Abstract: International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.

Abstract: The dominance hierarchy of a herd of 10 Thoroughbred mares was determined twice, at an interval of 18 months, using paired feeding tests. Each mare's rank was correlated significantly between the 2 tests. This indicated that the hierarchy within the herd was stable. The offspring of dominant and subordinate mares were also tested for dominance in their own age groups. The offspring of dominant mares tended to be near the top of the hierarchy while those of middle and low ranking mares were not consistently found in the middle or bottom of their own hierarchies. Paired feeding tests were carried out on 8 ponies. During tests the time that each pony spent eating and the ponies' aggressive interactions were recorded. Two situations were used. Each pony-pair was tested when both ponies were in the same paddock and also when they were separated by a rail fence. The subordinate ponies spent significantly more time eating and the domonant pony was significantly less aggressive, when the pony-pair was separated by a fence than when they were in one paddock. It was concluded that the dominance hierarchies of adult horse groups changed very little over time and that the foals of dominant mares will tend to be dominant in their own age groups. Management practices can be used to reduce aggression and consequent injury that may arise in group feeding situations.

Abstract: Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.