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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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English |
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ISSN |
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 |
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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ISSN |
0041-008X |
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Notes |
PMID:16081118 |
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no |
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Call Number |
refbase @ user @ |
Serial |
68 |
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Author |
Westerduin, F.E.; Lankveld, D.P.K.; van der Velden, M.A.; Back, W.; Sloet van Oldruitenborgh-Oosterbaan, M.M. |
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Title |
[Splenectomy in a dressage pony: end of sports career?] |
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Journal Article |
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Year |
2003 |
Publication |
Tijdschrift Voor Diergeneeskunde |
Abbreviated Journal |
Tijdschr Diergeneeskd |
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Volume |
128 |
Issue |
13 |
Pages |
406-411 |
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Keywords |
Animals; Biopsy/veterinary; Colic/surgery/veterinary; Horse Diseases/pathology/*surgery/ultrasonography; Horses; Laparotomy/veterinary; Male; Splenectomy/*veterinary; Splenomegaly/surgery/ultrasonography/*veterinary; *Sports |
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Abstract |
A 14-year-old Arabian cross-bred gelding was referred to the University Clinic because of mild, recurrent signs of colic for 5 days. The pony showed icteric mucous membranes, haemolytic blood, and dark coloured urine. Internal examination did not give a clear diagnosis. Unidentified intra-abdominal strands were found and haemorrhagic abdominocentesis led to the decision to perform an exploratory laparatomy. An extremely enlarged spleen was the sole finding. A splenal biopsy sample was taken and surgery was completed. The pony remained colicky, so the spleen was examined by ultrasonography. After this examination, the tentative diagnosis 'tumour of the spleen' was made and splenectomy was performed. Pathological examination of the spleen revealed splenomegaly caused by infarctions of unknown origin. Eight weeks after surgery, the pony started again in dressage competition. Six months after splenectomy, the pony won the provincial dressage competition. |
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Hoofdafdeling Gezondheidszorg Paard, Faculteit der Diergeneeskunde, Universiteit Utrecht, Yalelaan 12-16, 3584 CM Utrecht. fenna-lambert@planet.nl |
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Dutch |
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Original Title |
Splenectomie bij een dressuurpony: einde sportcarriere? |
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0040-7453 |
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Notes |
PMID:12870176 |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3722 |
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Author |
Boissevain, I. |
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Title |
[Animal and human rights in installments] |
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Year |
2007 |
Publication |
Tijdschrift Voor Diergeneeskunde |
Abbreviated Journal |
Tijdschr Diergeneeskd |
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Volume |
132 |
Issue |
4 |
Pages |
132 |
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Keywords |
Animals; Clinical Competence/*standards; Horse Diseases/*diagnosis; Horses; Humans; Netherlands; Time Factors; Veterinary Medicine/*methods/*standards |
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Dutch |
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Original Title |
Dierenrechten en mensenrechten in termijnen |
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0040-7453 |
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PMID:17366876 |
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Call Number |
Equine Behaviour @ team @ |
Serial |
4018 |
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Author |
Sloet van Oldruitenborgh-Oosterbaan, M.M.; Blok, M.B.; Begeman, L.; Kamphuis, M.C.D.; Lameris, M.C.; Spierenburg, A.J.; Lashley, M.J.J.O. |
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Title |
Workload and stress in horses: comparison in horses ridden deep and round ('rollkur') with a draw rein and horses ridden in a natural frame with only light rein contact |
Type |
Journal Article |
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Year |
2006 |
Publication |
Tijdschrift Voor Diergeneeskunde |
Abbreviated Journal |
Tijdschr Diergeneeskd |
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131 |
Issue |
5 |
Pages |
152-157 |
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Keywords |
Animal Husbandry/methods; Animals; Biomechanics; Blood Glucose/analysis; Female; Heart Rate/physiology; Hematocrit/veterinary; Horses/blood/*physiology; Hydrocortisone/blood; Lactic Acid/blood; Physical Conditioning, Animal/adverse effects/*physiology; Stress, Physiological/blood/etiology/veterinary |
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Abstract |
'Rollkur' or 'overbending' is the low and deep riding of a dressage horse during training or warming up. Lately, this technique has been criticized, and not necessarily objectively, on welfare grounds. To be able to evaluate these criticisms, more needs to be known about the workload and stress of horses being ridden 'rollkur'. The aim of the present study was to compare the workload of eight riding-school horses when being ridden deep and round with a draw rein ('rollkur') and when being ridden in a natural frame with only light rein contact ('free'). Workload (as measured by heart rate and blood lactate concentration) was slightly higher when horses were ridden 'rollkur' than when they were ridden 'free'. There were no differences in packed cell volume, or glucose and cortisol concentrations. No signs of uneasiness or stress could be determined when the horses were ridden 'rollkur'. Subjectively, all horses improved their way of moving during 'rollkur' and were more responsive to their rider. |
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Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 12, 3584 CM Utrecht, The Netherlands. m.sloet@vet.uu.nl |
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0040-7453 |
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Notes |
PMID:16532786 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
5638 |
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Author |
Nitschelm D, H.V.D.C. |
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Title |
The influence of chlormadinone acetate treatment on the concentration of some stereoids in the blood, on the ovarian activity and on.. |
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Journal Article |
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Year |
1977 |
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Abbreviated Journal |
Tijdschr Diergeneesk |
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Volume |
102 |
Issue |
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Pages |
861-872 |
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Notes |
from Professor Hans Klingels Equine Reference List |
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no |
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Call Number |
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Serial |
1419 |
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Author |
Nitschelm D, H.V.D.C. |
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Title |
The influence of chlormadinone acetate treatment on the concentration of some stereoids in the blood, on the ovarian activity, and on the sexual behaviour of the.. |
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Journal Article |
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1977 |
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Tijdschr Diergeneesk |
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102 |
Issue |
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61-872 |
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Notes |
from Professor Hans Klingels Equine Reference List |
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no |
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1420 |
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Author |
Java Rl, |
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Title |
Census of wild Ass |
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Journal Article |
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Year |
1983 |
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Abbreviated Journal |
Tigerpaper |
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Volume |
10 |
Issue |
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Pages |
23 |
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Notes |
from Professor Hans Klingels Equine Reference List |
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no |
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Serial |
1218 |
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Author |
Shaki Sp, |
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Title |
About the indian Wild ass |
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Journal Article |
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Year |
1983 |
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Abbreviated Journal |
Tigerpaper |
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Volume |
10 |
Issue |
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Pages |
13-16 |
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Notes |
from Professor Hans Klingels Equine Reference List |
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no |
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Serial |
1588 |
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Author |
Huebener, E. |
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Title |
Die Bewegungen von Pferderumpf und -rücken aus der Sicht des Reiters |
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Journal Article |
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Year |
2004 |
Publication |
Tierärztliche Umschau |
Abbreviated Journal |
Tierärztl. Umschau |
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Volume |
6 |
Issue |
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Pages |
327-334 |
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Keywords |
Schritt – Trab – Galopp – Schmerz – Schäden |
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Abstract |
Die Bewegungen von Rumpf und Rücken des Pferdes in der Fortbewegung bestimmen Sitz und Schenkelhilfen – Grundlagen pferdgerechten und kultivierten, feinfühligen Reitens. In ihrer Tendenz ließen sich diese Bewegungen jetzt aus den Fußfolgen der Grundgangarten ableiten. Die Erkenntnisse sind per Video verifiziert. Mit ihrer Übersetzung in Diagramme wurde versucht, den gegenwärtigen Wissensstand für nicht-reitende Wissenschaftler und denkende Reiter gleichermaßen verständlich darzustellen. Die Akzeptanz des aufbereiteten Wissens in der Reiterei würde verbessert, wenn man zu gemessenen Werten für die Bewegungen des Pferderückens und des Pferderumpfes käme. Plädoyer eines “Nur-Reiters” für einschlägige, universitäre Forschung. |
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German |
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refbase @ user @ |
Serial |
420 |
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