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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. |
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Title |
Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species |
Type |
Journal Article |
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Year |
2005 |
Publication  |
Toxicology and applied pharmacology |
Abbreviated Journal |
Toxicol Appl Pharmacol |
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Volume |
207 |
Issue |
2 Suppl |
Pages |
354-366 |
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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. |
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Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada |
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0041-008X |
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PMID:16081118 |
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no |
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Call Number |
refbase @ user @ |
Serial |
68 |
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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. |
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Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
Journal Article |
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Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
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Volume |
82 |
Issue |
2 |
Pages |
374-380 |
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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 |
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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. |
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Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA |
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1096-6080 |
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PMID:15456926 |
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no |
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Call Number |
refbase @ user @ |
Serial |
71 |
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Author |
Hunt, G.R.; Gray R.D.; Taylor, A.H. |
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Title |
Why is tool use rare in animals? |
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Book Whole |
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Year |
2013 |
Publication |
Tool Use in Animals: Cognition and Ecology |
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Cambridge University Press |
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Cambridge, MA. |
Editor |
anz C, Call J, Boesch C |
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Equine Behaviour @ team @ |
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6658 |
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Author |
Wiesner, J.; V. Hegel, G. |
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Title |
Zur Immobilisation von Wildequiden mit STH 2130 und Tiletamin/Zolazepam |
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Journal Article |
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Year |
1990 |
Publication |
Tierärtzliche Praxis |
Abbreviated Journal |
Tierärzl Prax |
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18 |
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151-154 |
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Notes |
from Professor Hans Klingels Equine Reference List |
Approved |
yes |
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1707 |
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Pinchbeck, G.L.; Clegg, P.D.; Proudman, C.J.; Morgan, K.L.; French, N.P. |
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Title |
Case-control investigation of the factors affecting the risk of horses falling during steeplechase racing in the UK |
Type |
Journal Article |
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Year |
2004 |
Publication |
The Veterinary Record |
Abbreviated Journal |
Vet. Rec. |
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Volume |
155 |
Issue |
1 |
Pages |
11-15 |
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Keywords |
Accidental Falls/*prevention & control/*statistics & numerical data; Animals; Athletic Injuries/epidemiology/etiology/prevention & control/*veterinary; Case-Control Studies; England/epidemiology; Horses/*injuries; Risk Factors; Running/*injuries |
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Abstract |
A concurrent case-control study of 12 UK racecourses was made between March 1, 2000, and August 31, 2001, to identify and quantify the factors associated with the risk of horses falling in steeplechase races. Cases were defined as a jumping effort at a steeplechase fence that resulted in a fall and controls were defined as a successful jumping effort over any steeplechase fence at any of the 12 racecourses within 14 days before or after the case fall. Information on the horse, the jockey and the race were collected and all the fences on all the courses were surveyed. Conditional logistic regression was used to examine the relationships between the predictor variables and the risk of falling. There was one fall per 254 jumping efforts. The risk of a horse falling decreased the more times it had raced on a particular racecourse. The number of fences, the distance from the previous fence and the nature of the previous fence also affected the risk of falling. If the previous fence was a water jump the risk of falling increased; fences that were sited on flat or slight uphill gradients (up to approximately 1 in 25) were associated with a lower risk of horses falling than downhill fences, and higher takeoff boards were associated with a higher risk of falling. |
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Department of Veterinary Clinical Science, University of Liverpool, Leahurst, Neston CH64 7TE |
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English |
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0042-4900 |
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PMID:15264483 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3773 |
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Author |
Pinchbeck, G.L.; Clegg, P.D.; Proudman, C.J.; Morgan, K.L.; French, N.P. |
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Title |
Case-control study to investigate risk factors for horse falls in hurdle racing in England and Wales |
Type |
Journal Article |
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Year |
2003 |
Publication |
The Veterinary Record |
Abbreviated Journal |
Vet. Rec. |
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Volume |
152 |
Issue |
19 |
Pages |
583-587 |
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Keywords |
Accidental Falls/*statistics & numerical data; Animals; Athletic Injuries/epidemiology/etiology/*veterinary; Case-Control Studies; England/epidemiology; Horses/*injuries; Risk Factors; Running/injuries; Wales/epidemiology |
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Abstract |
Between March 1, 2000 and August 31, 2001, a case-control study was conducted on 12 racecourses in England and Wales to identify and quantify the risk factors associated with horse falls in hurdle races. The cases and controls were defined so that variables relating to the horse, the jockey, the race and racecourse, and the jump could be considered. The cases were defined as a jumping effort at a hurdle flight that resulted in a fall, and the controls were defined as a successful jump over a hurdle at any of the 12 racecourses within 14 days before or after the case fall. Conditional logistic regression was used to examine the univariable and multivariable relationships between the predictor variables and the risk of falling. The risk of falling was significantly associated with the position of the jump in the race, and with the distance and speed of the race. A horse's previous racing experience and history were also significantly associated with the risk of falling and horses participating in their first hurdle race were at almost five times greater risk of falling than horses that had hurdled before. |
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Address |
Epidemiology Group, Department of Veterinary Clinical Science and Animal Husbandry, University of Liverpool, Leahurst, Neston CH64 7TE |
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English |
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0042-4900 |
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Notes |
PMID:12762486 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3782 |
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Author |
Pinchbeck, G.L.; Clegg, P.D.; Proudman, C.J.; Stirk, A.; Morgan, K.L.; French, N.P. |
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Title |
Horse injuries and racing practices in National Hunt racehorses in the UK: the results of a prospective cohort study |
Type |
Journal Article |
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Year |
2004 |
Publication |
The Veterinary Journal |
Abbreviated Journal |
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Volume |
167 |
Issue |
1 |
Pages |
45-52 |
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Keywords |
Racehorse; Horse; Injury; Cohort; National Hunt |
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Abstract |
A prospective cohort study was conducted on horses starting in hurdle and steeplechase races on six UK racecourses in 2000 and 2001. Trainers or carers were questioned on the horses' pre-race routine and observational data were collected in the stables and parade ring. Some practices were common to many starters, such as withholding food and water before racing whereas other practices, such as schooling frequency, were more variable. There was a total of 2879 starts and a total of 83 injuries or medical events (28.8/1000 starts). The commonest types of injury were tendon/suspensory injuries and lacerations/wounds. Multivariable logistic regression models were used to identify the relationship between predictor variables and the risk of injury. Risk of injury or medical event was associated with distance of the race and weight carried. The risk of injury, excluding medical events, was associated with the speed of the race and foot conformation. |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3672 |
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Author |
Landsberg, G.; Araujo, J.A. |
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Title |
Behavior problems in geriatric pets |
Type |
Journal Article |
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Year |
2005 |
Publication |
The Veterinary Clinics of North America. Small Animal Practice |
Abbreviated Journal |
Vet Clin North Am Small Anim Pract |
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Volume |
35 |
Issue |
3 |
Pages |
675-698 |
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Keywords |
Aging/*pathology/physiology/*psychology; Animals; *Behavior, Animal; Cats/*physiology/psychology; Cognition/physiology; Diagnosis, Differential; Dogs/*physiology/psychology; Preventive Medicine |
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Abstract |
Aging pets often suffer a decline in cognitive function (eg, memory,learning, perception, awareness) likely associated with age-dependent brain alterations. Clinically, cognitive dysfunction may result in various behavioral signs, including disorientation; forgetting of previously learned behaviors, such as house training; alterations in the manner in which the pet interacts with people or other pets;onset of new fears and anxiety; decreased recognition of people, places, or pets; and other signs of deteriorating memory and learning ability. Many medical problems, including other forms of brain pathologic conditions, can contribute to these signs. The practitioner must first determine the cause of the behavioral signs and then determine an appropriate course of treatment, bearing in mind the constraints of the aging process. A diagnosis of cognitive dysfunction syndrome is made once other medical and behavioral causes are ruled out. |
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Address |
Doncaster Animal Clinic, 99 Henderson Avenue, Thornhill, Ontario L3T2K9, Canada. gmlandvm@aol.com |
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English |
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ISSN |
0195-5616 |
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Notes |
PMID:15833565 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2855 |
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Author |
Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
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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 |
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Year |
2005 |
Publication |
The Journal of pharmacology and experimental therapeutics |
Abbreviated Journal |
J Pharmacol Exp Ther |
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Volume |
312 |
Issue |
1 |
Pages |
69-76 |
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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 |
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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. |
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Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA |
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English |
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0022-3565 |
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Notes |
PMID:15356214 |
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no |
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Call Number |
refbase @ user @ |
Serial |
73 |
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Author |
Skedros, J.G.; Dayton, M.R.; Sybrowsky, C.L.; Bloebaum, R.D.; Bachus, K.N. |
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Title |
The influence of collagen fiber orientation and other histocompositional characteristics on the mechanical properties of equine cortical bone |
Type |
Journal Article |
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Year |
2006 |
Publication |
The Journal of Experimental Biology |
Abbreviated Journal |
J Exp Biol |
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Volume |
209 |
Issue |
Pt 15 |
Pages |
3025-3042 |
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Keywords |
Animals; Biomechanics; Bone and Bones/*physiology; Collagen/*physiology; Forelimb; Horses/*physiology |
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Abstract |
This study examined relative influences of predominant collagen fiber orientation (CFO), mineralization (% ash), and other microstructural characteristics on the mechanical properties of equine cortical bone. Using strain-mode-specific (S-M-S) testing (compression testing of bone habitually loaded in compression; tension testing of bone habitually loaded in tension), the relative mechanical importance of CFO and other material characteristics were examined in equine third metacarpals (MC3s). This model was chosen since it had a consistent non-uniform strain distribution estimated by finite element analysis (FEA) near mid-diaphysis of a thoroughbred horse, net tension in the dorsal/lateral cortices and net compression in the palmar/medial cortices. Bone specimens from regions habitually loaded in tension or compression were: (1) tested to failure in both axial compression and tension in order to contrast S-M-S vs non-S-M-S behavior, and (2) analyzed for CFO, % ash, porosity, fractional area of secondary osteonal bone, osteon cross-sectional area, and population densities of secondary osteons and osteocyte lacunae. Multivariate multiple regression analyses revealed that in S-M-S compression testing, CFO most strongly influenced total energy (pre-yield elastic energy plus post-yield plastic energy); in S-M-S tension testing CFO most strongly influenced post-yield energy and total energy. CFO was less important in explaining S-M-S elastic modulus, and yield and ultimate stress. Therefore, in S-M-S loading CFO appears to be important in influencing energy absorption, whereas the other characteristics have a more dominant influence in elastic modulus, pre-yield behavior and strength. These data generally support the hypothesis that differentially affecting S-M-S energy absorption may be an important consequence of regional histocompositional heterogeneity in the equine MC3. Data inconsistent with the hypothesis, including the lack of highly longitudinal collagen in the dorsal-lateral ;tension' region, paradoxical histologic organization in some locations, and lack of significantly improved S-M-S properties in some locations, might reflect the absence of a similar habitual strain distribution in all bones. An alternative strain distribution based on in vivo strain measurements, without FEA, on non-Thoroughbreds showing net compression along the dorsal-palmar axis might be more characteristic of the habitual loading of some of the bones that we examined. In turn, some inconsistencies might also reflect the complex torsion/bending loading regime that the MC3 sustains when the animal undergoes a variety of gaits and activities, which may be representative of only a portion of our animals, again reflecting the possibility that not all of the bones examined had similar habitual loading histories. |
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Address |
Utah Bone and Joint Center, 5323 S. Woodrow Street #202, Salt Lake City, UT 84107, USA. jskedros@utahboneandjoint.com |
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English |
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0022-0949 |
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Notes |
PMID:16857886 |
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no |
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Call Number |
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Serial |
1868 |
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