effect on reproductive tissue in cholesterol-fed female and male rabbits

Estrogen replacement therapy retards the development of cardiovascular disease and osteoporosis in postmenopausal women. However, long-term unopposed use increases the risk of cancer in endometrium and possibly in breast. The racemic compound ormeloxifene, widely used in India as an antifertility agent, is a partial estrogen receptor agonist with antiosteoporotic properties. The present study was undertaken to investigate the effect of the L-enantiomer (levormeloxifene) and the d-enantiomer (d-ormeloxifene) on the development of atherosclerosis. In a short-term experiment (6 weeks), 4 x 10 ovariectomized female rabbits were fed a 0.25% cholesterol-enriched diet and the effect on plasma cholesterol levels was studied. In a long-term experiment (13 weeks), 4 x 15 ovariectomized female and 4 x 15 shamoperated male rabbits were maintained at a similar plasma cholesterol level of 25 mmol/L and the effect on undamaged and balloon-injured arterial wall was studied. In both experiments, the rabbits were treated with levormeloxifene, d-ormeloxifene, 17 beta-estradiol, or placebo, respectively. In the short-term experiment, levormeloxifene, in contrast to d-ormeloxifene, significantly reduced plasma cholesterol by 30% compared with the placebo group. In the long-term experiment, levormeloxifene, in contrast to d-ormeloxifene, significantly reduced atherosclerosis by 50% in the undamaged arterial wall of both female and male rabbits. Because these rabbits were cholesterol-clamped, the antiatherogenic effect was not mediated via plasma cholesterol lowering. Like estrogen, levormeloxifene did not inhibit atherosclerosis in the endothelium-denuded site of aorta. The antiatherogenic effects of levormeloxifene were thus similar to those of estrogen, but produced in the absence of any noticeable estrogenic effect on uterine or testicular tissue.     

Relationships between mastitis and functional longevity in Danish Black and White dairy cattle estimated using survival analysis

The relationship between mastitis and functional longevity was assessed with survival analysis on data of Danish Black and White dairy cows. Different methods of including the effect of mastitis treatment on the culling decision by a farmer in the model were compared. The model in which mastitis treatment was assumed to have an effect on functional longevity until the end of the lactation had the highest likelihood, and the model in which mastitis treatment had an effect for only a short period had the lowest likelihood. A cow with mastitis had 1.69 times greater risk of being culled than did a healthy herdmate with all other effects being the same. A model without mastitis treatment was used to predict transmitting abilities of bulls for risk of being culled, based on longevity records of their daughters, and was expressed in terms of risk of being culled. The correlation between the risk of being culled and the national evaluations of the bulls for mastitis resistance was approximately -0.4, indicating that resistance against mastitis was genetically correlated with a lower risk of being culled and, thus, a longer functional length of productive life.