| Records |
| Author |
Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
| Title |
Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide |
Type |
Journal Article |
| Year |
2005 |
Publication  |
The Journal of pharmacology and experimental therapeutics |
Abbreviated Journal |
J Pharmacol Exp Ther |
| Volume |
312 |
Issue |
1 |
Pages |
69-76 |
| Keywords |
Animals; Cell Line; Gene Expression/drug effects; Macrophages/drug effects/metabolism; Mice; Mice, Inbred C57BL; Nitric Oxide/*metabolism; Nitric Oxide Synthase/*metabolism; Nitric Oxide Synthase Type II; PPAR delta/metabolism; PPAR gamma/*agonists/deficiency; Thiazolidinediones/pharmacology |
| Abstract |
Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 microM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 microM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation. |
| Address |
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA |
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Place of Publication |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
0022-3565 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:15356214 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
73 |
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| Author |
Wilkins, L.J.; Brown, S.N.; Zimmerman, P.H.; Leeb, C.; Nicol, C.J. |
| Title |
Investigation of palpation as a method for determining the prevalence of keel and furculum damage in laying hens |
Type |
Journal Article |
| Year |
2004 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
| Volume |
155 |
Issue |
18 |
Pages |
547-549 |
| Keywords |
Animal Husbandry/methods; Animal Welfare; Animals; Bone and Bones/*injuries; Chickens/*injuries; Female; Fractures, Bone/diagnosis/epidemiology/*veterinary; Great Britain/epidemiology; Housing, Animal/standards; Oviposition; Palpation/methods/*veterinary; Poultry Diseases/*diagnosis/epidemiology; Prevalence; Sensitivity and Specificity |
| Abstract |
Old breaks of the keel and furculum were identified by palpation in 500 end-of-lay hens from 10 flocks housed in free-range and barn systems, and the results were compared with the results obtained by a full dissection and inspection. The method was considered to be sufficiently precise to be used as a diagnostic tool although people using it would need to be trained. The results obtained by dissection indicated that 50 to 78 per cent of the birds in the flocks had breaks of the furculum and keel, but no other breaks of bones were detected. |
| Address |
Department of Clinical Veterinary Science, University of Bristol, Bristol BS40 5DU |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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| Series Volume |
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Series Issue |
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Edition |
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| ISSN |
0042-4900 |
ISBN |
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Medium |
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| Area |
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Expedition |
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Conference |
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| Notes |
PMID:15559420 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
70 |
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| Author |
Nicol, C.J.; Davidson, H.P.D.; Harris, P.A.; Waters, A.J.; Wilson, A.D. |
| Title |
Study of crib-biting and gastric inflammation and ulceration in young horses |
Type |
Journal Article |
| Year |
2002 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
| Volume |
151 |
Issue |
22 |
Pages |
658-662 |
| Keywords |
Animal Husbandry/methods; Animals; Antacids/therapeutic use; *Behavior, Animal; Diet/veterinary; Endoscopy, Gastrointestinal/veterinary; Feces/chemistry; Female; Gastritis/diet therapy/physiopathology/*veterinary; Horse Diseases/diet therapy/*physiopathology/psychology; Horses; Hydrogen-Ion Concentration; Male; Random Allocation; Stereotyped Behavior/*physiology; Stomach Ulcer/diet therapy/physiopathology/*veterinary; Treatment Outcome; Weaning |
| Abstract |
Nineteen young horses that had recently started to perform the stereotypy of crib-biting were compared with 16 non-stereotypic horses for 14 weeks. After initial observations of their behaviour and an endoscopic examination of the condition of their stomachs, the horses were randomly allocated to a control or an antacid diet At the start of the trial, the stomachs of the crib-biting foals were significantly more ulcerated and inflamed than the stomachs of the normal foals. In addition, the faecal pH of the crib-biting foals (6.05) was significantly lower than that of the normal foals (6.58). The antacid diet resulted in a significant improvement in the condition of the horses' stomachs. The crib-biting behaviour declined in most of the foals, regardless of their diet, but tended to decline to a greater extent in the foals on the antacid diet. |
| Address |
Department of Clinical Veterinary Science, University of Bristol, Langford House, Bristol BS40 5DU |
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Place of Publication |
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Editor |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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| Series Volume |
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Series Issue |
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Edition |
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| ISSN |
0042-4900 |
ISBN |
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Medium |
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| Area |
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Expedition |
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Conference |
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| Notes |
PMID:12498408 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
83 |
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| Author |
McGreevy, P.D.; Webster, A.J.; Nicol, C.J. |
| Title |
Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses |
Type |
Journal Article |
| Year |
2001 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
| Volume |
148 |
Issue |
19 |
Pages |
592-596 |
| Keywords |
Animals; Behavior, Animal/*physiology; Case-Control Studies; *Digestion; *Gastrointestinal Motility/drug effects; Horse Diseases/*physiopathology; Horses/*physiology/psychology; Male; Stereotyped Behavior/*physiology; Sulfapyridine/blood; Sulfasalazine/diagnostic use/pharmacology |
| Abstract |
The spontaneous behaviour and the apparent digestibility of dry matter and fibre and transit times of digesta were compared in four normal horses and four crib-biters. A technique was developed for measuring total gut transit times (TGTT) by using single-stool analysis of the passage of radio-opaque polyethylene markers. Longer TGTT were recorded in the crib-biters than in the normal horses but the orocaecal transit times did not differ. The crib-biters rested less than the normal horses. |
| Address |
Department of Clinical Veterinary Science, University of Bristol, Langford |
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English |
Summary Language |
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Original Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
0042-4900 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:11386445 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
86 |
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| Author |
McGreevy, P.D.; French, N.P.; Nicol, C.J. |
| Title |
The prevalence of abnormal behaviours in dressage, eventing and endurance horses in relation to stabling |
Type |
Journal Article |
| Year |
1995 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
| Volume |
137 |
Issue |
2 |
Pages |
36-37 |
| Keywords |
Animal Husbandry/*methods; Animals; *Behavior, Animal; Horse Diseases/*psychology; Horses; *Physical Conditioning, Animal; Prevalence; Questionnaires; *Stereotyped Behavior |
| Abstract |
The behaviour of horses competing in different disciplines was studied and the relationship between the time they spent out of the stable and the prevalence of abnormal behaviour was examined. The owners of dressage, eventing and endurance horses were sent a questionnaire and a total of 1101 responses were received, giving data on 1750 horses. The behaviours studied were wood-chewing, weaving, crib-biting/wind-sucking and box-walking. The reported percentage prevalences of abnormal behaviour for the dressage, eventing and endurance horses were 32.5, 30.8 and 19.5, respectively. The relationship between the time spent in the stable and the prevalence of abnormal behaviour was examined by chi 2 tests which showed that there were significant linear trends for the eventing group (P < 0.001) and the dressage group (P < 0.05). It is concluded that the time a horse spends out of the stable is related to the discipline for which it is being trained and in dressage and eventing horses the time spent in a stable is correlated with an increased risk of abnormal behaviour. |
| Address |
University of Bristol, Department of Clinical Veterinary Science, Langford |
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| Language |
English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
0042-4900 |
ISBN |
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Medium |
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| Area |
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Expedition |
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Conference |
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| Notes |
PMID:8525580 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
89 |
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| Author |
Guo, G.L.; Moffit, J.S.; Nicol, C.J.; Ward, J.M.; Aleksunes, L.A.; Slitt, A.L.; Kliewer, S.A.; Manautou, J.E.; Gonzalez, F.J. |
| Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
Journal Article |
| Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
| Volume |
82 |
Issue |
2 |
Pages |
374-380 |
| Keywords |
Acetaminophen/pharmacokinetics/*toxicity; Analgesics, Non-Narcotic/pharmacokinetics/*toxicity; Animals; Aryl Hydrocarbon Hydroxylases/biosynthesis; Biotransformation; Blotting, Northern; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Membrane Proteins; Mice; Mice, Knockout; Oxidoreductases, N-Demethylating/biosynthesis; Pregnenolone Carbonitrile/pharmacology; Receptors, Cytoplasmic and Nuclear/*drug effects; Receptors, Steroid/*drug effects; Sulfhydryl Compounds/metabolism |
| Abstract |
The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation. |
| Address |
Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA |
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Thesis |
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Place of Publication |
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English |
Summary Language |
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Original Title |
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Series Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
1096-6080 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:15456926 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
71 |
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| Author |
Wells, P.G.; Bhuller, Y.; Chen, C.S.; Jeng, W.; Kasapinovic, S.; Kennedy, J.C.; Kim, P.M.; Laposa, R.R.; McCallum, G.P.; Nicol, C.J.; Parman, T.; Wiley, M.J.; Wong, A.W. |
| Title |
Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species |
Type |
Journal Article |
| Year |
2005 |
Publication |
Toxicology and applied pharmacology |
Abbreviated Journal |
Toxicol Appl Pharmacol |
| Volume |
207 |
Issue |
2 Suppl |
Pages |
354-366 |
| Keywords |
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| Abstract |
Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. |
| Address |
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada |
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English |
Summary Language |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
0041-008X |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:16081118 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
68 |
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| Author |
Hothersall, B.; Nicol, C. |
| Title |
Role of Diet and Feeding in Normal and Stereotypic Behaviors in Horses |
Type |
Journal Article |
| Year |
2009 |
Publication |
Veterinary Clinics of North America: Equine Practice |
Abbreviated Journal |
Clinical Nutrition |
| Volume |
25 |
Issue |
1 |
Pages |
167-181 |
| Keywords |
Equine behavior; Diet; Crib-biting; Stereotypy; Weaning; Tryptophan; Insulin |
| Abstract |
This article reviews the effects of diet on equine feeding behavior and feeding patterns, before considering the evidence that diet affects reactivity in horses. A growing body of work suggests that fat- and fiber-based diets may result in calmer patterns of behavior, and possible mechanisms that may underpin these effects are discussed. In contrast, there is little evidence that herbal- or tryptophan-containing supplements influence equine behavior in any measurable way. The role of diet in the development of abnormal oral behaviors, particularly the oral stereotypy crib-biting, is also reviewed, and suggestions for future work are presented. |
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Series Title |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
0749-0739 |
ISBN |
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Approved |
no |
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Equine Behaviour @ team @ |
Serial |
4945 |
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