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| Author | Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. | ||||
| Title | Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha | Type | Journal Article | ||
| Year | 2004 | Publication | Cancer research | Abbreviated Journal | Cancer Res |
| Volume | 64 | Issue | 11 | Pages | 3849-3854 |
| Keywords | Animals; Anticholesteremic Agents/pharmacology; Carcinogens/pharmacology; Cell Division; DNA Replication/drug effects; Fatty Acids/metabolism; Hepatocytes/cytology/drug effects/metabolism/*physiology; Humans; Mice; Mice, Transgenic; Oxidation-Reduction; Peroxisome Proliferators/pharmacology; Pyrimidines/pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Species Specificity; Transcription Factors/genetics/*physiology | ||||
| 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. | ||||
| Address | Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA | ||||
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| Language | English | Summary Language | Original Title | ||
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| ISSN | 0008-5472 | ISBN | Medium | ||
| Area | Expedition | Conference | |||
| Notes | PMID:15172993 | Approved | no | ||
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refbase @ user @ | Serial | 74 | ||
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| Author | Alexander, F.; Collett, R.A. | ||||
| Title | Proceedings: Some observations on the pharmacokinetics of trimethoprim in the horse | Type | Journal Article | ||
| Year | 1974 | Publication | British journal of pharmacology | Abbreviated Journal | Br J Pharmacol |
| Volume | 52 | Issue | 1 | Pages | 142p |
| Keywords | Animals; Half-Life; Horses/*metabolism; Kinetics; Trimethoprim/*metabolism | ||||
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| Language | English | Summary Language | Original Title | ||
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| Series Volume | Series Issue | Edition | |||
| ISSN | 0007-1188 | ISBN | Medium | ||
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| Notes | PMID:4451793 | Approved | no | ||
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refbase @ user @ | Serial | 112 | ||
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| Author | Alexander, F.; Collett, R.A. | ||||
| Title | Pethidine in the horse | Type | Journal Article | ||
| Year | 1974 | Publication | Research in veterinary science | Abbreviated Journal | Res Vet Sci |
| Volume | 17 | Issue | 1 | Pages | 136-137 |
| Keywords | Animals; Half-Life; Horses/*metabolism; Injections, Intravenous/veterinary; Male; Meperidine/administration & dosage/analysis/*metabolism/pharmacology | ||||
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| Language | English | Summary Language | Original Title | ||
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| ISSN | 0034-5288 | ISBN | Medium | ||
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| Notes | PMID:4421117 | Approved | no | ||
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refbase @ user @ | Serial | 113 | ||
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| Author | Minero, M.; Zucca, D.; Canali, E. | ||||
| Title | A note on reaction to novel stimulus and restraint by therapeutic riding horses | Type | Journal Article | ||
| Year | 2006 | Publication | Applied Animal Behaviour Science | Abbreviated Journal | Appl. Anim. Behav. Sci. |
| Volume | 97 | Issue | 2-4 | Pages | 335-342 |
| Keywords | Horse; Therapeutic riding; Behavioural indicators; Heart rate; Lymphocyte proliferation | ||||
| Abstract | Little research has been done to measure reactivity objectively in therapeutic riding horses (TRH). As individual reactivity and chronic stress could be assessed by exposing animals to acute, novel stressors, the authors of this work aimed at comparing reactions of TRHs and jumping horses (JH) to two challenges. Four TRHs and four JHs were exposed to a restraint covering their head with a hood for 1 h and to a startling stimulus (a 40 cm long, red and white synthetic holiday garland shaken with a rustling noise inside the box). Heart rate (HR) and heart rate variability (HRV) were recorded continuously and telemetrically, the reaction was video-recorded and analysed with a software for behavioural analysis. Blood samples were collected before and after each challenge to determine lymphocyte proliferation and other biochemical parameters. Horses spent most of the time immobile, during the challenges (p < 0.05). TRHs had a significantly higher average basal HR than JH (p < 0.05), probably due to their better condition. HR varied among different behaviours during the restraint (p < 0.05): the average HR during “pawing” was higher than during other behaviours (p < 0.005). A significant decrease in the proliferation of lymphocytes in samples taken after the removal of the hood (p < 0.05) was found, while the other stress related parameters did not vary significantly after the challenges. The authors conclude that TRHs did not react less than JHs to the new stimuli and this should be taken into consideration while planning their daily work and management. | ||||
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| Notes | Approved | no | |||
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refbase @ user @ | Serial | 279 | ||
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| Author | Dall, Sasha R. X; Houston, Alasdair I.; McNamara, John M. | ||||
| Title | The behavioural ecology of personality: consistent individual differences from an adaptive perspective | Type | Journal Article | ||
| Year | 2004 | Publication | Ecology Letters | Abbreviated Journal | Ecol. Letters |
| Volume | 7 | Issue | Pages | 734-739 | |
| Keywords | Adaptive individual differences, behavioural ecology, behavioural syndromes, evolutionary game theory, life history strategies, personality differences, state-dependent dynamic programming | ||||
| Abstract | Individual humans, and members of diverse other species, show consistent differences in aggressiveness, shyness, sociability and activity. Such intraspecific differences in behaviour have been widely assumed to be non-adaptive variation surrounding (possibly) adaptive population-average behaviour. Nevertheless, in keeping with recent calls to apply Darwinian reasoning to ever-finer scales of biological variation, we sketch the fundamentals of an adaptive theory of consistent individual differences in behaviour. Our thesis is based on the notion that such .personality differences. can be selected for if fitness payoffs are dependent on both the frequencies with which competing strategies are played and an individual`s behavioural history. To this end, we review existing models that illustrate this and propose a game theoretic approach to analyzing personality differences that is both dynamic and state-dependent. Our motivation is to provide insights into the evolution and maintenance of an apparently common animal trait: personality, which has far reaching ecological and evolutionary implications. |
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| Notes | Approved | no | |||
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refbase @ user @ | Serial | 494 | ||
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| Author | Berger, J | ||||
| Title | Wild horses of the Great Basin | Type | Book Whole | ||
| Year | 1986 | Publication | University of Chicago Press, | Abbreviated Journal | Univ. of Chic. Press |
| Volume | Issue | Pages | |||
| Keywords | wildlife equine behaviour ecology | ||||
| Abstract | Describes the behavior of wild horses living in the Great Basin Desert of Nevada and discusses the role of the horses in the area's ecology | ||||
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| Publisher | University of Chicago Press | Place of Publication | Chicago | Editor | |
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| ISSN | ISBN | 0-226-04367-3 | Medium | ||
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| Notes | Approved | no | |||
| Call Number |
refbase @ user @ | Serial | 659 | ||
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